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Background Adverse cardiac remodeling is an important precursor to anthracycline-related cardiac dysfunction, however conventional remodeling indices are limited. We sought to examine the utility of statistical atlas-derived measures of ventricular shape to improve the identification of adverse anthracycline-related remodeling in childhood cancer survivors. Methods We analyzed cardiac magnetic resonance imaging from a cross-sectional cohort of 20 childhood cancer survivors who were treated with low (2 [N = 10]) or high (≥250 mg/m2 [N = 10]) dose anthracyclines, matched 1:1 by sex and age between dose groups. We reconstructed 3D computational models of left ventricular end-diastolic shape for each subject and assessed the ability of conventional remodeling indices (volume, mass, and mass to volume ratio) vs. shape modes derived from a statistical shape atlas of an asymptomatic reference population to stratify anthracycline-related remodeling. We compared conventional parameters and five atlas-based shape modes: 1) between survivors and the reference population (N = 1991) using multivariable linear regression, and 2) within survivors by anthracycline dose (low versus high) using two-sided T-tests, multivariable logistic regression, and receiver operating characteristic curves. Results Compared with the reference population, survivors had differences in conventional measures (lower volume and mass) and shape modes (corresponding to lower overall size and lower sphericity; all p p = 0.039). Collectively, atlas-based shape modes in conjunction with conventional measures discriminated survivors who received low vs. high anthracycline dosage (area under the curve [AUC] 0.930, 95% confidence interval 0.816, 1.00) significantly better than conventional measures alone (AUC 0.710, 95% confidence interval 0.473, 0.947; AUC comparison p = 0.0498). Conclusions Compared with a reference population, heart size is smaller in anthracycline-exposed childhood cancer survivors. Atlas-based measures of left ventricular shape may improve the detection of anthracycline dose-related remodeling differences.

Background The number of patients undergoing autologous haematopoietic cell transplant (HCT) is growing, but little is known about the factors that predict adverse outcomes. Low muscle mass and obesity are associated with disability and premature mortality in individuals with non‐malignant diseases and may predict outcomes after autologous HCT. Methods This was a retrospective cohort study of 320 patients who underwent autologous HCT for Hodgkin or non‐Hodgkin lymphoma between 2009 and 2014. Sarcopenia {skeletal muscle index male

Background High intensity treatments such as hematopoietic cell transplantation (HCT) can be curative for patients with hematologic malignancies, but this needs to be balanced by the high risk of nonrelapse mortality (NRM) during the first 2 years after HCT. Sarcopenia (low muscle mass) is associated with physical disability and premature mortality in individuals with nonmalignant diseases and may be a predictor of NRM and poor overall survival in patients undergoing HCT. Methods This was a retrospective cohort study of 859 patients with acute leukemia or myelodysplastic syndrome who underwent a first HCT as adults (≥18 years) between 2007 and 2014. Sarcopenia was assessed from pre-HCT abdominal computed tomography scans. Two-year cumulative incidence of NRM was calculated, with relapse/progression considered as a competing risk event. Fine-Gray subdistribution hazard ratio estimates and 95% confidence intervals (CI) were obtained and adjusted for relevant covariates. Kaplan-Meier method was used to examine overall survival. All statistical tests were two-sided. Results Median age at HCT was 51 years (range = 18–74 years); 52.5% had a high [≥3] HCT-comorbidity index; 33.7% had sarcopenia pre-HCT. Sarcopenia was an independent predictor of higher NRM risk (hazard ratio = 1.58, 95% CI = 1.16 to 2.16) compared with patients who were not. The 2-year incidence of NRM approached 30% in patients with sarcopenia and high (≥3) HCT-comorbidity index. Patients with sarcopenia had on average a longer hospitalization (37.2 days vs 31.5 days, P Conclusions Sarcopenia is an important and independent predictor of survival after HCT, with potential additional downstream impacts on health-economic outcomes. This information can be used to facilitate treatment decisions prior to HCT and guide interventions to decrease the risk of treatment-related complications after HCT.

