Mayo Clinic Florida Research Articles

Coronavirus Disease 2019 Vaccine-Breakthrough Infections Requiring Hospitalization in Mayo Clinic Florida Through August 2021.

We characterized coronavirus disease 2019 (COVID-19) breakthrough cases admitted to a single center in Florida. With the emergence of delta variant, an increased number of hospitalizations was seen due to breakthrough infections. These patients were older and more likely to have comorbidities. Preventive measures should be maintained even after vaccination.

The role research gap years play in a successful dermatology match.

A new trend includes taking a dedicated year away from medical school to complete a research fellowship. There is minimal data on the benefit of a gap year. We aimed to identify if a gap year makes a dermatology applicant more successful in The Match. Dermatology applicants who applied to Mayo Clinic Arizona for the 2018-2019 application cycle and Mayo Clinic Rochester, Arizona, and Florida for the 2019-2020 application cycle were surveyed. In total, 291 dermatology applicants completed the initial survey, and 236 completed the follow-up survey. Ninety applicants took a gap year, 198 applicants did not. There was no significant difference in match rates. When comparing match rates at top dermatology residency programs, 40.6% of gap-year applicants matched to these residencies versus 19.0% of no gap-year applicants (P < 0.01). Applicants should weigh the opportunity costs before pursuing research gap years as they may not be universally helpful. Applicants who want to match at a top dermatology program may benefit from a research gap year. This data may have limited generalizability outside of the United States.

Investigation of the correlation between immature reticulocyte fraction and reticulocyte hemoglobin content with common tests for iron deficiency anemia

Abstract Reticulocyte hemoglobin content (Ret-He, the hemoglobin within reticulocytes or immature red blood cells) and immature reticulocyte fraction (IRF, the immature fraction of the absolute-reticulocyte-count) are tests that provide insight into erythropoiesis and iron status earlier than conventional iron studies offering the added benefit of not being acute-phase-reactants. Studies have shown that Ret-He is a diagnostic marker for iron-deficiency-anemia (IDA), but fewer studies have investigated IRF. Our laboratory is currently planning to report these parameters when reticulocyte is ordered. Since these are new parameters, we wanted to investigate their overall correlation with complete blood count (CBC) and other iron studies to gain a better appreciation of their utility in our patient population. The aim of this study was to compare the overall correlation of Ret-He and IRF with seven tests used in the evaluation of IDA. To our knowledge these parameters have not all been directly correlated within a single study. CBC and reticulocytes were quantified using XN 9000 hematology analyzers (Sysmex Corporation), ferritin (DXI 800, Beckman Coulter Inc.), and % iron-saturation (measured using total iron-binding-capacity (TIBC)=transferrin*1.18 on Cobas 6000, Roche Diagnostics). Two de-identified cohorts of patients undergoing physician-ordered reticulocyte testing were used for this analysis. Dataset 1 (DS1): (N=2026 from Mayo Clinic Florida) had Ret-He and IRF compared to absolute-reticulocyte-count (Ret), ferritin and % iron saturation. Dataset 2 (DS2): (N=3990 from Mayo Clinic Rochester) had Ret-He and IRF compared to the red-cell-indices of the CBC including hemoglobin (Hgb), mean-corpuscular-volume (MCV), mean-corpuscular-hemoglobin (MCH), and mean-corpuscular-hemoglobin-concentration (MCHC). Correlation coefficients were calculated using Spearman rank-order (ρ) wherein values below +/-0.39 are weak, between +/-0.40-0.59 are considered moderate, and values above +/-0.60 are considered strong. For DS1, Ret-He demonstrated the following correlations: Ret (ρ=0.01), ferritin (ρ=0.33), % iron saturation (ρ=0.63). IRF demonstrated: Ret (ρ=0.46), ferritin (ρ=-0.05), % iron saturation (ρ=-0.22). For DS2, Ret-He demonstrated the following correlations: Hgb (ρ=0.17), MCV (ρ=0.64), MCH (ρ=0.74), MCHC (ρ=0.56). IRF demonstrated Hgb (ρ=-0.41), MCV (ρ=0.10), MCH (ρ=0.04), MCHC (ρ=-0.11). Ret-He and IRF demonstrated different correlative profiles suggesting they may have differing uses. Ret-He was strongly positively-correlated with % iron saturation, MCV, MCH and moderately positively-correlated with MCHC. These positive-correlations are consistent with relationships established in the literature. Interestingly, Ret-He was only weakly correlated with ferritin, possibly owing to ferritin being an acute-phase-reactant. IRF had a moderate positive correlation with Ret and moderate inverse correlation with Hgb. Both of these IRF relationships are consistent with other reports, but both relationships have not been shown in the same study before, preventing direct comparison until now. The literature suggests IRF may have more potential in monitoring treatment than in diagnosis. One limitation of these datasets is their lack of clinical correlation such as established iron-deficiency, anemia status, or treatment information.

P40.18 Second Line Immunotherapy After Progression on a Different First Line Immunotherapy in Advanced Non-Small Cell Lung Cancer With Focus On Elderly

