Allogeneic and Autologous Hematopoietic Transplants Can be Safely Performed after COVID-19 Infections
Authors: Ramdial Jeremy L. , Saliba Rima M. , Alousi Amin M. , Rondon Gabriela , Chen Julianne , Ledesma Celina , Shpall Elizabeth J. , Chemaly Roy , Champlin Richard E. 
Published: November 2021

Abstract
We are in the midst of a pandemic with the COVID-19 virus, a pathogen with potential severe manifestations. A major clinical question is whether it is safe to undergo hematopoietic stem cell transplantation (HSCT) shortly after COVID-19 infection. A total of 21 patients received HSCT following a diagnosis of COVID-19 infection at our institution between 7/30/2020 and 4/14/2021. The majority (n=13, 62%) received an allogeneic (ALLO) HSCT from an HLA-matched related (n=5), -matched unrelated (n=6), or haploidentical (n=2) donor. The remaining 8 patients received autologous (AUTO) HSCT. Among ALLO-HSCT recipients, 4 (31%), 5 (38%), 3 (23%), and 1 (8%) patients had grade 1, 2, 3, and 4, manifestations respectively, scored according to the WHO COVID-19 infection severity grading system. Among AUTO-HSCT recipients, 5 (62%), 1 (12%), and 2 (25%) patients had grade 0, 1, and 2 manifestations, respectively. All patients had resolution of COVID-19 symptoms before HSCT. In recipients of ALLO-SCT, the median time from diagnosis of the COVID infection to HSCT was 134 (range: 55-311) days. Median age of recipients was 53 (range: 17-71) years and the majority (69%) of patients were male. Only one patient was &lt;18 years old, and 38% were &gt;60 years. Patients received ALLO-HSCT for treatment of acute myeloid leukemia or myelodysplastic syndrome (n=7, 54%), acute lymphoblastic leukemia (n=2, 15%), chronic lymphoblastic leukemia (n=2, 15%), and Hodgkin's (n=1, 8%) or non-Hodgkin's lymphoma (n=1, 15%). Most (62%) patients were not in remission at the time of HSCT. The median hematopoietic cell transplant-co-morbidity index (HCT-CI) score was 3 (range 0-6); one patient had a history of diabetes and another of hypertension before HSCT. Conditioning regimen was myeloablative in 61%, and stem cell source was peripheral blood (PB) in 92% of transplants. Median time to neutrophils engraftment was 15 (range: 10-20) days. With a median follow-up of 3.5 (range: 0.4-8) months since ALLO-HSCT, two patients died and another two experienced progression of the underlying malignancy. Three patients were diagnosed with grade 2 and none with grade 3 or 4 acute graft-versus-host disease (GvHD). The deaths occurred among patients with COVID-19 infection grade 2 and 3. The primary cause of death was attributed to alveolar hemorrhage/pneumonitis (no organism identified) and acute GvHD, respectively. Overall survival was 89% (95% confidence interval [CI]:43-98) and 76% (95% CI 33-93) at 3 and 6 months, respectively. In recipients of AUTO-HSCT, the median time from diagnosis of the COVID-19 infection to HSCT was 55 (range: 20-157) days. Median age of recipients was 55 (range: 34-75) years, and the majority (62%) of patients were male. One (12%) patient was &gt;60 years. Patients received AUTO-HSCT for treatment of Hodgkin's (n=1, 15%) or non-Hodgkin's (n=4, 50%) lymphoma, or multiple myeloma (n=3, 37%). Six (75%) patients were in remission at the time of HSCT. The median HCT-CI score was 2 (range 0-6). None of the patients had a history of diabetes or hypertension before transplant. Conditioning regimen was myeloablative and stem cell source was PB for all patients. Median time to neutrophils engraftment was 10 (range: 9-13) days. With a median follow-up of 4 (range: 0.8-9) months since AUTO-HSCT, one patient with grade 1 COVID infection died as a result of a candida/cytomegalovirus infection, and none of the patients experienced progression of the underlying malignancy. Overall survival was 100% and 75% (95% CI 13-96) at 3 and 6 months respectively. After HSCT, one ALLO and two AUTO asymptomatic patients had a positive nasal swab COVID-19 PCR assay possibly due to delayed shedding of the virus. None of the 21 patients developed active COVID infections post-transplant. In conclusion, allogeneic and autologous hematopoietic transplantation can be performed in patients after COVID-19 infection. Two of 13 allogeneic and one of 8 autologous recipients experienced non-relapse mortality, none directly related to COVID-19 infection. Patients recovering from COVID-19 infection should be considered eligible for hematopoietic transplantation as clinically indicated.

Disclosures
Shpall: Magenta: Honoraria; Affimed: Patents & Royalties; Novartis: Honoraria; Navan: Consultancy; Magenta: Consultancy; Axio: Consultancy; Adaptimmune: Consultancy; Bayer HealthCare Pharmaceuticals: Honoraria; Novartis: Consultancy; Takeda: Patents & Royalties. Chemaly: Other: Other: Compensation: I am a consultant and advisor on companies who are developing new agents such as Merck, Ansun, and Janssen.