The donor pool for allogeneic stem cell transplantation could be greatly increased, improving access to transplant for minorities who are currently excluded for transplantation according to findings of this big American study.
Antonio Jimenez Jimenez MD MS; ASH 2025: Donor Choice No Longer a Barrier to Allogeneic Stem Cell Transplantation for Patients with Hematologic Malignancies
An interview with:
Antonio Jimenez Jimenez MD MS, Associate Professor of Medicine, Division of Transplantation and Cellular Therapy, University of Miami Miller School of Medicine, Sylvester Cancer Center, Co-Chair National Marrow Donor Program Access Trial, Miami, FL, United States
ORLANDO, USA—A wider, more ethnically diverse range of patients could safely receive allogeneic hematopoietic cell transplantations from unrelated donors according to findings from the USA-based National Marrow Donor Program Access Trial reported at the 2025 Annual Meeting of the American Society of Hematology.
The use of post-transplant cyclophosphamide appears to be levelling the playing field for patients who do not have access to a fully matched donor, according to Antonio Jimenez Jimenez MD MS, from the University of Miami Miller School of Medicine, who co-chairs the National Marrow Donor Program Access Trial. After telling the conference about his new data he gave the details to the Audio Journal of Oncology’s Peter Goodwin:
Audio Journal of Oncology: Antonio Jimenez Jimenez MD MS
IN [GOODWIN]”Here from the American Society of ….
OUT: …..I’m Peter Goodwin 10:58secs
REFERENCE:
ASH 2025 Abstract Number: 936
ABSTRACT TITLE :
Mismatching of unrelated donors beyond a single HLA-locus does not adversely impact outcomes at one year following transplantation: Results from the NMDP sponsored ACCESS study
(Category: 700s - Transplantation and Adoptive Cell Therapies
Review Category: 722. Allogeneic Transplantation: Acute and Chronic GVHD and Immune Reconstitution)
AUTHORS
Monzr M. Al Malki1, Stephanie Bo-Subait2, Brent Logan3, 4, Sarah Smith2, Erin Leckrone2, Heather Stefanski2, Jeffery Auletta2, Stephen Spellman2, Craig Malmberg2, Medhat Askar2, 5, Rachel Cusatis4, Brian Shaffer6, Dipenkumar Modi7, Farhad Khimani8, Mahasweta Gooptu9, Mehdi Hamadani4, Martin Maiers2, Joseph Stanek2, Javier Meade10, Uttam Rao11, Jordan Milner12, Ramzi Abboud13, Katarzyna Jamieson14, George Carrum15, Bhagirathbhai Dholaria16, William Hogan17, Ran Reshef18, Satyajit Kosuri19, Rachel Cook20, Karen Ballen21, Alison Loren22, Karilyn Larkin23, Sally Arai24, Muna Qayed25, Sung Choi26, Larisa Broglie4, 27, Bronwen Shaw4, Steven Devine2, Antonio Jimenez Jimenez28
INSTITUTIONS:
1 City of Hope National Medical Center, Duarte, CA, United States, 2 CIBMTR® (Center for International Blood and Marrow Transplant Research), NMDP, Minneapolis, MN, United States, 3 Division of Biostatistics, Data Science Institute, Medical College of Wisconsin, Milwaukee, WI, United States, 4 CIBMTR® (Center for International Blood and Marrow Transplant Research), Medical College of
Wisconsin, Milwaukee, WI, United States, 5 Health Sector & College of Medicine, Qatar University, Doha, Qatar, 6 Adult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, United States, 7 Barbara Ann Karmanos Cancer Institute, Wayne State University, Detroit, MI, United States, 8 Department of Blood and Marrow Transplantation and Cellular Immunotherapy, Moffitt Cancer Center, Tampa, FL, United States, 9 Department of Hematology/Oncology, Dana-Farber Cancer Institute, Boston, MA, United States, 10 Division of Hematologic Malignancies, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Boston, MA, United States, 11 Sarah Cannon Transplant and Cellular Therapy Program at St. David's South Austin Medical Center, Austin, TX, United States, 12 Shands HealthCare & University of Florida, Gainesville, FL, United States, 13 Washington University in St. Louis School of Medicine, St. Louis, United States, 14 University of North Carolina Hospitals, Chapel Hill, NC, United States, 15 Baylor College of Medicine Center for Cell and Gene Therapy, Baylor College of Medicine-Methodist Hospital, Houston, TX, United States, 16 Vanderbilt University Medical Center, Nashville, TN, United States, 17 Division of Hematology/BMT, Mayo Clinic, Rochester, MN, United States, 18 Blood and Marrow Transplant and Cell Therapy Program, Columbia University Irving
Medical Center, New York, NY, United States, 19 University of Chicago Medicine, Chicago, IL, United States, 20 Knight Cancer Institute, Oregon Health & Science University, Portland, MN, United States, 21 Division of Hematology/Oncology, University of Virginia Health, Charlottesville, VA, United States, 22
Division of Hematology/Oncology, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, United States, 23 The Ohio State University Comprehensive Cancer Center, Columbus, OH, United States, 24 Stanford Health Care, Palo Alto, CA, United States, 25 Aflac Cancer and Blood Disorders Center, Emory University and Children’s Healthcare of Atlanta, Atlanta,
