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Shanafelt, Tait D.

https://orcid.org/0000-0002-7106-5202

Mayo Clinic

Stanford Cancer Institute

Citations 372

Occupational Characteristics Associated with Professional Fulfillment and Burnout Among U.S. Physiatrists
Trockel, Mickey , Kinney, Carolyn L. , Sliwa, James A. , Knowlton, Tiffany, Stautzenbach, Tom, Shanafelt, Tait D. , Makowski, Maryam S , Verduzco-Gutierrez, Monica , Kinney, Carolyn , Sliwa, James , Shanafelt, Tait D , Paganoni, Sabrina , Weinstein, Stuart L. , Verduzco‐Gutierrez, Monica , Kennedy, David J. , Wang, Hanhan

PM&R | February 16, 2023 | Volume: 15 | Issue: 5 | Pages: 541-551

10.1002/pmrj.12961 Get It

AbstractIntroductionMultiple national studies suggest that, among physicians, physiatrists are at increased risk for occupational burnout.ObjectiveTo identify characteristics of the work environment associated with professional fulfillment and burnout among U.S. physiatrists.DesignBetween May and December 2021, a mixed qualitative and quantitative approach was used to identify factors contributing to professional fulfillment and burnout in physiatrists.SettingOnline interviews, focus groups, and survey.ParticipantsPhysiatrists in the AAPM&R Membership Masterfile.Main Outcome MeasuresBurnout and professional fulfillment assessed using the Stanford Professional Fulfillment Index.ResultsIndividual interviews with 21 physiatrists were conducted to identify domains that contributed to professional fulfillment followed by focus groups for further definition. Based on themes identified, scales were identified or developed to evaluate: control over schedule (6 items; Cronbach's alpha = 0.86); integration of physiatry into patient care (3 items; Cronbach's alpha = 0.71); personal‐organizational values alignment (3 items; Cronbach's alpha = 0.90); meaningfulness of physiatrist clinical work (6 items; Cronbach's alpha = 0.90); teamwork and collaboration (3 items; Cronbach's alpha = 0.89). Of 5760 physiatrists contacted in the subsequent national survey, 882 (15.4%) returned surveys (median age 52 years; 46.1% women). Overall, 42.6% (336 of 788) experienced burnout and 30.6% (244 of 798) had high levels of professional fulfillment. In multivariable analysis, each one‐point improvement in control over schedule (odds ratio [OR] = 1.96; 95% confidence interval [CI] = 1.45–2.69), integration of physiatry into patient care (OR = 1.77; 95% CI = 1.32–2.38), personal‐organizational values alignment (OR = 1.92; 95% CI = 1.48–2.52), meaningfulness of physiatrist clinical work (OR = 2.79; 95% CI = 1.71–4.71) and teamwork and collaboration score (OR = 2.11; 95% CI = 1.48–3.03) was independently associated with higher likelihood of professional fulfillment.ConclusionsControl over schedule, optimal integration of physiatry into clinical care, personal‐organizational values alignment, teamwork, and meaningfulness of physiatrist clinical work are strong and independent drivers of occupational well‐being in U.S. physiatrists. Variation in these domains by practice setting and subspecialty suggests tailored approaches are needed to promote professional fulfillment and reduce burnout among U.S. physiatrists.
Progression and survival of MBL: a screening study of 10 139 individuals
Slager, Susan L. , Parikh, Sameer A. , Achenbach, Sara J., Rabe, Kari G. , Boddicker, Nicholas , Kleinstern, Geffen , Lesnick, Connie , Call, Timothy G. , Vachon, Celine M. , Braggio, Esteban , Hanson, Curtis A. , Shanafelt, Tait D. , Chaffee, Kari G. , Boddicker, Nicholas J , Lesnick, Connie E, Cerhan, James R , Vachon, Celine M. , Kay, Neil E , Braggio, Esteban , Parikh, Sameer A , Shanafelt, Tait D , Slager, Susan L , Norman, Aaron D. , Olson, Janet E. , Cerhan, James R. , Kay, Neil E.

