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COVID-19 Resources

COVID-19 and Aplastic Anemia: Frequently Asked Questions

(Version 3.0; last updated May 6, 2021)

Written by Neal Young, MD; with input from Robert Brodsky, MD; Cynthia Dunbar, MD; Judith Marsh, MD; and Regis Peffault de Latour, MD, PhD.

Note: Please review ASH's disclaimer regarding the use of the following information.

How do patients with aplastic anemia (AA) fare if they get COVID-19?

Relatively little is known about the course of people with aplastic anemia and COVID-19, with scattered case reports and one larger case series. Patients may be discovered to have AA at the time of presentation with COVID-19 infection or become infected while still significantly immunosuppressed due to antithymocyte globulin (ATG) and cyclosporine (CSA) treatment or during remission while off therapy for AA. Immunosuppression may place patients with AA at a higher risk for serious infection but may also be beneficial if immunosuppression decreases late hyperinflammatory tissue destruction. A serious viral infection such as COVID-19 could serve as an initiating event for AA or drop blood counts in patients with ongoing disease or those in remission. To date, the outcomes reported in patients appear to fall within expected ranges based on other known COVID-19 prognostic factors such as age, cardiovascular risk factors, metabolic factors, and others.

For the new patient with severe AA (SAA), what are realistic treatment options now?

The definitive therapies for SAA remain transplant or immunosuppression with horse ATG, CSA, and eltrombopag (IST). In patients with an absolute neutrophil count (ANC) lower than 200/μL (super-severe AA), delaying transplantation or IST therapy has known risks that likely outweigh the unknown risks of exposure to the coronavirus during hospitalization, or the impact of immunosuppression during the course of COVID-19. While those with an ANC higher than200/μL may want to defer transplantation during any COVID-19 surge in their location, patients at high risk of death without transplantation should move to transplant promptly if a healthy, matched, COVID-19–vaccinated donor is available.

ATG and CSA are not profoundly immunosuppressive. ATG affects mainly T cells and declines in circulating lymphocytes are relatively brief. While increased viral load for herpesviruses after ATG are frequent, clinical viral disease is not, in contrast to following allogeneic transplantation, with caution needed for extrapolation from herpesviruses to a novel coronavirus. More frequent and more severe viral infections are not expected with CSA alone. In patients with stable disease and an ANC greater than 200/μL, a single-dose SARS-CoV-2 vaccine regimen could be administered at least two weeks prior to initiating ATG/CSA.

Hospitalization of patients for ATG administration may be problematic given lack of bed availability and risk of exposure to COVID-19 patients in areas experiencing surges. Expectant care, with oral CSA and eltrombopag alone is a possibility, particularly in patients with an ANC greater than 200/μL. The for patients unable to receive ATG immediately that is approved; starting low dose CSA and full dose eltrombopag as an outpatient supervised by the local physician, with drugs supplied by the National Institutes of Health, and telemedicine utilized to enroll on protocol and to monitor for toxicity.

Should I modify blood count monitoring and transfusion? Can I treat febrile neutropenia at home?

Schedules can be modified depending on the stability of levels and established patterns in an individual patient. The goal is to keep patients out of clinics and hospitals as much as possible while still ensuring adequate follow-up and clinical oversight, for instance combining laboratory testing and transfusion visits. Cyclosporine blood concentrations in a patient who has demonstrated stability of levels may be determined less frequently than weekly to avoid laboratory visits. Platelets are conventionally administered prophylactically to maintain levels greater than 10,000/μL, but in a marrow failure patient without bleeding, expectant transfusion could be acceptable, with platelet transfusions only as needed. Granulocyte colony-stimulating factor has not been shown to improve outcomes in SAA, and should not be instituted, nor should corticosteroids other than as required with horse ATG to prevent serum sickness.

Patients with SAA and febrile neutropenia should still be hospitalized for initial management. Early discharge home with continued oral antibiotics or home infusion may be possible in stable patients.

Patients with PNH, frequent in the setting of AA, who require anti-complement therapy should not have it interrupted because of the risk of serious and irreversible thrombosis. Ravulizumab, requiring administration only every eight weeks, would be preferable eculizumab to minimize visits to a physician’s office or infusion center.

What is the role of monitoring for COVID-19 in patients who are neutropenic and/or immunosuppressed?

Patients being considered for rapid definitive treatment with transplantation or with IST should be screened, and if positive, therapy should be delayed until the virus has cleared. While early treatment is preferred, hematologic improvement after immunosuppressive therapy is not immediate, usually only occurring after several weeks to months, so delaying IST for a week or two for viral clearance would not greatly impact on time to improvement in blood counts.

Should patients with AA receive a SARS-C0V-2 vaccine when available?

There are case reports of AA developing postvaccination, and of recovered AA patients relapsing following vaccine administration. In the setting of the COVID-19 pandemic, current known risk-versus-benefit considerations favor vaccine administration, particularly in any patient with additional risks for severe COVID-19 disease (i.e., age, obesity, and other comorbidities associated with increased risk). Within six months of ATG/CSA initiation, patients are unlikely to mount an appropriate immune response to a vaccine, and instead could be considered for passive antibody therapies following high-risk exposure, or within three days of infection/initiation of symptoms. Those patients with AA remaining on CSA more than six to 12 months following ATG treatment may respond to a SARS-CoV-2 vaccine, but no data on efficacy, specifically in patients with AA, are available. Patients with AA who are within six months of allogeneic transplantation or at later time points in the setting of active graft-versus-host disease are unlikely to respond to a SARS-CoV-2 vaccine. Post-transplantation patients with AA should follow standard post-transplantation guidelines for vaccine administration. More information on considerations surrounding SARS-CoV-2 vaccine administration in immunocompromised hematology patients can be found in the General Principles of COVID-19 Vaccines for Immunocompromised Patients FAQ.

Reference

Paton C, Mathews L, Groarke EM, et al. . Br J Haematol. 2021. doi:10.1111/bjh.17415.

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