Outcome of Stem Cell Transplantation for Pediatric Acute Lymphoblastic Leukemia. A Comparison of Cyclophosphamide and Total Body Irradiation Versus VP16 and Total Body Irradiation Conditioning Regimens.

Stem cell transplantation (SCT) has become the standard therapy for children with relapsed acute lymphoblastic leukemia (ALL) or certain high-risk features at diagnosis. The authors report their experience with SCT for 108 children with ALL conditioned with 2 different regimens over 14 years period. Children (0–18y) who received fully matched-related (MRD) or fully matched-unrelated (MUD) for a diagnosis of ALL in the Hospital for Sick Children, Toronto between 1990–1998 were conditioned with a single dose of VP16 (60mg/kg infused over 4 hours) and fractionated total body irradiation (TBI; 1200cGy) in six fractions over 3 days (VP/TBI). Between 1998–2003, children with ALL were conditioned with cyclophosphamide 50mg/kg infused over 1 hour daily for 4 days followed by fractionated total body irradiation (TBI; 1200cGy) in six fractions over 3 days (CY/TBI). All children received cyclosporine A and a short course of methotrexate for graft versus host disease (GVHD) prophylaxis.

Results: Sixty-two children with ALL were conditioned with VP16/TBI, 36 MRD transplantation and 26 MUD transplantation. Median age at SCT was 9.4y (range 0.8–19.4). Remissions status at SCT were; complete remission (CR) 1 (n=17), CR 2 (n=32), and CR 3 (n=12) and one patient received SCT in relapse. Forty-six patients were conditioned with CY/TBI, 23 MRD transplantation and 23 MUD transplantation. Median age at SCT was 9.2y (range 1–17.5) Remissions status at SCT time were; CR 1 (n=11), CR 2 (n=29), and CR 3 (n=6). Neutrophils engraftment (defined as absolute neutrophil count (ANC) of > 0.5 x 10⁹/l for 2 consecutive days) occurred at 19d (range 10–28d) and 17d (range 10–28d) for the VP16/TBI and the CY/TBI groups, respectively. Two patients failed to engraft in the VP16/TBI group, one required re- conditioning with cyclophosphamide and ATG and a second dose of stem cells from the same donor, the other patient sustained a fatal intracranial hemorrhage. There was no significant difference in three years event free survival (EFS) and overall survival (OS) between the groups with EFS and OS of 47 ± 7%, 55 ± 7% for the VP16/TBI and 51 ± 8%, 53 ± 8% for the CY/TBI group. There was no significant difference in the incidence of acute or chronic graft versus host disease (GVHD), transplant related mortality (TRM) between the 2 groups.

Conclusion: Both VP16/TBI and CY/TB regimen are equally effective preparative regimens for SCT in pediatric ALL.