Here, Jennifer Saultz, DO, and Eneida Nemecek, MD, MBA, reflect on the debate over the optimal graft source for allogeneic hematopoietic cell transplantation, in light of recent data from Blood and Marrow Transplant Clinical Trials Network (BMT-CTN) studies.
Graft source for allogeneic hematopoietic cell transplantation has evolved over the past 40 years, shifting from marrow toward granulocytic colony-stimulating factor–mobilized peripheral blood grafts. As of 2019, transplantations using peripheral blood grafts accounted for roughly 80% of hematopoietic cell transplants from unrelated adult donors.1
The benefits of peripheral blood graft for the recipient include faster engraftment and lower risk of graft failure. For the donor, the benefits include a nearly painless apheresis collection, compared with having to undergo marrow harvesting in the operating room under general anesthesia.
Still, do contemporary data truly support this predilection for donor source?
Several studies designed to examine this question have been launched, but BMT CTN 0201 is the only study in which patients with hematologic malignancies who were undergoing unrelated donor transplant were randomized to receive either bone marrow or peripheral blood as graft source.2 Results of this study were published in the New England Journal of Medicine in 2012 and showed similar rates of overall survival, disease-free survival, and transplant-related mortality between the two graft sources. However, patients who received peripheral blood grafts had significantly higher rates of chronic graft-versus-host disease (GVHD) compared with those who received marrow grafts (53% vs. 41%, respectively; p=0.01). Importantly, at five years, recipients of unrelated donor marrow grafts had better psychological well-being and were 50% more likely to have returned to work.3
In haploidentical transplantation, marrow grafts are associated with less cytokine release syndrome (CRS) compared with peripheral blood grafts.4 These results have not changed the practice of favoring peripheral blood grafts.
The preference for peripheral blood by the community at large is clear, but the continued debate is not changing the standard of care.
With the onset of the COVID-19 pandemic, the National Marrow Donor Program (NMDP) required cryopreservation of all products to ensure timely arrival of a necessary product prior to conditioning. In effect, this would prevent a wait for a graft or, worse yet, not having a graft to infuse following conditioning.5 Not surprisingly, the request for marrow grafts decreased by 30% while the number of requests for peripheral blood grafts increased 15%. Since this requirement was lifted, there has been no shift back to marrow as a preferred source, despite the many documented benefits.
Are collection centers proficient in collecting marrow anymore? Fewer centers are performing marrow harvests year after year, resulting in loss of competency skills and credentialing for this procedure. Many centers have stopped collecting marrow altogether. Most trials in BMT CTN have left donor graft choice open to centers' discretion to broaden eligibility for enrollment. However, the resultant lack of consistency has made interpretation of contemporary trial results more difficult. For example, the long-awaited results of the BMT CTN 1301 study, comparing GVHD prophylaxis regimens in unrelated donor transplantation and post-transplant cyclophosphamide with marrow grafts and peripheral blood CD34 selection, were recently reported at the 2021 Transplant and Cellular Therapy meetings. The findings demonstrated a preference again for marrow product. Despite these and other reports, most adult transplant centers are using peripheral blood grafts rather than marrow.
As we gather more data about this clinical scenario, we hope to continue to improve upon donor grafts both to decrease the burden of GVHD and reduce relapse while maintaining graft-versus-leukemia effect. The preference for peripheral blood by the community at large is clear, therefore, future trials may need to be designed to compare new approaches using preferred graft sources. Clearly, the continued debate over marrow or peripheral blood is not changing the standard of care.
- Dehn J, Spellman S, Hurley CK, et al. Selection of unrelated donors and cord blood units for hematopoietic cell transplantation: guidelines from the NMDP/CIBMTR. Blood. 2019;134(12):924-934.
- Anasetti C, Logan BR, Lee SJ, et al. Peripheral-blood stem cells versus bone marrow from unrelated donors. N Engl J Med. 2012;367(16):1487-1496.
- Lee SJ, Logan B, Westervelt P, et al. Comparison of patient-reported outcomes in 5-year survivors who received bone marrow vs peripheral blood unrelated donor transplantation: long-term follow-up of a randomized clinical trial. JAMA Oncol. 2016;2(12): 1583-1589.
- Raj RV, Hamadani M, Szabo A, et al. Peripheral blood grafts for T cell-replete haploidentical transplantation increase the incidence and severity of cytokine release syndrome. Biol Blood Marrow Transplant. 2018;24(8):1664-1670.
- Auletta JJ, Novakovich JL, Stritesky GL, et al. Meeting the demand for unrelated donors in the midst of the COVID-19 pandemic: rapid adaptations by the National Marrow Donor Program and its network partners ensured a safe supply of donor products. Transplant Cell Therapy. 2021;27(2):133-141.
- Pasquini MC, Logan B, Wu J, et al. Calcineurin inhibitor-free graft-versus-host disease (GVHD) prophylaxis in hematopoietic cell transplantation (HCT) with myelablative conditioning regimens (MAC) and HLA-matched donors: results of the BMT CTN 1301 Progress II trial. Abstract LBA1. Presented at the 2021 Transplantation & Cellular Therapy Meetings, February 12, 2021.