Busulfan/etoposide--initial experience with a new preparatory regimen for
autologous bone marrow transplantation in patients with acute
nonlymphoblastic leukemia
NJ Chao, AS Stein, GD Long, RS Negrin, MD Amylon, RM Wong, SJ Forman and KG Blume
Department of Medicine, Stanford University Medical Center, CA 94305.
Current intensive chemotherapy for acute nonlymphoblastic leukemia (ANLL)
results in a complete remission in the majority of patients. Unfortunately,
the duration of remission is short and most of the patients will experience
a relapse of their underlying disease. Autologous bone marrow (BM)
transplantation is being explored as a treatment modality designed to
improve relapse-free survival. We have conducted a phase II trial exploring
the combination of busulfan (16 mg/kg) and etoposide (60 mg/kg) in an
attempt to improve antitumor efficacy using this novel preparative regimen.
To date, 50 patients (48 with ANLL and 2 patients with biphenotypic acute
leukemia) have been treated. The first 20 patients received unmanipulated
BM; 28 patients subsequently received 4-hydroperoxycyclophosphamide (4-HC)
(60 micrograms/mL)-purged bone marrow, and 2 patients with biphenotypic
acute leukemia received both 4-HC (60 micrograms/mL) and etoposide (5
micrograms/mL)-purged BM. Thirty-four patients were in first complete
remission (CR1), 12 patients in second complete remission (CR2), and 4
patients in relapse. The median time from first complete remission to BM
harvest was 3 months (range, 0.8 to 4) compared with median time of 2
months (range, 1.5 to 5.0) for patients in second complete remission. The
median time from harvest to transplant was 1 month for both groups (range,
0.4 to 36). A median of 0.7 x 10(8) (range, 0.2 to 1.4) mononuclear cells
were infused. Patients achieved an absolute neutrophil count of > or =
500/microL at a median of 26 days (range, 13 to 96), an untransfused
platelet count > or = 20,000/microL at a median of 56 days (range, 15 to
278) and a sustained hematocrit > or = 30% at a median of 50 days
(range, 19 to 116). Twenty-six patients are alive and in continued CR.
Follow-up of the surviving patients ranged from 6 months to 66 months with
a median follow-up of 31 months. Patients receiving purged BM have an
actuarial disease-free survival of 57% with a relapse rate of 28% compared
with patients receiving unpurged BM whose actuarial disease-free survival
is 32% with a relapse rate of 62% (P = .06 for relapse rate). The most
significant extramedullary toxicities for this regimen are hepatic and
cutaneous (including mucositis). The BU/VP-16 regimen is associated with a
significant proportion of patients surviving disease free, especially in
the group receiving purged BM. Whether this regimen offers a substantial
improvement in disease-free survival over currently used regimens will
require a prospective randomized study.
Volume 81,
Issue 2,
pp. 319-323,
01/15/1993
Copyright © 1993 by The American Society of Hematology