Blood | August 15, 2022 | Volume: 140 | Issue: 15 | Pages: 1702-1709

10.1182/blood.2022016279 Get It

Abstract Monoclonal B-cell lymphocytosis (MBL) is a common hematological premalignant condition that is understudied in screening cohorts. MBL can be classified into low-count (LC) and high-count (HC) types based on the size of the B-cell clone. Using the Mayo Clinic Biobank, we screened for MBL and evaluated its association with future hematologic malignancy and overall survival (OS). We had a two-stage study design including discovery and validation cohorts. We screened for MBL using an eight-color flow-cytometry assay. Medical records were abstracted for hematological cancers and death. We used Cox regression to evaluate associations and estimate hazard ratios and 95% confidence intervals (CIs), adjusting for age and sex. We identified 1712 (17%) individuals with MBL (95% LC-MBL), and the median follow-up time for OS was 34.4 months with 621 individuals who died. We did not observe an association with OS among individuals with LC-MBL (P = .78) but did among HC-MBL (hazard ratio, 1.8; 95% CI, 1.1-3.1; P = .03). Among the discovery cohort with a median of 10.0 years follow-up, 31 individuals developed hematological cancers with two-thirds being lymphoid malignancies. MBL was associated with 3.6-fold risk of hematological cancer compared to controls (95% CI, 1.7-7.7; P < .001) and 7.7-fold increased risk for lymphoid malignancies (95% CI:3.1-19.2; P < .001). LC-MBL was associated with 4.3-fold risk of lymphoid malignancies (95% CI, 1.4-12.7; P = .009); HC-MBL had a 74-fold increased risk (95% CI, 22-246; P < .001). In this large screening cohort, we observed similar survival among individuals with and without LC-MBL, yet individuals with LC-MBL have a fourfold increased risk of lymphoid malignancies. Accumulating evidence indicates that there are clinical consequences to LC-MBL, a condition that affects 8 to 10 million adults in the United States.
PB1878: CROSS-TRIAL ANALYSIS OF FIXED-DURATION IBRUTINIB (I) PLUS VENETOCLAX (V) VS FLUDARABINE (F), CYCLOPHOSPHAMIDE (C), AND RITUXIMAB (R) AS FIRST-LINE TREATMENT FOR CHRONIC LYMPHOCYTIC LEUKEMIA (CLL)
Mato, Anthony R. , Moreno, Carol , Szafer‐Glusman, Edith , Zhou, Cathy , Neumayr, Lynne , Krigsfeld, Gabriel , Barrientos, Jacqueline C. , Barr, Paul M. , Tam, Constantine S. , Ghia, Paolo , Kay, Neil E. , Siddiqi, Tanya , Wierda, William G. , Shanafelt, Tait D.

HemaSphere | June 24, 2022 | Volume: 6 | Issue: No issue available | Pages: 1758-1759

10.1097/01.hs9.0000850364.78915.d9 Get It

Abstract 5256: Incidence of squamous cell carcinoma (SCC) in a large screening cohort of monoclonal B-cell lymphocytosis (MBL)
Ansari, Ahmed Nadeem, Achenbach, Sara J., Kleinstern, Geffen , Lesnick, Connie , Call, Timothy G., Vachon, Celine M. , Hanson, Curtis A. , Baum, Christian L. , Parikh, Sameer A. , Norman, Aaron D. , Rabe, Kari G. , Olson, Janet E. , Cerhan, James R. , Kay, Neil E. , Vachon, Celine M. , Braggio, Esteban , Shanafelt, Tait D. , Slager, Susan L.

