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Major molecular response prior to allogeneic hematopoietic stem cell transplantation predicts better outcome in adult Philadelphia-positive acute lymphoblastic leukemia in first remission

Bone Marrow Transplantation volume 52, pages 470–472 (2017)Cite this article

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Ph chromosome and BCR-ABL fusion gene mark the most unfavorable subgroup of ALL.1 Currently, the integration of imatinib into traditional chemotherapy-based induction therapy has been proved to increase overall rate of CR and improve long-term survival. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is recommended as the mainstay of post-remission therapy.2 In spite of these exciting improvements, a substantial number of transplant patients subsequently die on account of disease progression. Identifying early warning predictors for relapse has consequentially become of paramount importance. Relying on the breakthrough in molecular biotechniques, modern minimal residual disease (MRD) monitoring has been gradually accepted as an accurate and reliable prognostic indicator superior to conventional factors.3 Nevertheless, which timepoint displaying the strongest prognostic power in adult Ph+ ALL transplants remains inconclusive.

From July 2006 to October 2014, a total of 65 adult Ph+ ALL patients who underwent allo-HSCT in first remission were enrolled in this retrospective study, which followed approval by the Ethics Committee and the observation of Declaration of Helsinki conditions. All patients received a combined chemotherapy regimen of CDVP for induction, and a regimen comprising high-dose methotrexate (MTX) and high-dose Ara-C for consolidation.4 Imatinib at a dose of 600 mg daily was introduced as a supplement of induction in 48 patients (26 patients during the first 14 days) and at a dose of 400 mg daily in all patients as part of consolidation. Patients with an HLA-matched donor then proceeded to transplantation. The conditioning regimen and GvHD prophylaxis of our center were reported elsewhere.5 Imatinib was administered at a dose of 400 mg daily, 1 month after transplantation. Marrow examination was performed after each course of treatment regimen, before allo-HSCT and at 1, 3, 6, 12 months after transplantation. Major molecular response (MMR) was defined as BCR-ABL/ABL ratio of <0.1% or a reduction in BCR-ABL transcript level by at least 3-log from pretreated baseline.6

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Acknowledgements

We express our gratitude to all the participants for contribution to this study, and we also extend our thanks to all the patients in this study. This study was funded by National Natural Science Foundation of China (81270617), Jiangsu Province’s Key Medical Center (ZX201102) as well as Jiangsu Province’s Key Medical Center (ZX201102).

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  1. W-Z Cai and J-N Cen: These authors equal contributed to this work.

Authors and Affiliations

  1. Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, China

    W-Z Cai, J-N Cen, J Chen, F Chen, C-C Fu, Y Han, Z-M Jin, X Ma, M Miao, H-Y Qiu, X-W Tang, S-L Xue, A-N Sun, S-N Chen & D-P Wu

  2. Institute of Blood and Marrow Transplantation, Suzhou, China

    F Chen, X Ma, S-L Xue, S-N Chen & D-P Wu

  3. Collaborative Innovation Center of Hematology, Soochow University, Suzhou, China

    S-N Chen & D-P Wu

  4. Key Laboratory of Thrombosis and Hemostasis of Ministry of Health, Suzhou, China

    S-N Chen & D-P Wu

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Correspondence to S-N Chen or D-P Wu.

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Cai, WZ., Cen, JN., Chen, J. et al. Major molecular response prior to allogeneic hematopoietic stem cell transplantation predicts better outcome in adult Philadelphia-positive acute lymphoblastic leukemia in first remission. Bone Marrow Transplant 52, 470–472 (2017). https://doi.org/10.1038/bmt.2016.307

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