T-Cell Replete Haploidentical Stem Cell Transplantation with Post-Transplantation Cyclophosphamide (PTCy) for Pediatric Patients with Primary Immunodeficiencies (PID) - a Survey of the Pediatric Transplantation Working Group of the Brazilian Society of Bone Marrow Transplantation (SBTMO)

Abstract

Introduction Allogeneic hematopoietic stem cell transplantation (HSCT) is a curative treatment for several primary immunodeficiencies. In the absence of a matched sibling or a well matched unrelated donor, the use of an haploidentical family donor can be considered. Historically, most part of haploidentical HSCT were performed with in vitro T-cell depletion techniques that aren't worldwide available, especially in middle or low income countries. The use of T-cell replete haploidentical HSCT with PTCy in children with PID has been described in only a few case-series. Objectives To report the outcomes of haploidentical HSCT with PTCy for children with severe PID Methods Retrospective chart review of 73 patients with PID who underwent haploidentical HSCT with PTCy from July 2012 to May 2019 at 9 centers in Brazil. Results Fifty-five patients received first allogeneic transplants, and 18 were rescued after graft failure of a previous transplant. Median age was 1.6 years (2 months to 19 years). Most patients were male (n=54) and had active infection at the time of transplant (n=50). Diagnoses were: severe combined immunodeficiency (n=34), Wiskott-Aldrich Syndrome (n=14), chronic granulomatous disease (n=10) and other PID (n=15). Donors were father (N=46), mother (N=24), or siblings (N=3); and cell source was predominantly bone marrow (94% of patients). Conditioning regimen was non-myeloablative (fludarabine 150mg/m2 + cyclophosphamide 29mg/Kg + TBI 200cGy) in 35 patients; and myeloblative in 38 patients (most part receiving: bussulfan + fludarabine 160mg/m2 + ATG 4-7,5 mg/Kg or alemtuzumab 0,5-1mg/Kg). GVHD prophylaxis was PT-Cy, CsA or Tacrolimus and MMF. The median follow-up of surviving patients was 24 months. Four patients died before 28 days and were not evaluable for engraftment. Sixty-one patients engrafted in a median of 15 days. The 100-day incidence of acute GVHD grades II–IV was 33% and grades III–IV, 14%. The incidence of Chronic GVHD at 1 year was 16%. Twenty-two patients died, most of them due to infection (n=15). The two-year overall survival was 66%. There was no difference in OS between patients receiving first allogeneic or rescue transplants, suggesting survival bias. Patients transplanted for WAS or SCID had a better OS compared to those transplanted for CGD (p=0,02). Conclusion In conclusion, 66% of Brazilian children with severe PID and no matched donor could be cured with haploidentical HSCT with PTCy. The high proportion of patients in our cohort transplanted with an active infection (70%) may have had a major impact in our results. The optimal conditioning regimen for these patients and long term follow up data are the objective of our ongoing studies.