Cancer patients can initiate SARS-CoV-2 vaccination three months after bone marrow transplant

Reviewed by Megan Craig, M.Sc.May 16 2023

Patients with cancer whose immune systems are being supported or rebuilt by bone marrow transplantation should begin receiving vaccines for protection against SARS-CoV-2 three months post-transplant, according to a large, prospective, observational study led collaboratively by the Center for International Blood and Marrow Transplant Research, the Blood & Marrow Transplant Clinical Trials Network and Fred Hutchinson Cancer Center. The research, involving 22 cancer centers and research institutions in the United States and focusing on mRNA-based vaccines, published in The Lancet journal eClinicalMedicine.

"People with cancer, and especially those undergoing bone marrow transplantation as part of their treatment, are highly vulnerable to infection. Initial studies showed that up to 30% of these patients who became infected with the virus that causes COVID-19 died within four to six weeks," said Dr. Joshua Hill, a Fred Hutch specialist in treating infectious diseases in people who have cancer and the study's lead author. Dr. Hill also is an associate professor of medicine at University of Washington School of Medicine.

The study is one of the largest prospective analyses of vaccination for any pathogen within the first year after hematopoietic cell transplant. It evaluated strength of immune response against the virus, comparing results in participants who initiated vaccination earlier than four months versus those who received their first shot four to 12 months after bone marrow transplant.

We undertook this study to help patients and their doctors determine the best time to begin SARS-CoV-2 vaccination because there was little information on these vaccines in this group of patients. We found that initiating an mRNA vaccination series between three to four months after bone marrow transplant should be routinely performed as part of a comprehensive infection prevention strategy."

Dr. Joshua Hill, a Fred Hutch specialist

Although current guidelines in the U.S. call for SARS-CoV-2 vaccination to start three to six months post-transplant, those recommendations were based on limited evidence, such as historical experience with previous vaccines that targeted other pathogens and did not use the mRNA platform. Further, the COVID-19 vaccine efficacy clinical trials did not include participants who had undergone bone marrow transplantation.

Until now, studies of SARS-CoV-2 vaccines in this patient population had been relatively small and primarily focused on patients vaccinated after the three- to 12-month time frame. Some also lacked data on T-cell responses and neutralizing antibodies, which are important measures for accurately assessing protection from severe COVID-19. This study tracked immune responses and safety data in 175 patients who received a first mRNA vaccination within 12 months of bone marrow transplant. All but one patient received mRNA-based vaccines. Of the total, 76 participants were vaccinated within the first four months following bone marrow transplantation; 99 participants were vaccinated between four and 12 months of the procedure.

"There are few studies of mRNA vaccine formulations for SARS-CoV-2 or other pathogens in patients who have undergone bone marrow transplantation," Hill said. "Our study provides encouraging proof-of-concept for using early vaccination to target this and other pathogens using the mRNA platform."

Additional study details:

• Participants at comprehensive cancer centers were eligible to join the study, which enrolled between April 22, 2021, and Nov. 17, 2021.
• Researchers obtained blood before and after each vaccine dose for up to four doses.
• The investigators tested for immune response to SARS-CoV-2 spike protein, neutralizing antibodies for several coronavirus variants and SARS-CoV-2-specific T-cell receptors (TCR).
• SARS-CoV-2 antibody titers, neutralizing antibody titers and TCR data did not significantly differ at the tested time points following the second vaccination, whether patients started vaccinations before four months or during the period of four to 12 months after bone marrow transplant.
• Results did not appear to be impacted by the use of immunosuppressive medications or a diagnosis of graft versus host disease.

The Fred Hutch Bone Marrow Transplant Program, one of the world's leaders in this treatment, has performed more than 17,000 bone marrow transplants and earned national recognition for outperforming expected one-year survival rates. The program is credited with expanding the clinical use of bone marrow and stem cell transplant more than 40 years ago. Dr. E. Donnall Thomas' groundbreaking work in transplantation won the Nobel Prize in physiology or medicine in 1990.

Nearly 12,000 bone marrow transplants, called hematopoietic cell transplants, are performed each year in the U.S. BMT can be used to treat blood cancers, like leukemia, lymphoma, multiple myeloma and myelodysplastic syndrome. It can also be used to treat non-cancerous diseases like aplastic anemia, myelofibrosis and immune deficiency disorders. During the procedure, a patient first undergoes chemotherapy and/or radiation to destroy their diseased bone marrow. A donor's healthy, blood-forming stem cells are then given directly into the patient's bloodstream.

The study was funded by the National Marrow Donor Program/Be the Match, the Leukemia and Lymphoma Society, the Multiple Myeloma Research Foundation, Novartis, LabCorp, the American Society for Transplantation and Cellular Therapy, Adaptive Biotechnologies and the National Institutes of Health U24 HL138660, P01 CA23766, P30 CA008748 to co-senior author Miguel-Angel Perales of Memorial Sloan Kettering Cancer Center and Weil Cornell Medical College, and P30 CA 015704-47 to Hill. Hill receives research funding from AlloVir and is a consultant for Pfizer, Gilead and Moderna. Additional declarations of potential conflicts of interest and funding acknowledgements are identified in the article.