Medication risks in older patients (70 +) with cancer and their association with therapy-related toxicity.

BACKGROUND: To evaluate medication-related risks in older patients with cancer and their association with severe toxicity during antineoplastic therapy. METHODS: This is a secondary analysis of two prospective, single-center observational studies which included patients ≥ 70 years with cancer. The patients' medication lists were investigated regarding possible risks: polymedication (defined as the use of ≥ 5 drugs), potentially inappropriate medication (PIM), and relevant potential drug-drug interactions (rPDDI). The risks were analyzed before and after start of cancer therapy. Severe toxicity during antineoplastic therapy was captured from medical records according to the Common Terminology Criteria for Adverse Events (CTCAE). The association between grade ≥ 3 toxicity and medication risks was evaluated by univariate as well as multivariate regression adjusted by ECOG and age. RESULTS: The study cohort comprised 136 patients (50% female, mean age 77 years, 42% hematological malignancies). Before the start of cancer therapy, patients took on average 5 drugs as long-term medication and 52% of patients were exposed to polymedication. More than half of patients used at least one PIM. Approximately one third of patients exhibited rPDDI. The prevalence of medication risks increased after start of cancer therapy. rPDDI were significantly associated with severe overall toxicity (OR, 5.07; p = 0.036; 95% Confidence Interval (CI) 1.11-23.14; toxicity in patients with rPDDI 94.1% (32/34) vs 75.9% (60/79) in patients without rPDDI) and hematological toxicity (OR, 3.95; p = 0.010; 95% CI 1.38-11.29; hematological toxicity in patients with rPDDI 85.3% (29/34) vs 59.5% (47/79) in patients without rPDDI). In the multivariate analysis adjusted by ECOG and age, only the association for rPDDI with hematological toxicity remained statistically significant (OR, 4.51; p = 0.007; 95% CI 1.52-13.38). These findings should be further investigated in larger studies. CONCLUSION: Medication risks are common in older patients with cancer and might be associated with toxicity. This raises the need for tailored interventions to ensure medication safety in this patient cohort.

Comparing the performance of the CARG and the CRASH score for predicting toxicity in older patients with cancer.

OBJECTIVES: To compare the CARG (Cancer and Aging Research Group) and CRASH (Chemotherapy Risk Assessment Scale for High-Age Patients) score regarding the predictive performance for severe toxicity in older patients with cancer. METHODS: We recruited patients ≥70 years and applied the CARG and CRASH score before the start of systemic cancer treatment. The CARG predicts severe overall toxicity; the CRASH additionally predicts hematologic and nonhematologic toxicity. We captured ≥ grade 3 toxicity according to Common Terminology Criteria for Adverse Events (CTCAE) from medical records. Predictive performance was assessed using logistic regression and the area under the receiver operating characteristic curve (ROC-AUC). RESULTS: The study cohort comprised 120 patients (50% female, mean age 77.2 years, 57% solid tumors). The median of the CARG (range 0-23) and the combined CRASH (range 0-12) were 9 and 8, respectively. 81% of patients experienced toxicity; 67% showed hematologic toxicity. The predictive performance of the CARG and the combined CRASH was similar for overall toxicity (CARG: Odds ratio per unit increase (OR) 1.266, P = .015; ROC-AUC 0.681, P = .010; combined CRASH: OR 1.337, P = .029; ROC-AUC 0.650, P = .032). For hematologic toxicity, the hematologic CRASH was a significant predictor and showed numerically a higher ROC-AUC than the CARG which was not statistically different (CARG: OR 1.048, P = .462; ROC-AUC 0.564, P = .271; hematologic CRASH: OR 1.602, P = .007; ROC-AUC 0.665, P = .005). CONCLUSION: Both scores exhibited similar predictive performance for toxicity in older patients with cancer.

Increased effect of IMiDs by addition of cytokine-induced killer cells in multiple myeloma.

Immunomodulatory drugs (IMiDs), such as thalidomide, lenalidomide and pomalidomide, represent the basic principle of multiple myeloma treatment. However, the development of resistance is a limiting factor. Over the last years, the efficient application of cytokine-induced killer (CIK) cells has been reported as an alternative strategy to treat hematological neoplasms. In this study, we tested for a potential synergistic effect by combining the IMiDs thalidomide, lenalidomide and pomalidomide with CIK cells in different myeloma cell lines in vitro. Myeloma cells tested with CIK cells were significantly reduced. In the combination, myeloma cells were significantly reduced compared with cells only tested with IMiDs but not to the cells tested with CIK cells. Otherwise, the number of CIK cells was significantly reduced when treated with IMiDs. Because IMiDs are active in patients with myeloma, these results lead to the expectation that combination of IMiDs and CIK cells achieve better results in the treatment of multiple myeloma compared with the single use of IMiDs. Therefore, further examinations in an in vivo setting are necessary to have a closer look on the cellular interactions. Copyright © 2015 John Wiley & Sons, Ltd.

