A prospective randomized trial of therapy for severe aplastic anemia was designed to compare early bone marrow transplantation with conventional treatments. All patients with a sibling matched at the major histocompatibility region were transplanted. Transplantation was performed with 17–100 (median 33) days of original diagnosis. Conventional treatments included transfusion support with or without androgens. Twenty-four of 36 patients intered on the transplant arm are alive after 4–20 (median 9) mo with full marrow reconstitution. Only two are limited by chronic graft-versus-host disease. In contrast only 12 of 31 conventionally treated patients are alive. Six of these survivors have improved, five incompletely. The 19 nontransplant deaths have occurred within 1–11 (median 3) mo of diagnosis. Compared to nontransplant regimens, early transplantation more effectively restores normal marrow function and decreases the acute mortality of severe marrow aplasia (p = 0.006). Pending longer follow-up, early marrow transplantation appears to be the most effective available treatment for severe aplastic anemia.

The likelihood that a person with SCD will receive a transfusion depends in large part on age and genotype. Although estimates are confounded by the fact that hospital-based studies may not adequately account for those who do not seek or require medical attention," it seems clear that the majority of persons affected with SCD receive at least one transfusion during their lifetime. The recent Cooperative Study of SCD survey suggests that approximately 60% have received blood, rates varying from 0% to 95% with age, sex, and genotype.

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Isolated thrombocytopenia after bone marrow transplantation was investigated in 65 fully engrafted patients surviving at least 60 days posttransplant. Twenty-four patients (37%) developed this complication, which occurred most frequently in patients receiving pretransplant preparation with total body irradiation or busulfan. Two distinct thrombocytopenic syndromes were identified: (1) transient thrombocytopenia (nine patients), in which a normal platelet count (greater than 100,000/microL) was initially established by day +40 but then diminished to less than 10,000 to 45,000/microL on day +40 to +70, with subsequent resolution of the thrombocytopenia by day +90; (2) chronic thrombocytopenia (15 patients), in which a platelet count greater than 100,000/microL was not achieved at any time during the first four months posttransplant, despite the simultaneous presence of normal granulocyte and reticulocyte counts. Although the transient syndrome did not adversely affect prognosis, the chronic syndrome carried a high mortality (21% actuarial survival at 1,000 days posttransplant compared with 67% survival for all patients, P less than .01) and had a high association with both severe (grades 3 to 4) acute graft-versus-host disease (GVHD) and chronic GVHD. In three of nine patients with transient thrombocytopenia, a temporal association with trimethoprim-sulfamethoxazole administration was observed, whereas in all other patients, no drug association could be found. Bone marrow biopsies in those patients with drug-associated thrombocytopenia showed decreased numbers of megakaryocytes, whereas biopsies in the remainder of the transiently thrombocytopenic patients demonstrated adequate numbers of platelet precursors, suggesting peripheral platelet destruction or ineffective thrombopoiesis. Biopsies in the chronic thrombocytopenic patients included those with and without adequate numbers of platelet precursors, although the association with chronic GVHD was strongest in patients demonstrating normal numbers of megakaryocytes. We conclude that isolated thrombocytopenia represents a significant complication of bone marrow transplantation, particularly in patients receiving hematopoietic ablative preparatory regimens, and that it is the chronic, not the transient, thrombocytopenic syndrome that is associated with an adverse patient prognosis.

One hundred ten patients with severe aplastic anemia were entered into a prospective study. Forty-seven patients who had HIA-identical siblings were treated with marrow transplantation. Sixty-three patients without marrow donors were randomized to supportive care with oral androgen (27 patients). intramuscular androgen (23 patients). or no androgen (1 3 patients). The distributions of the survival times for the patients in the three nontransplantation arms of the study were not different. Transplanted patients had significantly better survival than nontransplanted patients (p 0.0002). Evaluation of prognostic factors for nontransplanted patients showed a better prognosis for patients with unknown etiology than for those with a probable etiology (p = 0.01 ). Also, patients with larger mean red blood cell volumes tended to live longer (p = 0.03). For patients given marrow transplants. significant prognostic fators were age (p 0.01 5) and sex (p 0.027). with better survival for younger male patients. Twenty-seven transplant recipients (57 % ) are alive; 5 have severe chronic graft-versus-host disease, and 22 (47 % ) are living and well. Sixteen nontransplanted patients (25 % ) are alive; 3 continue to have severe disease, and 13 (21 % ) are clinically well and no longer require transfusion support. As used in this study, androgens were of no value in the treatment of patients with severe aplastic anemia. If a suitable donor is available, marrow transplantation is clearly superior to conventional management. at least in younger patients.