To assess the impact of minimal residual disease (MRD) and tyrosine kinase inhibitor (TKI) administration on allogeneic hematopoietic cell transplantation (allo-HCT) for Ph-positive ALL (Ph+ALL), we retrospectively analyzed data from a registry database for 432 adult Ph+ALL patients in first CR (CR1) who received pre-transplant TKI administration. Negative MRD (MRD(−)) at allo-HCT was achieved in 277 patients. OS in patients transplanted in MRD(−) was significantly better than that in patients transplanted in MRD(+) (MRD(−): 67% vs MRD(+): 55% at 4 years; P=0.001). MRD(−) at allo-HCT was a significant risk factor for survival along with age at allo-HCT in multivariate analyses. Incidence of relapse in patients transplanted in MRD(−) was significantly lower than that in patients transplanted in MRD(+) (MRD(−): 19% vs MRD(+): 29% at 4 years; P=0.006). In multivariate analyses, MRD(+) at allo-HCT was a significant risk factor for relapse. A post-transplant TKI was administered to 103 patients. In subanalyses regarding the effect of post-transplant TKI administration, post-transplant TKI administration was a significant risk factor for relapse in multivariate analyses (P<0.0001). MRD status at allo-HCT is one of the most important predictive factors for Ph+ALL patients transplanted in CR1.
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Machine learning-aided risk stratification in Philadelphia chromosome-positive acute lymphoblastic leukemia
Biomarker Research Open Access 18 February 2021
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This study was supported in part by the Japan Leukemia Research Fund grant to SN, by a Research Grand for Allergic Disease and Immunology from the Japanese Ministry of Health, Labor and Welfare to YA and by a Japanese Grant-in-Aid for Scientific Research to JT.
YO has received honoraria from Novartis and Bristol-Myers Squibb. ST has received honoraria and research funding from Novartis. NU has received honoraria from Otsuka Pharmaceutical Co., Kyowa Hakko Kirin Co., Chugai Pharmaceutical Co., Sumitomo Dainippon Pharma, Bristol-Myers Squibb, Daiichi Sankyo Company and Yakult Honsha, and travel, accommodations, expenses from Yakult Honsha and Kyowa Hakko Kirin Co. HN has received honoraria, speaker’s bureau, research funding, and travel, accommodations, expenses from Novartis and Bristol-Myers Squibb. TN-I has research funding from Tsubakimoto Co. and Wanbishi Archives Co. and patent pending with Tsubakimoto Co. YA has received honoraria from Otsuka Pharmaceutical Co., MDS Co. Ltd, Meiji Seika Pharma and Chugai Pharmaceutical Co., and travel, accommodations, expenses from Kyowa Hakko Kirin Co. The remaining authors declare no competing financial interests.
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Nishiwaki, S., Imai, K., Mizuta, S. et al. Impact of MRD and TKI on allogeneic hematopoietic cell transplantation for Ph+ALL: a study from the adult ALL WG of the JSHCT. Bone Marrow Transplant 51, 43–50 (2016). https://doi.org/10.1038/bmt.2015.217
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