HLA-Haploidentical Transplantation in Children with Primary Immunodeficiency Using Post Cyclophosphamide

Abstract

Introduction Hematopoietic Stem Cell Transplantation (HCT) is considered the curative treatment for patients with Primary Immune Deficiencies (PIDs). Finding a full matched Human leukocyte donor remains an obstacle for performing the bone marrow transplant in a timely fashion. Haplo-identical HCT is an alternative treatment option for patients, who do not have access to full-matched donor. We are reporting preliminary data on our experience of HCT in PID patients using haplo-identical donor with post-transplant Cyclophosphamide. Methods Eleven transplant naive PID patients were infused from June 2017 to August 2018 using a haplo-identical HLA donor at our institution. Eight (72.7%) of the recipients were male. Median age at infusion was 0.9 years (Min: 5.5 months Max: 2.3 years). Primary indications for transplantation included Severe Combined Immune Deficiency (SCID) in seven (63.6%), Omenn Syndrome in two (18.2%), and Chediak-Higashi syndrome and Combined Immunedeficiency in one (9.1%) each. All received GVHD prophylaxis comprising of Cyclophosphamide, Mycophenolate mofetil (MMF), and Cyclosporine regimen. Conditioning regimen was BU/FLU/Thiotepa (±ATG) in six (54.5%) recipients followed by BU/FLU/ATG in four (36.4%). Source of stem cells was bone marrow in ten patients (90.9%) while for the remaining one child PBSC was utilized. Results Eight patients (72.7%) had ANC engraftment with a median time to ANC recovery 15.5 days (Minimum: 13, maximum: 22) whereas, seven (63.6%) of our patients achieved platelets recovery (Median: 33 days, minimum: 16, maximum: 150). In terms of chimeric studies, all but one patient, engrafted at Day +100. Cumulative incidence of aGVHD was 27.3% (n=3); no chronic GVHD was recorded. At a median follow-up of 18.8 months (95% CI: 14.6-23.1), cumulative probability of overall survival at one year from infusion, for our patients is 72.7% (±13.4%). Hemorrhagic cystitis was seen in only one (9.1%) patient while two (18.2%) experienced mucositis (Grade1 or 2). Three (27.3%) contracted CMV infection and were successfully treated.At one-year follow-up lymphoid chimerism remains >95% donor type and CD3:1717 mm3 and CD19 521 mm3 Conclusion Preliminary outcome data on our small cohort of immunodeficiency patients who underwent HCT using Haplo-identical donor with Post-Cy is quite encouraging with durable and stable donor chimerism and CD3 and CD19 engraftment.