Autologous Bone Marrow Transplantation in Patients with Acute Nonlymphocytic Leukemia, Using ex Vivo Marrow Treatment with 4-Hydroperoxycyclophosphamide

Andrew M. Yeager, Herbert Kaizer, George W. Santos, Rein Saral, O. Michael Colvin, Robert K. Stuart, Hayden G. Braine, Philip J. Burke, Richard F. Ambinder, William H. Burns, Donald J. Fuller, Janice M. Davis, Judith E. Karp, W. Stratford May, Scott D. Rowley, Lyle L. Sensenbrenner, Georgia B. Vogelsang, John R. Wingard

Research output: Contribution to journalArticlepeer-review

Abstract

We studied 25 patients with acute nonlymphocytic leukemia in second remission (20 patients) or third remission (5 patients) in whom autologous bone marrow transplantation was performed with use of marrow incubated ex vivo with the alkylating agent 4-hydroperoxycyclophosphamide. Patients received intensive cytoreductive therapy with busulfan and cyclophosphamide or cyclophosphamide and total body irradiation, followed by an infusion of marrow that had been collected in remission, treated with 4-hydroperoxycyclophosphamide, and cryopreserved. Four patients died from bacterial or fungal sepsis within the first month after transplantation, and one patient with persistent marrow hypoplasia died from gram-negative sepsis 155 days after infusion with autologous marrow. In the remaining patients, peripheral-blood levels of neutrophils in excess of 0.5 x109 per liter and platelet counts over 50x109 per liter were attained at median intervals of 29 and 57 days after transplantation, respectively. Nine patients had leukemic relapses at 73 to 316 days (median, 182 days) after infusion of autologous marrow, for an actuarial relapse rate of 46 percent. Eleven patients (eight in second remission and three in third) remained in remission at a median of more than 400 days (range, >230 to >1653 days) after transplantation. The observed disease-free survival after transplantation with autologous marrow treated with 4-hydroperoxycyclophosphamide compares favorably with the results of syngeneic or allogeneic transplantation in similar groups of patients. (N Engl J Med 1986; 315:141–7.), Current intensive regimens of chemotherapy for the treatment of acute nonlymphocytic leukemia result in prolonged first remissions in a substantial proportion of patients, who may ultimately be cured of their leukemia.1 2 3 However, patients who have one or more hematologic relapses have an extremely poor prognosis and a minimal chance of leukemia-free survival. Allogeneic bone marrow transplantation in such patients provides an opportunity for cure of leukemia, although graft-versus-host disease and opportunistic infections — notably viral interstitial pneumonitis — account for most of the mortality after allogeneic transplantation.4 5 6 7 Furthermore, 60 to 75 percent of the patients who might benefit from allogeneic.

Original languageEnglish (US)
Pages (from-to)141-147
Number of pages7
JournalNew England Journal of Medicine
Volume315
Issue number3
DOIs
StatePublished - Jul 17 1986

ASJC Scopus subject areas

  • Medicine(all)

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