American journal of hematology
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Chronic Myeloid Leukemia (CML) is a myeloproliferative neoplasm with an incidence of one-two cases per 100,000 adults and accounts for ∼15% of newly diagnosed cases of leukemia in adults. ⋯ For patients who fail standard-dose imatinib therapy, imatinib dose escalation is a second-line option. Alternative second-line options include 2nd generation TKIs. Although both are potent and specific BCR-ABL TKIs, dasatinib and nilotinib exhibit unique pharmacological profiles and response patterns relative to different patient characteristics, such as disease stage and BCR-ABL mutational status. Patients who develop the T315I "gatekeeper" mutation display resistance to all currently available TKIs and are candidate for clinical trials. Allogeneic transplantation remains an important therapeutic option for CML-CP harboring the T315I mutation, patients who fail 2nd generation TKIs, and for all patients in advanced phase disease.
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Comparative Study
Comparative rates of adverse events with different formulations of intravenous iron.
Oral iron replacement is the standard therapy in iron-deficiency anemia (IDA). However, 59% of patients have gastrointestinal toxicity. With impaired iron uptake from the gastrointestinal tract (in anemia of chronic disease (ACD) or after bariatric surgery), suboptimal responsiveness to exogenous erythropoietin (in chronic renal failure), in patients with cancer receiving chemotherapy, or when oral iron is poorly tolerated, IV iron therapy is the preferred mode of repletion. ⋯ In a multivariate model, there was no difference in AE rates between low-molecular-weight iron dextran (LMWD) and ferric gluconate; however, iron sucrose had significantly higher odds ratio of AEs (OR = 5.7; 95% CI = 1.6–21.3). Our data suggest that AE rates with IV iron are acceptable. More widespread use of LMWD, in particular, which can be given safely as a total dose infusion (TDI), should be considered.
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BCR/ABL (Breakpoint Cluster Region protein/Abelson tyrosine-protein kinase 1) kinase domain (KD) mutations represent the most frequently described mechanism of resistance to the treatment with tyrosine kinase inhibitors (TKI) in patients with chronic myeloid leukemia (CML). Mutations may impair TKI activity by directly or indirectly impairing the drug binding to the protein. We report the discovery of three new BCR/ABL mutations, L248R, T315V, and F317R identified in two patients with CML (L248R and T315V) and in one patient with Ph+ acute lymphoblastic leukemia (ALL) (F317R). ⋯ L248R and T315V showed high resistance to imatinib, bosutinib, dasatinib, and nilotinib, intermediate resistance to ponatinib, but were sensitive to DCC-2036. Interestingly, F317R showed a moderate resistance to imatinib and nilotinib, but is resistant/highly resistant to dasatinib, bosutinib, ponatinib, and DCC-2036. The availability of drugs activity profiles may become a useful tool for clinicians dealing with the treatment of drug-resistant CML patients.