Tyrosine Kinase Inhibitors and Allogeneic Hematopoietic Cell Transplantation for Chronic Myeloid Leukemia: Targeting Both Therapeutic Modalities

2009 ◽  
Vol 16 (2) ◽  
pp. 153-157 ◽  
Author(s):  
Hugo F. Fernandez ◽  
Mohamed A. Kharfan-Dabaja
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitors ◽  
Cell Transplantation ◽  
Myeloid Leukemia ◽  
Kinase Inhibitors ◽  
Hematopoietic Cell Transplantation ◽  
Hematopoietic Cell ◽  
Allogeneic Hematopoietic Cell Transplantation ◽  
Therapeutic Modalities

scholarly journals Tyrosine kinase inhibitors and immune checkpoint blockade in allogeneic hematopoietic cell transplantation

Blood ◽  
2018 ◽  
Vol 131 (10) ◽  
pp. 1073-1080 ◽  
Author(s):  
Robert J. Soiffer ◽  
Matthew S. Davids ◽  
Yi-Bin Chen
Keyword(s):  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitors ◽  
Cell Transplantation ◽  
Immune Checkpoint ◽  
Kinase Inhibitors ◽  
Hematopoietic Cell Transplantation ◽  
Checkpoint Inhibitors ◽  
Hematopoietic Cell ◽  
Allogeneic Hematopoietic Cell Transplantation ◽  
Therapeutic Window

Abstract Advances in the prevention of graft-versus-host disease (GVHD) and opportunistic infection have improved survival after allogeneic hematopoietic cell transplantation (allo-HCT) in the past decade. However, few inroads have been made into the treatment or prevention of relapse of the underlying malignancy for which allo-HCT is being performed. The introduction of US Food and Drug Administration–approved agents with significant activity in a variety of hematologic malignancies provides an opportunity to evaluate these interventions in the allo-HCT setting. Some of the most promising new agents include tyrosine kinase inhibitors (TKIs) directed at bcr-abl, kinase inhibitors targeting fms-like tyrosine kinase 3, and immune checkpoint inhibitors blocking both CTLA4 and PD-1. Data have emerged indicating potential efficacy of these agents in preventing or treating relapse, though definitive evidence remains elusive. However, potential toxicity can be considerable, highlighting the need for further clinical trials to define the therapeutic window. This review explores the immunologic and clinical consequence of treatment with both TKIs and checkpoint inhibitors in the peri- and post–allo-HCT setting.

scholarly journals Outcomes and toxicity of allogeneic hematopoietic cell transplantation in chronic myeloid leukemia patients previously treated with second-generation tyrosine kinase inhibitors: a prospective non-interventional study from the Chronic Malignancy Working Party of the EBMT

2021 ◽  
Author(s):  
Stavroula Masouridi-Levrat ◽  
Eduardo Olavarria ◽  
Simona Iacobelli ◽  
Mahmoud Aljurf ◽  
Elena Morozova ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitors ◽  
Myeloid Leukemia ◽  
Kinase Inhibitors ◽  
Hematopoietic Cell Transplantation ◽  
Interventional Study ◽  
Post Transplant ◽  
Previously Treated ◽  
Transplant Complications

AbstractAllogeneic hematopoietic cell transplantation (allo-HCT) remains a treatment option for patients with chronic myeloid leukemia (CML) who fail to respond to tyrosine kinase inhibitors (TKIs). While imatinib seems to have no adverse impact on outcomes after transplant, little is known on the effects of prior use of second-generation TKI (2GTKI). We present the results of a prospective non-interventional study performed by the EBMT on 383 consecutive CML patients previously treated with dasatinib or nilotinib undergoing allo-HCT from 2009 to 2013. The median age was 45 years (18–68). Disease status at transplant was CP1 in 139 patients (38%), AP or >CP1 in 163 (45%), and BC in 59 (16%). The choice of 2GTKI was: 40% dasatinib, 17% nilotinib, and 43% a sequential treatment of dasatinib and nilotinib with or without bosutinib/ponatinib. With a median follow-up of 37 months (1–77), 8% of patients developed either primary or secondary graft failure, 34% acute and 60% chronic GvHD. There were no differences in post-transplant complications between the three different 2GTKI subgroups. Non-relapse mortality was 18% and 24% at 12 months and at 5 years, respectively. Relapse incidence was 36%, overall survival 56% and relapse-free survival 40% at 5 years. No differences in post-transplant outcomes were found between the three different 2GTKI subgroups. This prospective study demonstrates the feasibility of allo-HCT in patients previously treated with 2GTKI with a post-transplant complications rate comparable to that of TKI-naive or imatinib-treated patients.

Three decades of transplantation for chronic myeloid leukemia: what have we learned?

Blood ◽  
2011 ◽  
Vol 117 (3) ◽  
pp. 755-763 ◽  
Author(s):  
Jiří Pavlů ◽  
Richard M. Szydlo ◽  
John M. Goldman ◽  
Jane F. Apperley
Keyword(s):  
Stem Cell ◽  
Chronic Myeloid Leukemia ◽  
Stem Cell Transplantation ◽  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitors ◽  
Cell Transplantation ◽  
Myeloid Leukemia ◽  
Kinase Inhibitors ◽  
Chronic Phase ◽  
Hematopoietic Stem

Abstract Last year marked 30 years of hematopoietic stem cell transplantation as a curative treatment of chronic myeloid leukemia (CML). Initially studies used stem cells from identical twins but techniques rapidly developed to use cells first from HLA-identical siblings and later unrelated donors. During the 1990s CML became the most frequent indication for allogeneic transplantation worldwide. This, together with the relative biologic homogeneity of CML in chronic phase, its responsiveness to graft-versus-leukemia effect and the ability to monitor low level residual disease placed CML at the forefront of research into different strategies of stem cell transplantation. The introduction of BCR-ABL1 tyrosine kinase inhibitors during the last decade resulted in long-term disease control in the majority of patients with CML. In those who fail to respond and/or develop intolerance to these agents, transplantation remains an effective therapeutic solution. The combination of tyrosine kinase inhibitors with transplantation is an exciting new strategy and it provides inspiration for similar approaches in other malignancies.

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