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


Biology of Blood and Marrow Transplantation