Haplo-Identical Stem Cell Transplantation with Post-Transplant Cyclophosphamide in High-Risk Pediatric Hematologic Malignancies: A Comparison of TBI-Based Conditioning Regimen with Thiotepa-Based Conditioning Regimen

Abstract

Patients diagnosed as ALL, AML or MDS with high-risk features need myeloablative conditioning regimen prior to SCT. Total body irradiation (TBI) contacting regimens have been commonly used, whereas thiotepa can mimic the effect of radiation. We would like to evaluate clinical outcomes and assess complications of haplo-identical SCT with post-transplant cyclophosphamide (PTCY) using TBI-based condition regimen (TBI-regimen) versus thiotepa (thio)-based conditioning regimen (Thio-regimen) in high-risk childhood hematologic malignancies. We retrospectively reviewed medical record of patients with high-risk hematologic malignancies, aged less than 20 years old, between August 2012 and September 2018. HLA studying of all patients and their parents were done by high-resolution technique searching for A, B, C, DR and DQ subunits. Parents with greater HLA matching or those with presence of KIR B haplotype were chosen to be a donor for patients. Patients received TBI-regimen (low-dose TBI, fludarabine, busulfan and melphalan) during August 2012 to April 2017. While patients received Thio-regimen (thio, fludarabine and busulfan) during March 2015 to September 2018 due to an availability of thio in Thailand. Patients were given unmanipulated stem cell products on day 0, then received PTCY, and continued either a calcineurin inhibitor or an mTOR inhibitor with mycophenolate as a graft-versus-host-disease (GvHD) prophylaxis regimen. Survival analysis was calculated by Kaplan-Meier analysis and log-rank test was used to compare variables. Forty-three patients (21 of male) were enrolled; 22, 19 and 2 patients were diagnosed as ALL, AML and MDS, respectively. Twenty-three patients received TBI-regimen, and 26 patients received mother derived stem cell products. Most of the donors had 5/10 or 6/10 HLA-matched. The median CD34+ cell dose was 9.24 (2.06-21.8) cells ×106/kg. One patient died from disseminated adenoviral infection prior to neutrophil engraftment. For 42 evaluable patients, the median time to neutrophil and platelet engraftment was 15 (12-26) days and 22 (12-100) days, respectively. At the median follow-up time of 18.5 (0.6-74.2) months, the overall survival rates of TBI-regimen and Thio-regimen were 63.68 and 61.98%, respectively (p=0.69), while the event-free survival rates of TBI-regimen and Thio-regimen were 68.82 and 66.67%, respectively (p=0.61). Viral infections, CMV, BKV and adenovirus, were the most common infectious complications and were comparable in both groups. Moreover, rates of acute and chronic GVHD in both groups were not significantly different. Relapse was the most common cause of death in both regimens while non-relapse mortality rates of both regimens were approximately 17%. Haplo-identical SCT in high-risk pediatric hematologic malignancies using Thio-regimen had comparable clinical outcomes and complications as those using TBI-regimen.