Background: Immune check point inhibitors (ICI) have become the standard of care in treatment of patients with advanced non-small cell lung cancer (NSCLC). After progression on first line ICI, 2nd line treatment with chemotherapy poses a challenge especially in elderly (age ≥70) or borderline performance status (ECOG ≥2) patients, as potential adverse effects could negatively impact quality of life. Current guidelines do not recommend switching to another immunotherapy after progression of disease (POD); however, there are some case series showing effectiveness of this strategy in select patients. We report here our experience in patients treated with a second line ICI after POD on first line ICI at Mayo Clinic, Florida, between 2016-2020, with focus on elderly and borderline performance status patients. A list of 153 NSCLC patients undergoing ICI therapy for advanced NSCLC was obtained from Mayo Clinic Florida database. A comprehensive chart review was conducted to identify patients who received a subsequent ICI therapy after progression on initial PD1-PDL1 inhibitor. Data collection included demographics, performance status, PDL1 status, overall survival (OS) ,progression free survival (PFS) and adverse events. 27 out of 153 patients were treated with a second ICI after the first ICI was stopped due to progression (25 pts) or due to adverse effects (2 pts). Among the 27 pts, 14 were elderly (≥70) and 11 had ECOG ≥2. All patients had advanced NSCLC with 22 of 27 patients having metastatic NSCLC. 15 patients were positive for PDL1 expression (>1%) while 9 patients had no PDL1 expression (<1%). Of the 27 patients, 22 were initially treated with a PD1 inhibitor (17 with pembrolizumab and 5 with nivolumab) and 5 were treated with a PDL1 inhibitor (durvalumab). After progression, therapy was switched as following: • 18 patients were switched from a PD1 inhibitor (pembrolizumab or nivolumab), to a PDL1 inhibitor (atezolizumab, durvalumab and tremelimumab, or avelumab) • 3 patients were switched from a PDL1 inhibitor (Durvalumab) to PD1 inhibitor (pembrolizumab). • 6 patients were switched to a different agent of the same class. The median overall survival in our population was 27.4 months. The median PFS on a second ICI was 4.3 months. Median PFS on a second ICI in elderly patients and those with ECOG ≥ 2 was 4.8 months and 3.6 months, respectively. Grade ≥3 adverse events were reported in 7 patients (26%) including one patient who had the drug discontinued due to grade 3 hepatitis. Specifically, in the elderly patients, grade ≥3 adverse events were reported in 21% of patients (3/14) while the same was reported in 27% of patients (3/11) with ECOG ≥2. In patients with advanced NSCLC and borderline performance status or age ≥70, treatment with 2nd line immunotherapy after progression on a different 1st line immunotherapy was well tolerated and led to a PFS that is comparable to standard 2nd line chemotherapy.

IBCL-085: Assessment of Fixed-Duration Therapies for Treatment-Naïve Waldenström Macroglobulinemia

Context Waldenstrom macroglobulinemia (WM) is a rare lymphoma for which scant comparative data exist to guide frontline therapy. Objective To compare the efficacy of the most frequently used rituximab-based fixed-duration anti-WM regimens in routine practice [rituximab, bendamustine (R-Benda); dexamethasone, rituximab, cyclophosphamide (DRC); and bortezomib, dexamethasone, rituximab (BDR)] to inform clinicians about the benefits/limitations of choosing one regimen over the other. Design A retrospective cohort study. Participants Patients with active WM seen at Mayo Clinic Rochester, Arizona, and Florida campuses between 10/01/2000 and 10/31/2019 who received R-Benda, DRC, or BDR as primary therapy were included. Outcomes Measures Overall response rate (ORR), event-free survival (EFS), progression-free survival (PFS), overall survival (OS), time-to-next therapy (TTNT) and treatment related adverse-effects (AEs) based on the three treatment regimens. The MYD88L265P mutation status was assessed using allele-specific polymerase-chain-reaction (sensitivity 1%). Response rates were assessed by Consensus Criteria. Time-to-event analyses were performed from the frontline therapy, using Kaplan-Meier method. CTCAE v4.03 was used to grade toxicities. Results The study included 220 patients with active WM who were treated with R-Benda (n=83), DRC (n=92) or BDR (n=45). The median follow-up was 4.5 (95% CI: 4-5) years. The R-Benda cohort demonstrated superior ORR (98%), in comparison to DRC (78%) or BDR (84%) cohorts, p=0.003. Similarly, longer PFS was evident with R-Benda use [median 5.2 versus 4.3 (DRC) and 1.8 years (BDR), p=0.0003]. The TTNT favored R-Benda [median, not-reached, versus 4.4 (DRC) and 2.6 years (BDR), p=0.0002]. These endpoints were comparable between the DRC and BDR cohorts. Overall survival (OS) was similar across the three cohorts, p=0.77. In a subset analysis of 142 patients genotyped for MYD88L265P mutation, the ORR, PFS and TTNT were unaffected by the MYD88 signature within each cohort. Toxicity profiles across the three groups were comparable, barring a higher incidence of neutropenia and neuropathy in patients who received R-Benda and BDR regimens, respectively. Conclusions The ORR, PFS and TTNT with R-Benda are superior compared to DRC or BDR in treatment-naive patients with active WM. The patient outcomes with any one of these three regimens are unaffected by the MYD88L265P mutation status.

The relationship between ventilatory function and cognitive and behavioral impairment in ALS

Objective: To study the association between ventilatory function and cognitive and behavioral impairment in ALS patients accounting for the effects of pertinent covariates. Methods: Four hundred and eighty-one patients were identified from the Mayo Clinic Florida ALS registry who had concurrent forced vital capacity (FVC) and cognitive and behavioral testing using the ALS Cognitive Behavioral Screen (ALS-CBS). Multiple linear regression analysis was used to study the effects of FVC and relevant covariates on the ALS-CBS cognition score, subscores, and caregiver behavioral inventory. Results: FVC was positively correlated to the cognitive and behavioral subscores on the ALS-CBS (p < 0.001), and the correlation was independent of the effects of site of ALS onset, age, and years of education. Conclusion: Cognitive and behavioral function may be adversely affected by ventilatory impairment in ALS. The presence of cognitive and behavioral impairment warrants a detailed assessment of ventilatory function.

