COVID-19 and Hematopoietic Cell Transplantation: Frequently Asked Questions
(Version 1.2; last updated January 13, 2021)
Input from Marco Mielcarek, MD; Helene Schoemans, MD; Sergio Giralt, MD; and Helen Elisabeth Heslop, MD, DSc.
Note: Please review ASH's disclaimer regarding the use of the following information.
Are transplant and immunotherapy programs accepting new patients?
Transplant and immunotherapy centers are modulating new patient numbers based on COVID-19 activity in their regions. Some centers never decreased their activity. Other transplant and immunotherapy programs curtailed clinical activity preparing for or responding to a COVID-19 surge, but most have started the process of reopening, with the majority of centers back to normal patient numbers.
Centers that have reopened are generally using the same criteria for recommending transplantation or cell therapies that they were using pre-COVID-19. The exception is centers located in communities with ongoing or increasingly high levels of COVID-19 activity; these centers may still be deferring non-urgent patients. Even at these centers, patients are being treated urgently if delay would result in greater risk of disease progression than COVID-19. Patients who are positive for SARS-CoV-2 should have transplantation delayed until their viral test is negative, or at least 14 days removed from symptoms or first positive test.
How are patients, donors and caregivers protected from SARS-CoV-2 at transplant centers?
Given the intense immunosuppression associated with HCT, the number of these patients infected with SARS-CoV-2 seems to be lower than expected. This may be due to the rigorous infection-control procedures already in place before COVID-19, as well as patient awareness and risk-adverse behavior. For patients undergoing transplant, rigorous use of personal protective equipment (PPE) and infection control measures are very effective in preventing infections in health care providers and nosocomial cross infection. Visitors are still limited at most centers; caregivers are not being tested at most centers unless they are symptomatic. All medical staff are screened for symptoms daily. At most programs, patients are tested on arrival and/or prior to the start of conditioning regimens. Some centers are testing asymptomatic patients intermittently after transplant.
Since March 2020, there has been a move to cryopreserve unrelated donor products with most retrospective studies showing no compromise of transplant success, but no prospective studies. There is geographic variability in this practice now, with some registries requiring justification for cryopreservation. The one exception is bone marrow destined for a patient with aplastic anemia; this is the one case where cryopreservation has been associated with poor engraftment and higher mortality. A few centers are cryopreserving family member stem cells.
What is known about outcomes in transplanted patients with COVID-19?
Immunosuppressed transplant patients have variable presentations of COVID-19 disease. At MSKCC, 70 transplant patients were diagnosed with COVID-19. EBMT, CIBMTR and ASH are collecting data on transplant patients with COVID-19. Outcome data on COVID-19 in HCT patients is difficult to interpret due to limited publications and a tendency of more severe cases to be reported. Although no formal head-to-head comparison with matched controls from the general population has yet been done, data-collection from CIBMTR, ASH , the European Society for Blood and Marrow Transplantation and the Spanish Hematopoietic Stem Cell Transplantation and Cell Therapy Group1 and the French Society of Bone Marrow Transplantation2 suggest that HCT patients with COVID-19 have reasonable survival perspectives but are at a high risk of developing severe complications.
Are SARS-CoV-2 PCR and antibody tests accurate in transplant patients?
There is no evidence that the standard COVID-19 PCR and antibody tests are misleading in HCT patients. Studies need to be performed to see if patient receiving rituximab or B-cell directed CAR-T therapy are able to mount a detectable and sustained antibody response. However, evidence shows that immunocompromised patients may shed virus for a longer period than otherwise healthy patients,3,4 so the transplant team should therefore carefully monitor HCT patients after COVID-19.
My patient has graft-versus-host disease and is being treated with immunosuppressive drugs. Should I take them off these medications, adjust dosages or switch regimens?
Generally not. This decision needs to be individualized, considering the risk that stopping, adjusting dosages or switching regimens for GVHD treatment will incite a flare (for example, 50% of people who stop immunosuppression when chronic GVHD is controlled will subsequently flare their symptoms and need to restart, a median of 3-6 months after stopping) versus a potentially worse outcome if they get COVID-19 while on immunosuppression. If a GVHD flare occurs, then more intensive immunosuppressive treatment may be needed initially to control symptoms, putting patients at higher risk for severe COVID-19 disease. Thus, if a patient is doing well on their current immunosuppressive regimen, we would not adjust GVHD treatments due to COVID-19 risk or actual infection.
Any special considerations for CAR-T patients?
Centers that have reopened and have ICU capacity and access to tocilizumab are giving patients CAR-T therapy.
Should transplant patients receive a vaccine for SARS-CoV-2?
In general, it is considered safe and appropriate for transplanted patients to receive vaccines, as long as they are not live, attenuated virus vaccines. Specific to SARS-CoV-2, data regarding the safety and efficacy of vaccines in immunocompromised patients have not yet been released. As a general statement we support transplanted people receiving a SARS-CoV-2 vaccine (non-live) although they may not mount an effective immune response, but await trial results. For more information about SARS-CoV-2 vaccines and immunocompromised patients, see the various guidelines on this topic.
- Ljungman P, De La Camara R, Mikulska M, et al. COVID-19 and Stem Cell Transplantation; Results from the Prospective Survey By the Infectious Diseases Working Party of the European Society for Blood and Marrow Transplantation (EBMT) and the Spanish Hematopoietic Stem Cell Transplantation and Cell Therapy Group (GETH). Blood 2020;136(Suppl 1):32–33.
- Xhaard A, Xhaard C, D'Aveni M, et al. Risk Factors for Severe Form of COVID-19 after Allogeneic Hematopoietic Stem Cell Transplantation: A SFGM-TC Multicentre Cohort Study. Blood 2020;136(Suppl 1):34.
- Infante MS, González-Gascón Y Marín I, Muñoz-Novas C, et al. COVID-19 in patients with hematological malignancies: A retrospective case series. Int J Lab Hematol. 2020;42:e256-e259.
- Shah V, Ko Ko T, Zuckerman M, et al. Poor outcome and prolonged persistence of SARS-CoV-2 RNA in COVID-19 patients with haematological malignancies; King's College Hospital experience. Br J Haematol. 2020;190:e279-e282.