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Patients with cancer have been identified in several studies to be at high risk of developing severe COVID-19; however, rates of SARS-CoV-2 IgG seroconversion and its association with cancer types and anti-cancer therapy remain obscure. We conducted a retrospective cohort study in patients with cancer that underwent SARS-CoV-2 IgG testing. Two hundred and sixty-one cancer patients underwent SARS-CoV-2 IgG testing and demonstrated a high rate of seroconversion (92%). However, significantly lower seroconversion was observed in patients with hematologic malignancies (82%), patients that received anti-CD-20 antibody therapy (59%), CAR-T/cellular therapy (33%) and stem cell transplant (60%). Interestingly, all 17 patients that received immunotherapy, including 16 that received anti-PD-1/PD-L1 monoclonal antibodies, developed SARS-Cov-2 IgG antibodies (100% seroconversion). These data show differential rates of seroconversion in specific patient groups and bear importance for clinical monitoring and vaccination strategies that are being developed to mitigate the COVID-19 pandemic

It is well established that COVID-19 carries a higher risk of morbidity and mortality in patients with hematologic malignancies, however, very little data on ethnicity specific responses in this particular patient population currently exist. We established a program of rapid vaccination and evaluation of antibody-mediated response to all EUA COVID-19 vaccines in an inner city minority population to determine the factors that contribute to the poor seroconversion to COVID-19 vaccination in this population. We conducted a cross-sectional cohort study of 126 patients with hematologic malignancies in the outpatient practices of our institution who completed their vaccination series with one of the three FDA EUA COVID-19 vaccines, Moderna, Pfizer, or Johnson & Johnson (J&J). We qualitatively measured Spike IgG production in all patients using the AdviseDx SARS-CoV-2 IgG II assay and quantitatively in 106 patients who completed their vaccination series with at least 14 days after the 2nddose of the Moderna or Pfizer vaccines or 28d after the single J&J vaccine. Patient characteristics were analyzed using standard descriptive statistics and associations between patient characteristics, cancer subtypes, treatments, and vaccine response were assessed using Fisher Exact test or Kruskal-Wallis Rank Sum test. The majority of patients (74%) were minorities. Seventy patients (60%) received Pfizer, 36 patients (31%) Moderna, and 10 patients (9%) J&J. We observed a high-rate of seropositivity (86%) with 16 pts (14%) having a negative Spike IgG. Of the 86 minority patients included, 94% Blacks (30/32) and 87% (39/45) Hispanics showed seropositivity. The factors that contributed to significantly lower seroconversion rates included patients with Non-Hodgkin lymphoma (p=0.005), those who received cytotoxic chemotherapy (p=0.002), IVIG (p=0.01), CAR-T cell therapy (p=0.00002), and CD20 monoclonal antibodies (Ab) (p=0.0000008). Plasma cell neoplasms (p=0.02), immunomodulatory agents (p=0.01), and proteasome inhibitors (p=0.01) had significantly higher seroconversion rates, and those with a history of prior COVID-19 (11%, 12/106) had significantly higher antibody titers (p=0.0003). The positivity rate was 86% (37 seropositive, 6 seronegative) for autologous HSCT and 75% (3 seropositive, 1 seronegative) for allogeneic HSCT. No life-threatening AE were observed. We show high seroconversion rates after SARS-CoV-2 vaccination in non-White patients with hematologic malignancies treated with a wide spectrum of therapeutic modalities. Vaccination is safe, effective, and should be encouraged in most patients with hematologic malignancies. Our minorities based study could be employed as an educational tool to dispel myths and provide data driven evidence to overcome vaccine hesitancy.

Anti-COVID-19 immunity dynamics were assessed in patients with cancer in a prospective clinical trial. Waning of immunity was detected 4-6 months post-vaccination with significant increases in anti-spike IgG titers after booster dosing, and 56% of seronegative patients seroconverted post-booster vaccination. Prior anti-CD20/BTK inhibitor therapy was associated with reduced vaccine efficacy.

Background: Patients with hematologic malignancy (HM) are hypothesized to be at high risk of poor outcomes with coronavirus disease 2019 (COVID-19), due to disease and therapy-related immunosuppression. Despite this, there are minimal reported data describing the outcomes of HM patients with COVID-19. Methods: The COVID-19 and Cancer Consortium (CCC19) (NCT04354701) is an international registry aimed at investigating the clinical course and complications of COVID-19 in patients with cancer. The CCC19 cohort includes patients with active cancer or a history of cancer with presumed or laboratory-confirmed COVID-19. The registry contains de-identified patient demographics, information regarding cancer diagnosis and treatment history, COVID-19 treatments, and clinical outcomes. Patients greater than 18 years of age with laboratory-confirmed, symptomatic COVID-19 and HM diagnoses were included in this study. The primary outcome is a composite of severe COVID-19 illness (composed of mechanical ventilation, severe illness requiring hospitalization, intensive care unit (ICU) requirement, or death); mechanical ventilation, ICU level of care, supplemental oxygen, and 30-day mortality are reported as secondary outcomes. Baseline characteristics are reported for the entire cohort. Reported clinical outcomes are stratified by cancer type, cancer status, line of therapy received (never treated, first, second or later), receipt of cellular therapy or transplant (none, within 12 months, >12 months prior to COVID-19 diagnosis), last receipt of cytotoxic therapy (within 4 weeks, 1-3 months, 3-12 months prior to COVID-19 diagnosis), and receipt of HM therapies under investigation as repurposed treatments for COVID-19 (Bruton tyrosine kinase (BTK) inhibitors, Janus kinase (JAK) inhibitors, Bcr-Abl kinase inhibitors). Results: From March 17, 2020 to July 31, 2020, a total of 757 patients with HM and COVID-19 were enrolled and met inclusion criteria. Median follow-up was 30 days (IQR 17-70 days). Median age was 65 years (IQR 55-75), 62% (470) were over age 60, 57% were men, 45% were non-Hispanic white (22% Black, 18% Hispanic, 5% other), 39% were former or current smokers, 27% were obese, 18% had Eastern Cooperative Oncology Group (ECOG) performance status ≥2, and 51% were on active treatment within 3 months of COVID-19 diagnosis. Among patients with HM, 281 (37%) developed the primary endpoint. Five-hundred and eleven patients (67%) were hospitalized (some with non-severe disease), 188 (25%) required ICU level of care, 133 (18%) required mechanical ventilation, 409 (54%) required supplemental oxygen, and 143 (19%) died within 30 days of COVID-19 diagnosis. Stratified rates of severe outcomes are shown in the Table. The rate of severe COVID-19 was highest in patients with chronic lymphocytic leukemia (53%), and lowest in patients with Hodgkin lymphoma (23%). Patients receiving cytotoxic systemic therapy within 3 months of COVID-19 diagnosis had higher rates of severe COVID-19 (41%) and 30-day mortality (28%) than patients who completed treatment 3-12 months (26% severe COVID-19, 16% 30-day mortality) or more than 12 months (29% severe COVID-19, 13% 30-day mortality) prior to COVID-19 diagnosis. Patients receiving cellular therapy or transplant within a year prior to COVID-19 diagnosis had similar rates of severe COVID-19 (36% v. 38%) and 30-day mortality (23% v. 19%) to patients who had not received such therapies within a year prior to COVID-19 diagnosis. Patients on second-line or later therapy experienced similar rates of poor outcomes (42% severe COVID-19, 20% 30-day mortality) to patients on first-line therapy (39% severe COVID-19, 18% 30-day mortality) and untreated patients (42% severe COVID-19, 20% 30-day mortality). Outcomes for patients receiving therapies under investigation as repurposed COVID-19 treatments were similar to the cohort at large. Conclusions: This is the largest cohort study to date describing COVID-19 outcomes in patients with HM. Rates of severe COVID-19 outcomes including death were high. Unadjusted rates of severe COVID-19 outcomes were higher in patients with previously described risk factors such as advanced age, poor performance status, and progressive disease, as well as those receiving recent cytotoxic therapy. Outcomes varied widely by malignancy but were similar across treatment contexts. Additional data collection and analyses are ongoing. Disclosures Lynch: Bayer: Research Funding; Rhizen Pharmaceuticals: Research Funding; Incyte: Research Funding; TG Therapeutics: Research Funding; Takeda: Research Funding; Juno Therpeutics: Research Funding; Genentech: Research Funding; MorphoSys: Consultancy; Cyteir: Research Funding. Bakouny:BMS: Research Funding; Genentech: Research Funding. Bhutani:Sanofi: Consultancy, Research Funding. Shah:American Cancer Society and the Hope Foundation for Cancer Research: Research Funding; National Cancer Institute: Research Funding. Lyman:Mylan: Consultancy; Beyond Spring: Consultancy; Samsung: Consultancy; Sandoz: Consultancy; Invitae: Consultancy; Spectrum: Consultancy; G1 Therapeutics: Consultancy; Amgen: Research Funding. Kuderer:Janssen: Consultancy; G1 Therapeutics: Consultancy; Beyond Springs: Consultancy; Spectrum Pharmaceuticals: Consultancy; Bayer: Consultancy; Bristol-Myers Squibb: Consultancy; celldex: Consultancy; Total Health: Consultancy; Invitae: Consultancy. Warner:HemOnc.orgLLC: Other: Shareholder/Stockholder/Stock options; National Cancer Institute: Research Funding; IBM Watson Health: Consultancy; Westat: Consultancy. Mesa:Bristol Myers Squibb: Research Funding; Incyte: Research Funding; AbbVie: Research Funding; Samus Therapeutics: Research Funding; Genentech: Research Funding; Promedior: Research Funding; CTI BioPharma: Research Funding; Novartis: Consultancy; Sierra Oncology: Consultancy; LaJolla Pharmaceutical Company: Consultancy. Thompson:AIM Specialty Health, BMS, GlaxoSmithKline, Takeda, Via Oncology: Membership on an entity's Board of Directors or advisory committees; Doximity: Current equity holder in publicly-traded company, Membership on an entity's Board of Directors or advisory committees; Synapse Precision Medical Council: Other: Travel expenses.

