In mid-May, the Centers for Disease Control and Prevention (CDC) provided new guidance that caused vaccinated Americans to celebrate: a return to mask-free dining, shopping, and indoor gatherings. But it caused us and the patients we treat — those with serious illnesses of the blood and bone marrow — to shudder and redouble our efforts to keep them safe. Experience during the first year of the pandemic has shown that patients with hematologic malignancies are at high risk of severe illness and even death ( from SARS-CoV-2.

So, after 14 months of strict isolation and fear, our patients welcomed news of effective COVID-19 vaccines with anticipation that their lives could soon improve. Plans were made to visit new grandchildren born during the pandemic and seen thus far only on Zoom or FaceTime. Family members and friends, unable to gather even with strict precautions, knowing that a misstep could be deadly, finally made plans to visit their loved ones. During office visits and in a deluge of phone calls, emails, and patient portal messages, our patients reached out for reassurance that they could return to normal life now that they were vaccinated.

Unfortunately, we have had disappointing news for them. Early data on immune responses to COVID-19 vaccines published in Blood (, and previous information on responses to other vaccines such as those for hepatitis ( and influenza ( indicate that many patients with hematologic malignancies have limited or no humoral response to vaccination and presumably receive little to no protection.

One such phone call was from a scientist recently treated for lymphoma who discovered he had no anti–SARS-CoV-2 spike protein antibodies detected despite receiving both doses of the vaccine. He had hoped to see his grandchildren and is now devastated. Another patient vaccinated in April had hoped to go back to work in person after vaccination and wanted a letter stating it was safe to do so.

It is important to emphasize that the clinical trials showing COVID-19 vaccines to be safe and effective enrolled healthy volunteers. Therefore little is known about how well immunocompromised individuals respond to vaccination and how well they will be protected. Evidence is accumulating that many patients with hematologic malignancies and other conditions that result in poor immune function or require treatment with immunosuppressive therapy including radiation are likely not fully protected by vaccination ( This group includes patients with sickle cell disease; severe autoimmune diseases such as lupus, rheumatoid arthritis, or Crohn's disease; non-blood cancers treated with therapies that impair immune function; and those who have undergone bone marrow or solid organ transplantation. These individuals, representing millions of people in the United States, may be immune compromised for prolonged periods due to their underlying disease, its treatment, or both. Patients receiving anti-CD20 antibody therapy for treatment of B-cell lymphomas and for some autoimmune disorders may be particularly vulnerable. How much of a role cellular response plays in protection from SARS-CoV-2 in the absence of humoral response remains unknown. We have had to break the news to our patients that they likely remain at high risk, and that loosening of social distancing and mask restrictions may paradoxically put them at higher risk than prior to the CDC announcement.

Research into the efficacy of the COVID-19 vaccines in patients with impaired immune systems and development of better treatments for those who become infected is critically important to allow our patients to re-enter the world. Although clinical trials testing vaccination in patients with hematologic malignancies are ongoing at several academic centers, as well as the National Institutes of Health and through The Leukemia & Lymphoma Society and Blood Cancer UK, the results of these clinical trials won't provide guidance for some time. Alternatives to vaccination such as antibody infusions may be required for some individuals. Others may benefit from vaccine boosters or changes in their cancer treatments (see the ASH COVID-19 FAQs at There are many new therapies for hematologic malignancies and for other diseases, that may be less likely to blunt the response to vaccination. Some patients may be able to take a vacation from treatment to allow for immune system recovery and more effective responses to vaccines.

The CDC is advising against measuring antibody responses to vaccination, but our patients are clamoring to know whether they've had any response whatsoever. We are struggling to respond to the changing messaging and to the absence of hard data on which to base our recommendations. We are data-driven by nature and training but are at a loss when it comes to responding empathetically to our patients' anxiety and isolation. How did we get here? How can we learn from this pandemic? Can we open clinical trials more effectively to answer these kinds of questions in the future? We must answer these questions to be our patients' best advocates.

In the meantime, individuals with hematologic malignancies and compromised immune systems should receive the COVID-19 vaccine, because some benefit is better than none. They should continue social distancing and adhere to other proven mitigation strategies until there is information to indicate otherwise. Vaccination of their families and contacts will help keep them safe. Widespread vaccination of the population at large and continued masking in indoor spaces if unvaccinated individuals are present will be required until COVID-19 disappears from our midst; it is the only way our most vulnerable fellow citizens will be able to return safely to any activities. With COVID-19 mortality rates of 20 to 30 percent ( in patients with many types of blood cancers, and increased circulation of highly infective variant strains of SARS-CoV-2, we worry that the sudden shift from masking and distancing requirements to personal choice and an honor system may place our patients at grave risk. Lastly, those who mask voluntarily regardless of public policy or local statutes must be treated with respect and empathy as they advocate for themselves and their loved ones by taking additional precautions to reduce risks of infection with COVID-19.

The COVID-19 vaccines are modern miracles that have the potential to protect us all if those of us with healthy immune systems show compassion for others by getting vaccinated.