Winkler, Julia and Tittlbach, Hannes and Schneider, Andrea and Vasova, Ingrid and Strobel, Julian and Herold, Susanne and Maas, Stefanie and Spriewald, Bernd M. and Repp, Roland and Kordelas, Lambros and Mach, Michael and Wolff, Daniel and Edinger, Matthias and Mackensen, Andreas and Winkler, Thomas H. (2024) Adoptive transfer of donor B lymphocytes: a phase 1/2a study for patients after allogeneic stem cell transplantation. BLOOD ADVANCES, 8 (10). pp. 2373-2383. ISSN 2473-9529, 2473-9537
Full text not available from this repository. (Request a copy)Abstract
Immune reconstitution after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is slow and patients carry a high and prolonged risk of opportunistic infections. We hypothesized that the adoptive transfer of donor B cells can foster after HSCT immunoreconstitution. Here, we report, to our knowledge, the results of a first-in-human phase 1/2a study aimed to evaluate the feasibility and safety of adoptively transferred donor B cells and to test their activity upon recall vaccination. Good manufactoring practice (GMP) B-cell products were generated from donor apheresis products using 2-step magnetic cell separation. Fifteen patients who had undergone allo-HSCT were enrolled and treated after taper of immunosuppression (median, day +148; range, 130-160). Patients received 4 different doses of B cells (0.5 x 106 to 4.0 x 106 B cells per kg body weight). To test the activity of infused donor memory B cells in vivo, patients were vaccinated with a pentavalent vaccine 7 days after B-cell transfer. We observed the mobilization of plasmablasts and an increase in serum titers against vaccine antigens, with a stronger response in patients receiving higher B-cell numbers. Analysis of immunoglobulin VH-sequences by nextgeneration sequencing revealed that plasmablasts responding to vaccination originated from memory B-cell clones from the donor. Donor B-cell transfer was safe, as no EpsteinBarr virus (EBV) reactivation was observed, and only low-grade graft-versus-host disease (GVHD) occurred in 4 out of 15 patients. This pilot trial may pave the way for further studies exploring the adoptive transfer of memory B cells to reduce the frequency of infections after allo-HSCT. This trial was registered at ClinicalTrial.gov as #NCT02007811.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | POSTTRANSPLANT LYMPHOPROLIFERATIVE DISORDERS; VERSUS-HOST-DISEASE; INFLUENZAE TYPE-B; BONE-MARROW; EUROPEAN CONFERENCE; VACCINATION; RECIPIENTS; INFECTIONS; LEUKEMIA; IMMUNIZATION |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin III (Hämatologie und Internistische Onkologie) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 22 Jan 2026 07:31 |
| Last Modified: | 22 Jan 2026 07:31 |
| URI: | https://pred.uni-regensburg.de/id/eprint/64936 |
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