CD45 RA Depletion As an Allogeneic Hematopoietic Transplantation Platform in Children from HLA-Identical Donors

Abstract

Background In hematopoietic transplantation, graft T lymphocytes play a determining role in promoting hematopoiesis, transferring immunity to pathogens and acting as mediators of the graft-versus-leukemia effect (GVL). However, they are also responsible for graft-versus-host disease (GVHD), the main cause of post-transplant morbidity and mortality. Depletion of CD45 RA lymphocytes, by eliminating naive T lymphocytes from inoculum, aims to conserve GVL without GVHD. Methods Since April 2016, 20 patients (12 boys and 8 girls), with a median age of 8 years, have undergone an allogeneic hematopoietic transplant from an HLA identical donor with CD45 RA depletion. Indication for transplant was: acute lymphoblastic leukemia (n=7), acute myeloblastic leukemia (n=7) and myelodysplasia (n=6). Donor was familiar in 7 cases and unrelated in 13. Conditioning regimen consisted on fludarabine, busulfan and thiotepa. Median of CD34 + cells infused was 6.82 × 106/ Kg. On day 0, +15 and +30 a programmed infusion of 1 × 106 / Kg lymphocytes CD45RA- was performed. Results All patients grafted with a median neutrophil (> 0.5 × 109/ L) and platelet (> 20 × 109/ L) engraftment time of 15 and 10 days, respectively. Only one patient has developed acute GVHD grade I and another patient has developed moderate chronic GVHD. Immune reconstitution was early and rapid in all lymphocyte subsets (see Figure 1). Four patient have relapsed so far. There was no case of toxic mortality. Overall survival was 77 ± 10% with a median follow-up of 1 year (2 months-2 years). At present, 17 patients are alive and doing well (Figure 2). Conclusions Allogeneic transplantation with CD45 lymphocytes RA depletion resulted on encouraging results, with a very low incidence of acute and chronic GVHD, but preserving the GVL effect by infusing CD45 RA- donor lymphocytes. Conflict of interest Miguel Angel Diaz, Marta Gonzalez-Vicent, Blanca Molina, Elena Sebastian, Josune Zubicaray, Julian Sevilla: Nothing to disclose. Keywords CD45RA depletion, Allogeneic transplant, Children