期刊
TRANSFUSION
卷 44, 期 4, 页码 555-566出版社
WILEY
DOI: 10.1111/j.1537-2995.2004.03285.x
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资金
- NHLBI NIH HHS [P01HL63357, HL61223, HL47193] Funding Source: Medline
BACKGROUND: Delayed megakaryocytic engraftment occurs in approximately 8 percent of patients undergoing autologous transplantation with PBPCs, and a reliable assay to predict engraftment is not yet available. STUDY DESIGN AND METHODS: The correlation between human cell engraftment in a mouse xenotransplantation model with the rate of megakaryocytic recovery for individual patients after autologous PBPC transplantation was evaluated. Engraftment into nonobese diabetic (NOD)-severe combined immunodeficient (SCID) and NOD-SCID-beta(2)m(null) mice was compared for patients with rapid (11 days) PLT recovery (good engrafters, GEs) versus those with delayed (18 days) PLT engraftment (poor engrafters, PEs). PBPCs (1 x 10(6) CD34+ cells) were transplanted into sublethally irradiated (300 cGy) mice, and human WBC and human PLT engraftment were analyzed by FACS in the blood weekly. Human WBCs and human CFU-megakaryocytes (Mks) in the marrow were determined 6 to 7 weeks after transplant. RESULTS: Six PEs and five GEs were analyzed. Four of six PEs showed no human cell engraftment, whereas five of five GEs showed multilineage human hematopoiesis including the presence of CFU-Mks. Human WBC engraftment and human CFU-Mks differed significantly between GEs and PEs (p < 0.01). NOD-SCID-beta(2)m(null) had significantly higher levels of human engraftment than NOD-SCID mice (p < 0.05). The two PEs whose PBPCs were capable of engrafting in the mice had underlying liver abnormalities that may have played a role in their delayed engraftment. CONCLUSIONS: Time to PLT recovery in patients correlates strongly with human PLT and human WBC engraftment and with the number of human CFU-Mks (p < 0.05) in a xenogeneic transplant model. This model may be useful for future studies to test therapeutic strategies for enhancement of engraftment.
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