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Aplastic anemia treated by allogeneic bone marrow transplantation: a report
on 49 new cases from Seattle
R Storb, ED Thomas, PL Weiden, CD Buckner, RA Clift, A Fefer, LP Fernando, ER Giblett, BW Goodell, FL Johnson, KG Lerner, PE Neiman and JE Sanders
Forty-nine patients with severe aplastic anemia, 33 due to unknown cause,
11 drug or chemical related, 2 associated with hepatitis, 1 with paroxysmal
nocturnal hemoglobinuria, and 2 possibly associated with Fanconi syndrome
did not show recovery after 0.5-96 (median 2) mo of conventional therapy.
Twenty-two were infected and 21 were refractory to random platelet
transfusions at the time of admission. All were given marrow grafts from
HLA-identical siblings. Forty-five were conditioned for grafting by
cyclophosphamide (CY), 50 mg/kg on each of 4 successive days, and four by
1000 rad total body irradiation. All were given intermittent methotrexate
therapy within the first 100 days of grafting to modify graft-versus-host
disease (GVHD). Three patients died from infection too early to evaluate
(days 1-8). Forty-six had marrow engraftment. Of these, 20 are surviving
with good peripheral blood counts between 186 and 999 days, and 18 have
returned to normal activities. Chronic GCHD is a problem in five. Twelve
patients died of infection following rejection of the marrow graft. Twelve
patients died with bacterial or fungal infections or interstitial pneumonia
and active GVHD or soon following resolution of GVHD. Two patients died
with marrow engraftment and no GVHD, one with an interstitial, and the
other with a bacterial pneumonia. Thirty-six patients who had received
random donor blood transfusions were randomly assigned to receive either CY
or procarbazine-antithymocyte globulin-CY as conditioning regimens to test
whether the incidence of graft rejection could be decreased. There was no
difference in the incidence of graft rejection between the two regimens. In
13 patients with rejection, second transplants were attempted either with
the original marrow donor (9 patients) or another HLA-identical sibling (4
patients). Three of these transplants were not evaluable, seven were
unsuccessful and three were successful with only one of the three surviving
for more than 468 days. In conclusion, the long-term survival of 41% of the
patients in the present study is similar to that achieved in our first 24
patients, and confirms the importance of marrow transplantation for the
treatment of severe aplastic anemia. Marrow graft rejection, GVHD, and
infections continue to be the major causes of failure.
Volume 48,
Issue 6,
pp. 817-841,
12/01/1976
Copyright © 1976 by The American Society of Hematology
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