Cancer Research | June 15, 2022 | Volume: 82 | Issue: 12_Supplement | Pages: 5256-5256

10.1158/1538-7445.am2022-5256 Get It

Abstract MBL is a common pre-malignant condition characterized by circulating clonal B-cells with an absolute B-cell count <5x109/L and no lymphadenopathy, organomegaly, or cytopenias. MBL is the precursor to CLL. The incidence of cutaneous SCC in CLL is significantly higher compared to controls. The incidence of SCC in MBLs has not yet been determined. Study participants from the Mayo Clinic Biobank who had no prior history of hematologic malignancy, were 40 years or older, and were Olmsted County residents completed a health questionnaire and provided blood samples between 7/2009 and 12/2020. Stored peripheral blood mononuclear cells were screened for MBL using flow cytometry. We defined three MBL immunophenotypes: CLL-like MBL (CD5+, CD20dim), atypical MBL (CD5+, CD20+), and non-CLL-like MBL (CD5-, CD20+). MBL individuals were also classified by cell count into low-count MBL (LC-MBL) and high-count MBL (HC-MBL), with HC-MBL having a percent clonal B-cell count ≥85%. Data on newly diagnosed SCC was abstracted from the medical records, and prior history of skin cancer before sample collection was ascertained from patient questionnaires. Individuals were followed from sample date to the earliest of SCC, death, loss to follow-up, progression, or 12/31/2020. Cumulative SCC incidence was adjusted for competing risk of death. Cox regression was used to calculate hazard ratios (HR) and 95% confidence intervals (CIs) adjusted for age and sex. A total of 5,470 participants were screened for MBL and included 949 (17%) with LC-MBL, 63 (1%) with HC-MBL, and 4,458 (81%) controls (negative for MBL). Individuals with HC-MBL (median age 75 years) or LC-MBL (median age 73 years) were significantly older (P<0.001) than controls (median age 66 years). There were 41 (65%) males among HC-MBL, 447 (47%) among LC-MBL, and 1,551 (35%) among controls. Prior skin cancer history was highest among HC-MBLs (N=17, 27%) or LC-MBLs (N=236, 25%) compared to controls (N=767, 17%). After a median follow-up of 18 months (range 0-138), 154 of the 5,470 individuals were identified to have incident SCC following MBL screening. At least one SCC was observed in 3 individuals with HC-MBL, 33 individuals with LC-MBL, and 118 controls. The 5- and 10-year cumulative incidence of SCC in individuals with MBLs was 7% and 16%, respectively; control estimates were 4% and 8%, respectively. However, after adjusting for age and sex, we observed no evidence of an association between MBL and risk of incident SCC (HR=0.95, CI=0.65-1.40, P=0.80), nor when we stratified individuals by age or by sex (all P>0.05). In the largest MBL screening cohort to date, individuals with MBL do not have an increased risk of incident SCC compared to controls. In contrast to individuals with CLL, these individuals with screening MBL do not need increased dermatologic examination for skin cancer, which is important given the high prevalence of MBL (18% of the population above age 40). Citation Format: Ahmed Nadeem Ansari, Sara J. Achenbach, Sameer A. Parikh, Geffen Kleinstern, Aaron D. Norman, Kari G. Rabe, Connie E. Lesnick, Timothy G. Call, Janet E. Olson, James R. Cerhan, Neil E. Kay, Celine M. Vachon, Esteban Braggio, Curtis A. Hanson, Tait D. Shanafelt, Christian L. Baum, Susan L. Slager. Incidence of squamous cell carcinoma (SCC) in a large screening cohort of monoclonal B-cell lymphocytosis (MBL) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5256.
Neighborhood socioeconomic disadvantage, tobacco use, and cessation indicators among adults with cancer in the United States: Results from 10 ECOG-ACRIN trials.
Lee, Ju‐Whei , Gareen, Ilana F. , Kircher, Sheetal , Herman, B. , Kumar, Shaji , Neal, Joel W. , Hodi, F. Stephen , Kyriakopoulos, Christos E. , Tempany, Clare M. , Walter, Angela Wangari , Streck, Joanna M. , Mayer, Ingrid A. , Saba, Nabil F. , Atkins, Michael B. , Shanafelt, Tait D. , Wagner, Lynne I. , Land, Stephanie R , Ostroff, Jamie S , Park, Elyse R

Journal of Clinical Oncology | June 6, 2022 | Volume: 40 | Issue: 16_suppl | Pages: 6514-6514

