The NCCN Guidelines for Acute Myeloid Leukemia (AML) provide recommendations for the diagnosis and treatment of adults with AML based on clinical trials that have led to significant improvements in treatment, or have yielded new information regarding factors with prognostic importance, and are intended to aid physicians with clinical decision-making. These NCCN Guidelines Insights focus on recent select updates to the NCCN Guidelines, including familial genetic alterations in AML, postinduction or postremission treatment strategies in low-risk acute promyelocytic leukemia or favorable-risk AML, principles surrounding the use of venetoclax-based therapies, and considerations for patients who prefer not to receive blood transfusions during treatment.
Approximately 40-45% of younger and 10-20% of older adults with acute myeloid leukemia (AML) will be cured with current standard chemotherapy. The outlook is particularly gloomy for patients with relapsed and/or refractory disease (cure rates no higher than 10%). Allogeneic hematopoietic stem cell transplantation (HSCT), the only realistic hope of cure for these patients, is an option for only a minority. In recent years, much has been learned about the genomic and epigenomic landscapes of AML, and the clonal architecture of both de novo and secondary AML has begun to be unraveled. These advances have paved the way for rational drug development as new "drugable" targets have emerged. Although no new drug has been approved for AML in over four decades, with the exception of gemtuzumab ozogamycin, which was subsequently withdrawn, there is progress on the horizon with the possible regulatory approval soon of agents such as CPX-351 and midostaurin, the Food and Drug Administration "breakthrough" designation granted to venetoclax, and promising agents such as the IDH inhibitors AG-221 and AG-120, the smoothened inhibitor glasdegib and the histone deacetylase inhibitor pracinostat. In our practice, we treat most patients with relapsed/refractory AML on clinical trials, taking into consideration their prior treatment history and response to the same. We utilize targeted sequencing of genes frequently mutated in AML to identify "actionable" mutations, e.g., in FLT3 or IDH1/2, and incorporate small-molecule inhibitors of these oncogenic kinases into our therapeutic regimens whenever possible. In the absence of actionable mutations, we rationally combine conventional agents with other novel therapies such as monoclonal antibodies and other targeted drugs. For fit patients up to the age of 65, we often use high-dose cytarabine-containing backbone regimens. For older or unfit patients, we prefer hypomethylating agent-based therapy. Finally, all patients with relapsed/refractory AML are evaluated for allogeneic HSCT.
The development of immune checkpoint inhibitors (ICIs) has revolutionized the treatment of patients with advanced stage cancers. However, immune-related adverse events are frequently observed. Cardiac toxicity from ICI therapy can range from asymptomatic troponin-I elevations to conduction abnormalities of the heart and even fulminant myocarditis. Although rare, myocarditis is a potentially fatal adverse effect of ICI therapy. We present a series of five cases of ICI-related cardio-toxicity diagnosed and managed at Roswell Park Comprehensive Cancer Center along with a review of published case reports in the literature. Our series highlights the importance of high clinical suspicion, early diagnosis of myocarditis, and prompt initiation of immunosuppressive therapy.
BackgroundUveal melanoma (UM) is the most common intraocular malignancy in adults. In contrast to cutaneous melanoma (CM), there is no standard therapy, and the efficacy and safety of dual checkpoint blockade with nivolumab and ipilimumab is not well defined.MethodsWe conducted a retrospective analysis of patients with metastatic UM (mUM) who received treatment with ipilimumab plus nivolumab across 14 academic medical centers. Toxicity was graded using National Cancer Institute Common Terminology Criteria for Adverse Events V.5.0. Progression-free survival (PFS) and overall survival (OS) were calculated using Kaplan-Meier methodology.Results89 eligible patients were identified. 45% had received prior therapy, which included liver directed therapy (29%), immunotherapy (21%), targeted therapy (10%) and radiation (16%). Patients received a median 3 cycles of ipilimumab plus nivolumab. The median follow-up time was 9.2 months. Overall response rate was 11.6%. One patient achieved complete response (1%), 9 patients had partial response (10%), 21 patients had stable disease (24%) and 55 patients had progressive disease (62%). Median OS from treatment initiation was 15 months and median PFS was 2.7 months. Overall, 82 (92%) of patients discontinued treatment, 34 due to toxicity and 27 due to progressive disease. Common immune-related adverse events were colitis/diarrhea (32%), fatigue (23%), rash (21%) and transaminitis (21%).ConclusionsDual checkpoint inhibition yielded higher response rates than previous reports of single-agent immunotherapy in patients with mUM, but the efficacy is lower than in metastatic CM. The median OS of 15 months suggests that the rate of clinical benefit may be larger than the modest response rate.
The technological age has resulted in children spending prolonged hours in front of television (TV) and computer screens (on the Internet). The aim of this prospective cross-sectional study is to determine the effect of this phenomenon on both childhood obesity and low vision in the State of Qatar. A total of 3000 school students aged 6 to 18 years were approached from September 2009 to March 2010 and 2467 (82.2%) students agreed to participate. Face-to-face interviews based on a designed questionnaire were conducted. The highest proportion of obese children were aged between 15-18 years (9.4%; p < 0.001); spent ≥ 3 hours on the Internet (5.6%; p < 0.001), and spent between 5-7 hours or less sleeping (4.1%; p < 0.001). Forty-six (1.9%) children spent ≥ 3 hours/day on the Internet, and were either overweight/obese and had low vision. The study findings confirmed a positive association between obesity and low vision as a result of excessive time spent on the TV view and Internet use.
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