Bill's Pre-comment: Savannah, this one's for you.
3 Doors Down Singer Recovers From Accident
By Associated Press
3 hours ago
BILOXI, Miss. - The lead singer of 3 Doors Down is recovering at home from injuries sustained in a one-car accident on a rain-soaked Mississippi road earlier this month.
Brad Arnold, 27, was a passenger in the car driven by his wife, Terika, when the accident occurred on Feb. 1, according to the band's Web site.
Terika Arnold reportedly wasn't injured.
"They were coming back from a casino, hit some kind of water on the road. The car hydroplaned, went down a high embankment and they hit a tree. I guess if Brad hadn't been wearing his seat belt, he'd probably be dead now," band member Todd Harrell said Thursday.
Harrell said Arnold has "35 or 40 stitches in the side of his face."
"He had a plastic surgeon come in and work on him, sewed his ear back on," Harrell said. "He's going to be all right. He was hit hard, though."
Harrell said the band, originally from Escatawpa, plan to tour Europe next month. They have been promoting their third studio album, "Seventeen Days."
Their hits include "Let Me Go," "Kryptonite," "When I'm Gone" and "Here Without You."
On the Net:
Copyright 2006 The Associated Press. All rights reserved
Friday, February 10, 2006
Bill's Pre-comment: Savannah, this one's for you.
Posted by William N. Phillips, Jr. at 2/10/2006 07:08:00 PM
Actor Who Played 'Jeffersons' Neighbor Dies
By Associated Press
4 hours ago
LOS ANGELES - Franklin Cover, who became a familiar face as George and Louise Jefferson's white neighbor in the long-running TV sitcom "The Jeffersons," has died, his publicist said Thursday. He was 77.
Cover died of pneumonia Sunday at the Lillian Booth Actor's Fund of America home in Englewood, N.J., said publicist Dale Olson. He had been living at the home since December 2005 while recuperating from a heart condition.
In his nearly six decades in show business, Cover made numerous appearances on television shows, including "The Jackie Gleason Show," "All in the Family," "Who's the Boss?" "Will & Grace," "Living Single," "Mad About You" and "ER."
He began his career on the stage, appearing in Shakespeare's "Hamlet" and "Henry IV," and later in numerous Broadway productions, including "Any Wednesday," "Wild Honey and "Born Yesterday."
But Cover was best known for his role as Tom Willis, who was in an interracial marriage with a black woman, in "The Jeffersons."
He and his wife lived in the same "deluxe apartment building" that Sherman Hemsley moved his family to after making money in the dry-cleaning business. There, Cover often played a comic foil to Hemsley's blustering, opinionated black businessman. The show ran from 1975 to 1985.
Cover also appeared in several films, including "The Great Gatsby," "The Stepford Wives" and "Wall Street."
He is survived by his widow, Mary, a son and a daughter.
Copyright 2006 The Associated Press. All rights reserved.
Posted by William N. Phillips, Jr. at 2/10/2006 06:22:00 PM
Barry Manilow's New Album Opens at No. 1
By Associated Press
Fri Feb 10, 9:29 AM
NEW YORK - Barry Manilow has landed on the top of the charts with a just-released album for the first time in 29 years. Manilow's "The Greatest Songs of the Fifties," debuted at No. 1 on the Billboard 200 chart, followed by Mary J. Blige's "The Breakthrough" and Andrea Bocelli's "Amore."
The album, 13 standards such as "Are You Lonesome Tonight?" and "Unchained Melody," has sold more than 156,000 copies in the United States since it arrived Jan. 31st.
His previous debut chart-topper was the 1977 concert recording, "Live." His last album, "Scores: Songs From Copacabana and Harmony," had a weak debut in 2004, peaking at No. 47.
Manilow, 62, said he was inspired to sing the 1950s pop classics because he feels they deserve more attention.
"The reason I connected with it is when I looked at the list of songs that came out of the '50s, it seemed to me that they had been neglected," he told Associated Press Television.
"Nobody seems to have done `Unchained Melody' or `It's Not for Me to Say' or `Beyond the Sea,' any of these songs that were wonderfully written that came out of the '50s. So that turned me on. I dove in."
Copyright 2006 The Associated Press. All rights reserved.
Posted by William N. Phillips, Jr. at 2/10/2006 06:18:00 PM
Tuesday, February 07, 2006
Diseases Treated with Stem Cells
Stem cell transplants have been used since the 1960’s to treat a variety of diseases. In 1988 cord blood stem cells were used for the first time in hematopoietic (blood) stem cell transplantation. Umbilical cord blood stem cells have now been used in over 3,500 transplants worldwide as a valuable alternative to traditional sources of hematopoietic stem cells. Utilizing the process of stem cell banking, cord blood stem cells also show great promise for potential future applications including treatment and repair of non-hematopoietic tissues, gene therapies, mini-transplants, among others.
Current Stem Cell Applications
Acute Lymphoblast Leukemia (ALL)
Acute Myelogenous Leukemia (AML)
Acute Biphenotypic Leukemia
Acute Undifferentiated Leukemia
Chronic Myelogenous Leukemia (CML)
Chronic Lymphocytic Leukemia (CLL)
Juvenile Chronic Myelogenous Leukemia (JCML)
Juvenile Myelomonocytic Leukemia (JMML)
Refractory Anemia (RA)
Refractory Anemia with Ringed Sideroblasts (RARS)
Refractory Anemia with Excess Blasts (RAEB)
Refractory Anemia with Excess Blasts in Transformation (RAEB-T)
Chronic Myelomonocytic Leukemia (CMML)
Stem Cell Disorders
Aplastic Anemia (Severe)
Paroxysmal Nocturnal Hemoglobinuria (PNH)
Pure Red Cell Aplasia
Agnogenic Myeloid Metaplasia (myelofibrosis)
Chronic Granulomatous Disease
Neutrophil Actin Deficiency
Other Inherited Disorders
Inherited Platelet Abnormalities
Amegakaryocytosis / Congenital Thrombocytopenia
Inherited Metabolic Disorders
Hurler's Syndrome (MPS-IH)
Scheie Syndrome (MPS-IS)
Hunter's Syndrome (MPS-II)
Sanfilippo Syndrome (MPS-III)
Morquio Syndrome (MPS-IV)
Maroteaux-Lamy Syndrome (MPS-VI)
Sly Syndrome, Beta-Glucuronidase Deficiency (MPS-VII)
Mucolipidosis II (I-cell Disease)
Familial Erythrophagocytic Lymphohistiocytosis
Inherited Erythrocyte Abnormalities
Beta Thalassemia Major
Sickle Cell Disease
Inherited Immune System Disorders
Leukocyte Adhesion Deficiency
Bare Lymphocyte Syndrome
Severe Combined Immunodeficiency (SCID)
SCID with Adenosine Deaminase Deficiency
Absence of T & B Cells SCID
Absence of T Cells, Normal B Cell SCID
Common Variable Immunodeficiency
X-Linked Lymphoproliferative Disorder
Plasma Cell Disorders
Plasma Cell Leukemia
Renal Cell Carcinoma
Potential Future Stem Cell Applications
Spinal Cord Injury
This list represents major categories of diseases treated with stem cells and is not exhaustive. For instance, there are over twenty (20) specific types of Non-Hodgkin’s Lymphoma and numerous types of Chronic Lymphocytic Leukemia, to name just two among many others.
Other cord blood banks include diseases such as breast cancer and testicular cancer. CorCell has chosen not to include these diseases as clinical data has demonstrated that these diseases are not effectively treated with stem cell transplantation.
CURRENT CLINICAL APPLICATIONS OF ADULT STEM CELLS
Combination of high-dose chemotherapy with stem cell transplant from the patients themselves shows good response in treatment of brain tumors.
Dunkel, IJ; “High-dose chemotherapy with autologous stem cell rescue for malignant brain tumors”; Cancer Invest. 18, 492-493; 2000.
“Patients with recurrent medulloblastoma had a significant improvement in long-term survival (median: 34 months) as compared with historical reports; two patients with glioblastoma survive beyond four years without progression.”
Abrey, LE et al.; “High dose chemotherapy with autologous stem cell rescue in adults with malignant primary brain tumors”; J. Neurooncol. 44, 147-153; Sept. 1999
“Review of HDCT and stem cell transplant for children with brain tumors. Studies demonstrating durable disease- free survival for a proportion of patients with recurrent malignant gliomas and medulloblastomas/PNET, as well as encouraging data in some of those patients with newly diagnosed brain tumors.”
Finlay, JL; “The role of high-dose chemotherapy and stem cell rescue in the treatment of malignant brain tumors: a reappraisal”; Pediatr. Transplant 3 Suppl. 1, 87-95; 1999
A localized retinoblastoma of the left eye in a 7-year-old girl, was treated by enucleation. She received no additional therapy. Four months later, metastases of retinoblastoma in the lymph nodes, bone and bone marrow were diagnosed. Relapse chemotherapy consisting of three courses of vincristine, cyclophosphamide, etoposide and carboplatin led to a second complete remission. Subsequent high-dose chemotherapy with thiotepa, etoposide and carboplatin and autologous stem cell transplantation with CD34-selected stem cells were successful, with no
adverse effects. No radiotherapy was given and the girl remains in continuous second
remission with a follow-up of more than 4 years.
Hertzberg H et al.; “Recurrent disseminated retinoblastoma in a 7-year-old girl treated successfully by high-dose chemotherapy and CD34-selected autologous peripheral blood stem cell transplantation”; Bone Marrow Transplant 27(6), 653-655; March 2001
Patients with metastatic retinoblastoma have a poor prognosis with conventional treatments. This study used intensive conventio nal chemotherapy, high-dose chemotherapy, with autologous stem cell rescue, and radiation therapy. The treatment strategy was effective for all four patients with metastatic retinoblatoma that does not involve the central nervous system, surviving event free from 46-80 months after diagnosis.
Dunkel IJ et al.; “Successful treatment of metastatic retinoblastoma”; Cancer 89, 2117-2121; Nov. 15, 2000
Report studying whether patients benefit more from autologous stem cell transplantation. “Some patients with ovarian cancer seem to have good outcomes after autotransplantation”.
Stiff PJ et al.; “High-dose chemotherapy and autologous stem-cell transplantation for ovarian cancer: An autologous blood and marrow transplant regis try report”; Ann. Intern. Med. 133, 504-515; Oct. 3, 2000
“Developing data suggest that this approach in both of these settings merit further evaluation for the treatment of epithelial ovarian carcinoma.” Used autologous, purified peripheral blood stem cells
Schilder, RJ and Shea, TC; “Multiple cycles of high-dose chemotherapy for ovarian cancer”; Semin. Oncol. 25, 349-355; June 1998
Use of patients’ own bone marrow or blood stem cells leads to long-term recovery from various types of solid tumors.
Nieboer P et al.; “Long-term haematological recovery following high-dose chemotherapy with autologous bone marrow transplantation or peripheral stem cell transplantation in patients with solid tumours”; Bone Marrow Transplant 27, 959-966; May 2001
Merkel cell carcinoma is a rare cutaneous tumor with neuroendocrine differentiation; there is no standard protocol for treatment of the metastatic disease. This study used high-dose chemotherapy and autologous peripheral blood stem cell transplantation to achieve complete remission that lasted for 6 months.
Waldmann V et al.; “Transient complete remission of metastasized merkel cell carcinoma by highdose polychemotherapy and autologous peripheral blood stem cell transpla ntation”; Br. J. Dermatol. 143, 837-839; Oct. 2000
Patients with metastatic or locally advanced, unresectable soft tissue sarcoma are seldom curable, with 5- year survival rates of less than 10%. Used high-dose chemotherapy with autologous hematopoietic stem cell transplant; “a high survival rate was observed in HDCT-treated patients who were in complete remission after conventional chemotherapy.”
