Abstract
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.
Augmenting Total Body Irradiation with a Cranial Boost before Stem Cell Transplantation Protects Against Post-Transplant Central Nervous System Relapse in Acute Lymphoblastic Leukemia
