Twenty-four patients with severe aplastic anemia, 14 due to unknown cause, four associated with hepatitis, four drug or chemical related, one with paroxysmal nocturnal hemoglobinuria, and one possibly associated with a Fanconi syndrome did not show spontaneous recovery after 2-24 mo of conventional therapy. Eleven were infected and nine were refractory to random platelet transfusions at the time of admission. All received marrow grafts from HL-A identical siblings. Eighteen were conditioned for grafting by cyclophosphamide (CY), 50 mg/kg on each of 4 successive days, and 6 by 1000 rad total body irradiation (TBI). All received intermittent methotrexate (MTX) therapy within the first 100 days postgrafting to modify graftversus-host disease (GvHD). One patient died on the day of grafting of congestive heart failure possibly related to CY cardiac toxicity. One died on day 6 with septicemia. One died on day 24 without engraftment. Twenty-one patients showed prompt hemopoietic engraftment indicated by rising blood counts, return of marrow cellularity, and in most instances confirmed by blood genetic markers. Four rejected the graft and died on days 33, 41, 51, and 67. Four died between days 45 and 85 with GvHD. One died of cytomegalovirus infection on day 91. One with chronic active hepatitis died on day 427 of unknown causes. Eleven are alive with grafts and without GvHD more than 141, 144, 163, 186, 189, 255, 344, 472, 641, 746, and 823 days after grafting, and ten have returned to normal activity. These results show that normal stem cells will repopulate the marrow in patients with aplastic anemia and demonstrate that long-term stable chimerism is possible in man. They suggest that marrow grafting in patients with complete marrow failure and an HL-A matched sibling should be undertaken before major infections and refractoriness to blood transfusions complicate their course.

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