The combination of melphalan, cyclophosphamide and cytosine arabinoside as a conditioning regimen for autologous bone marrow transplantation for acute leukemia

Abstract

Objective: To explore more effective and less toxic conditioning regimen without total body irradiation for autologous bone marrow transplantation (ABMT) for acute leukemia (AL).

Material and methods: Twenty patients with AL were treated with ABMT, including 13 cases of acute myelocytic leukemia (AML) and 7 cases of acute lymphocytic leukemia (ALL). A median of 1.06 (range, 0.69-1.75) x 10(8) nucleated BM cells/kg was harvested and stored in normal salt solution containing heparin at 4 degrees C. The conditioning regimen (MAC) consisted of high-dose melphalan (M, 140-160 mg/m2), cyclophosphamide (CY, 120 mg/kg) and cytosine arabinoside (Ara-C, 2.0 g/m2). These 3 drugs were administered within 25 hours and the unpurged autologous marrow infusion began after another 24-hour interval.

Results: MAC regimen could result in myeloblastic efficacy in a week. All marrow cells were reinfused within 56 hours after the harvest so that hemopoietic reconstitutions could occur in all the patients. The median time to reach a neutrophil count of > 1.0 x 10(9)/L and a platelet count of > 50 x 10(9)/L was 20 and 26 days respectively. With a median observation period of 25 months, the median duration on continuous complete remission in our patients was 22 months, and the longest reached 56 months. The median survival was 33 months, and the longest was over 6 years. The event-free survival at 2 years had reached 72%. In seven patients with leukemic relapse, six (86%) relapsed within 8 months after ABMT. The relapse rate and mortality in AML patients were significantly lower than those in ALL patients. In 7 patients with M3, relapse had not yet been observed. The nonhematologic toxic effects of MAC conditioning regimen occurred mainly in the gastrointestinal tract.

Conclusions: The preliminary results indicated that the ABMT using MAC conditioning regimen had some advantages in stronger antileukemic efficacy, less extrahematologic toxicity and earlier recovery of platelet and could greatly prolong the duration of remission and survival in some patients with AL.