FLT3 inhibitors potentially improve response rates in acute myeloid leukemia harboring t(6;9)(DEK::NUP214): The Mayo Clinic experience.

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Signs, Sources, Coping Strategies, and Suggested Interventions for Burnout Among Preclerkship Students at a U.S. Medical School: A Qualitative Focus Group Study.

PURPOSE: Research suggests that burnout can begin early in medical school, yet burnout among preclerkship students remains underexplored. This study aimed to characterize burnout signs, sources, coping strategies, and potential interventions among preclerkship students at one U.S. medical school. METHOD: The authors conducted a qualitative study of preclerkship students at Mayo Clinic Alix School of Medicine (MCASOM) during June 2019. Participants completed 2 Maslach Burnout Inventory (MBI) items (measuring frequency of emotional exhaustion and depersonalization) and 2 free-text questions on burnout before participating in 1 of 3 semistructured focus groups. Focus group questions were derived from a literature review on medical student burnout with input from the MCASOM Student Life and Wellness Committee. Group discussions were recorded, transcribed, coded inductively, and analyzed iteratively (along with free-text comments) using a general inductive approach from a constructivist perspective. RESULTS: Eighteen of 111 eligible students (16%) participated, with 5/18 (28%) reporting weekly emotional exhaustion and/or depersonalization on MBI items. Analysis of focus group transcripts showed that most students had experienced burnout symptoms during their first or second year, corresponding with school-related stressors and manifesting in cognitive-emotional, physical, and verbal-behavioral ways. Students identified systemic, institutional, and individual burnout drivers and discussed how these drivers interacted (e.g., high standards of excellence at the system level interacted with anxiety and maladaptive thinking at the individual level, creating pressure to always do more). Students used various coping strategies (e.g., self-care, peer support, reframing, and compartmentalization) but emphasized limitations of these strategies and recommended interventions directed toward systemic and institutional burnout drivers. CONCLUSIONS: This study offers insights into burnout signs and sources among preclerkship medical students that can inform future large-scale studies. Results suggest that burnout emerges from dynamic interactions among systemic, institutional, and individual factors and may benefit from multipronged interventions.

Academic Promotions in Medicine: An Appraisal of Fairness.

OBJECTIVE: To investigate whether the process of conferring academic rank or components of the promotion packet contribute to the lack of parity in academic advancement for women and individuals underrepresented in medicine (URMs). PATIENTS AND METHODS: We retrospectively reviewed prospective promotion applications to the position of associate professor or professor at Mayo Clinic from January 2, 2015, through July 1, 2019. Individuals with doctorate degrees who applied for either rank were included in the study. Data collected included demographic characteristics, curriculum vitae at time of application, committee score sheets, and deferral and approval decisions. Deferral rates for women compared with men and for URMs compared with non-URMs was the primary outcome. RESULTS: Of 462 people who applied for associate professor, 10% (n=46) were deferred. Those promoted had worked longer at Mayo Clinic (median, 6 years vs 2 years; P=.01), had more mentees (median, 6 vs 4; P=.02), authored more publications (median [interquartile range (IQR)], 39 [32-52] vs 30 [24-35]; P<.001), and were more likely to be on a National Institutes of Health or institutional grant (P<.05). Of the 320 people who applied for professor, 8.8% (n=28) were deferred. Those promoted had authored more publications (median [IQR], 77 [60-99] vs 56 [44-66]; P<.001) and were less likely to hold an elected office to a professional society (22.6% vs 39.3%; P=.05). There was no significant association between deferral status and sex (P>.4) or race/ethnicity (P>.9) for either rank. CONCLUSION: The process for academic advancement for professorships does not contribute to the gap in promotion rates for women and URMs.

One thousand patients with essential thrombocythemia: the Mayo Clinic experience.

We describe 1000 patients with essential thrombocythemia seen at the Mayo Clinic between 1967 and 2023: median age 58 years (18-90), females 63%, JAK2/CALR/MPL-mutated 62%/27%/3%, triple-negative (TN) 8%, extreme thrombocytosis (ExT; platelets ≥1000 × 109/L) 26%, leukocytosis (leukocyte count >11 × 109/L) 20%, and abnormal karyotype 6%. JAK2-mutated patients were older (median 71 years), and CALR mutated (52 years), and TN (50 years) younger (p < 0.01). Female gender clustered with TN (73%) and JAK2 (69%) vs. CALR/MPL (49%/47%) mutations (p < 0.01). ExT clustered with CALR (type-2 more than type-1) and TN and leukocytosis with JAK2 mutation (p < 0.01). In multivariable analysis, risk factors for overall survival were older age (p < 0.01), male gender (HR 1.8), absolute neutrophil count (ANC) ≥ 8 × 109/L (HR 1.6), absolute lymphocyte count (ALC) < 1.7 × 109/L (HR 1.5), hypertension (HR 1.7), and arterial thrombosis history (HR 1.7); for leukemia-free survival, ExT (HR 2.3) and abnormal karyotype (HR 3.1); for myelofibrosis-free survival, ANC ≥ 8 × 109/L (HR 2.3) and MPL mutation (HR 3.9); for arterial thrombosis-free survival, age ≥60 years (HR 1.9), male gender (HR 1.6), arterial thrombosis history (HR 1.7), hypertension (HR 1.7), and JAK2 mutation (HR 1.8); for venous thrombosis-free survival, male gender (HR 1.8) and venous thrombosis history (HR 3.0). Associations between ExT and leukemic transformation and between ANC and fibrotic progression were limited to JAK2-mutated cases. Aspirin therapy appeared to mitigate both arterial (HR 0.4) and venous (HR 0.4) thrombosis risk. HR-based risk models delineated patients with median survivals ranging from 10 years to not reached and 20-year leukemia/myelofibrosis incidences from 3%/21% to 12.8%/49%. The current study provides both novel and confirmatory observations of essential thrombocythemia.