10.1200/jco.2022.40.16_suppl.6514 Get It

6514 Background: Tobacco use is a modifiable risk factor for adverse outcomes among patients diagnosed with cancer. Despite ASCO’s recommendation for assessment and treatment of tobacco use, integration into cancer care is suboptimal. Socioeconomic contexts influence access and utilization of tobacco treatment, but little is known about the relationship between neighborhood socioeconomic disadvantage (NSD) and tobacco assessment, assistance, and cessation among cancer patients enrolled in clinical trials. Methods: The NCI Cancer Patient Tobacco Use Questionnaire (C-TUQ) was centrally administered to participants enrolled in 10 ECOG ACRIN clinical trials (9 therapeutic, 1 imaging). We examined associations of NSD with patient-reported rates of receiving brief tobacco cessation support (i.e., Ask, Assist (counseling)) and cessation (past 30d quit attempts and duration). NSD was measured using the national Area Deprivation Index (ADI) based on participant’s zip code. Associations between ADI (low, intermediate, and high) and tobacco variables were evaluated using logistic regression and ANOVA. Results: 740 patients, completing the C-TUQ between June 2017-October 2021, can be classified as 402 (54%) never smokers, 81 (11%) current smokers, and 257 (35%) former smokers. Patients were 70% male; 94% white; 3% Hispanic; mean age 58.8 (SD 9.0). Cancer diagnoses were 36% leukemia; 19% lymphoma, 18% prostate, 11% breast; 9% melanoma, 7% myeloma, and 0.5% head and neck. Patients were categorized into high (33%), intermediate (34%) and low (33%) disadvantaged neighborhoods. Patients in high (vs. low) disadvantaged neighborhoods were more likely to report being asked about smoking (OR = 3.90; 95% CI (confidence interval), 1.61 to 9.46; p = 0.0062) but less likely to report receiving counseling to help quit smoking (OR = 0.20; 95% CI, 0.06 to 0.73; p = 0.0234). Patients from high disadvantaged neighborhoods had the shortest quit duration, followed by patients from intermediate and low disadvantaged neighborhoods (mean = 145.78, 187.66, and 210.98 months, respectively, p = 0.0372). Conclusions: Greater socioeconomic neighborhood disadvantage was associated with increased assessment of tobacco use but decreased tobacco treatment referral, and the shortest quit duration. More research is needed to promote increased referral to tobacco treatment for individuals with cancer from disadvantaged neighborhoods to promote and sustain cessation.
Physicians’ Experiences With Mistreatment and Discrimination by Patients, Families, and Visitors and Association With Burnout
Sinsky, Christine A. , Trockel, Mickey , Tutty, Michael , Satele, Daniel , Carlasare, Lindsey E. , Shanafelt, Tait D. , Dyrbye, Liselotte N. , Shanafelt, Tait D , West, Colin P.

JAMA Network Open | May 19, 2022 | Volume: 5 | Issue: 5 | Pages: e2213080

10.1001/jamanetworkopen.2022.13080 Get It

Long-term outcomes for ibrutinib–rituximab and chemoimmunotherapy in CLL: updated results of the E1912 trial
Shanafelt, Tait D. , Wang, Victoria , Hanson, Curtis A. , Paietta, Elisabeth , O’Brien, Susan , Jelinek, Diane F., Braggio, Esteban , Leis, José F., Zhang, Cong Christine, Cashen, Amanda F. , Mato, Anthony R. , Singh, Avina K., Mullane, Michael P., Little, Richard F. , Stone, Richard M. , Litzow, Mark R. , Tallman, Martin S. , Braggio, Esteban , Barr, Paul M , Little, Richard F , Erba, Harry Paul , Litzow, Mark R. , Kay, Neil E , Shanafelt, Tait D , Barrientos, Jacqueline C. , Coutré, Steven , Barr, Paul M. , Kay, Neil E.