Blay JY et al.; “High-dose chemotherapy with autologous hematopoietic stem-cell transplantation for advanced soft tissue sarcoma in adults”; J. Clin. Oncol. 18, 3643-3650; Nov. 1, 2000
“The prognosis of metastatic malignant mesenchymal tumors (MMT) remains poor.” Used high-dose chemotherapy with bone marrow or peripheral blood stem cell transplant. “A response exceeding 50% was observed in 6/18 patients (response rate 33%).”
Lafay-Cousin L et al.; “High-dose thiotepa and hematopoietic stem cell transplantation in pediatricmalignant mesenchymal tumors: a phase II study”; Bone Marrow Transplant 26, 627-632; Sept. 2000
High-dose chemotherapy followed by autologous haematopoietic rescue is widely used in the treatment of patients with paediatric malignancies. It is now well established as a major component for the treatment of children with metastatic neuroblastoma over the age of one at diagnosis. Its place for other tumours, such as metastatic Ewing and rhabdomyosarcoma, needs to be better established.”
Michon, J and Schleiermacher, G. “Autologous haematopoietic stem cell transplantation for paediatric solid tumors”, Baillieres Best Practice Research in Clinical Haematology 12, 247-259, March-June 1999.
Used for malignant solid tumors. Overall response rate 96%, complete clinical response rate 67%. Treatment described as safe, feasible, and active.
Schilder, RJ et al.; “Phase I trial of multiple cycles of high-dose chemotherapy supported by autologous peripheral-blood stem cells”; J. Clin. Oncol. 17, 2198-2207; July 1999
“Thirty-seven (57%) of the 65 patients are continuously disease- free. Three additional patients are disease- free with subsequent surgery. High-dose chemotherapy was associated with significant morbidity but no treatment-related mortality. High-dose chemotherapy as initial salvage chemotherapy achieved impressive long-term survival with acceptable toxicity in patients with relapsed testicular cancer.”
Bhatia S et al.; “High-dose chemotherapy as initial salvage chemotherapy in patients with relapsed testicular cancer”; J. Clin. Oncol. 18, 3346-3351; Oct. 19, 2000
“High-dose chemotherapy with the transplantation of peripheral blood stem cells (PBSC) has been performed for the treatment of advanced testicular cancer patients.” “After mobilization of peripheral blood stem cells with G-CSF alone, sufficient amounts of MNC were obtained from testicular cancer patients who had undergone chemotherapy several times.”
Hanazawa, K et al.; “Collection of peripheral blood stem cells with granulocyte-colony-stimulating factor alone in testicular cancer patients”; Int. J. Urol. 7, 77-82; March 2000.
MULTIPLE MYELOMA, LEUKEMIAS
Umbilical Cord Blood Effective At Treating Adult Blood Disorders
A new report shows that umbilical cord blood can provide effective treatment of various blood disorders in adults. It had previously been assumed that there were too few stem cells in cord blood to treat adults, and only children were treated. The results of this study show that cord blood stem cells can proliferate extensively and provide sufficient numbers of cells for adult treatments.
Laughlin MJ et al.; “Hematopoietic engraftment and survival in adult recipients of umbilical-cord blood from unrelated donors”, New England Journal of Medicine 344, 1815-1822; June 14, 2001
Bone marrow/peripheral blood stem cell treatments can be used to treat older patients
Tabata M et al.; “Peripheral blood stem cell transplantation in patients over 65 years old with malignant lymphoma--possibility of early completion of chemotherapy and improvement of performance status”; Intern Med 40, 471-474; June 2001
Successfully treated lymphoma using patient’s own stem cells.
Koizumi M et al.; “Successful treatment of intravascular malignant lymphomatosis with high-dose chemotherapy and autologous peripheral blood stem cell transplantation”; Bone Marrow Transplant 27, 1101-1103; May 2001
This retrospective study included 21 children with acute lymphoblastic leukaemia, 15 with acute myelogenous leukaemia and one each with chronic myelogenous leukaemia, refractory anaemia with myelodysplastic syndrome (MDS) and juvenile myelomonocytic leukaemia (JMML). These data confirm that HLA-mismatched, unrelated Cord Blood Transplant is a feasible procedure to cure a significant proportion of children with leukaemia, especially if conducted in a favourable phase of the disease.
Ohnuma K et al.; “Cord blood transplantation from HLA- mismatched unrelated donors as a treatment for children with haematological malignancies”; Br J Haematol 112(4), 981-987; March 2001
Angioimmunoblastic lymphadenopathy with dysproteinemia (or dysgammaglobulinemia) (AILD) is a lymphoproliferative disorder with abnormalities characteristic of malignant T-cell lymphoma (angioimmunoblastic T-cell lymphoma -- AITL). We report the clinical course of a 58-year-old male patient with unusually aggressive AILD, At relapse, treatment with high-dose chemotherapy followed by autologous peripheral stem cell transplantation (APSCT) with CD34 selected cells was shown to be successful. The patient is alive and disease-free 3 years after diagnosis and 32 months after APSCT. Considering the poor prognosis of the majority of patients with AILD, intensive treatment followed by APSCT, may be a subject for further studies.
Lindahl J et al.; “High-dose chemotherapy and APSCT as a potential cure for relapsing hemolysing AILD”; Leuk Res 25(3), 267-270; March 2001
Patients given high-dose chemotherapy followed by allogeneic stem cell transplants. Peripheral blood stem cells rather than bone marrow results in higher rates of overall and disease- free survival, and restores blood counts faster. Patients in whom the benefit of peripheral-blood cells was most apparent were those with advanced hematologic cancer. Other studies have also shown that the use of peripheral-blood cells is associated with fewer days of hospitalization and lower overall costs.
Bensinger WI et al.; “Transplantation of bone marrow as compared with peripheral-blood cells from HLA- identical relatives in patients with hematologic cancers”; New England Journal of Medicine 344, 175-181; Jan. 18, 2001
**Review of new procedures involving stem cell transplantation. The authors note that “Stem cell transplantation has been successfully used to treat a wide variety of hematologic malignancies. New and exciting strategies being developed for use in conjunction with transplant will be useful in overcoming tumor resistance.”
Margolis J et al.; “New approaches to treating malignances with stem cell transplantation”; Semin. Oncol. 27, 524-530; Oct. 2000
**Study notes that “autologous stem cell transplantation is a potential therapeutic approach in patients with acute myelocytic leukemia over 60 years of age.”
Gorin NC et al.; “Feasibility and recent improvement of autologous stem cell transplantation for acute myelocytic leukaemia in patients over 60 years of age: importance of the source of stem cells”; Br. J. Haematol. 110, 887-893; Sept. 2000
“Infants with acute leukemia have a poor prognosis when treated with conventional chemotherapy.” 5-year overall survival 64%. “SCT is a valid option in the treatment of infant acute leukemia, and it may overcome the high risk of relapse with conventional chemotherapy showing very reduced toxicity.”
Marco F et al.; “High Survival Rate in Infant Acute Leukemia Treated With Early High-Dose Chemotherapy and Stem-Cell Support”; J Clin Oncol 18, 3256-3261; Sept. 15, 2000
“Actuarial survival and disease-free survival at 34 months are 56% and 50% respectively, with 95% confidence interval (25-78%).These results suggest that nonmyeloablative conditioning significantly reduces transplant-related toxicity, thus making a second transplant feasible.”
Nagler A et al.; “Second allogeneic stem cell transplantation using nonmyeloablative conditioning for patients who relapsed or developed secondary malignancies following autologous transplantation”; Exp. Hematol. 28, 1096-1104, Sept. 1, 2000
Review of autologous stem cell treatment strategies. “Controlled clinical trials have demonstrated a long-term disease- free survival of 40%-50% for patients treated with at least two courses of HIDAC. Other studies have demonstrated that postremission autologous bone marrow transplantation results in a disease-free survival equal to or better than conventional chemotherapy. However, autotransplantation with mobilized peripheral blood stem cells (PBSC) would now be preferred instead of autologous bone marrow, due to the shorter hematopoietic reconstitution period.”
Bruserud O et al.; “New strategies in the treatment of acute myelogenous leukemia: mobilization and transplantation of autologous peripheral blood stem cells in adult patients”; Stem Cells 18, 343-351; 2000
Study to evaluate high-dose melphalan followed by autologous stem-cell transplantation in patients with refractory multiple myeloma. High-dose therapy with melphalan 200 mg/m(2) is feasible with high response rates (58% overall) and an OS of 19 months in patients with refractory multiple myeloma.”
Vesole, DH et al.; “High-Dose Melphalan With Autotransplantation for Refractory Multiple Myeloma: Results of a Southwest Oncology Group Phase II Trial”; J Clin Oncol 17, 2173-2179; July 1999.
The “data suggest that high-dose chemotherapy with hematopoietic stem cell rescue is safe and can be beneficial to patients with high-risk primary breast cancer and for those with metastatic breast cancer achieving complete response/no evidence of disease.”
Damon LE et al.; “High-dose chemotherapy and hematopoietic stem cell rescue for breast cancer: experience in California”; Biol. Blood Marrow Transplant 6, 496-505; 2000
Stem cells in circulating blood can be isolated, expanded in number in culture, and provide better clinical results.
Paquette, RL et al., “Ex vivo expanded unselected peripheral blood: progenitor cells reduce posttransplantation neutropenia, thrombocytopenia, and anemia in patients with breast cancer”, Blood 96, 2385-2390; October 2000.
“The collection of small aliquots of bone marrow (BM), followed by ex vivo expansion for autologous transplantation may be less morbid, and more cost-effective, than typical BM or blood stem cell harvesting. Passive elimination of contaminating tumor cells during expansion could reduce reinoculation risks.” “It is feasible to perform autotransplants solely with BM cells grown ex vivo in perfusion bioreactors from a small aliquot.” “This procedure could reduce the risk of tumor cell reinoculation with autotransplants and may be valuable in settings in which small stem cell doses are available, eg, cord blood transplants.”
Stiff P et al.; “Autologous transplantation of ex vivo expanded bone marrow cells grown from small aliquots after high-dose chemotherapy for breast cancer”; Blood 95, 2169-2174; March 15, 2000
“This report is the first describing infusion of autologous MSCs with therapeutic intent. We found that autologous MSC infusion at the time of PBPC transplantation is feasible and safe. The observed rapid hematopoietic recovery suggests that MSC infusion after myeloablative therapy may have a positive impact on hematopoiesis and should be tested in randomized trials.”
Koc, ON et al.; “Rapid Hematopoietic Recovery After Coinfusion of Autologous-Blood Stem Cells and Culture-Expanded Marrow Mesenchymal Stem Cells in Advanced Breast Cancer Patients Receiving High-Dose Chemotherapy”; J Clin Oncol 18, 307-316; January 2000
“According to initial reports, stage 4 neuroblastoma patients with amplification of the MYCN protooncogene developed progressive disease within 8 months. The prognosis for such patients, however, should now be reevaluated in light of recent results achieved with up-to-date combination chemotherapy. Not all patients with advanced neuroblastoma who have more than 10 copies of MYCN will die. The requisites for survival in such patients seem to be intensive induction chemotherapy, effective surgery, irradiation, and the use of SCT” (stem cell transplant).
Kawa, K et al.; “Long-Term Survivors of Advanced Neuroblastoma With MYCN Amplification: A Report of 19 Patients Surviving Disease-Free for More Than 66 Months”; J Clin Oncol 17:3216-3220; October 1999
Tabata M et al.; “Peripheral blood stem cell transplantation in patients over 65 years old with malignant lymphoma--possibility of early completion of chemotherapy and improvement of performance status”; Intern Med 40, 471-474; June 2001
“To determine differences in prognosis between primary progressive Hodgkin's disease (HD) and aggressive non-Hodgkin's lymphoma (NHL), we retrospectively analyzed patients with progressive lymphoma who were treated with different salvage chemotherapy regimens including high-dose chemotherapy (HDCT) followed by autologous stem-cell support (ASCT). There are striking differences in the prognosis of patients with progressive HD and aggressive NHL. The prognosis of progressive NHL patients is dismal. Most patients have rapidly progressive disease after salvage treatment and are, therefore, excluded from HDCT programs. In contrast, progressive HD patients can achieve long-term survival after HDCT.”
