Description:

The prognosis and life expectancy of chronic myeloid leukemia (CML) patients have improved significantly with the launch of first tyrosine kinase inhibitor (TKI), imatinib. Maintaining at least one major molecular response in CML patients without the use of TKI is known as treatment-free remission (TFR). The safety of the first TFR (TFR1) effort has been reported by numerous studies. However, some patients relapse during TFR1. A second TFR (TFR2) can be tried again in those patients. This systematic review aims to evaluate individual patient characteristics for a TFR2, factors predicting successful TFR2, monitoring, consequences of the cessation of TKI, and studies about TFR2. We identified 5 studies related TFR2. The results showed that the first failed TKI discontinuation attempt is not an indicator of a second TKI discontinuation failure. TKIs could safely and successfully be discontinued for a second time in chronic phase CML patients despite a TFR1 failure. The most important factors for estimating TFR2 success are the speed of molecular relapse and the TKI-free duration after the first TKI discontinuation attempt. New trends in the management of CML patients are reducing the side effects of treatment, lessening the financial burden, and improving the quality of life of patients as CML has developed into a manageable chronic disease rather than an aggressive cancer. Although there are many studies and guidelines on TFR1, there are few studies on TFR2 and predictive factors. More data is still needed regarding TFR2 attempt in patients with CML.

Dasatinib, an effective second-generation tyrosine kinase inhibitor, is used to treat breakpoint cluster region-Ableson-positive chronic myeloid leukemia or Philadelphia chromosome-positive acute lymphocytic leukemia. One common adverse event associated with dasatinib use is fluid retention, including pleural effusion. Chylothorax, however, is a rare adverse event. Although the precise mechanism of dasatinib-induced chylothorax is unclear, almost all cases involve right or bilateral chylothorax, and mostly occur within 5 years of dasatinib initiation. Here, we report a rare case of a patient with dasatinib-induced massive left chylothorax 10 years after dasatinib initiation, which improved after dasatinib termination and a switch to bosutinib. Tyrosine kinase inhibitors are anticancer drugs that disrupt signal transduction pathways in protein kinases by different mechanisms. This group of pharmacologic agents has significantly improved the outcome of patients with chronic myeloid leukemia. However, their effect is not limited to cancer cells, and various complications, particularly cutaneous reactions, have been reported. We report a very rare case of a 35-year-old female with a history of chronic myeloid leukemia who presented with elephantine psoriasis after the treatment with nilotinib.

Chronic Myeloid Leukaemia (CML) is a hematologic neoplasia, characterized as a proliferative disease of the hematopoietic system. Imatinib mesylate (IM), a selective tyrosine kinase inhibitor, is considered a first-line therapy for CML, indicated for both adult and pediatric patients presenting the Philadelphia chromosome (Ph+). However, patients in treatment with IM may show different responses due to interindividual pharmacokinetic variability. Therapeutic drug monitoring should be routinely performed to identify treatment response profile, adherence to treatment, or possible drug interactions, thus supporting better treatment management.  The assay was fully validated according to bioanalytical validation guidelines. Estimated plasma concentrations of IM were not statistically different between groups according to adherence (p = 0.15), with median of 789 ng ml-1 in the group with some level of non-adherence versus 1141.9 ng ml-1 in the group with adherence, classified with the Morisky-Green questionnaire. This study included 33 patients with CML in treatment with IM. These patients answered socioeconomic, sociodemographic, and adherence profile (Morisky-Green) questionnaires. Patients also received instructions for home blood collection with VAMS devices. Afterwards, the samples were analysed by LC-MS/MS. The mean age of the patients was 52 years, 84.8% were ingesting doses of 400 mg/day and the majority were male (69.7%). IM and its metabolite NIM were extracted from VAMS with an aqueous solution with 0.1% formic acid, followed by protein precipitation with acetonitrile. The methodology developed in this study was satisfactory for the determination of IM and NIM in VAMS and can be used in hospital and office routines for the therapeutic monitoring of patients with CML.

With Regards

Ethan Michael
Journal Coordinator
Global Journal of Research and Review