Blood | April 15, 2022 | Volume: 140 | Issue: 2 | Pages: 112-120

10.1182/blood.2021014960 Get It

Abstract Herein, we present the long-term follow-up of the randomized E1912 trial comparing the long-term efficacy of ibrutinib–rituximab (IR) therapy to fludarabine, cyclophosphamide, and rituximab (FCR) and describe the tolerability of continuous ibrutinib. The E1912 trial enrolled 529 treatment-naïve patients aged ≤70 years with chronic lymphocytic leukemia (CLL). Patients were randomly assigned (2:1 ratio) to receive IR or 6 cycles of FCR. With a median follow-up of 5.8 years, median progression-free survival (PFS) is superior for IR (hazard ratio [HR], 0.37; P < .001). IR improved PFS relative to FCR in patients with both immunoglobulin heavy chain variable region (IGHV) gene mutated CLL (HR: 0.27; P < .001) and IGHV unmutated CLL (HR: 0.27; P < .001). Among the 354 patients randomized to IR, 214 (60.5%) currently remain on ibrutinib. Among the 138 IR-treated patients who discontinued treatment, 37 (10.5% of patients who started IR) discontinued therapy due to disease progression or death, 77 (21.9% of patients who started IR) discontinued therapy for adverse events (AEs)/complications, and 24 (6.8% of patients who started IR) withdrew for other reasons. Progression was uncommon among patients able to remain on ibrutinib. The median time from ibrutinib discontinuation to disease progression or death among those who discontinued treatment for a reason other than progression was 25 months. Sustained improvement in overall survival (OS) was observed for patients in the IR arm (HR, 0.47; P = .018). In conclusion, IR therapy offers superior PFS relative to FCR in patients with IGHV mutated or unmutated CLL, as well as superior OS. Continuous ibrutinib therapy is tolerated beyond 5 years in the majority of CLL patients. This trial was registered at www.clinicaltrials.gov as #NCT02048813.
Prevalence and Overall Survival of Low Count Monoclonal B-Cell Lymphocytosis (LC-MBL): A Screening Study of 8,297 Individuals from the Mayo Clinic Biobank
Achenbach, Sara J., Kleinstern, Geffen , Lesnick, Connie , Call, Timothy G. , Vachon, Celine M. , Hanson, Curtis A. , Shanafelt, Tait D. , Shanafelt, Tait D , Slager, Susan L. , Parikh, Sameer A. , Boddicker, Nicholas , Norman, Aaron D. , Rabe, Kari G. , Olson, Janet E. , Cerhan, James R. , Kay, Neil E. , Vachon, Celine M. , Braggio, Esteban

