VDJ-recombination of the B-cell Receptor Following Hematopoietic Stem Cell Transplantation

Condition(s) studied

Study summary

When a person undergoes a stem cell transplant-an important procedure used to treat serious blood diseases such as leukaemia, lymphoma, or myeloma-the entire immune system is affected. The transplant essentially "resets" the immune system, meaning that the patient loses much of the protection against infections that has been built up over a lifetime. After the transplant, the patient therefore needs to be revaccinated against several diseases, such as tetanus, diphtheria, polio, COVID-19, and pneumococcal disease.

In this study, we aim to investigate how B cells-the immune cells that produce antibodies-reconstitute after a stem cell transplant. We are particularly interested in a genetic process called VDJ recombination, through which each B cell develops a unique receptor that enables it to recognize and fight a specific virus or bacterium. This process is what makes our immune system so effective. But what happens to this diversity after the entire immune system has been restarted with new stem cells? Does the body regain the same ability to recognize pathogens? Are there differences between patients who receive their own stem cells (autologous transplantation) and those who receive stem cells from another person (allogeneic transplantation)?

To answer these questions, we will follow patients undergoing stem cell transplantation at Umeå University Hospital. We will collect blood samples before and after the transplantation and will assess whether-and how well-patients generate antibodies in response to the vaccines given after transplantation. Using flow cytometry and genetic analyses, we will examine both which B-cell populations are generated and what their genetic architecture looks like. The goal is to understand how the new immune system is rebuilt after transplantation and, ultimately, to help improve vaccination strategies and infection prevention for this vulnerable patient group

Eligibility

Primary outcome measure(s)

• VDJ recombination of the B-cell receptor (BCR) after autologous and allogenic stem cell transplantation compared to samples from before transplantation or to samples from stem cell donor. For comparison IgM and IgG antibody levels will also be measured. — From inclusion until end of study which is 24 months after transplantation
  The study will examine the BCR development and VDJ recombination after stem cell transplantation in response to exposure to different vaccine antigens compared to the samples taken before transplantation or samples from the stem cell donor when available. Because the lack of previous studies and by being an exploratory study it is not possible to define quantitative measurable endpoints.
• Differences in response to vaccine antigens following autologous stem cell transplantation compared to allogenic stem cell transplantation in VDJ recombination of the B-cell receptor and in IgM and IgG antibody levels. — From inclusion until end of study which is 24 months after transplantation
  The study will examine the BCR development and VDJ recombination after stem cell transplantation in response to exposure to vaccine antigens compared to the before transplantation or to the stem cell donor. Because the lack of previous studies and by being an exploratory study it is not possible to define quantitative measurable endpoints..

Trial sites (1)

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