A review in the treatment of oncologic emergencies.

AIM: Oncologic emergencies are often categorized as a group of metabolic abnormalities associated with the diagnosis of cancer or the initiation of chemotherapy for treatment. These syndromes often arise in the acute setting, demanding an accurate knowledge of the associated condition and current treatment. In this review, we evaluate five oncologic emergencies: tumor lysis syndrome, hypercalcemia, hyponatremia, spinal cord compression, and disseminated intravascular coagulation. SUMMARY: Oncologic emergencies are often diverse in etiology and are often associated with the initiation of chemotherapy. Tumor lysis syndrome presents as severe electrolyte abnormalities that need to be addressed urgently, sometimes prior to initiation of chemotherapy. Hypercalcemia of malignancy is treated with aggressive rehydration, furosemide, and intravenous bisphosphonates. If a patient with cancer presents with normovolemic hyponatremia, syndrome of inappropriate antidiuretic hormone should be suspected. Malignant spinal cord compression happens when cancer cells grow in, or near to, the spine and press on the spinal cord and nerves. This causes swelling and a reduction in the blood supply to the spinal cord and nerve roots. Disseminated intravascular coagulation is characterized by systemic activation of blood coagulation, which results in generation and deposition of fibrin, leading to microvascular thrombi in various organs and contributing to multiple organ dysfunction syndrome. CONCLUSION: Knowledge of oncology emergencies is critical to the understanding of these emergent syndromes in oncology patients. Each of these disease states requires careful evaluation of the patient's symptoms, monitoring parameters for conditions and supportive care measures and interventions.

Idarubicin appears equivalent to dose-intense daunorubicin for remission induction in patients with acute myeloid leukemia.

Daunorubicin has historically been considered the anthracycline of choice at many cancer centers for the treatment of acute myeloid leukemia (AML). Drug shortages have required the substitution of daunorubicin with idarubicin. Randomized studies have shown idarubicin (10-12mg/m(2)) to be comparable or superior to standard dose daunorubicin (45-60mg/m(2)) for achieving complete remission (CR). Whether these results can be extrapolated to dose-intense daunorubicin (90mg/m(2)), recently shown to improve CR rates when compared to standard daunorubicin doses remains uncertain. This observational study was conducted at Northwestern Memorial Hospital (NMH) to compare CR rates. The results suggest idarubicin is equivalent to daunorubicin, and for some subsets of patients, idarubicin may have superior CR rates.

Changing epidemiology of Clostridium difficile-associated disease during stem cell transplantation.

The incidence and severity of Clostridium difficile-associated disease (CDAD) within the general population has risen dramatically over the past decade, yet little data are available from hematopoietic stem cell transplantation (HSCT) centers. In the present study, we performed a chart review of 822 consecutive autologous and allogeneic HCST recipients treated at Northwestern Memorial Hospital between 2004 and 2008 to determine the incidence of CDAD at our institution. Variables including age, sex, diagnosis, chemotherapy regimen, transplantation type, microbial colonization, coinfections, diet, antibiotic use, neutropenic fever, comorbid conditions, time to engraftment, growth factor administration, and occurrence of graft-versus-host disease were assessed as potential risk factors for the development of CDAD. Eighty-five CDAD cases (10.3%) were identified. Bivariate analysis revealed a significant association between CDAD and neutropenic fever, administration of a neutropenic diet, ciprofloxacin and aztreonam use and duration of therapy, vancomycin and aztreonam use and duration of therapy, receipt of an allogeneic transplantation, bacterial coinfection, and vancomycin-resistant Entereococcus faecium (VRE) colonization. Cox regression analysis identified the following as factors associated with the development of CDAD: age >60 years, allogeneic transplantation, and prior VRE colonization. Allogeneic recipients with CDAD experienced increased higher rates of grades II to IV gastrointestinal graft-versus-host disease and nonrelapse mortality. A risk stratification model was developed to identify HSCT recipients at different levels of risk. With an incidence >10%, CDAD is a significant infectious complication of stem cell transplantation.

