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Allografting

The impact of graft composition on clinical outcomes in unmanipulated HLA-mismatched/haploidentical hematopoietic SCT

Abstract

This study examines the absolute numbers and relative proportions of CD4+, CD8+, CD14+ and CD34+ cells contained in allografts and their impact on early engraftment and later clinical outcomes in 141 patients with hematological malignancies who underwent unmanipulated HLA-mismatched/haploidentical hematopoietic SCT without in vitro T-cell depletion. These patients received G-CSF-primed BM grafts (G-BM) and peripheral blood grafts (G-PB) following a modified regimen of BU/CY 2 plus antithymocyte globulin. Multivariate analysis showed that high CD34+ cell numbers were associated with accelerated plt engraftment (P=0.001). Meanwhile, patients with a higher CD4/CD8 ratio in G-BM (1.16) had a survival disadvantage (P<0.01) and a trend towards relapse (P=0.086) after controlling for disease status. A higher CD4/CD8 was also associated with a significantly increased risk of acute GVHD grades II–IV (P=0.013), even after adjusting for an ABO major mismatch. No aspect of graft composition affected neutrophil engraftment or chronic GVHD. In conclusion, the differences in CD34+ cell dose and the CD4/CD8 ratio in grafts seem to affect engraftment and clinical outcomes; in particular, a lower CD4/CD8 ratio in primed BM graft is associated with a survival benefit.

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Acknowledgements

This work was supported by the Hi-Tech Research and Development Program of China (No. 2006AA02Z4A0), and the China National Funds for Distinguished Young Scientist's (Grant no. 30725038), and the Funds for Creative Research Groups of China (IRT0702). We thank San Francisco Edit (www.sefedit.net) for their assistance in editing this manuscript.

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Correspondence to X-J Huang.

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Supplementary Information accompanies the paper on Bone Marrow Transplantation website (http://www.nature.com/bmt)

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Luo, XH., Chang, YJ., Xu, LP. et al. The impact of graft composition on clinical outcomes in unmanipulated HLA-mismatched/haploidentical hematopoietic SCT. Bone Marrow Transplant 43, 29–36 (2009). https://doi.org/10.1038/bmt.2008.267

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