Clinical features of autopsy-confirmed multiple system atrophy in the Mayo Clinic Florida brain bank

BackgroundMultiple system atrophy (MSA) presents with various combinations of autonomic dysfunction, parkinsonism, and cerebellar ataxia. Although clinical diagnostic criteria have been widely used, the sensitivity and specificity are suboptimal. This study aims to provide evidence supporting the revision of the current diagnostic criteria for MSA. MethodsMedical records of 171 patients with autopsy-confirmed MSA in the Mayo Clinic brain bank were reviewed with regard to their clinical features and diagnoses. Pathologic features, including concomitant pathologies (i.e., Alzheimer-related and Lewy-related pathologies), were also assessed. ResultsThe cohort included 133 MSA-parkinsonian type, 36 MSA-cerebellar type, and 2 unclassified MSA patients who did not show significant motor symptoms. Twenty-three patients (13%) were not clinically diagnosed with MSA, but instead with progressive supranuclear palsy, Parkinson's disease (PD), PD with dementia (PDD), or dementia with Lewy bodies (DLB). Three patients with PDD and DLB also had concomitant Lewy body pathology. Six patients had late-onset MSA, with an age of onset greater than 75 years. Erectile dysfunction was frequent in male patients (60/63; 95%) in all age ranges. REM sleep behavior disorder (RBD) was present in 82 patients (48%) and was the initial symptom in 13 patients. Cognitive impairment was present in 60 patients (35%), but was an initial symptom in only two patients. ConclusionsOur findings support the conclusion that late-onset presentation should not exclude MSA. The findings of this large autopsy-based cohort provides valuable insights for improving clinical criteria for MSA.

Utility of 24-hour ambulatory blood pressure monitoring in potential living kidney donors

IntroductionHypertension (HTN) is a risk factor for cardiovascular disease; therefore, it is imperative to risk stratify potential kidney donors during evaluation. Clinic blood pressure (CBP) measurement is inaccurate in assessing presence or absence of HTN. There is paucity of data about utility of 24-h ambulatory blood pressure monitoring (ABPM) during kidney donor evaluation.Methods24-h ABPM is performed on all kidney donors at Mayo Clinic Florida. We conducted retrospective review of 264 consecutive potential kidney donors from 1/1/2012 to 12/31/2017. Demographic, comorbid conditions, laboratory results and 24-h ABPM data were collected. Subjects were divided into two groups: Group1: Subjects with no prior history of HTN and new diagnosis of HTN using 24-h ABPM; Group 2: Subjects with no prior history of hypertension and normal BP on 24-h ABPM.ResultsBaseline demographic included mean age 46.40 years, 39% males, 78.4% Caucasians, and mean BMI was 26.94. Twenty one subjects (8.0%) had prior diagnosis of HTN. Among 243 subjects without prior HTN, 62 (25.5%) were newly diagnosed with HTN using 24-h ABPM. CBP was high only in 27 out of 62 (43.6%) of newly diagnosed HTN subjects. Thirty-five subjects (14.4%) had masked HTN and 14 subjects (5.8%) had white-coat HTN. Newly diagnosed hypertensive subjects were more likely to be males as compared to Group 2 (53.2% vs 34.3% P = 0.008). There was a trend of more non-Caucasians subjects (30.6% vs 19.9% P = 0.08) and more active smokers (17.7% vs 11.6%, P = 0.054) in Group1 as compared to Group 2. Only 17 (27.4%) out of 62 newly diagnosed hypertensive subjects were deemed suitable for kidney donation as compared to 105 (58.0%) out of 181 normotensive subjects (P < 0.001).ConclusionIn our cohort, use of ABPM resulted in new diagnosis of HTN in 1 out of 4 potential kidney donors. Newly diagnosed HTN was more common in men, those with non-Caucasian race, and in active smokers. There was a significantly reduced acceptance rate for kidney donation among newly diagnosed HTN subjects. Further studies are needed to determine the value of 24-h ABPM among these high risk groups.

Physician Satisfaction With Telemedicine During the COVID-19 Pandemic: The Mayo Clinic Florida Experience.

ObjectiveTo evaluate physician perceptions and attitudes toward telemedicine use at a tertiary care academic institution in northeast Florida during the coronavirus disease 2019 pandemic.Patients and MethodsAn anonymous 38-question cross-sectional survey was developed using Qualtrics survey software (Qualtrics) and e-mailed to all staff physicians from all specialty disciplines at Mayo Clinic in Florida. The survey was open from August 17, 2020, through September 1, 2020. Collected data included general demographic characteristics and employment information, attitude and experience with telemedicine use before and during the coronavirus disease 2019 pandemic, perception of patients’ experience, and the effect of telemedicine on burnout.ResultsThe survey was distributed to 529 eligible physicians at our institution, with 103 physicians responding (20%). The distribution of specialties was 22% primary care specialties, 41% other internal medicine subspecialties, and 18% surgical specialties. Collectively, 63% found comparable quality of care when provided virtually (vs in-person) whereas 80% perceived telemedicine as cost-effective. A total of 76% of physicians felt that telemedicine increased flexibility and control over patient care activities, with 36% reporting improved work-life balance and 30% reporting improved burnout symptoms. Overall, 42% preferred using telemedicine over in-person visits when possible.ConclusionPhysicians generally had positive attitudes regarding the adoption of telemedicine and perceived that the quality of health care delivery as generally comparable to in-person care. Future studies are needed to explore attitudes regarding telemedicine after the pandemic and how this virtual technology may be further used to improve physicians’ professional and personal well-being.