Introduction Chimeric antigen receptor (CAR) T-cell therapy has revolutionized the treatment of B- cell malignancies leading to durable responses in patients with relapsed/refractory disease. 1,2 One of the most severe toxicities associated with this treatment is immune effector cell-associated neurotoxicity syndrome (ICANS), which was seen in 65-75% of patients treated with axicabtagene ciloleucel (axi-cel) in initial clinical trials. ICANS can range from mild headache to coma, and can occur with or without cytokine release syndrome (CRS). Due to the recent development of CAR T-cell therapy, the long-term effects of ICANS are unknown. This study sought to determine the long-term outcomes in patients with neurotoxicity from axi-cel. Methods We conducted a retrospective chart review of patients who received CAR T-cell therapy with axi-cel between June 2018 and June 2021. Neurotoxicity was graded according to the American Society for Transplantation and Cellular Therapy (ASTCT) ICANS grading system. 3 The primary outcome was percentage of patients who had neurotoxicity defined as ICANS grade ≥ 1 as well as the percentage of patients with neurotoxicity lasting ≥ 1 month. We captured descriptive data such as age, sex, ethnicity, comorbidities, IPI score, stage, baseline neurologic dysfunction, performance status, and number of prior treatments. Secondary outcomes included progression free survival (PFS) and overall survival (OS). Results Thirty-four patients received axi-cel between June 2018 and June 2021 at our institution. Median age of patients was 65. Twenty patients (59%) were male and 14 (41%) were female. The majority of patients received axi-cel for diffuse large B-cell lymphoma (97%). Study population was predominantly hispanic (35%), white (32%), African american (29%) and asian (3%). (Sixteen patients (47%) developed neurotoxicity of any grade, with 7 patients (21%) ≥ grade 3. Of note, 4 patients (12%) died during admission for CAR T-cell therapy and 3/4 deaths were in patients with ICANS ≥ grade 3. Median follow up time was 8 months. Of the 12 patients with neurotoxicity who survived initial admission for CAR-T, 9 (75%) patients recovered from neurotoxicity and mental status was at baseline at discharge without recurrence during follow up. Three (25%) of patients had prolonged neurotoxicity lasting > 1 month. Long-term neurotoxicity included confusion, disorientation, and mild cognitive impairment in the three patients. One patient recovered 15 months after CAR T-cell infusion. 2 patients had prolonged neurotoxicity resulting in deterioration of functional status and death in 1 patient, and 1 patient transitioning to hospice and being lost to follow up. Conclusions Neurotoxicity from axicabtagene ciloleucel is a common adverse event, with half of patients in our cohort having neurotoxicity of some degree, and 20% ≥ grade 3. Twenty-five percent of patients that developed neurotoxicity had long-term effects lasting > 1 month, which resulted in deterioration of functional status in 2 patients. Long-term neurotoxicity included disorientation, confusion, and memory impairment. Our study is limited by a small sample size. Larger studies with longer follow-up times are needed to further characterize the long-term outcomes of neurotoxicity associated with CAR T-cell therapy. Neurotoxicity can be confounded by other causes of neurological dysfunction in these patients such as hospital delirium, chemotherapy toxicity, encephalopathy from infection, and subtle baseline neurologic dysfunction that may not be apparent at presentation. Next steps include prospective evaluation of patients with formal neurology evaluation prior to CAR T-cell therapy and periodically after treatment, in order to objectively monitor late neurologic effects of CAR T-cell therapy. 1. Fl, L. et al. Long-term safety and activity of axicabtagene ciloleucel in refractory large B-cell lymphoma (ZUMA-1): a single-arm, multicentre, phase 1-2 trial. Lancet Oncol. 20, (2019). 2. Jacobson, C. Primary Analysis of Zuma-5: A Phase 2 Study of Axicabtagene Ciloleucel (Axi-Cel) in Patients with Relapsed/Refractory (R/R) Indolent Non-Hodgkin Lymphoma (iNHL). in (ASH, 2020). 3. Dw, L. et al. ASTCT Consensus Grading for Cytokine Release Syndrome and Neurologic Toxicity Associated with Immune Effector Cells. Biol. Blood Marrow Transplant. J. Am. Soc. Blood Marrow Transplant. 25, (2019). Disclosures Gritsman: iOnctura: Research Funding. Shastri: Onclive: Honoraria; Guidepoint: Consultancy; GLC: Consultancy; Kymera Therapeutics: Research Funding. Verma: Celgene: Consultancy; BMS: Research Funding; Stelexis: Current equity holder in publicly-traded company; Curis: Research Funding; Eli Lilly: Research Funding; Medpacto: Research Funding; Novartis: Consultancy; Acceleron: Consultancy; Stelexis: Consultancy, Current equity holder in publicly-traded company; Incyte: Research Funding; GSK: Research Funding; Throws Exception: Current equity holder in publicly-traded company.

Background Globally, 5 million to 10 million people are infected with human T-cell leukemia virus type 1, which causes adult T-cell leukemia/lymphoma (ATLL) in 2% to 5% of the carriers. ATLL is a rare but extremely aggressive malignancy that can be challenging to diagnose. Very little data exist on the incidence patterns of ATLL in the United States. Methods ATLL cases reported to the National Program of Cancer Registries, the Surveillance, Epidemiology, and End Results (SEER) program, and the New York State Cancer Registry were used for the study. Age-adjusted incidence rates were calculated by age, race/ethnicity, sex, and year of diagnosis. The 5-year survival rate was compared among race/ethnicity groups with the SEER data. Results During 2001-2015, 2148 ATLL cases were diagnosed in the United States, 18% of which were in New York State. New York State had the highest incidence rate for ATLL, with a rising trend especially among non-Hispanic blacks (NHBs), whereas the incidence was stable across the remainder of the United States. NHBs were diagnosed at a younger median age (54 years) and had a shorter overall survival (6 months). In New York City, only 22.6% of the ATLL cases diagnosed were born in North America. Conclusions This is the largest epidemiological study of ATLL in the United States and shows a rising incidence in New York City. NHBs have a younger age at presentation and poor overall survival. The rising incidence is largely due to NHBs originating from the Caribbean.

Introduction In the United States, autologous hematopoietic cell transplantation (autoHCT) has fallen out of favor over chemotherapy consolidation for non–high-risk acute myeloid leukemia (AML) when allogeneic hematopoietic cell transplantation (alloHCT) is unfeasible, which is common in racial minorities because of donor registry under-representation and socioeconomic challenges. We compared autoHCT consolidation outcomes with chemotherapy alone in a minority-rich cohort in the Bronx. Patients and Methods We identified adults with favorable or intermediate cytogenetic risk AML in first complete remission after induction at Montefiore Medical Center from 1999 to 2015, and analyzed 81 patients who received consolidation with ≥2 cycles of chemotherapy, of whom 28 received autoHCT. Results The cohort predominantly consisted of ethnic/racial minorities (69%). Age, sex, race, presenting white cell count, and cytogenetic risk were similar between groups. The autoHCT group had longer relapse-free (RFS; 43 vs. 11 months; P = .003) and overall (OS) survival (not reached vs. 36 months; P = .043). Adjusted multivariable analysis showed significant benefit of autoHCT over chemotherapy alone for RFS (hazard ratio [HR], 0.53; 95% confidence interval [CI], 0.37-0.75; P Conclusion In this inner-city non–high-risk AML cohort, autoHCT provided OS and RFS benefit compared with chemotherapy alone. AutoHCT might constitute a valuable option for ethnic/racial minorities affected by significant barriers to alloHCT, whereas integration of measurable residual disease can help select patients more likely to benefit.

In the United States adult T cell lymphoma–leukemia (ATLL) carries a dismal prognosis and mainly affects immigrants from human T cell lymphotropic virus 1 endemic areas. Allogeneic hematopoietic stem cell transplant (alloHSCT) can be effective and is recommended as an upfront treatment in the National Comprehensive Cancer Network guidelines. We studied the barriers to alloHSCT in one of the largest ATLL populations in the United States. Comprehensive chart and donor registry reviews were conducted for 88 ATLL patients treated at Montefiore Medical Center from 2003 to 2018. Among 49 patients with acute and 32 with lymphomatous subtypes, 48 (59.5%) were ineligible for alloHSCT because of early mortality (52%), loss to follow-up (21%), uninsured status (15%), patient declination (10%), and frailty (2%). Among 28 HLA-typed eligible patients (34.6%), matched related donors were identified for 7 (25%). A matched unrelated donor (MUD) search yielded HLA-matched in 2 patients (9.5%), HLA mismatched in 6 (28.5%), and no options in 13 (62%). Haploidentical donors were identified for 6 patients (46%) with no unrelated options. There were no suitable donors for 7 (25%) alloHSCT-eligible patients. The main limitation for alloHSCT after donor identification was death from progressive disease (82%). AlloHSCT was performed in 10 patients (12.3%) and was associated with better relapse-free survival (26 versus 11 months, P = .04) and overall survival (47 versus 10 months, P = .03). Early mortality and progressive disease are the main barriers to alloHSCT, but poor follow-up, uninsured status, and lack of suitable donor, including haploidentical, are also substantial limitations that might disproportionally affect this vulnerable population. AlloHSCT can achieve long-term remissions, and strategies aiming to overcome these barriers are urgently needed to improve outcomes in ATLL.

As COVID-19 has been shown to adversely affect patients with cancer, prophylactic strategies are critically needed. We determined the immunogenicity of COVID-19 vaccination in a cohort of cancer patients that had received full dosing with one of the FDA-approved COVID-19 vaccines. 201 oncology patients underwent anti-spike protein SARS-CoV-2 IgG testing post vaccination and demonstrated a high rate of seroconversion (94%) overall. When compared to solid tumors (98%), a significantly lower rate of seroconversion was observed in patients with hematological malignancies (85%), particularly recipients of anti-CD20 therapies (70%) and stem cell transplantation (74%). Patients receiving immune checkpoint inhibitor therapy (97%) or hormonal therapies (100%) demonstrated high seroconversion post-vaccination. Patients with prior COVID-19 infection demonstrated higher anti-spike IgG titers post-vaccination. Relatively lower IgG titers were noted following vaccination with the adenoviral when compared to the mRNA-based vaccines. These data demonstrate generally high immunogenicity of COVID-19 vaccination in oncology patients and identify vulnerable cohorts that need novel vaccination or passive immunization strategies.

Multiple myeloma (MM) in Hispanics has never been studied. We therefore sought to determine the clinical characteristics and overall survival in MM of Hispanics compared to non-Hispanic whites (NHW) and non-Hispanic blacks (NHB).A single-center analysis of 939 patients diagnosed with MM from 2000 to 2017 with a large representation of NHB (n = 489), Hispanics (n = 281), and NHW (n = 169) was conducted to evaluate outcomes and disease characteristics. We used the Connect MM Registry, a large US multicenter prospective observational study with newly diagnosed MM patients, as a validation cohort.Hispanics had a higher incidence of MM compared to NHW. The median age at presentation was 5 years younger (median, 65 years) in Hispanics compared to NHW (median, 70 years), and patients were more likely to present with renal dysfunction (estimated glomerular filtration rate 30 mL/min). Hispanics had a higher proportion of Revised International Staging System (R-ISS) stage I disease compared to NHW and NHB (P = .03), while there was no difference in cytogenetics between Hispanics and NHB/NHW. In the multivariate analysis, only high-risk disease and response to first-line therapy significantly affected survival.In this first and largest analysis of MM in Hispanics, we found that Hispanics present at a younger age, have a higher incidence of renal dysfunction, and have low R-ISS stage disease at presentation. With equal access to therapy, Hispanics have survival similar to NHW/NHB.

Monoclonal Gammopathy of Undetermined Significance (MGUS) is a pre‐malignant clonal plasma cell disorder, with 25 to 30% life‐long risk of progression to multiple myeloma (MM).1 It is usually asymptomatic, but infrequently associated with several serious conditions, such as neuropathies, glomerulonephritis, and acquired angioedema.2 Moreover, a higher risk of infection and deep venous thrombosis has been reported in patients with MGUS.3,4

Umbilical cord blood (CB) transplantation has been used successfully in humans for three decades due to its rapid availability for patients lacking a suitable allogeneic donor, less stringent HLA matching requirements, and low rates of relapse and chronic graft-versus-host disease (GVHD). However, CB transplantation is associated with complications, such as delayed hematopoietic engraftment, graft failure, which increases infection and bleeding and causes longer hospital stays, and transplant-related mortality. The majority of these biological limitations are due to the unforeseeable functional potency of multipotent hematopoietic stem cells (HSCs), which reduce the predictability of successful transplantation; however, several strategies have been developed to increase the number of hematopoietic stem progenitor cells (HSPCs) infused during CB transplantation. This review primarily addresses the methods that promote ex vivo CB expansion within the context of symmetrical and asymmetrical HSC division and those that rely on epigenetic mechanisms, along with the reportedly most successful cytokine combinations. We also review recent clinical research on small molecules (StemRegenin-1, UM171, and nicotinamide) in ex vivo expanded CB and discuss yet unvalidated preclinical strategies. Expanding and transplanting CB graft enriched in HSPCs in a single CB unit is a particularly exciting prospect with the potential to improve the use and availability of CB grafts. Greater knowledge of optimal ex vivo expansion strategies, cell longevity, and graft potency will expand the scope of cellular therapies. Also the development of adequate ex vivo HSPC expansion strategies could bring expanded cord blood grafts to the forefront of transplant therapy and regenerative medicine.