Josting, A; “Treatment of Primary Progressive Hodgkin’s and Aggressive Non-Hodgkin’s
Lymphoma: Is There a Chance for Cure?”; J Clin Oncol 18, 332-339; 2000
“Patient achieved complete remission and has survived in continuous complete remission for more than 72 months to date. Marrow-ablative chemotherapy facilitated by PBSCT is thought to be useful as part of the primary therapy for patients with NHL who have poorer prognoses.”
Kirita T et al.; “Primary non-Hodgkin’s lymphoma of the mandible treated with radiotherapy, chemotherapy, and autologous peripheral blood stem cell transplantation”; Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 90, 450-455; Oct. 2000
“These results suggest first that ex vivo expansion of hematopoietic stem cells in patients with non-Hodgkin's lymphoma is feasible without incurring the parallel risk of amplifying tumor cells; second, that Flt3-L did not stimulate the growth of tumor cells while it clearly favored the growth of normal progenitors.”
Yao M et al.; “Ex vivo expansion of CD34-positive peripheral blood progenitor cells from patients with non-Hodgkin’s lymphoma: no evidence of concomitant expansion of contaminating bcl2/JH-positive lymphoma cells”; Bone Marrow Transplant 26, 497-503; Sept. 2000
“Nonmyeloablative allogeneic stem-cell transplantation can induce sustained regression of metastatic renal-cell carcinoma in patients who have had no response to conventional immunotherapy.”
Childs R et al., “Regression of Metastatic Renal-Cell Carcinoma after Nonmyeloablative Allogeneic Peripheral-Blood Stem-Cell Transplantation”, New England Journal of Medicine 343, 750-758; Sept. 14, 2000
“The complete regression of metastatic disease, which has now been maintained for more than 1 year, is compatible with a graft-versus-tumor effect.”
Childs, RW; “Successful Treatment of Metastatic Renal Cell Carcinoma With a Nonmyeloablative Allogeneic Peripheral-Blood Progenitor-Cell Transplant: Evidence for a Graft-Versus-Tumor Effect:; J Clin Oncol 17, 2044-2049; July 1999
–multiple sclerosis, systemic lupus erythematosus, juvenile rheumatoid
arthritis, rheumatoid arthritis
Adult Stem Cells Treat Potentially Fatal Skin Disorder
A man with scleromyxedema, a rare and potentially fatal skin disease, is reported free of symptoms after receiving a transplant of adult stem cells taken from his own bone marrow. Like scleroderma, scleromyxedema causes the skin to thicken and become hard. Prior to the adult stem cell treatment, the patient could not completely close his eyes, and had lost the ability to eat. Three months after treatment the patient could once again close his eyes and open his mouth to eat. The results are reported in the August issue of Archives of Dermatology.
A.M. Feasel et al., "Complete remission of scleromyxedema following autologous stem cell transplantation," Archives of Dermatology 137, 1071-1072; Aug. 2001."Stem Cell Transplant Treats Rare Skin Disorder," Reuters Health, August 17, 2001
Patients’ own stem cells to treat severe multiple sclerosis
Use of combined therapy with using a patient’s own stem cells for treatment of severe cases of multiple sclerosis. Treatment decreased tissue damage in the patients, and had the capacity to completely suppress further tissue damage, an effect that is sustained with time.
Mancardi GL et al.; “Autologous hematopoietic stem cell transplantation suppresses Gd-enhanced MRI activity in MS”; Neurology 57, 62-68; July 10, 2001
Adult Stem Cells Show Success in Treating Another Autoimmune Disease—Crohn’s Disease
Physicians at Chicago's Northwestern Memorial Hospital report initial success in using adult stem cells to treat two patients with Crohn's disease, a potentially disabling inflammatory bowel disease. One patient was said to be doing "phenomenally well" 2 ½ months after undergoing the procedure using the adult stem cells, which were extracted from her blood, leading doctors to try it on a second patient. Results in both patients were very encouraging, according to Dr. Richard Burt, who performed the procedures. Burt noted that results of similar procedures on multiple sclerosis patients have also shown progress, and that adult stem cell therapy on patients with lupus had repaired damage to their organs. According to Burt: " 'If you're able to use your own stem cells,' the embryonic stem cell issue is 'not just ethically moot, it's practically moot.' "
"Adult Stem Cells Hold Hope for Autoimmune Patients," Reuters Health, Aug. 13, 2001.
High-dose chemotherapy followed by autologous HSCT is feasible and safe, and can result in longterm improvement of disease activity in patients whose condition previously did not respond to conventional antirheumatic drugs or TNF blocking agents. The persistence of active disease in some patients may reflect the heterogeneity of the underlying disease process.
Verburg RJ et al.; “High-dose chemotherapy and autologous hematopoietic stem cell transplantation in patients with rheumatoid arthritis: results of an open study to assess feasibility, safety, and efficacy”; Arthritis Rheum 44(4), 754-760; April 2001
Wulffraat NM et al.; “Prolonged remission without treatment after autologous stem cell transplantation for refractory childhood systemic lupus erythematosus”; Arthritis Rheum 44(3), 728-731; March 2001
“Autoimmune diseases that are resistant to conventional treatment cause severe morbidity and even mortality. In the present study we demonstrate that complete remissions can be achieved in refractory polychondritis and systemic lupus erythematosus (SLE), even at advanced stage, with the use of autologous stem-cell transplantation (SCT). Remissions persisted after reconstitution of the immune system. In the treatment of advanced systemic sclerosis (SSc), stable disease may be achieved with autologous SCT.”
Rosen O et al.; “Autologous stem-cell transplantation in refractory autoimmune diseases after in vivo immunoablation and ex vivo depletion of mononuclear cells”; Arthritis res. 2, 327-336; 2000
Nineteen patients (14 female, 5 male) with severe autoimmune diseases were treated. Nine had a rheumatologic disorder (5 juvenile chronic arthritis, 1 rheumatoid arthritis, 1 systemic vasculitis, 1 Sjogren's syndrome, 1 Behct's disease), 4 a neurologic disorder (3 multiple sclerosis, 1 myasthenia), 3 a haematologic disease (2 pure red cell aplasia, 1 autoimmune thrombocytopenia), 2 had a gastrointestinal disease (1 Crohn's disease, 1 autoimmune enteropathy) and 1 had a multiple autoimmune disorder. There was no regimen-related toxicity and no opportunistic infections occurred. Ninety percent of the patients improved and/or had a complete remission after the procedure. Fifty percent of the subjects went into complete or partial remission after a median follow-up of 15 months. A non- myeloablative conditioning regimen was able to induce persistent remission in some patients with severe autoimmune diseases. There was no mortality or morbidity related to the procedure. The extent of remission remains to be established.
Rabusin M et al.; “Immunoablation followed by autologous hematopoietic stem cell infusion for the treatment of severe autoimmune disease”; Haematologica 85(11 Suppl), 81-85; Nov. 2000
Study that supports the concept that patients with autoimmune cytopenias with severe resistant disease might be appropriate candidates for autologous stem cell transplantation.
Papadaki HA et al.; “Assessment of bone marrow stem cell reserve and function and stromal cell function in patients with autoimmune cytopenias”; Blood 96, 3272-3275; Nov. 1, 2000
Patients (including several children) with severe lupus were treated with their own bone marrow stem cells, and had relief of symptoms, with little or no need for medication after treatment.
Traynor AE et al.; “Treatment of severe systemic lupus erythematosus with high-dose chemotherapy and haemopoietic stem-cell transplantation: a phase I study”; Lancet 356, 701-707; August 26, 2000
Numerous studies showing efficacy of adult stem cell transplants in the successful treatment of autoimmune diseases.
Burt, RK and Traynor, AE; “Hematopoietic Stem Cell Transplantation: A New Therapy for
Autoimmune Disease”; Stem Cells17, 366-372; 1999
Overview—juvenile rheumatoid arthritis; multiple sclerosis; rheumatoid arthritis; systemic lupus erythematosus.
Burt RK et al.; “Hematopoietic stem cell transplantation of multiple sclerosis, rheumatoid arthritis, and systemic lupus erythematosus”; Cancer Treat. Res. 101, 157-184; 1999
Traynor A and Burt RK; “Haematopoietic stem cell transplantation for active systemic lupus erythematosus”; Rheumatology 38, 767-772; August 1999
Martini A et al.; “Marked and sustained improvement 2 years after autologous stem cell transplant in a girl with system sclerosis”; Rheumatology 38, 773; August 1999
Hawkey CJ et al.; “Stem cell transplantation for inflammatory bowel disease: practical and ethical
issues”; Gut 46, 869-872; June 2000
Burt, RK et al., “Autologous hematopoietic stem cell transplantation in refractory rheumatoid
arthritis: sustained response in two of four patients”, Arthritis & Rheumatology 42, 2281-2285, November 1999.
Burt, R.K. et al., “Gene-marked autologous hematopoietic stem cell transplantation of autoimmune disease”, Journal of Clinical Immunology 20, 1-9; January 2000.
Follow- up study from previous transplant shows improved local cellular function or engraftment of implanted adult stem cell line in some stroke patients.
Meltzer CC et al.; “Serial [18F]Fluorodeoxyglucose Positron Emission Tomography after
Human Neuronal Implantation for Stroke”; Neurosurgery 49, 586-592; 2001.
A cultured stem cell line (originally derived from an adult tumor; a “teratocarcinoma”, sometimes called an “embryonal carcinoma” because it mimics some of the characteristics of embryonic cells.) The cultured and adapted cell line was used in successful treatment of several stroke patients.
Kondziolka D et al.; “Transplantation of cultured human neuronal cells for patients with stroke”; Neurology 55, 565-569; August 2000
Banked unrelated umbilical cord blood was used to reconstitute the immune system in 2 brothers with X-linked lymphoproliferative syndrome and 1 boy with X-linked hyperimmunoglobulin-M syndrome. Two years after transplantation, all 3 patients have normal immune systems. These reports support the wider use of banked partially matched cord blood for transplantation in primary immunodeficiencies.
Ziegner UH et al.; “Unrelated umbilical cord stem cell transplantation for X- linked
immunodeficiencies”; J Pediatr 138(4), 570-573; April 2001
Eight children with severe immunodeficiencies treated by adult bone marrow stem cell
transplants. Six of 8 showed relatively normal immune systems after 1 year.
Amrolia, P. et al., “Nonmyeloablative stem cell transplantation for congenital
immunodeficiencies”, Blood 96, 1239-1246, Aug. 15, 2000.
Successful treatment of sickle cell anemia using umbilical cord blood stem cells
Used sibling cord blood stem cells.
Gore L. et al.; “Successful cord blood transplantation for sickle cell anemia from a sibling who is human leukocyte antigen- identical: implications for comprehensive care”, J Pediatr Hematol Oncol 22(5):437-440; Sep-Oct 2000
Inherited anemia treated using donor bone marrow stem cell transplant.
Ayas M et al.; “Congenital sideroblastic anaemia successfully treated using allogeneic stem cell transplantation”; Br J Haematol 113, 938-939; June 2001
Anagnostopoulos A et al.; “High-dose chemotherapy followed by stem cell transplantation in patients with resistant Waldenstrom's macroglobulinemia”; Bone Marrow Transplant 27, 1027-1029; May 2001
Allogeneic peripheral blood stem cell transplantation (PBSCT) is rarely applied for the treatment of severe aplastic anemia (SAA) because of questionable durability of engraftment and increased risk of graft versus host disease (GVHD). We performed allogeneic PBSCT in 3 SAA patients from their human leukocyte antigen (HLA)- identical siblings. In 2 cases, no graft failure has been observed, and a successful and complete hematological recovery was achieved and maintained for 28 and 25 months, respectively. In conclusion, PBSCT provides a quick and complete hematological recovery in SAA patients.
