A de novo germline RUNX1 variant preceding development of concurrent T-lymphoblastic leukemia and myelodysplastic syndrome.

Germline variants of the RUNX1 gene are associated with RUNX1 Familial Platelet Disorder with Associated Myeloid Malignancies (RUNX1-FPDMM), which is characterized by an increased risk of developing myelodysplastic syndrome (MDS) and/or acute myeloid leukemia. Patients with FPDMM have also been described to develop B- or T-cell acute lymphoblastic leukemia. We present a pediatric patient with RUNX1-FPDMM that evolved into concurrent MDS and T-cell acute lymphoblastic leukemia after a decade of monitoring with serial blood counts. We aim to highlight the treatment challenges and clinical decision-making that may be anticipated in this unique disorder, as well as the potentially curative role for allogenic hematopoietic stem cell transplant in the first complete remission.

Screening for Chemotherapy-induced Peripheral Neuropathy and Utilization of Physical Therapy in Pediatric Patients Receiving Treatment for Hematologic Malignancies.

Physical therapy (PT) has been shown to be a helpful intervention in the treatment of chemotherapy-induced peripheral neuropathy (CIPN). Our aim was to screen for CIPN in patients with hematologic malignancies receiving vincristine chemotherapy and obtain a baseline assessment on the percentage of patients utilizing PT in the treatment of CIPN. A retrospective review of surveys administered to parents and patients regarding the severity of peripheral neuropathy symptoms from October 2016 through March 2018 was conducted. Of 116 patients, a total of 102 patients (67 male and 35 female; 4 to 10 y of age, N=63; 11 to 15 y of age, N=19; 16 to 20 y of age, N=20) were eligible for the study, with 67.6% (N=69) reporting symptoms of CIPN. Of these patients, 16.7% scored 4 or greater on the surveys, suggesting clinically severe CIPN. Common parental concerns included decreased strength, difficulty walking up stairs, tripping, and foot drops. Approximately 55.1% of the 69 patients who reported CIPN symptoms were referred to outpatient PT, while 44.9% were not referred. A simple survey consisting of 4 questions that only took several minutes to administer was capable of identifying CIPN in 67.6% of patients receiving vincristine chemotherapy.

Safety evaluation of emicizumab prophylaxis in individuals with haemophilia A.

INTRODUCTION: Emicizumab is a bispecific-humanized monoclonal antibody that improves hemostasis by bridging activated factor IX and factor X to substitute for the function of missing activated FVIII. It is an alternative to prophylaxis with factor VIII replacement and is associated with improved outcomes in individuals with hemophilia A with and without inhibitors. AREAS COVERED: Emicizumab is efficacious in reducing bleeding events when compared to on-demand treatment and factor-based prophylaxis. Except for the few thrombotic microangiopathy and thrombotic event cases mainly seen in the HAVEN 1 trial, emicizumab has an overall excellent safety profile with minimal side effects. EXPERT OPINION: Knowledge gaps include the efficacy and safety of emicizumab in younger age groups and those with mild or moderate hemophilia A. Future directions for research include exploring the risk of inhibitor recurrence in patients with a history of high titer inhibitor who have been successfully tolerized, who switch from factor prophylaxis to emicizumab, as well as conducting 'real world studies' to evaluate the patient's perception of emicizumab in regard to ease and tolerability in order to optimize individualized treatment plans.