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Synergistic effect of sorafenib and cGvHD in patients with high-risk FLT3-ITD+AML allows long-term disease control after allogeneic transplantation

Tschan-Plessl, A. and Halter, Jörg and Heim, Dominik and Medinger, Michael and Passweg, Jakob and Gerull, Sabine. (2015) Synergistic effect of sorafenib and cGvHD in patients with high-risk FLT3-ITD+AML allows long-term disease control after allogeneic transplantation. Annals of hematology, 94 (11). pp. 1899-1905.

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Official URL: http://edoc.unibas.ch/43897/

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Abstract

The multikinase inhibitor sorafenib has shown a strong anti-leukemic effect in FMS-like tyrosine kinase 3 (FLT3)-mutated acute myeloid leukemia (AML); however, remission is often transient. To better understand the role of sorafenib, we performed a retrospective analysis of all patients who received sorafenib in combination with allogeneic hematopoietic stem cell transplantation (HSCT) at our center. Seventeen patients with FLT3-ITD positive AML were treated with sorafenib in combination with allogeneic HSCT. Seven patients received sorafenib therapy pre- and posttransplant, and 10 patients were given sorafenib only posttransplant. Median duration of sorafenib treatment was 13 months (range 1-42); median dose was 600 mg (range 100-1200). Fourteen patients (82 %) achieved a complete remission (CR), while 5 patients (29 %) eventually developed progressive disease. Developing chronic graft-versus-host disease (GvHD) had a strong protective influence on the risk of sorafenib resistance (p = 0.028, HR 0.08, 95 % CI 0.01-0.76). In a total of 8 patients, sorafenib had to be stopped, paused or dose-reduced due to toxicity. In 5 patients with pronounced toxicity, we switched to an alternating dosing schedule with 1 month on/1 month off sorafenib. These patients subsequently remained in sustained complete molecular remission, with a median follow-up of 20 months. Our data indicate that sorafenib can achieve high rates of sustained remission in high-risk patients treated in combination with HSCT.
Faculties and Departments:03 Faculty of Medicine
UniBasel Contributors:Medinger, Michael
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Springer
ISSN:0939-5555
Note:Publication type according to Uni Basel Research Database: Journal article
Identification Number:
Last Modified:05 Jan 2017 09:16
Deposited On:05 Jan 2017 09:16

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