ABSTRACT
[Formula presented] Background: Patients with B-cell lymphoma have poor clinical outcomes to SARS-CoV-2 infection (COVID-19) and are also more likely to have suboptimal responses to immunization. An understanding of which lymphoma patients are at greatest risk of poor COVID-19 vaccine response and what aspects of immunity are most impaired is critical for developing strategies to protect these patients from a potentially fatal infection. Methods: We enrolled 149 participants, including 129 with lymphoma and 20 age-matched controls, who received a complete COVID-19 vaccination series to assess how B- and T-cell vaccine responses vary among clinically relevant subgroups and over time. This cohort included 99 patients with prior anti-CD20 treatment, ranging from 1 week to 17 years prior, allowing us to assess relationships between timing and intensity of anti-CD20 exposure and vaccine response. The cohort also included 18 patients who began treatment with an anti-CD20-containing regimen after being fully vaccinated, in whom we are assessing the potential efficacy of a pre-therapy vaccination strategy. Peripheral blood samples were taken on average 28 days and 4 months after last vaccine dose. B-cell responses are being profiled by measuring anti-Spike serum IgG, RBD-ACE2 blocking activity, and spike-specific memory B cells. T cell assessments include quantitation of spike-specific activation and cytokine production via interferon-gamma ELISPOTs and multiparameter flow cytometry. Results: The 129 participants with lymphoma had a median age of 68, were 59% male, and 70% had either diffuse large B-cell lymphoma (DLBCL) or follicular lymphoma (FL). Thirteen percent had no therapy prior to vaccination, half had not been treated in the past six months and 36% had been treated recently or were currently being treated. Ninety-three percent received an mRNA COVID-19 vaccine. Although we did not detect a statistically significant difference in vaccine response between previously untreated lymphoma patients and controls, 3/17 were negative for blocking antibodies post-vaccine, compared to 0/20 controls (Fishers exact test p=0.09, Figure 1A). Lymphoma patients with any history of treatment had impaired serologic responses to the vaccine compared to previously untreated patients (p=0.01). Responses did not vary by specific lymphoma histology. Blocking antibodies were evident in only 45% and 3% of patients recently/currently treated with a BTK inhibitor or an anti-CD20 antibody, respectively (Figure 1A). Closely evaluating all patients who had ever received anti-CD20 antibody therapy, we found a strong linear correlation between time since last anti-CD20 treatment and RBD-ACE2 binding inhibition (p<0.0001, Figure 1B-C). T cell and memory B cell assays are ongoing as is analysis of response persistence and of the pre-therapy vaccination cohort, and results from these efforts will be included in the final presentation. Conclusions: Treatment with anti-CD20 antibodies significantly impaired COVID-19 vaccine-induced humoral responses in patients with lymphoma in a manner dependent on the time elapsed since last anti-CD20 treatment. Vaccination at least six months after anti-CD20 treatment, likely co-incident with recovery of the B-cell compartment, was associated with positive blocking antibody titers. These data suggest that booster vaccination strategies are more likely to succeed in lymphoma patients who have not received anti-CD20 treatment for at least 6 months and that those patients with recent anti-CD20 treatment may benefit most from passive immunization strategies. Forthcoming results from the pre-therapy vaccination cohort will also help inform sequencing of additional vaccine doses, passive immunization, and anti-cancer treatments. [Formula presented] Disclosures: Shree: Gilead: Other: Spouse's employment. Beygi: Kite/Gilead: Current Employment. Advani: Astellas/Agensys: Research Funding;AstraZeneca: Membership on an entity's Board of Directors or advisory committees;Bayer: Membership on an entity's Board of Directors or dvisory committees;Bristol Myer Squibb: Membership on an entity's Board of Directors or advisory committees;Cell Medica: Membership on an entity's Board of Directors or advisory committees;Forty Seven: Membership on an entity's Board of Directors or advisory committees, Research Funding;Genetech Inc.: Membership on an entity's Board of Directors or advisory committees, Research Funding;Gilead: Membership on an entity's Board of Directors or advisory committees;Janssen Pharmaceutical: Research Funding;Juno: Membership on an entity's Board of Directors or advisory committees;Kite Pharma: Membership on an entity's Board of Directors or advisory committees;Kura: Research Funding;Kyowa: Membership on an entity's Board of Directors or advisory committees;Merck: Research Funding;Millenium: Research