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Promise and Progress - The Key to Safe Bone Marrow Transplants Revealed

Reprogramming Cancer Cells - The Story of Epigenetics
Issue No. 1

The Key to Safe Bone Marrow Transplants Revealed

Date: July 16, 2014

Science Translational Medicine, November 2013

Bone marrow transplant researchers provided greater insight into how the chemotherapy drug cyclophosphamide prevents graft-versus-host disease (GVHD) in patients after bone marrow transplantation (BMT). (GVHD is a serious, life-threatening complication of BMT in which the transplanted immune cells attack the patient’s tissue and organs.) BMT researchers Leo Luznik, M.D., Christopher Kanakry, M.D., and team found that regulatory T cells, a certain type of immune cell responsible for curbing GVHD, are protected from cyclophosphamide by expressing high levels of the enzyme aldehyde dehydrogenase (ALDH) after BMT

Richard Jones, M.D. revealed in the 1980s that cells containing ALDH evade the toxic effects of cyclophosphamide and reconstitute the patient’s immune system.  Building upon this work, Drs. Luznik and Kanakry found that in BMT, regulatory T-cells also use ALDH to resist cyclophosphamide and that this persistence of regulatory T cells after cyclophosphamide treatment is necessary for the GVHD protective effects of this approach.

More than a decade ago Drs. Luznik and Ephraim Fuchs, M.D., found that high doses of cyclophosphamide thwarted acute and chronic GVHD, and more recently have used it to safely administer half-matched bone marrow transplants, a procedure once impossible due to terribly high rates of life-threatening immune reactions. This research fills in an important piece of the puzzle in understanding how post-transplant cyclophosphamide works to prevent GVHD.  The team is building upon these findings to study methods to improve the treatment.

The research was funded by the National Institutes of Health’s National Cancer Institute and National Heart. Lung, and Blood Institute grants HL 110907, CA 122779, CA 15396, UL 1-RR025005, and HL007525, the Conquer Cancer Foundation of the American Society of Clinical Oncology, and Otsuka Pharmaceutical.

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