Background: Autologous hematopoietic stem cell transplant (auto-HSCT) is a commonly used treatment for multiple myeloma (MM) and for relapsed/refractory non-Hodgkin lymphomas (NHL) for patients who are 65 years old, and nearly half of those are in patients >75 years old. While some studies have evaluated the use of auto-HSCT in older patients 65-75 years of age, there are few studies evaluating the relative safety of this treatment in patients above the age of 75 years. Such patients and their providers require outcome data of auto-HSCT in the elderly in order to help guide informed decision-making. Methods: We conducted a retrospective cohort study comparing short-term outcomes for auto-HSCT in patients >75 years old and 55-65 years old for the diagnosis of MM or NHL, who were conditioned with either melphalan or BEAM (carmustine, etoposide, cytarabine, melphalan) respectively. To identify patients, we used an internal database of auto-HSCT performed between 2005 - 2021. The study group included patients >75 years old. The control group included patients 55-65 years old that were matched to the study group patients by sex and time of transplant. Medical records were reviewed to gather data on demographics, pre-transplant functional status, transplant indication and conditioning regimen, length of stay, admission mortality, 30-day rehospitalization rate, ICU admission, neutropenic fever and infectious workup results, and time to WBC and platelet engraftment. The primary outcomes of the study were admission mortality, length of stay, time to WBC and platelet engraftment incidence, incidence of neutropenic fever, positive blood culture, ICU admission, and 30-day rehospitalization rate. Averages were calculated using medians and IQR. Admission mortality was evaluated using log rank test. P values were calculated using Fisher's test for categorical data and Wilcoxon rank sum test for continuous data. Significance was denoted by α =0.05. Results: We identified 43 patients aged >75 years old who underwent autologous stem cell transplant for multiple myeloma or lymphoma with melphalan or BEAM conditioning at Montefiore Medical Center between 2005-2021. Patient characteristics (Table 1) The earliest transplant in out cohort was in 12/2005 and the latest was in 3/2021. The median time between transplants of patients in the study and cohort groups was 14 [7.5, 24] days. 24 (55.8%) patients were female. The median age in the study group was 77.1 [76.2, 77.9] years old and 61.9 [57.4, 63.0] years old in the control group. Both groups predominantly included patients from minority populations: 55.8 and 46.5% were Spanish/Hispanic/Latino and 25.6% and 14.0% were African American, in study and control groups respectively. Multiple myeloma was the most common indication for auto-HSCT. Primary outcomes (Table 2) Admission mortality did not differ significantly between the groups, with only one death in the control group (p = 0.083). The length of stay was comparable at 18 [17, 22] days and 19 [16, 20] days (p = 0.2) for study and control groups, respectively. Time to WBC engraftment in the study group was 12 [11, 12] days and 11 [11, 12] days in the control group (p = 0.032). Time to platelet engraftment in the study group was 14 [12, 15] days and 12 [11, 14] days in the control group (p = 0.014). Although both time to WBC and platelet engraftment was significantly longer in the study group, the clinical significance of this finding is questionable, especially as it did not seem to prolong length of stay. There was no significant difference between incidence of neutropenic fever, or between incidence of positive blood cultures in patients with neutropenic fever. There was a non-statistically significant increase in the rate of ICU admissions in the study group vs control group 4/43 and 0/43 respectively (p=0.12). 30-day rehospitalization rate was comparable between the two groups. Conclusion: We did not find a statistically significant increase in morbidity or mortality for patients 75-80 years of age undergoing auto-HSCT compared with patients 55-65 years old. To our knowledge this is the largest cohort to date demonstrating the safety of auto-HSCT in this elderly population. Figure 1 Figure 1. Disclosures Gritsman: iOnctura: Research Funding. Shastri: Onclive: Honoraria; GLC: Consultancy; Kymera Therapeutics: Research Funding; Guidepoint: Consultancy. Verma: Medpacto: Research Funding; Curis: Research Funding; Eli Lilly: Research Funding; Stelexis: Consultancy, Current equity holder in publicly-traded company; Novartis: Consultancy; Acceleron: Consultancy; Celgene: Consultancy; Stelexis: Current equity holder in publicly-traded company; Throws Exception: Current equity holder in publicly-traded company; Incyte: Research Funding; GSK: Research Funding; BMS: Research Funding.

Introduction: Peripheral T-cell lymphomas (PTCLs) are rare and heterogeneous with poor prognosis. There is a paucity of data on outcomes in minority populations. We studied relationships between socioeconomic status (SES), race, and ethnicity and access to hematopoietic stem cell transplant (HSCT) and survival. For analyses of SES we used a measure of neighborhood disadvantage called the Area Deprivation Index (ADI), a composite of 17 measures of education, employment, housing quality, and poverty validated across a range of diseases (Kind et al NEJM 2018). Methods: To identify subjects with PTCL, we used SQL to query our Enterprise Data Warehouse for ICD 10 codes C84 and C91.5. We used medical record numbers for chart review and recorded the following in Excel: WHO 2016 PTCL classification (Swerdlow et al 2016 Blood), sex, race, ethnicity, address, date of birth, date of death/last contact, stem cell source (autologous [auto] vs. allogeneic [allo]), donor sources for allo (matched related [MRD], matched unrelated [MUD], haploidentical [haplo], or syngeneic), conditioning regimen, and date of stem cell infusion (HSCT D0). ADIs were obtained by geocoding subjects' addresses using an online tool (https://geocoding.geo.census.gov/) and matching census block groups to ADI 2019 national percentiles. Conditioning intensity was determined by the Center for International Blood and Bone Marrow Transplant Research operational definition (Giralt et al 2009). For survival analyses, subjects with more than 1 histology were analyzed according to that at HSCT D0. For subjects who underwent auto with subsequent allo, analyses were carried out on the allo. When there was an interval between last date known alive and first date known to have died, death was assumed at the end of the interval. Overall survival (OS) probabilities were estimated using the Kaplan-Meier method. Python, pandas, Matplotlib, and lifelines were used for data analysis and visualization. Results: We identified 407 patients with PTCL, of which 48 underwent HSCT between 9/19/2006 and 4/5/2021 - 22 autos and 26 allos. Data on access to HSCT are summarized in Figure 1 and Table 1. There was not a significant relationship between ADI or ethnicity and access to HSCT. The relationship between race and access to HSCT was significant (p = 0.024). Baseline characteristics of the HSCT cohort are summarized in Tables 2 and 3. Notably, 12/26 allos had adult T-cell leukemia/lymphoma (ATLL). Looking at survival by type of HSCT (Figure 2, Table 4), autos had median OS not reached. Autos' 2 and 4-year OS probabilities were both 81.57%, whereas these were both 40.49% for allos (p = 0.03 for 2 year and 4 year OS). No differences were observed in survival by ADI among autos or allos (Figure 3, Table 5). There was no statistically significant association between race and survival by the log rank test (Figure 4, Table 6). P-values could not be calculated for autos' 2 or 4-year OS. Among allos, p-values suggested a statistical difference in 2 and 4-year OS between white subjects (n = 1) and black/African American (AA) as well as other subjects. Finally, examining survival by ethnicity, no significant differences were seen between Hispanics and Non-Hispanics (Figure 5, Table 7). Conclusions: In our inner-city, minority-rich PTCL cohort, neighborhood disadvantage and ethnicity did not preclude access to HSCT. The autologous transplant survival curve with median OS not reached (longest survivor 14.71 years) indicates that our patients did have optimal, potentially curative outcomes. Although our sample size is small our population is predominantly inclusive of ethnic minorities and low SES. Analyzing larger datasets of ethnically and socioeconomically diverse individuals can provide further insight into HSCT access and outcomes. Figure 1 Figure 1. Disclosures Gritsman: iOnctura: Research Funding. Shastri: Onclive: Honoraria; GLC: Consultancy; Kymera Therapeutics: Research Funding; Guidepoint: Consultancy. Verma: Acceleron: Consultancy; Novartis: Consultancy; Stelexis: Consultancy, Current equity holder in publicly-traded company; Eli Lilly: Research Funding; Curis: Research Funding; Medpacto: Research Funding; Incyte: Research Funding; GSK: Research Funding; BMS: Research Funding; Celgene: Consultancy; Stelexis: Current equity holder in publicly-traded company; Throws Exception: Current equity holder in publicly-traded company.

Introduction: Lenalidomide (LEN) is approved for treatment of Myelodysplastic Syndrome (MDS) with chromosome 5q deletion (del 5q) as it has shown to induce disease remission and transfusion independence in close to 65% of this population. For patients (pts) without del 5q, LEN has shown to reduce transfusion needs in one-quarter of pts, but its use is limited by significant thrombocytopenia, and pts with platelet counts (PLTs) Methods: Pts aged ≥18 years with low/int risk MDS per IPSS, or non-proliferative chronic myelomonocytic leukemia (CMML), with bone marrow blasts Results: 51 pts were accrued, with 44 evaluable pts. Of evaluable pts, most were male (70%), median age was 71 years (range 34-93). 42 (95%) pts had MDS and 2 (5%) CMML. 24 (55%) pts were low-risk per IPSS-R score. 28 (64%) pts were treatment-naïve and 16 (36%) had received ≥1lines of treatment, including erythropoiesis stimulating agents. 24 (55%) pts were assigned to arm A and 20 (45%) pts to arm B. ELT/LEN was well tolerated. Non-hematological grade 3-4 treatment-related adverse events were few, including G3 hyperbilirubinemia (7%), G3 transaminitis (2%), G3 diarrhea (2%), G3 arthralgias (2%). 2 pts had major bleeding events; there were 2 deaths, one attributable to pneumonia and one to gallbladder cancer. 1 of 31 pts who received ELT had a reversible increase in peripheral blasts while on treatment, and 1 pt had development of marrow fibrosis after 6 years of ELT. ITT analysis of total population (51) revealed an objective response (ORR) of 35%; ORR of 32% (9/28) in arm A (PLTs ≥50,000),and 39% (9/23) in arm B (PLTs 17 pts received ELT alone, among these ORR was 41% (7/17), with 29% achieving bilineage responses, 1 CR. 13 pts received LEN alone, ORR was 46% (6/13), of these 100% achieved RBC-TI. 14 pts received ELT/LEN combination, ORR was 36%, 2 (14%) achieved bilineage responses and 2 (14%) CR. There were 2 HIV-positive MDS pts, both achieved sustained CRs, one with ELT alone and one with ELT/LEN combination. Mean time to response was 9.4 wks (range 6-12.4) for ELT alone, 10.9 wks (range 2.4-16) for LEN alone, and 9.9 wks (range 2-20) for ELT/LEN combination. Mean duration of response was 102 wks for ELT (range 8-ongoing), 63 wks (range 25-ongoing) for LEN, and 66 wks (range 8.3-ongoing) for ELT/LEN as of last follow-up. Conclusions: Treatment with ELT/LEN demonstrates good efficacy with ORR of 40.9%, response durability and an acceptable safety profile for evaluable pts with low/int risk MDS. ELT can lead to single agent responses with an acceptable safety profile and sizable proportion of multilineage responses. One patient developed bone marrow fibrosis and one patient had a transient increase in blasts, hence, undermining these pre-existing safety concerns. Lastly, using our study schema 32% of pts were able to initiate or continue LEN achieving a 36% ORR whereas in prior studies these pts would have been excluded. Figure 1 Figure 1. Disclosures Yacoub: Agios: Membership on an entity's Board of Directors or advisory committees; Acceleron Pharma: Membership on an entity's Board of Directors or advisory committees; CTI Biopharma: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; Incyte: Speakers Bureau. Gritsman: iOnctura: Research Funding. Shastri: Kymera Therapeutics: Research Funding; Onclive: Honoraria; GLC: Consultancy; Guidepoint: Consultancy. Verma: Celgene: Consultancy; Acceleron: Consultancy; Novartis: Consultancy; Stelexis: Consultancy, Current equity holder in publicly-traded company; Eli Lilly: Research Funding; Curis: Research Funding; Medpacto: Research Funding; Incyte: Research Funding; Stelexis: Current equity holder in publicly-traded company; Throws Exception: Current equity holder in publicly-traded company; GSK: Research Funding; BMS: Research Funding. OffLabel Disclosure: Lenalidomide has shown to be effective achieving RBC Transfusion Independence in Myelodysplastic Syndromes without deletion 5q Eltrombopag is a TPO-R agonist, its purpose in this trial is to evaluate if it would increase platelet counts in patients with Myelodisplastic Syndrome.