Funding;Pharmacyclics: Consultancy, Research Funding;Portola Pharmaceuticals: Consultancy;Regeneron: Research Funding;Roche: Membership on an entity's Board of Directors or advisory committees;Sanofi: Membership on an entity's Board of Directors or advisory committees;Seattle Genetics: Research Funding;Takeda: Membership on an entity's Board of Directors or advisory committees. Khodadoust: CRISPR Therapeutics, Nutcracker Therapeutics: Research Funding;Myeloid Therapeutics: Membership on an entity's Board of Directors or advisory committees;Alexion, AstraZeneca Rare Disease: Other: Study investigator. Kurtz: Roche: Consultancy;Foresight Diagnostics: Consultancy, Current holder of stock options in a privately-held company;Genentech: Consultancy. Alizadeh: Bristol Myers Squibb: Research Funding;Gilead: Consultancy;Celgene: Consultancy, Research Funding;Janssen Oncology: Honoraria;Roche: Consultancy, Honoraria;Foresight Diagnostics: Consultancy, Current holder of individual stocks in a privately-held company, Current holder of stock options in a privately-held company;Forty Seven: Current holder of individual stocks in a privately-held company, Current holder of stock options in a privately-held company;CAPP Medical: Current holder of individual stocks in a privately-held company, Current holder of stock options in a privately-held company;Cibermed: Consultancy, Current holder of individual stocks in a privately-held company, Current holder of stock options in a privately-held company. Levy: GigaGen: Membership on an entity's Board of Directors or advisory committees;Teneobio: Membership on an entity's Board of Directors or advisory committees;Nurix: Membership on an entity's Board of Directors or advisory committees;Dragonfly: Membership on an entity's Board of Directors or advisory committees;Apexigen: Membership on an entity's Board of Directors or advisory committees;Viracta: Membership on an entity's Board of Directors or advisory committees;Spotlight: Membership on an entity's Board of Directors or advisory committees;Immunocore: Membership on an entity's Board of Directors or advisory committees;Walking Fish: Membership on an entity's Board of Directors or advisory committees;Kira: Membership on an entity's Board of Directors or advisory committees;Abintus Bio: Membership on an entity's Board of Directors or advisory committees;Khloris: Membership on an entity's Board of Directors or advisory committees;Virsti: Membership on an entity's Board of Directors or advisory committees;BiolineRx: Membership on an entity's Board of Directors or advisory committees;BeiGene: Membership on an entity's Board of Directors or advisory committees;Quadriga: Membership on an entity's Board of Directors or advisory committees.
ABSTRACT
Objective: Prior studies have shown maternal viral infections are associated with fetal growth restriction (FGR);however, the relationship between FGR and Sars-CoV-2 (SCOV2) infection during pregnancy remains unclear. In this study, we investigate the association between FGR & parental SCOV2 infection at a county hospital in Atlanta, Georgia. Study Design: A prospective cohort study was created by matching patients who had positive SCOV2 (PSCOV2) and negative SCOV2 (NSCOV2) PCR tests between 1/2020-4/2021 utilizing an institutional database. Cohorts were drawn from patients who received a 3rd trimester ultrasound (3TUS) & were matched by gestational age & month SCVO2 testing was performed. FGR was present when estimated fetal weight (EFW) was ≤10% or abdominal circumference (AC) ≤10% at time of either late 2nd or 3rd trimester ultrasound. Sample size calculations were performed to investigate a 15% difference in FGR rate requiring 74 subjects per group. Univariate analyses, chi-square tests and logistic regression were performed. Regression models were adjusted for comorbidities including preeclampsia, gestational diabetes, chronic hypertension, gestational hypertension, and maternal race. Results: 157 subjects were in the analyses (n=78 PSCOV2 and n=79 NSCVO2). 83.4% (n =131) self-identified as African American. FGR rates were 15.3% and 16.4% among PSCOV2 and NSCOV2 respectively. After adjusting for confounders, no difference in FGR was observed between the groups (adjusted OR: 1.12, 95% CI 0.46-2.73). Absolute EFW at time of FGR diagnosis was lower in PSCOV2 vs NSCOV2 (1,250 grams vs.1,337 grams, p= 0.015), a relationship that remained after adjusting for confounders (p=0.015). Conclusion: Our data suggest that despite a high background FGR rate (15.2%), there was no significant association between FGR and SCOV2. Also, EFW was lower in PSCOV2 cohort vs NSCOV2 cohort. Therefore, unlike other viral illnesses, while SCOV2 may not clinically drive FGR, further studies are necessary to investigate the effects of maternal SCVO2 on fetal growth & examine whether growth exams improve outcomes in this setting.
