Superior Survival Rate Following Conditioning with Etoposide in Childhood ALL

This retrospective study compared the outcome following three different conditioning regimens used for allogeneic haematopoietic stem cell transplantation (SCT) of 445 Nordic children with acute lymphoblastic leukemia (ALL). The children received myeloablative conditioning with cyclophosphamide (n=325), Cytarabine (Ara-C) (n=68), Etoposide (n=47) or other (n=8) in combination with total body irradiation (85%). The mean age at SCT was 9.0 years (0.58-17.42), the median follow up 9.25 years (1.89-20.3). Grafts were from sibling donors (n=150), unrelated donors (n=274) or other related (n=24). Disease status at SCT was CR1 (n=176), CR2 (n=204), CR3 (n=51) or in relapse (n=14). Children conditioned with Etoposide and Ara-C had significantly better overall survival compared with those who received Cyclophosphamide (pOS 0.74, 0.65 and 0.44 respectively, p<0.0001). The cumulative incidence of relapse was 0.4 (0.35-0.46) for the Cyclophosphamide group vs 0.23 and 0.19 (p=0.008) for the Etoposide and Ara-C group. The cumulative incidence for non leukemia mortality was 0.17 vs 0.07 and 0.16 (p=0.19) respectively.  In a multivariate analysis conditioning regimen was an independent prognostic factor with the hazard ratio of 0.44 (Etoposide) and 0.56 (Ara-C), overall p=0.002.  In conclusion we suggest that high dose Etoposide is superior to high dose Cyclophosphamide in conditioning for childhood ALL.