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Acute Leukemia

Real-time assessment of relapse risk based on the WT1 marker in acute leukemia and myelodysplastic syndrome patients after hematopoietic cell transplantation

Bone Marrow Transplantation volume 50, pages 26–33 (2015)Cite this article

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Abstract

Relapse is the major cause of treatment failure after allogeneic hematopoietic cell transplantation (alloHCT) for acute leukemia and myelodysplastic syndrome (MDS). Wilms' tumor Ag (WT1) is overexpressed in the majority of acute leukemia and MDS patients and has been proposed as a universal diagnostic marker for detection of impending relapse. Comprehensive studies have shown that WT1 transcript levels have predictive value in acute leukemia patients in CR after chemotherapy. However, the focus of this study is the period after alloHCT for predicting relapse onset. We analyzed the accumulation of WT1 mRNA transcripts in PB of 82 leukemia and MDS patients and defined specific molecular ratios for relapse prediction. The extensively validated WT1/c-ABL ratio was used to normalize increases in WT1 transcript levels. The observed lead time of crossing or exceeding set WT1 levels is presented along with linear interpolation to estimate the calculated day the WT1 thresholds were crossed. The WT1/c-ABL transcript ratio of 50 or above yielded 100% specificity and 75% sensitivity reliably predicting future relapse with an observed average of 29.4 days (s.d.=19.8) and a calculated average of 63 days (s.d.=29.3) lead time before morphologic confirmation. A lower ratio of 20 or above gave lower specificity, but higher sensitivity (84.8% and 87.5%, respectively) identified more patients who relapsed, at earlier times, providing an earlier warning with actual average lead time of 49.1 days (s.d.=30.8) and calculated average of 78 days (s.d.=28.8). WT1 transcript levels serve as a diagnostic relapse test with greater sensitivity than the morphologic approach used in the clinic as a readout.

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Acknowledgements

We thank the staff of the Department of Hematology and Hematopoietic Cell Transplant for their unwavering support of the program. The dedication of the hematology nurse coordinators and staff in facilitating the study, assisting the patients with informed consent and collecting the blood specimens is greatly appreciated. We are most grateful to the patients who participated in the study. This work was partially supported by the Tim Nesvig Lymphoma Fellowship and Research Fund (RN and DJD) and by the ThinkCure Foundation (RN and DJD), and PHS Grants CA077544 (DJD) and CA030206 to DJD and SJF. The City of Hope Cancer Center is supported by CA33572. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

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  1. R Nakamura and D J Diamond: These authors contributed equally to this work.

Authors and Affiliations

  1. Division of Translational Vaccine Research, Beckman Research Institute of City of Hope, Duarte, CA, USA,

    A Israyelyan & D J Diamond

  2. Division of Biostatistics, Department of Information Sciences, Duarte, CA, USA,

    L Goldstein

  3. Department of Hematology/Hematopoietic Cell Transplantation, Duarte, CA, USA,

    W Tsai, S J Forman & R Nakamura

  4. Clinical Trials Office, City of Hope Comprehensive Cancer Center, Duarte, CA, USA

    L Aquino

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  1. A Israyelyan
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Israyelyan, A., Goldstein, L., Tsai, W. et al. Real-time assessment of relapse risk based on the WT1 marker in acute leukemia and myelodysplastic syndrome patients after hematopoietic cell transplantation. Bone Marrow Transplant 50, 26–33 (2015). https://doi.org/10.1038/bmt.2014.209

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