Gurman G et al.; “Allogeneic peripheral blood stem cell transplantation for severe aplastic anemia”; Ther Apher 5(1), 54-57; Feb. 2001
Results suggest that treatment can reverse progression of vasculopathy. Bone marrow
transplantation may enable stenoses to heal and can substantially reduce cranial blood velocity, suggesting that allogeneic bone marrow transplantation may prevent infarction or brain damage.
Steen RG et al.; “Improved cerebrovascular patency following therapy in patients with sickle cell disease: initial results in 4 patients who received HLA- identical hematopoietic stem cell allografts”; Ann Neurol 49(2), 222-229; Feb. 2001
Able to treat severe anemias using transplants of adult bone marrow stem cells.
References Gonzalez MI et al.; “Allogeneic peripheral stem cell transplantation in a case of hereditary sideroblastic anaemia”; British Journal of Haematology 109, 658-660; 2000 Kook H et al.; “Rubella-associated aplastic anemia treated by syngeneic stem cell transplantations”; Am. J. Hematol. 64, 303-305; August 2000
Possibility of using adult stem cell transplantation as cure for sickle cell anemia.
Wethers DL; “Sickle cell disease in childhood: Part II. Diagnosis and treatment of major complications and recent advances in treatment”; Am. Fam. Physician 62, 1309-1314; Sept. 15, 2000
Successful treatment of a congenital thrombocytopenia using allogeneic peripheral blood stem cell transplantation.
Yesilipek et al.; “Peripheral stem cell transplantation in a child with amegakaryocytic thrombocytopenia”; Bone Marrow Transplant 26, 571-572; Sept. 2000
Chronic Viral Infection With Complications
Fujii N et al.; “Allogeneic peripheral blood stem cell transplantation for the treatment of chronic active epstein-barr virus infection”; Bone Marrow Transplant 26, 805-808; Oct. 2000
Okamura T et al.; “Blood stem-cell transplantation for chronic active Epstein- Barr virus with lymphoproliferation”; Lancet 356, 223-224; July 2000
Cartilage and Bone Diseases
Biopsies removed from 57 patients considered for cartilage transplantation were grown. Explant cultures allowed cell number expansion. Fifty- four out of 57 biopsies grew cells. Fanning out of the cells began after 5-15 days in culture. Two passages later, cell numbers in the 10(7) range were achieved. Explants of articular chondrocytes cultured in vitro consistently yield monolayer cultures. The cells appear to revert to dedifferentiated chondrocytes, expressing a mesenchymal stem cell protein profile. Simultaneously, these cells regained their capacity to proliferate.
Robinson D et al.; “Characteristics of cartilage biopsies used for autologous chondrocytes transplantation”; Cell Transplant 10(2), 203-208; 2001 Mar-Apr
Horwitz, EM et al.; “Transplantability and therapeutic effects of bone marrow-derived
mesenchymal cells in children with osteogenesis imperfecta”; Nat. Med. 5, 309-313;
Confluent sheets of cultured corneal epithelial cells, suitable for grafting, can be produced from limbal tissue taken from eye bank organ-cultured corneas, although it takes longer, on average, to reach confluence (17–21 days) than an equivalent sample from a fresh eye (9–12 days).
James SE et al.; “The Potential for Eye Bank Limbal Rings to Generate Cultured Corneal Epithelial Allografts”; Cornea 20, 488-494; July 2001
Fifteen of 16 eyes (93.7%) achieved epithelialization with a mean time to epithelial healing of 15.2 days. The only eye that failed to heal was subsequently diagnosed with total limbal stem cell deficiency. Visual acuity improved in five of nine (44%) sighted eyes. No patient experienced any major surgical or medical complication after the procedure. Amniotic membrane transplantation represents a safe and effective method to restore a stable corneal epithelium in eyes after primary surgical removal of band keratopathy arising from ocular causes.
Anderson DF et al.; “Amniotic Membrane Transplantation After the Primary Surgical
Management of Band Keratopathy”; Cornea 20(4), 354-361; May 2001
Amniotic membrane transplantation appears to be a safe and effective method of restoring a stable corneal epithelium for cases of partial limbal stem cell deficiency and can be considered as an alternative to limbal autograft or allograft. 17 eyes of 15 patients; All eyes exhibited a stable, intact corneal epithelial surface after a mean follow up period of 25.8 months with no eyes developing recurrent erosion or persistent epithelial defect. The mean time to re-epithelialisation was 22.8 days. Overall improvement in visual acuity was observed in 92.9% of 14 eyes with visual potential.
Anderson DF et al.; “Amniotic membrane transplantation for partial limbal stem cell
deficiency”; Br J Ophthalmol 85(5), 567-575; May 2001
An objective long term benefit from the procedure (improved Snellen acuity, reduced frequency of epithelial defects, reduced vascularisation, and scarring) was recorded for four out of five patients. Some subjective benefit was also reported. However, in no instances were donor cells recovered from the ocular surface at 3-5 years post-graft. Initial experiments to examine sensitivity indicated that any surviving donor cells must have constituted less than 2.5% of cells sampled. Limbal stem cell allotransplantation can provide long term benefits, as measured by objective criteria. However, such benefits do not necessarily correlate with survival of
measurable numbers of donor cells on the ocular surface.
Henderson TR et al.; “The long term outcome of limbal allografts: the search for surviving cells”; Br J Ophthalmol 85(5), 604-609; May 2001
Adult stem cells from relatives used to restore vision
Nine living related donors, 8 recipients (10 eyes, various conditions). Restoration of corneal epithelium, opacification reduced, visual improvement; 2 initial failures.
Daya SM, Ilari FA; “Living related conjuctival limbal allograft for the treatment of stem cell deficiency”; Opthalmology 180, 126-133; January 2001
Adult Stem Cells Used to Grow New Corneas
Researchers in the United States and Taiwan have used corneal adult stem cells to grow new corneas for patients with previously untreatable eye damage. Adult stem cells were taken from the patients themselves in 16 cases, or a family member for 4 other patients. The cells were then grown in culture before transplantation onto the damaged eyes. Sixteen of the 20 patients had improved vision. Dr. Ivan Schwab, professor of ophthalmology at the University of California at Davis Medical School, leader of the U.S. team, said “We think this is the beginning of a very exciting change in terms of how we manage surface disease of many kinds, not just in the eye.”
Schwab IR et al.; “Successful transplantation of bioengineered tissue replacements in patients with ocular surface disease”; Cornea 19, 421-426; July 2000.
Tsai et al.; “Reconstruction of damaged corneas by transplantation of autologous limbal epithelial cells.”; New England Journal of Medicine 343, 86-93, 2000.
Tsubota K et al.; “Treatment of severe ocular-surface disorders with corneal epithelial stem-cell transplantation”; New England Journal of Medicine 340, 1697-1703; June 3, 1999
BLOOD AND LIVER DISEASE
Stem Cell- Rich Cord Blood Successfully Treats Often Fatal Blood Disorder
In a joint statement, doctors at Singapore's National Hospital and Singapore General Hospital announced a "medical first" in transplanting umbilical cord blood from a non-related donor to successfully treat thalassaemia. Thalassaemia is a hereditary blood disorder that often causes severe anemia and is usually fatal to children if untreated. The statement noted that umbilical cord blood is rich in "haemopoietic stem cells" from which the different types of blood cells evolve.
"SCH scores another first in stem cell transplants," Singapore General Hospital,
"Singapore scores medical first in treatment of thalassaemia," Agence France Presse, Aug. 14, 2001
4-month-old girl received stem cell transplant after receiving living-related liver transplant from same donor (mother). Four months after stem cell transplant the patient was disease-free, complete donor chimerism in bone marrow and stable hepatic function without any immunosuppressive therapy.
Matthes-Martin S et al.; “Successful stem cell transplantation following orthotopic liver transplantation from the same haploidentical family donor in a girl with hemophagocytic lymphohistiocytosis”; Blood 96, 3997-3999; Dec 1, 2000
Primary amyloidosis is a plasma cell disorder in which deposits of amyloid protein cause progressive organ failure; most common target is the kidney, although heart, liver, and nervous tissue effects are also seen. Compared to standard treatments, high-dose chemotherapy with autologous peripheral blood stem cell transplantation is shown to be much more effective in the clinical condition of patients.
Sezer O et al.; “Novel approaches to the treatment of primary amyloidosis”; Exper Opin. Investig. Drugs 9, 2343-2350; Oct. 2000
*First successful trial of human therapy, re- injecting the infants’ own bone marrow stem cells containing a normal copy of the gene that they lacked.
Cavazzana-Calvo M et al.; “Gene therapy of human severe combined immunodeficiency
(SCID)-X1 disease”; Science 288, 669-672; April 28, 2000
Successful treatment of heart disease using adult stem cells
Doctors in Germany reported the successful use of a patient’s own adult stem cells from bone marrow for regenerating tissue damaged after a heart attack. They injected the man’s own bone marrow stem cells into his damaged heart muscle. Ten weeks after treatment, the damaged area of heart tissue had been reduced, replaced by new cells, and the function of the patient’s heart had increased by 20-30 %. The authors note that their results demonstrate that “transplantation of human autologous adult stem cells is possible under clinical conditions and that it can lead to regeneration of the myocardial scar after… infarction.” They also point out that the therapeutic
benefits can be ascribed to the adult stem cells. They plan to perform the same operation on 20 more patients in the coming months. The use of the patient’s own adult stem cells from bone marrow or muscle to treat damage from heart attack is also in clinical trials in France and the U.S. (Reuters Health, July 23, 2001)
Strauer BE et al.; “Myocardial regeneration after intracoronary transplantation of human autologous stem cells following acute myocardial infarction”; Dtsch Med Wochenschr 126, 932-938; Aug 24, 2001
First successful human stem cell treatment for heart disease uses adult stem cells
The first reports of successful treatment for heart disease using the patient’s own adult muscle stem cells are encouraging news regarding therapy after heart attack. French physicians implanted skeletal muscle stem cells back into the patient; the encouraging result after eight months’ follow- up underlines the potential of this new approach using adult stem cells. Further clinical trials are now underway in Europe and the U.S. for other patients with heart disease. No embryonic stem cells have ever been reported to be used in human trials. A review of potential heart treatments notes that cell transplantation is a potential therapeutic approach for patients with chronic heart failure. Experimental transplantation of muscle cells showed that the grafted cells can functionally integrate with and augment the function of the recipient heart. The scientists note that skeletal stem cells are abundant and can be grafted successfully into the animal’s own heart even after genetic manipulation in vitro.
Menasché P et al. “Myoblast transplantation for heart failure.” Lancet 357, 279-280; Jan 27, 2001
Menasché P et al. [“Autologous skeletal myoblast transplantation for cardiac insufficiency. First
clinical case.”] [article in French] Arch Mal Coeur Vaiss 94(3), 180-182; March 2001
“Doctor Puts Arm Muscle Cells Into Patient's Heart”, Associated Press, May 30, 2001
“First Percutaneous Endovascular Case of Heart Muscle Regeneration Completed with
Bioheart's MyoCell(TM) Product”, PRNewswire, May 30, 2001.
