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COVID-19 Resources

COVID-19 and Myelodysplastic Syndromes: Frequently Asked Questions

(Version 4.2; last updated May 17, 2021)

Input from Mikkael A. Sekeres, MD; David P. Steensma, MD; Amy DeZern, MD; Gail Roboz, MD; Guillermo Garcia-Manero, MD; and Rami Komrokji, MD.

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

Are patients with Myelodysplastic Syndromes (MDS) or related conditions more likely to contract COVID-19 or to get seriously ill from it?

There are no data indicating that patients with MDS are more likely to contract COVID-19 than patients with healthy bone marrows. Studies from Italy, the US, UK, and China indicate a higher mortality rate from COVID-19 among patients with a history of cancer, including hematological malignancy, compared to those without such a history. While most studies did not assess Covid-19 disease severity or death in patients with MDS independently, multiple studies have now indicated that related conditions such as acute myeloid leukemia are associated with higher death rates due to Covid-19, and we consider patients with MDS to be a high-risk group.

Patients with MDS who have recently undergone allogeneic hematopoietic cell transplant have a markedly increased risk of viral infection, and this risk is likely to extend to coronaviruses. It is thus reasonable to presume that patients with MDS, particularly those who are more lymphopenic or who have undergone transplant within the last year, are compromised in their ability to contain the virus once infected, and have a higher likelihood of hospitalization. Neutropenia may also increase the risk of a secondary bacterial infection after viral infection.

Patients with MDS should continue to practice physical distancing and exercise caution with contacts, even after being vaccinated, until vaccine efficacy in similarly immunocompromised patients has been demonstrated.

Should the approach to therapy in patients with MDS and related conditions be altered? (starting treatment, choice of treatment, transplant considerations)

Patients with higher-risk MDS (IPSS-R score of >3.5) should still be started on therapy with a hypomethylating agent without delay, and without dose adjustment. Those already on such therapy who are tolerating it adequately and who have achieved a clinical response should continue maintenance treatment, given the relapse risk if hypomethylating agents are discontinued. It is unclear if hypomethylating agents influence the clinical course of COVID-19 infection; hypomethylating agents do alter cellular type 1 interferon response, which could hypothetically alter replication of or cellular response to viruses, but there is no evidence of clinical significance of this observation. Moreover, studies in cancer patients have indicated that those receiving chemotherapy do not appear to be at higher risk for untoward outcomes to Covid-19.

For patients with lower-risk MDS (IPSS-R score <3.5), the primary goals of therapy are to minimize transfusions and improve quality of life. In these patients, treatments that risk compromising the immune system can reasonably be delayed. Therapy that results in increased contact with a health care environment (e.g., with frequent laboratory draws for monitoring or visits for injections) can be delayed or scheduled at less frequent intervals during times of high regional viral prevalence. Therapies that can reduce transfusion needs, such as erythropoiesis stimulating agents or luspatercept, may result in a net decrease of health care visits and potential viral exposure, and thus initiation or continuation can be considered.

For some patients, such as those for whom hypomethylating agents have failed, clinical trials may represent the only treatment option. Such trials should continue to be pursued on a case-by-case basis.

Some patients may prefer an oral hypomethylating agent to minimize visits to the infusion center for parenterally administered azacitidine or decitabine, and reduce potential exposure to COVID-19 on public transportation or in crowded facilities. Oral decitabine-cedazuridine was approved by the FDA for treatment of MDS in July 2020, and clinical response, pharmacokinetics and pharmacodynamics appear comparable to injectable decitabine, though the two drugs have not been compared in a formal, non-crossover phase 3 trial. However, oral chemotherapy has potential problems, including a higher out-of-pocket cost for patients, distinct adverse event profile, and risk of non-adherence to therapy. Oral azacitidine was approved by the FDA in September 2020 for maintenance therapy of patients with AML who are in remission after intensive chemotherapy and are unable to complete further intensive chemotherapy. Oral azacitidine lacks a co-administered cytidine deaminase inhibitor and is therefore extensively degraded in the gut, so bioavailability is reduced compared to injectable azacitidine, and drug absorption of oral azacitidine varies widely between patients. Oral azacitidine is not approved for MDS and should not be used as a substitute for injectable azacitidine in MDS.

Allogeneic transplant is feasible, although donors may have to delay unexpectedly if exposed to COVID-19, and it may be more difficult to obtain donor cells from unrelated donors during times of viral surge. Similarly, during times in which local COVID-19 infection rates are high, some institutions have delayed allogeneic transplants due to concern about lack of hospital beds, particularly in intensive care units, but most hospitals do not have a shortage of beds, and deferring transplant in higher-risk patients may increase risk of disease progression.

