Clinical characteristics of chronic myeloid leukemia with T315I mutation and the efficacy of ponatinib.
10.12122/j.issn.1673-4254.2019.03.16
- Author:
Chen CHEN
1
;
Na XU
1
;
Xuejie JIANG
1
;
Waner WU
1
;
Xuan ZHOU
1
;
Liang LIU
1
;
Jixian HUANG
1
;
Changxin YIN
1
;
Rui CAO
1
;
Libin LIAO
1
;
Dan XU
1
;
Yuming ZHANG
2
;
Qifa LIU
1
;
Xiaoli LIU
1
Author Information
1. Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
2. Department of Hematology, Affiliated Hospital of Guangdong Medical University, Zhanjiang 524000, China.
- Publication Type:Journal Article
- Keywords:
BCR-ABL;
T315I;
chronic myeloid leukemia;
hematopoietic stem cell transplantation;
ponatinib
- MeSH:
Drug Resistance, Neoplasm;
Fusion Proteins, bcr-abl;
Humans;
Imidazoles;
Leukemia, Myelogenous, Chronic, BCR-ABL Positive;
Mutation;
Pyridazines;
Retrospective Studies
- From:
Journal of Southern Medical University
2019;39(3):364-368
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE:To analyze the clinical features of chronic myeloid leukemia (CML) with T315 I mutation (CML-T315I) and compare the effectiveness of different treatments.
METHODS:We retrospectively analyzed the clinical data and outcomes of 19 patients with CML-T315I receiving different treatments. The T315 I mutations in these patients were detected by examination of BCR-ABL kinase domain (KD) mutation by RTQ-PCR and Sanger sequencing. The relapse following the treatments, defined as hematological, cytogenetic and molecular biological recurrences, were analyzed in these patients.
RESULTS:Of the 19 patients with CML-T315I, 14 (73.7%) were in CML-CP stage at the initial diagnosis, and 13 (81.2%) were high-risk patients based on the Sokal scores. All the 19 patients were treated with TKI after the initial diagnosis, and during the treatment, 15 (78.9%) patients were found to have additional chromosomal aberrations, and 10 (52.6%) had multiple mutations; 13 (68.4%) of the patients experienced disease progression (accelerated phase/blast crisis) before the detection of T315I mutation, with a median time of 40 months (5-120 months) from the initial diagnosis to the mutation detection. After detection of the mutation, 12 patients were treated with ponatinib and 7 were managed with the conventional chemotherapy regimen, and their overall survival rates at 3 years were 83.3% and 14.2%, respectively ( < 0.001).
CONCLUSIONS:CML patients resistant to TKI are more likely to have T315I mutations, whose detection rate is significantly higher in the progressive phase than in the chronic phase. These patients often have additional chromosomal aberrations and multiple gene mutations with poor prognoses and a high recurrence rate even after hematopoietic stem cell transplantation. Long-term maintenance therapy with ponatinib may improve the prognosis and prolong the survival time of the patients.