ABSTRACT
Introduction: Mature T and NK-cell lymphomas represent a heterogeneous group of lymphoid disorders (29 subtypes according to the 2016 WHO classification) arising from mature T cells of post-thymic origin with different morphological characteristics, phenotypes, and clinical presentation. Following the success of the T Cell Project (TCP), which allowed the analysis of more than 1,500 cases of peripheral T-Cell lymphomas (PTCLs) collected prospectively in 18 Countries, in 2018 the TCP 2.0 was launched. Here we report the global distribution of PTCLs, from the cases registered so far based on the locally established histological diagnosis. Methods: The TCP2.0 (ClinicalTrials.gov Identifier: NCT03964480) is a prospective, international, observational study which adapts to changes made in the new WHO classification. Results: Since the beginning of the study (October 2018), 648 patients with newly diagnosed PTCL were registered by 75 active centers across 14 countries. Of these data, 594 patients have been validated by the centralized trial office. Overall, PTCL-NOS, Anaplastic large cell lymphoma (ALCL) ALK-negative, and Angioimmunoblastic T-cell lymphoma (AITL), represent the most frequent subtypes, representing 31.3%, 18,9% and 13,5% of cases, respectively. As reported in Table 1, PTCL-NOS represents the most frequent subtype worldwide, whereas Adult T-cell leukemia/lymphoma was more frequent in Brazil, AITL and ALCL ALK-negative in Australia/ India, and ALCL ALK-positive in North America and Europe. Extranodal NK/T-cell lymphoma, nasal type was relatively frequent in Brazil and quite rare in the other Latin America Countries. Finally, many sub-types represent less than 5% of cases in all geographic areas. Conclusions: The TCP2.0 continues to recruit very well, despite the difficulties linked to the COVID-19 pandemic, and may represent a useful resource for the prospective study of this group of rare lymphomas.
ABSTRACT
INTRODUCTION: Liver complications associated with the novel corona virus, COVID-19 (SARSCoV- 2) are well-described phenomena occurring in approximately 60% of infected patients. The degree and extent in the level of transaminitis is not yet well defined. In the evaluation of transaminitis in pregnant patients, consideration of the differential diagnoses is important in order to provide appropriate timely treatment and management. Determining the exact etiology for transaminitis in the pregnant patient with COVID-19 is particularly challenging given other competing diagnosis in this patient population. We present a case of a pregnant woman with acute liver enzyme elevation in the setting of COVID-19 infection. CASE DESCRIPTION/METHODS: A 34 year old female with COVID-19 presented at 33 weeks twin gestation with right upper quadrant pain, vomiting for 2 days and acute respiratory distress which improved with supplemental oxygen. Initial labs showed elevated inflammatory markers, mildly elevated liver enzymes (AST 102, ALT 53 IU/L), low platelets (139 K/uL), lactate dehydrogenase was 375 IU/L, and INR was 1.0. Total bilirubin was normal. An abdominal ultrasound demonstrated cholelithiasis without evidence of cholecystitis, patent portal and hepatic veins, and no biliary ductal dilation. The next day, her liver enzymes increased (ALT;119 IU/L and AST;228 IU/L), and LDH rose to 750 IU/L while vital signs were unchanged. She was treated with N-acetyl-cysteine (non-acetaminophen-induced liver failure protocol) without improvement. The next day her liver enzymes peaked (ALT;307 IU/L and AST;641 IU/L). Due to rising liver enzymes, increased abdominal pain she underwent an emergency c-section to minimize maternal and fetal risk. Postoperatively, her ALT and AST down trended. On post-op day 4, aminotransferases markedly improved (AST of 20 IU/L, ALT of 49 IU/L), patients symptoms improved and patient was discharged home. DISCUSSION: Clinical presentation and associated liver complications of COVID-19 infection are not well described. Due to the rapid global spread of COVID-19, prompt identification of associated liver test abnormalities from other causes especially in pregnant patients is vital. It is also important to consider that COVID-19 may cause severe acute viral hepatitis rather than a mild elevation in liver enzymes in pregnant patients, possibly exacerbating underlying conditions such as pre-eclampsia or HELLP syndrome.