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Cord Blood Stem Cells

Double umbilical cord blood transplantation with reduced intensity conditioning and sirolimus-based GVHD prophylaxis

Bone Marrow Transplantation volume 46, pages 659–667 (2011)Cite this article

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Abstract

The main limitations to umbilical cord blood (UCB) transplantation (UCBT) in adults are delayed engraftment, poor immunological reconstitution and high rates of non-relapse mortality (NRM). Double UCBT (DUCBT) has been used to circumvent the issue of low cell dose, but acute GVHD remains a significant problem. We describe our experience in 32 subjects, who underwent DUCBT after reduced-intensity conditioning with fludarabine/melphalan/antithymocyte globulin and who received sirolimus and tacrolimus to prevent acute GVHD. Engraftment of neutrophils occurred in all patients at a median of 21 days, and platelet engraftment occurred at a median of 42 days. Three subjects had grade II–IV acute GVHD (9.4%) and chronic GVHD occurred in four subjects (cumulative incidence 12.5%). No deaths were caused by GVHD and NRM at 100 days was 12.5%. At 2 years, NRM, PFS and OS were 34.4, 31.2 and 53.1%, respectively. As expected, immunologic reconstitution was slow, but PFS and OS were associated with reconstitution of CD4+ and CD8+ lymphocyte subsets, suggesting that recovery of adaptive immunity is required for the prevention of infection and relapse after transplantation. In summary, sirolimus and tacrolimus provide excellent GVHD prophylaxis in DUCBT, and this regimen is associated with low NRM after DUCBT.

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Acknowledgements

Supported by NCI P01 CA142106, NCI R01 CA123855, the Jock and Bunny Adams Research and Education Fund, and the Ted and Eileen Pasquarello Research Fund. Funded in part by unrestricted research grants from Astellas, Inc and Genzyme, Inc. CC is supported by the Stem Cell Cyclists of the Pan Mass Challenge.

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Authors and Affiliations

  1. Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA

    C Cutler, S McDonough, M Herrera, C Reynolds, D Liney, G Kao, V Ho, P Armand, J Koreth, E Alyea, J Ritz, R Soiffer & J H Antin

  2. Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, MA, USA

    K Stevenson & H T Kim

  3. Department of Medicine, Division of Hematology, Oncology and Cancer Biology, Beth Israel Deaconess Medical Center, Boston, MA, USA

    J Brown & V A Boussiotis

  4. Department of Medicine, Division of Hematology/Oncology, Massachusetts General Hospital, Boston, MA, USA

    B R Dey, E Attar, T Spitzer & K Ballen

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  1. C Cutler
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Correspondence to C Cutler.

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Cutler, C., Stevenson, K., Kim, H. et al. Double umbilical cord blood transplantation with reduced intensity conditioning and sirolimus-based GVHD prophylaxis. Bone Marrow Transplant 46, 659–667 (2011). https://doi.org/10.1038/bmt.2010.192

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