83% of stem cell recipients produce antibodies after 2 COVID-19 vaccine doses

COVID vaccination viewed from above
COVID vaccination viewed from above

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Stem cell transplant recipients with cancers like leukemia had an antibody response rate of 83% to the second dose of the Pfizer/BioNTech mRNA COVID-19 vaccine, with almost two-thirds having very strong responses, an observational, single-center study today in JAMA Network Open finds.

Researchers from Nantes University Hospital in France studied 117 coronavirus-naïve adults who received a donor stem cell transplant for the treatment of hematologic cancer and were given two doses of the Pfizer COVID-19 vaccine from Jan 20 to Apr 17. The median interval between the two doses was 22 days.

The study expands on a report by the same team in eJHaem on Jun 1 showing an antibody response to one vaccine dose of 55% in 112 stem cell transplant recipients.

Hematologic cancers—such as leukemia, lymphoma, and multiple myeloma—begin in blood-forming tissue, such as in the bone marrow or in immune system cells.

Mild adverse reactions in some

The researchers tested antibody responses twice, once at the time of the second dose and again roughly 1 month later. Antibody concentrations of 0.8 units per milliliter (U/mL) or higher were considered positive. The median patient age was 57 years, and 60% were men.

Sixty-three patients (54%) had a positive antibody response at the time of the second injection, with a median immunoglobulin G concentration of 15.8 U/mL (range, 0.9 to greater than 250 U/mL). Four other patients who had been previously infected with SARS-CoV-2 reached the maximum antibody level of at least 250 U/mL before the second vaccine dose.

At the second antibody test, conducted a median of 35 days after the second injection, 97 patients (83%) tested positive for SARS-CoV-2 antibodies. Seventy-two patients (62%) reached the highest possible antibody level.

"This is much more than the 54% rate of seroconversion [detectable antibodies in the blood] that has been reported after 2 doses in solid-organ transplant recipients and compares favorably with data obtained in patients treated for solid tumors, for whom a 95% of response rate was obtained after the second dose," the researchers wrote. They cautioned, however, that antibody response is only one marker of immunity and that stem cell recipients will likely have different T-cell responses, which requires future research.

Risk factors for lack of antibody response were receipt of a stem cell transplant in the previous year, lymphopenia (fewer than 1,000 lymphocyte white blood cells per microliter), and immunosuppressive treatment or chemotherapy at the time of vaccination.

Patient-completed questionnaires showed that two vaccine doses were safe, with mild adverse reactions in 51 of 106 patients (48%) within 7 days after the first dose and 34 of 87 patients (39%) 7 days after the second dose.

The adverse event rates were similar to those of a healthy vaccinated cohort of 25 healthcare workers, who all reached the highest antibody concentration after two doses. No COVID-19 infections were reported after a median follow-up of 58 days.

The authors noted that vaccination of hematologic cancer patients is particularly important because they tend to have poor COVID-19 outcomes, with a roughly 40% death rate.

Vaccine only part of COVID-19 prevention

In a commentary in the same journal, Joshua Hill, MD, of Fred Hutchinson Cancer Research Center in Seattle, said that the more than 10,000 US allogeneic stem cell transplants that are performed each year in hematologic cancer patients place a large population of patients at high risk for COVID-19 illness.

Hill wrote that, in general, guidelines recommend giving routine killed-virus vaccines 6 or more months after stem cell transplant because of relatively poor response rates when given earlier. Based on historical data, however, the National Comprehensive Cancer Network and other organizations suggest considering COVID-19 vaccination as soon as 3 months after transplant.

Hill added that while COVID-19 vaccination is a priority after stem cell transplant, it is only one part of a broader treatment strategy. "For now, patients who are in the first year after [stem cell transplant] or remain otherwise immunosuppressed should regard SARS-CoV-2 as a serious threat despite vaccination and follow behaviors with which they are already familiar," he wrote.

Research into ways to better prevent COVID-19 in stem cell transplant recipients is under way, including studies on third vaccine doses and infusions of preventive monoclonal antibodies or T-cell infusions, according to Hill.

"For infected individuals, a variety of therapies are currently available, but efficacious antivirals that can be easily administered both inside and outside of hospital settings are still desperately needed," he wrote. "The preliminary findings reported here are reason for optimism, yet there is clearly room for improvement and much more to learn about preventing and managing COVID-19 after [stem cell transplant]."

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