Blunted Response to COVID-19 Vaccines in Transplant and Cellular Therapy Recipients

Many patients who undergo bone marrow transplant and CAR-T cell therapy do not mount a detectable humoral response to authorized COVID-19 vaccines, according to study findings published in Blood.

Study author Mehdi Hamadani, MD, of the Medical College of Wisconsin, told ASH Clinical News that these findings suggest routine testing of humoral responses to COVID-19 vaccines should be strongly considered in immunocompromised patients.

“Checking these antibody responses can help clinicians educate vaccine recipients about the continued use of caution, social distancing, and wearing masks,” said Dr. Hamadani. “And once vaccine boosters are made available in the future, antibody testing may help targeted delivery of booster doses to patients with no or weak humoral responses to the vaccine.”

Vaccines represent the most effective evidence-based strategy to prevent severe COVID-19 and reduce the spread of infection. Despite the high efficacy of the vaccines in the overall population, previous reports have suggested that patients with hematologic malignancies have an inadequate immune response to vaccination. Larger studies are needed to determine the benefit of COVID-19 vaccines in these patients.

In this retrospective study, Dr. Hamadani and colleagues examined serological response to full COVID-19 vaccination among people who had undergone hematopoietic cell transplantation (HCT) and cellular therapy for hematologic malignancies. Blood samples of these patients were previously tested for antibodies to the S1 domain of the novel coronavirus’ spike protein.

Patients included in the analysis had undergone either autologous HCT (AHCT; n=45), allogeneic HCT (alloHCT; n=71), or CAR T-cell therapy (n=14). Approximately 60% of these 130 patients tested positive for SARS-CoV-2 antibodies following vaccination. Positivity rates, stratified by procedure, were as follows:

  • AHCT: 60%
  • alloHCT: 69%
  • CAR T-cell therapy: 11%

In a subgroup analysis focused on AHCT recipients, the researchers found no significant difference in seropositivity rates based on age, time between HCT and vaccination, disease type, and immunoglobulin G (IgG) level.

The subgroup analysis for alloHCT also found no differences for the seropositivity rates by age, time between alloHCT and vaccination, or even by immunosuppression status, presence of active graft-versus-host disease (GVHD), or recipient CD4 and CD8 counts at vaccination.

In the alloHCT group, higher levels of IgG were observed in patients who were seropositive (p=0.01). There was a significant association between the use of corticosteroids for post-alloHCT GVHD and lower seropositivity rates when compared with patients who did not receive corticosteroids (31% vs. 69%, respectively; p=0.001).

The seropositivity rates for the small group of patients who were fully vaccinated less than six months after HCT were 50% for AHCT recipients, 37% for alloHCT recipients, and 0% for CAR-T therapy recipients.

According to the researchers, the finding of low anti-spike antibody titers in HCT and CAR-T therapy recipients following vaccination with available COVID-19 vaccines “suggest[s] that such patients may remain at high risk of COVID-19 infection despite vaccination.” However, the study didn’t specify which vaccines each patient received, possibly warranting future studies focused on each specific vaccine.

Limitations of the study included its small sample size, as well as a lack of a control group featuring patients not receiving HCT and CAR-T therapy. Dr. Hamadani added that the study relied on a commercially available test to examine whether the vaccine elicited anti-spike protein antibodies, but whether this test correlates with virus neutralizing antibodies remains unknown.

“Checking these antibody responses can help clinicians educate vaccine recipients about the continued use of caution, social distancing, and wearing masks.”

—Mehdi Hamadani, MD

“Other unknowns surround the clinical significance of cellular immune response in the absence of humoral response and whether patients without humoral responses develop a cellular immune response,” he added. “Further studies to examine these questions are required.”

Ultimately, the researchers noted, the findings from “this study underscore the importance of masking, social distancing, and vaccination” for the households of HCT and CAR-T therapy recipients.

The authors report no relevant conflicts of interest.


Dhakal B, Abedin SM, Fenske TS, et al. Response to SARS-CoV-2 vaccination in patients after hematopoietic cell transplantation and CAR-T cell therapy [published online ahead of print, 2021 Aug 2]. Blood. doi: 10.1182/blood.2021012769.