Immunotherapy-associated Autoimmune Hemolytic Anemia.

Over the past decade, the role of immunotherapy treatment in cancer has expanded; specifically, indications for immune checkpoint inhibitors (ICI) have multiplied and are used as first-line therapy. ICIs include cytotoxic T-lymphocyte-associated protein 4 and programmed cell death protein 1 inhibitors, as monotherapies or in combination. Autoimmune hemolytic anemia (AIHA) has emerged as a rare yet serious immune-related adverse event in ICI use. This review describes diagnosis and management of immunotherapy related AIHA (ir-AIHA) including an algorithmic approach based on severity of anemia. Suggested mechanisms are discussed, guidance on ICI resumption provided and prognosis reviewed including risk of recurrence.

Cytogenetic abnormalities in essential thrombocythemia: Clinical and molecular correlates and prognostic relevance in 809 informative cases.

Cytogenetic studies among 809 consecutive patients with essential thrombocythemia (ET; median age 59 years; 65% females) revealed normal karyotype in 754 (93%), loss of chromosome Y only (-Y) in 16 (2%), and abnormalities other than -Y in 39 (4.8%), the most frequent being sole 20q- (n = 8). At presentation, abnormal karyotype, excluding -Y, was associated with older age (p = 0.04), higher leukocyte count (p = 0.03) and arterial thrombosis history (p = 0.02); no associations were apparent for JAK2/CALR/MPL mutations whereas ASXL1 mutations clustered with normal karyotype/-Y and TP53 with abnormal karyotype. Survival was significantly shorter in patients with abnormal karyotype or -Y, compared to those with normal karyotype (median 12, 10, and 21 years, respectively; p < 0.0001). During multivariable analysis that included IPSET (international prognostic score for ET) variables, abnormal karyotype (p < 0.01, HR 2.0), age >60 years (p < 0.01, HR 4.5), leukocytosis >11 × 109/L (p < 0.01, HR 1.5), and male gender (p < 0.01, HR 1.4) were independently associated with inferior survival; abnormal karyotype and age >60 years remained significant, along with SF3B1/SRSF2/U2AF1/TP53 mutations (p = 0.04; HR 2.9), when the latter was included in the multivariable model. The current study suggests prognostic relevance for karyotype in ET.

Mayo Clinic experience with 1123 adults with acute myeloid leukemia.

Between 2004 and 2017, a total of 1123 adult patients (median age 65 years; 61% males) with newly diagnosed acute myeloid leukemia (AML), not including acute promyelocytic leukemia, were seen at the Mayo Clinic. Treatment included intensive (n = 766) or lower intensity (n = 144) chemotherapy or supportive care (n = 213), with respective median survivals of 22, 9, and 2 months (p < 0.01). Intensive chemotherapy resulted in complete remission (CR) and CR with incomplete count recovery (CRi) rates of 44 and 33%, respectively, with no difference in survival outcome between the two (p = 0.4). Allogeneic hematopoietic stem cell transplant (AHSCT) was documented in 259 patients and provided the best survival rate (median 55 months; p < 0.01). After a median follow-up of 13 months, 841 (75%) deaths were recorded. Multivariate analysis identified age >60 years (HR 2.2, 1.9-2.6), adverse karyotype (HR 2.9, 1.9-4.9), intermediate-risk karyotype (HR 1.6, 1.02-2.6), post-myeloproliferative neoplasm AML (HR 1.9, 1.5-2.4), and other secondary AML (HR 1.3 (1.1-1.6) as risk factors for shortened survival. These risk factors retained their significance after inclusion of FLT3/NPM1 mutational status in 392 informative cases: FLT3+NPM1- (HR 2.8, 1.4-5.6), FLT3+/NPM+ (HR 2.6 (1.3-5.2), and FLT3-NPM1- (HR 1.8, 1.0-3.0).

The Impact of Obesity on the Outcomes of Adult Patients with Acute Lymphoblastic Leukemia - A Single Center Retrospective Study.

