The emergence of immune checkpoint inhibitors for the treatment of cancer has led to major changes to the therapeutic landscape of lung cancer. Improvements in overall survival relative to standard chemotherapy have been observed in the first-line and second-line therapy settings for patients with advanced non-small cell lung cancer (NSCLC) who are treated with immune checkpoint inhibitors. Consequently, every patient with advanced-stage NSCLC is now a candidate for immune checkpoint inhibitor therapy. However, it is clear that the benefit from therapy is not universal, and identification of biomarkers to select therapy has assumed importance. In addition to programmed cell death receptor ligand 1 expression, both tissue-based and blood-based markers are under evaluation to select patients. In an era of increasing costs of care and potential for toxicities related to immune checkpoint inhibition, proper patient selection is critical to the optimal use of this new class of agents. In addition, development of novel combination approaches has also emerged as an important way to improve the efficacy of immune checkpoint inhibition. Studies in earlier stages of NSCLC are already underway with the hope of improving the cure rate. In this article, the authors review the current landscape of immune checkpoint inhibitors in the treatment of advanced NSCLC. Cancer 2018;124:248-61. © 2017 American Cancer Society.

Myelodysplastic syndromes (MDS) encompass a heterogeneous group of clonal hematopoietic stem cell disorders characterized by a broad clinical spectrum related to ineffective hematopoiesis leading to unilineage or multilineage cytopenias, with a high propensity for transformation to acute myeloid leukemia. Iron overload has been recently identified as one of the important conditions complicating the management of these diverse disorders. The accumulation of iron is mainly related to chronic transfusions; however, evidence suggests a possible role for ineffective erythropoiesis and increased intestinal absorption of iron, related to altered hepcidin and growth differentiation factor-15 levels in the development of hemosiderosis in patients with MDS. In addition to its suggested role in the exacerbation of ineffective erythropoiesis, multiple reports have identified a prognostic implication for the development of iron overload in patients with MDS, with an improvement in overall survival after the initiation of iron chelation therapy. This review includes a detailed discussion of iron overload in patients with MDS whether they are undergoing supportive therapy or curative hematopoietic stem cell transplantation, with a focus on the mechanism, diagnosis, and effect on survival as well as the optimal management of this highly variable complication.

Despite therapeutic progress in acute myeloid leukemia (AML), relapse post-allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains a major challenge. Here, we aim to provide an overview of prevention and treatment of relapse in this population, including cell-based and pharmacologic options. Post-transplant maintenance therapy is used in patients who have undetectable measurable residual disease (MRD), while pre-emptive treatment is administered upon detection of MRD. Prompt transfusion of prophylactic donor lymphocyte infusion (DLI) was found to be effective in preventing relapse and overcoming the negative impact of detectable MRD. In addition, patients with persistent targetable mutations can benefit from targeted post-transplant pharmacological interventions. IDH inhibitors have shown promising results in relapsed/refractory AML. Hypomethylating agents, such as decitabine and azacitidine, have been studied in the post-allo-HSCT setting, both as pre-emptive and prophylactic. Venetoclax has been shown effective in combination with hypomethylating agents or low-dose cytarabine in patients with newly diagnosed AML, especially those unfit for intensive chemotherapy. FLT3 inhibitors, the topic of another section in this review series, have significantly improved survival in FLT-3-ITD mutant AML. The role of other cell-based therapies, including CAR-T cells, in AML is currently being investigated.

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Introduction. Decisions regarding whether advanced cancer patients should be admitted to the ICU are based on a complex suite of considerations, including short- and long-term prognosis, quality of life, and therapeutic options to treat cancer. We aimed to describe demographic, clinical, and survival data and to identify factors associated with mortality in critically ill advanced cancer patients with nonelective admissions to general ICUs. Materials and Methods. Critically ill adult (≥18 years old) cancer patients nonelectively admitted to the intensive care units at the American University of Beirut Medical Center between August 1st 2015 and March 1st 2019 were included. Demographic, clinical, and laboratory data were prospectively collected from the first day of ICU admission up to 30 days after discharge. This study was strictly observational, and clinical decisions were left to the discretion of the ICU team and attending physician. Results. 272 patients were enrolled in the study between August 1st 2015 and March 1st 2019, with an ICU mortality rate of 43.4%, with the number rising to 59% within 30 days of ICU discharge. The mean length of stay in our ICU was 14 days (IQR: 1–120) with a median overall survival of 22 days since the date of ICU admission. The major reasons for unplanned ICU admission were sepsis/septic shock (54%) and respiratory failure (33.1%). Cox regression analysis revealed 7 major predictors of poor prognosis. Direct admission from the ED was associated with a higher risk of mortality (48.9%) than being transferred from the floor (32.6%) ( p = 0.014 ). Conclusion. Our study has shown that being directly admitted to the ICU from the ED rather than being transferred from regular wards, developing AKI, sepsis, MOF, and ARDS, or having an uncontrolled malignancy are all predictive factors for short-term mortality in critically ill cancer patients nonelectively admitted to the ICU. Vasopressor use and mechanical ventilation were also predictors of mortality.