Dasatinib-Induced Chylothorax Beyond 5 Years of Treatment: Is There Actually Any Limit?

Dasatinib is a tyrosine kinase inhibitor used for treatment of some specific types of leukaemia. The development of pleural effusion is a known adverse effect of dasatinib and chylothorax is exceptional. No case has been reported beyond 5 years of treatment and extensive search for an alternative diagnosis is currently suggested in such scenario. The underlying mechanism is not currently clear. We describe a woman on dasatinib treatment for more than 10 years who developed chylothorax. Drug withdrawal resolved the chylous pleural effusion. We were able to find 14 additional cases of dasatinib-related chylothorax reported up until now. LEARNING POINTS: Dasatinib is a tyrosine kinase inhibitor used for the treatment of some specific types of leukaemia.Development of pleural effusion is a potential adverse effect, mostly in the first 6 years of treatment. The underlying mechanism is not known.Chylothorax is exceptional, and no case had been described beyond 5 years of treatment; our case would be the first one. We found 14 additional cases of dasatinib-related chylothoraces in a PubMed research.

Usability of human-computer interaction in neonatal care.

While a goal for Electronic Health Record (EHR) technologies was to improve quality, efficiency, and safety, the usability of EHRs has remained poor. The relation to patient harm and user satisfaction cannot be ignored. Optimization of EHR usability is imperative to improving the outcomes for critically ill patients, especially neonates who are at the extremes of physiologic variability. Further development and integration of metadata with predictive modeling and clinical protocols can support provider decision making, increase efficiency and safety, and reduce clinician burnout. This paper reviews EHR usability and identifies opportunities to improve the EHR specific to neonatal care.

MTXPK.org: A Clinical Decision Support Tool Evaluating High-Dose Methotrexate Pharmacokinetics to Inform Post-Infusion Care and Use of Glucarpidase.

Methotrexate (MTX), an antifolate, is administered at high doses to treat malignancies in children and adults. However, there is considerable interpatient variability in clearance of high-dose (HD) MTX. Patients with delayed clearance are at an increased risk for severe nephrotoxicity and life-threatening systemic MTX exposure. Glucarpidase is a rescue agent for severe MTX toxicity that reduces plasma MTX levels via hydrolysis of MTX into inactive metabolites, but is only indicated when MTX concentrations are > 2 SDs above the mean excretion curve specific for the given dose together with a significant creatinine increase (> 50%). Appropriate administration of glucarpidase is challenging due to the ambiguity in the labeled indication. A recent consensus guideline was published with an algorithm to provide clarity in when to administer glucarpidase, yet clinical interpretation of laboratory results that do not directly correspond to the algorithm prove to be a limitation of its use. The goal of our study was to develop a clinical decision support tool to optimize the administration of glucarpidase for patients receiving HD MTX. Here, we describe the development of a novel 3-compartment MTX population pharmacokinetic (PK) model using 31,672 MTX plasma concentrations from 772 pediatric patients receiving HD MTX for the treatment of acute lymphoblastic leukemia and its integration into the online clinical decision support tool, MTXPK.org. This web-based tool has the functionality to utilize individualized demographics, serum creatinine, and real-time drug concentrations to predict the elimination profile and facilitate model-informed administration of glucarpidase.

Successful discontinuation of eltrombopag after complete remission in patients with primary immune thrombocytopenia.

Eltrombopag is effective and safe in immune thrombocytopenia (ITP). Some patients may sustain their platelet response when treatment is withdrawn but the frequency of this phenomenon is unknown. We retrospectively evaluated 260 adult primary ITP patients (165 women and 95 men; median age, 62 years) treated with eltrombopag after a median time from diagnosis of 24 months. Among the 201 patients who achieved a complete remission (platelet count >100 × 10(9) /l), eltrombopag was discontinued in 80 patients. Reasons for eltrombopag discontinuation were: persistent response despite a reduction in dose over time (n = 33), platelet count >400 × 10(9) /l (n = 29), patient's request (n = 5), elevated aspartate aminotransferase (n = 3), diarrhea (n = 3), thrombosis (n = 3), and other reasons (n = 4). Of the 49 evaluable patients, 26 patients showed sustained response after discontinuing eltrombopag without additional ITP therapy, with a median follow-up of 9 (range, 6-25) months. These patients were characterized by a median time since ITP diagnosis of 46.5 months, with 4/26 having ITP < 1 year. Eleven patients were male and their median age was 59 years. They received a median of 4 previous treatment lines and 42% were splenectomized. No predictive factors of sustained response after eltrombopag withdrawal were identified. Platelet response following eltrombopag cessation may be sustained in an important percentage of adult primary ITP patients who achieved CR with eltrombopag. However, reliable markers for predicting which patients will have this response are needed.