The molecular determinants of clinical responses to decitabine therapy in patients with acute myeloid leukemia (AML) or myelodysplastic syndromes (MDS) are unclear. We enrolled 84 adult patients with AML or MDS in a single-institution trial of decitabine to identify somatic mutations and their relationships to clinical responses. Decitabine was administered at a dose of 20 mg per square meter of body-surface area per day for 10 consecutive days in monthly cycles. We performed enhanced exome or gene-panel sequencing in 67 of these patients and serial sequencing at multiple time points to evaluate patterns of mutation clearance in 54 patients. An extension cohort included 32 additional patients who received decitabine in different protocols. Of the 116 patients, 53 (46%) had bone marrow blast clearance (<5% blasts). Response rates were higher among patients with an unfavorable-risk cytogenetic profile than among patients with an intermediate-risk or favorable-risk cytogenetic profile (29 of 43 patients [67%] vs. 24 of 71 patients [34%], P<0.001) and among patients with TP53 mutations than among patients with wild-type TP53 (21 of 21 [100%] vs. 32 of 78 [41%], P<0.001). Previous studies have consistently shown that patients with an unfavorable-risk cytogenetic profile and TP53 mutations who receive conventional chemotherapy have poor outcomes. However, in this study of 10-day courses of decitabine, neither of these risk factors was associated with a lower rate of overall survival than the rate of survival among study patients with intermediate-risk cytogenetic profiles. Patients with AML and MDS who had cytogenetic abnormalities associated with unfavorable risk, TP53 mutations, or both had favorable clinical responses and robust (but incomplete) mutation clearance after receiving serial 10-day courses of decitabine. Although these responses were not durable, they resulted in rates of overall survival that were similar to those among patients with AML who had an intermediate-risk cytogenetic profile and who also received serial 10-day courses of decitabine. (Funded by the National Cancer Institute and others; ClinicalTrials.gov number, NCT01687400.)

Introduction: Growing evidence suggests disparities in the prevalence, management, progression, and outcomes of chronic, nonmalignant pain-related conditions, especially for African American patients. Objective: The purpose of this review is to explore studied causative factors that influence the management of chronic pain among African Americans, including factors that result in disparate care that may contribute to unfavorable outcomes. Methods: This narrative review is based on available literature published on this topic published within the last 10 years. Results: Assessment of chronic pain is multifaceted, often complicated by patient medical comorbidities and a complex set of biopsychosocial/spiritual/financial and legal determinants. These complexities are further exacerbated by a patient's race, by provider bias, and by structural barriers—all intersecting and culminating in disparate outcomes. Conclusions: A comprehensive analysis is needed to identify quality improvement interventions and to mitigate major barriers contributing to disparities in the management of chronic pain in the African American population.

Asparaginase is a critical component of acute lymphoblastic leukemia (ALL) treatment in children; however, its use in adults is often avoided as a result of toxicities including hepatotoxicity, thrombosis, and pancreatitis which have been reported more commonly in adults than in children. In this retrospective analysis, short-acting L-asparaginase (L-ASP) and long-acting polyethylene glycol (PEG)-asparaginase (PEG-ASP) were compared for grade 3–4 toxicities and characterized by patient and drug-related factors to identify strategies for toxicity avoidance in adults with ALL. Asparaginase was administered during sequential courses of chemotherapy using a pediatric-inspired treatment regimen. Forty-eight patients who received PEG-ASP and nine patients who received L-ASP were identified. The rates of toxicity were as follows for the PEG-ASP and L-ASP groups, respectively: hepatotoxicity (60% vs. 33%, P = 0.275), pancreatitis (17% vs. 22%, P = 0.650), thrombosis (19.0% vs. 0%, P = 0.328), or any grade 3–4 toxicity (71% vs. 44%, P = 0.143). Toxicity did not correlate with dose, either by individual dose based on flat or BSA-based measures. Logistic regression identified obesity as a risk factor for heptatotoxicity (OR = 8.44, 95% CI: 1.395–51.117). Hypofibrinogenemia was identified as a pharmacodynamic marker for predicting hepatotoxicity. In conclusion, grade 3–4 toxicity was not statistically different between adult ALL patients receiving PEG-ASP and L-ASP, but toxicity was strongly associated with obesity and hypofibrinogenemia, not dose.

Purpose: Rasburicase is a recombinant urate oxidase enzyme generally reserved for the treatment or prevention of hyperuricemia in patients that are at high risk of developing tumor lysis syndrome (TLS). The primary objective of this study is to evaluate and characterize the outcomes of patients receiving low dose rasburicase for treatment or prophylaxis of hyperuricemia secondary to TLS. Patients/Methods: A retrospective chart review between April 1, 2007 and September 31, 2008 was completed. All adult patients who received a dose of 0.05mg/kg with either a leukemia or lymphoma diagnosis in addition to at least two TLS risk factors: WBC ≥ 50 × 109/L, LDH 2 × ULN, uric acid ≥ 8 mg/dl, SCr ≥ 1.5 mg/dl were included. Forty-eight patients received rasburicase for prophylaxis (n = 18) or treatment (n = 30) of TLS. Results: Forty patients achieved and maintained a uric acid less than 8 mg/dL, 24 h after receipt of a single dose of rasburicase without the requirement for renal replacement therapy. A statistically significant decrease in UA was achieved in all patients when compared to baseline (p < 0.001). Cost analysis revealed a $ 1.96 million (96%) direct cost savings for the 48 patients in this study when compared to the cost of manufacturer’s dosing recommendation. Conclusions: Low dose rasburicase was efficacious and cost effective for both prophylaxis and treatment of TLS. Administration of a single dose of 0.05mg/kg of rasburicase was sufficient in correcting uric acid levels for most patients.

Cancer therapy has environmental costs. In this simulation analysis, @garthstrohbehn and colleagues show how less frequent dosing and shorter durations of therapy might improve public health without making patients with cancer worse off.