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Treatment with dasatinib or nilotinib in chronic myeloid leukemia patients who failed to respond to two previously administered tyrosine kinase inhibitors--a single center experience.

ABSTRACT: To evaluate hematological, cytogenetic and molecular responses as well as the overall, progression-free and event-free survivals of chronic myeloid leukemia patients treated with a third tyrosine kinase inhibitor after failing to respond to imatinib and nilotinib/dasatinib.Bone marrow karyotyping and real-time quantitative polymerase chain reaction were performed at baseline and at 3, 6, 12 and 18 months after the initiation of treatment with a third tyrosine kinase inhibitor. Hematologic, cytogenetic and molecular responses were defined according to the European LeukemiaNet recommendations. BCR-ABL1 mutations were analyzed by Sanger sequencing.We evaluated 25 chronic myeloid leukemia patients who had been previously treated with imatinib and a second tyrosine kinase inhibitor. Nine patients were switched to dasatinib, and 16 patients were switched to nilotinib as a third-line therapy. Of the chronic phase patients (n=18), 89% achieved a complete hematologic response, 13% achieved a complete cytogenetic response and 24% achieved a major molecular response. The following BCR-ABL1 mutations were detected in 6/14 (43%) chronic phase patients: E255V, Y253H, M244V, F317L (2) and F359V. M351T mutation was found in one patient in the accelerated phase of the disease. The five-year overall, progression-free and event-free survivals were 86, 54 and 22% (p<0.0001), respectively, for chronic phase patients and 66%, 66% and 0% (p<0.0001), respectively, for accelerated phase patients. All blast crisis patients died within 6 months of treatment. Fifty-six percent of the chronic phase patients lost their hematologic response within a median of 23 months.Although the responses achieved by the third tyrosine kinase inhibitor were not sustainable, a third tyrosine kinase inhibitor may be an option for improving patient status until a donor becomes available for transplant. Because the long-term outcome for these patients is poor, the development of new therapies for resistant chronic myeloid leukemia patients is necessary.

SUBMITTER: Ribeiro BF

PROVIDER: S-EPMC4518767 | biostudies-literature | 2015 Aug

REPOSITORIES: biostudies-literature

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Treatment with dasatinib or nilotinib in chronic myeloid leukemia patients who failed to respond to two previously administered tyrosine kinase inhibitors--a single center experience.

Ribeiro Beatriz Felicio BF Miranda Eliana C M EC Albuquerque Dulcinéia Martins de DM Delamain Márcia T MT Oliveira-Duarte Gislaine G Almeida Maria Helena MH Vergílio Bruna B Silveira Rosana Antunes da RA Oliveira-Duarte Vagner V Lorand-Metze Irene I De Souza Carmino A CA Pagnano Katia B B KB

Clinics (Sao Paulo, Brazil) 20150801 8

<h4>Objective</h4>To evaluate hematological, cytogenetic and molecular responses as well as the overall, progression-free and event-free survivals of chronic myeloid leukemia patients treated with a third tyrosine kinase inhibitor after failing to respond to imatinib and nilotinib/dasatinib.<h4>Methods</h4>Bone marrow karyotyping and real-time quantitative polymerase chain reaction were performed at baseline and at 3, 6, 12 and 18 months after the initiation of treatment with a third tyrosine ki ...[more]

PMID: 26247667

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Project description:BackgroundPatients with a history of degenerative joint disease secondary to an acute or remote episode of septic arthritis of the native knee or hip present a unique challenge for the orthopaedic surgeon. This study describes our experience with two-stage primary arthroplasty for such patients.MethodsWe reviewed 42 patients with a history of septic arthritis treated with two-stage primary arthroplasty between 2008 and 2018. Patients were evaluated using modified Harris Hip Score, Knee Society Score (KSS), and KSS functional component (KSSF). Paired t-tests were used to compare changes for continuous variables within cohorts. Multivariate linear and logistic regression models were constructed to determine predictors of outcomes and complications.ResultsAt a mean of 3.3-year follow-up, there were 14 (33.3%) complications and the infection cure rate was 95.2%. On average, patients improved in the modified Harris Hip Score (42.9 ± 11.8 vs 83.3 ± 11.1, P < .001), KSS (35.9 ± 16.9 vs 80.1 ± 16.6, P < .001), KSSF (38.0 ± 15.1 vs 71.5 ± 24.0, P < .001), knee flexion (90.9 ± 14.9 vs 100.5 ± 17.1), and hip flexion (73.8 ± 21.2 vs 102.1 ± 11.8, P < .001). Age (β: -0.78, P = .004) was independently associated with lower Harris Hip Score in the hip cohort. There were no independent predictors of the KSS or KSSF. The erythrocyte sedimentation rate (odds ratio: 1.07, P = .043) and C-reactive protein (odds ratio: 1.43, P = .018) at stage 2 were independently associated with a higher likelihood of complications at the final follow-up.ConclusionPatients with a history of native septic arthritis of the hip and knee, and secondary end-stage degenerative joint disease, showed significant postoperative improvements and a high rate of complications after two-stage primary total joint arthroplasty. Despite improvements, some patients may necessitate a third operation because of the incidence of reinfection and spacer exchange. This information should be used to counsel patients who present with this challenging clinical scenario.

Dataset Information

Treatment with dasatinib or nilotinib in chronic myeloid leukemia patients who failed to respond to two previously administered tyrosine kinase inhibitors--a single center experience.

Publications

Treatment with dasatinib or nilotinib in chronic myeloid leukemia patients who failed to respond to two previously administered tyrosine kinase inhibitors--a single center experience.

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