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Acute Leukemia

Risk factors and timing of relapse after allogeneic transplantation in pediatric ALL: for whom and when should interventions be tested?

Bone Marrow Transplantation volume 50, pages 1173–1179 (2015)Cite this article

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Abstract

We previously showed that minimal residual disease (MRD) detection pre-hematopoietic cell transplant (HCT) and acute GvHD (aGvHD) independently predicted risk of relapse in pediatric ALL. In this study we further define risk by assessing timing of relapse and the effects of leukemia risk category and post-HCT MRD. By multivariate analysis, pre-HCT MRD <0.1% and aGvHD by day +55 were associated with decreased relapse and improved event-free survival (EFS). Intermediate leukemia risk status predicted decreased relapse, and improved EFS and overall survival (OS). Patients with pre-HCT MRD ⩾0.1% who did not develop aGvHD compared with those with MRD <0.1% who did develop aGvHD had much worse survival (2 years EFS 18% vs 71%; P=0.001, 2 years OS 46 vs 74%; P=0.04). Patients with pre-HCT MRD <0.1% who did not experience aGvHD had higher rates of relapse than those who did develop aGvHD (40% vs 13%; P= 0.008). Post-HCT MRD led to a substantial increase in relapse risk (HR=4.5, P<0.01). Patients at high risk of relapse can be defined after transplant using leukemia risk category, presence of MRD pre or post HCT, and occurrence of aGvHD. An optimal window to initiate intervention to prevent relapse occurs between day +55 and +200 after HCT.

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Acknowledgements

This study was supported in part by N01 HC-45220/HHSN268200425220C, U10 CA098543 and R01CA1116660. PBMTC activities were supported by 2U01HL069254 and a consortium grant from the St Baldrick’s Foundation.

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Authors and Affiliations

  1. Division of Hematology and Hematological Malignancies, Huntsman Cancer Institute/University of Utah School of Medicine, Primary Children’s Hospital, Salt Lake City, UT, USA

    M A Pulsipher & E Raetz

  2. Department of Preventive Medicine, USC Keck School of Medicine, Los Angeles, CA, USA

    B Langholz

  3. Manitoba Blood and Marrow Transplant Program, Winnepeg, Manitoba, Canada

    D A Wall

  4. Department of Pediatrics University of BC, BC Children's Hospital, Vancouver, British Columbia, Canada

    K R Schultz

  5. Division of Oncology, Children's Hospital of Philadelphia, Philadelphia, PA, USA

    N Bunin, D Teachey & S A Grupp

  6. NYU Department of Pediatrics and Cancer Institute, NYU Langone Medical Center, New York, NY, USA

    W Carroll & S Gardner

  7. Division of Blood and Marrow Transplantation and Cellular Therapies, Children’s Hospital of Pittsburgh, University of Pittsburgh Medical Center, Pittsburgh, PA, USA

    R K Goyal

  8. Department of Pathology and Laboratory Medicine, Nationwide Children’s Hospital, Columbus, OH, USA

    J Gastier-Foster

  9. Department of Pathology, The Ohio State University College of Medicine, Columbus, OH, USA

    J Gastier-Foster

  10. Department of Pediatrics, The Ohio State University College of Medicine, Columbus, OH, USA

    J Gastier-Foster

  11. Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD, USA

    M Borowitz

  12. Department of Pathology, Children's Hospital of Philadelphia, Philadelphia, PA, USA

    S A Grupp

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  1. M A Pulsipher
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Correspondence to M A Pulsipher.

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The authors declare no conflict of interest.

Additional information

This study was presented in part at the American Society of Hematology Meeting, December 2012 and the Second International Workshop: Biology Prevention and Treatment of Relapse After Allogeneic Hematopoietic Stem Cell Transplantation, November 5–6, 2012, Bethesda MD, Plenary Oral Presentation, Best Abstracts Session.

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Pulsipher, M., Langholz, B., Wall, D. et al. Risk factors and timing of relapse after allogeneic transplantation in pediatric ALL: for whom and when should interventions be tested?. Bone Marrow Transplant 50, 1173–1179 (2015). https://doi.org/10.1038/bmt.2015.103

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