Current status and perspectives of tyrosine kinase inhibitor treatment in the posttransplant period in patients with chronic myelogenous leukemia (CML)

TY - JOUR

T1 - Current status and perspectives of tyrosine kinase inhibitor treatment in the posttransplant period in patients with chronic myelogenous leukemia (CML)

AU - Klyuchnikov, Evgeny

AU - Kröger, Nicolaus

AU - Brummendorf, Tim H

AU - Wiedemann, Bettina

AU - Zander, Axel Rolf

AU - Bacher, Ulrike

N1 - Copyright (c) 2010 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

PY - 2010/3/1

Y1 - 2010/3/1

N2 - Following the introduction of tyrosine kinase inhibitors (TKIs) in chronic myelogenous leukemia (CML), allogeneic stem cell transplantation (SCT) took a shift toward high-risk patients. Considering the high relapse rates posttransplant in these selected patients, several studies evaluated posttransplant use of the TKI imatinib. Although the number of studies are still limited, and data have to be confirmed by additional studies, safety of imatinib even within the first months after SCT seems to be acceptable. Imatinib was shown to be effective in patients with molecular or hematologic relapse of chronic or accelerated phase posttransplant (CP, AP), whereas outcomes in blast phase were more unfavorable. The compound further seemed beneficial for prophylactic use in patients who achieved complete remission posttransplant. The combination of imatinib with donor lymphocytes did not result in increased toxicity or graft-versus-host disease (GVHD). First studies suggest that second-generation TKIs such as dasatinib or nilotinib are manageable posttransplant with acceptable toxicity as well. In conclusion, TKIs of the first- and second-generation are promising options for the posttransplant period of patients with CML, but algorithms for dosage, intervals from SCT, duration of application, and the combination with donor lymphocytes still have to be developed.

AB - Following the introduction of tyrosine kinase inhibitors (TKIs) in chronic myelogenous leukemia (CML), allogeneic stem cell transplantation (SCT) took a shift toward high-risk patients. Considering the high relapse rates posttransplant in these selected patients, several studies evaluated posttransplant use of the TKI imatinib. Although the number of studies are still limited, and data have to be confirmed by additional studies, safety of imatinib even within the first months after SCT seems to be acceptable. Imatinib was shown to be effective in patients with molecular or hematologic relapse of chronic or accelerated phase posttransplant (CP, AP), whereas outcomes in blast phase were more unfavorable. The compound further seemed beneficial for prophylactic use in patients who achieved complete remission posttransplant. The combination of imatinib with donor lymphocytes did not result in increased toxicity or graft-versus-host disease (GVHD). First studies suggest that second-generation TKIs such as dasatinib or nilotinib are manageable posttransplant with acceptable toxicity as well. In conclusion, TKIs of the first- and second-generation are promising options for the posttransplant period of patients with CML, but algorithms for dosage, intervals from SCT, duration of application, and the combination with donor lymphocytes still have to be developed.

KW - Humans

KW - Leukemia, Myelogenous, Chronic, BCR-ABL Positive

KW - Protein Kinase Inhibitors

KW - Protein-Tyrosine Kinases

KW - Stem Cell Transplantation

U2 - 10.1016/j.bbmt.2009.08.019

DO - 10.1016/j.bbmt.2009.08.019

M3 - SCORING: Journal article

C2 - 19744571

VL - 16

SP - 301

EP - 310

JO - BIOL BLOOD MARROW TR

JF - BIOL BLOOD MARROW TR

SN - 1083-8791

IS - 3

ER -