Molecular Epidemiology of Acute Myeloid Leukemia (AML): Novel Association of Clinical Epidemiologic Exposures with Unique Mutation Groups on Exome Sequencing of Leukemia DNA in the Mayo Clinic AML Epidemiology Cohort

Background: Clinical epidemiologic risk factors associated with leukemia development are prevalent, and can be identified in over 90% of AML patients. We previously demonstrated an association of clinical exposures with cytogenetic risk group and outcome after therapy, but the molecular impact of such exposures is unclear, and specifically it is not known whether specific epidemiologic exposures are associated with unique genetic lesions. We therefore performed Exome Sequencing in 98 patients from our clinical epidemiology cohort to determine whether there was an association of clinically relevant AML risk factors and exposures with unique deleterious non-synonymous (nonsyn.) mutations.Methods: The Mayo Clinic AML Epidemiology cohort comprises a highly annotated series of n=295 unselected and consecutive patients diagnosed and treated at Mayo Clinic Florida & Arizona [Cancer Epidemiol 39:1084, 2015]. We obtained AML DNA from remnant diagnostic cytogenetic pellets identified in 98 patients in the cohort, and performed Exome Sequencing [ExSeq] using standard techniques. The ~100 million paired-end 100bp reads from each sample were mapped to human genome build hg19 using BWA-MEM 1. The single nucleotide variants (SNVs) and small INDELs in the exome capture regions were identified using Mayo Clinic in-house developed analytic pipeline GenomeGPS 4.0.1 following Broad GATK 2 variant discovery best practices of alignment, realignment and recalibration, haplotype caller, and multi-sample joint genotyping. The variants passed the GATK's Variant Quality Score Recalibration (VQSR) quality control were kept. Since no patient matched normal were sequenced, SNVs and INDELs were filtered using both germline whole exome and whole genome sequencing of ~1200 Mayo Clinic Biobank samples and the public germline variant databases of 1000 genome project, 6500 individuals sequenced in the exome sequencing project (ESP), and HapMap phase 3. The remaining variants were annotated using ANNOVAR 3, and potential functional variants of non-synonymous, truncating, frame-shift, and splice-sites were used in the statistical association analyses. We evaluated the association of unique mutations occurring in 10 or more patients and in TP53, and also gene categories according to algorithm of Lindsley et al (Blood 125:1367, 2015) with relevant clinical and epidemiology exposures identified in our prior analysis. Risk factors and exposures were compared between patients with and without a mutation in different genes of interest using Fisher's exact test.Results: The read quality was excellent, and results from 97 evaluable samples were included in analysis. Results are noted in Table. We found a strong and significant association of prior history of immunosuppressive therapy (IST) or solid organ transplantation (SOT) with RUNX1 mutation (p=0.0001), and of regular Statin use with ASXL1 mutation (p=0.008). Statin use was also associated with mutations in genes involved in DNA methylation (p=0.036) and in Chromatin Modifier genes (p=0.049). We identified a novel inverse association of obesity - the most prevalent AML risk factor - with spliceosome mutation (p=0.010), and of IST/SOT with mutations in Myeloid Transcription Factors (TF, p=0.015) and Activated Signaling pathways [RAS, FLT3, KIT, CBL, NF1] (p=0.026). We confirm the association of secondary AML [sAML] with spliceosome mutation (p=0.018), observed as expected most strongly for Antecedent Hematologic Disorder (p=0.008, not shown). Other borderline associations (p≤0.10) are noted in Table. We did not identify any association of family history [FHx] of hematologic malignancy or of smoking [TOB] with unique mutations, nor did we identify clinical exposures associated with TP53 mutation.Conclusion: For the first time (apart from sAML) we have identified a unique leukemia genotype associated with some common clinical and epidemiologic exposures. Some mutations groups (Cohesin, TP53) were not associated with any clinical exposures, suggesting alternate mechanisms of leukemogenesis. ExSeq was for the first time successfully performed on archived diagnostic cytogenetic cell pellets, we believe a novel source of leukemia DNA. These results will guide a planned prospective study to determine frequency and mechanism of leukemogenesis after exposures, and development of strategies for prediction of leukemia risk and ultimately prevention. [Display omitted] DisclosuresCerhan:Janssen: Other: Scientific Advisory Board (REMICADELYM4001); Janssen: Other: Multiple Myeloma Registry Steering .

Acute Lymphoblastic Leukemia/Lymphoma in the Elderly: The Mayo Clinic Experience

IntroductionElderly patients (≥60 years of age) with acute lymphoblastic leukemia/lymphoma (ALL) have a poor prognosis compared to younger adults. This is thought to be due to comorbidities, treatment-related mortality, adverse disease biology, low rates of complete remission (CR), high risk of relapse, and ineligibility for allogeneic hematopoietic stem cell transplantation (HSCT). Since it is unclear how all these factors play into the poor prognosis of elderly ALL, we sought to describe the presentation, treatment outcomes, and predictors of survival at our multi-site institution.MethodsAfter IRB approval, we performed a retrospective study of patients (pts) ≥60 years old diagnosed with ALL from 2000-2017 at Mayo Clinic Rochester, Arizona, and Florida. Statistical analysis was performed using JMP 10.0 software.ResultsBaseline characteristicsWe identified 124 consecutive pts with elderly ALL. The median age at time of diagnosis was 67 (60-86) and 74 (60%) were male. Median time of follow-up was 15.6 months (range 0.2-132). 77 (62%) were deceased at the time of last follow-up: 37 deaths related to disease, 24 due to infection or other causes, and 16 unknown.At time of diagnosis, 108 (87%) pts had B-cell ALL, of which 40 (37%) were Philadelphia chromosome positive (Ph+). Only 16 (13%) pts had T-cell ALL. Overall, 24 (19%) had an ECOG performance status (PS) ≥2, and 22 (18%) had a Charlson Comorbidity Index (CCI) ≥3. Further baseline characteristics including cytogenetics and FISH studies are detailed in Table 1.Treatment and Outcomes102/124 (82%) elected to undergo induction. Of these, 19 (19%) had an up-front dose reduction. The most common induction regimen was Hyper-CVAD, which was used in 62 (61%), concomitantly with rituximab in 21, and tyrosine kinase inhibitors (TKIs) in 17. Asparaginase-based chemotherapy was used in 27 (26%) pts. The remaining 13 (13%) received other regimens. Complete remission (CR/CRi) was achieved in 92 (90%) pts. 11 (11%) had primary refractory disease, of which 7 were refractory to multiple lines of therapy. Median time to CR was 30 days (range 10-352), requiring a median of 1 cycle (range 1-8) of chemotherapy. 5 (5%) died within 60 days of starting treatment, and by Day 100 there were a total of 10 (10%) deaths; these were related to subdural hematoma (3), infection (2), treatment discontinuation (1), and unknown causes (4).Palliative therapy up-front was chosen in 22/124 (18%), which included chemotherapy (e.g. vincristine and steroids), TKIs or hospice. 7 (32%) of these pts achieved CR within a median time of 54 days (range 23-128). The median overall survival (mOS) in the palliative group was 5.7 months (interquartile range [IQR] 1.7-12.1).Relapse occurred in 42 (42%) pts within a median time of 9.9 months (range 0-71.5); 10 (24%) of these pts had an extramedullary relapse, including 3 with CNS leukemia. 31 (74%) were treated with salvage chemotherapy, while 10 (21%) chose palliative care. Median survival from the time of relapse was 5.7 months (IQR 2-18).Overall, 34 (27%) underwent HSCT: allogeneic HSCT in 33, and autologous HSCT in 1. Of these, 29 (85%) were in CR1, and 5 (15%) were in CR2. The median age at time of HSCT was 65 (range 60-73). 3 (9%) died within 100 days of HSCT, due to early relapse (2; both were in CR1) and acute graft-versus-host disease (1). 11 (31%) relapsed after HSCT, within a median time of 9 months (range 1-30). Median survival after HSCT was 27.4 months (IQR 0.7-not reached [NR]).Predictors of SurvivalElderly ALL across the three Mayo Clinic campuses had a mOS of 20.8 months (IQR 9.4-87.3), which was inferior compared to our adult ALL (age 18-59) cohort in Rochester, who had a mOS of 51.1 months (IQR 15.3-NR) (Figure 1). In univariate analysis, which included the presenting variables shown in Table 1, only age, ECOG PS, CCI, and LDH negatively influenced survival (P <0.05). These factors continued to significantly predict for poor survival in multivariate analysis (Table 2).ConclusionsALL has worse outcomes in elderly pts compared to younger adults. However, treatment-related mortality was relatively low in our cohort even though the majority of pts underwent induction. Interestingly, we found that survival was influenced by age, ECOG PS, CCI, and LDH at time of diagnosis, rather than by cytogenetics or other biological features. Our data needs to be verified in a larger cohort. Nevertheless, this could be the first step toward a prognostic model in elderly ALL. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Therapy-Related Acute Lymphoblastic Leukemia/Lymphoma in the Elderly

