High-Dose Cryopreserved Bone Marrow from Deceased Donors May Reduce Relapse in HLA-Mismatched Allogeneic Transplantation: Day 180 Post-Transplant HOPE Update

Document Type

Conference Proceeding

Publication Date

2-1-2026

Publication Title

Transplant Cell Ther

Keywords

cyclophosphamide, granulocyte colony stimulating factor, mycophenolate mofetil, steroid, tacrolimus, acute graft versus host disease, acute myeloid leukemia, aged, allotransplantation, bone marrow, case report, cell count, child, chimera, chronic graft versus host disease, clinical article, clinical trial, compassionate use, complication, conference abstract, cytokine release syndrome, deceased donor, diagnosis, drug combination, drug therapy, engraftment, female, graft versus host reaction, HLA matching, HLA system, human, human tissue, living donor, male, microchimerism, myeloablative conditioning, neutrophil, oral drug administration, organ donor, prevention, reduced intensity conditioning, relapse, remission, side effect, special situation for pharmacovigilance, therapy

Abstract

Introduction and Objectives: Historically, transplant outcomes have been closely tied to the degree of HLA matching, with higher degrees of mismatch correlating with poorer survival. We are evaluating the safety and efficacy of 4–8/8 HLA-matched cryopreserved hematopoietic progenitor cells (HPCs) derived from bone marrow harvested from deceased solid organ donors (ages 7–55 years) under two programs: the HOPE Expanded Access Program and the PRESERVE-I clinical trial (NCT05589896). These cells are processed using minimal manipulation. Initial engraftment success has been reported in the first patient treated with cryopreserved HPC-marrow. Four patients have enrolled in HOPE. This report presents Day 180 data for the first three HOPE-treated patients. Methods and Results: Three patients had acute myeloid leukemia (AML) in first complete remission (CR1) and lacked suitable matched donors. A fourth patient had a living donor who could not donate due to an allergic reaction to G-CSF. Patient 1 (age 68) and Patient 2 (age 69) received reduced-intensity conditioning (RIC); Patient 3 (age 63) and Patient 4 (age 34) received myeloablative conditioning (MAC). Transplants used 4/8 HLA-matched grafts for Patients 1–3 and 6/8 for Patient 4. CD34+ cell doses were 5.27, 4.45, 4.80, and 5.57 × 10^6 cells/kg, respectively. GVHD prophylaxis included tacrolimus, mycophenolate mofetil, and post-transplant cyclophosphamide (50 mg/kg on Days +3 and +4). Day 180 update: three of four patients remain Day +180 post-transplant. Neutrophil engraftment occurred on Days +16, +20, and +15; platelet engraftment on Days +21, +34, and +18, respectively, for the first three patients. Full donor chimerism (100%) was confirmed on Days +30 and +60 for the first three patients. No cytokine release syndrome (CRS) events were reported. Acute GVHD was manageable in these three patients: Patient 1 Grade 2 GI with Stage 2 lower GI involvement, onset Day +26; Patient 2 Grade 3 GI with Stage 2 GI and Stage 1 skin involvement, onset Day +54; Patient 3 Grade 2 GI with Stage 1 skin involvement. All GVHD cases were steroid-responsive and resolved. No significant viral reactivation was reported. At Day 180, all patients remained relapse-free with sustained cell counts. Survival at Day 180 was 100%. Patient 1 subsequently died on Day 282 from non-relapse causes, determined not to be related to HPC-marrow. Conclusion: These preliminary findings indicate that high-dose, cryopreserved HPC, marrow cells from deceased donors are feasible and safe for infusion, supporting timely engraftment and disease control in HLA-mismatched allo-HCT. The absence of relapse and chronic GVHD through Day 180, together with manageable acute GVHD, highlights the potential of this novel graft source for patients with unmet medical needs.

Volume

32

Issue

2

First Page

S214

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