PURPOSE To examine the incidence and risk factors for de novo atrial fibrillation (AF) after allogeneic hematopoietic cell transplantation (HCT) and to describe the impact of AF on HCT-related outcomes. METHODS A retrospective cohort study design was used to examine AF and associated outcomes in 487 patients who underwent allogeneic HCT from 2014 to 2016 and to characterize patient- and HCT-related risk factors. A nested case-control study design was used to describe the association between pre-HCT echocardiographic measures and future AF events. RESULTS The median age at HCT was 52.4 years (18.1-78.6); the median time to AF was 117.5 days (4.0-1,405.0). The 5-year cumulative incidence of AF was 10.6%. Older (≥ 50 years) age (hazard ratio [HR], 2.76; 95% CI, 1.37 to 5.58), HLA-unrelated donor (HR, 2.20; 95% CI, 1.18 to 4.12), dyslipidemia (HR, 2.40; 95% CI, 1.23 to 4.68), and pre-HCT prolonged QTc interval (HR, 2.55; 95% CI, 1.38 to 4.72) were independent risk factors for AF. Despite having comparable left ventricular systolic function, patients who developed AF were significantly more likely to have lower left atrial ejection fraction, left atrial reservoir function, and elevated tricuspid regurgitant jet velocity prior to HCT, compared with patients who did not. The incidence rate of stroke after AF was 143 per 1,000 person-years. In adjusted analyses, AF was associated with a 12.8-fold (HR, 12.76; 95% CI, 8.76 to 18.57) risk of all-cause mortality and 15.8-fold (HR, 15.78; 95% CI, 8.70 to 28.62) risk of nonrelapse mortality. CONCLUSION The burden of AF after allogeneic HCT population is substantial, and the development of AF is associated with poor survival. We identified important associations between patient demographics, pre-HCT cardiac parameters, HCT-related exposures, and risk of AF, setting the stage for targeted prevention strategies during and after HCT.

Background Hematopoietic cell transplantation (HCT) is a curative option for a growing number of patients with hematologic diseases and malignancies. However, HCT-related factors, such as total body irradiation used for conditioning, graft-versus-host disease, and prolonged exposure to immunosuppressive therapy, result in very high risk for melanoma and non-melanoma skin cancer (NMSC). In fact, skin cancer is the most common subsequent neoplasm in HCT survivors, tending to develop at a time when survivors’ follow-up care has largely transitioned to the primary care setting. The goal of this study is to increase skin cancer screening rates among HCT survivors through patient-directed activation alone or in combination with physician-directed activation. The proposed intervention will identify facilitators of and barriers to risk-based screening in this population and help reduce the burden of cancer-related morbidity after HCT. Methods/design 720 HCT survivors will be enrolled in this 12-month randomized controlled trial. This study uses a comparative effectiveness design comparing (1) patient activation and education (PAE, N = 360) including text messaging and print materials to encourage and motivate skin examinations; (2) PAE plus primary care physician activation (PAE + Phys, N = 360) adding print materials for the physician on the HCT survivors’ increased risk of skin cancer and importance of conducting a full-body skin exam. Patients on the PAE + Phys arm will be further randomized 1:1 to the teledermoscopy (PAE + Phys+TD) adding physician receipt of a portable dermatoscope to upload images of suspect lesions for review by the study dermatologist and an online course with descriptions of dermoscopic images for skin cancers. Discussion When completed, this study will provide much-needed information regarding strategies to improve skin cancer detection in other high-risk (e.g. radiation-exposed) cancer survivor populations, and to facilitate screening and management of other late effects (e.g. cardiovascular, endocrine) in HCT survivors. Trial registration ClinicalTrials.gov, NCT04358276. Registered 24 April 2020.

