Allogeneic marrow grafting for treatment of aplastic anemia

Abstract

24 patients with severe aplastic anemia, 14 due to unknown cause, 4 associated with hepatitis, 4 drug or chemical related, 1 with paroxysmal nocturnal hemoglobinuria, and 1 possibly associated with a Fanconi syndrome did not show spontaneous recovery after 2-24 mth of conventional therapy. 11 were infected and 9 were refractory to random platelet transfusions at the time of admission. All received marrow grafts from HL A identical siblings. 18 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 graft versus host disease (GvHD). 1 patient died on the day of grafting of congestive heart failure possibly related to CY cardiac toxicity. 1 died on day 6 with septicemia. 1 died on day 24 without engraftment. 21 patients showed prompt hemopoietic engraftment indicated by rising blood counts, return of marrow cellularity, and in most instances confirmed by blood genetic markers. 4 rejected the graft and died on days 33, 41, 51, and 67. 4 died between days 45 and 85 with GvHD. 1 died of cytomegalovirus infection on day 91. 1 with chronic active hepatitis died on day 427 of unknown causes. 11 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 10 have returned to normal activity. These results show that normal stem cells will repopulate the marrow in patients with aplastic anemia and demonstrate that longterm 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.