Lactate level is an independent predictor of mortality in patients with hematologic malignancy receiving urgent chemotherapy in intensive care unit.

BACKGROUND: Intensive care unit (ICU) survival of cancer patients has improved. Urgent chemotherapy has become feasible in critically ill patients with specific organ dysfunction due to hematological malignancies. OBJECTIVE: The aim of the study was to assess ICU mortality rates and the factors associated with mortality in patients with hematologic malignancies receiving urgent chemotherapy in the ICU. METHODS: We retrospectively included all patients admitted to the ICU who received chemotherapy due to hematologic malignancy in 2012-2022. RESULTS: Of the 129 patients undergoing chemotherapy in the ICU, 50 (38.7 %) died during the ICU follow-up. The following conditions were significantly more common among nonsurvivors: presence of infection at the time of ICU admission (p < 0.001), the requirement for mechanical ventilation during ICU stay (p < 0.001), the need for noninvasive mechanical ventilation during ICU stay (p = 0.014), vasopressor support (p < 0.001), and sepsis (p < 0.001). Logistic regression analysis revealed that among laboratory parameters on ICU admission, lactate (p = 0.008), albumin (p = 0.022), C-reactive protein (p = 0.046), baseline sequential organ failure assessment (SOFA) score (p < 0.001), newly developed heart failure (p = 0.006), and the requirement for vasopressor agents during ICU stay (p < 0.001) significantly influenced the risk of mortality in the univariate analysis. The multivariate analysis revealed lactate levels (p = 0.047) on ICU admission as an independent predictor of mortality. CONCLUSION: The development of heart failure and lactate levels on admission were the main predictors of mortality. Additionally, higher SOFA scores revealed that illness severity was closely associated with mortality. Future studies should focus on strategies to further reduce these risks and achieve the best outcomes for these patients.

Biomarker diversity in increased inflammation: Secondary hemophagocytic syndrome vs. systemic inflammatory response syndrome.

INTRODUCTION: Secondary hemophagocytic syndrome (HPS) and systemic inflammatory response syndrome (SIRS) share similar clinical findings as a result of hyperinflammation. Due to high mortality rates in HPS; it is critical to diagnose promptly. Thus, this study aimed to evaluate the diagnostic and prognostic significance of inflammatory markers in these two increased inflammatory states. METHODS: We conducted a prospective observational study including patients hospitalized in the intensive care unit of the Internal Medicine Department of Ege University Hospital. RESULTS: Thirty-three patients with HPS and 46 patients with SIRS were evaluated. Serum ferritin and sIL-2r levels were significantly higher in the HPS group than in the SIRS group, as expected. Receiver operating curve (ROC) analysis showed that the optimal cutoff for ferritin to distinguish HPS from SIRS was 1703 µg/L (sensitivity: 75%, specificity: 94.1%, area under the curve (AUC): 0.871, p < 0.001), and that for sIL-2r was 5888 U/ml (sensitivity: 45.5%, specificity: 89.1%, AUC: 0.698, and p = 0.001). Temporal changes (Δ) in ferritin were determined as a mortality predictor. When evaluated in terms of prognostic significance in ROC analysis, a decrease in ferritin of less than 38% was the cutoff value (sensitivity: 92.3%, specificity: 76.9%, AUC: 0.888, and p < 0.001), in mortality. Contrarily, neither baseline nor temporal change in sIL-2r did not achieve prognostic significance as a mortality predictor. CONCLUSION: In this single-center study, serum ferritin level was found to be a particularly more valuable diagnostic and prognostic marker than sIL-2r in patients with HPS.

Investigating the cytotoxic and apoptotic effects of sunitinib upon K-562 chronic myelogenous leukemia cell line and assessment of gene profiling.

