Haploidentical Stem Cell Transplantation with Post-Transplant Cyclophosphamide As Graft-Versus-Host Disease Prophylaxis in Pediatric Hematologic Malignancies

Background Hematopoietic stem cell transplantation (HSCT) is used in pediatric patients with acute leukemia, after a relapse to bone marrow, or in first remission in case of high risk disease. If necessary, 75% of the cases do not have a compatible related donor and it is not always possible to have a compatible unrelated donor or an umbilical cord blood unit. Therefore, using haploidentical alternative donors of hematopoietic stem cells (HSC) is becoming more frequent. Objective The purpose of this is to report the results of haploidentical hematopoietic stem cell transplantation with post-transplant cyclophosphamide (PTCy) in a group of pediatric patients, which lacks a related HLA compatible donor, at the National Pediatrics Institute in Mexico City, Mexico, in the period between January 2012 thru December 2016. Methods We retrospectively reviewed 27 patients´ files 2 , days -6 to -2, cyclophosphamide 14.5 mg/kg, days -6 and -5, and low-dose total body irradiation 200 cGy at day -1. Graft versus host disease prophylaxis comprised Cy 50 mg/kg intravenous on day 3 and 4 after transplantation, followed by tacrolimus 0.06 mg/kg and mycophenolate mofetil 15 mg/kg, each beginning on day 5. According to the availability of bone marrow harvesting kit, the HSC source was peripheral blood in twenty patients and bone marrow in seven. The median number of CD34+ cells infused was 5.41 × 10 6 /kg (range, 1.27-22.6). Results Fourteen patients (51.6%) presented complete and sustained chimerism. Overall survival is presented in Figure 1. Graft failure occurred (48.1%) more frequently in the group of patients in whom bone marrow was used as a source of HSC ( p =0.26). Nine patients with complete chimera, whose HSC source turned out to be PB, presented acute-GVHD III-IV (p = 0.06). Four of the patients whom presented full engraftment died, three of them due to infectious processes (cytomegalovirus pneumonia, AH1N1 pneumonia, abdominal sepsis secondary to intestinal perforation and E. coli sepsis), before +100-day post-transplantation. All these patients presented acute-GVHD III-IV. The fourth patient who died, also the cause was infectious (pulmonary sepsis secondary to Morganella morganii ), thirteen months after the transplant and without history of GVHD. Of the thirteen patients who presented primary graft failure, seven of them are alive and without evidence of tumoral activity Discussion Haploidentical transplantation with PTCy is a feasible therapeutic option in pediatric patients with malignant hematological diseases who require a HSCT and do not have a matched sibling or unrelated donor available. Conflict-of-interest disclosure: The authors declare they have nothing to disclose. Correspondence: Gerardo Lopez-Hernandez. loherge@gmail.com Bibliography Klein OR, Buddenbaum J, Tucker N, et al. Nonmyeloablative Haploidentical Bone Marrow Transplantation with Post-Transplant Cyclophosphamide for Pediatric and Young Adult Patients with High-Risk Hematologic Malignancies. Biol Blood Marrow Transplant. 2017; 23(2): 325-332. Gonzalez-Llano O, Gonzalez-Lopez EE, Ramirez-Cazares AC, et al. Haploidentical peripheral blood stem cell transplantation with posttransplant cyclophosphamide in children and adolescents with hematological malignancies. Pediatr Blood Cancer . 2016; 63: 2033-2037. Robinson TM, O9Donnell PV, Fuchs EJ, Luznik L. Haploidentical bone marrow and stem cell transplantation: experience with post-transplantation cyclophosphamide. Semin Hematol . 2016; 53(2): 90-97. Fuchs EJ, Huang XJ, Miller JS. HLA-haploidentical stem cell transplantation for hematologic malignancies. Biol Blood Marrow Transplant. Biol Blood Marrow Transplant . 2010; 16 (1 Suppl): S57-S63. Disclosures No relevant conflicts of interest to declare.