Product Information

Ossium Health’s bone marrow (“HPC, Marrow”) is derived from the hematopoietic cell rich cancellous bone within vertebral bodies recovered from organ donors. 

Benefits and unmet needs addressed by organ donor bone marrow:

  • Donor Accessibility: Every year, 18,000 patients in the US are diagnosed with life-threatening illnesses where a HCT is their best treatment option, but nearly 9,000 of these patients are unable to receive a transplant.1 HPC, Marrow will complement the current bone marrow sources, improving donor accessibility for underserved patients.
  • Time to Transplant: HPC, Marrow is available for immediate shipment on-demand, which eliminates the time necessary to conduct a search and secure a graft from a living unrelated donor. The ability to proceed to HCT faster is associated with improved survival, especially for those patients with high-risk malignant disease.2 
  • Cell Dose: A high CD34+ cell dose is recommended for optimal graft function and low transplant mortality, but patients often receive an inadequate dose.3 Production of HPC, Marrow results in more cells per donor than can be practically obtained from living donors, giving physicians the ability to select an optimal cell dose. 

Evidence from Nonclinical Studies

In vivo studies in non-lethally irradiated NSG mice demonstrated similar engraftment kinetics between HPC, Marrow (organ donor bone marrow) and living donor bone marrow. Engraftment of selected CD34+ cells from HPC, Marrow was directly compared to selected CD34+ cells from living donor aspirated bone marrow infused at doses of 0.5×106 and 1×106/mouse. Engraftment kinetics were compared by determining human CD45+ cell levels in peripheral blood mononuclear cells (PBMCs) every two weeks from weeks 4 to 18. The time to engraftment and average total durable engraftment were similar between the two cell sources (Figure 1).

Figure 1. Engraftment kinetics of HPC, Marrow vs. living donor bone marrow

A separate in vivo study demonstrated that infusing higher cell doses of organ donor BM led to higher levels of engraftment. In this study, HPC, Marrow was infused in non-lethally irradiated NSG mice at doses of either 4×10⁵ , 2×10⁵, 1×10⁵, 5×104 and 2.5×104 CD34+ cells. Engraftment kinetics were compared by determining human CD45+ cell levels in PBMCs every two weeks from weeks 4 to 18. The results of this study demonstrated higher engraftment levels in the higher dose groups (Figure 2).

Figure 2. Engraftment kinetics of organ donor BM by dose

Evidence from Previous Clinical Use

Transplantation of deceased organ donor-derived bone marrow recovered using very similar processes have been performed successfully to treat conditions other than blood cancers, and these treatments have been shown to be safe and effective. The first deceased organ donor derived, cryopreserved bone marrow infusion was performed in 1957.4 More recently, organ donor bone marrow has been used safely with minimal conditioning in over 700 cases to promote immune tolerance of transplanted solid organs and vascularized composite allografts.5-17

Furthermore, recovery of highly functional bone marrow from deceased organ donors is conceptually similar to the procurement of organs and tissues from deceased donors, a system which is robust and well-established in the US. In 2023, 39,680 deceased donor organ transplantations and 2.5 million tissue transplantations were performed in the US.18-19

Actively-Recruiting Clinical Study

Study title: PRESERVE I: A First-in-Human Study of HLA-Partially to Fully Matched Allogeneic Cryopreserved Deceased Donor Bone Marrow Transplantation for Patients with Hematologic Malignancies

Study purpose: This study evaluates the safety and feasibility of transplantation with bone marrow from a deceased organ donor as a treatment for acute leukemias. The primary study objectives are to determine neutrophil engraftment by Day 28 and to assess product safety. This study is sponsored by Ossium Health with partnership from NMDP.

Cell dose: The target cell dose is 4 to 8 x 106 CD34+ per kg patient weight, with a minimum cell dose of 3 x 106 CD34+ per kg. 

Participation: The study will enroll eligible acute leukemia patients and actively follow participants for 12 months. 

Eligibility

Patients must meet key eligibility criteria to participate in the study:

  1. Age 18-70
  2. Diagnosed with acute leukemia (ALL, AML, ABL, or AUL)
  3. Eligible for allogeneic bone marrow transplant with PTCy
  4. HLA partially or fully matched (4–8/8 allele matched at HLA-A, -B, -C, DRB1) to an available HPC, Marrow product
  5. Meet additional eligibility criteria during screening procedure

Study status: Enrolling

Study details: https://clinicaltrials.gov/study/NCT05589896

Contact information: For more information, email [email protected] or call 415-513-5535.