Introduction: Chimeric antigen receptor T cell (CAR-T) therapy is an effective treatment for patients with relapsed/refractory diffuse large B cell lymphoma (DLBCL) or other B-cell lymphomas. However, the potent anti-lymphoma effect of CAR-T is balanced by the risk of acute toxicities, namely cytokine release syndrome (CRS) and Immune effector cell-Associated Neurotoxicity Syndrome (ICANS), as well as the variable length of progression-free survival (PFS) after CAR-T. Tools to better risk-stratify for adverse outcomes and to guide targeted interventions are lacking. Sarcopenia (loss of lean muscle mass) is an important cause of age-related functional decline in the general population and is an independent predictor of health outcomes in patients with solid and hematologic cancers, irrespective of age or comorbidity. Advances in software technology have facilitated the near real-time integration of body composition measurements into imaging studies obtained as part of standard clinical care. To date, there have been no studies to examine the association between sarcopenia and outcomes after CAR-T therapy. Methods: Using a retrospective cohort design, 280 consecutive patients with DLBCL or B-cell lymphoma, age ≥18y, and treated with CAR-T therapy between 2015 to 2020 at a single center were included in the study. This analysis was restricted to 226 (80.7%) patients with available computed tomography scans ≤60d from CAR-T. Skeletal muscle area was ascertained from abdominal scans using an automatic image analysis software (APACS; Voronoi Health Analytics; Vancouver, Canada); 3rd lumbar vertebra was used as a landmark because of its high correlation with whole-body muscle mass (J Clin Oncol 2016 34:1339); Figure. Trained researchers blinded to patient demographics and outcomes manually validated these measurements (SliceOmatic; Tomovision; Quebec, Canada). Skeletal muscle index (SMI) was calculated as the ratio of skeletal muscle area (cm 2) divided by height (m). Sarcopenia was defined according to sex-based cutoffs (lowest SMI tertile). Kaplan-Meier method was used to examine PFS at one-year. Multivariable regression was used to calculate the hazard ratio (HR) for PFS and odds ratio (OR) for toxicities with 95% confidence intervals (CI), adjusted for covariates (demographics [age, race/ethnicity], disease characteristics [largest lymph node diameter, blood lactate dehydrogenase], CAR-T product, ECOG performance status). Results: Median age at CAR-T was 63y (range: 18-84); 65.9% were male; 50.9% were non-Hispanic white; 8.8% had ECOG ≥2; 80.5% had a diagnosis of DLBCL; CAR-T products: axicabtagene ciloleucel (51.3%), lisocabtagene maraleucel (31.9%), other (16.8%); 46.9% were treated on a clinical trial; median residual lymph node diameter prior to CAR-T was 2.3cm (range: 0-17.2); 8.0% underwent HCT Figure 1 Figure 1. Disclosures Artz: Radiology Partners: Other: Spouse has equity interest in Radiology Partners, a private radiology physician practice. Budde: Merck, Inc: Research Funding; Amgen: Research Funding; Astra Zeneca: Research Funding; Mustang Bio: Research Funding; Novartis: Consultancy; Gilead: Consultancy; Roche: Consultancy; Beigene: Consultancy. Herrera: Merck: Consultancy, Research Funding; Gilead Sciences: Research Funding; Bristol Myers Squibb: Consultancy, Research Funding; AstraZeneca: Consultancy, Research Funding; Karyopharm: Consultancy; Kite, a Gilead Company: Research Funding; Seagen: Consultancy, Research Funding; ADC Therapeutics: Consultancy, Research Funding; Takeda: Consultancy; Tubulis: Consultancy; Genentech: Consultancy, Research Funding. Popplewell: Novartis: Other: Travel; Pfizer: Other: Travel; Hoffman La Roche: Other: Food. Shouse: Kite Pharmaceuticals: Speakers Bureau; Beigene Pharmaceuticals: Honoraria. Siddiqi: Kite Pharma: Membership on an entity's Board of Directors or advisory committees; Juno therapeutics: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Abbvie: Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; BeiGene: Other: DSM Member, Speakers Bureau; PCYC: Speakers Bureau; Jannsen: Speakers Bureau; Dava Oncology: Honoraria; ResearchToPractice: Honoraria. Forman: Lixte Biotechnology: Consultancy, Current holder of individual stocks in a privately-held company; Allogene: Consultancy; Mustang Bio: Consultancy, Current holder of individual stocks in a privately-held company.