El Oakley RM et al.; “Myocyte transplantation for cardiac repair: A few good cells can mend a broken heart”; Annals of Thoracic Surgery 71, 1724 –1733; 2001
General References Related to Clinical Uses of Adult Stem Cells
Recent studies have revealed that much of this remarkable developmental potential of embryonic stem cells is retained by small populations of cells within most tissues in the adult. Intercellular signals that control the proliferation, differentiation and survival of stem cells are being identified and include a diverse array of growth factors, cytokines and cell adhesion molecules. Intracellular mechanisms that regulate stem cell fate are also emerging and include established second messenger pathways, novel transcription factors and telomerase. The possibility that a decline in the numbers or plasticity of stem cell populations contributes to aging and age-related disease is suggested by recent findings. The remarkable plasticity of stem cells suggests that endogenous or transplanted stem cells can be 'tweaked' in ways that will allow them to replace lost or dysfunctional cell populations in diseases ranging from neurodegenerative and hematopoietic disorders to diabetes and cardiovascular disease.
Rao MS and Mattson MP; “Stem cells and aging: expanding the possibilities”; Mech Ageing Dev 122(7), 713-734; May 31, 2001
Mesenchymal stem cells (MSCs) are the first non-hematopoietic progenitors to be isolated from the bone marrow and extensively characterized. In addition to their ability to support hematopoiesis, MSCs can differentiate into osteocytes, chondrocytes, tenocytes, adipocytes and smooth muscle cells. This article will review our current understanding of bone marrow stroma and MSCs and their potential therapeutic role in the setting of hematopoietic stem cell transplantation.
Koc ON and Lazarus HM; “Mesenchymal stem cells: heading into the clinic”; Bone Marrow
Transplant 27(3), 235-239; Feb. 2001
It appears that basal haematopoiesis is maintained throughout life, yet, the capacity to cope with haematological stress is decreased in advanced age. In principle, stem cells derived from aged donors can be used for autologous transplantation, when needed to recover basic haematopoiesis. Current methods for expansion and maintenance of stem cells in vitro enable examination of stem cell potential for long-term expansion and function. Understanding of the mechanisms underlying these processes will enable the fidelity of stem cell expansion and maintenance of their potential for long-term function.
Globerson A; “Haematopoietic stem cell ageing”; Novartis Found Symp 235, 85-96; discussion 96-100, 101-4; 2001
This study examined whether cryopreservation following expansion has a detrimental effect on the ability of cells to engraft, using the NOD-SCID mouse model. Cord blood (CB) CD34(+) cells were incubated for 7 days with stem cell factor (SCF), flt-3 ligand (FL), and megakaryocyte growth and development factor (MGDF). Expanded CD34(+) cells were transplanted into NOD-SCID mice either fresh or following cryopreservation and thawing. Thawed expanded CD34(+) cells had significantly higher SCID Engrafting Potential (SEP) than freshly expanded CD34(+) cells. Results suggest that prior cryopreservation does not prevent expanded cells engrafting in NOD-SCID mice.
Rice AM et al.; “Prior cryopreservation of ex vivo-expanded cord blood cells is not detrimental to engraftment as measured in the nod-scid mouse model”; J Hematother Stem Cell Res 0(1), 157-165; Feb. 2001
Represents the first case of successful transplantation of PBSC, cryopreserved twice and purged after cryopreservation. Indicates that purging procedures can successfully be carried out with cryopreserved cell material and that purified CD34+ cells can be cryopreserved a second time before transplantation, without affecting their hematopoietic capacity.
Humpe A et al.; “Successful transplantation and engraftment of peripheral blood stem cells after cryopreservation, positive and negative purging procedures, and a second
cryopreservation cycle”; Ann Hematol 80(2), 109-112; Feb. 2001
General review of growth factors using in hematopoietic stem cell transplants. Recently, EPO has been shown to significantly accelerate hematopoietic reconstitution after peripheral blood stem cell transplantation (PBSCT) resulting in reduced infection rates. Both, GCSF and GM-CSF have been shown, in numerous trials, to shorten the period of chemotherapy-induced neutropenia, with reduction in attendant morbidity and to mobilize PBSC. In addition, administration of both cytokines after PBSCT significantly reduced the use of antibiotics and duration of hospitalization suggesting an economic benefit.
Dempke W et al.; “Human hematopoietic growth factors: old lessons and new perspectives”; Anticancer Res 20(6D), 5155-5164; 2000 Nov-Dec
Review of increasing use of umbilical cord blood for transplants; banking of cells, etc.
Surbek DV and Holzgreve W; “Fetal cells from cord blood as stem cell source: current status and possible implications in gynaecologic oncology”; Eur J Gynaecol Oncol 22(1), 6-12; 2001
Mobilized peripheral blood progenitor cells (PBSC) are increasingly being used instead of bone marrow for allogeneic transplantation. This article gives a concise and clinically oriented overview on current results and perspectives of allogeneic peripheral blood stem cell transplantation, with particular focus on reconstitution of hematopoiesis and the immune system, graft-versus-host disease, graft- versus-leukemia effects, intensity-reduced conditioning, and graft engineering.
Dreger P and Schmitz N; “Allogeneic transplantation of blood stem cells: coming of age?”; Ann Hematol 80(3), 127-136; March 2001
Previously reported human stem cell frequencies and their in vivo self- renewal activity have been markedly underestimated.
Cashman JD and Eaves CJ; “High marrow seeding efficiency of human lymphomyeloid
repopulating cells in irradiated NOD/SCID mice”; Blood 96, 3979-3981; Dec. 1, 2000
Evidence for expansion protocol to maintain cord blood stem cells for clinical applications.
Kobari L et al.; “In vitro and in vivo evidence for the long-term multilineage (myeloid, B, NK, and T) reconstitution capacity of ex vivo expanded human CD34(+) cord blood cells”; Exp Hematol 28, 1470-1480, December 2000
Study notes that disease recurrence is lower after peripheral blood stem cell transplants than with bone marrow; “The general opinion is that peripheral blood grafts are indicated for patients with advanced disease, whereas for patients with early-phase disease the two sources may give comparable results.”
Bacigalupo A et al.; “Bone marrow or peripheral blood as a source of stem cells for allogeneic transplants”; Curr. Opin. Hematol. 7, 343-347; Nov. 2000
Quality of life for 415 adult patients who received hematopoietic stem cell transplants was measured; typical patients can look forward to a quality of life after transplantation that is broadly comparable to that of the normal population.
Bush NE et al.; “Conditional and unconditional estimation of multidimensional quality of life after hematopoietic stem cell transplantation: a longitudinal follow-up of 415 patients”; Biol. Blood Marrow Transplant 6, 576-591; 2000
Review of techniques to mobilize hematopoietic bone marrow stem cells into peripheral blood.
Fu S, Liesveld J; “Mobilization of hematopoietic stem cells”; Blood Rev 14, 205-218; Dec. 2000
Technique to expand numbers of human hematopoietic stem cells in culture. Cells from
umbilical cord blood and adult patient peripheral blood were expanded with 2 factors, flt-3 ligand and thrombopoietin/c-mpl ligand, and maintained for prolonged periods (up to 16 weeks), and sufficient numbers were generated for adult transplantation.
Gilmore GL et al.; “Ex vivo expansion of human umbilical cord blood and peripheral blood CD34(+) hematopoietic stem cells”; Exp. Hematol. 28, 1297-1305; Nov. 1, 2000
Review of records for cord blood stem cell transplants. Results showed survival comparable to bone marrow transplants. “This large registry study confirms the potential benefit of using umbilical cord blood hematopoietic stem cells for allogeneic transplants.”
Gluckman E; “Current status of umbilical cord blood hematopoietic stem cell transplantation”; Exp. Hematol. 28, 1197-1205; Nov. 1, 2000
Review of potentials for stem cell transplantation.
Steward CG; “Stem cell transplantation for non- malignant disorders”; Baillieres Best Pract. Res. Clin. Haematol. 13, 343-363; Sept. 2000
Slavin S; “new strategies for bone marrow transplantation”; Curr. Opin. Immunol. 12, 542-551; Oct. 2000
Improved technique to quickly expand numbers of cord blood cells in culture, allowing adequate numbers for treatment of adult patients.
McNiece I et al.; “Increased expansion and differentiation of cord blood products using a twostep expansion culture”; Exp. Hematol. 28, 1181-1186; Oct. 2000
“Can expand primitive hematopoietic progenitors from Cord Blood and Peripheral Blood and expanded cells retain the capacity for myeloid and lymphoid differentiation. These findings emphasize the importance of assessing multi- lineage differentiation capacity following ex- vivo expansion.
Lewis ID, Verfaillie CM; “Multi- lineage expansion potential of primitive hematopoietic progenitors. Superiority of umbilical cord blood compared to mobilized peripheral
blood”; Exp. Hematol. 28, 1087-1095; Sept. 1, 2000
Generating a high frequency of clonally repopulating stem cells from blood.
Cho RH, Muller-Sieburg CE; “High frequency of long-term culture-initiating cells retain in vivo repopulation and self-renewal capacity”; Exp. Hematol. 28, 1080-1086; Sept. 1, 2000
Jacobs P et al.; “Allogeneic stem cell transplantation. An economic comparison of bone marrow, peripheral blood, and cord blood technologies”; Int. J. Technol. Assess Health Care 16, 874-884; Summer 2000
Autologous (same patient) circulating blood stem cell transplants show faster recovery, less transplant problems, shorter hospital stay, and reduced cost compared to bone marrow transplants.
“Overview of autologous stem cell transplantation”, Saba, N et al., Critical Reviews of Oncology and Hematology 36, 27-48, October 2000.
Allogeneic peripheral blood stem cell transplants as good or better than bone marrow.
Reference Ringden O et al., “Peripheral blood stem cell transplantation from unrelated donors: a comparison with marrow transplantation”, Blood 94, 455; July 15, 1999
Reviews of current protocols allowing better methods for collection of stem cells from peripheral blood.
Hester J; “Peripheral blood stem cell collection: the interaction of technology, procedure, and biological factors”; Transfus. Sci. 23, 125-132; Oct. 2000
Kessinger A; “Collection of autologous peripheral blood stem cells in steady state”; Baillieres Best Pract. Res. Clin. Haematol. 12, 19-26; Mar-Jun, 1999
Korbling M; “In vivo expansion of the circulating stem cell pool”; Stem Cells 16 Suppl 1, 131-138; 1998.
Kessinger A, Sharp JG; “Mobilization of blood stem cells”; Stem Cells 16 Suppl 1, 139-143; 1998
Review of cord blood stem cell transplants
Huhn RD; “Umbilical cord blood stem cell transplantation and banking”; N J Med 97, 53-57;
“Bibliography. Current world literature. Hematopoietic stem cell transplantation”; Curr. Opin.
Hematol. 7, B171-189; Nov. 2000
Treating Parkinson’s with Adult Stems Cell and Other Alternatives
Using adult neural stem cells, Dr. Michel Levesque, at the Cedars-Sinai Medical Center in Los Angeles, reports a total reversal of symptoms in the first Parkinson’s patient treated. The patient, a 57-year old former fighter pilot, is still without symptoms three years after the adult neural stem cells were removed from his brain, coaxed into becoming dopamine-producing cells, and then reimplanted. Because the stem cells came from the patient, there was no need for immunosuppression to overcome rejection. "I think transplantation of the patient's own neural stem cells and differentiated dopaminergic neurons is more biologically and physiologically compatible - more efficacious and more elegant," said Levesque. In addition to its use for Parkinson’s, the technique is under study for juvenile diabetes, stroke, brain tumors, spinal cord injury, and other conditions.
Results presented April 8th, at the meeting of the American Association of Neurological Surgeons.
Retinal Cell Implants Improve Parkinson’s
A team at Emory University School of Medicine has shown that implanting retinal cells into the brains of people with advanced Parkinson's disease can improve motor function by almost half, according to a follow-up study of six patients. The team noted: "We've been following these six participants for over a year, and we've found they've improved, on average, nearly 50 per cent in motor function." The retinal cells used were taken from deceased donors and grown in the lab. The team is not using immunosuppressants.
Result presented April 18 at the annual conference of the American Academy of Neurology in Denver and reported in the New Scientist , April 18, 2002.
