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Perspective
Selling Bone Marrow — Flynn v. Holder
On December 1, 2011, in Flynn v. Holder, the U.S. Court of Appeals for the Ninth Circuit held that the ban on selling "bone marrow" that is part of the National Organ Transplant Act (NOTA) of 1984 does not encompass "peripheral blood stem cells" obtained through apheresis. This ruling means that…
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Clinical Implications of Basic Research
Diabetic Stem-Cell “Mobilopathy”
Hematopoietic stem-cell (HSC) transplantation remains the primary curative treatment for patients with a variety of hematologic cancers. Transplantation of either autologous or allogeneic stem cells requires the acquisition of sufficient numbers of HSCs to ensure rapid and consistent trilineage…
Correspondence
Myeloma and Second Primary Cancers
To the Editor: In December 2010, results from three randomized, phase 3 trials of treatments for multiple myeloma showed an excess of hematologic cancers among patients with multiple myeloma who received lenalidomide maintenance therapy (see Table 1 in the Supplementary Appendix, available with the…
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Acute leukemia after myeloma has been attributed to exposure to alkylating agents. However, leukemia is now being seen in patients receiving lenalidomide maintenance therapy. Patients with monoclonal gammopathy of undetermined significance also have an increased risk of leukemia without ever being treated.
Original Article
Interleukin-2 and Regulatory T Cells in Graft-versus-Host Disease
Allogeneic hematopoietic stem-cell transplantation (HSCT) invokes donor-derived immune responses that can result in therapeutic graft-versus-tumor activity and toxic graft-versus-host disease (GVHD). Chronic GVHD, a systemic inflammatory disorder with pleomorphic autoimmune manifestations that is…
Editorial
The Yin and Yang of Interleukin-2–Mediated Immunotherapy
In this issue of the Journal, the findings of two case series suggest that in vivo treatment with interleukin-2 can suppress immune-mediated diseases. In one study, Koreth et al. found that low-dose interleukin-2 was associated with reversal of glucocorticoid-refractory chronic graft-versus-host…
Clinical Implications of Basic Research
Illuminating Immune Privilege — A Role for Regulatory T Cells in Preventing Rejection
Bone marrow transplantation has had a substantive therapeutic impact on survival, but its usefulness can be limited by the lack of matched donors, as well as by the risks of graft rejection and graft-versus-host disease (GVHD). Current strategies attempt to address these issues with conditioning…
Original Article
Cord Colitis Syndrome in Cord-Blood Stem-Cell Transplantation
Hematopoietic stem-cell transplantation (HSCT) with the use of umbilical-cord blood is effective in patients for whom a sibling or matched, unrelated donor is not available.– Acute graft-versus-host disease (GVHD), a major cause of illness in patients undergoing HSCT, is less severe with cord…
Original Article
Horse versus Rabbit Antithymocyte Globulin in Acquired Aplastic Anemia
Acquired aplastic anemia in its severe form is fatal without treatment. The disease is characterized pathologically by an "empty" bone marrow, in which hematopoietic precursor cells are replaced by fat, resulting in pancytopenia. Severe aplastic anemia was first definitively treated with the…
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Review Article
Mechanisms of Disease: The Coagulopathy of Chronic Liver Disease
Chronic liver disease, particularly in the end stage, is characterized by clinical bleeding and decreased levels of most procoagulant factors, with the notable exceptions of factor VIII and von Willebrand factor, which are elevated. Decreased levels of the procoagulants are, however, accompanied by…
Clinical Implications of Basic Research
In Utero Hematopoietic Stem-Cell Transplantation — A Match for Mom
Once researchers recognized that adult stem cells can generate multiple cell types and contribute to tissue homeostasis, it became conceivable to exploit this potential to treat genetic or acquired disorders characterized by tissue degeneration or organ dysfunction. The concept of regenerative…
Review Article
Medical Progress: Multiple Myeloma
Multiple myeloma is a neoplastic plasma-cell disorder that is characterized by clonal proliferation of malignant plasma cells in the bone marrow microenvironment, monoclonal protein in the blood or urine, and associated organ dysfunction. It accounts for approximately 1% of neoplastic diseases and…
- CME
Case Records of the Massachusetts General Hospital
Case 36-2010 — A 50-Year-Old Woman with Pain and Loss of Hearing in the Left Ear
Presentation of Case. A 50-year-old woman was seen in the emergency department at Massachusetts Eye and Ear Infirmary (MEEI), affiliated with this hospital, because of pain and decreased hearing in the left ear. The patient had been in her usual state of health until 6 weeks earlier, when she noted…
Editorial
The Role of Allogeneic-Cell Transplantation in Leukemia
In the early 1970s, patients with high-risk hematologic cancers had a small chance of long-term survival. This chance began to increase with allogeneic blood or bone marrow transplantation, which combines high-dose chemotherapy, total-body irradiation, and graft-versus-leukemia effects. In…
Original Article
Reduced Mortality after Allogeneic Hematopoietic-Cell Transplantation
Infections, graft-versus-host disease (GVHD), and liver, kidney, and pulmonary complications have been associated with high mortality after allogeneic hematopoietic-cell transplantation since the introduction of this procedure 40 years ago. Changes in practice have decreased organ toxicity,– and…
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- CME
This comparison of outcomes of allogeneic hematopoietic stem-cell transplantation in 1993–1997 and 2003–2007 shows that although patients had a somewhat poorer overall prognosis in the more recent period, the rate of death not preceded by relapse, the risk of relapse, and overall mortality decreased.
