Outcome of hematopoietic stem cell transplantation for adenosine deaminase-deficient severe combined immunodeficiency

Blood. 2012 Oct 25;120(17):3615-24; quiz 3626. doi: 10.1182/blood-2011-12-396879. Epub 2012 Jul 12.

Abstract

Deficiency of the purine salvage enzyme adenosine deaminase leads to SCID (ADA-SCID). Hematopoietic cell transplantation (HCT) can lead to a permanent cure of SCID; however, little data are available on outcome of HCT for ADA-SCID in particular. In this multicenter retrospective study, we analyzed outcome of HCT in 106 patients with ADA-SCID who received a total of 119 transplants. HCT from matched sibling and family donors (MSDs, MFDs) had significantly better overall survival (86% and 81%) in comparison with HCT from matched unrelated (66%; P < .05) and haploidentical donors (43%; P < .001). Superior overall survival was also seen in patients who received unconditioned transplants in comparison with myeloablative procedures (81% vs 54%; P < .003), although in unconditioned haploidentical donor HCT, nonengraftment was a major problem. Long-term immune recovery showed that regardless of transplant type, overall T-cell numbers were similar, although a faster rate of T-cell recovery was observed after MSD/MFD HCT. Humoral immunity and donor B-cell engraftment was achieved in nearly all evaluable surviving patients and was seen even after unconditioned HCT. These data detail for the first time the outcomes of HCT for ADA-SCID and show that, if patients survive HCT, long-term cellular and humoral immune recovery is achieved.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Deaminase / deficiency
  • Adenosine Deaminase / immunology
  • Agammaglobulinemia / drug therapy*
  • Agammaglobulinemia / immunology
  • Agammaglobulinemia / mortality
  • Agammaglobulinemia / pathology
  • Child
  • Child, Preschool
  • Female
  • Graft Survival
  • Hematopoietic Stem Cell Transplantation*
  • Histocompatibility Testing
  • Humans
  • Immunity, Cellular
  • Immunity, Humoral
  • Infant
  • Infant, Newborn
  • Kaplan-Meier Estimate
  • Lymphocyte Count
  • Male
  • Myeloablative Agonists / therapeutic use
  • Retrospective Studies
  • Severe Combined Immunodeficiency / drug therapy*
  • Severe Combined Immunodeficiency / immunology
  • Severe Combined Immunodeficiency / mortality
  • Severe Combined Immunodeficiency / pathology
  • Siblings
  • T-Lymphocytes / immunology
  • Transplantation Conditioning*
  • Treatment Outcome
  • Unrelated Donors

Substances

  • Myeloablative Agonists
  • Adenosine Deaminase

Supplementary concepts

  • Severe combined immunodeficiency due to adenosine deaminase deficiency