Thompson, Carrie A.

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.

Abstract Background Factors associated with chronic immune stimulation such as transplantation, autoimmune disorders and chronic infections have been linked to the development of lymphoma, while atopic conditions have been associated with a lower risk of lymphoma. Vaccinations, in part due to their ability to induce immune responses, have been hypothesized to play a role in lymphoma etiology, but there are few studies with mixed results and limited data on lymphoma subtypes. Methods We used a clinic-based study of 2461 newly diagnosed lymphoma cases and 2253 frequency-matched controls enrolled from 2002-2015. Participants self-reported lymphoma risk factors and history of vaccinations for hepatitis A, hepatitis B, chicken pox, yellow fever and influenza. Pathology was centrally reviewed, and included 644 chronic lymphocytic leukemia, 528 follicular (FL), 414 diffuse large B-cell (DLBCL), 170 marginal zone, 127 mantle cell, 119 T-cell, 181 Hodgkin, and 278 other lymphoma subtypes. We used polytomous logistic regression to estimate odds ratio (OR) and 95% confidence intervals (CI) of vaccinations with lymphoma risk overall and for subtypes, adjusting for age, sex, socioeconomic status, body mass, alcohol use, smoking history, recreational sun exposure, and family history of hematological malignancies. Results The median age at diagnosis for lymphoma cases was 64 years (range: 18-93) and 58% were male; the median age at enrollment for controls was 62 years (range: 18-91) and 53% were male. The most common vaccinations among controls were influenza (90%) followed by hepatitis B (41%), hepatitis A (30%), chicken pox (20%), and yellow fever (11%). Vaccination for influenza was inversely associated with lymphoma risk overall (OR=0.75, CI:0.61-0.93, P=0.01), with an inverse trend for increasing number of vaccinations (P=0.0001). In subtype analyses, Influenza vaccination was inversely associated with risk of FL (OR=0.59, CI:0.43-0.80, P=0.001), DLBCL (OR=0.64, CI:0.44-0.92, P=0.02) and other lymphoma subtypes (OR=0.66, CI:0.43-1.00, P=0.05). Vaccination for hepatitis A was inversely associated with lymphoma risk (OR=0.79, CI:0.65-0.96, P=0.02), with no significant subtype-specific associations. No evidence of association with vaccination for hepatitis B (OR=0.95, CI:0.79-1.14) and chicken pox (OR=0.83, CI:0.68-1.02) for lymphoma risk overall or for any subtypes. Although no evidence of an association with vaccination for yellow fever (OR=0.81, CI:0.62-1.06) for lymphoma risk, it was inversely associated with DLBCL risk (OR=0.42, CI:0.22-0.80). Conclusion Vaccination for influenza and hepatitis A were inversely associated with overall lymphoma risk. DLBCL was associated with vaccination for influenza and yellow fever. FL was associated with vaccination for influenza. Understanding the underlying mechanisms for a putative protective effect of certain vaccines could provide new clues to the etiology and prevention of lymphoma. Citation Format: Geffen Kleinstern, Dennis P. Robinson, Carrie A. Thompson, Melissa C. Larson, Cristine Allmer, Grzegorz S. Nowakowski, Timothy G. Call, Stephen M. Ansell, Andrew L. Feldman, Neil E. Kay, Thomas M. Habermann, Susan L. Slager, James R. Cerhan. Vaccination history and risk of lymphoma and its major subtypes [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 1054.

