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T315I mutation exerts a dismal prognosis on adult BCR-ABL1-positive acute lymphoblastic leukemia, and salvage therapy with ponatinib or CAR-T cell and bridging to allogeneic hematopoietic stem cell transplantation can improve clinical outcomes.
Ting, Shi; Mixue, Xie; Lixia, Zhu; Xueying, Li; Wanzhuo, Xie; Xiujin, Ye.
Affiliation
  • Ting S; Senior Department of Hematology, The First Affiliated Hospital of Medical School of Zhejiang University, Hangzhou, Zhejiang Province, China.
  • Mixue X; Program in Clinical Medicine, School of Medicine of Zhejiang University, Hangzhou, Zhejiang Province, China.
  • Lixia Z; Senior Department of Hematology, The First Affiliated Hospital of Medical School of Zhejiang University, Hangzhou, Zhejiang Province, China.
  • Xueying L; Senior Department of Hematology, The First Affiliated Hospital of Medical School of Zhejiang University, Hangzhou, Zhejiang Province, China.
  • Wanzhuo X; Senior Department of Hematology, The First Affiliated Hospital of Medical School of Zhejiang University, Hangzhou, Zhejiang Province, China.
  • Xiujin Y; Senior Department of Hematology, The First Affiliated Hospital of Medical School of Zhejiang University, Hangzhou, Zhejiang Province, China.
Ann Hematol ; 99(4): 829-834, 2020 Apr.
Article in En | MEDLINE | ID: mdl-32107574
ABSTRACT
A single-center retrospective was performed with consecutive de novo BCR-ABL1-positive acute lymphoblastic leukemia (ALL) patients who received TKI-containing therapy between January 2010 and December 2018 to review the incidence, treatment, and outcome of the T315I mutation. A total of 38 (18%) patients harbored the T315I mutation in this period. According to the type of salvage therapy, patients were divided into subgroups of hematopoietic stem cell transplantation (HSCT) recipients (n = 9) and HSCT nonrecipients (n = 29). In the latter subgroup, there were 7 patients who newly acquired the T315I mutation after HSCT, and the median time was 10.8 months. In addition to these 7 cases, 5 out of 22 patients were managed with chimeric antigen receptor (CAR) T cells and ponatinib. There were 4 patients in the HSCT recipient subgroup who were treated with CAR-T cells or ponatinib before HSCT. The complete molecular remission (CMR) and recurrence rate of HSCT recipients were both 67%, and the median recurrence time was 3.6 months. A better overall survival (OS) was observed in the HSCT recipient subgroup than in the HSCT nonrecipient subgroup (median of 12.3 months vs 3.3 months, respectively; p = 0.004). Compared with patients who were not bridging to HSCT, the patients who were treated with CAR-T cells and/or ponatinib and bridged to HSCT tended to have a better OS (median of 3.3 months vs 13.3, respectively; p = 0.09). In conclusion, the outcomes in ALL patients with the T315I BCR-ABL1 mutation were poor. A better OS can be achieved through ponatinib, CAR-T cells, and bridging to HSCT, but it also has a higher risk of recurrence.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Pyridazines / Genes, abl / Fusion Proteins, bcr-abl / Mutation, Missense / Protein Kinase Inhibitors / Precursor Cell Lymphoblastic Leukemia-Lymphoma / Molecular Targeted Therapy / Imidazoles / Antineoplastic Agents Type of study: Etiology_studies / Incidence_studies / Prognostic_studies / Risk_factors_studies Limits: Adolescent / Adult / Female / Humans / Male / Middle aged Language: En Journal: Ann Hematol Journal subject: HEMATOLOGIA Year: 2020 Type: Article Affiliation country: China

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Pyridazines / Genes, abl / Fusion Proteins, bcr-abl / Mutation, Missense / Protein Kinase Inhibitors / Precursor Cell Lymphoblastic Leukemia-Lymphoma / Molecular Targeted Therapy / Imidazoles / Antineoplastic Agents Type of study: Etiology_studies / Incidence_studies / Prognostic_studies / Risk_factors_studies Limits: Adolescent / Adult / Female / Humans / Male / Middle aged Language: En Journal: Ann Hematol Journal subject: HEMATOLOGIA Year: 2020 Type: Article Affiliation country: China