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Stem cell transplantation

Disease risk and GVHD biomarkers can stratify patients for risk of relapse and nonrelapse mortality post hematopoietic cell transplant

Leukemia volume 34, pages 1898–1906 (2020)Cite this article

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Abstract

The graft-versus-leukemia (GVL) effect after allogeneic hematopoietic cell transplant (HCT) can prevent relapse but the risk of severe graft-versus-host disease (GVHD) leads to prolonged intensive immunosuppression and possible blunting of the GVL effect. Strategies to reduce immunosuppression in order to prevent relapse have been offset by increases in severe GVHD and nonrelapse mortality (NRM). We recently validated the MAGIC algorithm probability (MAP) that predicts the risk for severe GVHD and NRM in asymptomatic patients using serum biomarkers. In this study we tested whether the MAP could identify patients whose risk for relapse is higher than their risk for severe GVHD and NRM. The multicenter study population (n = 1604) was divided into two cohorts: historical (2006–2015, n = 702) and current (2015–2017, n = 902) with similar NRM, relapse, and survival. On day 28 post-HCT, patients who had not developed GVHD (75% of the population) and who possessed a low MAP were at much higher risk for relapse (24%) than severe GVHD and NRM (16 and 9%); this difference was even more pronounced in patients with a high disease risk index (relapse 33%, NRM 9%). Such patients are good candidates to test relapse prevention strategies that might enhance GVL.

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Fig. 1: One-year outcomes of the entire population.
Fig. 2: Distribution of grades II–IV GVHD and relapse within 1 year post-HCT.
Fig. 3: One-year outcomes for patients with no early GVHD and low MAP.
Fig. 4: Relapse, NRM, and OS by DRI for current cohort patients without early GVHD and low MAP.

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Acknowledgements

Supported by grants (R21CA173459, P01CA03942, and P30CA196521) from the National Cancer Institute, an American Cancer Society Clinical Research Professorship (to JLMF), and a Doris Duke Charitable Foundation Clinical Research Mentorship (to MDA and MJH).

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Author notes

  1. These authors contributed equally: Umut Özbek, James L.M. Ferrara, John E. Levine

Authors and Affiliations

  1. Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA

    Mina D. Aziz, Jay Shah, Urvi Kapoor, Christina Dimopoulos, Allan Augustine, Mohammed Chaudhry, Aaron Etra, Stephanie Gergoudis, Matthew J. Hartwell, Steven Kowalyk, George Morales, Hrishikesh Srinagesh, Rachel Young, James L. M. Ferrara & John E. Levine

  2. Blood and Marrow Transplantation Program, University of Michigan, Ann Arbor, MI, USA

    Sarah Anand & Gregory Yanik

  3. Department of Stem Cell Transplantation, University Medical Center, Hamburg-Eppendorf, Germany

    Francis Ayuk & Nicolaus Kröger

  4. Bone Marrow Transplantation Program, Massachusetts General Hospital, Boston, MA, USA

    Yi-Bin Chen

  5. Blood and Marrow Transplantation Program, Ohio State University, Columbus, OH, USA

    Hannah K. Choe

  6. Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, USA

    Elizabeth O. Hexner

  7. Blood and Marrow Transplantation Program, Mayo Clinic, Rochester, MN, USA

    William J. Hogan

  8. Pediatric Blood and Marrow Transplantation Program, Vanderbilt University Medical Center, Nashville, TN, USA

    Carrie L. Kitko

  9. Department of Pediatric Hematology and Oncology, Bambino Gesù Children’s Hospital, Rome, Italy

    Pietro Merli

  10. Hematology and Hematopoietic Cell Transplantation, City of Hope Medical Center, Duarte, CA, USA

    Ryotaro Nakamura

  11. Medical Department 1, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany

    Rainer Ordemann

  12. Children’s Center for Cancer and Blood Diseases, Blood and Marrow Transplantation Section, Children’s Hospital Los Angeles, Los Angeles, CA, USA

    Michael A. Pulsipher

  13. Pediatric Blood and Marrow Transplantation Program, Aflac Cancer and Blood Disorders Center, Emory University and Children’s Healthcare of Atlanta, Atlanta, GA, USA

    Muna Qayed

  14. Blood and Marrow Transplantation Program, Columbia University, New York, NY, USA

    Ran Reshef

  15. Department of Internal Medicine 5, Hematology/Oncology, University Hospital Erlangen, Erlangen, Germany

    Wolf Rösler

  16. Division of Hematology/Oncology, Department of Pediatrics, University of Toronto, The Hospital for Sick Children, Toronto, ON, Canada

    Tal Schechter

  17. Blood and Marrow Transplantation Program, University of Regensburg, Regensburg, Germany

    Elisabeth Schreiner

  18. Pediatric Blood and Marrow Transplantation Program, Children’s Hospital, University of Würzburg, Würzburg, Germany

    Matthias Wölfl

  19. Blood and Marrow Transplantation Program, Chulalongkorn University, Bangkok, Thailand

    Kitsada Wudhikarn

  20. Biostatistics Shared Resource Facility, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA

    Umut Özbek

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Correspondence to John E. Levine.

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UÖ, JLMF, and JEL are co-inventors on a GVHD biomarker patent and receive royalties from Viracor.

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Aziz, M.D., Shah, J., Kapoor, U. et al. Disease risk and GVHD biomarkers can stratify patients for risk of relapse and nonrelapse mortality post hematopoietic cell transplant. Leukemia 34, 1898–1906 (2020). https://doi.org/10.1038/s41375-020-0726-z

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