Introduction: Hematopoietic cell transplantation (HCT)-related factors, such as total body irradiation (TBI) used for conditioning, graft-versus-host disease (GvHD), and prolonged exposure to calcineurin-inhibitors, can result in high risk for subsequent skin cancers in long-term survivors. Previous studies examining skin cancers after HCT have largely focused on patients transplanted in earlier eras ( Methods: 2338 consecutive patients who underwent a first HCT between 2005 and 2014 at City of Hope (COH) and survived ≥1 year, were included in the study. Patients with a history of skin cancer prior to HCT were excluded from the cohort. All skin cancers were validated using pathology reports, and physician notes (20%) whenever the former was not available. Skin cancers included SCC, BCC, melanoma, atypical fibroxanthoma, and merkel cell carcinoma. Patients were followed from HCT to death, second HCT, last known alive date, or December 31, 2018, whichever occurred first. Cumulative incidence of skin cancer was estimated taking into consideration competing risk of death. Fine-Gray sub-distributional hazard regression was used to calculate hazard ratio (HR) estimates, adjusted for relevant covariates. Results: Median age at HCT was 51.8y (range: 0.7-78.7); 57.6% were male; 56.5% were non-Hispanic white (NHW); 4.4% had a history of Pre-HCT cancer (antecedent to primary diagnosis); 47.7% underwent allogeneic HCT; 22.0% received myeloablative TBI (≥1200 cGy)-based conditioning. Among survivors of allogeneic HCT, 57.2% developed ≥moderate chronic GvHD (84% involving the skin); the most common immunosuppressive agents used for the management of ≥moderate chronic GvHD were tacrolimus (84.6%), followed by sirolimus (76.5%), and cyclosporine (28.4%). Burden of skin cancer over time: 179 survivors developed a total of 450 skin cancers after HCT; median time from HCT to first skin cancer was 2.8 years (range: 0.2-13.6). SCC was the most common subtype (59.1%), followed by BCC (31.3%), melanoma (5.1%), and other (4.4%); 43.4% of patients with SCC had invasive or high grade disease at presentation. The cumulative incidence of de novo skin cancer after HCT was 8.3% at 5 years, and 14.8% at 10 years (figure). Eighty-nine patients with skin cancer had a second skin cancer at a median of 0.5 years (range: 0.2 to 7.2) from the first; 55.1% were of a different histology. The cumulative incidence of a second skin cancer was 41.9% at 5-years (figure). Risk factors: Multivariate analysis revealed male sex (HR=1.7, p=0.0008), NHW race/ethnicity (HR=9.0, p Conclusions: This study confirms the higher risk of skin cancer by sex, race/ethnicity, and age at HCT, and highlights the greater than two-fold risk of skin cancer among allogeneic HCT survivors compared to autologous patients, a finding that is not entirely explained by GvHD and its treatment. Further, we identified a previously unreported association between pre-HCT (non-skin) cancer and post-HCT cancer risk, and describe the very high burden of multiple histologically distinct skin cancers over time. Taken together, these data set form the basis for implementation of updated risk-based screening and prevention practices in survivors at highest risk of skin cancer after HCT. Disclosures Abdulla: Johnson & Johnson: Research Funding; Elorac: Research Funding; Trillium: Research Funding; Stemline: Research Funding; MiRagen: Research Funding; Bionz: Research Funding; Mallinckrodt: Research Funding; Mallinckrodt: Consultancy; Mallinckrodt: Speakers Bureau. Nakamura:Merck: Membership on an entity's Board of Directors or advisory committees; Celgene: Other: support for an academic seminar in a university in Japan; Alexion: Other: support to a lecture at a Japan Society of Transfusion/Cellular Therapy meeting ; Kirin Kyowa: Other: support for an academic seminar in a university in Japan.

Introduction: High intensity treatments such as autologous hematopoietic cell transplantation (HCT) can be curative for patients with relapsed/refractory lymphoma (Hodgkin [HL], non-Hodgkin [NHL]), but this needs to be balanced by the risk of non-relapse mortality (NRM) associated with HCT and potentially sub-optimal disease response with less intensive treatments. Measures of pre-treatment body composition such as quantity and quality of muscle are prognostic in patients with solid tumors, but their association with post-HCT outcomes is unknown. We examined the prognostic significance of muscle depletion prior to HCT, defined by having both low muscle quantity (lumbar skeletal muscle index [SMI]) and quality (muscle attenuation [MA]) on computed tomography (CT) imaging, in a population-based cohort of patients undergoing autologous HCT for lymphoma. Next, we examined the prognostic significance of muscle depletion after HCT in a subset of patients with normal muscle composition prior to HCT, allowing us to examine the impact of change in body composition over time. Methods: 440 consecutive patients with lymphoma, age ≥18y, who underwent a first HCT between 2009 and 2014 at a single institution were included in the study. Measures of muscle quantity (SMI) and quality (MA) were ascertained