The impacts of BCR-ABL1 mutations in patients with Philadelphia chromosome-positive acute lymphoblastic leukemia who underwent allogeneic hematopoietic cell transplantation

The prognostic impacts of BCR-ABL1 fusion gene mutations in Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph + ALL) remain unknown. Using data from a nationwide Japanese registry, we have evaluated the prognostic impact of BCR-ABL1 mutations prior to the first allogeneic hematopoiet...

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Published in:Annals of hematology 2020-10, Vol.99 (10), p.2393-2404
Main Authors: Tachibana, Takayoshi, Najima, Yuho, Akahoshi, Yu, Hirabayashi, Shigeki, Harada, Kaito, Doki, Noriko, Uchida, Naoyuki, Fukuda, Takahiro, Sawa, Masashi, Ogata, Masao, Takada, Satoru, Tanaka, Masatsugu, Matsuhashi, Yoshiko, Tanaka, Junji, Onizuka, Makoto, Ichinohe, Tatsuo, Atsuta, Yoshiko, Kako, Shinichi
Format: Article
Language:English
Subjects:
Hematology
Leukemia
Medical prognosis
Medicine
Medicine & Public Health
Mutation
Oncology
Original Article
Stem cell transplantation
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Summary:The prognostic impacts of BCR-ABL1 fusion gene mutations in Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph + ALL) remain unknown. Using data from a nationwide Japanese registry, we have evaluated the prognostic impact of BCR-ABL1 mutations prior to the first allogeneic hematopoietic cell transplantation (HCT). The cohort included 289 patients with a median of 48 years of age (range: 16–70). Point mutations were detected in 110 patients. Of these, 90 (82%) harbored T315I mutations, while 20 had other mutations. With a median follow-up period of 29 months (range: 1–125), outcomes after 2 years were worse with mutations than without (overall survival [OS]: 34% vs 68%, p < 0.001; relapse rate [RR]: 48% vs 18%, p < 0.001), particularly with the presence of the T315I mutation (OS: 29% vs 68%, p < 0.001; RR: 54% vs 18%, p < 0.001). OS was significantly worse in the T315I group even among the cohort with hematological ( p < 0.001) or molecular complete remission ( p = 0.025) as compared to the no mutation group. Multivariate analysis determined the prognostic impact of the T315I mutation (OS: hazard ratio [HR] = 2.19, 95% confidence interval [CI]: 1.5–3.3, p < 0.001; RR: HR = 2.51, 95% CI: 1.5–4.2, p < 0.001). This study is the first to report on the prognostic significance of BCR-ABL1 mutations in Ph + ALL.
ISSN:0939-5555
1432-0584
DOI:10.1007/s00277-020-04212-1