OBJECTIVE: Tyrosine kinase inhibitors (TKIs) which efficiently inhibit BCR-ABL are highly effective for clinical treatment of chronic myeloid leukemia (CML), but development of resistance to TKIs is a big challenge to treatment. Sunitinib is a multitargeted TKI targeting vascular endothelial growth factor receptor and is defined a safe and effective candidate target, but its effect on other signaling pathways is unknown. To investigate the cytotoxic and apoptotic effect of sunitinib in CML cell model K-562 on JAK-STAT signaling pathway components, suppressor genes and oncogenes, hematopoiesis-related genes, cell cycle and VEGF pathway components, and mRNA level expression changes was aimed. MATERIALS AND METHODS: Sunitinib's effective dose cytotoxic IC50 was determined by trypan blue and WST-1 cell proliferation assay tests. Expression levels of target genes were determined by quantitative reverse transcriptase polymerase chain reaction simultaneously after sunitinib application. Protein expression analysis was determined by "WesternBreeze Chromogenic Kit-Anti-Rabbit" based on the principles of the application kit by Western blot analysis. RESULTS: Assessing the cytotoxicity of K-562 cells following sunitinib treatment revealed that sunitinib decreased cell proliferation in a time- and dose-dependent manner. According to the sunitinib inhibition curve, IC50 dose was calculated as 3.5 µM at 48th h for K-562 cells and apoptosis assays pointed that sunitinib induces apoptotic cell death of leukemic cells at moderate levels. CONCLUSION: Our study supports that sunitinib might be used as a novel therapeutic target to trigger apoptosis in CML cells which in turn might accelerate therapeutic response in regard to inhibiting oncogenes and enhancing tumor suppressors in cooperation with cell cycle regulatory genes.

Determining Toxoplasma high-risk autologous and allogeneic hematopoietic stem cell transplantation patients by systematic pre-transplant PCR screening of stem cell originated buffy coat.

The diagnosis of Toxoplasma infection or disease in hematopoietic stem cell transplantation (HSCT) patients is achieved mainly by PCR screening; however screening did not find wide field of use in practice due to costly expenditures of PCR. This study aimed to determine patients at high risk of Toxoplasma infection or disease before transplantation by stem cell originated buffy coat PCR and subsequently to screen them. Buffy coats collected from 12 autologous and 18 allogeneic HSCT patients' donors were investigated by PCR before transplantation. After transplantation, blood and sera collected at fixed time intervals were screened by two PCR methods and serological assays. Screening results first time assessed a toxoplasmosis incidence level as 25% in autologous HSCT patients and increased incidence level in allogeneic HSCT patients to 22%. Importantly, buffy coat PCR was first time performed before transplantation, to determine the risk of toxoplasmosis. Buffy coat PCR results showed that four patients were at high risk of toxoplasmosis before transplantation. After transplantation, these patients experienced toxoplasmosis. In conclusion, for the determination of patients at risk of toxoplasmosis, clinicians should consider buffy coat PCR in combination with serology before transplantation. After transplantation, PCR screening can be initiated in high risk patients upon clinical suspicion.

Primary testicular lymphoma.

We evaluated clinical features, management and survival of 12 patients with primary testicular non-Hodgkin's lymphoma presented to our hematology unit between January 1992 and July 2006, retrospectively. The median age of patients was 47 years at presentation (range 29-78 years) and > 80% of them were < 50 years old. In the majority of cases, orchidectomy was performed as diagnostic and first-line therapeutic procedures. Dominant histological subtype was diffuse large B-cell non-Hodgkin's lymphoma. Seven patients out of 12 (58%) were Ann Arbor stages I and II, and the remaining five patients (42%) were stages III and IV. All the patients received doxorubicin-based chemotherapy and achieved complete remission. The addition of rituximab and central nervous system prophylaxis with intrathecal combined chemotherapy containing methotrexate, cytarabine and dexametasone were applied to three patients who were recently admitted. The rate of relapse was 8% and progression-free survival (PFS) at 10 years was 88%. Median duration of response was 84 months (range 14-173 months), median 97.5 months of follow-up. All patients are alive and in case remission. Because of the spreading nature and relapse probability at different sites, including central nervous system and contralateral testis, systemic treatment with doxorubicin-based chemotherapy with or without prophylaxis for contralateral testis and the central nervous system seems to improve the outcome of primary testicular lymphoma.