Cytotherapy · 2025
Cryopreserved organ donor bone marrow achieves robust engraftment and chimerism in mismatched allogeneic transplantation.
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Woods Erik J, Munjal Sagar, Abidi Muneer H, Pantin Jeremy, Graves Vicki L, Nowak Hans, Weinstein Nicholas, Blankenberger Kevin, Musall Kelsey, Prasad Preethi, Goebel W Scott, Johnstone Brian H
Аннотация
BACKGROUND AIMS: Significant procedural variability exists across centers in the production of hematopoietic progenitor cells (HPCs) for allogeneic transplant, particularly regarding cryopreservation, which enables shelf life and facilitates transplant but is currently recommended only when fresh products are not feasible. In addition, there is significant variation in product quality among collecting centers.
METHODS: With their consent, we established a cryopreserved bone marrow bank using vertebral segments from organ donors (ages 7-55 years) via an optimized Good Manufacturing Practice-aligned process.
RESULTS: This consistently yields large numbers of CD34+ cells with high post-thaw viability, confirmed by flow cytometry and colony-forming unit analysis of every lot. Ongoing, long-term stability studies demonstrate cell viability after cryo-storage for 6+ years. Three high-risk patients with acute myeloid leukemia in first complete remission (ages 63-69 years) received 4/8 human leukocyte antigen-matched cryopreserved grafts with post-transplant cyclophosphamide (PTCy) for graft-versus-host disease (GVHD) prophylaxis. All patients achieved successful engraftment with neutrophil recovery on days +15 to +20 and platelet recovery on days +18 to +34, with full donor chimerism. Grade 2 acute GVHD occurred in two patients, and grade 3 acute GVHD in one patient, but all were steroid-responsive and resolved completely. One patient died from respiratory failure unrelated to the graft on day +282. Relapse or chronic GVHD was not observed.
CONCLUSIONS: This organ donor-derived cryopreserved bone marrow bank represents a novel HPC source for allogeneic transplantation, potentially delivering consistent, high-quality grafts for rapid engraftment. This off-the-shelf product could provide timely options for patients with limited donor availability, particularly when combined with PTCy-based prophylaxis. Ongoing clinical trials will confirm safety and long-term efficacy.
METHODS: With their consent, we established a cryopreserved bone marrow bank using vertebral segments from organ donors (ages 7-55 years) via an optimized Good Manufacturing Practice-aligned process.
RESULTS: This consistently yields large numbers of CD34+ cells with high post-thaw viability, confirmed by flow cytometry and colony-forming unit analysis of every lot. Ongoing, long-term stability studies demonstrate cell viability after cryo-storage for 6+ years. Three high-risk patients with acute myeloid leukemia in first complete remission (ages 63-69 years) received 4/8 human leukocyte antigen-matched cryopreserved grafts with post-transplant cyclophosphamide (PTCy) for graft-versus-host disease (GVHD) prophylaxis. All patients achieved successful engraftment with neutrophil recovery on days +15 to +20 and platelet recovery on days +18 to +34, with full donor chimerism. Grade 2 acute GVHD occurred in two patients, and grade 3 acute GVHD in one patient, but all were steroid-responsive and resolved completely. One patient died from respiratory failure unrelated to the graft on day +282. Relapse or chronic GVHD was not observed.
CONCLUSIONS: This organ donor-derived cryopreserved bone marrow bank represents a novel HPC source for allogeneic transplantation, potentially delivering consistent, high-quality grafts for rapid engraftment. This off-the-shelf product could provide timely options for patients with limited donor availability, particularly when combined with PTCy-based prophylaxis. Ongoing clinical trials will confirm safety and long-term efficacy.