Questioning the role of a neutropenic diet following hematopoetic stem cell transplantation.

The use of a neutropenic diet (ND) after hematopoietic stem cell transplantation (HSCT) was instituted more than 30 years ago as a means of preventing infection from organisms colonizing the gastrointestinal tract. Evidence supporting this practice is lacking, however, and the actual efficacy of the ND remains unknown. Institutional policy at Northwestern Memorial Hospital discontinued the use of ND in 2006. We conducted a retrospective study of 726 consecutive HSCT recipients, 363 who received an ND and 363 who received a general hospital diet, to determine the incidence of microbiologically confirmed infections during and after transplantation. Our findings indicate a higher rate of infections in the HSCT recipients who received an ND.

Serial plasma voriconazole concentrations after allogeneic hematopoietic stem cell transplantation.

Plasma voriconazole concentrations vary considerably between patients receiving standard dosing, and trough voriconazole concentrations are known to affect efficacy and toxicity. Temporal variations in serial plasma voriconazole concentrations through the course of therapy in hematopoietic stem cell transplantation patients has not been carefully described. Paired voriconazole concentrations in 64 patients were studied to determine the predictability of the second concentration based on the first. The difference between the two values was < or = 5% in six patients. In 25 patients, the second concentration was higher by a median of 40%. In 33 patients, the subsequent concentration was lower by a median of 59%. For patients with an initial concentration of < 2 microg/ml, the correlation between the two values was poor (r = 0.24; P < 0.17). For those with an initial concentration of > or = 2 microg/ml, the correlation was good (r = 0.72; P < 0.0001). There was no relationship between the magnitude of the change and the time elapsing between the two measurements. Among the 43 patients who had an initial concentration of > or = 1 microg/ml, the two voriconazole measurements were strongly correlated (r = 0.66, P < 0.0001), but only 67% had a voriconazole serum concentration of > or = 1 microg/ml on the second measurement. No studied variables were reliable predictors in identifying concentrations above or below 1 or 2 microg/ml. Our data suggest that variations in voriconazole concentrations are unpredictable despite standard dosing, and the acceptability of a concentration on one occasion cannot be extrapolated to future concentrations in the same patient. This suggests that ongoing therapeutic drug monitoring and dose adjustment may be beneficial in patients requiring prolonged voriconazole therapy.

Monitoring plasma voriconazole levels may be necessary to avoid subtherapeutic levels in hematopoietic stem cell transplant recipients.

BACKGROUND: Low voriconazole levels have been associated with a higher failure rate in patients with confirmed fungal infections. METHODS: Steady-state plasma trough voriconazole levels were measured after at least 5 days of therapy in 87 patients with hematologic malignancies on 201 separate occasions (1-5 levels per patient; median, 2). Most patients (90%) had undergone allogeneic hematopoietic stem cell transplantation. The daily voriconazole dose, administered in 2 divided doses, was 200 mg (n = 4), 400 mg (n = 151), 500 mg (n = 20), 600 mg (n = 18), and 800 mg (n = 8); corresponding to 2.0-16.3 (median, 5.4) mg/kg. Plasma voriconazole levels were 0-12.5 microg/mL (median, 1.2). Voriconazole was undetectable (<0.2 mug/mL) in 15%. RESULTS: The correlation between dose and levels was weak (r = 0.14; P = .045). The median absolute daily drug dose (400 mg) was identical in groups of patients with levels of 0, 0.2 to 0.5, >0.5 to 2.0, >2.0 to 5.0, and >5.0. Whereas the daily drug dose in mg/kg was significantly higher when the levels were >5.0 microg/mL, there was no consistent relation between dose and level below that threshold. In adult patients getting standard doses of voriconazole orally, the drug levels are highly variable. Based on limited available data, between a quarter and two-thirds of these levels could potentially be associated with a lower likelihood of response or a higher likelihood of failure. CONCLUSIONS: Future voriconazole studies should incorporate prospective therapeutic drug monitoring and consideration should be given to checking levels in patients receiving the drug for confirmed, life-threatening fungal infections.