8550 Background: Waldenström Macroglobulinemia (WM) is a rare lymphoplasmacytic malignancy characterized by the presence of a recurrent point mutation in the MYD88 gene (MYD88L265P) in 80-95% of cases. Patients with MYD88WT genotype comprise a small subset that responds poorly to ibrutinib and other Bruton tyrosine kinase inhibitors. We examined the characteristics and outcome of WM patients with MYD88WT genotype predominantly treated with non-BTK inhibitor based therapies. Methods: Patients with a diagnosis of WM seen at Mayo Clinic, Rochester, between 1996 and 2018 were included. Their characteristics and outcomes were assessed from the time of active disease. Marrow MYD88 genotyping was assessed with an allele specific PCR assay (analytic sensitivity 1%). Categorical and continuous variables were compared using Chi square and Wilcoxon tests, respectively. Time-to-event analyses were performed using Kaplan Meier test. Results: Of 986 patients with active WM, MYD88 genotype data were available in 331 (34 %) patients; 72 (22%) and 260 (78%) patients harbored MYD88WT and MYD88L265P genotypes, respectively. The median follow-up was 5.8 years (95% CI: 5.0-6.5 years) from active WM; 6 years MYD88WT vs 5.4 years for MYD88L265P cohort. Median age was 63 years and 66 years in the MYD88WT and MYD88L265P cohorts, respectively (p = 0.07) with 46% and 53% patients being ≥65 years of age, respectively (p = 0.36). Pre-treatment marrow lymphoplasmacytic (LPL) infiltrate (median 40% for MYD88WT vs 60% for MYD88L265P; p = 0.001) and beta-2 microglobulin (median 3 µg/mL for MYD88WT vs 3.9 µg/mL for MYD88L265P; p = 0.02) were lower in the MYD88WT compared to the MYD88L265P cohort; other laboratory parameters at active disease were comparable. Per IPSSWM prognostic criteria, MYD88WT had fewer patients in the high risk group (18% for MYD88WT vs 42% MYD88L265P; p = 0.03). Patients with MYD88WT had higher likelihood of histological transformation [18% for MYD88WT vs 4% for MYD88L265P; odds ratio 5.8 (95% CI: 2.5-13.5; p < 0.0001)]. Among patients with treatment data available, only 35 (11%) patients received ibrutinib. The 5-year overall survival (OS) from active disease was comparable (85% in MYD88WT vs 82% in MYD88L265P cohort; p = 0.7). Conclusions: MYD88WT genotype in WM is associated with lower marrow LPL infiltration, lower likelihood of high-risk IPSSWM categorization and a higher likelihood of histological transformation in comparison to MYD88L265P mutant subpopulation. MYD88 genotype does not affect the OS from active disease in predominantly non-BTK inhibitor treated patients.

e19112 Background: We sought to study the longitudinal QOL, financial burden and perception of care (PoC) in patients with multiple myeloma (MM) or lymphoma (LYM) enrolled on CTs vs. those receiving standard care (Non-CT). Methods: QOL was evaluated using the FACT-G questionnaire (baseline, 1, 2, 3, 6 & 12 months). Financial burden was evaluated using 10 questions adapted from the MEPS survey and PoC was evaluated using 6 questions adapted from the CAHPS survey (baseline, 3, 6 & 12 months). Results: 35 (28%) of 123 enrolled patients were treated on CTs. Demographics, QOL and financial burden are shown in the Table. Baseline QOL scores were similar in CT vs non-CT groups. Age, gender and self-reported performance status were significantly associated with baseline QOL, while lines of therapy & cancer type were not. There were no significant differences in change in QOL vs. baseline in patients treated on CTs vs. non-CTs at 1, 2, 3, 6 and 12 months from baseline, including the total FACT-G score and the subdomains of functional, physical, emotional and social well-being. Within each group, there was a decline in QOL over the first 3 months, specifically physical WB, which gradually returned to baseline. Baseline answers to financial burden questions were similar, except patients on CTs reported less need for taking extended time-off from work (22% vs. 46%, p = 0.02). The only statistically significant difference in individual Qs over 1 year was ‘worry about having to pay large medical bills’ at the 6-month timepoint (CT: 0%, non-CT: 52%, p = 0.01). Using a composite score from 4 MEPS questions, financial burden over time was lower in the CT group, though the differences were not statistically significant. There were no significant differences in PoC at baseline, 3, 6 and 12 months in the two groups based on answers to each of the six questions adapted from the CAHPS survey. Conclusions: Over 1 year, patients on CTs experienced a similar QOL and perceived their care to be similar as non-CT patients. Financial burden was lower in the CT group, though differences were not statistically significant. [Table: see text]

