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Association between measurable residual disease kinetics and outcomes of Philadelphia chromosome-positive acute lymphoblastic leukemia

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Abstract

The prognosis of Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph + ALL) has improved dramatically. Although measurable residual disease (MRD) kinetics during pretransplant treatment has been recently reported to correlate with patient outcomes, it is unclear whether prognosis is better if the MRD falls below the detection sensitivity soon after induction therapy. We retrospectively analyzed data of 37 Ph + ALL patients who were treated with autologous or allogeneic stem cell transplantation (auto-SCT, allo-SCT) at our institute from 2003 to 2019. Based on MRD kinetics, patients were divided into three groups: early responders (MRD became negative after induction therapy [n = 10, 27.0%]); late responders (MRD remained positive after induction therapy and became negative just before SCT [n = 12, 32.4%]); and poor responders (MRD was positive until just before SCT [n = 15, 40.5%]). The 5-year disease-free survival (DFS) rates for the three groups were 80.0%, 60.0%, and 29.9%, respectively (P = 0.037). The 5-year overall survival rates were not significantly different. The 5-year relapse rates were 0.0%, 31.7%, and 49.5%, respectively (P = 0.045). Non-relapse mortality (NRM) rates were similar among the three groups. Subgroup analysis for the cases that received posttransplantation tyrosine kinase inhibitor maintenance therapy revealed that DFS was similarly dependent on MRD kinetics (P = 0.022). This study clarified that MRD kinetics was a significant prognosticator for DFS and relapse rate in Ph + ALL.

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Acknowledgements

We would like to thank Editage (www.editage.com) for English language editing. The results of this study were presented in part at the 76th Japanese Society of Hematology Annual Meeting in Osaka, Japan, 2014, and at the 40th Annual Meeting of the Japan Society for Hematopoietic Cell Transplantation in Hokkaido, Japan, 2018.

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  1. Ryujiro Hara and Makoto Onizuka contributed equally to this work

Authors and Affiliations

  1. Division of Hematology/Oncology, Department of Internal Medicine, Tokai University School of Medicine, Isehara, Kanagawa, 259-1193, Japan

    Ryujiro Hara, Makoto Onizuka, Eri Kikkawa, Sawako Shiraiwa, Kaito Harada, Yasuyuki Aoyama, Daisuke Ogiya, Masako Toyosaki, Rikio Suzuki, Sinichiro Machida, Ken Ohmachi, Yoshiaki Ogawa, Hiroshi Kawada & Kiyoshi Ando

  2. Department of Laboratory Medicine, Tokai University School of Medicine, Isehara, Japan

    Hiromichi Matsushita

  3. Department of Laboratory Medicine, National Cancer Center Hospital, Tokyo, Japan

    Hiromichi Matsushita

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  1. Ryujiro Hara
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Contributions

RH and MO designed the research study. RH, MO, SS, KH, YA, DO, MT, RS, SM, KO, YO, HK, and KA sourced patients for the study. RH, HM, and EK were involved in the collection and analysis of the data. RH, MO, and KA drafted the paper. All authors were involved in revising the manuscript and approved the final version.

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Correspondence to Ryujiro Hara.

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This study was carried out following the Code of Ethics of the World Medical Association (Declaration of Helsinki) and was approved by the Institutional Review Board of Tokai University Hospital.

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Written informed consent was obtained from patients who could provide it. In the event that written consent could not be obtained from the patient, the research contents of the study were published on the homepage of the facility and outpatient department website.

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Written informed consent was obtained from patients who could provide it. In the event that written consent could not be obtained from the patient, the research contents of the study were published on the homepage of the facility and outpatient department website.

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Hara, R., Onizuka, M., Kikkawa, E. et al. Association between measurable residual disease kinetics and outcomes of Philadelphia chromosome-positive acute lymphoblastic leukemia . Ann Hematol 100, 2479–2486 (2021). https://doi.org/10.1007/s00277-021-04587-9

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