IntroductionTherapy-related ALL (t-ALL) is a rare entity. It was recently estimated to occur in about 4.7%-6.9% of adult ALL cases and has been associated with a worse prognosis(Aldoss et al ., 2017; Abdulwahab et al ., 2012). However, these studies included very few patients over the age of 60. Since t-ALL specifically in the elderly has never been described, we sought to characterize its clinical features and treatment outcomes.MethodsAfter IRB approval, we performed a retrospective study of patients (pts) ≥60 years old diagnosed with ALL from 2000-2017 at Mayo Clinic Rochester, Arizona, and Florida. We included pts who received known leukemogenic chemotherapy prior to being diagnosed with ALL. We excluded pts with malignancies who were not exposed to leukemogenic chemotherapy. We also excluded pts diagnosed with chronic myeloid leukemia (CML) with blast crisis. Moreover, we excluded pts treated with radiation therapy other than to the whole pelvic region. Statistical analysis was performed using JMP 10.0 software.ResultsBaseline characteristicsOut of 124 consecutive pts with elderly ALL, we identified 20 (16%) pts who fit our inclusion criteria. 16 (80%) were female. The median latent time to developing ALL was 9.25 years (range 0.26-28.67). The median time of follow-up was 12.6 months (range 0.9-63.2). 11 (55%) were deceased at the time of follow-up: 3 deaths related to disease, 6 from infection or other causes, and 2 unknown.Of the 20 pts with t-ALL, 13 (65%) had been treated for hematological malignancies prior to ALL, which included multiple myeloma (3), acute myeloid leukemia in remission (2), diffuse large B-cell lymphoma (2), myelofibrosis (2), myelodysplastic syndrome (1), MALT lymphoma (1), hairy cell leukemia (1), chronic lymphocytic leukemia (1), and light-chain (AL) amyloidosis (1). Additionally, 6 pts had prior treatment for breast cancer; 1 of these was the pt who also had AL amyloidosis. Finally, 1 pt had a history of receiving cyclophosphamide for bronchiolitis obliterans with organizing pneumonia and myositis.Median age at time of ALL diagnosis was 67 (60-82). 19 (95%) had B-cell ALL, of which 5 (26%) were positive for the Philadelphia chromosome. Only 1 (5%) pt had T-cell ALL.Cytogenetics and FISH studies18 pts had available cytogenetic data at time of diagnosis. 8 (44%) had complex cytogenetics (≥5 abnormalities), 7 (39%) had a monosomal karyotype, 4 (22%) were hyperdiploid, 2 (11%) were hypodiploid, 1 (6%) was a mixture of hyper- and hypo-diploid. Furthermore, FISH analysis was available in 10 pts: 3 had CDKN2A deletion, 2 had a duplication of 1q, 2 had a TCF3-PBX1 translocation, 1 had a MLL rearrangement, and 1 had a deletion of IKZF1 .Treatment and Outcomes15/20 (75%) underwent induction chemotherapy. 6 of them received Hyper-CVAD. The other 9 received various regimens, including asparaginase-based chemotherapy in 6 (67%). 13 (87%) had a complete remission (CR/CRi), within a median time of 32 days (range 19-128). 1 (7%) had primary refractory disease. The other 5 (25%) pts chose palliative treatment up-front; this included chemotherapy (e.g. vincristine and steroids), tyrosine kinase inhibitors, or hospice. 3 (60%) of these pts got into CR.Of the 16 total pts who achieved CR, 5 (31%) relapsed within a median time of 20.67 months (range 9-22.3). All of them were treated with salvage chemotherapy. Median survival after relapse was 4.8 months (range 0.1-42.2). Overall, 7/20 (35%) underwent allogeneic HSCT; all were in CR1. Median survival after HSCT was not reached (IQR 7.6-NR). Only 2 (29%) relapsed after HSCT within a median time of 6.4 months (range 3.1-9.6).The median overall survival (mOS) in patients with t-ALL was 13.83 months (interquartile range [IQR] 11.73-not reached), which was not significantly different (P=0.9935) from elderly patients without t-ALL, who had a mOS of 20.93 months (IQR 8.73-56.63) (Figure 1).ConclusionsTherapy-related ALL (t-ALL) seems to be relatively more common in the elderly compared to younger adults, with an incidence of 16% in our elderly ALL cohort. Almost all cases were B-cell ALL. In addition, MLL rearrangements appeared to be less frequent in our elderly cohort (7%), in contrast to what has been reported in younger adults (25-35%). Moreover, the overall survival in elderly t-ALL was not significantly different compared to elderly ALL. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Pre-diagnosis major life stressors and breast cancer outcomes.