Expanded Access Program

The HOPE Program expands access to HPC, Marrow to patients eligible for HCT who are unable to participate in the PRESERVE I study. For more information or to see if a patient qualifies to participate, visit ossiumhealth.com/hope, email [email protected], or call (628) 677-4863. 

References

  1. HRSA website. https://bloodstemcell.hrsa.gov
  2. Pagel JM, Othus M, Garcia-Manero G, et al. Rapid Donor Identification Improves Survival in High-Risk First-Remission Patients With Acute Myeloid Leukemia. JCO Oncol Pract. 2020;16(6):e464-e475. doi:10.1200/JOP.19.00133
  3. Gauntner TD, Brunstein CG, Cao Q, et al. Association of CD34 Cell Dose with 5-Year Overall Survival after Peripheral Blood Allogeneic Hematopoietic Cell Transplantation in Adults with Hematologic Malignancies. Transplant Cell Ther. 2022;28(2):88-95. doi:10.1016/j.jtct.2021.11.004
  4. Thomas ED, Lochte HL Jr, Lu WC, Ferrebee JW. Intravenous infusion of bone marrow in patients receiving radiation and chemotherapy. N Engl J Med. 1957;257(11):491-496. doi:10.1056/NEJM195709122571102
  5. Burke GW, Ricordi C, Karatzas T, et al. Donor bone marrow infusion in simultaneous pancreas/kidney transplant recipients: a preliminary study. Transplant Proc. 1995;27(6):3121-3122.
  6. Burke GW, Ricordi C, Karatzas T, et al. Donor bone marrow infusion in simultaneous pancreas/kidney transplantation with OKT3 induction: evidence for augmentation of chimerism. Transplant Proc. 1997;29(1-2):1207-1208. doi:10.1016/s0041-1345(96)00553-2
  7. Carroll PB, Fontes P, Rao AS, et al. Simultaneous solid organ, bone marrow, and islet allotransplantation in type I diabetic patients. Transplant Proc. 1994;26(6):3523-3524.
  8. Ciancio G. Donor bone marrow infusion in cadaveric renal transplantation. Transplant Proc. 2003;35(2):871-872. doi:10.1016/s0041-1345(02)04034-4
  9. Corry RJ, Chakrabarti PK, Shapiro R, et al. Simultaneous administration of adjuvant donor bone marrow in pancreas transplant recipients. Ann Surg. 1999;230(3):372-381. doi:10.1097/00000658-199909000-00010
  10. De Pauw L, Abramowicz D, Donckier V, et al. Isolation and infusion of donor CD34+ bone marrow cells in cadaver kidney transplantation. Nephrol Dial Transplant. 1998;13(1):34-36. doi:10.1093/ndt/13.1.34
  11. Fontes P, Rao AS, Demetris AJ, et al. Bone marrow augmentation of donor-cell chimerism in kidney, liver, heart, and pancreas islet transplantation. Lancet. 1994;344(8916):151-155. doi:10.1016/s0140-6736(94)92756-1
  12. Pham SM, Rao AS, Zeevi A, et al. A clinical trial combining donor bone marrow infusion and heart transplantation: intermediate-term results. J Thorac Cardiovasc Surg. 2000;119(4 Pt 1):673-681. doi:10.1016/S0022-5223(00)70001-8
  13. Pham SM, Rao AS, Zeevi A, et al. Effects of donor bone marrow infusion in clinical lung transplantation. Ann Thorac Surg. 2000;69(2):345-350. doi:10.1016/s0003-4975(99)01471-x
  14. Rao AS, Fontes P, Iyengar A, et al. Augmentation of chimerism with perioperative donor bone marrow infusion in organ transplant recipients: a 44 month follow-up. Transplant Proc. 1997;29(1-2):1184-1185. doi:10.1016/s0041-1345(96)00536-2
  15. Rao AS, Fontes P, Zeevi A, et al. Enhancement of donor cell chimerism in whole organ allograft recipients by adjuvant bone marrow transplantation. Transplant Proc. 1995;27(6):3387-3388.
  16. Rao AS, Fontes P, Zeevi A, et al. Augmentation of chimerism in whole organ recipients by simultaneous infusion of donor bone marrow cells. Transplant Proc. 1995;27(1):210-212.
  17. Schneeberger S, Gorantla VS, Brandacher G, et al. Upper-extremity transplantation using a cell-based protocol to minimize immunosuppression. Ann Surg. 2013;257(2):345-351. doi:10.1097/SLA.0b013e31826d90bb
  18. Organ Procurement and Transplantation Network (OPTN) Data. https://optn.transplant.hrsa.gov/data/view-data-reports/national-data/#
  19. CDC Transplant Safety: Key Facts. https://www.cdc.gov/transplantsafety/overview/key-facts.html