TCRαβ+ and CD19+ cell depleted Haploidentical and Mismatched Hematopoietic Stem Cell Transplantation in Primary Immune Deficiency

Publication date: Available online 3 August 2017
Source:Journal of Allergy and Clinical Immunology
Author(s): Ravi M. Shah, Reem Elfeky, Zohreh Nademi, Waseem Qasim, Persis Amrolia, Robert Chiesa, Kanchan Rao, Giovanna Lucchini, Juliana M.F. Silva, Austen Worth, Dawn Barge, David Ryan, Jane Conn, Andrew J. Cant, Roderick Skinner, Intan Juliana Abd Hamid, Terence Flood, Mario Abinun, Sophie Hambleton, Andrew R. Gennery, Paul Veys, Mary Slatter
BackgroundAllogeneic hematopoietic stem cell transplantation (HSCT) is used as a therapeutic approach for primary immunodeficiencies (PIDs). The best outcomes have been achieved using HLA-matched donors, but when a matched donor is not available, a haploidentical or mismatched unrelated donor (mMUD) can be useful. Various strategies are used to mitigate the risk of graft versus host disease (GvHD) and rejection associated with such transplants.ObjectiveWe sought to evaluate the outcomes of haploidentical or mMUD HSCT after depleting GvHD causing TCRαβCD3+ cells from the graft.MethodsCD3+TCRαβ+/CD19⁺ depleted grafts were given in conditioned (except three) children with PIDs. Treosulfan (busulfan in one), fludarabine, thiotepa and ATG or alemtuzumab conditioning was used in 77% cases, and all but four received GvHD prophylaxis.Results25 patients with 12 types of PIDs received 26 HSCTs. Three were transplanted for refractory GvHD developing after first cord transplantation. At 20.8 months (5 month- 3.3 years) median follow up, 21/25 patients survived and were cured of underlying immunodeficiency. Overall and Event Free Survival at 3 years was 83.9% and 80.4% respectively. Cumulative incidence (CI) of Grade II-IV acute GvHD was 22±8.7%. No case of visceral or chronic GvHD was seen. CI of graft failure, CMV or/and adeno viral infections and transplant related mortality at 1 year were 4.2±4.1%, 58.8±9.8% and 16.1±7.4% respectively. Patients going into transplant with systemic viral infections had poor survival in comparison to those with absent or resolved infection (33.3% vs.100%).ConclusionCD3+TCRαβ⁺ and CD19⁺ depleted haploidentical or mMUD HSCT is a practical and viable alternative for children with a range of PIDs.

Teaser

CD3+TCRαβ⁺ and CD19+ cell depleted haploidentical or mMUD HSCT has reproducible outcomes in children with a range of PIDs resulting in good immune reconstitution. Viral infections before or after HSCT are major contributors to mortality and morbidity.


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