Related Donor Bone Marrow Transplantation Research Articles

Late onset Epstein–Barr virus-associated lymphoproliferative disease after allogeneic bone marrow transplant presenting as breast masses

We report a patient who developed breast masses 17 months after a T cell-depleted partially mismatched related donor (PMRD) bone marrow transplant (BMT) for chronic myeloid leukemia. The patient had severe chronic graft-versus-host disease (GVHD) and the masses were due to Epstein-Barr virus (EBV) lymphoproliferative disease (LPD). The patient expired from fungal pneumonia after chemotherapy for the EBV-LPD.

Erratum: De novo chronic graft-versus-host disease presenting as hemolytic anemia following partially mismatched related donor bone marrow transplant

Erratum: De novo chronic graft-versus-host disease presenting as hemolytic anemia following partially mismatched related donor bone marrow transplant

De novo chronic graft-versus-host disease presenting as hemolytic anemia following partially mismatched related donor bone marrow transplant

Chronic graft-versus-host disease (cGVHD) is a disease of immune dysregulation that resembles an autoimmune disease. It usually involves the skin, mucosal and serosal surfaces and, less commonly, the hematopoietic system. We report hemolytic anemia (HA) as the primary manifestation of de novo cGVHD in recipients of partially mismatched related donor transplants. Five of 40 eligible patients developed HA at a median of 168 days post-transplant. Recipients were mismatched for one to three major HLA antigens. Conditioning therapy consisted of total body irradiation, etoposide, Ara-C, cycle-phosphamide and steroids. GVHD prophylaxis included partial T cell depletion, using anti alpha/beta CD3 antibody (T10B9) and complement, in addition to post-transplant immunosuppression. At presentation, all patients were receiving cyclosporine with or without low-dose steroids. Along with a mean Hb of 7.1 g%, patients had an increased reticulocyte count, a mild raised lactic dehydrogenase and a positive Coombs' test (in 2/5 patients). Four patients had also demonstrated a decrease in platelet count. Treatment was initiated with high-dose steroids and intravenous gamma globulin and response was observed within 1 week. Awareness of this presentation of cGVHD and early therapeutic intervention can result in successful reversal of presumed immune-mediated red cell and platelet destruction.

Increased frequency of TCR gamma delta + T cells in disease-free survivors following T cell-depleted, partially mismatched, related donor bone marrow transplantation for leukemia.

Recent interest has focused on the function of gamma delta + T cells in immune responses. However, their role in allogeneic bone marrow transplantation (BMT) remains undefined. We report on a group of 43 leukemia patients who survived for at least 100 days following transplantation using partially HLA-mismatched grafts from related donors that were T cell depleted with the anti-TCR alpha beta monoclonal antibody T10B9.1A-31 and complement. Ten patients (23.2%) were found to have an increased (> or = 10%) proportion of gamma delta + T cells in the peripheral blood at 60-270 days after BMT. All of these patients remain alive, and 9 (90% of patients with > or = 10% gamma delta + cells) are free of disease at 2.5 years compared with a disease-free survival probability of 31% among patients with a normal proportion and concentration of gamma delta + T cells. No other factor was found to be independently associated with improved survival in these patients. These data suggest a possible association between an increase in the percentage and number of gamma delta + T cells and improved disease-free survival following transplantation from a partially mismatched related donor.

Bone Marrow Transplantation for Fanconi Anemia

Abstract Fanconi anemia is a genetic disorder associated with diverse congenital abnormalities, progressive bone marrow failure, and increased risk of leukemia and other cancers. Affected persons often die before 30 years of age. Bone marrow transplantation is an effective treatment, but there are few data regarding factors associated with transplant outcome. We analyzed outcomes of HLA-identical sibling (N = 151) or alternative related or unrelated donor (N = 48) bone marrow transplants for Fanconi anemia performed between 1978 and 1994 and reported to the International Bone Marrow Transplant Registry. Fanconi anemia was documented by cytogenetic studies in all cases. Patient, disease, and treatment factors associated with survival were determined using Cox proportional hazards regression. Two-year probabilities (95% confidence interval) of survival were 66% (58% to 73%) after HLA-identical siblings transplants and 29% (18% to 43%) after alternative donor transplants. Younger patient age (P .0001), higher pretransplant platelet counts (P = .04), use of antithymocyte globulin (P = .005), and use of low-dose (15 to 25 mg/kg) cyclophosphamide plus limited field irradiation (P = .009) for pretransplant conditioning and cyclosporine for graft-versus-host disease prophylaxis (P = .002) were associated with increased survival. Bone marrow transplants are effective therapy for Fanconi anemia. The adverse impact of increasing age and lower pretransplant platelet count on transplant outcome favors earlier intervention, especially when there is an HLA-identical sibling donor.

Bone marrow transplantation for Fanconi anemia

Fanconi anemia is a genetic disorder associated with diverse congenital abnormalities, progressive bone marrow failure, and increased risk of leukemia and other cancers. Affected persons often die before 30 years of age. Bone marrow transplantation is an effective treatment, but there are few data regarding factors associated with transplant outcome. We analyzed outcomes of HLA-identical sibling (N = 151) or alternative related or unrelated donor (N = 48) bone marrow transplants for Fanconi anemia performed between 1978 and 1994 and reported to the International Bone Marrow Transplant Registry. Fanconi anemia was documented by cytogenetic studies in all cases. Patient, disease, and treatment factors associated with survival were determined using Cox proportional hazards regression. Two-year probabilities (95% confidence interval) of survival were 66% (58% to 73%) after HLA-identical siblings transplants and 29% (18% to 43%) after alternative donor transplants. Younger patient age (P .0001), higher pretransplant platelet counts (P = .04), use of antithymocyte globulin (P = .005), and use of low-dose (15 to 25 mg/kg) cyclophosphamide plus limited field irradiation (P = .009) for pretransplant conditioning and cyclosporine for graft-versus-host disease prophylaxis (P = .002) were associated with increased survival. Bone marrow transplants are effective therapy for Fanconi anemia. The adverse impact of increasing age and lower pretransplant platelet count on transplant outcome favors earlier intervention, especially when there is an HLA-identical sibling donor.

Treatment of moderate and severe acute GVHD after allogeneic bone marrow transplantation.

We analyzed the treatment of acute GVHD following allogeneic, related or unrelated donor bone marrow transplantation (BMT). Of 510 patients transplanted between January 1986 and July 1991, 272 (53.0%) developed acute GVHD. Patients (n = 240) received treatment with either corticosteroids (n = 209), antithymocyte globulin (ATG)/prednisone (n = 26), or an anti-T cell immunotoxin (n = 5). After 28 days, 33% (79/240) had achieved a response to primary therapy; 24% a complete response. Ninety-five patients received 1 or more courses of salvage immunotherapy and 26 (27%) responded. In multivariate analysis, a response to primary therapy was the single most important factor independently predicting a lower risk of subsequent chronic GVHD (P < .0001) and improved long-term survival (P = .01). The GVHD clinical stage score, which we previously described, had significant predictive value for response to therapy and freedom from chronic GVHD. The conventional clinical grade had no such predictive value. In multivariate analysis, transplantation from a mismatched or an unrelated donor was not of independent importance in predicting either acute GVHD treatment response or chronic GVHD. However, these alternative donor transplants led to poorer survival. This analysis identifies patient subsets having GVHD with a low likelihood of response to conventional immunosuppressive treatment and may be used to indicate those needing early application of more intensive therapy. More important, however, the overall low response rates observed suggest that more effective treatment for acute GVHD is still required to improve the results of transplantation therapy.