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