| 1. |
- Brissot, Eolia, et al.
(författare)
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Tyrosine kinase inhibitors improve long-term outcome of allogeneic hematopoietic stem cell transplantation for adult patients with Philadelphia chromosome positive acute lymphoblastic leukemia.
- 2015
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Ingår i: Haematologica. - : Ferrata Storti Foundation (Haematologica). - 1592-8721 .- 0390-6078. ; 100:3, s. 392-399
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Tidskriftsartikel (refereegranskat)abstract
- This study aimed to determine the impact of tyrosine-kinase inhibitors given pre- and post-allogeneic stem cell transplantation on long term outcome of patients allografted for Philadelphia chromosome-positive acute lymphoblastic leukemia. This retrospective analysis from the Acute Leukemia Working Party of EBMT included 473 de novo Philadelphia chromosome-positive acute lymphoblastic leukemia patients in first complete remission who underwent an allogeneic stem cell transplantation using an human leucocyte antigen-identical sibling or human leucocyte antigen-matched unrelated donor between 2000 and 2010. Three hundred ninety patients received tyrosine-kinase inhibitors before transplant, 329 at induction and 274 at consolidation. The Kaplan-Meier estimates of leukemia-free survival, overall survival, cumulative incidences of relapse incidence, and non-relapse mortality at 5 years were 38%, 46%, 36% and 26%, respectively. In multivariate analysis, tyrosine-kinase inhibitors given before allogeneic stem cell transplantation was associated with a better overall survival (HR=0.68; P=.04) and was associated with lower relapse incidence (HR=0.5; P=.01). In the post-transplant period, multivariate analysis identified prophylactic tyrosine-kinase inhibitors administration to be a significant factor for improved leukemia-free survival (HR=0.44; P=.002) and overall survival (HR=0.42; P=.004), and a lower relapse incidence (HR=0.40; P=.01). In conclusion, over the past decade, tyrosine-kinase inhibitors administration before allogeneic stem cell transplantation has significantly improved the long term allogeneic stem cell transplantation outcome of adult Philadelphia chromosome-positive acute lymphoblastic leukemia. Prospective studies will be of great interest to further confirm the potential benefit of the prophylactic use of tyrosine-kinase inhibitors in the post-transplant setting.
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| 2. |
- Ottmann, Oliver, et al.
(författare)
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Dasatinib induces rapid hematologic and cytogenetic responses in adult patients with Philadelphia chromosome-positive acute lymphoblastic leukemia with resistance or intolerance to imatinib : interim results of a phase 2 study
- 2007
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Ingår i: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 110:7, s. 2309-2315
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Tidskriftsartikel (refereegranskat)abstract
- Patients with Philadelphia (Ph) chromosome-positive acute lymphoblastic leukemia (ALL) have a rapid disease course and a poor prognosis. Dasatinib, a novel, oral, multitargeted kinase inhibitor of BCR-ABL and SRC family kinases, has previously induced responses in patients with imatinib-resistant or -intolerant Ph-positive ALL. We present the interim results of a phase 2 study designed to further assess the efficacy, safety, and tolerability of dasatinib 140 mg in this patient population (n = 36). With a minimum follow-up of 8 months, treatment with dasatinib resulted in substantial hematologic and cytogenetic response rates. Major hematologic responses were achieved in 42% (15/36) of patients, 67% of whom remained progression-free. Complete cytogenetic responses were attained by 58% (21/36) of patients. The presence of BCR-ABL mutations conferring imatinib resistance did not preclude a response to dasatinib. Dasatinib was also tolerable, with 6% (2/36) of patients discontinuing therapy as a result of study-drug toxicity. Most adverse events (AEs) were grade 1 or 2; febrile neutropenia was the most frequent severe AE, but this and other cytopenias were manageable with dose reduction. Dasatinib represents a safe and effective treatment option and an important therapeutic advance for patients with Ph-positive ALL. This trial was registered at www.clinicaltrials.gov as #CA180015.
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