To the Editor:
Data concerning the impact of COVID-19 on hematopoietic stem cell transplant (HSCT) patients are scarce and variable. It is thought that HSCT patients may be at higher risk of COVID-19-associated complications secondary to immunosuppressive therapy, and the subsequent delayed immune reconstitution at the post-transplant phase .
In this report, we describe the clinical course of seven stem cell transplant recipients at the Nasser’s Institute for Research and Treatment Hospital who survived a diagnosis of COVID-19. Patients were identified as being SARS‐CoV‐2 positive by real-time polymerase chain reaction. Nasopharyngeal swabs were performed in the context of symptoms (fever, cough, dyspnea, and fatigue), radiological findings, or contact with a documented SARS‐CoV‐2 positive individual. The median age of patients was 30 years (range, 3–43 years), two patients (28%) were females and five (72%) were males, and the median time from stem cell infusion to the diagnosis of COVID-19 was 8 months (range, 3–113 months).
All patients received allogeneic stem cell transplantation (allo‐SCT) from human leukocyte antigen (HLA) 10/10-matched related donors. All patients received myeloablative conditioning regimens. Four patients (66%) received post‐transplant cyclophosphamide (PTCy), and one patient received antithymocyte globulin rabbit for primary graft-versus-host disease (GvHD) prophylaxis. None of our patients had a relapse at the point of being diagnosed with a COVID-19 infection. All patients were receiving immunosuppressant therapy at diagnosis, with a stable graft function before COVID-19 positivity. Immunosuppressants were continued after the diagnosis of COVID-19 was confirmed. All patients not previously receiving corticosteroids were given prednisone at a dose of 0.5 mg/kg/day PO for 10 days (0.4 mg/kg/day methylprednisolone equivalent), azithromycin 500 mg/day PO for 6 days (10 mg/kg/day for pediatrics), voriconazole 200 mg PO q12h for 1 month (7 mg/kg/dose q12h PO for pediatrics), and high-dose cotrimoxazole for PCP coverage (15 mg/kg/day trimethoprim PO for 2 weeks). Adult patients were given rivaroxaban 20 mg/day PO according to their platelet counts for one month.
All patients were lymphopenic with a median absolute lymphocyte count of 0.76 × 109/L (range, 0.31–0.97 × 109/L). The median platelet count was 115 × 109/L (range, 80–230 × 109/L) at the diagnosis of COVID-19. Only one patient (14%) had acute grade II GvHD of the skin and gut (overall grade II per Glucksberg criteria) and was receiving prednisone (2 mg/kg/day PO) and mycophenolate. Two patients had chronic GvHD of the skin and liver; one patient was receiving prednisone 1 mg/kg/day PO, while the other patient was receiving cyclosporine, mycophenolate, and prednisone (0.5 mg/kg/day PO). Except for systemic corticosteroids, none of our patients received specific treatment for COVID-19. Patients’ characteristics and their outcome are summarized in Table 1.
Regarding COVID-19 symptoms, four patients (57%) experienced mild lower respiratory tract symptoms, three (43%) experienced high-grade fever, and all of them had chest infiltrates on both chest radiographs and computed tomography scans. The median follow-up was 82 days (range, 77–112) from the onset of COVID-19.
Our observations are inconsistent with those reported by Kanellopoulos et al., where they reported a mortality rate of 43%. However, their patients’ characteristics were different. The median age in their patient population was 61 years, half of the allo-SCT were HLA 10/10-matched unrelated donor transplants, two (34%) had a haploidentical transplant, one (16%) had an HLA 9/10-matched unrelated donor transplant, and no patient received a myeloablative allo-SCT. Of note, out of the three patients who received PTCy, only one patient (64 years) died due to CNS bleeding secondary to AML relapse .
Our observations also differ from those reported by Malard et al. from the hematology department of Saint Antoine hospital in Paris, where they reported 52% of their patients developed ARDS and a 1-month mortality rate of 40%. Remarkably, only one out of three patients who received cyclophosphamide-based regimens died. Half of their patients were older than 65 years of age, and all patients who died were older than 65 years. This suggests that COVID-19 mortality risk factors in HSCT patients may be similar to those in the general population .
We propose a few remarks for consideration. First, despite receiving myeloablative conditioning regimens, we had no mortality among our patients secondary to COVID-19. Second, we observed that all patients who received PTCy for GvHD prophylaxis experienced mild COVID-19 symptoms. Cytokine release syndrome (CRS) that is frequently associated with haploidentical HSCT and mitigated by PTCy- shares similar pathophysiology with severe COVID-19-associated CRS [4, 5]. We hypothesize that PTCy might have a protective role against COVID-19-associated CRS.
We recommend controlled studies with a greater number of patients and longer follow up periods—with special attention to the impact of cyclophosphamide on COVID-19 outcome—to reach a definite conclusion concerning the outcome of COVID-19 in HSCT.
Ogonek J, Juric MK, Ghimire S, Varanasi PR, Holler E, Greinix H, et al. Immune reconstitution after allogeneic hematopoietic stem cell transplantation. Front Immunol. 2016;7:507.
Kanellopoulos A, Ahmed MZ, Kishore B, Lovell R, Horgan C, Paneesha S, et al. COVID-19 in bone marrow transplant recipients: reflecting on a single centre experience. Br J Haematol. 2020;190:e67–70.
Malard F, Genthon A, Brissot E, van de Wyngaert Z, Marjanovic Z, Ikhlef S, et al. COVID-19 outcomes in patients with hematologic disease. Bone Marrow Transplant. 2020;55:2180–4. https://doi.org/10.1038/s41409-020-0931-4.
Abboud R, Keller J, Slade M, DiPersio JF, Westervelt P, Rettig MP, et al. Severe cytokine-release syndrome after T cell–replete peripheral blood haploidentical donor transplantation is associated with poor survival and anti–IL-6 therapy is safe and well tolerated. Biol Blood Marrow Transplant. 2016;22:1851–60. https://doi.org/10.1016/j.bbmt.2016.06.010.
Moore JB, June CH. Cytokine release syndrome in severe COVID-19. Science 2020;368:473–4.
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Sultan, A.M., Mahmoud, H.K., Fathy, G.M. et al. The outcome of hematopoietic stem cell transplantation patients with COVID-19 infection. Bone Marrow Transplant 56, 971–973 (2021). https://doi.org/10.1038/s41409-020-01094-9