225: The addition of etoposide to Bu16/Cy200 in the conditioning of children with acute myeloid leukemia (AML) undergoing allogeneic stem cell transplantation (SCT) is associated with improved survival

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Relapse remains the major concern for children with AML undergoing SCT, and we have previously shown that intensifying the conditioning by adding etoposide at 60 mg/kg and consequently reducing the busulfan (Bu) dose to 12 mg/kg and the cytoxan (Cy) to 90 mg/kg did not result in any significant improvement of the survival; we suggested then that the reduction of Bu/Cy doses necessitated by addition of the high dose of etoposide could have affected the outcome and we hypothesized that adding a lower dose of etoposide and keeping the Bu/Cy at the conventional doses may offer better survival to AML patients undergoing allogeneic SCT. We present here our results using such a protocol.
Patients and Methods: From March 2003 until December 2006, 33 patients with AML (24 in CR1, 8 in CR 2) underwent allogeneic SCT and were conditioned with Bu 16 mg/kg po, Cy 200 mg/kg iv plus etoposide 900 mg/m2 iv, median age was 9.6 years. This cohort of patients (group B) was compared with 18 AML patients (17 in CR 1, 1 in CR 2) who underwent SCT from July 93 thru February 96, median age at SCT was 7.25 years, patients were conditioned with only Bu 16 mg/kg po and Cy 200 mg/kg iv (group A).
Results: Median days to ANC ≥ 500 × 106/l was 21 days and 15 days in groups A and B respectively, median days to platelet count ≥ 20 × 109/l was 22 days and 26 days in groups A and B respectively (P= NS). The incidence of complications was similar, acute GVHD grade 2 or higher developed in 5% and 9% in groups A and B respectively (P= NS), hemorrhagic cystitis developed in 11% and 15% in groups A and B respectively, no VOD developed in either group. The 4 year overall survival for groups A and B respectively was 50% and 68.2% (P = 0.3) and the 4 year event-free survival for groups A and B respectively was 33% and 68.2% (P = 0.1).
Conclusions: The addition of etoposide to Bu16/Cy200 was not associated with increased toxicity, and although it did not reach statistical significance, it does appear to be associated with a better overall and event-free survival. Larger scale studies are advised to further corroborate our findings.


This work was published before the author joined Aga Khan University

Publication (Name of Journal)

Biology of Blood and Marrow Transplantation