N.B: There are no clinical treatments for Parkinson’s based on cloning or embryonic stem cells.
Adult Skin Cells Reprogrammed Without Cloning
A team of scientists from Norway has succeeded in coaxing one type of adult cell to start behaving like a completely different type of adult cell. The scientists have made human skin cells in a test tube behave as if they were immune system cells, by bathing the skin cells in extracts of the immune cells. In other work, they have been able to get skin cells to behave as if they were nerve cells.
"We can take a skin cell from your body and turn it directly into a cell type that you need to treat a particular disease," said Dr. Philippe Collas, the leader of the team, whose work was published 5/1/02 in the respected journal Nature Biotechnology.
The technique being developed would allow skin cells from a patient to be turned directly into other types of cells without having to revert first to an embryonic state and without needing women's eggs. They told Reuters, "That's the beauty of our system -- we are not working with embryos or dealing with stem cells at all. You get around all these issues." "It would be a one-day procedure, in principal. The patient would come in and give a skin biopsy to the lab to reprogram and the day after you could put the cells back into the patient." The technique would have immediate applications in cancer. The group is also looking at making insulin-secreting pancreatic cells.
The approach will aid investigation of the mechanisms by which adult stem cells revert to cells capable of differentiating into other types of cells with potential use in therapies for conditions like diabetes, Parkinson's disease, and heart disease. From a clinical perspective, approaches based on this technology would allow replacement cells to be generated that are compatible with a patient's immune system, without the ethical problems of generating or destroying embryos.
A.M. Hakelien et al.; "Reprogramming fibroblasts to express T-cell functions using cell extracts;" Nature Biotechnology 20, 460-466; May 2002
Adult Bone Marrow Stem Cells Transformed Into Functional Liver Cells
Dr. Catherine Verfaillie’s group at Minnesota continues to show more and more uses for the multipotent adult progenitor cells (MAPC) from bone marrow. The team has now shown that these adult stem cells can transform into functional liver cells. The adult stem cells also were grown in culture for over 100 generations, twice the length of time previously thought possible with adult cells.
R. E. Schwartz et al.; "Multipotent adult progenitor cells from bone marrow differentiate into functional hepatocyte-like cells;" J. Clin. Invest. 109,1291–1302; May 2002
“Therapeutic” Cloning No Longer Needed, Says Leading Embryonic Stem Cell Scientist
Alan Trounson, Australian embryonic stem cell expert and a leader in the field worldwide, says that stem cell research (both adult and embryonic) has advanced so rapidly in the past few months that therapeutic cloning is now unnecessary. “My view is there are at least three or four other alternatives that are more attractive already,” he said. Professor Trounson said therapeutic cloning faces logistical problems, and that other techniques are showing great promise and offer better options.
Tom Noble, “Stem-cell cloning not needed, says scientist,” The Age (Melbourne), pg. 2, July 29, 2002.
Jim Buckell, “Stem-cell research outpaces cloning,” The Australian, pg. 3, July 29, 2002.
“Therapeutic cloning no longer necessary: expert,” AAP Newsfeed, July 29, 2002.
Adult Stem Cells More Effective Than Embryonic Stem Cells in Blood Formation
Because hematopoietic (blood forming) stem cells (HSCs) can restore and maintain blood formation following transplantation into immune deficient hosts, growth of HSCs in culture is important for many clinical applications. Previously, researchers in Sweden used a gene therapy technique to add a growth gene to embryonic stem cells to get adequate growth in culture. According to the authors, however, “HSCs of early embryonic origin, including those derived from differentiated embryonic stem cells, are inefficient in engrafting adult recipients upon transplantation.” The researchers have now shown that adding the same growth gene, Lhx2, to adult bone marrow stem cells allows unlimited growth of the cells. These adult stem cells efficiently rescued immune-compromised mice and generated all blood cells.
Ó. P. do Pinto et al.; “Hematopoietic progenitor/stem cells immortalized by Lhx2 generate functional hematopoietic cells in vivo”; Blood 99, 3939-3946; June 1, 2002
Adult Bone Marrow Stem Cells Show Immune Tolerance, Not Rejected
Researchers in Canada and Japan have shown in animal studies that adult stem cells from bone marrow have a unique immunity tolerance. When selected bone marrow stem cells of mice were injected into rats, without immunosuppression, the injected cells survived and thrived without being rejected by the host immune system. The cells incorporated not only into bone marrow but also into damaged heart to aid repair.
T. Saito et al.; “Xenotransplant cardiac chimera: immune tolerance of adult stem cells”; Annals of Thoracic Surgery 74, 19-24; July 2002
Adult stem cells stimulated to form insulin-secreting pancreatic cells
Scientists at Massachusetts General Hospital have successfully turned adult stem cells into insulin-producing cells that could reverse diabetes. They found that treating adult stem cells in the pancreas with a naturally occurring hormone can transform the stem cells into beta cells, which secrete insulin. This means new beta cells could be made from a patient’s own pancreatic stem cells to treat their diabetes.
E.J Abraham et al.; “Insulinotropic hormone glucagon-like peptide-1 differentiation of human pancreatic islet-derived progenitor cells into insulin-producing cells”; Endocrinology 143, 3152-3161; August 2002
Adult Bone Marrow Stem Cells Can Repair Retina
Adult bone marrow stem cells injected into the eyes of rats with damaged retinas formed new retinal cells. The bone marrow stem cells incorporated and differentiated into retinal neural cells in the injured retina. Bone marrow stem cells may be useful in repair of damaged retinal cells.
M. Tomita et al.; “Bone marrow-derived stem cells can differentiate into retinal cells in injured rat retina”; Stem Cells 20, 279-283; July 2002
Adult Bone Marrow Stem Cells Could Prevent Blindness, Grow New Blood Vessels
Scientists at Scripps Research Institute used bone marrow stem cells to grow new blood vessels in the eyes of mice, a development researchers say could lead to treatments for some forms of blindness in humans, including diabetic retinopathy and macular degeneration. The injected adult stem cells homed in on the parts of the eye where they were needed, grew new blood vessels, and prevented blindness in the mice. Diabetic retinopathy is the leading cause of blindness in working age Americans, and age-related macular degeneration is a common cause of vision loss in people over age 60. Both conditions are caused by damaged retinal blood vessels.
A. Otani et al.; “Bone marrow-derived stem cells target retinal astrocytes and can promote or inhibit retinal angiogenesis”; Nature Medicine published online, www.nature.com; doi:10.1038/nm744; July 29, 2002
Adult Bone Marrow Stem Cells Stimulate Growth in Children With Bone Disease
Adult bone marrow stem cells implanted into children with osteogenesis imperfecta, a severe bone and cartilage disease, have stimulated growth of bone in these patients. During the 6 months immediately following the transplant, the children’s growth reached 60% to 94% of expected normal values for children their age.
Horwitz EM et al.; “Isolated allogeneic bone marrow-derived mesenchymal cells engraft and stimulate growth in children with osteogenesis imperfecta: implications for cell therapy of bone”; Proc Natl Acad Sci USA 99, 8932-8937; June 25, 2002
January 17, 2006, 9:04 a.m.
Let’s Be Adult About This
Politics can be free of embryonic entanglements.
O nce upon a time, you were an embryo. Had researchers “harvested” your stem cells, you never would have learned to read or kissed your mom and dad good night. Indeed, you never would have been born, and your life would have been squandered for nothing. Embryonic stem-cell research has yet to produce a single cure, while adult stem-cell research already treats 65 diseases and benefits human patients, not just lab rats.
Embryonic-stem-cell research (ESCR) suffered a severe blow last month as one of its most promising proponents, South Korean researcher Hwang Woo-Suk, turned out to be a monumental fraud. The stem-cell lines he claimed to have created from cloned human embryos now have been exposed as utter fabrications. Donald Kennedy, editor of the journal Science has ordered “an immediate and unconditional retraction” of two papers in which Dr. Hwang discussed these bogus stem cells. Hwang — who had credited his earlier “successes” to “his workers’ dexterity with chopsticks,” the Associated Press reports — has resigned from Seoul National University with his reputation and “work” in tatters.
For the broader ESCR community, Hwang’s phony findings are akin to learning in 1879 that Thomas Edison’s light bulb was made of nothing more than candles, mirrors, and lies.
“The bottom line is that it’s a major disaster for our whole field,” Israeli researcher Joseph Itskovitz told the Associated Press, adding: “Now we are back to square one.”
For these reasons, among others, Congress, should abandon its foolish quest to use taxpayer dollars to dissect embryos.
Impracticality aside, this technology is bathed in moral problems. ESCR fatally divides microscopic humans (or at least pre-humans) into clumps of cells. The cells that would have been some child’s gleaming eyes some day might help make Alzheimer’s a memory. But that kid would not be here to see that happen.
Harvard scientists on August 22 announced a technique to make adult cells mimic embryonic cells without harming the latter. This eventually may do wonders. However, “Our technology is not ready for prime time yet,” assistant professor Kevin Eggan told the Boston Globe. “Our results do not offer an alternative now.”
Thankfully, medical innovation does not require Frankencells to be created by destroying Microscopic Americans. The Coalition of Americans for Research Ethics in Washington and Comment on Reproductive Ethics in London are among the organizations trumpeting the triumphs of embryo-free alternatives
* Since 1993, 1,801 individuals have received stem-cell-rich umbilical-cord blood from New York Blood Center alone. These have included 66 with lymphoma and 1,150 leukemia patients. NYBC supplies non-embryonic cord blood to 90 transplant facilities across America and 86 overseas.
* “I haven’t felt better in myself for 30 years,” Englishman Richard Lane told London’s Guardian newspaper last March. “I have to pinch myself to ensure I am not dreaming.” After receiving three transplants of normal pancreatic islet cells from a deceased donor, Lane’s type-1 diabetes stopped, as did his insulin injections. “It’s almost like being a totally different person,” he said. According to King’s College Hospital professor Stephanie Amiel, “Eventually this could mean the end of insulin dependence for all type-1 diabetes sufferers.”
The Lancet, a British medical journal, reported last April on a 56-year-old Japanese mother whose donated pancreatic islet cells have healed her 27-year-old daughter’s insulin-dependent diabetes.
* The August 2004 Lancet discussed the replacement of a German mouth-cancer patient’s removed jawbone. Using his own stem cells, doctors spent seven weeks growing him a new mandible around wire mesh. Once implanted, he tested it by biting into a Frankfurter. He soon resumed eating normally.
* Adult stem cells have helped some 60 paraplegics and quadriplegics regain sensation and movement. Stem cells from their own nasal cavities helped spinal-injury victims Laura Dominguez, Susan Fajt, and Erica Nader stand up and walk with braces.
“I am now preparing to shed the shell of this wheelchair,” Fajt told the Senate Science, Technology, and Space Subcommittee on July 14, 2004. “This is something my doctors in America told me would never be possible with my level of injury and to accept my fate.” Americans Dominguez, Fajt, and Nader have advanced under the care of Dr. Carlos Lima in Lisbon, Portugal.
Similar treatments empowered six Russians to boost their mobility. Bedridden for 19 years, South Korea’s Hwang Mi-Soon stepped gingerly with a walker one month after doctors injected cord blood into her damaged spine. “This is already a miracle for me,” she said in the November 30, 2004 London Daily Telegraph.
* Blind people now can see, thanks to doctors who extract stem cells from patients’ own eyes, then culture healthy tissue to repair their corneas. “I feel like a human being again,” Deborah Catlyn told the Telegraph last April. She regained her sight after losing it in 2002 when a woman at a nightclub threw acid in her face. Catlyn is one of 20 Britons who this adult-stem-cell-research procedure has enriched. It was developed at Hyderabad, India’s Prasad Eye Institute, where some 200 blind people have been treated, most of them successfully.