Blood | November 24, 2021 | Volume: 138 | Issue: Supplement 1 | Pages: 2632-2632

10.1182/blood-2021-153320 Get It

Abstract Monoclonal B-cell lymphocytosis (MBL) is one of the most common pre-malignant conditions and is characterized by a circulating population of clonal B-cells with an absolute clonal B-cell count < 5x10 9/L and no evidence of lymphadenopathy, organomegaly, or cytopenias. MBL can be classified by the immunophenotype: CLL-like MBL (CD5+, CD20dim), atypical MBL (CD5+, CD20+), or non-CLL-like MBL (CD5-, CD20+), as well as by the size of the clone (low-count or high-count) with low-count MBL (LC-MBL) defined as clonal B-cell <0.5x10 9/L or percent clonal B-cell count <85% out of total B-cell count. The prevalence of MBL varies depending on detection methods and population tested. In a Spanish screening study of 608 individuals, they identified 73 MBLs (12%) with CLL-like MBL; moreover, these authors also evaluated overall survival (OS) compared to 290 individuals without MBL and found a significantly shorter OS among these predominantly LC-MBLs. Here, we evaluate the prevalence and OS of LC-MBL in a large screening cohort of 8,297 individuals. Study participants from the Mayo Clinic Biobank, a large-scale biorepository of adult patients, who had no prior history of hematologic malignancy, provided blood samples between 7/2009 to 4/2021. Stored peripheral blood mononuclear cells were screened for MBL with an eight-color flow cytometry assay capable of detecting clonal B-cell event to the 0.005% level. We classified each MBL by immunophenotype as CLL-like MBL, atypical MBL, and non-CLL-like MBL. Individuals with more than one immunophenotype were classified into one immunophenotype based on the following hierarchy: CLL-like MBL, then atypical MBL, then non-CLL like MBL. Based on previously published evidence, individuals were also classified by clonal counts using the percent clonal B-cell count <85% out of the total B-cell count to define LC-MBL. Individuals were followed from sample date to the earliest of death, loss to follow-up, or 5/31/2021. OS for LC-MBL and controls (individuals who screened negative for MBL) was assessed by Kaplan-Meier method. Age- and sex-adjusted OS was analyzed using inverse weights methods. Cox regression was used to calculate hazard ratios (HR) and 95% confidence intervals (CIs), adjusted for age and sex. We screened 8,297 individuals 40 years or older (median age 67 years, 39% male) and identified 1,326 (16%) with LC-MBL and 6,651 (80%) controls. Those individuals detected with high-count MBL (N=90, 1%) or individuals who had insufficient cells for flow cytometry interpretation (N=230, 3%) were excluded from subsequent analyses. The prevalence of LC-MBL was higher in males (21%) than females (14%; p<0.01) and significantly increased with age (p<0.01) ranging from 3% among those 40-49 years, 10% among those 50-59 years, 15% among those 60-69 years, 23% among those 70-79 years, and 29% for those 80+ years. Sixty-one individuals had clones with more than one type of immunophenotype. Based on our hierarchy, CLL-like MBL was the most common (N=1,155), followed by non-CLL-like (N=168) and atypical MBL (N=67). The median follow-up time in our cohort was 26 months (range 0-142), and 432 individuals had subsequently died. The 5-year and 10-year OS adjusted for age and sex among LC-MBLs was 