Bone marrow transplantation for severe combined immune deficiency

JAMA. 2006 Feb 1;295(5):508-18. doi: 10.1001/jama.295.5.508.


Context: Bone marrow transplantation (BMT) using stem cells obtained from a family-related, HLA-identical donor (RID) is the optimal treatment for patients with severe combined immune deficiency (SCID). In the absence of an RID, HLA-mismatched related donors (MMRDs) are often used. However, compared with RIDs, use of MMRDs for BMT is associated with reduced survival and inferior long-term immune reconstitution. Use of HLA-matched unrelated donors (MUDs) represents another potential alternative for BMT.

Objective: To compare outcomes and immune reconstitution in a large cohort of patients with SCID who received RID, MUD, or MMRD BMT.

Design, setting, and patients: Retrospective study of medical records from 94 infants diagnosed as having SCID who received BMT between 1990 and 2004 at 1 Canadian and 1 Italian pediatric referral center. Thirteen, 41, and 40 patients received RID, MUD, and MMRD BMT, respectively.

Main outcome measures: Survival and graft failure, along with incidence of graft-vs-host disease, infections, and other complications; immune reconstitution was assessed in children who survived for more than 2 years after BMT.

Results: Survival after RID BMT was highest. Twelve (92.3%) of 13 patients who received RID BMT, 33 (80.5%) of 41 who received MUD BMT, and 21 (52.5%) of 40 patients who received MMRD BMT survived. Compared with MMRD BMT, survival was significantly higher with RID (P = .008) or with MUD (P = .03). Graft failures and need for repeat BMT were more common in patients receiving MMRD BMT than in those who underwent MUD BMT. Long-term reconstitution of a full T-cell repertoire was achieved more frequently following MUD BMT (94.7%) than after MMRD BMT (61.1%) (P = .02). Acute graft-vs-host disease was documented in 73.1% of patients following MUD BMT but in only 45% after MMRD BMT (P = .009). Conversely, interstitial pneumonitis was observed more frequently after MMRD BMT (14 [35.0%] of 40) than after MUD BMT (3 [7.3%] of 41; P = .002).

Conclusion: Our study suggests that in the absence of a relative with identical HLA, MUD BMT may provide better engraftment, immune reconstitution, and survival for patients with SCID than MMRD BMT.

Publication types

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

MeSH terms

  • Bone Marrow Transplantation* / immunology
  • Cohort Studies
  • Female
  • Histocompatibility Testing
  • Histocompatibility*
  • Humans
  • Infant
  • Male
  • Proportional Hazards Models
  • Retrospective Studies
  • Severe Combined Immunodeficiency / immunology
  • Severe Combined Immunodeficiency / therapy*
  • Survival Analysis
  • Treatment Outcome