Adult-stem-cell and cord-blood successes render inexcusable congressional efforts to fund embryonic-stem-cell research. With dilemma-free treatments already curing patients, why on Earth did the GOP House of Representatives last May 24 vote 238-194 to approve federal funds to slice tiny boys and girls into laboratory specimens? Before bumbling into his own insider-trading probe, Senate Majority Leader Bill Frist, M.D., of Tennessee enraged many fellow Republicans by flip-flopping and endorsing the same ESCR legislation he previously opposed and President Bush justifiably promises to veto. Republicans have no business initiating subsidies for homicidal medical research. For now, pharmaceutical companies remain free to finance this activity, if they must.
When it comes up for a vote, the U.S. Senate should defeat this measure and let adult stem cells work their magic. Taxpayers should not be forced to sponsor the destruction of Microscopic Americans, especially when “surplus” embryos are being adopted, implanted, and are being born alive as so-called "Snowflakes" babies — 99 of them so far. Washington should let these souls on ice live happily ever after.
— Deroy Murdock is a New York-based columnist with the Scripps Howard News Service and a senior fellow with the Atlas Economic Research Foundation.
Posted by Joyce Kavitsky at 2/07/2006 03:27:00 PM
Prepared by Lee Tien, Electronic Frontier Foundation Senior Counsel, Sep. 27, 2001
1. What is FISA?
FISA is the Foreign Intelligence Surveillance Act, which establishes a legal regime for "foreign intelligence" surveillance separate from ordinary law enforcement surveillance. Foreign Intelligence Surveillance Act of 1978, Pub. L. No. 95- 511, 92 Stat. 1783 (codified as amended at 50 U.S.C. §§ 1801-1811, 1821-1829, 1841-1846, 1861-62).
2. What is the purpose of FISA?
FISA is aimed at regulating the collection of "foreign intelligence" information in furtherance of U.S. counterintelligence, whether or not any laws were or will be broken. See 50 U.S.C. § 401(a)(3) (defining "counterintelligence" as information gathered and activities conducted to protect against espionage, other intelligence activities, sabotage, or assassinations conducted by or on behalf of foreign governments or elements thereof, foreign organizations, or foreign persons, or international terrorist activities). Department of Defense (DOD) guidelines state that the purpose of counterintelligence collection is to detect espionage, sabotage, terrorism, and related hostile intelligence activities to "deter, to neutralize, or to exploit them."
In short, counterintelligence and criminal prosecution are different.
3. How does FISA fit with regulation of electronic surveillance?
Given the "tendency of those who execute the criminal laws . . . to obtain conviction by means of unlawful seizures," the Supreme Court has viewed commumications interception as an especially grave intrusion on rights of privacy and speech. Berger v. New York, 388 U.S. 41, 50 (1967) (quotation and citation omitted). "By its very nature eavesdropping involves an intrusion on privacy that is broad in scope," and its "indiscriminate use . . . in law enforcement raises grave constitutional questions." Id. at 56 (quotation and citation omitted). "Few threats to liberty exist which are greater than those posed by the use of eavesdropping devices." Id. at 63.
Thus, the Court outlined seven constitutional requirements: (1) a showing of probable cause that a particular offense has been or is about to be committed; (2) the applicant must describe with particularity the conversations to be intercepted; (3) the surveillance must be for a specific, limited period of time in order to minimize the invasion of privacy (the N.Y. law authorized two months of surveillance at a time); (4) there must be continuing probable cause showings for the surveillance to continue beyond the original termination date; (5) the surveillance must end once the conversation sought is seized; (6) notice must be given unless there is an adequate showing of exigency; and (7) a return on the warrant is required so that the court may oversee and limit the use of the intercepted conversations.
Indeed, the Court said that if "neither a warrant nor a statute authorizing eavesdropping can be drawn so as to meet the Fourth Amendment's requirements . . . then the Ôfruits' of eavesdropping devices are barred under the Amendment." Id., at 63.
Where intelligence operations are concerned, however, the bounds of the Fourth Amendment are less clear than they are for ordinary criminal investigations. FISA creates a special court and legal regime for counterintelligence surveillance orders.
Executive Order 12,333 (1981) provides the general framework for U.S. intelligence activities, and it also addresses electronic surveillance. "[A]gencies are not authorized to use such techniques as electronic surveillance, unconsented physical searches, mail surveillance, physical surveillance, or monitoring devices unless they are in accordance with procedures established by the head of the agency concerned and approved by the Attorney General." EO 12,333, para. 2.4. Dep't. of Defense (DOD) Directive 5240.1-R implements FISA and EO 12,333 within DOD. These authorities govern the collection of intelligence by the U.S. government against United States persons, whether they are located within the United States or outside the United States.
FISA does not regulate the use of electronic surveillance outside of the United States. For instance, electronic surveillance of electronic communications like e-mail is only governed by §1801(f)(4) if the surveillance device is installed "in the United States." When e-mail sent by a U.S. person to a foreign person is intercepted outside the United States, that interception does not meet this definition.
4. Why is there a special legal regime for "foreign intelligence" surveillance?
The path to FISA has two branches, political and judicial.
The government had long maintained that it had extensive discretion to conduct wiretapping or physical searches in order to protect national security. In Katz v. United States, 389 U.S. 347 (1967), the Supreme Court acknowledged that the President had claimed special authority for warrantless surveillance in national security investigations, and explicitly declined to extend its holding to cases "involving the national security." Id. at 358 n. 23. Similarly, Congress in Title III stated that "nothing in Title III shall . . . be deemed to limit the constitutional power of the President to take such measures as he deems necessary to protect the United States against the overthrow of the Government by force or other unlawful means, or against any other clear and present danger to the structure or existence of the Government."
On the political front, such executive branch activities, charitably described as "some degree of domestic overreaching of intelligence into domestic areas," had long been tolerated. Staff of House Permanent Select Comm. on Intelligence, 104th Cong., Staff Study, IC21: Intelligence Community in the 21st Century at 272 (comm. print 1996).
But in the 1970s the political winds changed. The 1975-76 Church Committee hearings documented extraordinary federal government abuse of surveillance powers. Examples included the the NSA's Operation Shamrock and Operation Minaret, CIA's Operation CHAOS, the FBI's COINTELPRO domestic harassment of dissenters and anti-war protesters that included illegal wiretapping, and the illegal burglaries of the Nixon White House "plumbers."
The Church Committee Report found that covert action had been excessive, had circumvented the democratic process, and had violated the Constitution. It concluded that Congress needed to prescribe rules for intelligence activities.
On the judicial front, the Supreme Court first confronted the tension between unmonitored executive branch surveillance and civil liberties in United States v. U.S. District Court, 407 U.S. 297 (1972), in which the United States charged defendants with conspiracy to destroy government property. Defendants sought electronic surveillance information, held by the prosecution, that the CIA obtained during a potentially illegal wiretap, wanting to ascertain whether the government had relied on information in the indictment or the case for conviction and to suppress any tainted evidence at trial. The Attorney General admitted that a warrantless wiretap had intercepted conversations involving the defendants.
Before the Supreme Court, the government defended its actions on the basis of the Constitution and the Title III national security disclaimer. The Court rejected the statutory argument, saying that "Congress . . . simply did not legislate with respect to national security surveillances." As for the constitutional argument, the Court accepted that the President had the power "to protect our Government against those who would subvert or overthrow it by unlawful means" and that this power justified electronic surveillance of would-be subversives.
Invoking the "broader spirit" of the Fourth Amendment and "the convergence of First and Fourth Amendment values" in national security wiretapping cases, however, the Court was especially wary of possible abuses of the national security power. The Court then balanced "the duty of Government to protect the domestic security, and the potential danger posed by unreasonable surveillance to individual privacy and free expression," and found that waiving the Fourth Amendment probable cause requirement could lead the executive to "yield too readily to pressures to obtain incriminating evidence and overlook potential invasions of privacy and protected speech." Justice Powell wrote that the inconvenience to the government is "justified in a free society to protect constitutional values."
The Court emphasized that this case involved only the domestic aspects of national security: "We . . . express no opinion as to, the issues which may be involved with respect to activities of foreign powers or their agents." It invited Congress to act: "Given these potential distinctions between Title III criminal surveillances and those involving the domestic security, Congress may wish to consider protective standards for the latter which differ from those already prescribed for specified crimes in Title III. Different standards may be compatible with the Fourth Amendment if they are reasonable both in relation to the legitimate need of Government for intelligence information and the protected rights of our citizens."
These two paths, political and judicial, converged in the enactment of FISA.
5. Can FISA be used for ordinary criminal investigation?
Yes, but with qualifications. Under current law, any FISA investigation must have FII collection as its "primary purpose." Crossing the "primary purpose" line for information collection (from counterintelligence to law enforcement) subjects the investigation and evidence to extensive legal scrutiny and policy concerns. For instance, under DOD Dir. 5240.1-R, procedure 1, A, 3, DOD components cannot use the procedures for collecting intelligence information as a subterfuge for collecting evidence for a prosecutorial purpose.
This would change under draft Anti-Terrorism Act of 2001 (ATA).
6. Is there really a secret FISA court?
Yes. FISA established a special court, composed of seven federal district court judges appointed by the Chief Justice for staggered terms and are from different circuits. See 50 U.S.C.A. § 1803. Individual judges of the FISC review the Attorney General's applications for authorization of electronic surveillance aimed at obtaining foreign intelligence information. The proceedings are nonadversarial and are based solely on the DOJ's presentations through its Office of Intelligence Policy and Review.
The records and files of the cases are sealed and may not be revealed even to persons whose prosecutions are based on evidence obtained under FISA warrants, except to a limited degree set by district judges' rulings on motions to suppress. 50 U.S.C. §1803(c). There is no provision for the return of each executed warrant to the FISC, much less with an inventory of items taken, nor for certification that the surveillance was conducted according to the warrant and its "minimization" requirements.
The FISC meets two days monthly, and two of the judges are routinely available in the Washington, D.C. area on other days. Statement of Mary C. Lawton, Counsel for Intelligence Policy, Before the House Subcommittee on Courts, Civil Liberties, and the Administration of Justice, June 8, 1983, at 8.
7. What kind of surveillance can be authorized under FISA?
Originally, FISA was limited to electronic eavesdropping and wiretapping. 50 U.S.C. § 1801(f). In 1994 it was expanded to permit covert physical entries in connection with "security" investigations. 50 U.S.C. §§ 1821-1829. In 1998, it was amended to permit pen/trap orders, 50 U.S.C. §§ 1841-1846. FISA can also be used to obtain certain business records. §§ 1861-62.
8. How is surveillance authority different under FISA?
Although orders issued under FISA are sometimes called FISA "warrants," this is misleading because it suggests that the FISA order is like an ordinary search warrant or Title III intercept order -- and it isn't. Under the Fourth Amendment, a search warrant must be based on probable cause to believe that a crime has been or is being committed. This is not the general rule under FISA.
9. What is the basic "trigger" for permitting FISA surveillance?
Under FISA, surveillance is generally permitted based on a finding of probable cause that the surveillance target is a foreign power or an agent of a foreign power -- not whether criminality is in any way involved. §1801(b)(1).
10. What is a "foreign power"?
Examples of groups that would likely meet the definition of "foreign power" are the Irish Republican Army, Hezbollah, the PFLP, the ANC, and the FMLN. Note that a "foreign power" need not engage in activities hostile to U.S. interests.
A "foreign power" is
* a foreign government or a component thereof, whether or not recognized by the United States, 50 U.S.C. § 1801(a)(1).
* a "faction" of a foreign nation or nations, not substantially composed of United States persons, 50 U.S.C. § 1801(a)(2). The term "substantially" is not defined.
* any entity that a foreign government acknowledges it controls and directs, such as government trading or business corporations, § 1801(a)(3). It is unclear whether general regulation of a foreign corporation constitutes control and direction.
* any entity that in fact is controlled and directed by a foreign government. § 1801(a)(6). Given FISA's structure, it appears that this is decided by the FISA court.