95% and 87%, respectively; control estimates were 95% and 84%, respectively. We did not observe a significant difference in OS between those individuals with LC-MBL versus controls (HR=0.98, CI=0.77-1.24, P=0.84, Fig 1a), nor when we stratified individuals by age <65 (P=0.77) or age >= 65 (P=0.68). Among females, OS was longer among LC-MBL compared to controls (HR=0.61, CI=0.38-0.97, P=0.04); but no evidence of a difference in OS among males was observed (HR=1.22, CI=0.92-1.62, P=0.17). When we evaluated OS by MBL immunophenotype, we observed no statistically significant difference (Fig 1b, log rank P=0.44). When we stratified the MBLs by immunophenotype versus controls, we also did not observe a difference: CLL-like (HR=0.91, CI=0.71-1.18, P=0.5), atypical (HR=1.73, CI=0.92-3.27, P=0.09), non-CLL like (HR=0.98, CI=0.58-1.66, P=0.95). In the largest MBL screening cohort to date, LC-MBL was a common condition among adults 40 years or older reaching a prevalence as high as 29% among individuals 80 years of age or older. OS among those with and without LC-MBL was similar, regardless of immunophenotype and age. The longer survival in females with MBL versus controls requires further evaluation. Figure 1 Figure 1. Disclosures Parikh: Pharmacyclics, AstraZeneca, Genentech, Gilead, GlaxoSmithKline, Verastem Oncology, and AbbVie: Membership on an entity's Board of Directors or advisory committees; Pharmacyclics, MorphoSys, Janssen, AstraZeneca, TG Therapeutics, Bristol Myers Squibb, Merck, AbbVie, and Ascentage Pharma: Research Funding. Kay: Juno Therapeutics: Membership on an entity's Board of Directors or advisory committees; Pharmacyclics: Membership on an entity's Board of Directors or advisory committees, Research Funding; Bristol Meyer Squib: Membership on an entity's Board of Directors or advisory committees, Research Funding; Targeted Oncology: Membership on an entity's Board of Directors or advisory committees; TG Therapeutics: Research Funding; Sunesis: Research Funding; Dava Oncology: Membership on an entity's Board of Directors or advisory committees; Genentech: Research Funding; Behring: Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees, Research Funding; Acerta Pharma: Research Funding; MEI Pharma: Research Funding; Tolero Pharmaceuticals: Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees; CytomX Therapeutics: Membership on an entity's Board of Directors or advisory committees; Oncotracker: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Agios Pharm: Membership on an entity's Board of Directors or advisory committees; Morpho-sys: Membership on an entity's Board of Directors or advisory committees; Rigel: Membership on an entity's Board of Directors or advisory committees. Shanafelt: Genentech, Pharmacyclics: Research Funding.
Relationship and Susceptibility to Serious Infections Among Monoclonal B-Cell Lymphocytosis (MBL), Monoclonal Gammopathy of Undetermined Significance (MGUS), and Clonal Hematopoiesis (CH) Premalignant Conditions
Kleinstern, Geffen , Call, Timothy G. , Murray, David , Kumar, Shaji , Hanson, Curtis A. , Shanafelt, Tait D. , Vachon, Celine M. , Shanafelt, Tait D , Boddicker, Nicholas , Parikh, Sameer A. , Norman, Aaron D. , Rabe, Kari G. , Olson, Janet E. , Dispenzieri, Angela , Rajkumar, S. Vincent , Cerhan, James R. , Kay, Neil E. , Braggio, Esteban , Vachon, Celine M. , Slager, Susan L.