GA, United States, 26 University of Michigan, Blood and Marrow Transplantation Program, Ann Arbor, MI, United States, 27 Division of Pediatric Hematology/Oncology/Blood and Marrow Transplant, Department
of Pediatrics, Medical College of Wisconsin, Milwaukee, WI, United States, 28 Division of Transplantation and Cellular Therapy, University of Miami Miller School of Medicine, Miami, FL, United States
ABSTRACT
Allogeneic hematopoietic cell transplantation (HCT) remains inaccessible to many patients, particularly those of non-European ancestry, due to the limited availability of matched unrelated donors (URD). While single-HLA mismatched donors (7/8) often yield acceptable outcomes, URD HCT mismatched at ≥ 2 HLA alleles (<7/8) has historically been associated with poor survival and prohibitive toxicity. Post-transplant cyclophosphamide (PTCy) has improved outcomes following mismatched unrelated donor (MMUD) HCT, potentially enabling less stringent donor matching. Whether the degree of donor-recipient HLA disparity remains prognostic after MMUD HCT when PTCy is used is unknown. The ACCESS trial (NCT04904588) was conducted by the Center for International Blood and Marrow Transplant Research Clinical Research Organization and prospectively evaluated PTCy-based graft versus host disease (GVHD) prophylaxis in adult recipients of 4–7/8 (HLA-A, -B, -C and -DRB1) MMUD peripheral blood stem cells (PBSC) from donors age ≤35 years old following either myeloablative (MAC) or reduced intensity/non-myeloablative (RIC/NMA) conditioning. This analysis focused on all adult recipients of <7/8 grafts enrolled on the study across both conditioning strata, with descriptive comparison to patients who received 7/8 MMUD PBSC grafts.
The primary endpoint was 1-year overall survival (OS). Secondary endpoints included primary graft failure (PGF), non-relapse mortality (NRM), relapse, acute and chronic GVHD, and GVHD-free relapse-free survival (GRFS).
A total of 268 adults received MMUD PBSC grafts: 85 with <7/8 matches (MAC: n=23; RIC/NMA: n=62) and 183 with 7/8 matches (MAC: n=52; RIC/NMA: n=131). Among <7/8 recipients, median age was 57 years old (range, 24–78), 49% were male, with diagnoses of acute myeloid leukemia (AML) (55%), myelodysplastic syndromes (MDS) (15%), and lymphoma (14%). HLA mismatch distribution in the <7/8 group was 6/8 in 82%, 5/8 in 14%, and 4/8 in 4%. Most received fludarabine/melphalan (44%) or myeloablative busulfan/fludarabine (21%). Median CD34+ cell dose was 5.5 ×10^6/recipient kg (range: 3.2-8.0) and 75% of grafts were cryopreserved prior to infusion. Median donor age was 25.8 (range: 18.7-35.7) in the 7/8 group and 25.0 (range: 18.3-34.8) in the <7/8 group. The <7/8 cohort was racially and ethnically diverse, with 61% identifying as other than non-Hispanic white. The 7/8 cohort had a median age of 63 years old (range, 20–79), with 52% male. Disease distribution, conditioning intensity, and infused cell doses were similar to the <7/8 group. A smaller proportion of grafts were cryopreserved (61%), and 47% of patients identified as other than non-Hispanic White.
One-year OS for <7/8 recipients was 86% (95% CI: 76–92%), compared to 79% (95% CI: 72–84%) in 7/8 recipients. One-year incidence of relapse was 23% (95% CI: 14–33%) in the <7/8 group and 17% (95% CI: 12–23%) in 7/8 recipients; NRM was 8% (95% CI: 4–16%) and 14% (95% CI: 9–19%), respectively. GRFS was 55% (95% CI: 43–65%) for <7/8 and 51% (95% CI: 44–58%) for 7/8 recipients.
PGF occurred in 8% (95% CI: 3–18%) of <7/8 RIC recipients and 3% (95% CI: 1–8%) of 7/8 RIC recipients; no MAC recipients had PGF. At 6 months post-HCT, grade II–IV acute GVHD occurred in 34% (95% CI: 24–44%) of <7/8 patients and 39% (95% CI: 32–46%) of 7/8; grade III–IV acute GVHD was observed in 7% (95% CI: 3–14%) and 8% (95% CI: 5–13%), respectively. Moderate to severe chronic GVHD (NIH consensus criteria) at one year occurred in 8% (95% CI: 3–15%) of <7/8 recipients and 11% (95% CI: 7–16%) of 7/8 recipients.
When grouped by conditioning intensity, 1-year outcomes within the <7/8 cohort were: OS 91% after MAC and 84% after RIC/NMA; relapse in 32% after MAC and 20% after RIC/NMA, respectively; GRFS was 53% for MAC and 55% for RIC/NMA; and NRM remained low at 9% after MAC and 8% after RIC/NMA.
In this cohort of adult recipients of <7/8 MMUD PBSC grafts with PTCy-based GVHD prophylaxis enrolled on the ACCESS study, 1-year OS exceeded 80% and was comparable to 7/8 recipients. Relapse, NRM, and GVHD rates were similarly favorable and consistent with outcomes reported in 7/8 donor recipients. These findings support extending suitable MMUD match considerations to include 4-6/8 in the context of PTCy, potentially enabling near-universal donor access, while allowing for optimization of other non-HLA donor factors.
AUDIO JOURNAL OF ONCOLOGY January 19, 2025