* any group engaged in international terrorism or "activities in preparation therefor," not only governments or their components. § 1801(a)(4).
* any "foreign-based political organization, not substantially composed of United States persons." § 1801(a)(5). What do "foreign-based," "political," "organization," and "substantially" mean? Would FISA include a group of foreign college or graduate students that engages in political activism? A group of people who exchange opinions about world affairs by e-mail, some of whom live in the United States and others abroad?
11. What is an "agent of a foreign power"?
FISA §1801(b) defines this phrase in two ways, depending on whether the target is a U.S. person. §1801(b)(1) covers non-U.S. persons, while § 1801(b)(2) covers "any person."
Non-U.S. persons are "agents" under FISA if they
* act in the United States as an officer or employee of a foreign power, or as a member of a terrorist organization, § 1801(b)(1)(A)
* act for or on behalf of a foreign power that engages in clandestine intelligence activities in the United States contrary to U.S. interests when (1) the circumstances of such persons' presence in the United States "indicate that such person may engage in such activities, or (2) when such person knowingly aids or abets any person, or conspires with any person to engage in such activities." 50 U.S.C. § 1801(b)(1)(B).
So, for instance, a British national who works for the British embassy in the United States is an agent of a foreign power.
American citizens and permanent residents are "agents" if they knowingly engage in espionage for a foreign power or intelligence service, and such activities "are about to involve" a violation of U.S. laws--any criminal laws, not just espionage. §1801(b)(2)(B).
12. So FISA doesn't treat aliens and U.S. citizens equally?
If the target is a "U.S. person," which includes permanent resident aliens and associations and corporations substantially composed of U.S. citizens or permanent resident aliens, 50 U.S.C.A. § 1801(i), there must be probable cause to believe that the U.S. person's activities "may" or "are about to" involve a violation of the criminal statutes of the United States. § 1801(b)(2)(A),(B); see also § 1801(b)(2)(C) (knowingly engages in activities in preparation for sabotage or "international terrorism" on behalf of a foreign power); § 1801(b)(2)(D) (knowingly enters the United States under a false or fraudulent identity for or on behalf of a foreign power or, while in the United States, knowingly assumes a false or fraudulent identity for or on behalf of a foreign power).
A "United States person" may not be determined to be an agent of a foreign power "solely upon the basis of activities protected by the first amendment to the Constitution of the United States." 50 U.S.C. § 1805(a)(3)(A).
13. What is "foreign intelligence" information (FII)?
Under 50 U.S.C. §1801(e)(1), FII is information that "relates to" U.S. ability to protect against:
1. possible hostile acts of a foreign power or an agent of a foreign power,
2. sabotage or terrorism by a foreign power or agent, and
3. clandestine intelligence activities by a foreign power or agent.
FII includes information with respect to a foreign power or foreign territory that "relates to" the national defense, national security, or conduct of foreign affairs of the United States. § 1801(e)(2),
Under both sections, if the intended surveillance target is a U.S. person, the information must instead be "necessary to" U.S. self-protective ability or U.S. national defense, national security, or foreign affairs.
The difference between "relates to" and "necessary to" is undefined in the statute, although there may exist a secret FISA "case law."
Note that because the key FISA definitions are not tied to criminal conduct or even conspiracies, FISA can extend to FII in plain public view or in open archives (such as legal photographs of a city, a facility, or a public street, or newspaper clippings copied from a "morgue").
14. Can the FBI use FISA surveillance to get evidence for criminal prosecution?
FISA surveillances must have an intelligence purpose. 50 U.S.C. §1804 (a) (7)(B). But courts allow FISA-obtained information to be used in criminal trials. See, e.g., Exec. Order No. 12,333, 3 C.F.R. 200, 211 (1982), reprinted in 50 U.S.C. § 401 note (1994) (allowing the dissemination of information incidentally obtained during intelligence gathering that indicates activities potentially violating any law).
Courts that have allowed evidence gathered during the surveillance to support a criminal conviction have required that intelligence be the "primary" purpose of the surveillance. United States v. Humphrey, 456 F. Supp. 51 (E.D. Va. 1978), aff'd sub nom. United States v. Truong Dinh Hung, 629 F.2d 908, 913 (4th Cir. 1980), ("the Executive Branch need not always obtain a warrant for foreign intelligence surveillance"), cert. denied, 454 U.S. 1144 (1982); United States v. Megahey, 553 F. Supp. 1180, 1189-90 (E.D.N.Y. 1982), aff'd sub nom. United States v. Duggan, 743 F.2d 59 (2d Cir. 1984).
In the Megahey litigation, the district court found that the phrase "primary purpose" is the guidepost for FISA-derived surveillance, given that "Congress clearly viewed arrest and criminal prosecution as one of the possible outcomes of a foreign intelligence investigation." The Second Circuit agreed, noting that, it is foreseeable that collected intelligence may be used in a criminal proceeding and "Congress recognized that in many cases the concerns of government with respect for foreign intelligence will overlap with those with respect to law enforcement." See also United States v. Johnson, 952 F.2d 565, 572 (1st Cir. 1991) (holding that the fact that the terrorist activity was directed at Northern Ireland was of no consequence to the legality of the FISA surveillance); United States v. Pelton, 835 F.2d 1067, 1076 (4th Cir. 1987) (concluding that "FISA surveillance is not tainted simply because the government can anticipate that the fruits of the surveillance may later be used... in a criminal trial").
15. Why is FISA dangerous?
Most important, FISA powers are broad and vague, and the secrecy of FISA proceedings makes FISA powers susceptible to abuse.
FISA power extends well beyond spies and terrorists. It can be used in connection with ordinary criminal investigations involving United States citizens who live in this country and who may be charged with offenses such as narcotics violations or breaches of an employer's confidentiality. 50 U.S.C. §§ 1806, 1825.
For instance, electronic surveillance under § 1801(f)(1) only reaches wire or radio communications "sent by or intended to be received by a particular, known United States person who is in the United States, if the contents are acquired by intentionally targeting that United States person" and a warrant would ordinarily be required. If the U.S. person is not "known," or more important, not "intentionally" targeted, it simply isn't "electronic surveillance" under § 1801(f)(1).
Note also that FISA expressly contemplates that it will produce "unintentionally acquired information." § 1806(i). But while this section requires the destruction of such information, it only applies to "the contents of any radio communication," only if a warrant would have been required, and only if both the sender and intended recipients are within the United States.
Given these limits, one may presume that "unintentionally acquired information" outside these lines is not destroyed. That would include all "unintentionally acquired"wire or electronic communications.
16. How does FISA work?
Under FISA, requests for counterintelligence warrants are funneled through the Justice Department, which reviews applications by the CIA as well as other agencies before submitting them to the FISA court. 50 U.S.C. §§ 1804(a), 1822(a)(1) (1994). Each application to the FISA court must first be personally approved by the Attorney General. See 50 U.S.C. § 1804(a).
The application must contain, among other things,
a statement of reasons to believe that the target of the surveillance is a foreign power or agent of a foreign power, specified information on the implementation of the surveillance, and a "certification" from a high-ranking executive branch official stating that the official "deems the information sought to be foreign intelligence information" and that the information sought "cannot reasonably be obtained by normal investigative techniques."
See generally 50 U.S.C. §§ 1804(a)(7), 1805(a) (setting forth the findings necessary to support the issuance of an order authorizing surveillance).
Particular facts or representations required include: statements regarding all previous applications involving the target; "detailed description of the nature of the information sought and of the type of communication or activities to be subject to the surveillance," § 1804(a)(6); the length of time surveillance is required, § 1804(a)(10); whether physical entry into a premises is necessary, and proposed procedures to minimize the acquisition, use, and retention of information concerning nonconsenting U.S. persons. § 1804(b).
On the basis of the application, a FISC judge must find probable cause that the target is a foreign power or agent of a foreign power, and that the facilities where the surveillance is directed are or will be used by the target.
For U.S. persons, the FISC judge must find probable cause that one of four conditions has been met: (1) the target knowingly engages in clandestine intelligence activities on behalf of a foreign power which "may involve" a criminal law violation; (2) the target knowingly engages in other secret intelligence activities on behalf of a foreign power pursuant to the direction of an intelligence network and his activities involve or are about to involve criminal violations; (3) the target knowingly engages in sabotage or international terrorism or is preparing for such activities; or (4) the target knowingly aids or abets another who acts in one of the above ways.
Courts have attached conditions to the executive's use of warrantless surveillance, including the requirement that the President or Attorney General authorize the search, the search targets a foreign power or its agents, and the primary purpose of the search is to gather foreign intelligence information. See Exec. Order No. 12,333, § 2.5, 3 C.F.R. 200 (1982), reprinted in 50 U.S.C. § 401 note (1994) (requiring approval of attorney general for warrantless searches).
An order of the FISC may approve electronic surveillance of an agent of a foreign power for ninety days and of a foreign power for a year. Extensions may be granted on the same terms, except that targets who are foreign powers may be subject to surveillance for an additional year if there is probable cause to believe that no communication of any U.S. person will be acquired.
17. What happens if a criminal defendant challenges the validity of FISA surveillance?
Suppose a defendant moves to suppress evidence obtained via FISA surveillance. FISA provides that the district court must review in camera and ex parte the FISA application and other materials necessary to rule upon a defendant's suppression motion "if the Attorney General files an affidavit under oath that disclosure or an adversary hearing would harm the national security of the United States." 50 U.S.C. § 1806(f). See United States v. Belfield, 692 F.2d 141, 147 (D.C.Cir.1982) ("The language of section 1806(f) clearly anticipates that an ex parte, in camera determination is to be the rule. Disclosure and an adversary hearing are the exception, occurring only when necessary.").
In such circumstances, neither defendant nor defendant's counsel is likely to have access to the underlying information. 50 U.S.C. § 1806(f) (The district court "may disclose to the aggrieved person, under appropriate security procedures and protective orders, portions of the application, order, or other materials relating to the surveillance only where such disclosure is necessary to make an accurate determination of the legality of the surveillance.").
18. Does FISA authorize surveillance without a court order?
Yes. In general, the Justice Department may engage in electronic surveillance to collect FII without a court order for periods up to one year. 50 U.S.C. § 1802. There must be no "substantial likelihood" that the intercepted communications include those to which a U.S. person is a party. § 1802(a)(1)(B).
Such electronic surveillance must be certified by the Attorney General and then noticed to the Senate and House intelligence committees. § 1802(a)(2). A copy of the certification must be filed with the FISC, where it remains sealed unless (a) an application for a warrant with respect to it is filed, or (b) the legality of the surveillance is challenged in another federal district court under § 1806(f). § 1802(a)(3). Common carriers must assist in the surveillance and maintain its secrecy. § 1802(a)(4).
In emergencies, the Attorney General may authorize immediate surveillance but must "as soon as practicable, but not more than twenty-four hours" later, seek judicial review of the emergency application. § 1805(e).
19. Is FISA really constitutional?
Lower courts have found FISA constitutional. See e.g., United States v. Duggan, 743 F.2d 59(2d Cir. 1984); United States v. Belfield, 692 F.2d 141 (D.C.Cir 1982); United States v. Nicholson, 955 F.Supp. 588 (E.D. Va. 1997).
In United States v. U.S. District Court, the Supreme Court used a two-part Fourth Amendment reasonableness test. It is doubtful whether the FISA review process satisfies the Court's first measure of the reasonableness of warrantless surveillance -- whether the citizens' interest in privacy and free expression are better served by a warrant requirement.
The second element --whether a judicially imposed law enforcement warrant requirement would "unduly frustrate the efforts of Government to protect itself" -- may be more easily met in the foreign intelligence setting. But Title III has for more than 30 years required more stringent procedures for criminal investigatory wiretaps.
Posted by Joyce Kavitsky at 2/07/2006 11:38:00 AM