While the association between diagnosis of breast cancer and post-diagnosis psychological distress has been well documented, data regarding pre-diagnosis psychological distress in the breast cancer population are limited. Here, we assessed pre-diagnosis major life stressors and breast cancer outcomes, namely stage of disease and choice of surgery, in a single-center population. Patients with newly diagnosed clinical stage 0-3 breast cancer seen at Mayo Clinic Florida between June 11, 2018, and October 7, 2019, were administered voluntary telephone surveys to assess major life stressors during the 24months preceding their cancer diagnosis. Subsequent clinical outcomes of cancer stage at diagnosis and surgical treatment were obtained through retrospective chart review. Study subjects who had experienced major life stressors and those who had not were compared using Chi-square tests. Of 222 patients who were included, 51.3% reported experiencing a major life event before breast cancer diagnosis. 43.9% of these patients endorsed family-related stress. 21.1% had experienced multiple stressors. 1.8% described financial stress. Although more patients in the group with pre-diagnosis stress had carcinoma in situ (21.1% versus 13.0%, p = 0.11) and fewer had stage T1/T2 disease (64% versus 73.1%, p = 0.14) than in the group without stress, these differences were not statistically significant. More patients with pre-diagnosis stress chose mastectomy (34.2% versus 22.2%, p = 0.048). Psychological distress is prevalent prior to breast cancer diagnosis and may merit early intervention. While additional study in diverse populations is needed, current data suggest possible associations between pre-diagnosis psychological distress and surgical decision making, specifically mastectomy.

Abstract PS9-46: Pre-diagnosis major life stressors and breast cancer outcomes

Abstract Background: Multiple studies have identified an association between diagnosis of breast cancer and post-diagnosis psychological distress. Some have taken a step further, identifying predictive markers of distress in diagnosed patients and interventions to minimize post-diagnosis distress. Data regarding pre-diagnosis psychological distress and its impact on surgical decision making and clinical outcomes in the breast cancer population are limited. Here, we assessed pre-diagnosis major life stressors and breast cancer outcomes in a single-center population. Methods: Patients with newly diagnosed stage 0-3 breast cancer seen at Mayo Clinic Florida between June 11, 2018, and October 7, 2019, were included. Prior to their initial visit, patients were administered a voluntary telephone survey regarding the incidence of major life events and stressors during the 18 months preceding their diagnosis. Demographic data including age and ethnicity were also included. Subsequent clinical outcomes were obtained through retrospective chart review. Clinical outcomes were assessed with descriptive statistics. Chi-square tests were used to compare subgroups, with p &amp;lt; 0.05 considered statistically significant. Results: Of 469 patients seen for a new breast cancer diagnosis, 222 patients completed the intake survey and met inclusion criteria. Median age was 60 (27-84) years. 80.6% of patients were white, 7.7% were black, 5.4% were Asian/Pacific Islander, and 2.3% were Latino. Over 95% endorsed having some form of social support. 51.3% reported experiencing a major life event prior to breast cancer diagnosis. Of these patients (n = 114), 43.9% denoted this stressor as family-related, as compared to 20.2% citing non-breast cancer illness, 14.9% claiming relationship stress, and 14% describing employment-related stress. Only 1.8% endorsed stress caused by financial concerns. Multiple major life events were reported by 10.8% of all included patients. Subgroup analysis of the patients with pre-diagnosis stress revealed a similar demographic distribution to the overall sample. Compared to the subgroup without pre-diagnosis stress (n = 108), there were more patients with carcinoma in situ and stage T3/T4 disease (21.1% versus 13.0%, p = 0.11) and 11.4% versus 10.2%, p = 0.77), respectively) in the subgroup with pre-diagnosis stress, although these differences were not statistically significant. More patients with pre-diagnosis stress elected to undergo mastectomy (34.2% versus 22.2%, p = 0.048) as compared to the group without stress. Conclusions: With over half of sample patients reporting pre-diagnosis major life stressors, psychological distress is prevalent prior to breast cancer diagnosis and should be considered as a factor for early intervention, such as psychological and financial counseling, during breast cancer evaluation. The sample population was predominantly white and resource-rich in terms of financial and social support, highlighting a need for characterization of pre-diagnosis psychological distress in more ethnically diverse and/or resource-limited settings. Although additional study is recommended, current data suggest possible associations between pre-diagnosis psychological distress and treatment decision making, particularly the decision to pursue mastectomy. Citation Format: Tanmayi Pai, Laura Vallow, Danushka Seneviratne, Dawn Mussallem, Lauren Cornell. Pre-diagnosis major life stressors and breast cancer outcomes [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS9-46.

Association of Mitochondrial DNA Genomic Variation With Risk of Pick Disease.