Blood | November 23, 2021 | Volume: 138 | Issue: Supplement 1 | Pages: 3739-3739

10.1182/blood-2021-151929 Get It

Abstract Introduction Monoclonal B-cell lymphocytosis (MBL), monoclonal gammopathy of undetermined significance (MGUS), and clonal hematopoiesis (CH) are three common premalignant hematological conditions. MBL is a precursor to chronic lymphocytic leukemia (CLL), MGUS is a precursor to both multiple myeloma (MM) and Waldenström macroglobulinemia (WM), and CH is a possible precursor to myeloid disease. All three conditions are independently associated with aging. Furthermore, there is evidence that all three conditions are associated with increased risk of infection. The relationship among these conditions, the prevalence with which they co-exist, and the association between the number of premalignant conditions and risk of infection is unknown. Methods Study participants from the Mayo Clinic Biobank, a large-scale biorepository of adult patients, provided a peripheral blood sample between 7/14/2009 to 06/18/2015. Individuals were screened for MBL using eight-color flow cytometry capable of detecting clonal B-cells to the 0.005% level. MGUS was screened using a matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF) assay. CH was screened using a targeted sequencing panel of 42 CH-associated genes with at least 1000x read depth and the ability to detect variant allele fractions down to 1%. All study participants resided in Olmsted County, Minnesota, the county that includes Mayo Clinic. Serious infection, defined as hospitalization due to infection, was abstracted from medical records from the time of sample collection through 12/31/2020 or date of death. The medical record abstractor collecting data was blinded to condition. Logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI) for the association between each of the conditions. Cox regression was used to estimate hazard ratios (HR) and 95% CI to assess the association between number of premalignant conditions with risk of infection. All analyses were adjusted for age at sample collection and sex. Results A total of 407 individuals (55% male, median age 68 years) were screened for all three conditions. The prevalence was 19.9% (n=81) for MBL, 14.5% (n=59) for MGUS, and 25.6% (n=104) for CH. When we evaluated the association between each of the conditions, we found no evidence of an association between the prevalence of CH and risk of MBL (OR=0.79, 95% CI: 0.43-1.42), CH and risk of MGUS (OR=1.24, 95% CI: 0.66-2.27), or MGUS and risk of MBL (OR=1.32, 95% CI:0.66-2.52). The prevalence of co-existence of these conditions was assessed by grouping individuals based on their condition or conditions (Figure 1A). We found that 197 (48.4%) study participants had at least one premalignant condition and 10.6% had two or more. Individuals with 2 or more conditions were the oldest (median age 74 years), followed by 1 condition (median 69 years) and 0 conditions (median 67 years, P-trend <0.001). Sex was not significantly different across the groups, with 55%, 58%, and 47% male for 0, 1, and 2 conditions, respectively. Medical record abstraction identified 97 serious infection events in 80 individuals. Medical records were not available on 7 individuals. The most common infections were urinary tract (20 events), pneumonia (14 events), and cellulitis (14 events). Median follow-up time was 10.6 years (range 0.1-11.5 years). Compared to individuals with no condition, MBL (HR=1.75, 95% CI: 1.06-2.88) and MGUS (HR=1.75, 95% CI: 1.04-2.93) were associated with increased risk of serious infection. We found no evidence of an association with CH (HR=1.15, 95% CI: 0.71-1.87). When grouped by the number of conditions, we observed a significant trend (P-trend <0.01, Figure 1B) in risk of serious infections by the number of conditions: individuals with 1 condition had a 35% increased risk of infections (HR=1.35, 95% CI:0.83-2.20) and individuals with 2 or more conditions had a 2.6-fold increased risk (HR=2.58, 95% CI: 1.37-4.84). Discussion At least one premalignant condition was present in nearly 50% of the study population, with CH being the most prevalent. No evidence of a relationship between any of the three conditions was observed. However, we found increased susceptibility to serious infections as the number of conditions increased with individuals with at least two conditions had 2.6-fold increased risk of infections. Figure 1 Figure 1. Disclosures Parikh: Pharmacyclics, AstraZeneca, Genentech, Gilead, GlaxoSmithKline, Verastem Oncology, and AbbVie: Membership on an entity's Board of Directors or advisory committees; Pharmacyclics, MorphoSys, Janssen, AstraZeneca, TG Therapeutics, Bristol Myers Squibb, Merck, AbbVie, and Ascentage Pharma: Research Funding. Dispenzieri: Takeda: Research Funding; Alnylam: Research Funding; Pfizer: Research Funding; Oncopeptides: Consultancy; Sorrento Therapeutics: Consultancy; Janssen: Consultancy, Research Funding. Murray: Mayo Clinic: Other: Has received patents for the Mass-Fix technology which has been licensed to the Binding Site with potential royalties.. Kumar: Astra-Zeneca: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Merck: Research Funding; Oncopeptides: Consultancy; Beigene: Consultancy; Novartis: Research Funding; KITE: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Antengene: Consultancy, Honoraria; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Tenebio: Research Funding; Roche-Genentech: Consultancy, Research Funding; Bluebird Bio: Consultancy; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Carsgen: Research Funding; Amgen: Consultancy, Research Funding; Abbvie: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; BMS: Consultancy, Research Funding; Adaptive: Membership on an entity's Board of Directors or advisory committees, Research Funding; Sanofi: Research Funding. Cerhan: Regeneron Genetics Center: Other: Research Collaboration; Genentech: Research Funding; Celgene/BMS: Other: Connect Lymphoma Scientific Steering Committee, Research Funding; NanoString: Research Funding. Kay: TG Therapeutics: Research Funding; Morpho-sys: Membership on an entity's Board of Directors or advisory committees; Agios Pharm: Membership on an entity's Board of Directors or advisory committees; Targeted Oncology: Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees, Research Funding; Oncotracker: Membership on an entity's Board of Directors or advisory committees; Sunesis: Research Funding; MEI Pharma: Research Funding; Pharmacyclics: Membership on an entity's Board of Directors or advisory committees, Research Funding; Bristol Meyer Squib: Membership on an entity's Board of Directors or advisory committees, Research Funding; Acerta Pharma: Research Funding; Rigel: Membership on an entity's Board of Directors or advisory committees; Tolero Pharmaceuticals: Research Funding; Genentech: Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Behring: Membership on an entity's Board of Directors or advisory committees; CytomX Therapeutics: Membership on an entity's Board of Directors or advisory committees; Dava Oncology: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; Juno Therapeutics: Membership on an entity's Board of Directors or advisory committees. Shanafelt: Genentech, Pharmacyclics: Research Funding.