Eskazan AE, Keskin D

Eskazan AE, Keskin D. more rapid and profound responses than imatinib; however, these drugs can also be associated with additional specific non\haematologic toxicities resulting in morbidities that might interfere with patient HRQoL.4 Overall, haematologic toxicities (myelosuppression) during TKI treatment is quite common, and it occurs both due to the suppression of the leukemic clone and the inhibition of non\leukemic haematopoiesis.5 When leukemic haematopoiesis is reduced by Mouse monoclonal to CD20.COC20 reacts with human CD20 (B1), 37/35 kDa protien, which is expressed on pre-B cells and mature B cells but not on plasma cells. The CD20 antigen can also be detected at low levels on a subset of peripheral blood T-cells. CD20 regulates B-cell activation and proliferation by regulating transmembrane Ca++ conductance and cell-cycle progression the TKI treatment, normal stem and progenitor cells need time to recover from pre\existing suppression by the malignant clone and to re\populate the bone marrow. Myelosuppression is usually limited to the first weeks or months of TKI therapy, and the incidence of grade III\IV myelosuppression is usually predominant only at the initial phase of the TKI treatment, decreasing substantially with longer duration of any TKI therapy. Haematologic AEs of TKIs are mostly dose and concentration dependent, reversible on treatment cessation or dose reduction, and affect all three lineages to a variable degree.5 Thus, myelosuppression is an expression of exposure of the consumed TKI. It is important, because it is the major cause of temporary and/or permanent cessation of the TKI. In this issue of the em British Journal of Clinical Pharmacology /em , Fachi and coworkers performed a systematic review and a meta\analysis on the serious (grade III\IV) haematologic AEs (anaemia, leukopenia, neutropenia, and thrombocytopenia) of all TKIs (imatinib, dasatinib, nilotinib, bosutinib, radotinib, or ponatinib, at any dose or regimen) utilized in the management of CML in chronic phase (CML\CP) focusing on the randomized controlled trials (RCTs) mainly included newly diagnosed and treatment na?ve patients.6 After the initial evaluation, the authors included 17 trials for the final analysis. As expected, none of the trials were placebo controlled, CBiPES HCl majority of them were sponsored by pharmaceutical companies, and all of the studies were open\label and with direct em head /em \to\ em head comparison /em , including all TKIs (bosutinib [n?=?2], dasatinib [n?=?5], imatinib [n?=?16], nilotinib [n?=?4], ponatinib [n?=?1], and radotinib [n?=?1]).6 Imatinib was the main comparator in all trials but one, in which different doses of dasatinib were tested in the second\line setting among cases with CML\CP following imatinib CBiPES HCl failure/intolerance.7 Although dose equivalence between these agents is unclear, the authors demonstrated that doses above 100\mg dasatinib caused anaemia in significantly more patients than that caused CBiPES HCl by imatinib up to 600?mg/day, or 600\mg nilotinib. However, there was no significant difference between dasatinib 100?mg and imatinib 400?mg (the recommended daily doses in newly diagnosed CML\CP cases) regarding the number of cases with grade III\IV anaemia. Supporting this obtaining, in the DASISION trial, where dasatinib 100?mg was tested against imatinib 400?mg in the first\line setting among patients with CML\CP, the percentages of grade III\IV anaemia were found to be 10% and 7% for dasatinib and imatinib, respectively.5 Similarly, when the authors compared all TKIs that are approved in the upfront setting in CML\CP with the recommened daily doses (imatinib 400?mg/day, nilotinib 600?mg/day, dasatinib 100?mg/day, bosutinib 400?mg/day, and radotinib 600?mg/day) with each other, there were no significant differences between these TKIs at those doses for the generation of grade III\IV anaemia.6 Both dasatinib 100 and 140?mg and imatinib 400 and 800?mg caused more leukopenia than nilotinib daily doses of 600 or 800?mg. Although dasatinib 140?mg/day significantly caused more neutropenia than nilotinib 600 or 800? mg and ponatinib 45?mg, bosutinib 400?mg daily caused significantly more neutropenia than dasatinib 140?mg. If all TKIs approved for the upfront setting with the recommended daily doses were compared with each other, no significant differences between each other regarding the development of leukopenia or neutropenia were detected.6 Regarding thrombocytopenia, 140\mg dasatinib was the less safe option, imatinib (400\600?mg) and 600\mg radotinib presented the lowest probabilities.