BACKGROUND: Patients with severe combined immunodeficiency disease who have matched sibling donors (MSDs) can proceed to hematopoietic cell transplantation (HCT) without conditioning chemotherapy. OBJECTIVE: We sought to determine whether the results of HCT without chemotherapy-based conditioning from matched unrelated donors (URDs), either from volunteer adults or umbilical cord blood, are comparable with those from MSDs. METHODS: We performed a multicenter survey of severe combined immunodeficiency transplantation centers in North America, Europe, and Australia to compile retrospective data on patients who have undergone unconditioned HCT from either URDs (n = 37) or MSDs (n = 66). RESULTS: Most patients undergoing URD HCT (92%) achieved donor T-cell engraftment compared with 97% for those with MSDs; however, estimated 5-year overall and event-free survival were worse for URD recipients (71% and 60%, respectively) compared with MSD recipients (92% and 89%, respectively; P < .01 for both). URD recipients who received pre-HCT serotherapy had similar 5-year overall survival (100%) to MSD recipients. The incidences of grade II to IV acute and chronic graft-versus-host disease were higher in URD (50% and 39%, respectively) compared with MSD (22% and 5%, respectively) recipients (P < .01 for both). In the surviving patients there was no difference in T-cell reconstitution at the last follow-up between the URD and MSD recipients; however, MSD recipients were more likely to achieve B-cell reconstitution (72% vs 17%, P < .001). CONCLUSION: Unconditioned URD HCT achieves excellent rates of donor T-cell engraftment similar to that seen in MSD recipients, and reconstitution rates are adequate. However, only a minority will have myeloid and B-cell reconstitution, and attention must be paid to graft-versus-host disease prophylaxis. This approach might be safer in children ineligible for intense regimens to spare the potential complications of chemotherapy.

Centre for Immunodeficiency Molecular Immunology Unit UCL Institute of Child Health London United Kingdom

Department of Pediatric Hematology and Oncology Teaching Hospital Motol Prague Czech Republic

Department of Pediatrics Cincinnati Children's Hospital Medical Center Cincinnati Ohio

Department of Pediatrics Leiden University Medical Center Leiden The Netherlands

Department of Pediatrics University Medical Center Ulm Germany

Department of Pediatrics University of Oklahoma Oklahoma City Okla

Departments of Pediatrics and Immunology Duke University Medical Center Durham NC

Division of Hematology and Hematologic Malignancies Primary Children's Hospital University of Utah School of Medicine Huntsman Cancer Institute Salt Lake City Utah

Division of Hematology and Oncology Boston Children's Hospital and the Department of Pediatric Oncology Dana Farber Cancer Institute Boston Mass

Division of Immunology and The Manton Center for Orphan Disease Research Children's Hospital Boston Harvard Medical School Boston Mass

Division of Oncology Department of Pediatrics Children's Hospital of Philadelphia Philadelphia Pa

Division of Pediatric Allergy Immunology and Blood and Marrow Transplant Benioff Children's Hospital University of California San Francisco San Francisco Calif

Division of Pediatric Hematology Oncology University of Michigan Ann Arbor Mich

Hematology Oncology BMT Program British Columbia Children's Hospital Vancouver British Columbia Canada

Institute of Cellular Medicine Newcastle University Newcastle upon Tyne United Kingdom

Oncology Department The Children's Hospital at Westmead Westmead Australia

University Children's Hospital Stem Cell Transplantation Department Zurich Switzerland

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