Authors: Agnieszka Piekarska Lidia Gil Witold Prejzner Piotr Wiśniewski Aleksandra Leszczyńska Michał Gniot Mieczysław Komarnicki Andrzej Hellmann
Publish Date: 2015/07/29
Volume: 94, Issue: 11, Pages: 1891-1897
Abstract
Allogeneic hematopoietic cell transplantation HCT was a standard therapy in chronic phase CP chronic myeloid leukemia CML As a result of the effective therapy with tyrosine kinase inhibitors TKI HCT was shifted to defined clinical situations We present the results of observational prospective analysis of 28 CML patients undergoing HCT after exposure to at least two lines of TKI including dasatinib and/or nilotinib with respect to response overall survival OS treatment toxicity graft versus host disease GVHD and progression/relapse incidenceEighteen patients achieved deep molecular remission MR45 or MR40 Relapse incidence was 296 Median time to progression TTP differs significantly depending on the CML phase prior to HCT the best response achieved after HCT and development of chronic GvHDNRM yielded the values 71 125 and 50 in CP1 CP2/AcP and BC respectively Fatal outcome due to venoocclusive disease VOD was observed in two 7 patients In five 179 patients mild or moderate VOD was observed with no negative impact of preceding therapy with TKI2 Acute GvHD was diagnosed in 259 of patients while chronic GvHD developed in 429 of individualsAllogeneic hematopoietic cell transplantation HCT was historically a standard curative therapy for patients with chronic phase CP chronic myeloid leukemia CML As a result of the novel highly effective therapy with tyrosine kinase inhibitors TKI the use of HCT was shifted to defined clinical situations Following the European LeukemiaNet ELN guidelines patients with Philadelphia positive Ph+ CML diagnosed in the advanced phase accelerated phase AcP blast phase/crisis BC or resistant to imatinib or secondgeneration TKI TKI2 should be qualified to HCT 1 A number of published data shows no serious negative impact of imatinib mesylate therapy prior to HCT 2 3 4 5 but only few studies concerning the outcome of HCT in TKI2resistant patients are currently available 6Nonrelapse mortality NRM and organ toxicity in patients receiving TKI2 before transplantation are of interest Based on the toxicity profile of both dasatinib and nilotinib development of hepatic venoocclusive disease VOD cardiac toxicity as well as immune dysfunctions or delayed engraftment can be expected 7 8 The long term outcome of TKI2resistant patients remains another important issue Potentially poorer outcome of patients pretreated with TKI2 may result from the selection of more aggressive clones of malignant cells with additional molecular aberrations promoting their proliferation and survival abilities Moreover TKI2resistant patients are usually transplanted in more advanced phases of the disease or are simply older when they finally enter the procedure of HCT Additional problems are related to the late toxicity of HCT and chronic GvHD significantly affecting the quality of lifeIn this study we present the results of observational prospective analysis of CML patients undergoing allogeneic hematopoietic cell transplantation after exposure to TKI2 as the secondline therapy with respect to response overall survival treatment toxicity GVHD and progression/relapse incidence
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