Impact of Allogeneic Hematopoietic Cell Transplantation Post-Sars-Cov-2 Infection: A Retrospective Analysis By the German Cooperative Transplant Study Group

Introduction

Allogeneic hematopoietic cell transplantation (alloHCT) is a curative treatment for hematologic malignancies, but it carries a significant risk of non-relapse mortality (NRM) to infections. The emergence of the COVID-19 pandemic introduced the challenge for the correct timing and safety of alloHCT in patients with prior SARS-CoV-2 infection.

Methods

This retrospective analysis, conducted by the German Cooperative Transplant Study Group, evaluated the outcomes of 75 patients who underwent alloHCT after having survived COVID-19. Data were collected from May 2020 to May 2022 at 15 German and Austrian centers using standardized questionnaires. All patients were SARS-CoV-2-PCR negative before alloHCT.

Results

The cohort included 75 patients (40 (53%) female, 35 (47%) male) with a median age of 56 (range 22-77) years and varying COVID-19 severity: 31 with mild, 6 with moderate, 12 with severe, and 26 with unknown severity after WHO-grading. Time from diagnosis of neoplasia to COVID-19 (median 125 (range 0-3,990) days) and time from COVID-19 diagnosis to alloHCT (median 141 (range 1-661) days) did not differ significantly between severity groups (p=0.09 and p=0.40, respectively). 12 (16%) patients suffered from ALL, while 38 (52%) had an AML and 23 (32%) had other diagnosis (2 unknown). Myeloablative conditioning was chosen in 29 (62%) patients, while 18 (38%) received reduced intensity conditioning (unknown=28). Peak C-reactive protein (CRP) during COVID-19 was 5 mg/dl in mild, 7 mg/dl in moderate and 8 mg/dl in severe disease (p=0.9), while IL-6 was 71 ng/l in mild, 92 ng/l in moderate and 122 ng/l in severe disease (p=0.8) and PCT was 0.61 ng/ml in mild, 1.34 ng/ml in moderate and 0.38 ng/ml in severe disease. COVID-19 duration did not correlate significantly with COVID-19 severity (>30 days= 10 (38%) mild, 3 (50%) moderate, 2 (40%) severe. ≤30 days: 16 (62%) mild, 3 (50%) moderate, 3 (60%) severe; p=0.7). There was no statistically significant difference in the timing of alloHCT in relation to the interval between COVID-19 diagnosis and alloHCT (p=0.38, day 178, maximally selected rank statistics).

Patients with previous severe COVID-19 had a significantly lower 365-day survival rate (51.1%) compared to those with previous mild cases (90.9%, p=0.03). NRM at 365 days was higher in severe cases (19.6%) compared to mild cases (0%, p=0.03). There was no observed difference in acute (p=0.4) or chronic Graft-versus-Host-disease (p=0.4). Patients with a high Karnofsky index and mild COVID-19 had the best survival outcomes (p=0.12), while normal pre-transplant lung function, especially DLCO, was associated with better outcomes (HR: 0.91, p=0.04). Despite missing DRI (disease risk index) covariates, COVID-19 severity was not significantly associated with higher cytogenetic risk (64% abnormal in mild vs. 45.5% in severe disease, p= 0.37). However, patients with severe COVID-19 were less likely to be transplanted in CR (mild disease= 70.8% in CR at alloHCT, severe disease = 37.5% in CR, p= 0.21)

Discussion

Severe COVID-19 significantly impacts post-alloHCT survival, highlighting the need for rigorous prevention, comprehensive pre-transplant evaluation, and tailored management strategies for alloHCT patients. These findings support the deferral of aggressive treatments in symptomatic COVID-19 cases and the prioritization of antiviral treatments to mitigate risk. We aim to highlight the necessity of lung function testing following symptomatic COVID-19.

Kröger:Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Neovii: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; BMS: Membership on an entity's Board of Directors or advisory committees; Therakos: Honoraria, Speakers Bureau; Alexion: Honoraria, Speakers Bureau; Kite/Gilead: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; DKMS: Research Funding; Sanofi: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Takeda: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Provirex: Consultancy. Schetelig:Janssen: Consultancy, Honoraria; MSD: Consultancy; Novartis: Honoraria; Eurocept: Honoraria; Astellas: Honoraria; Medac: Honoraria; AstraZeneca: Consultancy, Honoraria. Mueller:Squibb: Honoraria, Other: travel grant; BMS: Honoraria, Other: Travel grant; Abbvie: Honoraria, Other: travel grant; Amgen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Membership on an entity's Board of Directors or advisory committees; Gilead: Membership on an entity's Board of Directors or advisory committees, Other: travel grant; Pfizer: Membership on an entity's Board of Directors or advisory committees. Holtick:Roche: Honoraria.