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Intensive serial biomarker profiling for the prediction of neutropenic Fever in patients with hematologic malignancies undergoing chemotherapy: a pilot study.

ABSTRACT: Neutropenic fever (NF) is a life-threatening complication of myelosuppressive chemotherapy in patients with hematologic malignancies and triggers the administration of broad-spectrum antimicrobials. The ability to accurately predict NF would permit initiation of antimicrobials earlier in the course of infection with the goal of decreasing morbid complications and progression to septic shock and death. Changes in the blood level of inflammatory biomarkers may precede the occurrence of NF. To identify potential biomarkers for the prediction of NF, we performed serial measurements of nine biomarkers [C-reactive protein (CRP), protein C, interleukin (IL)-6, IL-8, IL-10, IL-1?, tumor necrosis factor-?, monocyte chemotactic protein-1, and intercellular adhesion molecule-1] using a multiplex ELISA array platform every 6-8 hours in patients undergoing myelosuppressive chemotherapy for hematologic malignancies. We found that the blood levels of IL-6 and CRP increased significantly 24 to 48 hours prior to the onset of fever. In addition, we showed that frequent biomarker monitoring is feasible using a bedside micro sample test device. The results of this pilot study suggest that serial monitoring of IL-6 and CRP levels using a bedside device may be useful in the prediction of NF. Prospective studies involving a larger cohort of patients to validate this observation are warranted. This trial is registered at ClinicalTrials.gov (NCT01144793).

SUBMITTER: Chan SM

PROVIDER: S-EPMC4091290 | biostudies-literature | 2014 Apr

REPOSITORIES: biostudies-literature

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Project description:BACKGROUND:The objective of this study was to evaluate the short-term and long-term outcomes of adult patients with hematologic malignancies who received chemotherapy in the intensive care unit (ICU). METHODS:This was a retrospective, single-center study comparing the outcomes of patients with hematologic malignancies who received chemotherapy in the ICU with a matched cohort of ICU patients who did not receive chemotherapy. Conditional logistic regression and shared-frailty Cox regression were used to assess short-term (ICU and hospital) mortality and death by 12 months after hospital discharge, respectively. RESULTS:One hundred eighty-one patients with hematologic malignancies received chemotherapy in the ICU. The ICU and hospital mortality rates were 25% and 42% for chemotherapy patients and 22% and 33% for non-chemotherapy patients, respectively. Higher severity of illness scores on ICU admission were significantly associated with higher ICU mortality (odds ratio, 1.07; P < .001) and hospital mortality (odds ratio, 1.05; P ≤ .001). Six-month and 12-month survival estimates posthospital discharge were 58% and 50%, respectively. Compared with the matched cohort of patients who did not receive chemotherapy, those who did receive chemotherapy had a significantly longer length of stay in the ICU (median, 6 vs 3 days; P < .001) and in the hospital (median, 22 vs 14 days; P = .024). In multivariable analysis, the patients who received chemotherapy in the ICU had a trend toward a higher risk of dying by 12 months (hazard ratio, 1.45; P = .08). CONCLUSIONS:Short-term mortality was similar among patients with hematologic malignancies who did and did not receive chemotherapy in the ICU, although patients who received chemotherapy had increased resource utilization. These results may inform ICU triage and goals-of-care discussions with patients and their families regarding outcomes after receiving chemotherapy in the ICU. Cancer 2018;124:3025-36. © 2018 American Cancer Society.

Project description:Chemotherapy-induced thrombocytopenia (CIT) is a common complication of the treatment of non-hematologic malignancies. Many patient-related variables (e.g., age, tumor type, number of prior chemotherapy cycles, amount of bone marrow tumor involvement) determine the extent of CIT. CIT is related to the type and dose of chemotherapy, with regimens containing gemcitabine, platinum, or temozolomide producing it most commonly. Bleeding and the need for platelet transfusions in CIT are rather uncommon except in patients with platelet counts below 25x109/L in whom bleeding rates increase significantly and platelet transfusions are the only treatment. Nonetheless, platelet counts below 70x109/L present a challenge. In patients with such counts, it is important to exclude other causes of thrombocytopenia (medications, infection, thrombotic microangiopathy, post-transfusion purpura, coagulopathy and immune thrombocytopenia). If these are not present, the common approach is to reduce chemotherapy dose intensity or switch to other agents. Unfortunately decreasing relative dose intensity is associated with reduced tumor response and remission rates. Thrombopoietic growth factors (recombinant human thrombopoietin, pegylated human megakaryocyte growth and development factor, romiplostim, eltrombopag, avatrombopag and hetrombopag) improve pretreatment and nadir platelet counts, reduce the need for platelet transfusions, and enable chemotherapy dose intensity to be maintained. National Comprehensive Cancer Network guidelines permit their use but their widespread adoption awaits adequate phase III randomized, placebo-controlled studies demonstrating maintenance of relative dose intensity, reduction of platelet transfusions and bleeding, and possibly improved survival. Their potential appropriate use also depends on consensus by the oncology community as to what constitutes an appropriate pretreatment platelet count as well as identification of patient-related and treatment variables that might predict bleeding.

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Intensive serial biomarker profiling for the prediction of neutropenic Fever in patients with hematologic malignancies undergoing chemotherapy: a pilot study.

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