To determine whether stable polymorphisms that define mitochondrial haplogroups in mitochondrial DNA (mtDNA) are associated with Pick disease risk, we genotyped 52 pathologically confirmed cases of Pick disease and 910 neurologically healthy controls and performed case-control association analysis. Fifty-two pathologically confirmed cases of Pick disease from Mayo Clinic Florida (n = 38) and the University of Pennsylvania (n = 14) and 910 neurologically healthy controls collected from Mayo Clinic Florida were genotyped for unique mtDNA haplogroup-defining variants. Mitochondrial haplogroups were determined, and in a case-control analysis, associations of mtDNA haplogroups with risk of Pick disease were evaluated with logistic regression models that were adjusted for age and sex. No individual mtDNA haplogroups or superhaplogroups were significantly associated with risk of Pick disease after adjustment for multiple testing (p < 0.0021, considered significant). However, nominally significant (p < 0.05) associations toward an increased risk of Pick disease were observed for mtDNA haplogroup W (5.8% cases vs 1.6% controls, odds ratio [OR] 4.78, p = 0.020) and subhaplogroup H4 (5.8% cases vs 1.2% controls, OR 4.82, p = 0.021). Our findings indicate that mtDNA variation is not a disease driver but may influence disease susceptibility. Ongoing genetic assessments in larger cohorts of Pick disease are currently underway.

Sequential Protocol Biopsies Post-Liver Transplant From Donors With Moderate Macrosteatosis: What Happens to the Fat?

The number of steatotic deceased donor livers encountered has continued to rise as a result of the obesity epidemic. Little is known about the histological characteristics of moderately macrosteatotic livers over time in the recipient following liver transplantation (LT). All recipients undergoing LT at Mayo Clinic Florida with donor livers with moderate macrosteatosis (30%‐60%) from 2000‐2017 were identified (n = 96). Routine protocol liver biopsies were performed 1‐week and 6‐months following LT. All liver donor and protocol biopsies were read by an experienced liver pathologist. Of the 96 moderate macrosteatosis LTs, 70 recipients had post‐LT protocol liver biopsies available and comprised the study cohort. Median donor allograft macrosteatosis at the time of transplant was 33% (IQR, 30%‐40%) compared with 0% (IQR, 0%‐2%) at 1‐week ( P < 0.001) and 0% (IQR, 0%‐0%) at 6‐months ( P < 0.001) following LT. Biopsies at 1‐week post‐LT displayed pericentral necrosis in 57.1% of recipients and lipopeliosis in 34.3% of recipients. In the 6‐month post‐LT biopsies, cholestasis was seen in 3 (4.3%) of the recipients, whereas grade 2 fibrosis was seen in 6 recipients (8.6%). Graft survival at 5 years in the present cohort was 74.0%. Moderate macrosteatosis (30%‐60%) in the donor allograft demonstrates complete reversal on liver biopsies performed as early as 7 days following LT and remains absent at 6‐months following LT. Both pericentral necrosis and lipopeliosis are common features on day 7 biopsies. Despite these encouraging findings, the perioperative risks of using these livers (postreperfusion cardiac arrest and primary nonfunction) should not be understated. Long‐term graft survival is acceptable in patients who are able to overcome the immediate perioperative risk of using moderately steatotic donor livers.

Impact on urinary oxalate levels with use of ezetimibe.

BackgroundCalcium oxalate stones are the most common cause of nephrolithiasis in the United States. Smaller studies of <15 patients investigating ezetimibe, a selective cholesterol absorption inhibitor, have suggested increased urine oxalate levels with use of the drug. We attempt to better define this relationship of ezetimibe on urinary oxalate using a larger patient sample analysing multiple urine collections on and off treatment.Materials and MethodsWe retrospectively reviewed all consecutive patients from 01/2018 through 04/2019 evaluated for nephrolithiasis with use of ezetimibe documented in their medical record at Mayo Clinic Florida. Primary outcomes included increase in urinary oxalate with use of ezetimibe and reduction in urinary oxalate with discontinuation of medication.ResultsOf 57 reviewed patients, 30 (53%) met inclusion criteria yielding 117 24‐h urine measurements either on ezetimibe (72 measurements) or off ezetimibe (41 measurements). The mean urinary oxalate level off ezetimibe was 39.86 mg versus 40.45 mg with ezetimibe. After adjusting for age and sex, the estimated difference was 1.239 mg (95% CI, −4.856 to 7.335 mg; p = 0.93). A subset of six patients with urinary oxalate values both on and off ezetimibe showed a difference in 24‐h urinary oxalate levels ranged from −16.40 to 14.95 mg (mean difference = 0.93 mg; median difference = 3.84 mg).ConclusionUse of ezetimibe does not provide clear evidence of a difference in urinary oxalate levels.

V.I.T.A.M. in COVID 19: A Systematic Approach to a Global Pandemic.

IntroductionIn the unprecedented era of COVID-19, ongoing research and evolution of evidence has led to ever-changing guidelines for clinical monitoring and therapeutic options. Formulating treatment protocols requires the understanding and application of the evolving research.ObjectiveThe primary objective of this study is to present a systematic evidence-based approach to synthesize the necessary data in order to optimize the management of COVID-19.MethodsAt Mayo Clinic Florida, we developed a multidisciplinary centralized COVID Treatment Review Panel (TRP) of expert pulmonologists, intensivists, infectious disease specialists, anesthesiologists, hematologists, rheumatologists, and hospitalists that in real-time reviews the latest evidence in peer-reviewed journals, the available clinical trials, and help guide the rapid application of therapeutics or interventions to the patient and the bedside provider.Results/ConclusionsThe multi-disciplinary team approach of synthesizing clinical data and coordinating care is effective in responding to rapidly evolving and changing evidence. Systematic data collection and evidence-based treatment algorithms enable physicians to rapidly translate the current literature to clinical practice, and improve care and outcomes of patients.