AML versus ICU: outcome of septic AML patients in an intensive care setting.

PURPOSE: Intensive therapy regimens in patients with acute myeloid leukemia (AML) frequently result in sepsis and septic shock. In this study, we investigated the prognostic outcome of AML patients requiring intensive care treatment due to severe sepsis or septic shock. DESIGN: We present a retrospective cohort study in a medical intensive care unit (ICU) of a university hospital that serves as a tertiary care center. MATERIALS AND METHODS: Here we present data from 44 AML patients of our ICU with 29 requiring invasive mechanical ventilation due to sepsis and compared multiple clinical and laboratory parameters of ICU survivors and non-survivors. RESULTS: Mean age was 59.5 years, the overall mortality rate was 41% (18/44), and the mortality rate among patients who received mechanical ventilation was 55% (16/29). The mortality rate among younger patients (aged 60 years or less) was 17% (3/18), while 58% of the older patients died (15/26). The mortality rate among younger patients who received mechanical ventilation was 23% (3/13) compared with 81% (13/16) of the older patients. The mean invasive ventilation time was 415 h in non-survivors compared with 667 h in survivors. No differences could be identified between survivors and non-survivors, concerning multiple laboratory parameters or AML prognostic and therapeutic parameters; our analysis, however, confirmed a statistically significant difference in the patients' age. CONCLUSIONS: In previous studies, age was one of the most important prognostic factors in AML patients receiving mechanical ventilation due to severe sepsis or septic shock. In spite of improvements in diagnostic and treatment over the last couple of years, our study indicates that this fact still is true. However, the overall outcome has improved over the years due to improvements in intensive care medicine.

Severe thrombocytosis and anemia associated with celiac disease in a young female patient: a case report.

INTRODUCTION: Platelet counts exceeding 1.000 x 103/microl are usually considered secondary to another cause, particularly to chronic myeloproliferative disease (CMPD). Reactive thrombocytosis due to iron deficiency rarely exceeds platelet counts of 700 x 103/microl. CASE PRESENTATION: Here we report the case of a young woman presenting with clinical signs of severe anemia. Laboratory findings confirmed an iron-deficiency anemia associated with severe thrombocytosis of 1703 x 103/microl. Macroscopic gastrointestinal and genitourinary tract bleeding was excluded. The excessive elevation of platelets, slightly elevated lactate dehydrogenase and slightly elevated leukocytes along with the absence of other inflammation parameters raised the suspicion of an underlying hematological disease. However, bone marrow evaluation could not prove the suspected diagnosis of a CMPD, especially essential thrombocythemia (ET). In the further clinical course the platelet count returned to normal after raising the hemoglobin to a level close to normal range with erythrocyte transfusion, and normalization of serum iron and decline of erythropoietin. Finally, following small bowel biopsy, despite the absence of typical clinical signs, celiac disease was diagnosed. After discharge from hospital the patient was commenced on a gluten-free diet and her hemoglobin almost completely normalized in the further follow-up period. CONCLUSION: This case illustrates the rare constellation of an extreme thrombocytosis most likely secondary to iron deficiency due to celiac disease. This represents, to the best of the authors' knowledge, the highest reported platelet count coincident with iron deficiency. A potential mechanism for the association of iron-deficiency anemia and thrombocytosis is discussed. Even in the presence of 'atypically' high platelets one should consider the possibility of reactive thrombocytosis. Extreme thrombocytosis could emerge in the case of iron deficiency secondary to celiac disease.

Guidelines for antiemetic treatment of chemotherapy-induced nausea and vomiting: past, present, and future recommendations.

Clinicians should be aware that chemotherapy-induced nausea and vomiting (CINV) is still one of the most feared side effects of chemotherapy. With the correct use of antiemetics, CINV can be prevented in almost 70% to up to 80% of patients. Treatment guidelines are useful tools that enable physicians to integrate the latest clinical research into their practices. The large volume of rapidly evolving clinical data has been summarized and incorporated into treatment recommendations by well-known and reliable institutions, including the Multinational Association of Supportive Care in Cancer, the American Society of Clinical Oncology, and the National Comprehensive Cancer Network. Despite the availability of such guidelines, however, there is evidence that adherence to and implementation of treatment recommendations are less than optimal. This review focuses, in particular, on the conformity and differences of these three guidelines. Furthermore, open questions and trends in the field of antiemesis are discussed as well.