Original Article
Efficacy of Gene Therapy for X-Linked Severe Combined Immunodeficiency
The cytokine receptor common γ chain, which is encoded by the interleukin-2 receptor subunit gamma (IL2RG) gene, is a critical functional component of the receptors for interleukin-2, interleukin-4, interleukin-7, interleukin-9, interleukin-15, and interleukin-21. Naturally occurring mutations in…
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In a long-term (up to 11 years) follow-up of nine patients with X-linked severe combined immunodeficiency treated with retroviral insertion of a normal common γ-chain gene into hematopoietic progenitors, seven had durable T-cell reconstitution and long-term survival. B-cell immunity was not corrected. Acute leukemia developed in four patients. In patients without a matched marrow donor, gene therapy may be an option but is associated with serious risks.
Case Records of the Massachusetts General Hospital
Case 22-2009 — A 59-Year-Old Man with Skin and Pulmonary Lesions after Chemotherapy for Leukemia
Presentation of Case. Dr. Deborah L. Cummins (Dermatology): A 59-year-old man was seen by consultants in infectious disease and dermatology because of cutaneous and pulmonary lesions that developed after induction chemotherapy for acute myeloid leukemia. A diagnosis of myelodysplastic syndrome had…
A 59-year-old man was admitted to this hospital for induction chemotherapy for acute myeloid leukemia. On the seventh hospital day, neutropenia, fever, nausea, diarrhea, and abdominal pain developed. Despite the administration of broad-spectrum antimicrobial therapy, tender, erythematous skin lesions developed on the trunk, abdomen, and arms and legs, and bilateral pulmonary nodules were seen on computed tomographic scans of the chest. A diagnostic procedure was performed.
Original Article
Brief Report: HLA-Mismatched Renal Transplantation without Maintenance Immunosuppression
Long-term results of organ transplantation remain unsatisfactory, mainly because of chronic rejection and complications associated with immunosuppressive medications. Immune tolerance, which has been achieved in animal models, might provide a means for avoiding both of these problems. However, the…
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Five patients with end-stage renal disease received bone marrow and kidney transplants from HLA-mismatched living related donors. Transient hematopoietic chimerism developed in all five. In one patient, irreversible humoral rejection occurred. In the other four recipients, immunosuppressive therapy was discontinued after 9 to 14 months and renal function has subsequently remained stable.
Perspective
Hematopoietic-Cell Transplantation at 50
September 12, 2007, marked the 50th anniversary of E. Donnall (Don) Thomas's initial report of a radical new approach to cancer treatment: radiation and chemotherapy followed by the intravenous infusion of bone marrow. That publication represented the beginning of a long series of laboratory and…
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Correspondence
Mevalonic Aciduria Cured by Bone Marrow Transplantation
To the Editor: Neven et al. (June 28 issue) discuss the use of bone marrow transplantation in the treatment of severe mevalonic aciduria. We provide additional evidence for the effective cure of mevalonic aciduria by hematopoietic stem-cell transplantation. In February 2006, we performed…
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Original Article
Brief Report: Allogeneic Bone Marrow Transplantation in Mevalonic Aciduria
Mevalonic aciduria (number 251170 in the mendelian inheritance in Man [MIM] database) is a rare inborn error of isoprene biosynthesis.– The typical clinical picture in children is one of recurrent attacks of fever, developmental delay, ataxia, dysmorphic features, failure to thrive, cataracts,…
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