Allogeneic hematopoietic cell transplantation (alloHCT) is a potentially curative treatment for many hematologic malignancies. Historically, transplant outcomes have been closely tied to the degree of HLA matching, with higher degrees of mismatch correlating with poor survival. With Post transplant Cyclophosphamide the GVHD rates have reduced but unmet need in relapse prevention still exists. Cumulative mortality by day 180 for recipients of CD34+ cells from unrelated donors is approximately 10–15%.

We are currently evaluating the safety and efficacy of 4–8/8 HLA-matched cryopreserved hematopoietic progenitor cells (HPCs) derived from bone marrow (BM) harvested from vertebral bodies of deceased solid organ donors (aged 7–55 years) under two clinical programs: the HOPE Expanded Access Program and the PRESERVE-I clinical trial (NCT05589896). These cells are processed using proprietary methods with minimal manipulation. Initial engraftment success has been previously reported in the first patient treated with cryopreserved HPC-marrow (bone marrow). Four patients have enrolled in the HOPE Expanded Access Program. This report presents day 180 data for the first three patients treated under the HOPE program. The PRESERVE-I clinical trial is currently enrolling patients, with further data to follow.

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 had an allergic reaction to GCSF that prevented stem cell donation from the living donor. Patient 1 (age 68) and patient 2 (age 69) received reduced-intensity conditioning (RIC), while patient 3 (age 63) and patient 4 (age 34) received myeloablative conditioning (MAC). Transplants were performed using 4/8 HLA-matched grafts for patient 1,2 and 3 and 6/8 for patient 4. CD34+ cell doses were 5.27, 4.45, 4.80 and 5.57 × 10⁶ 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 are day 180+ post-transplant. Neutrophil engraftment was observed on Days +16, +20, and +15; platelet engraftment on Days +21, +34, and +18, respectively for first three patients who are day +180 post-transplant. Full donor chimerism (100%) was confirmed at Days +30 and +60 for the first three patients. No cytokine release syndrome (CRS) events reported. Acute GVHD was reported in these three patients: Patient 1 (overall Grade 2, stage 2 lower GI, onset Day +26), Patient 2 (Grade 3, stage 2 GI and stage 1 skin, onset Day +54), and Patient 3 (Grade 2, stage 1 GI and skin). All GVHD cases were steroid-responsive and resolved. No significant viral reactivation reported.

At Day 180, all patients remained relapse-free (0%) with sustained cell counts. Survival at Day 180 was 100%. Patient 1 later died on Day 282 from non-relapse causes, the death was determined to be not related to HPC-marrow; Patients 2 and 3 remain alive and in remission. No subsequent aGVHD or chronic GVHD requiring systemic treatment was reported.

These preliminary findings demonstrate that high-dose, cryopreserved CD34+ cells from deceased donors is feasible and safe for infusion. It can support timely successful engraftment and disease control in HLA-mismatched alloHCT. The absence of relapse and chronic GVHD through Day 180, combined with manageable acute GVHD, highlights the potential of this novel graft source for patients with unmet needs. This approach of using high dose bone marrow CD 34+ based cell dose may address key unmet needs in relapse prevention and GVHD management. Clinical studies with long term follow up are currently being conducted to further evaluate the safety and effectiveness of a cryopreserved HPC marrow product.

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2025
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