Allogeneic bone marrow transplantation after high-dose busulfan and cyclophosphamide in patients with acute nonlymphocytic leukemia

Abstract

Ninety-nine patients with acute nonlymphocytic leukemia (ANLL) received HLA-identical bone marrow transplants (BMTs) from sibling donors after preparation with high doses of busulfan and cyclophosphamide. Forty-nine patients were transplanted in first complete remission (CR), and 50 patients were transplanted in second and third CR and early relapse. Fifty-three received one of three regimens containing primarily low-dose cyclophosphamide (group I) for graft-v-host disease (GVHD) prophylaxis; since March 1983, 46 patients received intravenous (IV) cyclosporine (group II). After December 1983, only cytomegalovirus (CMV)-seronegative blood products were used in appropriate patients, and since April 1984 patients seropositive for herpes-simplex virus (HSV) and CMV received high-dose acyclovir prophylaxis. For patients transplanted in first CR, there was a significantly lower incidence of acute GVHD (P = .005) and deaths related to GVHD and interstitial pneumonitis (P = .001) in patients in group II. This was reflected in an improved Kaplan-Meier probability of disease-free survival (DFS) in the 22 patients transplanted in group II as compared with the 27 patients in group I (64% +/- 10% v 30% +/- 9%, P = .017). The probability of remaining in remission was slightly lower in group II (82% +/- 9% v 94% +/- 6%, P = .479). For patients transplanted in second and third CR and early relapse, the incidence of acute GVHD (P = .026) and deaths related to GVHD and interstitial pneumonitis was significantly lower in group II (P = .029); the probability of remaining in remission was also less (47% +/- 15% v 91% +/- 15%, P = .022). However, the probability of DFS was not significantly different between the two groups (26% +/- 10% v 35% +/- 18%, P = .957). We conclude that transplantation for patients in first CR who received IV cyclosporine therapy is effective treatment; patients with more refractory disease treated with the same cyclosporine regimen (group II) had a lower incidence of GVHD than those treated in group I, but survival did not improve because of an increase in the number of relapses and other nonleukemic complications.