e14018 Background: Cancer survival rates are improving. Therefore, management of cardiovascular complications has now become a crucial clinical concern. Cardio-oncology is the sub-specialty that assists in the overall management of cancer patients in a multi-disciplinary manner. Mayo Clinic cardio-oncology practice was initiated to work closely with our oncology colleagues for early detection of cardiovascular complications in response to cancer-therapy. Majority of the patients visit our cardio-oncology clinic once, we thought it is important to study the group of patients that visited frequently due to cardiovascular complications. Aim: To evaluate the most common cardiovascular complication in patients with 2 or more visits to our cardio-oncology clinic. Methods: From 2012-2017, there were > 2500 patients visits to our clinic, with 24 patients having 2 or more visits. Data including patients’ demographics, ethnicity, chemotherapeutic medications, primary cancer type, cardiovascular risk factors, echocardiography and clinical outcomes were collected. Cardiotoxicity was defined as the decrease in left ventricular ejection fraction (LVEF) of > 10% to a value of < 53%. Heart failure was diagnosed based on Framingham’s criteria or by a cardiologist. Results: There were 19 women (80%) and 5 men (20%). Median age at the time of diagnosis was 56 years [19-76]. The most common malignancy was breast cancer (70%), followed by B-cell lymphoma (12%) and acute myeloid leukemia (8%). Thirty percent had > 2 risk factors for cardiovascular disease. 75% of the patients had an LVEF of < 53, of these 67% developed heart failure with 58% preserved and 42% reduced ejection fraction. Those with heart failure had received a mean anthracycline dose of 305 ± 91.8mg/m2. With initiation of ACEI, B-Blockers, and diuretics (GDMT) 79% showed recovery of LVEF to ≥53 during the follow up. Conclusions: In our experience, most patients who were seen at least twice in the cardio-oncology clinic for heart failure had received a dose of > 300mg/m2 anthracycline. With GDMT over 75% of the patients recovered. Care in the cardio-oncology clinic plays a key role in optimizing these clinical outcomes.

Abstract Background AL amyloidosis can be associated with coagulopathy due to acquired factor X (FX) deficiency. Published experience, limited to case reports, suggests that infusion of fresh frozen plasma (FFP), platelets, plasma exchange, and vitamin K are of limited hemostatic efficacy for periprocedural management of coagulopathy. Therefore, we reviewed our cumulative experience of managing patients (pt) with FX deficiency due to AL amyloidosis who underwent an invasive procedure. Methods Pt with AL amyloidosis and isolated FX deficiency (≤ 50%), who underwent an invasive procedure between January 1975 and May 2007, were retrospectively identified from institutional databases. We excluded bone marrow biopsies as well as procedures &gt;3 months prior to the diagnosis of FX deficiency. Endpoints of the study were bleeding, thrombosis, and death. Results Sixty-one pt fit the study criteria. They were arbitrarily classified as having severe (&lt;10%; n=6), moderate (10–25%; n=16), or mild (26–50%; n=39) FX deficiency. The pt underwent a total of 115 procedures, 13 (11.3%) of which were considered major procedures and 102 (88.7%) were minor procedures. Major Procedures 13 pt underwent a major procedure; 4 had severe FX deficiency, 2 moderate, and 7 mild. Procedures included splenectomy, colon resection, renal transplant, and others. All 4 of the pt with severe deficiency were treated with hemostatic agents (FFP, plasma exchange, tranexamic acid, danazol, aminocaproic acid, and rFVIIa) in the perioperative period. Two (50%) of these patients had complications: intraabdominal hematoma and death. The death occurred in a patient with splenic rupture and uncontrolled hemorrhage refractory to rFVIIa and FFP. None of the pt with moderate deficiency experienced complications, despite not receiving hemostatic agents. Similarly, 0/7 patients with mild deficiency developed complications (2 received hemostatic agents FFP, platelets, vitamin K, and DDAVP). Minor Procedures All 61 pt underwent a minor procedure; central venous catheter placement was the most common (n=26), followed by EGD with biopsy (n=16) and renal biopsy (n=10). Six pt with severe deficiency underwent 7 minor procedures, 2 (29%) of which were associated with excess bleeding, despite rFVIIa treatment in both cases. An additional 3 procedures were performed with hemostatic agents and were uncomplicated. 2/16 (13%) pt with moderate deficiency had excess bleeding, 1 of whom was treated with rFVIIa and the other was not treated. Two others received perioperative treatment and did not have a complication. There were 7 complications in the 39 patients with mild deficiency (18%), including 1 AV fistula thrombosis after rFVIIa. Five of the patients with a bleeding complication did not receive treatment. One patient with mild deficiency received procoagulants and did not have excess bleeding. Conclusions -This is the largest series examining the perioperative management of pt with FX deficiency due to AL amyloidosis -Complications occurred in 11.3% of procedures, including one death -In this series, there were no clear predictors of bleeding -FX deficiency did not contribute to mortality, with the exception of 1 case -Bleeding risk is relatively infrequent in pt with mild or moderate FX deficiency, particularly with non-vascular procedures -Although optimal management of pt with severe FX deficiency is unclear, options include rhFVIIa +/− FFP and aminocaproic acid in those requiring procoagulant therapy.