570. “I don’t know”: The Typical Response When Taking Pneumococcal Immunization Histories in Kidney Transplant Candidates

BackgroundVaccine-preventable diseases account for significant morbidity and mortality in the kidney transplant (KT) patient population. AST Guidelines support review and documentation of pneumococcal vaccines in KT candidate infectious disease (ID) evaluations. The objective of this study is to determine the number of KT candidates screened for prior pneumococcal immunizations and the frequency of vaccines ordered by providers when indicated at Mayo Clinic Florida’s (MCF) Transplant Center.MethodsThis study was an institution-based retrospective analysis of all KT candidates evaluated at MCF from December 2, 2019 – January 14, 2020. Data collection was obtained by electronic health record review. Outcomes included known history and documentation rates of prior pneumococcal vaccinations (both Prevnar 13 and Pneumovax 23) by infectious disease (ID) providers, as well as pneumococcal vaccine order frequency during ID pre-transplant evaluation when indicated. Data analysis was done using simple descriptive statistics.ResultsSixty-one patients underwent KT evaluation during the study period. Among the 61 patients, 20 (32.8%) and 20 (32.8%) had a known prior history of receiving Prevnar 13 and Pneumovax 23 vaccinations, respectively. Vaccine history was unknown for Prevnar 13 and Pneumovax 23 in 39 (63.9%) patients. Vaccine status was not documented by ID providers in 2 (3.3%) patients. When appropriate, ID providers ordered Prevnar 13 and Pneumovax 23 in 38 (92.7%) and 41 (100%) patients, respectively. Orders included both electronic and written documentation to account for patients planning immunization elsewhere. Of the 38 patients advised to receive the Prevnar 13 vaccine, 17 (41.5%) patients were documented completing immunization. Pneumovax 23 order completion rates were not recorded since the study period only lasted six weeks due to closure by COVID-19.Table 1. Pneumococcal Vaccine History Documentation Rates Obtained by Patient Recall or Records Table 2. Pneumococcal Vaccine Order Rates at Pre-Kidney Transplant Consultations Table 3. Prevnar 13 Order Completion Rate by Documentation ConclusionThe data reflect a high number of patients who either do not recall or have documentation of prior pneumococcal vaccination available at time of KT ID evaluation. Providers documented history of pneumococcal vaccinations extremely well, ordering immunizations when necessary. This study highlights lack of portability of immunization histories in a given patient population and opportunity for improved care.Disclosures Claudia R. Libertin, MD, Pfizer, Inc. (Grant/Research Support, Research Grant or Support)

317. Case Series of Echinococcus Infections at Mayo Clinic Florida

BackgroundEchinococcus multilocularis is a destructive zoonotic cestode with low human incidence. Hydatid disease classically presents with hepatic or lung involvement with infrequent extrahepatic bone destruction. Diagnosis is challenging due to its latency and mimicry.Fig.1: Case 1 - X-ray imaging of the pelvis shows osseous destruction of the iliac crest secondary to known osteomyelitis status post left ilium debridement. Fig.2: Case 1 - Magnetic resonance imaging demonstrates extensive osteomyelitis throughout left ilium. Stable scattered focal fluid collections seen throughout the left lower quadrant. MethodsCASE 1: A 57 year-old Albanian male with diabetes, latent TB, and left iliac lytic lesion presented with 4 weeks of left flank pain and was treated with 6 weeks of IV Ceftriaxone and Flagyl. 2 years later he returned with flank pain and purulent lumbar drainage. Hip x-ray suggested chronic osteomyelitis, with left psoas fluid collections on CT. Bartonella, Q fever, Brucella, HIV, AFB and fungal serologies were negative. Hemipelvis debridement revealed structures concerning for hydatid disease. Echinococcus IgG was equivocal. Histopathology was consistent with Echinococcus multilocularis species, and albendazole was started. On follow-up, he presented with left hip tenderness and toe extensor weakness. Labs showed mild leukocytosis. CT revealed progressive destruction of the left iliac with sacroiliac extension concerning for abscess.CASE 2: A 36 year-old female presented with lung and liver cysts, progressive dyspnea, and non-productive cough. She lived in Africa, Asia, and Europe and consumed local street food and unpasteurized milk. Hobbies included spelunking and swimming in freshwater lakes. She had exposure to stray animals, but denied bites or scratches. Over 4 years dyspnea progressed to orthopnea. MR abdomen revealed a 10x6x12cm liver cyst and chest CT showed 2 fluid-attenuating lesions in the LLL and RLL, measuring 4.9 x 6.0 cm and 6.8 x 4.3 cm respectively. Echinococcus, Bartonella, Q fever, Brucella, HIV, AFB and fungal serologies were negative. Schistosomiasis serology was equivocal.Fig. 3: Case 2 - MRI abdomen demonstrating 10x6x12cm liver cyst Fig. 4: Case 2 - Chest CT showed 2 dominant fluid attenuating lesions within the LLL and RLL. The larger lesion in RLL measures 6.8 x 4.3 cm. The left lower lobe lesion measures 4.9 x 6.0 cm. ResultsPatient 1 underwent type I hemipelvectomy. Patient 2 underwent pulmonary segmentectomy and liver lobectomy. Both were continued on albendazole.Fig. 5: Case 1 - Photo taken during debridement of left ileac and hip. Note presence of white cysts discovered intraoperatively. Fig. 6: Case 1 - Histopathologic slides (H&E stain) demonstrating hooks and scolices consistent with Echinococcus multilocularis. A. Hooklet (100x magnification). B. Hydatid cyst with black-staining structures suggestive of degenerating hooklets. C. Zoomed detail of cyst wall. D. Degenerating hydatid cyst and hooklets. ConclusionEquivocal IgG serology does not exclude infection. History and clinical presentation are key to diagnosis, but histopathology remains the gold standard. Hydatid bone infection progresses insidiously and frequently recurs, depending upon excision and debridement. Finally, echinococcosis demands aggressive long-term therapy and surveillance.Disclosures Claudia R. Libertin, MD, Pfizer, Inc. (Grant/Research Support, Research Grant or Support)