Journal of Clinical Oncology, Vol 12, 1923-1930, Copyright © 1994 by American Society of Clinical Oncology
Etoposide, cyclophosphamide, total-body irradiation, and allogeneic bone marrow transplantation for hematologic malignancies
SA Giralt, CF LeMaistre, HM Vriesendorp, BS Andersson, M Dimopoulos, J Gajewski, K Van Besien, R Mehra, D Przepiorka and I Khouri
Department of Hematology, University of Texas, M.D. Anderson Cancer Center, Houston 77030.
PURPOSE: To determine the efficacy and toxicity of etoposide,
cyclophosphamide, and fractionated total-body irradiation (TBI) as the
conditioning regimen for allogeneic bone marrow transplantation (BMT) in
patients with hematologic malignancies. PATIENTS AND METHODS: Seventy-nine
patients underwent BMT from a human leukocyte antigen (HLA)-identical
sibling using cyclosporine/methotrexate for graft- versus-host disease
(GVHD) prophylaxis. Thirty-four patients had early leukemia (acute leukemia
or lymphoblastic lymphoma in first remission, chronic myelogenous leukemia
[CML], or refractory anemia [RA]), and 45 patients had more advanced
disease. Patients received etoposide 1,500 mg/m2 on day -8, followed by
cyclophosphamide 60 mg/kg/d on days -7 and -6, and 10.2 Gy of TBI
administered in six fractions of 1.7 Gy given twice daily for 3 days from
day -3 to -1. Donor bone marrow was harvested and infused on day 0.
RESULTS: Patients with early leukemia had a disease-free survival rate of
53% +/- 9% and an overall survival rate of 57% +/- 10% at 3 years. Patients
with advanced disease had a disease-free survival rate of 15% +/- 5% and
overall survival rate of 17% +/- 5%. The actuarial relapse rate for the
early-leukemia group is 33% +/- 9% versus 69% +/- 9% for patients with more
advanced disease. Severe toxicity was most frequently manifested as
pulmonary hemorrhage followed by multiorgan failure and death. The 100-day
mortality rate for the early-leukemia group was 10% versus 50% for patients
with more advanced disease. CONCLUSION: The combination of
cyclophosphamide, etoposide, and TBI is a relatively safe and effective
preparative regimen for patients with early hematologic malignancies.
Controlled trials are needed to evaluate critically this combination versus
other standard preparative regimens. Greater toxicity was observed in
patients with advanced disease, and this program does not appear to offer
any advantage over other regimens.