Bone marrow transplantation for severe combined immune deficiency

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.