Search

Purpose. The objectives were to describe the management and outcomes of acute leukemia (AL) patients admitted to the ICU and to identify predictors of ICU mortality.Methods. Data was retrospectively collected from the medical records of all patients with AML or ALL admitted to the Mount Sinai Hospital ICU from August 2009 to December 2012.Results. 151 AL patients (117 AML, 34 ALL) were admitted to the ICU. Mean age was 54 (SD 15) years, median APACHE II score was 27 (IQR 22–33), and 50% were female. While in ICU, 128 (85%) patients had sepsis and 56 (37%) had ARDS. The majority of patients required invasive organ support: 94 (62%) required mechanical ventilation while 23 (15%) received renal replacement therapy. Multivariable analysis identified SOFA score (OR 1.18, 95% CI 1.01–1.38) and invasive ventilation (OR 9.64, 95% CI 3.39–27.4) as independent predictors of ICU mortality. Ninety-four (62%) patients survived to ICU discharge. Only 39% of these 94 patients discharged were alive 12 months after ICU admission.Conclusions. AL patients admitted to the ICU had a 62% ICU survival rate; yet only 25% of cohort patients were alive 12 months after ICU admission. Higher admission SOFA scores and invasive ventilation are independently associated with a greater risk of dying in the ICU.

Hyperthermia adversely affects cell structure and function, but also induces adaptive responses that allow cells to tolerate these stressful conditions. For example, heat-induced expression of the molecular chaperone protein HSP70 can prevent stress-induced cell death by inhibiting signaling pathways that lead to apoptosis. In this study, we used high-resolution two-dimensional gel electrophoresis and phosphoprotein staining to identify signaling pathways that are altered by hyperthermia and modulated by HSP70 expression. We found that in heat-shocked cells, the actin-severing protein cofilin acquires inhibitory Ser3 phosphorylation, which is associated with an inhibition of chemokine-stimulated cell migration. Cofilin phosphorylation appeared to occur as a result of the heat-induced insolubilization of the cofilin phosphatase slingshot (SSH1-L). Overexpression of HSP70 reduced the extent of SSH1-L insolubilization and accelerated its resolubilization when cells were returned to 37°C after exposure to hyperthermia, resulting in a more rapid dephosphorylation of cofilin. Cells overexpressing HSP70 also had an increased ability to undergo chemotaxis following exposure to hyperthermia. These results identify a critical heat-sensitive target controlling cell migration that is regulated by HSP70 and point to a role for HSP70 in immune cell functions that depend upon the proper control of actin dynamics.