JOURNAL ARTICLE

Intravenous busulfan-cyclophosphamide as a preparative regimen before allogeneic hematopoietic stem cell transplantation for adult patients with acute lymphoblastic leukemia

Wei Tang, Ling Wang, Wei-Li Zhao, Yu-Bao Chen, Zhi-Xiang Shen, Jiong Hu
Biology of Blood and Marrow Transplantation 2011, 17 (10): 1555-61
21549217
The use of i.v. busulfan (BU) instead of the oral formulation can improve outcomes in patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) by reducing toxicity and transplantation-related mortality (TRM). There are limited reports of i.v. BU used to treat patients with acute lymphoblastic leukemia (ALL). The present study was performed to evaluate the efficacy and toxicity of i.v. BU/cyclophosphamide (CY) conditioning in adult ALL. We retrospectively analyzed 42 consecutive patients who underwent allo-HSCT with BU/CY conditioning between January 2007 and October 2010 with an HLA-matched donor (sibling, n = 18; unrelated, n = 24). Thirty-three patients were in first complete remission (CR1), 2 were in second complete remission (CR2), and 7 were in a more advanced stage. Median patient age was 28 years (range, 17∼55 years). The median follow-up was 15 months (range, 1∼48 months). Overall, 13 patients died, for a 30-month overall survival of 56.5% ± 10.6% (65.7% ± 12.5% for patients in CR1 vs 25.4% ± 15.5% for those in CR2 or beyond; P < .001). Eleven patients experienced relapse between 2 and 26 months after allo-HSCT, with a 30-month relapse rate (RR) of 40% ± 10.9% (32.0% ± 12.7% for patients in CR1 vs 71.4% ± 17.1% for those in CR2 or beyond; P = .001). The incidence of grade II-IV acute graft-versus-host disease (GVHD) was 39.2% ± 8.8%, and that of grade III-IV acute GVHD was 7.4% ± 4.1%. The incidence of chronic GVHD was 63.9% ± 11.7%, and that of extensive chronic GVHD was 19.3% ± 7.9%. Only 2 cases of clinically diagnosed veno-occlusive disease (VOD) were documented (4.7%), and 1 of these patients died of severe VOD. Other BU/CY conditioning-associated toxicities were diffuse alveolar hemorrhage in 1 patient and hemorrhagic cystitis in 8 patients. Four patients died due to TRM, for a 30-month TRM of 9.7% ± 4.6%. This study demonstrates that i.v. BU/CY can be considered a feasible conditioning regimen for adult ALL, with low incidences of VOD and TRM.

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