Decitabine (Dec) and Azacitidine (Aza) that target DNA methyltransferase 1 (DNMT1) are hypomethylating agents (HMAs) approved to treat acute myeloid leukemia (AML) in combination with Venetoclax (Ven). The combination is also used to treat high-risk myelodysplastic syndromes, especially TP53-mutated (TP53mut) cases in which responses to HMA alone are short-lived. In most patients (pts), however, myelosuppression from treatment leads to frequent Ven duration and/or dose-reductions, and/or cycle delays. An approach to decrease HMA-mediated myelosuppression but maintain S-phase dependent DNMT1-targeting, evaluated in a previous clinical trial (https://doi.org/10.1111/bjh.16281), is to administer noncytotoxic doses/concentrations of Dec (0.2 mg/kg; ~5 mg/m 2) by a frequent-distributed schedule of 1X/week. An approach to decrease Ven mediated myelosuppression but maintain cooperation with HMA, shown in pre-clinical studies, is to administer a single-dose prior to HMA. Ven can depolarize mitochondrial membranes; mitochondrial membrane-potential is essential to function of the mitochondrial enzyme DHODH that produces cytidine/deoxycytidine that competes with HMA in cells. Thus, Ven prior to HMA dosing temporarily inhibits de novo pyrimidine synthesis, to counter a major mechanism of resistance to HMA in MDS/AML, without suppressing normal myelopoiesis (https://doi.org/10.1182/blood-2020-143200). We conducted a retrospective analysis of all pts with TP53mut MDS or AML treated with weekly Ven and low-dose subcutaneous Dec at our institution. We analyzed the characteristics of these pts, response to therapy, and outcomes using standard descriptive statistics. Mutational testing was performed using a commercial next-generation sequencing (NGS) panel. Five pts, 3 male and 2 female, with TP53mut MDS or AML were treated with weekly Ven 400 mg on D1 and subcutaneous Dec 0.2 mg/kg on D2, administered weekly in 28 day cycles. Two pts had MDS (1 de novo, 1 treatment related) and 3 pts had AML (1 de novo, 2 secondary from prior MDS). Four pts (80%) received the treatment in frontline, all with poor performance status (PS), and 1 pt (20%) had R/R disease. Median age at diagnosis was 79 years [41-82]. The only young pt had prolonged severe cytopenias after 1 cycle Dec standard dosing during the peak of COVID-19 pandemic so was switched to this regimen. Of the 4 frontline treated pts, 2 pts had high-risk MDS, and 2 pts had adverse risk AML. The R/R pt had high-risk MDS transformed to AML that was refractory to 2 prior lines of therapy: standard Aza/Ven x5 cycles, then standard Vyxeos. Disease cytogenetics were complex in all pts. 60% (3/5) pts had sole TP53mut on NGS, with median variant allelic frequency (VAF) 48% [28-79]. 80% (4/5) pts were transfusion dependent prior to treatment. Median time to initiating therapy was 7 days from initial or refractory diagnosis [3-59] and median follow-up was 7.8 months (mo) [2.9-11.4]. The overall response rate (ORR) was 100%: 4/4 frontline pts had complete remissions (CR), and the 1 R/R pt achieved morphologic leukemia-free state (MLFS). Median time to best response was 2.9 mo. 50% (2/4) pts became transfusion independent. 40% (2/5) pts lost their TP53mut at best response, and another 40% (2/5) pts had significant reductions (83% and 38%) in TP53 mut VAF. The regimen was well tolerated with no pts stopping therapy due to adverse effects (AE) . AE included G3/G4 neutropenia (80%), G1 thrombocytopenia (40%), nausea (20%), fatigue (20%), lower extremity edema (20%), pneumonia (60%), and neutropenic fever (20%) with a median of 1 unplanned hospitalization per pt during follow-up. 60% (3/5) pts remain in CR on continued therapy for a median of 7.8 mo [7.2-9.4] thus far. One pt underwent allogeneic stem cell transplantation, however, died 11.4 mo after conditioning due to transplant related mortality. The R/R pt died after being lost to follow-up 2.9 mo after therapy initiation. No pt had measurable relapse during follow-up. Combination weekly Ven with subcutaneous low-dose Dec is well tolerated yielding high rates of clinical and molecular response in pts with TP53mut MDS/AML. Although small, this case-series extends previous clinical trial proof-of-activity of non-cytotoxic DNMT1-targeting to a high-risk, poor PS, historically chemorefractory patient population. The regimen allowed frequent, sustained exposure to therapy often not possible with standard HMA/Ven regimens. Figure 1 Figure 1. Disclosures Shastri: Kymera Therapeutics: Research Funding; Guidepoint: Consultancy; GLC: Consultancy; Onclive: Honoraria. Gritsman: iOnctura: Research Funding. Feldman: Glycomimetics: Current Employment, Current holder of stock options in a privately-held company. Verma: Celgene: Consultancy; Acceleron: Consultancy; Novartis: Consultancy; Stelexis: Consultancy, Current equity holder in publicly-traded company; Eli Lilly: Research Funding; Curis: Research Funding; Medpacto: Research Funding; Incyte: Research Funding; GSK: Research Funding; BMS: Research Funding; Stelexis: Current equity holder in publicly-traded company; Throws Exception: Current equity holder in publicly-traded company. Saunthararajah: EpiDestiny: Consultancy, Current holder of individual stocks in a privately-held company, Membership on an entity's Board of Directors or advisory committees, Patents & Royalties.

Introduction: North American-ATLL (NA-ATLL) is a distinct genomic and clinical entity when compared with Japanese ATLL. Despite the frequent CNS involvement by this entity there are no prognostication tools to identify variables associated with higher risk. We studied one of the largest NA-ATLL cohorts in the United States at a minority rich ethnically diverse New York City based tertiary care center to identify discrete variables that may be associated with CNS involvement. Additionally, we examined the predictive power of the previously validated International Prognostic Index (IPI) developed for Diffuse Large B-cell Lymphoma (DLBCL) in terms of CNS involvement as well as overall survival in our cohort. In our previous work, we assigned CNS involvement of ATLL if: 1) cerebrospinal fluid (CSF) cytology or flow cytometry was positive; 2) CNS imaging was positive for disease involvement or 3) physical exam was compatible with neurologic involvement. Methods and results: Of 65 NA-ATLL patients (pts), 20 (30.77%) had CNS involvement by ATLL meeting above mentioned criteria. The median age of all pts in our dataset was 59 years. Pts were divided into non- CNS involved NA-ATLL (non-CNS NA-ATLL) and CNS involved NA-ATLL (CNS NA-ATLL) groups. Parameters to predict CNS involvement were outlined as leukocytosis (>11000 per microliter [μL]), elevated acute lymphocytic count (>4000/ μL), elevated lactate dehydrogenase (LDH) (>190 units/liter [u/l]), generalized lymphadenopathy (LAD) defined as involvement of 2 or more non-contiguous nodal sites, elevated corrected serum calcium levels (>10.5 mg/deciliter), bone marrow (bm) involvement and serosal involvement defined as pleural or peritoneal involvement. These variables were chosen given our prior work identifying them as critical to predict OS in our general NA-ATLL population. We then performed the Fisher test of proportions to determine if the variables above mentioned were different between the CNS NA-ATLL and the non-CNS NA-ATLL. We did not find significant associations when analyzing gender (p=0.0535), leukocytosis (p= 0.4001), lymphocytosis (p =0.57), hypercalcemia (p= 0.7661), elevated LDH (p= 0.4898), generalized LAD (p=0.271), serosal involvement (p= 0.05088) or bone marrow involvement (p=1). We only found a strong association when examining ATLL subtypes, being the acute/lymphomatous variant strongly associated with CNS involvement (p=2.226e10 -5). To identify variables that can have an impact in OS in CNS NA-ATLL vs non-CNS NA-ATLL we calculated Kaplan Meier survival curves. We did not find any difference based on age (p=0.23), gender (p=0.95), leukocytosis (p= 0.074), lymphocytosis (p =0.21), hypercalcemia (p= 0.094), elevated LDH (p= 0.37), generalized LAD (p=0.28), and serosal involvement (p= 0.1) in the overall survival. The only significant association we found was bone marrow involvement in predicting poor OS in CNS NA-ATLL group (p= 0.038). Next, we determined IPI scores (age>60, ECOG performance status>2, Ann Arbor stage III/IV, serum LDH score >190 u/L and more than 1 extra-nodal site) in our CNS NA ATLL and non-CNS NA ATLL cohorts. We sought to determine if: 1) this prognostication tool is predictive in NA-ATLL and 2) if these variables can be used to identify CNS involvement in our cohort. CNS pts with a higher IPI score (>3) showed tendency towards a lower survival rate (p=0.089) than non-CNS pts (p=0.3). IPI score of 3 or more was not predictive of CNS involvement in our sample (p=1). Conclusions: NA-ATLL is a rare and protean disease with poor prognosis and CNS involvement is prevalent. With the variables used we did not find clear predictors of CNS associated disease other than patients presented with the lymphomatous and acute subtypes. We also observed than bone marrow involvement portends a dismal prognosis for individuals with CNS involvement. Future studies with a larger cohort could provider further insight on discovering predictors for CNS involvement in NA ATLL. Figure 1 Figure 1. Disclosures Shah: Celgene/BMS: Research Funding; Janssen: Research Funding. Gritsman: iOnctura: Research Funding. Shastri: GLC: Consultancy; Kymera Therapeutics: Research Funding; Guidepoint: Consultancy; Onclive: Honoraria. Verma: BMS: Research Funding; GSK: Research Funding; Incyte: Research Funding; Medpacto: Research Funding; Curis: Research Funding; Eli Lilly: Research Funding; Stelexis: Consultancy, Current equity holder in publicly-traded company; Novartis: Consultancy; Acceleron: Consultancy; Celgene: Consultancy; Stelexis: Current equity holder in publicly-traded company; Throws Exception: Current equity holder in publicly-traded company. Janakiram: Amgen: Honoraria.

BACKGROUND: Adoptive immunotherapy using CD19-targeted Chimeric antigen receptor T cells (CAR-T) has revolutionized the treatment of relapsed/refractory diffuse large B-cell lymphoma (DLBCL). Data is limited on the propensity of infections and lymphohematopoietic reconstitution after Day 30 (D30) following CAR-T cell therapy. In this study, we evaluated the prevalence and nature of infectious complications in an expanded cohort of DLBCL patients treated with CD19 CAR-T therapy and its association with the dynamics of leukocyte subpopulation reconstitution post-CAR-T cell therapy. METHODS: We conducted a retrospective study including 19 patients who received axicabtagene ciloleucel and investigated associations between cytopenia and infectious complications after D30. RESULTS: Nineteen patients were included, consisting of 42% Hispanic, 32% Caucasian, 21% African-American, and 5% Asian subjects. Post-D30 of CAR-T infusion, 47% patients (n=9) developed an infection and 53% (n=10) remained infection-free. The most common infection type observed was viral (7 patients) followed by bacterial (5 patients) and fungal (3 patients). Of 25 total infectious events, 56% were grade 1 or 2 and 44% were grade 3 with 10 being viral in etiology. To determine the kinetics of lymphohematopoietic reconstitution and its association with infection risk, we evaluated the relationship between cytopenias and rates of infection after D30. Notably, compared to non-infection group, infection group had a higher median absolute lymphocyte count (ALC) (1,000/µL vs. 600/µL, P1,500/µL in the infection group as opposed to 70% in the non-infection group at D90 (P

As COVID-19 adversely affects patients with cancer, prophylactic strategies are critically needed. Using a validated antibody assay against SARS-CoV-2 spike protein, we determined a high seroconversion rate (94%) in 200 patients with cancer in New York City that had received full dosing with one of the FDA-approved COVID-19 vaccines. Comparing to solid tumors (98%), a significantly lower rate of seroconversion was observed in patients with hematological malignancies (85%), particularly recipients following highly immunosuppressive therapies such as anti-CD20 therapies (70%) and stem cell transplantation (73%). Patients receiving immune checkpoint inhibitor therapy (97%) or hormonal therapies (100%) demonstrated high seroconversion post-vaccination. Patients with prior COVID-19 infection demonstrated higher anti-spike IgG titers post-vaccination. Relatively lower IgG titers were observed following vaccination with the adenoviral than mRNA-based vaccines. These data demonstrate generally high immunogenicity of COVID-19 vaccination in oncology patients and identify immunosuppressed cohorts that need novel vaccination or passive immunization strategies., Graphical Abstract, Evaluating the IgG levels against SARS-CoV-2 spike protein, Astha et al. demonstrate high rates of seroconversion in a diverse cohort of patients with cancer, while identifying lower immunogenicity in patients with hematological malignancies and in patients having received immunosuppressive therapies.

