Reduced Intensity (RI) Allogeneic Stem Cell Transplantation (ALLOSCT) with Umbilical Cord Blood (UCB) in Pediatric Patients with Malignant and Non-Malignant Diseases.
Authors: Bradley Mary Brigid , Harrison Lauren , Billote Genia , Cooney Erin , Reddy Gerard , Militano Olga , Wolownik Karen , Hawks Ria , George Diane , Del Toro Gustavo , Garvin James , Bhatia Monica , Satwani Prakash , Cairo Mitchell S. 
Published: October 2019

We and others have demonstrated that cord blood can be used successfully as an alternative allogeneic stem cell source in pediatric and adult recipients with both malignant and non malignant diseases (Cairo et al, Blood 1997). However, there is significant amount of morbidity and mortality following myeloablative UCBT (Kurtzberg et al, NEJM1996; Rubinstein et al, NEJM1998). Reduced intensity conditioning may potentially reduce the incidence of regimen related morbidity and mortality and the late effects associated with myeloablative regimens without increasing the risk of graft failure or relapse in children and adolescents undergoing unrelated cord blood transplantation (Del Toro/Cairo et al, BMT 2004). Successful engraftment has been demonstrated in adult recipients with advanced hematologic malignancies who received unrelated mismatched cord blood following reduced intensity conditioning regimens (Barker et al, Blood 2003). We report the results in 18 pediatric recipients, 6F:12M, median age 9 years (0.5 – 21). 17 received unrelated UCB, the majority mismatched at 1–2 HLA loci, 4/6 (n=11) 5/6 (n=4), 6/6 (n=2); 1 matched related UCB (6/6). Recipients were transplanted for malignant n=14, [HD(5), NBL(4), CML(1), NHL(1), MDS(2), AML(1)], and non malignant n=4 [B-thalassemia(1), HLH(2), WAS(1)] diseases. Poor risk disease was defined as induction failure, PD, SD, CR3 or greater and 2nd AlloSCT (n=5). RI conditioning consisted of: busulfan 8mg/kg, fludarabine 150mg/m2 (n=11); busulfan 8mg/kg, fludarabine 180mg/m2 (n=3); fludarabine 150mg/m2, cyclophosphamide 120 mg/kg (n=2); fludarabine 180 mg/m2, cyclophosphamide 60 mg/kg, etoposide 900 mg/m2 (n=2). Graft versus host disease (GVHD) prophylaxis: FK506 0.03 mg/kg/day and mycophenolate mofetil 900mg/m2 q6h (Osunkwo/Cairo et al, BBMT 2004). Median TNC was 5.3 x107/kg (0.58–10.8) and CD34 was 2.4x105/kg (0.34–6.95). The median day to neutrophil engraftment was 17 days (1– 47) and to platelet engraftment was 34.5 days (6–170). Engraftment was 72.2%. There were 5 primary graft failures observed (1 B-Thal, 1 CML, 2 HLH, 1 MDS). Within this subgroup of graft failures, 3 were regrafted with myeloablative conditioning followed by a second UCBT and 100% engrafted. The median percent of mixed donor chimerism in the remaining 13 patients at day 60 was 99 % (55–100). 5 of 13 evaluable patients developed acute GVHD, only 2 of those 5 patients developed grade III/IV aGVHD. 1 patient developed extensive cGVHD. There were 7 deaths (4 PD, 1 GVHD, 2 infection). The probability of 1 year OS in all patients was 63%. Despite a log less nuc/kg with UCB vs. PB or BM, the 1 yr OS in standard risk patients was 80%, and poor risk patients was 20%. These preliminary results indicate that RI AlloSCT using UCB may result in more rapid hematopoietic reconstitution while decreasing regimen related morbidity and mortality compared to myeloablative UCB Allo SCT and be associated with high to full mixed donor chimerism in most disease states. Patients with CML, B-Thal, MDS, and HLH require increased intensity of conditioning and we have modified our protocols so that subsequent B-Thal, HLH, and CML patients have had successful engraftment. Further follow-up is required to evaluate the difference, if any, in long-term effects following RI Allo UCBT.