The upcoming 5th edition of the World Health Organization (WHO) Classification of Haematolymphoid Tumours is part of an effort to hierarchically catalogue human cancers arising in various organ systems within a single relational database. This paper summarizes the new WHO classification scheme for myeloid and histiocytic/dendritic neoplasms and provides an overview of the principles and rationale underpinning changes from the prior edition. The definition and diagnosis of disease types continues to be based on multiple clinicopathologic parameters, but with refinement of diagnostic criteria and emphasis on therapeutically and/or prognostically actionable biomarkers. While a genetic basis for defining diseases is sought where possible, the classification strives to keep practical worldwide applicability in perspective. The result is an enhanced, contemporary, evidence-based classification of myeloid and histiocytic/dendritic neoplasms, rooted in molecular biology and an organizational structure that permits future scalability as new discoveries continue to inexorably inform future editions.

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.

Objectives To examine tumor infiltrating lymphocytes (TILs) and their prognostic value in patients with pancreatic ductal adenocarcinoma (PDAC) after neoadjuvant therapy. Methods Intra-tumoral CD4+, CD8+, and FOXP3+ lymphocytes was examined by immunohistochemistry using a computer-assisted quantitative analysis in 136 PDAC patients who received neoadjuvant therapy and pancreaticoduodenectomy. The results were correlated with clinicopathologic parameters and survival. Results High CD4+ TILs in treated PDAC were associated with high CD8+ TILs (P = 0.003), differentiation (P = 0.04) and a lower frequency of recurrence (P = 0.02). Patients with high CD4+ TILs had longer disease-free survival (DFS) and overall survival (OS) than did patients with low CD4+ TILs (P < 0.01). The median OS of patients with a high CD8+/FOXP3+ lymphocyte ratio (39.5 [standard deviation, 6.1] months) was longer than that of patients with a low CD8+/FOXP3+ lymphocyte ratio (28.3 [standard deviation, 2.3] months; P=0.01). In multivariate analysis, high CD4+ TILs were an independent prognostic factor for DFS [Hazard ratio (HR): 0.49, 95% CI, 0.30–0.81; P = 0.005] and OS (HR, 0.54; 95% CI, 0.33–0.89; P = 0.02). Conclusions High CD4+ lymphocytes is associated with tumor differentiation, lower recurrence and is an independent prognostic factor for survival in PDAC patients treated with neoadjuvant therapy.

Mammalian skin incorporates a local equivalent of the hypothalamic-pituitary-adrenal (HPA) axis that is critical in coordinating homeostatic responses against external noxious stimuli. Ultraviolet radiation B (UVB) is a skin-specific stressor that can activate this cutaneous HPA axis. Since C57BL/6 (B6) and DBA/2J (D2) strains of mice have different predispositions to sensorineural pathway activation, we quantified expression of HPA axis components at the gene and protein levels in skin incubated ex vivo after UVB or sham irradiation. Urocortin mRNA was up-regulated after all doses of UVB with a maximum level at 50 mJ/cm2 after 12 h for D2 and at 200 mJ/cm2 after 24 h for B6. Proopiomelanocortin mRNA was enhanced after 6 h with the peak after 12 h and at 200 mJ/cm2 for both genotypes of mice. ACTH levels in tissue and media increased after 24 h in B6 but not in D2. UVB stimulated β-endorphin expression was higher in D2 than B6. Melanocortin receptor 2 mRNA was stimulated by UVB in a dose-dependent manner, with a peak at 200 mJ/cm2 after 12 h for both strains. The expression of Cyp11a1 mRNA — a key mitochondrial P450 enzyme in steroidogenesis, was stimulated at all doses of UVB irradiation, with the most pronounced effect after 12–24 h. UVB radiation caused, independently of genotype, a dose-dependent increases in corticosterone production in the skin, mainly after 24 h of histoculture. Thus, basal and UVB stimulated expression of the cutaneous HPA axis differs as a function of genotype: D2 responds to UVB earlier and with higher amplitude than B6, while B6 shows prolonged (up to 48 h) stress response to a noxious stimulus such as UVB.

We conducted a phase I/II multicenter trial using 6 cycles of brentuximab vedotin (BV) in combination with rituximab, cyclophosphamide, doxorubicin, and prednisone (R-CHP) for treatment of patients with CD30-positive (+) B-cell lymphomas. Thirty-one patients were evaluable for toxicity and 29 for efficacy including 22 with primary mediastinal B-cell lymphoma (PMBCL), 5 with diffuse large B-cell lymphoma (DLBCL), and 2 with gray zone lymphoma (GZL). There were no treatment-related deaths; 32% of patients had non-hematological grade 3/4 toxicities. The overall response rate was 100% (95% CI: 88-100) with 86% (95% CI: 68-96) of patients achieving complete response at the end of systemic treatment. Consolidative radiation following end of treatment response assessment was permissible and used in 52% of all patients including 59% of patients with PMBCL. With a median follow-up of 30 months, the 2-year progression-free survival (PFS) and overall survival (OS) were 85% (95% CI: 66-94) and 100%, respectively. In the PMBCL cohort, 2-year PFS was 86% (95% CI: 62-95). In summary, BV-R-CHP with or without consolidative radiation is a feasible and active frontline regimen for CD30+ B-cell lymphomas (NCT01994850).