Patients being considered for potentially myeloablative therapy should undergo testing for COVID-19 prior to initiation. In some patients with a positive test, treatment may need be delayed, while in others a positive result should be incorporated into a risk-benefit assessment of therapy. It is unclear whether it is helpful to test for COVID-19 in asymptomatic patients undergoing less intensive therapies.

Should transfusion thresholds be altered in patients with MDS and related conditions?

If blood product availability is compromised during periods when COVID-19 infection rates are high, it is reasonable to attempt to increase transfusion intervals and lower transfusion thresholds for red blood cells to a hemoglobin of 7 g/dL or lower for patients with MDS who will tolerate this. This may need to be modified for symptomatic patients or those with certain comorbidities such as severe cardiopulmonary disease.

Platelets should be transfused for levels 10 x 109/L or lower, or for symptomatic bleeding, as per usual care. At this time there is no evidence that COVID-19 can be transmitted in blood products; respiratory viruses are usually not transmitted through transfusion. The U.S. Food and Drug Administration continues to report that there have been no reported or suspected cases of transfusion-transmitted COVID-19 to date. In addition, no cases of transfusion-transmission were reported for the other 2 coronaviruses that emerged during the past two decades (i.e., SARS, the Severe Acute Respiratory Syndrome Coronavirus, and MERS-CoV, which causes Mideast Respiratory Syndrome)..

Should frequency of visits for patients with MDS and related conditions be changed?

Acknowledging that patients with MDS and related conditions often have a significantly compromised bone marrow and require frequent transfusions and assessments, face-to-face visits should be reduced during time periods of high viral prevalence. For example, MDS patients who are being followed with a “watch and wait” approach can have visits delayed until after the risk of COVID-19 decreases; conducted via telehealth; or spaced out so that they occur less frequently.

For patients with severe cytopenias receiving regular transfusions or therapy with a hypomethylating agent, it may not be possible to alter visit frequency, as regular monitoring of blood counts is still medically necessary. In these patients, laboratory visits should continue, but direct examinations can be minimized on a case-by-case basis.

Should the management of a patient calling with neutropenic fever be altered during the current pandemic?

MDS patients with febrile neutropenia remain at increased risk for life-threatening infections. Clinical assessment in the standard expedited timelines remains appropriate with access to antibiotics as appropriate. Testing of COVID-19 should follow institutional guidelines but is appropriate in the presence of fever even without respiratory symptoms. Acetaminophen may be preferable to ibuprofen for reducing a fever in MDS patients, especially those with thrombocytopenia or patients who may have functional platelet defects.

Should MDS patients and those with related conditions (for example, those with Del (5q) being treated with lenalidomide) stockpile medications?

At the time of these recommendations, there have not been reported medication shortages specific to patients with MDS and related conditions. For a brief time, lenalidomide could be ordered in 56 day lots instead of the previous 28 day limit, but this policy ended in June 2020.

Are there any special considerations for patients with MDS/myeloproliferative neoplasm (MPN) overlap disorders?

Patients with overlap MDS/MPN such as chronic myelomonocytic leukemia (CMML) can develop leukemoid reactions and cytokine storm in the presence of an infection, which can lead to hypoxemia and hemodynamic instability, and may be fatal. Many of the cytokines released in MDS/MPN leukemoid reactions overlap with those detected in patients with severe COVID-19, and there are case reports of deaths in CMML patients with COVID-19. SARS-CoV-2 uses the angiotensin converting enzyme-related carboxypeptidase (ACE2) receptor to gain entry into cells, and ACE2 is expressed at a high level on monocytes and monocyte-derived macrophages; monocytes and macrophages frequently interact with ACE2-expressing cells in various tissues. For patients with MDS/MPN overlap disorders and leukocytosis, consideration for cytoreduction (e.g., with hydroxyurea) can be considered, but this must be balanced against the risk of increased cytopenias.

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

Yes. In general, it is considered safe and appropriate for patients with MDS to receive vaccines. Specific to SARS-CoV-2, data regarding the safety and efficacy of vaccines in immunocompromised patients have not yet been released, though there is a clear, preliminary signal that vaccine efficacy is significantly compromised in patients with lymphoid malignancies, particularly among those receiving active therapy. As a general statement we support people with MDS 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 ASH FAQs about SARS-CoV-2 vaccines and immunocompromised patients.

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