from pre- and post-HCT abdominal CT scans using image analysis software (SliceOmatic; Tomovision, Quebec, Canada). SMI was calculated as the ratio of skeletal muscle area (cm2) divided by height (m)2. Sex and body mass index (BMI)-specific cutoff values of low SMI and MA were used to identify patients with muscle depletion (J Clin Oncol 2013 31:1539). Measurements were made by trained researchers blinded to patient demographics and HCT outcome (Figure 1); 3rd lumbar vertebra was used as a landmark because of its high correlation with whole-body muscle mass (J Clin Oncol 2016 34:1339). This report is limited to 321 (73%) patients with CT scans performed ≤90 days from HCT. Cumulative incidence of NRM was calculated taking into consideration competing risk of disease-related mortality. Kaplan-Meier method was used to examine overall survival (OS). Multivariable Cox regression analysis was used to calculate the hazard ratio (HR) estimates and 95% confidence intervals (CI), adjusted for relevant covariates (demographics, diagnosis, pre-HCT Karnofsky performance score [KPS] and comorbidity index [HCT-CI]). Results: Sixty-two (19.3%) patients had muscle depletion pre-HCT. Median age at HCT was 53y (range: 18-78); 62.0% were male; 54.0% were non-Hispanic white; Diagnoses: HL (N=84 [26.2%]), NHL (N=237 [73.8%]); KPS ≤80 (N=87 [27.1%]); HCT-CI ≥3 (N=52 [16.2%]). Impact of pre-HCT muscle depletion: Patients with pre-HCT muscle depletion had significantly worse 5-y OS (56.4% vs. 77.8%, p Conclusion: Muscle depletion is an important and independent predictor of outcomes after HCT, with potential additional downstream impacts on health-economic outcomes such as length of hospitalization and the burden of chronic morbidity in long-term survivors. Taken together, these data form the basis for real-time decision making prior to HCT (e.g. pre-habilitation, less intensive treatment approaches), or during HCT (e.g. dietary optimization, increased supportive care services, resistance training), setting the stage for innovative strategies to improve outcomes after HCT. Disclosures Chen: Affimed: Research Funding; Merck & Co., Inc.: Consultancy, Research Funding, Speakers Bureau; Bristol-Myers Squibb: Consultancy, Research Funding; Seattle Genetics: Consultancy, Honoraria, Research Funding, Speakers Bureau; Genentech Inc.: Consultancy; Millennium Pharmaceuticals: Consultancy, Research Funding; Pharmacyclics: Consultancy, Research Funding. Forman:Mustang Therapeutics: Other: Licensing Agreement, Patents & Royalties, Research Funding.

Background: alloHCT is offered with curative intent to patients with malignant as well as some nonmalignant hematologic diseases, and conventionally-computed survival estimates are offered for prognosticating outcomes. However, conventionally-computed survival and mortality risk estimates do not account for patients' elapsed survival time which, among other factors, could affect subsequent mortality. Conditional survival overcomes these limitations by calculating the probability of survival after having already survived a certain period of time - such data are unavailable for alloHCT recipients. We describe conditional survival and cause-specific mortality (disease-related [DRM], non-disease-related [NDRM], and GvHD-related) after alloHCT to provide clinically relevant information for patients who have survived 6 mos, 1, 2, 5, and 10y after alloHCT. Methods: From 1976 to 2013, 4,315 consecutive patients underwent alloHCT for hematologic diseases at a single institution. Vital status and cause of death were determined using the National Death Index Plus and medical records. Results: Diagnoses included acute leukemia (54%), chronic leukemia (17%), lymphoma (11%), myelodysplastic syndrome (10%), severe aplastic anemia (5%), and other hematologic diseases (3%); median age at HCT was 38.5y (0.3-75.4). As of December 31, 2014, 1841 patients were still alive in whom the median follow-up was 8.5y (0.2-36.6). Of 2,474 deaths (57% of cohort) for whom causes of deaths are available, 42% was due to primary disease, 30% to graft versus host disease (GvHD), 12% to infection, 5% to cardiopulmonary diseases, 3% to subsequent malignant neoplasm (SMN), and 8% to other causes. Conventionally-computed probabilities of survival at 5, 10, 15, and 20y after alloHCT were 48%, 43%, 40%, and 34%, respectively. On the other hand, for patients who had survived 6 mo, 1, 2, 5, 10y after alloHCT, 5-y conditional survival rates were 62%, 72%, 80%, 88% and 93%, respectively (Figure A). Overall, the cohort was at a 24-fold (Standardized Mortality Ratio [SMR]=24.1, 95%CI=23.1-25.0) risk of any death, compared to the general population; the risk of death from pulmonary complications was 31-fold, that from SMN was 31-fold, and that from cardiovascular complications was 3.5-fold. SMR and cause-specific conditional mortality rates by primary diagnosis are shown in the Table. Significantly elevated risk of all-cause mortality persisted in patients who survived 5 and 10y post alloHCT (SMR=3.7, 2.6, respectively, p1.8, p Disclosures Forman: Mustang Therapeutics: Other: Licensing Agreement, Patents & Royalties, Research Funding.