Blood and Marrow Transplantation (BMT) within Four Weeks of Sars-Cov-2 Infection Is Associated with Increased Risk of Mortality: A National COVID Cohort Collaborative Study

Introduction The optimal timing of blood and marrow transplant (BMT) following acute SARS-CoV-2 infection is not known. Currently, the American Society for Transplantation and Cellular Therapy recommends proceeding with BMT in 2-3 weeks post-acute SARS-CoV-2 infection particularily in asymptomatic patients. This study aims to determine optimal timing of BMT following SARS-CoV-2 infection.

Methods For this analysis, we used patients from National COVID Cohort Collaborative (N3C) centralized-data resource, the largest multisite cohort of cancer and COVID-19 patients nationally. All patients with a diagnosis of hematological cancer who underwent BMT were identified. Among these, patients undergoing BMT after a documented SARS-CoV-2 infection were identified and further stratified according to time from infection to BMT. For this study the following time point were defined- acute SARS-CoV-2 infection is ≤ 4 weeks from test positivity, early SARS-CoV-2 within 4-8 weeks from test positivity and late SARS-CoV-2 >8 weeks after test positivity. Post BMT complications were defined as a composite of all the post-BMT adverse events that occur including hospital readmission but excluding mortality. All analyses were performed in the N3C Data Enclave.

Results A total of 5703 patients with hematological malignancies who underwent BMT between January 1^st,2020, and July 19^th,2022,were included. Most common indication for BMT in this cohort was acute myeloid leukemia (19.6%; n=1107). Among these, 547 (9.6%) patients had documented SARS-CoV-2 infection prior to BMT. Baseline characteristics are summarized in table 1. The median age was 57 (range 40-66) years. About 38% of patients were female and 7.4% were Blacks. Only 59 patients were fully vaccinated against SARS-CoV-2 prior to BMT. Next, we compared the subset of patients with and without SARS-COV-2 infection prior to BMT (table 1). Patients with history of SARS-CoV-2 infection going to BMT were younger (56 vs 57 years; p=0.009).Additionally, SARS-CoV-2 infection were more common in Blacks (11% vs 7.3%; p<0.001) and smokers (30% vs 25% ; p=0.005) compared to those without SARS-CoV-2 infection prior to BMT. In this cohort, 67% (n=372) of SARS-CoV-2 infections were mild to moderate and 30% (n=163) were asymptomatic infections. About 15% (n=83) patients were transplanted in the context of acute SARS-CoV-2 infection and 70% (n= 384) were transplanted in the late post SARS-CoV-2 infection period. Patients with prior SARS-CoV-2 infection had a longer median inpatient length of stay following BMT (17 vs 16 days; p<0.001) with similar rates hospital readmission (30% v 30%; p=0.85). In-hospital mortality following BMT in patients with and without prior SARS-CoV-2 infection were 2.9% and 1.7% (p=0.06),respectively. On multivariable regression analysis, patients with severe SARS-CoV-2 infections were at increased risk of 30-day mortality (OR= 49.6;95% CI 10.0-195; p<0.001). BMT in the context of acute SARS-CoV-2 infection (OR= 4.01; 95%1.14-10.7;p=0.013) was associated with a higher 30 day-post BMT complications. Following adjustment, BMT performed within 4 weeks (acute SARS-CoV-2 infection) was associated with an increased odds of 30-day mortality (aOR 4.63; 95% 1.34 - 12.1; p=0.005) compared to those without prior infection. This increased risk was not observed in patients undergoing BMT 4-8 weeks (aOR 1.17; 95% 0.06 - 5.77; p=0.88) or >8 weeks (aOR 1.45; 95% 0.50 - 3.36; 0.43) after a SARS-CoV-2 infection.

Conclusions In this large real-world dataset of patients with mostly asymptomatic to moderate infection, BMT within 4 weeks of SARS-CoV-2 infection was associated with higher 30-day post BMT complication and mortality. Future research is needed to better refine the best timing of BMT in this vulnerable patient population with underlying hematological cancer.

Mohan:GSK: Research Funding; BMS/Celgene: Research Funding; Takeda: Research Funding; Novartis: Research Funding. Shreenivas:Natera: Research Funding; Taiho: Honoraria. Dhakal:GlaxoSmithKline: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria; Janssen: Consultancy, Honoraria, Research Funding, Speakers Bureau; Natera: Consultancy; Sanofi: Consultancy, Honoraria, Research Funding, Speakers Bureau; Karyopharm Therapeutics: Honoraria, Speakers Bureau; BMS: Honoraria, Research Funding; Arcellx: Research Funding; Carsgen: Research Funding; Cartesian: Research Funding; Fate: Research Funding; Takeda: Honoraria; Pfizer: Membership on an entity's Board of Directors or advisory committees; AbbVie: Membership on an entity's Board of Directors or advisory committees; Genentech: Membership on an entity's Board of Directors or advisory committees. Chhabra:Sanofi: Research Funding; Janssen: Research Funding; GlaxoSmithKline: Honoraria; Amgen: Research Funding. Pasquini:Janssen: Research Funding; Bristol Myers Squibb: Consultancy, Research Funding; Novartis: Research Funding; Kite: Research Funding. D'Souza:Takeda, Sanofi, TeneoBio, Prothena, Caelum Biosciences, Janssen Oncology, Regeneron, Abbvie: Research Funding; Pfizer, Janssen Oncology, Bristol-Myers Squibb/Celgene, Prothena: Consultancy, Membership on an entity's Board of Directors or advisory committees. Hamadani:Gamida Cell: Consultancy; Incyte Corporation: Consultancy; Takeda: Research Funding; Novartis: Consultancy; Medical University of Wisconsin: Current Employment; SeaGen: Consultancy; ADC Therapeutics: Consultancy, Research Funding, Speakers Bureau; Spectrum Pharmaceuticals: Research Funding; Abbvie: Consultancy; Omeros: Consultancy; Genmab: Consultancy; Kadmon: Consultancy; Legend Biotech: Consultancy; MorphoSys: Consultancy; Kite: Consultancy; Sanofi Genzyme: Speakers Bureau; Astellas Pharma: Research Funding; AstraZeneca: Speakers Bureau; BioGene: Speakers Bureau.