INTRODUCTION: Obesity is a worldwide problem that is related to cardiac disease, thrombosis and cancer. However, little is known about the impact of obesity on the outcomes of adult acute lymphoblastic leukemia (ALL) patients. METHODS: We retrospectively evaluated a cohort of 154 newly diagnosed adult ALL patients between 1994 and 2011 at Mayo Clinic (Rochester). According to the World Health Organization (WHO) international BMI classification, patients were stratified as underweight, normal weight, overweight, and obese. For some analyses, patients were also stratified according to a two-sided non-obese or obese classification. RESULTS: The median follow-up time was 8.37 years. Obese patients were more likely to be women (p=0.024) and ≥60 years old (p=0.003). Five-year mortality rates were higher in obese patients than non-obese [HR 95% CI: 1.60 (1.03-2.50) p=0.035]. This was also the case in subgroup analysis among T-cell patients although the number of patients was small [HR 95% CI: 5.42 (1.84-15.98) p<0.001]. There was no difference in mortality among the B-cell patients. After adjusting for baseline variables, the difference in mortality remained in several models. There was no difference in EFS or cumulative incidence of relapse rates between obese and non-obese patients among the overall population. DISCUSSION: In conclusion, our study suggests that adult ALL patients with obesity have lower survival rates, especially in T-cell ALL.

Leukocytosis and Tobacco Use: An Observational Study of Asymptomatic Leukocytosis.

PURPOSE: This study aimed to characterize the white blood cell differential of tobacco smoking-induced leukocytosis and describe the longitudinal impact of smoking cessation on this peripheral blood abnormality. METHODS: Medical records of patients undergoing evaluation by hematologists for persistent leukocytosis were reviewed. Patients in whom leukocytosis was determined to be secondary to tobacco use after exclusion of other causes were identified. Demographic and laboratory data were collected at time of diagnosis. Patients were longitudinally followed and information regarding smoking cessation and follow-up white blood cell values were recorded. RESULTS: Forty patients were determined to have smoking-induced leukocytosis. The median age was 49.5 years (range: 28-75 years), 24 patients were female, and the mean body mass index (BMI) was 31.5 kg/m2. The mean white blood cell count was 13.3 × 109/L (range: 9.8-20.9 × 109/L); 39 patients had absolute neutrophilia (98%), 21 had lymphocytosis (53%), 20 had monocytosis (50%), and 19 had basophilia (48%). During follow-up, 11 patients either quit (n = 9) or reduced (n = 2) tobacco use. Reduction in tobacco smoking led to a significant decrease in mean white blood cell count (13.2 × 109/L vs 11.1 × 109/L, P = 0.02). The median time to decrease in white blood cell count following reduction in tobacco use was 8 weeks (range: 2-49 weeks). CONCLUSIONS: Tobacco-induced leukocytosis was characterized by a mild elevation in total white blood cell count and was most commonly associated with neutrophilia, lymphocytosis, monocytosis, and basophilia. Cessation of smoking led to improvement in leukocytosis. Tobacco history should be elicited from all patients presenting with leukocytosis to limit unnecessary diagnostic testing, and counseling regarding smoking cessation should be offered.

Parental health in fellowship trainees: Fellows' satisfaction with current policies and interest in innovation.

BACKGROUND: Parenthood during medical training is common and impacts trainee well-being. However, current graduate medical education parental health policies are often limited in scope. We explored current fellowship trainees' knowledge of/satisfaction with current policies as well as interest in potential changes/additions to existing policies. METHODS: Fellowship program directors/coordinators at a three-site academic institution were surveyed and information was collected from 2015 to 2019 regarding fellow demographics and parental health policies. We distributed an electronic survey to fellows containing Likert-type-scale questions rating knowledge/level of satisfaction with current parental health policies and interest in potential additions/modifications to current policies. RESULTS: Thirty-five of 47 (74%) fellowship programs responded. An average of 11% of female fellows and 15% of male fellows took parental leave during the study period. Three (9%) of the programs had at least one additional parental health policy beyond institutional graduate medical education policies. In the fellow survey, 175 of 609 fellows responded (28.7%), of which 84 (48.6%) were female. Although 89.1% agreed/strongly agreed that parental health is an important part of health and well-being for fellows, only 32% were satisfied/very satisfied with current policies (no significant sex-related differences). Fellows reported the following potential interventions as important/very important: 79.2% increased (paid) maternity leave (72.7% male, 86.7% female, p = 0.02), 78% increased (paid) paternity leave (76.4% male, 81.9% female, p = 0.37), 72.3% part-time return to work (60.2% male, 84.3% female, p = 0.0005), 63% coverage for workup/management of infertility (52.3% male, 74.7% female, p = 0.002), and 79.9% on-site day care (70.7% male, 89.2% female, p = 0.003). CONCLUSIONS: Parental health includes multiple domains, not all of which are covered by current policies. Fellows feel that parental health is an important part of overall health and well-being, but most are not satisfied with current policies. Expanded access to parental leave and new policies (part-time return to work, infertility management, and on-site day care) are opportunities for innovation.