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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Circulating red cells usually remain of host origin after bone marrow transplantation for severe combined immunodeficiency.

BACKGROUND: Patients with severe combined immunodeficiency (SCID) treated with allogeneic bone marrow transplantation often receive a milder conditioning regimen than patients who undergo transplantation for hematologic malignancy, and they regularly retain circulating white cells of host origin. The origin of circulating red cells following successful bone marrow transplantation to treat SCID is not known. STUDY DESIGN AND METHODS: Review of the medical records identified all patients with SCID who underwent ABO-mismatched bone marrow transplantation at the University of California, San Francisco, between 1982 and 1994. The ABO and Rh phenotype at >6 months after transplantation was determined for all successful transplants by review of the medical record or the taking of a fresh blood sample for analysis. Patient-conditioning and donor bone marrow-preparative regimens were reviewed to assess their possible influence on the red cell phenotype after successful bone marrow transplantation. RESULTS: Nine of 35 SCID patients who underwent successful transplantation received marrow from ABO-mismatched donors. Eight of the nine patients had only host red cells circulating at 6 to 84 months after transplantation, while one patient had only donor red cells circulating at 48 months after transplantation. None of the patients had circulating red cells of both host and donor origin. Conditioning regimens included cyclophosphamide and antithymocyte globulin for all nine patients; only three patients also received total body irradiation. Seven of the nine patients received related-donor, HLA-mismatched bone marrow, and two patients received HLA-identical bone marrow; eight patients received T-cell-depleted bone marrow. The one patient whose red cell phenotype converted to that of the donor received T-cell-depleted, haploidentical marrow, and the preparative regimen included chemotherapy and total body irradiation. CONCLUSION: SCID patients successfully treated with allogeneic bone marrow transplantation typically fail to show circulating red cells of donor phenotype; this finding is in contrast to the universal presence of circulating donor red cells following successful bone marrow transplantation to treat hematologic malignancies and other diseases. The milder conditioning regimens typically given to patients with SCID, along with T-cell depletion and HLA mismatching, may play a role in this different outcome. It is not known whether the inability to find circulating red cells of donor origin is due to a failure to engraft donor pluripotent stem cells or a failure of engrafted donor stem cells to differentiate along the erythroid lineage.[1]


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