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Stem Cells

High doses of transplanted CD34+ cells are associated with rapid T-cell engraftment and lessened risk of graft rejection, but not more graft-versus-host disease after nonmyeloablative conditioning and unrelated hematopoietic cell transplantation

Leukemia volume 19, pages 822–828 (2005)Cite this article

Abstract

This report examines the impact of graft composition on outcomes in 130 patients with hematological malignancies given unrelated donor granulocyte-colony-stimulating-factor-mobilized peripheral blood mononuclear cells (G-PBMC) (n=116) or marrow (n=14) transplantation after nonmyeloablative conditioning with 90 mg/m2 fludarabine and 2 Gy TBI. The median number of CD34+ cells transplanted was 6.5 × 106/kg. Higher numbers of grafted CD14+ (P=0.0008), CD3+ (P=0.0007), CD4+ (P=0.001), CD8+ (P=0.004), CD3–CD56+ (P=0.003), and CD34+ (P=0.0001) cells were associated with higher levels of day 28 donor T-cell chimerism. Higher numbers of CD14+ (P=0.01) and CD34+ (P=0.0003) cells were associated with rapid achievement of complete donor T-cell chimerism, while high numbers of CD8+ (P=0.005) and CD34+ (P=0.01) cells were associated with low probabilities of graft rejection. When analyses were restricted to G-PBMC recipients, higher numbers of grafted CD34+ cells were associated with higher levels of day 28 donor T-cell chimerism (P=0.01), rapid achievement of complete donor T-cell chimerism (P=0.02), and a trend for lower risk for graft rejection (P=0.14). There were no associations between any cell subsets and acute or chronic GVHD nor relapse/progression. These data suggest more rapid engraftment of donor T cells and reduced rejection rates could be achieved by increasing the doses of CD34+ cells in unrelated grafts administered after nonmyeloablative conditioning.

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Acknowledgements

We thank the data coordinators Heather Hildebrant Debbie Bassuk, and Chris Davis, and the study nurses Steve Minor, Mary Hinds, and John Sedgwick for their invaluable help in making the study possible. We also wish to thank Bonnie Larson and Helen Crawford for help with manuscript preparation, and the physicians, nurses, and support personnel for their care of patients involved in this study. This work was supported in part by Grants CA78902, CA92058, HL36444, CA18029, HD44175, DK56465, and CA15704 from the National Institutes of Health, Department of Health and Human Services (DHHS), Bethesda, MD. DGM was supported by a grant from the Gabrielle Rich Leukemia Foundation, and MS by a grant from the Oncology Research Faculty Development Program of the NCI. RS also received support from the Laura Landro Salomon Endowment Fund. FB is research associate of the National Fund for Scientific Research (FNRS) Belgium and supported in part by postdoctoral grants from the Fulbright Commission and from the Centre Anticancéreux près l'Université de Liège.

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Author notes

  1. F Baron and M B Maris: FB and MBM contributed equally to this work

Authors and Affiliations

  1. Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA

    F Baron, M B Maris, B E Storer, B M Sandmaier, J P Panse, T R Chauncey, M Sorror, M-T Little, D G Maloney, R Storb & S Heimfeld

  2. University of Washington School of Medicine, Seattle, WA, USA

    M B Maris, B E Storer, B M Sandmaier, T R Chauncey, D G Maloney & R Storb

  3. Department of Hematology, University of Liège, Belgium

    F Baron

  4. VA Puget Sound Health Care System, Seattle, WA, USA

    T R Chauncey

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  1. F Baron
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Correspondence to M B Maris.

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Baron, F., Maris, M., Storer, B. et al. High doses of transplanted CD34+ cells are associated with rapid T-cell engraftment and lessened risk of graft rejection, but not more graft-versus-host disease after nonmyeloablative conditioning and unrelated hematopoietic cell transplantation. Leukemia 19, 822–828 (2005). https://doi.org/10.1038/sj.leu.2403718

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