Second line BCR/ABK TKI-associated severe adverse events:preferential occurrence in patients with comorbidities

Valent, Peter

doi:10.3324/haematol.2011.052076

Cited by 19 publications

(7 citation statements)

References 20 publications

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“…Non-relapse 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 veno-occlusive disease (VOD), cardiac toxicity, as well as immune dysfunctions or delayed engraftment can be expected [ 7 , 8 ]. The long term outcome of TKI2-resistant patients remains another important issue.…”

Section: Introductionmentioning

confidence: 99%

Pretransplantation use of the second-generation tyrosine kinase inhibitors has no negative impact on the HCT outcome

et al. 2015

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IntroductionAllogeneic 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 incidence.ResultsAll the patients but one engrafted with median time 19 days. OS for patients in CP1 and CP2/accelerated phase (AcP) were 92.9 and 85.7 %, respectively. Six patients allotransplanted in blast crisis (BC) CML died early after HCT.Eighteen patients achieved deep molecular remission (MR4.5 or MR4.0). Relapse incidence was 29.6 %. 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 GvHD.NRM yielded the values 7.1, 12.5, and 50 % in CP1, CP2/AcP, and BC, respectively. Fatal outcome, due to veno-occlusive disease (VOD), was observed in two (7 %) patients. In five (17.9 %) patients, mild or moderate VOD was observed with no negative impact of preceding therapy with TKI2. Acute GvHD was diagnosed in 25.9 % of patients, while chronic GvHD developed in 42.9 % of individuals.ConclusionPretransplantation therapy with TKI2 in CP CML is safe and reasonable. In BC, the optimal approach before HCT is to reduce the leukemic burden and achieve subsequent CP.

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Section: Introductionmentioning

confidence: 99%

Pretransplantation use of the second-generation tyrosine kinase inhibitors has no negative impact on the HCT outcome

et al. 2015

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“…Additionally, elevated risk for cardiovascular complications, such as hypertension, heart failure (HF), left ventricular systolic dysfunction, myocardial ischemia (MI), and QT interval prolongation, has been reported in cancer patients receiving TKI treatment ( 4 , 5 ). It seems that TKI-related cardiotoxicities have preferential occurrence in patients with preexisting comorbidities ( 115 ). Hurley et al ( 116 ) reported that patients who have a history of hyperlipidemia, congestive heart failure, coronary artery diseases, and chronic obstructive pulmonary disease before TKI treatment have a greater risk of developing TKI-related cardiotoxicity.…”

Section: Evidence Linking Cancer Tyrosine Kinase Inhibitors and Cardi...mentioning

confidence: 99%

The two facets of receptor tyrosine kinase in cardiovascular calcification—can tyrosine kinase inhibitors benefit cardiovascular system?

Masbuchin

Widodo

Rohman

et al. 2022

Front. Cardiovasc. Med.

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Tyrosine kinase inhibitors (TKIs) are widely used in cancer treatment due to their effectiveness in cancer cell killing. However, an off-target of this agent limits its success. Cardiotoxicity-associated TKIs have been widely reported. Tyrosine kinase is involved in many regulatory processes in a cell, and it is involved in cancer formation. Recent evidence suggests the role of tyrosine kinase in cardiovascular calcification, specifically, the calcification of heart vessels and valves. Herein, we summarized the accumulating evidence of the crucial role of receptor tyrosine kinase (RTK) in cardiovascular calcification and provided the potential clinical implication of TKIs-related ectopic calcification. We found that RTKs, depending on the ligand and tissue, can induce or suppress cardiovascular calcification. Therefore, RTKs may have varying effects on ectopic calcification. Additionally, in the context of cardiovascular calcification, TKIs do not always relate to an unfavored outcome—they might offer benefits in some cases.

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“…Finally, also BCR-Abl1 inhibition typically causes several negative side effects, including cytopenia, hypothyroidism and cardiac abnormalities [ 43 – 46 ]. Furthermore, IM has been reported to induce, in patients subjected to a long-term therapy, a decrease of hematic phosphate levels (hypophosphatemia) associated to phosphaturia, and alterations of the bone turn-over markers.…”

Section: Tyrosine Kinase Inhibitorsmentioning

confidence: 99%

Tyrosine kinase inhibitors and mesenchymal stromal cells: effects on self-renewal, commitment and functions

et al. 2016

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The hope of selectively targeting cancer cells by therapy and eradicating definitively malignancies is based on the identification of pathways or metabolisms that clearly distinguish “normal” from “transformed” phenotypes. Some tyrosine kinase activities, specifically unregulated and potently activated in malignant cells, might represent important targets of therapy. Consequently, tyrosine kinase inhibitors (TKIs) might be thought as the “vanguard” of molecularly targeted therapy for human neoplasias. Imatinib and the successive generations of inhibitors of Bcr-Abl1 kinase, represent the major successful examples of TKI use in cancer treatment. Other tyrosine kinases have been selected as targets of therapy, but the efficacy of their inhibition, although evident, is less definite. Two major negative effects exist in this therapeutic strategy and are linked to the specificity of the drugs and to the role of the targeted kinase in non-malignant cells. In this review, we will discuss the data available on the TKIs effects on the metabolism and functions of mesenchymal stromal cells (MSCs). MSCs are widely distributed in human tissues and play key physiological roles; nevertheless, they might be responsible for important pathologies. At present, bone marrow (BM) MSCs have been studied in greater detail, for both embryological origins and functions. The available data are evocative of an unexpected degree of complexity and heterogeneity of BM-MSCs. It is conceivable that this grade of intricacy occurs also in MSCs of other organs. Therefore, in perspective, the negative effects of TKIs on MSCs might represent a critical problem in long-term cancer therapies based on such inhibitors.

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Second line BCR/ABK TKI-associated severe adverse events:preferential occurrence in patients with comorbidities

Cited by 19 publications

References 20 publications

Pretransplantation use of the second-generation tyrosine kinase inhibitors has no negative impact on the HCT outcome

Pretransplantation use of the second-generation tyrosine kinase inhibitors has no negative impact on the HCT outcome

The two facets of receptor tyrosine kinase in cardiovascular calcification—can tyrosine kinase inhibitors benefit cardiovascular system?

Tyrosine kinase inhibitors and mesenchymal stromal cells: effects on self-renewal, commitment and functions

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