Citations

AbstractBackgroundSecond hematologic cancers in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL) are well documented and include Hodgkin lymphoma, therapy‐related acute myeloid leukemia/myelodysplastic syndromes, and transformation to diffuse large B‐cell lymphoma. Although cutaneous T‐cell lymphoma (CTCL) has been reported in patients with CLL, the incidence and comparison to expected rates are unknown. We evaluated the incidence of CTCL among patients with CLL or other non‐Hodgkin lymphoma (NHL) subtypes using data from the Surveillance, Epidemiology, and End Results (SEER) Program.MethodsWe searched the SEER 13 registries for patients with a diagnosis of CLL and NHL between 1992 and 2008. Among patients identified, we evaluated the incidence of CTCL.ResultsAmong 31,286 patients with CLL, the incidence of CTCL was not significantly higher in men than women: 104.2 (95% CI, 50.0–191.8) and 28.1 (95% CI, 3.4–101.3) per 1,000,000 person‐years, respectively (P = 0.06). Among 97,691 patients with NHL, the incidence of CTCL was similar in men and women (97.9 [95% CI, 62.0–146.9] and 92.0 [95% CI, 56.2–142.1] per 1,000,000 person‐years, respectively; P = 0.84). The incidence of CTCL among males with CLL (standardized incidence ratio [SIR], 3.0 [95% CI, 1.4–5.5]), males with NHL (SIR, 3.7 [95% CI, 2.3–5.5]), and females with NHL (SIR, 5.9 [95% CI, 3.6–9.1]) was significantly higher than expected in the general population (all P < 0.001).ConclusionThe risk of CTCL is greater in men with CLL than in the general population. In patients with NHL, both men and women are at greater risk for CTCL than in the general population.

Summary The ultimate cause of death for most patients with newly diagnosed chronic lymphocytic leukaemia ( CLL ) and its relationship to co‐morbid health conditions is poorly defined. We conducted a prospective cohort study that systematically followed 1143 patients diagnosed with CLL between June 2002 and November 2014. Comorbid health conditions at the time of CLL diagnosis and their relationship to survival and cause of death were evaluated. Collectively, 1061 (93%) patients had at least one co‐morbid health condition at the time of CLL diagnosis (median number 3). Despite this, 89% of patients had a low‐intermediate Charlson Comorbidity Index score ( CCI ) at diagnosis. After a median follow‐up of 6 years, 225 patients have died. Death was due to CLL progression in 85 (46%) patients, infection in 14 (8%) patients, other cancer in 35 (19%) patients and comorbid health conditions in 50 (27%) patients. Higher CCI score and a greater number of major comorbid health conditions at the time of CLL diagnosis was associated with shorter non‐ CLL specific survival, but not with shorter CLL ‐specific survival on multivariate analysis. In conclusion, CLL and CLL ‐related complications (infections and second cancers) are the overwhelming cause of death in patients with CLL , regardless of CCI score and number of comorbid health conditions at diagnosis.

Job burnout is highly prevalent in graduate medical trainees. Numerous demands and stressors drive the development of burnout in this population, leading to significant and potentially tragic consequences, not only for trainees but also for the patients and communities they serve. The literature on interventions to reduce resident burnout is limited but suggests that both individual- and system-level approaches are effective. Work hours limitations and mindfulness training are each likely to have modest benefit. Despite concerns that physician trainee wellness programs might be costly, attention to physician wellness may lead to important benefits such as greater patient satisfaction, long-term physician satisfaction, and increased physician productivity. A collaborative of medical educators, academic leaders, and researchers recently formed with the goal of improving trainee well-being and mitigating burnout. Its first task is outlining this framework of initial recommendations in a call to action. These recommendations are made at the national, hospital, program, and nonwork levels and are meant to inform stakeholders who have taken up the charge to address trainee well-being. Regulatory bodies and health care systems need to be accountable for the well-being of trainees under their supervision and drive an enforceable mandate to programs under their charge. Programs and individuals should develop and engage in a “menu” of wellness options to reach a variety of learners and standardize the effort to ameliorate burnout. The impact of these multilevel changes will promote a culture where trainees can learn in settings that will sustain them over the course of their careers.

Key Points Pembrolizumab was first shown to be clinically active in CLL patients with RT. PD-1 and PD-L1 expression in tumor microenvironment are promising biomarkers to select RT patients for PD-1 blockade.

Akt is a downstream target of B cell receptor signaling and is a central regulator of CLL cell survival. We aim to investigate the safety and efficacy of the Akt inhibitor MK‐2206 in combination with bendamustine and rituximab (BR) in relapsed and/or refractory CLL in a phase I/II study. A standard phase I design was used with cohorts of three plus three patients to determine the maximum tolerated dose (MTD) of MK‐2206 in combination with BR in relapsed CLL. Single‐agent MK‐2206 (weekly dosed) was administered one‐week in advance before BR on cycle 1 and subsequently was given with BR at the same time for cycle 2‐6. Phase II employed the MTD of MK‐2206 with BR to evaluate safety and efficacy of this study combination. Thirteen relapsed/refractory CLL were treated for maximal 6‐cycle of therapy. The maximum tolerated dose of MK‐2206 was 90 mg by mouth once weekly. The most common grade 3/4 adverse events were neutropenia (46%), febrile neutropenia (23%), rash (15%), diarrhea (15%), and thrombocytopenia (15%). Overall response rate was 92% with a median progression free survival and treatment free survival of 16 and 24 months, respectively. Five patients (38%) achieved complete remission or complete remission with incomplete count recovery, two of whom were MRD negative. The efficacy and tolerability of this combination indicates that Akt inhibition combined with chemoimmunotherapy is a promising novel treatment combination in CLL and deserves further prospective clinical trial.