Recent developments in immunotherapy of acute myeloid leukemia

The advent of new immunotherapeutic agents in clinical practice has revolutionized cancer treatment in the past decade, both in oncology and hematology. The transfer of the immunotherapeutic concepts to the treatment of acute myeloid leukemia (AML) is hampered by various characteristics of the disease, including non-leukemia-restricted target antigen expression profile, low endogenous immune responses, and intrinsic resistance mechanisms of the leukemic blasts against immune responses. However, considerable progress has been made in this field in the past few years. Within this manuscript, we review the recent developments and the current status of the five currently most prominent immunotherapeutic concepts: (1) antibody-drug conjugates, (2) T cell-recruiting antibody constructs, (3) chimeric antigen receptor (CAR) T cells, (4) checkpoint inhibitors, and (5) dendritic cell vaccination. We focus on the clinical data that has been published so far, both for newly diagnosed and refractory/relapsed AML, but omitting immunotherapeutic concepts in conjunction with hematopoietic stem cell transplantation. Besides, we have included important clinical trials that are currently running or have recently been completed but are still lacking full publication of their results. While each of the concepts has its particular merits and inherent problems, the field of immunotherapy of AML seems to have taken some significant steps forward. Results of currently running trials will reveal the direction of further development including approaches combining two or more of these concepts

External validation of two prediction models identifying employees at risk of high sickness absence: cohort study with 1-year follow-up

Background: Two models including age, self-rated health (SRH) and prior sickness absence (SA) were found to predict high SA in health care workers. The present study externally validated these prediction models in a population of office workers and investigated the effect of adding gender as a predictor. Methods: SRH was assessed at baseline in a convenience sample of office workers. Age, gender and prior SA were retrieved from an occupational health service register. Two pre-defined prediction models were externally validated: a model identifying employees with high (i. e. >= 30) SA days and a model identifying employees with high (i. e. >= 3) SA episodes during 1-year follow-up. Calibration was investigated by plotting the predicted and observed probabilities and calculating the calibration slope. Discrimination was examined by receiver operating characteristic (ROC) analysis and the area under the ROC-curve (AUC). Results: A total of 593 office workers had complete data and were eligible for analysis. Although the SA days model showed acceptable calibration (slope = 0.89), it poorly discriminated office workers with high SA days from those without high SA days (AUC = 0.65; 95% CI 0.58-0.71). The SA episodes model showed acceptable discrimination (AUC = 0.76, 95% CI 0.70-0.82) and calibration (slope = 0.96). The prognostic performance of the prediction models did not improve in the population of office workers after adding gender. Conclusion: The SA episodes model accurately predicted the risk of high SA episodes in office workers, but needs further multisite validation and requires a simpler presentation format before it can be used to select high-risk employees for interventions to prevent or reduce SA