Incidence and outcome of BCR‐ABL mutated chronic myeloid leukemia patients who failed to tyrosine kinase inhibitors
In: ISSN: 2045-7634, 2019
Online
academicJournal
Zugriff:
International audience ; PurposeTo assess the incidence of BCR‐ABL kinase domain (KD) mutation detection and its prognostic significance in chronic phase chronic myeloid leukemia (CP‐CML) patients treated with tyrosine kinase inhibitors (TKIs).Patients and MethodsWe analyzed characteristics and outcome of 253 CP‐CML patients who had at least one mutation analysis performed using direct sequencing. Of them, 187 patients were early CP (ECP) and 66 were late CP late chronic phase (LCP) and 88% were treated with Imatinib as first‐line TKI.ResultsOverall, 80 (32%) patients harbored BCR‐ABL KD mutations. A BCR‐ABL KD mutation was identified in 57% of patients, who progressed to accelerated or blastic phases (AP‐BP), and 47%, 29%, 35%, 16% and 26% in patients in CP‐CML at the time of mutation analysis who lost a complete hematologic response, failed to achieve or loss of a prior complete cytogenetic and major molecular response, respectively.Overall survival and cumulative incidence of CML‐related death were significantly correlated with the disease phase whatever the absence or presence of a mutation was and for the latter the mutation subgroup (T315I vs P‐loop vs non‐T315I non‐P‐loop) (P<.001). Considering patients who were in CP at the time of mutation analysis, LCP mutated patients had a significantly worse outcome than ECP‐mutated patients despite a lower incidence of T315I and P‐loop mutations (P<.001). With a median follow‐up from mutation analysis to last follow‐up of 5 years, T315I and P‐loop mutations were not associated with a worse outcome in ECP patients (P = .817).ConclusionOur results suggest that early mutation detection together with accessibility to 2nd and 3rd generation TKIs have reversed the worst outcome associated with BCR‐ABL KD mutations whatever the mutation subgroup in CP‐CML patients.
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Incidence and outcome of BCR‐ABL mutated chronic myeloid leukemia patients who failed to tyrosine kinase inhibitors
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Autor/in / Beteiligte Person: | Etienne, Gabriel ; Dulucq, Stéphanie ; Huguet, Françoise ; Schmitt, Anna ; Lascaux, Axelle ; Hayette, Sandrine ; Fort, Marie-Pierre ; Sujobert, Pierre ; Bijou, Fontanet ; Morisset, Stéphane ; Tavitian, Suzanne ; Bidet, Audrey ; Turcq, Béatrice ; Robbesyn, Fanny ; Chollet, Claudine ; Belloc, Francis ; Durrieu, Françoise ; Mahon, François-Xavier ; Nicolini, Franck ; Institut Bergonié Bordeaux ; UNICANCER ; Laboratory of Mammary and Leukaemic Oncogenesis, INSERM U1218, Université de Bordeaux ; Laboratoire d'Hématologie, Hôpital Haut Lévêque CHU de Bordeaux, Pessac ; Bordeaux, CHU ; Service Hématologie - IUCT-Oncopole CHU Toulouse ; Pôle Biologie CHU Toulouse ; Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Pôle IUCT CHU Toulouse ; Centre Hospitalier Universitaire de Toulouse (CHU Toulouse) ; Service des maladies du sang, Hôpital Haut Lévêque CHU de Bordeaux, Pessac ; Service d'hématologie Hôpital Edouard Herriot -, HCL ; Hôpital Edouard Herriot CHU -, HCL ; Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL) ; Laboratoire d'Hématologie, Centre Hospitalier Lyon Sud, Pierre Bénite ; Hospices Civils de Lyon (HCL) ; Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037) ; Université Toulouse III - Paul Sabatier (UT3) ; Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM) ; Institut National de la Santé et de la Recherche Médicale (INSERM) ; Centre National de la Recherche Scientifique (CNRS) ; Service d’Hématologie Centre Hospitalier Lyon Sud -, HCL ; Centre Hospitalier Lyon Sud CHU - HCL (CHLS) |
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Zeitschrift: | ISSN: 2045-7634, 2019 |
Veröffentlichung: | HAL CCSD ; Wiley, 2019 |
Medientyp: | academicJournal |
DOI: | 10.1002/cam4.2410 |
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