COVID-19 Resources

COVID-19 and Hematopoietic Cell Transplantation: Frequently Asked Questions

(Version 2.0; last updated April 1, 2022)

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 many centers are back to normal patient numbers. However, ongoing COVID-19-related staffing shortfalls continue to cause disruptions at some transplant centers resulting in transplant numbers below previous baselines.

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. However, for patients with persistently low-level PCR-positivity, transplant practices are evolving and vary by center.

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 systematically at most centers provided they have undergone a (semi-) recent full vaccination regimen unless they are symptomatic. Vaccination requirements for caregivers vary by center, though. 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. Since early 2022, in response to the Omicron surge, NMDP, Antony Nolan and DKMS re-advocate cryopreservation of stem cell products (unrelated and related) due to risks of donor positivity or major travel disruptions.

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 French Society of Bone Marrow Transplantation suggest that HCT patients with COVID-19 are at a high risk of developing severe complications. Sharma and colleagues reported on a 30 et al mortality rate based on CIBMTR data. Data from the EBMT showed a slight improvement in the six weeks-mortality rate from 25 percent to 20 percent, between the first and second wave in HCT patients and a 50 percent mortality rate in CAR-T patients.

There does not seem to be a striking survival difference between patients with a history of autologous and allogeneic HCT, but age older than 50 years and the development of COVID-19 within the first year post-HCT have repeatedly been associated with higher risk of dying. Co-infection with other pathogens have been reported in up to 19 percent of cases, with a particularly high risk for fungal infection.

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. However, evidence shows that immunocompromised patients typically shed virus for longer than four weeks, so the transplant team should therefore carefully monitor HCT patients after COVID-19. The CDC recommends for in immunocompromised patients an isolation of at least 20 days after onset of symptoms or positive PCR test.

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 graft-versus-host disease (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.

Furthermore, current therapeutic guidelines recommend the use of dexamethasone as standard of care for hypoxemia in COVID-19 pneumonia, as well as the addition of other anti-inflammatory medication in specific COVID situations, making it even more unlikely that a reduction in immunosuppressive treatment be necessary for patients with GVHD.

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; however, since tocilizumab is also being used in COVD treatment, supply chain issues might come into play in some settings where the COVID pandemic is particularly prevalent.

Should transplant patients receive a vaccine for SARS-CoV-2?

For more information about SARS-CoV-2 vaccines and immunocompromised patients, see the specific guidelines on this topic.

Resources

Sharma A, Bhatt NS, St Martin A, Abid MB, Bloomquist J, Chemaly RF, et al. Clinical characteristics and outcomes of COVID-19 in haematopoietic stem-cell transplantation recipients: an observational cohort study. The Lancet Haematology. 2021;8(3):e185-e93.

Ljungman P, de la Camara R, Mikulska M, Tridello G, Aguado B, Zahrani MA, et al. COVID-19 and stem cell transplantation; results from an EBMT and GETH multicenter prospective survey. Leukemia. 2021:1-10.

Xhaard A, Xhaard C, D'Aveni M, Salvator H, Chabi ML, Berceanu A, et al. Risk factors for a severe form of COVID-19 after allogeneic haematopoietic stem cell transplantation: a Société Francophone de Greffe de Moelle et de Thérapie cellulaire (SFGM-TC) multicentre cohort study. British journal of haematology. 2021;192(5):e121-e4.

Ljungman P, de la Camara R, Mikulska M, Tridello G, Aguado B, Zahrani MA, et al. COVID-19 and stem cell transplantation; results from an EBMT and GETH multicenter prospective survey. Leukemia. 2021;35(10):2885-94.

Spanjaart AM, Ljungman P, de La Camara R, Tridello G, Ortiz-Maldonado V, Urbano-Ispizua A, et al. Poor outcome of patients with COVID-19 after CAR T-cell therapy for B-cell malignancies: results of a multicenter study on behalf of the European Society for Blood and Marrow Transplantation (EBMT) Infectious Diseases Working Party and the European Hematology Association (EHA) Lymphoma Group. Leukemia. 2021;35(12):3585-8.

Mushtaq MU, Shahzad M, Chaudhary SG, Luder M, Ahmed N, Abdelhakim H, et al. Impact of SARS-CoV-2 in Hematopoietic Stem Cell Transplantation and Chimeric Antigen Receptor T Cell Therapy Recipients. Transplant Cell Ther. 2021;27(9):796.e1-.e7.

Camargo JF, Mendoza MA, Lin R, Moroz IV, Anderson AD, Morris MI, et al. Clinical presentation and outcomes of COVID-19 following hematopoietic cell transplantation and cellular therapy. Transplant infectious disease : an official journal of the Transplantation Society. 2021;23(4):e13625.

Lafarge A, Mabrouki A, Yvin E, Bredin S, Binois Y, Clere-Jehl R, et al. Coronavirus disease 2019 in immunocompromised patients: a comprehensive review of coronavirus disease 2019 in hematopoietic stem cell recipients. Current opinion in critical care. 2022;28(1):83-..

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