Introduction: Adult T cell leukemia lymphoma (ATLL) is a rare T cell neoplasm caused by the human T-lymphotropic virus (HTLV-1) virus. Although there are indolent subtypes it is often a highly aggressive and chemotherapy refractory malignancy. We follow one of the largest cohorts in the United States and in this study, we sought to elucidate the prognostic factors associated with inferior survival. Methods: A retrospective analysis of patients diagnosed with ATLL at Montefiore Medical Center was conducted. Subjects included were censored at last point of contact. Variables collected included age, gender, race, ethnicity, ATLL subtype, white blood cell count (WBC), absolute lymphocyte count (ALC), corrected calcium level, lymphadenopathy (LAD) (two or more non-contiguous sites). Associations between WBC, ALC, corrected calcium level, LAD and median overall survival (mOS) were assessed using the Kaplan-Meier method with log-rank test. A four-point prognostic system was designed assigning one point to each: WBC > 11,000; ALC>4000; Corrected Ca≥10.5 and presence of LAD. Three risk groups were assigned based on the number of risk factors as follows: low (0-1 points), intermediate (2 points) and high (3-4 points) (Table 2). Association between these groups and OS was investigated using the Kaplan-Meier method with log-rank test. Results: A total of 61 ATLL subjects were included in this study (table 1). Hypercalcemia (Ca ≥10.5) was observed in 60.6% of subjects at diagnosis and was associated with inferior mOS (234 days) when compared to calcium < 10.5 (747days) (p=0.046), Figure 1A. WBC >11,000 had a strong association with inferior survival (175 days) compared to patients with a WBC ≤11,000 (666 days) (p= 0.0067) (Figure 1B). ALC > 4000 was also associated with inferior mOS (222 days) compared to ALC ≤4000 (666 days) (p=0.015) (Figure 1C). LAD was associated with mOS (188 days) compared with no LAD (847 days) (p=0.022) (Figure 1D). Based on these observations, we designed a prognostic system (0-4 points) (see above) to risk stratify newly diagnosed ATLL patients into: low (0-1 points), intermediate (2 points) and high (3-4 points) risk (Table 2). We divided our cohort into the above-mentioned risk groups and calculated their mOS. Kaplan Meier analysis (Figure 2) revealed a distinct mOS difference between the groups based on their risk score: Low: 419 days, Intermediate: 234 days and High: 181.5 days (p= 0.0042). Conclusions: We identify hypercalcemia (Ca≥10.5), leukocytosis (WBC> 11,000), lymphocytosis (ALC> 4000) and generalized LAD as poor prognostic factors in newly diagnosed ATLL. Using readily available information from basic laboratory and clinical parameters we propose a prognostic system to identify high risk individuals. Further validation will be needed using larger cohorts of this very rare disease. Disclosures Steidl: Aileron Therapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Stelexis Therapeutics: Consultancy, Current equity holder in private company, Membership on an entity's Board of Directors or advisory committees; Pieris Pharmaceuticals: Consultancy; Bayer Healthcare: Research Funding. Verma:stelexis: Current equity holder in private company; BMS: Consultancy, Research Funding; acceleron: Consultancy, Honoraria; Janssen: Research Funding; Medpacto: Research Funding. Janakiram:Takeda, Fate, Nektar: Research Funding. Shah:Celgene/BMS: Research Funding; Physicians Education Resource: Honoraria.

Introduction: Adult T-cell leukemia lymphoma (ATLL) is a rare hematologic malignancy caused by human T-cell lymphotropic virus (HTLV-1) with dismal cure rates and poor response to conventional chemotherapy. Allogeneic Hematopoietic Stem Cell Transplantation (AlloSCT) is the only therapeutic option which may offer the chance of long-term remission and cures in a subset of patients. We sought to investigate the outcomes of transplantation in one of the largest cohorts in North America. Methods: A retrospective chart review study was conducted using the North-American ATLL and the Hematopoietic Precursor Cell transplantation databases at Montefiore Medical Center from 2011 to 2020. Variables collected include age, sex, ethnicity, ATLL subtype, molecular profile, previous treatments, conditioning regimens, type of transplant, immunosuppressive regimen, progression free survival (PFS) post-transplant and overall survival (OS) post-transplant. Results: Fourteen patients with ATLL who received an AlloSCT from 2011-2020 were identified. Fifty-seven percent (8/14) of patients were male. Seventy-one percent (10/14) of patients were African American and twenty-nine percent (4/14) were Hispanic. Median age was 51 years. Sixty-four percent (9/14) of patients had Stage IV disease at the time of diagnosis. Forty-three percent (6/14) patients had acute and fifty-seven percent (8/14) had lymphomatous ATLL. Almost all patients (92%) were treated initially with EPOCH combination chemotherapy. Twenty-eight percent (4/14) of patients received interferon/zidovudine as bridge-to-transplant. Fifty-seven percent (8/14) of patients achieved complete remission (CR) prior to AlloSCT, 7% (1/14) were in partial remission, and 28% (4/14) were relapsed or refractory. Forty-three percent (6/14) of patients received SCT from a matched-related donor (MRD), 36% (5/14) from a haplo-identical donor and 21% (3/14) from a matched-unrelated donor (MUD). Ninety-three percent (13/14) of patients received a reduced-intensity conditioning (RIC) regimen pre-transplantation. Seven percent (1/14) received a myeloablative conditioning (MAC) regimen. RIC regimens consisted of fludarabine with melphalan +/- anti-thymocyte globulin (ATG) or fludarabine with cyclophosphamide with total-body irradiation in doses less than 500 cGy. Patients receiving haplo-identical SCT also received post-transplant cyclophosphamide (PTCy) for prevention of graft vs host disease (GVHD). The MAC regimen used included busulfan with cyclophosphamide at myeloablative doses. Twenty-eight percent (4/14) of patients relapsed post-alloSCT with a median relapse-free survival of 6 months (range 4-18 months). The median OS of the whole cohort was 27 months (8-82 months). Graft-versus-host disease (GVHD) developed in 28% (4/14) percent of patients. The most common manifestation was skin GVHD. Fifty-percent (7/14) of the patients are surviving to-date. Transplant-related mortality (TRM) at day 100 was 21% (3/14) of patients. Causes of death were complex and included several diagnoses in certain patients. The most frequent diagnoses associated with death were infection (28%), graft failure (14%), GVHD (14%), veno-occlusive disease of the liver (VOD) (7%), disease progression (14%) and unknown due to patient lost to follow-up (14%). The main infectious events included fungal (2), bacterial (1), and COVID-19 (1) infection. Forty-three percent (6/14) of patients remain in complete remission to date. Conclusions: Allogeneic Stem Cell Transplantation offers long-term survival with a TRM of 21% in a disease with an inherently dismal prognosis. AlloSCT using several graft sources, is thus, a safe and well tolerated treatment modality and offers long term remissions. Disclosures Steidl: Pieris Pharmaceuticals: Consultancy; Aileron Therapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Bayer Healthcare: Research Funding; Stelexis Therapeutics: Consultancy, Current equity holder in private company, Membership on an entity's Board of Directors or advisory committees. Verma:BMS: Consultancy, Research Funding; acceleron: Consultancy, Honoraria; Janssen: Research Funding; Medpacto: Research Funding; stelexis: Current equity holder in private company. Janakiram:ADC Therapeutics, FATE therapeutics, TAKEDA pharmaceuticals: Research Funding.

Adult T-cell leukemia/lymphoma (ATL) is an aggressive T-cell malignancy with a dismal prognosis, caused by HTLV-1. Although our previous study, mainly using whole-exome sequencing and SNP array karyotyping, discovered many driver mutations and copy number alterations (CNAs), the whole-genome landscape of ATL still remains elusive. To this end, we have performed high-depth whole-genome sequencing (WGS) of 155 ATL cases with a median sequencing depth of 96-fold for tumors. Among them, 75 cases were also analyzed by RNA sequencing (RNA-seq). In total, we detected 1,952,490 single nucleotide variants (SNVs) and 159,141 insertion-deletions (4.0 SNVs and 0.3 indels/Mb/case), 10,279 SVs (66.3 SVs/case), and 3,975 CN altered segments (25.7 segments/case). Using several driver discovery algorithms (dNdScv, MutSig2CV, and DriverPower), we identified 47 significantly mutated genes, 19 of which were mutated in more than 10% of cases. These included several novel mutations, such as those affecting XPO1 (7.1%), ZNF292 (6.5%), and ITGB1 (5.2%). Using GISTIC2.0, we identified 13 significant CNAs, such as IRF4 amplifications and CDKN2A deletions, consistent with previous SNP array data. To detect significantly recurrent SVs, we calculated SV breakpoint frequency and identified 13 genes affected by SVs, including the previously identified genes (such as CARD11, CD274, and TP73). In addition, we investigated recurrent mutations in non-coding elements by DriverPower and LARVA and discovered 12 recurrently mutated elements. Among them, the most frequent were splice site mutations, including those of HLA-A and HLA-B, most of which caused loss of function as revealed by RNA-seq. By contrast, we found recurrent mutations in TP73 splice site, which induced skipping of exons 2 and 3, generating a dominant-negative variant similar to their SVs. In addition, recurrent non-coding elements contained several novel regions, such as 3´-untranslated region (UTR) of NFKBIZ and 5´- UTR of TMSB4X. Altogether, a total of 56 genes were recurrently altered. The median number of driver alterations was eight per case, and at least one driver alteration was found in 149 cases (96.1%). Among 56 driver genes, 40 (71.4%) genes were affected by more than one alteration class. Some drivers, such as CDKN2A, IKZF2, and CD274, were affected almost exclusively by CNAs and/or SVs, while showing quite high alteration frequencies (11.6-29.0%). These observations suggest that WGS presented a substantially different overview of driver alterations from our previous study. The overall numbers of mutations and SVs were linked to these driver alterations, suggesting their etiology. In particular, inactivation of EP300 and immune-related molecules, such as HLA-A, HLA-B, and CD58, were associated with an increased number of mutations and SVs, especially deletions and tandem duplications. By contrast, cases with TP53-altered cases harbored more inversions and translocations. These results emphasize a pivotal role of immune evasion for acquiring genetic alterations to drive ATL progression. To define molecular subgroups in ATL, we integrated the 56 identified genetic drivers using non-negative matrix factorization clustering and identified two robust subgroups with discrete clinical and genetic characteristics. Group 1 was enriched with alterations affecting distal components of T-cell receptor (TCR)/NF-κB signaling (such as CARD11, PRKCB, and IRF4) and immune-related molecules (HLA-A, HLA-B, and CD58), whereas proximal regulators of TCR/NF-κB signaling (PLCG1, VAV1, and CD28) and a JAK/STAT signaling molecule (STAT3) were more frequently altered in group 2. In addition, group 1 cases had a larger number of mutations, SVs, and CNAs than group 2 cases. Clinically, most cases with lymphoma subtype were classified into group 1, whereas group 2 mainly consisted of cases with leukemic subtypes. Moreover, group1 cases showed a worse overall survival than group 2, independently of clinical subtype. These results suggest the biological and clinical relevance of the molecular classification of ATL. In summary, our WGS analysis not only identifies novel somatic alterations but also extends the overview of ATL genome. We also propose a new molecular classification of ATL, with its clinical relevance, which can lead to the future improvement of patient management. Disclosures Kogure: Takeda Pharmaceutical Company Limited.: Honoraria. Nosaka:Kyowa Kirin Co.Ltd: Honoraria; Chugai pharmaceutical Co. Ltd: Honoraria; Novartis international AG: Honoraria; Celgene K.K: Honoraria; Eisai Co., Ltd: Honoraria; Merck Sharp & Dohme K.K.: Honoraria; Bristol-Myer Squibb: Honoraria. Imaizumi:Kyowa Kirin Co. Ltd.: Honoraria; Bristol-Myers Squibb: Honoraria; Celgene: Honoraria; Eisai: Honoraria. Utsunomiya:Kyowa Kirin: Honoraria; Celgene: Honoraria. Shah:Celgene: Research Funding; BMS: Research Funding; Physicians Education Resource: Honoraria. Janakiram:Takeda, Fate, Nektar: Research Funding. Ramos:NIH: Research Funding. Takaori-Kondo:Astellas Pharma: Honoraria, Research Funding; Celgene: Honoraria, Research Funding; Bristol-Myers Squibb: Honoraria, Research Funding; Kyowa Kirin: Honoraria, Research Funding; Ono Pharmaceutical: Research Funding; Thyas Co. Ltd.: Research Funding; Takeda: Research Funding; CHUGAI: Research Funding; Eisai: Research Funding; Nippon Shinyaku: Research Funding; Otsuka Pharmaceutical: Research Funding; Pfizer: Research Funding; OHARA Pharmaceutical: Research Funding; Sanofi: Research Funding; Novartis Pharma: Honoraria; MSD: Honoraria. Miyazaki:Sumitomo Dainippon Pharma Co., Ltd.: Honoraria; Kyowa Kirin Co., Ltd.: Honoraria; Chugai Pharmaceutical Co., Ltd.: Honoraria; Celgene: Honoraria; NIPPON SHINYAKU CO.,LTD.: Honoraria; Otsuka Pharmaceutical: Honoraria; Novartis Pharma KK: Honoraria; Astellas Pharma Inc.: Honoraria. Matsuoka:Chugai Pharmaceutical Co. Ltd: Research Funding; Bristol-Myers Squibb: Research Funding; Kyowa Kirin Co. Ltd.: Research Funding. Ishitsuka:Takeda: Other: Personal fees, Research Funding; mundiharma: Other: Personal fees; Taiho Pharmaceuticals: Other: Personal fees, Research Funding; Janssen Pharmaceuticals: Other: Personal fees; Novartis: Other: Personal fees; Pfizer: Other: Personal fees; Astellas Pharma: Other, Research Funding; Genzyme: Other; Sumitomo Dainippon Pharma: Other, Research Funding; Eisai: Other, Research Funding; Mochida: Other, Research Funding; Shire: Other; Otsuka Pharmaceutical: Other; Ono Pharmaceutical: Other, Research Funding; Teijin Pharma: Research Funding; MSD: Research Funding; Asahi kasei: Research Funding; Eli Lilly: Research Funding; Daiichi Sankyo: Other; Huya Japan: Other; Celgene: Other: Personal Fees; Kyowa Hakko Kirin: Other: Personal fees, Research Funding; BMS: Other: Personal fees; Chugai Pharmaceutical: Other: Personal fees, Research Funding. Ogawa:Asahi Genomics Co., Ltd.: Current equity holder in private company; Chordia Therapeutics, Inc.: Membership on an entity's Board of Directors or advisory committees, Research Funding; KAN Research Institute, Inc.: Membership on an entity's Board of Directors or advisory committees, Research Funding; Sumitomo Dainippon Pharma Co., Ltd.: Research Funding; Otsuka Pharmaceutical Co., Ltd.: Research Funding; Eisai Co., Ltd.: Research Funding. Shimoda:Takeda Pharmaceutical Company: Honoraria; Bristol-Myers Squibb: Honoraria; Shire plc: Honoraria; Celgene: Honoraria; Perseus Proteomics: Research Funding; PharmaEssentia Japan: Research Funding; AbbVie Inc.: Research Funding; Astellas Pharma: Research Funding; Merck & Co.: Research Funding; CHUGAI PHARMACEUTICAL CO., LTD.: Research Funding; Kyowa Hakko Kirin Co., Ltd.: Research Funding; Pfizer Inc.: Research Funding; Otsuka Pharmaceutical: Research Funding; Asahi Kasei Medical: Research Funding; Japanese Society of Hematology: Research Funding; The Shinnihon Foundation of Advanced Medical Treatment Research: Research Funding; Novartis: Honoraria, Research Funding. Kataoka:CHUGAI PHARMACEUTICAL CO., LTD.: Research Funding; Takeda Pharmaceutical Company: Research Funding; Otsuka Pharmaceutical: Research Funding; Asahi Genomics: Current equity holder in private company.

