Vaccine Responses Hold Up a Year After Stem Cell Transplants, Study Finds

Patients who undergo allogeneic haematopoietic stem cell transplantation, in which blood-forming stem cells come from a donor rather than the patient, face a persistent immunological dilemma. The conditioning chemotherapy and immunosuppressive drugs required to prevent graft-versus-host disease strip away much of the immune memory a person has built over a lifetime, leaving transplant recipients unusually vulnerable to infections, including COVID-19. At the same time, the same immune impairment raises doubts about whether vaccines can mount a meaningful response in this population. A new study from researchers at Universitätsklinikum Jena in Germany, published in the Journal of Cancer Research and Clinical Oncology, offers reassurance on both counts, showing that most transplant recipients do develop antibodies against SARS-CoV-2 after mRNA vaccination, and that a third dose substantially closes the gap left by an incomplete initial series.

The team, led by Carl C. Crodel and Inken Hilgendorf, enrolled 114 patients between July and September 2022 and followed them up one year later. The cohort had a median age of 62 years, with ages ranging from 27 to 70, and included 55 women, or 48.2 percent of participants. Rather than relying solely on hospital records, the investigators combined retrospective chart review with a questionnaire that captured each patient’s vaccination status, any side effects experienced, and the course of any COVID-19 illness that occurred. This dual approach allowed them to assess not just laboratory measures of immunity but also the real-world tolerability of vaccination in a group whose immune systems are still rebuilding after transplantation.

Vaccine uptake in the cohort was high but not universal. Overall, 89.4 percent of patients had received at least two doses of a SARS-CoV-2 vaccine, and 66.7 percent had completed three vaccinations. A notable minority, 10.5 percent, refused vaccination altogether, a finding that underscores lingering hesitancy even among patients at elevated risk of severe disease. The mRNA vaccines dominated the vaccination landscape in this cohort, consistent with their widespread use across Germany during the pandemic. Because mRNA vaccines deliver the genetic instructions for the viral spike protein directly into host cells, they depend on the recipient’s own cellular machinery to produce antigen and on intact antigen-presenting cell function to prime T cells, both of which can be compromised in the months following transplantation.

The central immunological finding was encouraging. Most patients responded to vaccination, with 81.8 percent reaching detectable SARS-CoV-2 spike IgG titers after the second dose and 96.1 percent achieving seroconversion after the third. The spike protein, the surface molecule the virus uses to enter cells via the ACE2 receptor, is the principal target of neutralizing antibodies induced by all currently licensed vaccines, so anti-spike IgG levels serve as a widely used proxy for protective humoral immunity. The jump in response rates between the second and third doses suggests that a two-dose primary series is insufficient for many transplant recipients, and that a booster dose plays a genuine immunological role rather than being merely a formality.

One of the most clinically actionable results concerns timing. Patients who were vaccinated within 24 months of their transplant had significantly lower anti-spike IgG levels than those vaccinated later, a difference that reached statistical significance with a p-value of 0.017. This finding aligns with the known kinetics of immune reconstitution after allogeneic transplantation, in which B cell recovery and the re-establishment of functional B cell repertoires can take one to two years or longer. During this window, newly generated B cells are still learning to respond to new antigens, and the donor-derived immune system may not yet have fully replaced the recipient’s lymphocytes. Delaying vaccination, when clinically feasible, may therefore allow the immune system to mature enough to generate a stronger antibody response.

Safety data from the study were similarly reassuring. The most common side effect was pain at the injection site, reported by 34 percent of patients, followed by limb pain in 17 percent and swelling in 14 percent. These rates are broadly comparable to those seen in the general population and in other immunocompromised groups, and no alarming safety signals emerged. For clinicians counseling transplant recipients who may worry that vaccination could trigger graft-versus-host disease flares or other complications, these data provide a concrete evidence base for recommending vaccination as feasible and well tolerated. The authors concluded that vaccination in this population is both safe and effective, with the timing of administration relative to transplantation emerging as the key modifiable factor influencing immune response.

The study’s design has both strengths and limitations worth noting. By combining hospital records with patient questionnaires, the investigators captured a fuller picture of the vaccination experience than either source alone would provide, including self-reported side effects that might never appear in clinical documentation. The one-year follow-up also allowed assessment of longer-term outcomes rather than just immediate post-vaccination antibody titers. On the other hand, the cohort size of 114 patients, while respectable for a single-center transplant study, limits the statistical power to detect subtle subgroup effects, such as differences by donor type, conditioning regimen, or the degree of immunosuppression. The observational design also means that the association between vaccination timing and antibody levels, however biologically plausible, cannot be taken as proof of causation without randomized or prospective confirmation.

The findings arrive at a time when COVID-19 vaccination policy for immunocompromised populations continues to evolve. Many national guidelines already recommend additional vaccine doses for severely immunocompromised individuals, and this study provides direct evidence supporting that approach specifically for allogeneic transplant recipients. The near-universal seroconversion after three doses, reaching 96.1 percent, argues for ensuring that transplant recipients complete at least a three-dose series, while the timing effect suggests that clinicians and patients may reasonably weigh the benefits of earlier protection against the prospect of a stronger response if vaccination can be deferred until more than two years after transplantation. In practice, the risk of SARS-CoV-2 exposure during the waiting period will often tip the balance toward earlier vaccination, but the study gives clinicians a quantitative basis for that conversation.

Beyond its immediate clinical implications, the study contributes to a broader understanding of how the reconstructed immune system of a transplant recipient handles novel antigens. Allogeneic transplantation effectively resets the adaptive immune system, replacing it with donor-derived lymphocytes that must re-educate themselves in a new host environment. How quickly this new immune system can respond to vaccination reflects the pace of thymic output, B cell lymphopoiesis, and the establishment of functional immune cell communication. The Jena team’s observation that responses improve with time since transplant and with additional doses fits neatly into this framework and suggests that the same principles may apply to other vaccines, from influenza to newer respiratory syncytial virus immunizations, in this growing population of long-term transplant survivors.

As the number of allogeneic stem cell transplant survivors continues to grow worldwide, evidence-based vaccination strategies tailored to their unique immunology become increasingly important. This study, conducted without external funding and published open access, adds a valuable European dataset to the literature, confirming that mRNA vaccination against SARS-CoV-2 is feasible, well tolerated, and largely effective in transplant recipients, while highlighting that the third dose and the interval since transplantation are the factors that matter most. For the patients themselves, the message is one of cautious optimism: their rebuilt immune systems can indeed learn to recognize and respond to a virus they had never encountered, provided the vaccine is given the time and the doses it needs to do its work.

Subject of Research: Long-term humoral immune response and safety of SARS-CoV-2 mRNA vaccination in allogeneic haematopoietic stem cell transplant recipients

Article Title: Longer-term response to SARS-CoV-2 vaccination after allogeneic blood stem cell transplantation

Article References: Crodel, C. C., Gork, L., Göpel, W., Linke, P., Sinn, K., Miethke, J., Hochhaus, A., & Hilgendorf, I. (2026). Longer-term response to SARS-CoV-2 vaccination after allogeneic blood stem cell transplantation. Journal of Cancer Research and Clinical Oncology. https://doi.org/10.1007/s00432-026-06632-4

Image Credits: AI Generated

DOI: 10.1007/s00432-026-06632-4

Keywords: allogeneic stem cell transplantation, SARS-CoV-2, vaccination, mRNA vaccines, antibody response, immunogenicity, immunocompromised patients, COVID-19, immune reconstitution, booster dose, haematology, oncology