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

NCT07346820 | Not Yet Recruiting

• 1 other identifier: The VReST study
• Study Type: observational
• Target: 65
• Locations: 1 country
• Sites: 1

Brief 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

Conditions

Stem Cell Transplantation, Hematopoietic; V(D)J Recombination; Receptors, Antigen, B-Cel

Outcome Measures

Primary Outcomes (2)

• 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.

  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.

  From inclusion until end of study which is 24 months after transplantation

• 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.

  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..

  From inclusion until end of study which is 24 months after transplantation

Study Arms (3)

Patients undergoing autologous stem cell transplantation

Patients undergoing allogenic stem cell transplantation

Stem cell donors

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients who fulfill the inclusion criteria and will receive their stem cell transplantation at the department of hematology at the Umeå university hospital

You may qualify if:

• Age \> 18 years.
• Willing and able to participate in all parts of the study.
• Signed written consent.
• Patients with a plasma cell disease of lymphoma that qualify for autologous hematological stem cell transplantation determined by the attending physician OR Patients with a condition for which allogenic stem cell transplantation could be needed and qualify for haematological stem cell transplantation according to the attending physician OR Stem cell donor, donating to a study participant.

You may not qualify if:

• Unable to give informed consent.
• Not suitable for participation in the study according to the view of the attending physician.
• Previous participation in this trial.

Sponsors & Collaborators

• Umeå University: lead
• Region Västerbotten: collaborator

Study Sites (1)

Umeå university hospital

Umeå, Sweden

Location

Related Publications (8)

• Sorror ML, Maris MB, Storb R, Baron F, Sandmaier BM, Maloney DG, Storer B. Hematopoietic cell transplantation (HCT)-specific comorbidity index: a new tool for risk assessment before allogeneic HCT. Blood. 2005 Oct 15;106(8):2912-9. doi: 10.1182/blood-2005-05-2004. Epub 2005 Jun 30.

  PMID: 15994282 BACKGROUND

• Dernstedt A, Leidig J, Holm A, Kerkman PF, Mjosberg J, Ahlm C, Henriksson J, Hultdin M, Forsell MNE. Regulation of Decay Accelerating Factor Primes Human Germinal Center B Cells for Phagocytosis. Front Immunol. 2021 Jan 5;11:599647. doi: 10.3389/fimmu.2020.599647. eCollection 2020.

  PMID: 33469456 BACKGROUND

• Kaku CI, Champney ER, Normark J, Garcia M, Johnson CE, Ahlm C, Christ W, Sakharkar M, Ackerman ME, Klingstrom J, Forsell MNE, Walker LM. Broad anti-SARS-CoV-2 antibody immunity induced by heterologous ChAdOx1/mRNA-1273 vaccination. Science. 2022 Mar 4;375(6584):1041-1047. doi: 10.1126/science.abn2688. Epub 2022 Feb 10.

  PMID: 35143256 BACKGROUND

• Fisher JS, Adan-Barrientos I, Kumar NR, Lancaster JN. The aged microenvironment impairs BCL6 and CD40L induction in CD4+ T follicular helper cell differentiation. Aging Cell. 2024 Jun;23(6):e14140. doi: 10.1111/acel.14140. Epub 2024 Mar 13.

  PMID: 38481058 BACKGROUND

• Suzuki I, Milner EC, Glas AM, Hufnagle WO, Rao SP, Pfister L, Nottenburg C. Immunoglobulin heavy chain variable region gene usage in bone marrow transplant recipients: lack of somatic mutation indicates a maturational arrest. Blood. 1996 Mar 1;87(5):1873-80.

  PMID: 8634435 BACKGROUND

• Meier JA, Haque M, Fawaz M, Abdeen H, Coffey D, Towlerton A, Abdeen A, Toor A, Warren E, Reed J, Kanakry CG, Keating A, Luznik L, Toor AA. T Cell Repertoire Evolution after Allogeneic Bone Marrow Transplantation: An Organizational Perspective. Biol Blood Marrow Transplant. 2019 May;25(5):868-882. doi: 10.1016/j.bbmt.2019.01.021. Epub 2019 Jan 21.

  PMID: 30677510 BACKGROUND

• Cesaro S, Mikulska M, Hirsch HH, Styczynski J, Meylan S, Cordonnier C, Navarro D, von Lilienfeld-Toal M, Mehra V, Marchesi F, Besson C, Masculano RC, Beutel G, Einsele H, Maertens J, de la Camara R; ECIL 9; Ljungman P, Pagano L. Update of recommendations for the management of COVID-19 in patients with haematological malignancies, haematopoietic cell transplantation and CAR T therapy, from the 2022 European Conference on Infections in Leukaemia (ECIL 9). Leukemia. 2023 Sep;37(9):1933-1938. doi: 10.1038/s41375-023-01938-5. Epub 2023 Jul 17. No abstract available.

  PMID: 37460673 BACKGROUND

• Cordonnier C, Einarsdottir S, Cesaro S, Di Blasi R, Mikulska M, Rieger C, de Lavallade H, Gallo G, Lehrnbecher T, Engelhard D, Ljungman P; European Conference on Infections in Leukaemia group. Vaccination of haemopoietic stem cell transplant recipients: guidelines of the 2017 European Conference on Infections in Leukaemia (ECIL 7). Lancet Infect Dis. 2019 Jun;19(6):e200-e212. doi: 10.1016/S1473-3099(18)30600-5. Epub 2019 Feb 8.

  PMID: 30744963 BACKGROUND

Related Links

• Vaccination schedule after stem cell transplantation used in Umeå

Central Study Contacts

Martin Angelin, MD, PhD

CONTACT

+46-76-1465525; martin.angelin@umu.se

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 19, 2025
• First Posted: January 16, 2026
• Study Start: February 1, 2026
• Primary Completion (Estimated): December 31, 2036
• Study Completion (Estimated): December 31, 2036
• Last Updated: January 16, 2026

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

SE (1)