Background: Adoptive immunotherapy using CD19-targeted Chimeric Antigen Receptor T-cells (CAR-T) has revolutionized the treatment of relapsed/refractory diffuse large B-cell lymphoma (DLBCL). We have demonstrated the efficacy of FDA-approved axicabtagene ciloleucel (Yescarta) in a multiethnic New York City underserved population with 80% complete response (CR) rate in the first ten patients treated at our institution (Abbasi et al., 2020). There is limited data on the propensity of infections and lymphohematopoietic reconstitution after Day 30 (D30) following CAR-T cell therapy. In this study, we evaluated the prevalence and nature of infectious complications in an expanded cohort of DLBCL patients treated with CD19 CAR-T therapy and its association with the dynamics of leukocyte subpopulation reconstitution post-CAR-T cell therapy. Methods: We conducted a retrospective study of patients who received CAR-T therapy at our institution between 2018-2020. Variables collected include patient demographics, absolute neutrophil (ANC), lymphocyte (ALC) and monocyte counts (AMC) at Day 30, hematologic reconstitution (ANC≥ 1500/µL) at Day 90 (D90), presence or absence of infections after D30 by clinical and/or microbiological parameters. Associations between presence of infection and D30 ANC, ALC, AMC, ANC/ALC ratio, AMC/ALC ratio were assessed using Kruskal-Wallis test. Association between infection and hematologic reconstitution at D90 was done using Chi-square test. Kaplan-Meier curves with log-rank test were used to evaluate overall survival (OS) and progression-free survival (PFS). Results: Nineteen patients were evaluated in our study, consisting of 42% (8) Hispanic, 32% (6) Caucasian, 21% (4) African-American, and 5% (1) Asian subjects. Based on clinical and microbiologic data, 47% (9) developed an infection after D30 (infection group) while 53% (10) of subjects remained infection-free after D30 (non-infection group). The most common infection type observed was viral (11 patients) followed by bacterial (8 patients) and fungal (3 patients) (Table 1). Of 25 total infectious events, 44% (11) were grade 1 or 2 and 48% (12) were grade 3 with 10 being viral in etiology. Two deaths occurred due to an infectious process. Three patients tested SARS-CoV-2 positive and were hospitalized with COVID-19 pneumonia. Median OS and PFS has not been reached in either group. To determine the kinetics of lymphohematopoietic reconstitution and its association with infection risk, we evaluated the relationship between cytopenias and rates of infection after D30. Notably, compared to non-infection group, infection group had a higher median ALC (1000/µL vs 600/µL p=0.04), a lower median ANC/ALC ratio (1.4 vs 4.5 p1500/µL) at D90. We observed that only 22% (2) of patients had recovered ANC > 1500/µLin the infection group as opposed to 80% (8) in the non-infection group at D90 (p= 0.038). Rates of cytokine release syndrome (CRS) were comparable between the two groups (55.6% vs 70% p=0.52). Surprisingly, rates of immune-effector cell associated neurotoxicity syndrome (ICANS) was lower (55.6%) in the infection group compared to (90%) non-infection group (p=0.09). Fourteen of 19 patients had follow-up over one year, of which 8 (57%) remained in complete remission (CR). Conclusions: We demonstrate an infection rate of 47% (9) beyond D30 in patients undergoing CD19 CAR-T. Increased ALC, lower ANC/ALC and AMC/ALC ratios at D30 may be predictive of infectious complications. Median OS has not been reached in our cohort. Given the potential clinical impact, our observations should be corroborated using larger datasets. Disclosures Steidl: Pieris Pharmaceuticals: Consultancy; Bayer Healthcare: Research Funding; Stelexis Therapeutics: Consultancy, Current equity holder in private company, Membership on an entity's Board of Directors or advisory committees; Aileron Therapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding. Janakiram:ADC Therapeutics, FATE therapeutics, TAKEDA pharmaceuticals: Research Funding. Verma:BMS: Consultancy, Research Funding; acceleron: Consultancy, Honoraria; Janssen: Research Funding; stelexis: Current equity holder in private company; Medpacto: Research Funding.

Introduction Acquired Aplastic Anemia (AA) is a rare life-threatening immune-mediated bone marrow disorder. AlloHSCT is the only available curative therapy for SAA with a 3 year survival probability for adults between 72-80% in the United States. (D'Souza et all, Biol BMT 2020). The management of AA is complex and requires complicated regimens, recruitment of a BM donor, supportive care and close monitoring of hematopoietic response to therapy. Patients unable to follow closely with their physician or who lack sufficient social support are often deemed inappropriate candidates for BMT. The Bronx is one of the poorest urban counties in the US. 27.4% of Bronx residents live below the poverty line and 59% speak a language other than English at home. The socioeconomic circumstances for many Bronx residents present a multitude of health challenges that lead to poor health outcomes. Delivering the complex diagnosis and treatment strategies required for AA, a rare disease, can be particularly challenging for this population. Through this retrospective cohort study, we sought to find out the rate of utilization of curative therapies among patients with severe aplastic anemia in the Bronx, NY and to identify barriers to their care. We hypothesized that despite several social & financial barriers, SAA patients that can avail of IST +/- AlloHSCT at a tertiary care center will have similar survival trends as the national standard. Methods Our study used a data search tool called Clinical Looking Glass to identify adult patients diagnosed with AA at Montefiore Medical Center (MMC) between 2000 and 2018. Under an IRB approved protocol, we extracted all patients with a bone marrow biopsy performed between 2000 and 2018 and an ICD-9 diagnosis code of AA. Only patients aged 17 and above at the time of the index date (BM biopsy) were included. We also reviewed each chart to ensure the diagnosis of AA was confirmed by the BM biopsy. We performed a retrospective chart review of each patient in our cohort using our electronic medical records. Clinical data collected included patient demographic information, AA classification, date of diagnosis, date of last follow up or date of death, type of therapy received, and identification of socioeconomic barriers to receiving appropriate care. Results Thirty three adult patients (aged 17 and above at time of BM biopsy-confirmed diagnosis) were diagnosed with AA at Montefiore Medical Center between 2000 and 2018. Age at diagnosis ranged from 17-79, with a mean age of 36 and median age 28. Fifty five percent of patients were younger than 30 at the time of diagnosis. Forty two percent of patients were female and 57.6% were male. Fifty two percent of patients were African American or Black, 27.3% were Hispanic, 12.1% were White, and 9.1% were Asian or Asian Indian. Forty two percent of cases were non-severe, 18.2% were severe, and 36.4% were very severe. Additionally, approximately 70% of our cohort was unmarried. Thirty (90%) of the patients were treated with IST (CSA + ATG), and ten (30.3%) were also treated with eltrombopag. Of the 18 patients with severe and very severe disease, seven patients (38.9%) underwent AlloHSCT. Twenty five patients (76%) were noted to be alive at the time of data-cut off for analysis (March 2020), 4 of which were post-AlloHSCT. 45% of patients in our cohort noted significant social & financial barriers to their care. Discussion: Our study demonstrates that despite significant socio-economic barriers to care, adult patients with SAA that are treated with IST +/- AlloHSCT when indicated, have overall survival that equals the national standard. Notably, our patient cohort was more than 75% Black and Hispanic.Race in the US is strongly correlated to socioeconomic status, education, and health insurance status. Some specific social barriers were identified in provider notes. These included difficulty finding a donor match, recent immigration, housing & financial insecurity, difficulty keeping follow up appointments due to transportation issues, lack of adequate health insurance. We believe the first step toward addressing the inequities in AA treatment is the continued acknowledgement of social barriers to care and addressing them in a timely manner. Socio-demographic research should inform health policy and guide interventions to ultimately reduce inequities in access and treatment for rare diseases in some of the most vulnerable in our population. Figure Disclosures No relevant conflicts of interest to declare.

