Role of Conditioning Regimens in Pediatric Hematopoietic STEM CELL Transplant for Malignant Disorders: Reduced Toxicity Versus Standard Myeloablative Regimens

Introduction: Allogeneic hematopoietic stem cell transplantation (HSCT) for malignant disorders is complicated by the risk of early and late treatment related toxicities. Reduced toxicity conditioning (RTC) regimens using Busulfan/Fludarabine (Bu/Flu) +/- 400Gy of Total Body Irradiation (TBI) were designed to lower the risk of these complications while achieving similar outcomes to the standard myeloablative conditioning (sMAC) with Busulfan/Cyclophosphamide (Bu/Cy) or 1200 Gy TBI/ Cyclophosphamide (TBI/Cy). Methods We compared outcomes of children conditioned with sMAC versus RTC pre-HSCT between Jan 2008 and Dec 2011. In both regimens, the total dose of Bu was adjusted to target an AUC of 16000 µM*min. Long term outcome analysis included assessment of change in pulmonary function test (PFT), cardiac function, thyroid function and growth from baseline. Patients with GVHD of the lung were excluded for assessing pulmonary function. Results Sixty seven patients with AML/MDS (n=29), ALL (n= 32), others (n=6), transplanted were identified who received sMAC (n=50) and RTC (n=17). HSC source was peripheral blood (PB) (n=30), cord (n=14) and bone marrow (n=6) in sMAC group compared to all PBSC in the RTC group. 64/67 patients engrafted with no graft failure in the RTC group. The mean time to neutrophil engraftment was comparable in the both groups (18.0 and 18.4 days). The time to platelet count of >20K and >50K was significantly shorter in the RTC group compared to sMAC group (17 and 18days compared with 32 and 40 days respectively). OS, EFS, relapse rates, were comparable with no significant difference in 100 day mortality. There was no significant difference in the rates of >Gr 2 aGVHD (18% sMAC and 23% RTC p=0.7) or cGVHD between the two groups (36% sMAC versus 47% RTC p=0.5). A comparison of long term toxicity including thyroid function, growth and cardiac function showed no significant difference at 1 and 2yrs post HSCT. However analysis of PFT (FEV1, FEV1/FVC ratio and VC) in 25 sMAC and 7 RTC patients showed a significant worsening at 2 years post HSCT in the sMAC group versus the RTC group. (p=0.008, 0.04 and 0.02 respectively) Conclusions: RTC is an effective, safe conditioning regimen with comparable outcomes to standard regimens with a definite improvement in platelet recovery and decreased long term pulmonary toxicity. Larger studies are needed to modify the RTC protocol to further minimize toxicities and improve overall QoL of survivors.