Case Report: Favorable outcome of allogeneic hematopoietic stem cell transplantation in SARSCoV2 positive recipient, risk-benefit balance between infection and leukemia
Authors: Chiara Oltolini, Andrea Acerbis, Giorgio Orofino, Sara Racca, Maddalena Noviello, Stefania Dispinseri, Nicola Clementi, Simona Piemontese, Elisabetta Xue, Fabio Giglio, Maria Teresa Lupo Stanghellini, Elisa Diral, Alessandro Bruno, Elena Tassi, Valeria Beretta, Ilaria Marzinotto, Gabriella Scarlatti, Vito Lampasona, Anna Ardemagni, Michela Sampaolo, Chiara Bonini, Consuelo Corti, Jacopo Peccatori, Antonella Castagna, Fabio Ciceri, Raffaella Greco
Journal: Front Immunol (2023)
Keywords: covid – 19, sars – cov – 2, acute b-lymphoblastic leukemia, allogeneic transplant, veno-occlusive disease
MeSH terms: COVID-19 / complications, Graft vs Host Disease / etiology, Hematopoietic Stem Cell Transplantation / adverse effects, Hematopoietic Stem Cell Transplantation / methods, Leukemia / therapy, Case Reports, Adult, COVID-19 Testing, Female, Humans, RNA, Viral, SARS-CoV-2, RNA, Viral

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) in SARS-CoV-2 positive candidates is usually delayed until the clinical resolution of the infection's symptoms and a negative nasopharyngeal molecular test. However, prolonged SARS-CoV-2 positivity has been frequently observed in haematological malignancies, thus representing a challenge for the timing of transplant procedures. Here, we report on the case of a 34-year-old patient with recent pauci-symptomatic COVID-19 undergoing transplant for high-risk acute B-lymphoblastic leukemia before achieving viral clearance. Shortly before their scheduled allogeneic HSCT from a matched unrelated donor, the patient developed mild Omicron BA.5 infection receiving nirmatrelvir/ritonavir with fever resolution within 72 hours. Twenty-three days after COVID-19 diagnosis, because of increasing minimal residual disease values in the context of high-risk refractory leukemia and clinical resolution of SARS-2-CoV infection with reduction of viral load at surveillance nasopharyngeal swabs, it was decided not to delay further allo-HSCT. During myelo-ablative conditioning, the nasopharyngeal SARS-CoV-2 viral load increased while the patient remained asymptomatic. Consequently, two days before the transplant, intra-muscular tixagevimab/cilgavimab 300/300 mg and a 3-day course of intravenous remdesivir were administered. During the pre-engraftment phase, veno-occlusive disease (VOD) occurred at day +13, requiring defibrotide treatment to obtain a slow but complete recovery. The post-engraftment phase was characterized by mild COVID-19 at day +23 (cough, rhino-conjunctivitis, fever) that spontaneously resolved, achieving viral clearance at day +28. At day +32, she experienced grade I acute graft-versus host disease (a-GVHD, skin grade II) treated with steroids and photo-apheresis, without further complications during follow-up until day +180. Addressing the issue of allo-HSCT timing in patients recovering from SARS-CoV-2 infection with high-risk malignant diseases is challenging because of 1] the high risk of COVID-19 clinical progression, 2] the impact of transplant delay on leukemia prognosis and 3] the occurrence of endothelial complications such as VOD, a-GVHD, and transplant associated thrombotic micro-angiopathy. Our report describes the favourable outcome of allo-HSCT in a recipient with active SARS-CoV2 infection and high-risk leukemia thanks to timely anti-SARS-CoV-2 preventive therapies and prompt management of transplant-related complications.