Haploidentical Related Donor Hematopoietic Stem Cell Transplantation for Dedicator-of-Cytokinesis 8 Deficiency Using Post-Transplantation Cyclophosphamide.


Shah N. N. , Freeman A. F. , Su H., Cole K., Parta M., Moutsopoulos N. M. , ...More

Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation, vol.23, no.6, pp.980-990, 2017 (Journal Indexed in SCI) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 23 Issue: 6
  • Publication Date: 2017
  • Doi Number: 10.1016/j.bbmt.2017.03.016
  • Title of Journal : Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation
  • Page Numbers: pp.980-990
  • Keywords: Dedicator-of-cytokinesis-8 (DOCK8) deficiency, Haploidentical transplantation, Immune reconstitution, BONE-MARROW-TRANSPLANTATION, VERSUS-HOST-DISEASE, HYPER-IGE SYNDROME, CHRONIC GRANULOMATOUS-DISEASE, DOCK8 DEFICIENCY, HEMATOLOGIC MALIGNANCIES, COMBINED IMMUNODEFICIENCY, NONMALIGNANT DISORDERS, ALPHA-BETA, BLOOD

Abstract

Dedicator-of-cytokinesis 8 (DOCK8) deficiency, a primary immunodeficiency disease, can be reversed by allogeneic hematopoietic stem cell transplantation (HSCT); however, there are few reports describing the use of alternative donor sources for HSCT in DOCK8 deficiency. We describe HSCT for patients with DOCK8 deficiency who lack a matched related or unrelated donor using bone marrow from haploidentical related donors and post-transplantation cyclophosphamide (PT/Cy) for graft-versus-host disease (GVHD) prophylaxis. Seven patients with DOCK8 deficiency (median age, 20 years; range, 7 to 25 years) received a haploidentical related donor HSCT. The conditioning regimen included 2 days of low-dose cyclophosphamide, 5 days of fludarabine, 3 days of busulfan, and 200 cGy total body irradiation. GVHD prophylaxis consisted of PT/Cy 50 mg/kg/day on days +3 and +4 and tacrolimus and mycophenolate mofetil starting at day +5. The median times to neutrophil and platelet engraftment were 15 and 19 days, respectively. All patients attained >90% donor engraftment by day +30. Four subjects developed acute GVHD (1 with maximum grade 3). No patient developed chronic GVHD. With a median follow-up time of 20.6 months (range, 9.5 to 31.7 months), 6 of 7 patients are alive and disease free. Haploidentical related donor HSCT with PT/Cy represents an effective therapeutic approach for patients with DOCK8 deficiency who lack a matched related or unrelated donor. Published by Elsevier Inc. on behalf of the American Society for Blood and Marrow Transplantation.