Hematopoietic cell transplantation (HCT) is potentially curative for patients with hematologic disorders, but carries significant risks of infection-related morbidity and mortality. Infectious diseases are the second most common cause of death in HCT recipients, surpassed only by progression of underlying disease. Many infectious diseases are difficult to diagnose and treat, and may only be first identified by autopsy. However, autopsy rates are decreasing despite their value. The clinical and autopsy records of adult HCT recipients at our center who underwent autopsy between 1 January 2000 and 31 December 2017 were reviewed. Discrepancies between premortem clinical diagnoses and postmortem autopsy diagnoses were evaluated. Of 185 patients who underwent autopsy, 35 patients (18.8%) had a total of 41 missed infections. Five patients (2.7%) had >1 missed infection. Of the 41 missed infections, 18 (43.9%) were viral, 16 (39.0%) were fungal, 5 (12.2%) were bacterial, and 2 (4.9%) were parasitic. According to the Goldman criteria, 31 discrepancies (75.6%) were class I, 5 (12.2%) were class II, 1 (2.4%) was class III, and 4 (9.8%) were class IV. Autopsies of HCT recipients frequently identify clinically significant infectious diseases that were not suspected premortem. Had these infections been suspected, a change in management might have improved patient survival in many of these cases. Autopsy is underutilized and should be performed regularly to help improve infection-related morbidity and mortality. Illustrative cases are presented and the lessons learned from them are also discussed.

Lung involvement has been reported in HTLV-1 carriers and in patients with ATLL. Whether there are differences in the pattern of lung involvement between ATLL and HTLV carriers in North American patients is unknown. We aimed to compare CT pulmonary findings among patients with HTLV-1 infection with and without ATLL. Among 140 patients with HTLV-1 diagnosis, 97 had CT chest available. Of these, 72 (74.2%) had ATLL and 25 (25.8%) did not have ATLL. CT chest abnormalities were present in 90 (92.8%) participants (94.4% in ATLL; 88% in non-ATLL). Higher rates of lymphadenopathy (69.4% versus 24%

8063 Background: Information on central nervous system (CNS) involvement with NA-ATLL is limited. In this study, we describe CNS involvement in ATLL patients at a tertiary hospital in New York City. Methods: We considered CNS involvement if one of the following criteria was met 1) cerebrospinal fluid (CSF) cytology or flow cytometry was positive 2) CNS imaging was positive for disease involvement or 3) Physical exam findings were compatible with neurologic involvement. Results: Of 94 NA-ATLL patients, 21 (22.3%) had CNS involvement by ATLL. CSF was involved in 13/21 and 5/21 patients at diagnosis and relapse respectively. At diagnosis, MRI showed CNS involvement in brain and spine in 5/21 (24%) and 3/ 21 (14%) cases respectively. At relapse, imaging revealed brain and spine involvement in 2 patients each. Neurological exam was abnormal in 7 (33%) and 3 (14%) cases at diagnosis and relapse respectively. Next generation exon targeted sequencing was performed in 9 cases. Table shows the mutations (mtn) and functional groups with frequencies. XPO1 E571K mutation was present in 2 patients with extensive CNS disease and refractory to conventional treatment with an overall survival (OS) of 2 months. To our knowledge, this is the first time that XPO1 E571K is reported in a T-Cell malignancy. We also describe here a second set of mutations with CNS involvement (KLF2 and PI3KCD) in 2 patients. Median OS was 8.5 months, Median RFS was 6.5 months in our series. In most cases, the lymphomatous phenotype appeared to have direct mass-like extension (5/21) with several cases of accompanying osteolytic spine or skull lesions, whereas cases with hematogenous involvement tends to spread to the CSF by traversing the brain blood barrier. Conclusions: In this report we describe patterns of CNS involvement in ATLL and the associated mtns. We also describe two unique cases of XPO1E571K mtn in a TCL. [Table: see text]

Background: Autologous stem cell transplantation (ASCT) is a curative therapy for a significant proportion of patients with relapsed/refractory (R/R) classic Hodgkin lymphoma (cHL). We previously developed a conditioning regimen for R/R cHL patients undergoing ASCT incorporating gemcitabine and vinorelbine (GN-BVC), which enabled a reduction in the BCNU dose and toxicity without compromising efficacy (BBMT 2010;16:1145-54). Since this publication, several novel agents have been approved for treatment of R/R cHL including brentuximab vedotin (BV) and the immune checkpoint inhibitors (ICIs), which may be changing outcomes and toxicities following ASCT. We sought to determine whether post-ASCT outcomes have improved for R/R cHL in the era of novel agents, and to evaluate how BV and the ICIs have impacted toxicities after ASCT in a large cohort of patients treated with the same conditioning regimen. Methods: We conducted a single-center, retrospective analysis of outcomes for a large cohort of patients with R/R cHL who underwent ASCT using GN-BVC conditioning at Stanford University from 2001-2017 (n=268). We divided the cohort into two treatment eras: Era A: 2001-2009 (n=137) and Era B (increasing use of novel agents): 2010-2017 (n=131). We used Kaplan-Meier and Cox models to compare overall survival (OS), progression-free survival (PFS), and post-progression survival (PPS) between treatment eras. We also compared outcomes between patients who underwent ASCT in complete remission (CR, n=126) or with a partial response (PR, n=142). For patients treated in era B, we compared outcomes and toxicity profiles for patients treated with standard platinum-based salvage regimens (n=102) to those who received BV-based salvage regimens prior to ASCT (n=29). Results: Patients who underwent ASCT in era B had improved OS compared to those transplanted in era A (4-year OS: 87.8% vs 77.9%, HR 0.51, 95% CI 0.28-0.91, p=0.022), but PFS did not differ significantly between treatment eras (4-year PFS: 70.2% vs 62.7%, HR 0.78, 95% CI 0.52-1.2, p=0.24, Figure 1). For patients who relapsed after ASCT, PPS was significantly higher for those transplanted in era B compared to era A (84.7% vs 62.8% at 2 years, HR 0.47, 95% CI 0.23-0.98, p=0.045). Overall, patients who underwent ASCT in CR compared to those with a PR had significantly improved OS (88.3% vs 78.3% at 4 years, HR 0.50, 95% CI 0.29-0.88, p=0.016) and PFS (78.4% vs 55.1% at 4 years, HR 0.44, 95% CI 0.28-0.67, p=0.00016). Among patients who relapsed, those in era B who received novel agents (BV and/or an ICI) at any point in treatment exhibited higher OS compared to historical controls in era A (4-year OS: 72.2% vs 53.1%) but were statistically different only at the p=0.083 level which is above the p=0.05 significance threshold. Of the patients who underwent ASCT in era B (n=131), 102 (78%) received standard platinum-based salvage regimens (e.g. ICE or DHAP) and 29 (22%) received BV-based salvage regimens prior to ASCT, including 11 patients (8%) who received both BV and an ICI pre-ASCT. Outcomes were excellent for patients who received BV-based salvage regimens pre-ASCT (4-year OS 97% and PFS 76%) but were not statistically different compared to patients who received platinum-based regimens (4-year OS 86% and PFS 69%; p=0.56 and p=0.76, respectively). Pneumonitis requiring corticosteroids occurred in 8% of patients treated in era B, including 10% of patients receiving BV-based salvage regimens pre-ASCT and 7% of patients receiving standard platinum-based regimens. One patient who received BV and nivolumab pre-ASCT died from grade 5 pneumonitis. Conclusions: In this cohort of R/R cHL patients who underwent ASCT using the same conditioning regimen, OS was significantly higher for patients transplanted within the past decade. A potential survival benefit was observed among patients who relapsed post-ASCT, likely reflecting the more widespread use of BV and ICIs in the post-ASCT setting. Patients who received BV-based salvage regimens pre-ASCT had excellent outcomes without an apparent increase in toxicity, but the small number of patients limits comparisons to standard platinum-based regimens. Further studies are needed to better define the optimal sequencing of novel agents and ASCT in the treatment of R/R cHL in the modern era. Figure 1 Disclosures Sica: Physician's Education Resources (PER): Honoraria. Advani:Celgene: Research Funding; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees; Cell Medica, Ltd: Consultancy; Kyowa Kirin Pharmaceutical Developments, Inc.: Consultancy; Regeneron: Research Funding; Celmed: Consultancy, Membership on an entity's Board of Directors or advisory committees; Stanford University: Employment, Equity Ownership; Seattle Genetics: Consultancy, Research Funding; Agensys: Research Funding; AstraZeneca: Consultancy, Membership on an entity's Board of Directors or advisory committees; Autolus: Consultancy, Membership on an entity's Board of Directors or advisory committees; Bayer: Consultancy, Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Membership on an entity's Board of Directors or advisory committees, Research Funding; Kura: Research Funding; Merck: Research Funding; Infinity Pharma: Research Funding; Roche/Genentech: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Gilead Sciences, Inc./Kite Pharma, Inc.: Consultancy, Membership on an entity's Board of Directors or advisory committees; Janssen: Research Funding; Forty-Seven: Research Funding; Pharmacyclics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Millennium: Research Funding. Miklos:AlloGene: Membership on an entity's Board of Directors or advisory committees; Precision Bioscience: Membership on an entity's Board of Directors or advisory committees; Miltenyi Biotech: Membership on an entity's Board of Directors or advisory committees; Becton Dickinson: Research Funding; Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding; Adaptive Biotechnologies: Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees; Kite-Gilead: Membership on an entity's Board of Directors or advisory committees, Research Funding; Juno: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees. Muffly:Pfizer: Consultancy; Adaptive: Research Funding; KITE: Consultancy. Rezvani:Kaleido: Membership on an entity's Board of Directors or advisory committees, Other: one-time compensation from advisory boards; Nohla Therapeutics: Membership on an entity's Board of Directors or advisory committees, Other: one-time compensation from advisory boards; AbbVie: Other: Principal investigator ; U.S. Department of Justice: Other: Expert medical witness; Johnson & Johnson: Employment, Other: Brother is employed. Shizuru:Forty Seven Inc: Equity Ownership, Patents & Royalties.

Prior studies have evaluated incidence and survival trends for B-Acute Lymphoblastic Leukemia (B-ALL) in children and adults. However, there have been no recent studies evaluating the difference in survival between different race and ethnicities in the era of tyrosine kinase inhibitors and novel combination therapy. We wanted to determine 5-year observed survival for adult patients with B-ALL diagnosed in recent years and assess for any difference in survival by race-ethnicity. Methods: We used Surveillance Epidemiology End Results (SEER) 18 registry to identify B-ALL patients using ICD-O-3 codes 9811-9818 and 9836. SEER 18 covers ~28% of US population. The year of diagnosis was limited to 2010-2016 in order to capture a patient population most likely treated with modern therapies. We limited our study to adults aged 20 years (yrs) or more, which were then divided into the following age groups: 20-29, 30-39, 40-49, 50-59, 60-69,70-79,80+ yrs of age. Gender, race-ethnicity, median family income and observed overall survival (OS) were obtained from SEER. For multivariate survival analysis, Cox proportional hazard model was used to adjust for clinically important and other relevant variables (age, gender, race-ethnicity, median income). We included median family income, a county level characteristic in our analysis as a surrogate for access to care. We divided these counties into quintiles based on median family income and included that variable in the multivariate model. We did not adjust for genetic risk or patient insurance status, as the information provided in SEER was inadequate and would likely lead to misclassification bias. SEER Stat 8.3.5 and SAS student edition were used for analysis. Results: 4244 cases of B-ALL were identified with an age adjusted incidence rate of 0.92 per 100,000. B-ALL occurred at all ages, but incidence was higher in young adults ( Age adjusted incidence was the highest among Hispanics (1.61{1.53-1.71}), followed by Non-Hispanic Whites (NHW)(0.77{0.73-0.8}, Non-Hispanic Asian Pacific Islander (NHAPI)(0.7{0.63-0.78}) and Non-Hispanic Blacks (NHB)(0.54{0.47-0.61}); this difference was statistically significant (p-value About 52% of population died during the study period from any cause. We limited our survival analysis to patients without second malignancy to avoid the confounding effect of another cancer associated mortality. We evaluated OS differences between race-ethnicity in a multivariate model that adjusted for age, sex and income. We found that when compared to NHW, Hispanics (Hazard Ratio (HR) 1.3{1.16-1.46}; p Conclusion: Our study showed a significant survival disparity in adult B-ALL by race and ethnicity in the modern era. This can partly be attributed to differences in access to care as shown in our study. Interestingly, Hispanic and NHB have a significantly worse overall survival compared to NHW and NHAPI even after accounting for income differences, as a surrogate for access to care. This could be due to other unaccounted measure of health disparity, availability of allogeneic transplantation and/or difference in disease biology. Further studies are needed to evaluate such differences, identify barriers to care in minority populations and characterize potential differences in the genetic make-up of B-ALL in the various ethnic/racial groups. Disclosures Sica: Physician's Education Resources (PER): Honoraria. Verma:Stelexis: Equity Ownership, Honoraria; Acceleron: Honoraria; Celgene: Honoraria; BMS: Research Funding; Janssen: Research Funding.

