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Minimal Residual Disease

Lack of clinical utility of minimal residual disease detection in allogeneic stem cell recipients with childhood acute lymphoblastic leukemia: multi-institutional collaborative study in Japan

Bone Marrow Transplantation volume 31, pages 1127–1135 (2003)Cite this article

Summary:

The clinical utility of minimal residual disease (MRD) measurements following allogeneic stem cell transplantation (SCT) in childhood ALL is controversial. We therefore performed a multi-institutional study of MRD in bone marrow samples taken before SCT and at 1, 3, 6 and 12 months after SCT. Case-specific clonal rearrangements of IgH and TCR genes and expression levels of Wilms' tumor 1 (WT1) mRNA were determined by PCR or RT-PCR methods. In total, 95 cases met all criteria for analysis of informative IgH/TCR markers and quantitative WT1 mRNA expression levels. During the 2-year (median 414 days) study period, 20 patients relapsed. Although the proportion of patients with a positive IgH/TCR result before SCT was significantly reduced at 1 month after treatment (P<0.001), attesting the efficacy of SCT, serial measurements of IgH/TCR rearrangements did not correlate with leukemic relapse. Clonal switch was demonstrated in 11 of the 14 patients with bone marrow relapse, indicating that the poor predictive power of the MRD assay most likely reflected the loss of PCR targets. WT1 expression was not related to either MRD detection by IgH/TCR assays or to clinical leukemic relapse. The clinical value of serial MRD monitoring would be limited in ALL patients undergoing SCT.

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Acknowledgements

We are grateful to all physicians and transplant groups in the participating institutes (see Appendix A), to Kyoko Tanaka, Kyowa Media Service, Ltd for analyzing the data, and to Yasuko Hashimoto for secretarial assistance.

Author information

Authors and Affiliations

  1. Kyoto City Institute of Health and Environmental Sciences, Kyoto, Japan

    S Imashuku

  2. Hirosaki University, School of Medicine, Hirosaki, Japan

    K Terui

  3. Japanese Red Cross Nagoya First Hospital, Nagoya, Japan

    T Matsuyama

  4. Niigata Cancer Center, Niigata, Japan

    K Asami

  5. Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan

    S Tsuchiya

  6. Nagano Children's Hospital, Nagano, Japan

    E Ishii

  7. Osaka Medical Center and Research Institute for Child and Maternal Health, Osaka, Japan

    K Kawa

  8. School of Medicine, Kobe University, Kobe, Japan

    Y Kosaka

  9. School of Medicine, Kurume University, Kurume, Japan

    H Eguchi

  10. Ibaraki Children's Hospital, Ibaraki, Japan

    M Tsuchida

  11. School of Medicine, Yokohama City University, Yokohama, Japan

    K Ikuta

  12. School of Medicine, Tokai University, Isehara, Japan

    S Kato

  13. School of Medicine, Kanazawa University, Kanazawa, Japan

    S Koizumi

  14. National Kyushu Cancer Center, Fukuoka, Japan

    J Okamura

  15. Kyoto Prefectural University of Medicine, Kyoto, Japan

    A Morimoto, S Hibi & K Hamaoka

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Consortia

for the MRD Study Group in Allogeneic Bone Marrow Transplantation for Childhood ALL

Appendix A

Appendix A

Participating institutions and physicians are listed in Table 5.

Table 5 Participating institutions and Physicians
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Imashuku, S., Terui, K., Matsuyama, T. et al. Lack of clinical utility of minimal residual disease detection in allogeneic stem cell recipients with childhood acute lymphoblastic leukemia: multi-institutional collaborative study in Japan. Bone Marrow Transplant 31, 1127–1135 (2003). https://doi.org/10.1038/sj.bmt.1704067

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