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Clinical outcome of 27 imatinib mesylate-resistant chronic myelogenous leukemia patients harboring a T315I BCR-ABL mutation

From Hematology Department, Hôpital E. Herriot, 69437 Lyon(FEN, EB, QL, MM); Laboratory for Hematology and Cytogenetics, Centre Hospitalier Lyon Sud, 69495 Pierre-Bénite(SH); 3Hematology Department, CHRU 59037, Lille (SC); Laboratory for Hematology, Hôpital Henri Mondor, 94000 Créteil (DB, MT); Oncology, Cellular Therapy and Hematology Department, Hôpital J. Bernard, 86021 Poitiers (FG); Hematology Department, Hôpital de l’Archet, 06202 Nice (LL); Hematology Department, Hôpital Civil, 67100 Strasbourg (FM); Hematology Department, Hôpital Avicenne, 93000 Bobigny (J-JK); Laboratory for Hematology, Hôpital Pellegrin, 33076 Bordeaux (FXM); Laboratory for Medical Genetics, Hôpital Jeanne de Flandre, CHRU 59037 and U817 Inserm Lille (CR-L); Laboratory for Hematology, Hôpital Calmette, CHRU 59037 Lille and U817 Inserm Lille, France (CP)

Correspondence: Franck E. Nicolini, MD PhD, Hematology department, E Pavilion, Hôpital Edouard Herriot, 5, place d’Arsonval, 69437 Lyon, Cédex 03, France. E-mail: franck-emmanuel.nicolini{at}chu-lyon.fr

We analyzed 27 CML patients treated with imatinib (IM) who developed a BCR-ABL^T315I mutation. These patients had poor prognostic features: High or intermediate Sokal index (82%), and lack of CCyR under IM (59%). At T315I discovery, patients were in advanced phase (59%), with clonal evolution (84%). Median time since diagnosis was 39 months, and progression occurred 13 months after IM initiation, regardless of disease phase. Overall survival since IM initiation was 42.5 months for chronic, and 17.5 months for advanced phases, and all patients progressed. This mutation seems related to or (partially?) responsible for progression and poor survival.

Key words: CML, imatinib mesylate, BCR-ABL mutation, T315I.

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