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Objectives: Acute myeloid leukaemia (AML) is a disease of older adults, who are vulnerable to socio‐economic factors. We determined AML incidence in older adults and the impact of socio‐economic factors on outcomes. Methods: We included 3024 AML patients (1996–2016) identified from a population‐based registry. Results: AML incidence in patients ≥60 years increased from 11.01 (2001–2005) to 12.76 (2011–2016) per 100 000 population. Among 879 patients ≥60 years in recent eras (2010–2016), rural residents (<100 000 population) were less likely to be assessed by a leukaemia specialist (39% rural, 47% urban, p =.032); no difference was seen for lower (43%, quintile 1–3) vs. higher (47%, quintile 4–5) incomes (p =.235). Similar numbers received induction chemotherapy between residence (16% rural, 18% urban, p =.578) and incomes (17% lower, 17% high, p = 1.0). Differences between incomes were seen for hypomethylating agent treatment (14% low, 20% high, p =.041); this was not seen for residence (13% rural, 18% urban, p =.092). Among non‐adverse karyotype patients ≥70 years, 2‐year overall survival was worse for rural (5% rural, 12% urban, p =.006) and lower income (6% low, 15% high, p =.017) patients. Conclusions: AML incidence in older adults is increasing, and outcomes are worse for older rural and low‐income residents; these patients face treatment barriers. [ABSTRACT FROM AUTHOR]

There has been an explosion of knowledge about the role of metabolism and the mitochondria in acute myeloid leukemia (AML). We have also recently seen several waves of novel therapies change the treatment landscape for AML, such as the selective B-cell lymphoma 2 (BCL-2) inhibitor venetoclax. In this new context, we review the rapidly advancing literature on the role of metabolism and the mitochondria in AML pathogenesis, and how these are interwoven with the mechanisms of action for novel therapeutics in AML. We also review the role of oxidative phosphorylation (OxPhos) in maintaining leukemia stem cells (LSCs), how recurrent genomic alterations in AML alter downstream metabolism, and focus on how the BCL-2 pathway and the mitochondria are inextricably linked in AML. Thus, we provide an overview of the mitochondria and metabolism in the context of our new therapeutic world for AML and outline how targeting these vulnerabilities may produce novel therapeutic strategies. [ABSTRACT FROM AUTHOR]

Summary: Treatment of Burkitt lymphoma (BL) with intensive, multi‐agent chemotherapy with aggressive central nervous system (CNS) prophylaxis results in high cure rates, although no regimen is standard of care. We examined population‐based survival outcomes of adults with BL treated with a modified combination of cyclophosphamide, vincristine, doxorubicin, prednisone and systemic high‐dose methotrexate (MTX) (CODOX‐M) with IVAC (ifosfamide, mesna, etoposide, cytarabine and intrathecal MTX) (CODOX‐M/IVAC) ± rituximab over a 15‐year period in British Columbia. For the 81 patients identified (including 8 with CNS involvement and 18 with human immunodeficiency virus‐associated BL), 5‐year progression‐free survival (PFS) and overall survival (OS) were 75% [95% confidence interval (CI): 63–83%] and 77% (95% CI: 66–85%), respectively, with no treatment‐related deaths. Those who completed the regimen per protocol (n = 38) had significantly improved 5‐year PFS 86% (P = 0·04) and OS 92% (P = 0·008), as did those under 60 years with 5‐year PFS 82% (P = 0·005) and OS 86% (P = 0·002), which remained significant in multivariate analysis [PFS: hazard ratio (HR) 3·36, P = 0·018; OS HR 4·03, P = 0·012]. Incorporation of high‐dose systemic methotrexate also significantly affected multivariate survival outcomes (OS HR 0·28, P = 0·025). Stem cell transplant in first remission had no effect on OS or PFS. This large, real‐world analysis of BL patients treated with CODOX‐M/IVAC ± rituximab demonstrates excellent survival outcomes comparable to clinical trials. These results help to serve as a benchmark when comparing curative therapies for BL patients as novel regimens are incorporated into clinical practice. [ABSTRACT FROM AUTHOR]

The introduction of tyrosine kinase inhibitors has improved outcomes in Philadelphia chromosome-positive acute lymphoblastic leukemia, yet relapse due to the development of resistance mutations remains a major obstacle. Ponatinib is a novel tyrosine kinase inhibitor designed to overcome single-resistance mutations in the ABL kinase. Three clinical trials confirmed the efficacy of ponatinib in the relapsed and front-line setting in Philadelphia positive acute lymphoblastic leukemia, even in the presence of the T315I mutation, which confers resistance to other tyrosine kinase inhibitors. The rate of relapse appears to be very low when used in combination with chemotherapy, suggesting a role for ponatinib in newly diagnosed patients. A major concern with the use of ponatinib is the associated high risk of life-threatening vascular thrombotic events. Potential strategies to reduce this risk include minimizing the use of ponatinib in patients with significant baseline cardiovascular risk, careful surveillance and treatment of cardiovascular risk-factors and dose reduction of ponatinib. [ABSTRACT FROM AUTHOR]