Background aims Despite widespread use of umbilical cord blood (UCB) transplantation and distinct practice preferences displayed by individual UCB banks and transplant centers, little information exists on how processing variations affect patient outcomes. Methods We reviewed 133 adult double UCB transplants performed at a single center: 98 after reduced-intensity and 35 after myeloablative conditioning. Processing associated with contributing UCB banks and units was surveyed to identify differences in practice. We analyzed effect of selected variables on clinical outcomes of engraftment, dominance, transplant-related mortality, and survival. Results Eighty-eight percent of banks queried currently practice red blood cell (RBC) depletion before cryopreservation. This reflects a shift in practice because previously 65% of banks employed RBC-replete processing methods (i.e., cryopreservation or plasma/volume reduction). Neither neutrophil nor platelet engraftment was affected by processing conditions analyzed. RBC depletion was not associated with clinical outcomes, except in 17 recipients of 2 RBC-replete units, where survival was better than that observed in 116 recipients of ≥1 RBC-depleted units (hazard ratio 3.26, P = 0.004). When analyzed by attributes of the dominant unit, RBC depletion, time in storage, bank years in existence, and inventory size did not affect clinical outcomes. Postthaw viability and CD34 dose were factors impacting engraftment. Notably, all RBC-replete units in this cohort were washed in dextran-human serum albumin before infusion. Discussion These findings support continued utilization of the entire existing pool of cord blood units, despite recent trends in processing, and have important implications for banking resources and UCB selection practices.

Background Hematopoietic cell transplantation (HCT) is a potentially curative treatment option for patients with hematologic malignancies and other diseases but carries a significant risk of infection-related morbidity and mortality. Many of these infections are difficult to diagnose and treat. It is not infrequent that HCT recipients die from infection despite extensive investigations and broad-spectrum antimicrobial therapy. Autopsy is the gold standard for establishing the cause of death but rates of performing autopsies are decreasing despite their immense value. We present the most recent case series of infectious diseases found on autopsy in HCT recipients at our high-volume academic transplant center. Methods We retrospectively reviewed the medical charts and autopsy records of 131 HCT recipients who underwent autopsy between January 1, 2000 and December 31, 2016. The premortem clinical diagnoses as documented by the clinical teams were compared with autopsy findings. Discrepancies were identified and classified according to the Goldman Criteria (NEJM 1983; 308:1000–5). Results A total of 4,072 patients received 4,395 transplants between January 1, 2000 and December 31, 2016. Of the 1,937 patients who died, 131 (7%) had an autopsy performed. Of these 131 patients, 24 (18%) patients had a total of 29 infections that were identified only postmortem; 4 (3%) patients had >1 such infection. Of these 29 infections, 15 (52%) were viral, 9 (31%) were fungal, 3 (10%) were bacterial, and 2 (7%) were parasitic; no mycobacterial infections were found. According to the Goldman Criteria, 22 (76%) had class I discrepancies (“major diagnoses for which detection before death would in all probability have led to a change in management that might have resulted in cure or prolonged survival”). Illustrative cases of each infection type will be presented to highlight the challenges of infection management in HCT. Conclusion Autopsies of HCT recipients frequently identify clinically significant infections which were not suspected pre-mortem. Our study reinforces the educational value of the autopsy, which is underutilized but can be employed to help prevent future similar infectious complications and improve patient outcomes. Disclosures All authors: No reported disclosures.

110 Background: At the University of Illinois Hospital and Health Sciences System (UIC), inpatient IV chemotherapy administration occurs in the setting of specific protocols and multidisciplinary safety assessments while oral chemotherapy agent (OCA) inpatient administration occurs less formally. Baseline 8 week review of 174 admissions to the oncology service revealed that of 16 patients (9.2%) on outpatient OCA, 50% received OCAs while inpatient, with 12. 55% having a formal chemotherapy note in place. We aimed to increase the percentage of administered OCAs with associated provider generated chemotherapy notes from 12.5% to 75% over 16 weeks. Methods: A multidisciplinary task force comprised of oncology providers, clinical pharmacy, nursing leadership, and information technology was assembled. An actual and ideal process map was created, and using tools such as affinity sorting and root cause analysis, interventions were implemented focusing on residents (knowledge of OCA), nurses (documentation and policy adherence), pharmacists (education, policy adherence) and IT team (order modification). A standardized multidisciplinary hospital wide process was implemented for OCA ordering, administration, documentation, and patient education. A novel REDCap (research electronic data capture) auditing procedure was designed by which a weekly pharmacy report of every oral chemotherapy order at UI Health is automatically generated. Results: Between June and September 2015, a total of 67 OCA administration reports were audited. OCA notes were associated with OCA administration in 58% of cases in June, 100% in July, 78% in August and 93% in September. Furthermore, OCA notes were entered within 4 hours of OCA ordering in 58% of cases in June, 54% in July and 78% of the cases in August and September. No adverse events were reported. Conclusions: At the University of Illinois Hospital and Health Sciences System, a multidisciplinary team designed and implemented a standardized OCA administration, ordering, and documentation process focused on safe, appropriate and timely inpatient OCA administration. A novel REDCap auditing process assisted the team to identify the areas in need of optimization.

164 Background: A process to standardize ordering, documentation, and administration of inpatient oral chemotherapy was implemented at the University of Illinois Hospital and Health Sciences System. The process requires oncology clinician review and endorsement of inpatient oral chemotherapy drug orders via an oral chemotherapy note within the electronic health record. Pharmacists are instructed to reject oral chemotherapy drug orders that lack this required documentation. A novel auditing procedure was established in order to track adherence to these new requirements and provide real time and adaptable feedback to front-line staff critical to the project’s success. Methods: To support continuous quality improvement (QI) with this project, an auditing tool was developed in REDCap, a secure, web-based data management application. The auditing tool was originally developed as a traditional web-based data collection instrument with the primary purpose of tracking performance. By utilizing more advanced features offered by the REDCap platform, the auditing tool generated automated follow-up surveys to pharmacists involved in non-adherent outlier cases. The survey solicited information on the root cause of non-adherence, and based on the end-user response, provided adaptable continuing education tailored to this root cause. Results: Between June and September 2015, a total of 67 orders for oral chemotherapy were audited. Compliance with process improvement requirements was noted in 58%, 100%, 78%, and 93% of cases in June, July, August, and September, respectively. Outlier surveys were sent to 12 pharmacists in the non-adherent cases; of 11 responses, the most common response reflected an unfamiliarity with the process. Following targeted education, through September 2015, no single pharmacist has been involved in more than one non-adherent case. Conclusions: The novel auditing tool supported the continuous quality improvement process by engaging front-line staff, generating automated and real time surveys for outlier responses, and providing targeted and personalized education aimed at resolving the root cause in non-adherent cases. As such, it can be applied towards any REDCap QI projects.

559 Background: Renal cell carcinoma (RCC) tumor vasculature is abnormal and does not provide nutritive blood flow, which results in regions of hypoxia. This hypoxia contributes to the immune tolerance of tumor cells by impeding the homing of cytotoxic T cells into tumor parenchyma. In addition, tumor angiogenesis enhances activity of myeloid-derived suppressor cells (MDSC) and tumor-associated macrophages (TAM) that suppress innate anti-cancer immunity. It has been demonstrated in preclinical models that antiangiogenic therapy decreased the number of MDSCs and changed polarization of TAMs from an immunosuppressive (M2-like) to an immunostimulatory (M1-like) phenotype. We hypothesized that therapy with bevacizumab will normalize the tumor vasculature, promote M1-like phenotype of TAMs, and thus potentiate the immunotherapeutic activity of pembrolizumab. As a prerequisite to testing this hypothesis, the objective of this study was to establish the safe dose of bevacizumab when used in combination with pembrolizumab. Methods: Our subject population included males and females (age > 18 y) with metastatic clear cell RCC after failure of at least one systemic therapy. In this Phase Ib dose escalation study, pembrolizumab (200 mg fixed dose every 3 weeks) was given in combination with bevacizumab (either at 10 mg/kg or 15 mg/kg every 3 weeks). The primary endpoint was to establish the maximum safe dose. Results: 12 subjects have been enrolled: 10 males (ages 33-68 y, mean: 52.7, median: 54.5) and 2 females (ages 61 and 62 y). To date 3 patients have received 1 cycle; 2 patients have received 2, 3, and 4 cycles each; and there are single patients who have received 5, 6, and 7 cycles each. No dose-limiting toxicity or serious adverse events related to the study drug have been reported. There were no grade 3 or 4 drug-related toxicities noted, and the most common grade 1 and 2 toxicities were diarrhea, fatigue, fever, hypertension, nausea, rash, and rigors. Conclusions: The 200 mg fixed dose of pembrolizumab and 15 mg/kg dose of bevacizumab, both given every 3 weeks, was determined to be safe and recommended for a multicenter Phase 2 study that is ongoing. Clinical trial information: NCT02348008.

Relapse of acute myeloid leukemia (AML) following myeloablative allogeneic stem cell transplantation portends a dismal prognosis. Therapy aimed at enhancing graft-versus-leukemia (GVL) effect, e.g., by donor leukocyte infusion, has limited success in AML, and a second ablative transplant is associated with prohibitive mortality in adults. From April 2001 to March 2006, nine patients, ranging in age from 21 to 57, with high risk myeloid malignancy (7 AML and 2 advanced myelodysplasia) and overt bone marrow relapse less than one year after ablative busulfan/cyclophosphamide conditioning have been treated with a cytoreductive regimen of fludarabine (30 mg/m2/day) and cytarabine (2g/m2/day) for 5 days (-7 through -3) and G-CSF administration (5 ug/kg daily starting day -8) with or without idarubicin (8 mg/m2 days -7, -5, and -3) (8 cases) or fludarabine 30 mg/m2 for 3 days and 200 cGy total body irradiation (1 case). G-CSF mobilized peripheral blood stem cells from their original HLA-matched donor (8 siblings, 1 unrelated) were infused. Graft versus host disease (GVHD) prophylaxis was mycophenolate mofetil for 30 days and cyclosporine with a rapid taper. The mean onset of relapse after the initial ablative transplant was day 172 (range 106–271). Fludarabine-based therapy was well tolerated with no treatment related mortality. Full donor chimerism was established by day 72 (range 26–113) in 6 patients (67%). Five patients died: 2 from relapse without GVHD at day +30 and +301 after RIST (one patient with complex and one with Ph+ cytogenetic abnormalities), 3 from relapse with evidence of GVHD. Four patients survive: one has relapsed at 91 days after RIST and is receiving alternate therapy, while three patients (30%) survive in complete remission at 100+, 635+ and 1795+ days after salvage RIST. In 5 cases (56%), the duration of complete remission after RIST was longer than after the initial ablative transplant. We conclude that fludarabine-based RIST is a safe and effective salvage therapy offering a chance for increased survival with low morbidity in patients relapsing after ablative transplant. In addition, RIST therapy has resulted in long-term disease free survival in over 20% of cases in this study.

It has been assumed but not yet proved that cerebellar cortical Stimulation activates the Purkinje cells, with subsequent inhibition of the deep cerebellar nuclei. However, the relatively crude, widespread excitation induced by several surface electrode arrays and the parameters of Stimulation currently used, may produce other effects than selective activation of only one specific cellular type which, furthermore, seems to be rarely present in these particular patients, as demonstrated by biopsy studies prior to electrode placement.

This third volume of the Cambridge Studies in Modern Optics is a comprehensive and authoritative treatise on the design, construction, and analysis of measurements from these multiple-beam instruments. Its treatment of the Fabry-Perot interferometer is highly mathematical and unified, weaving together in a coherent and consistent format the work of over 400 different authors. The author is well qualified to discuss these topics, having used these devices to study the dynamics of the upper atmosphere for the past 25 years. During this time he has made several fundamental contributions to interferometry, in addition to aeronomy.