Chimeric Antigen Receptor T-cell (CAR-T) immunotherapy has emerged as an efficacious and life extending treatment modality with high response rates and durable remissions in patients with relapsed and refractory non-Hodgkin lymphoma (NHL), follicular lymphoma, and B-cell acute lymphoblastic leukemia (B-ALL) as well as in other diseases. Prolonged or recurrent cytopenias after CAR-T therapy have increasingly been reported at varying rates, and the pathogenesis of this complication is not yet well-understood but is likely contributed to by multiple factors. Current studies reported are primarily retrospective, heterogeneous in terms of CAR-Ts used and diseases treated, non-uniform in definitions of cytopenias and durations for end points, and vary in terms of recommended management. Prospective studies and correlative laboratory studies investigating the pathophysiology of prolonged cytopenias will enhance our understanding of this phenomenon. This review summarizes knowledge of these cytopenias to date.
Acute myeloid leukemia (AML) represents 80% of acute leukemia in adults and is characterized by clonal expansion of hematopoietic stem cells secondary to genomic mutations, rendering a selective growth advantage to the mutant clones. NPM1mut is found in around 30% of AML and clinically presents with leukocytosis, high blast percentage and extramedullary involvement. Considered as a “gate-keeper” mutation, NPM1mut appears to be a “first hit” in the process of leukemogenesis and development of overt leukemia. Commonly associated with other mutations (e.g., FLT 3, DNMT3A, TET2, SF3B1), NPM1 mutation in AML has an important role in diagnosis, prognosis, treatment and post-treatment monitoring. Several novel therapies targeting NPM1 are being developed in various clinical phases with demonstration of efficacy. In this review, we summarize the pathophysiology of the NPM1 gene mutation in AML, clinical implications and the novel targeted therapies to date.
Allogeneic hematopoietic stem cell transplantation (AHSCT) is currently the only treatment modality that is capable of curing myelofibrosis (MF). Although outcomes of AHSCT have improved vastly in recent years owing to advancements in HLA typing, conditioning regimens, and supportive care, it remains a procedure with a considerable risk in MF patients due to conditioning regimen related toxicity, higher rates of graft failure, infections, and graft versus host disease (GVHD). Recent progress in the treatment and prevention of GVHD with post-transplant cyclophosphamide has also rendered transplantation from alternative donors feasible and safer, thus improving access to patients without HLA-identical donors. Accordingly, all patients with intermediate or high-risk MF today should be referred for potential transplant evaluation to consider the pros and cons of an early versus a delayed transplant strategy. Individual risk assessment in MF is best facilitated by contemporary prognostic models that incorporate both clinical and genetic risk factors. The current review highlights new information regarding risk stratification in MF, anchored by practical algorithms that facilitate patient selection for specific treatment actions, including AHSCT.
Background: There are limited reports describing critically ill COVID-19 patients in New York. Methods: We conducted a retrospective analysis of 32 adult critically ill patients admitted to a tertiary community hospital in upstate NY, between March 14th and April 12th, 2020. We collected demographic, laboratory, ventilator, and treatment data, which were analyzed and clinical outcomes tabulated. Results: 32 patients admitted to the ICU were included, with mean (±SD) follow-up duration 21 ± 7 days. Mean (±SD) age was 62.2 ± 11.2 years, and 62.5% were men. 27 (84.4%) of patients had one or more medical co-morbidities and 50% of the patients were current or former smokers. The mean (±SD) duration of symptoms was 6.6 (±4.4) days before presentation, with cough (81.3%), dyspnea (68.7%), and fever (65.6%) being most common. 23 (71.9%) patients received invasive mechanical ventilation. 5 (15.6%) had died, 11 (34.4%) had been discharged home, and 16 (50%) remained hospitalized, 8 (25%) of which were still in ICU. Mean (±SD) length of ICU stay was 10.2 (±7.7) days, and mean (±SD) length of hospital stay was 14.8 (±7.7) days. Conclusion: Majority of patients were of older age and with medical co-morbidities. With adequate resource utilization, mortality of critically ill COVID-19 patients may not be as high as previously suggested.