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3345 Younger HLA-Matched Unrelated Donor Allogeneic Hematopoietic Cell Transplantation (allo-HCT) for Myelodysplastic Syndromes (MDS) Is Associated with Superior Disease-Free Survival Compared to Older HLA-Identical Sibling Donors: CIBMTR AnalysisClinically Relevant Abstract

Program: Oral and Poster Abstracts
Session: 732. Clinical Allogeneic Transplantation: Results: Poster III
Hematology Disease Topics & Pathways:
Diseases, MDS, Myeloid Malignancies
Monday, December 7, 2020, 7:00 AM-3:30 PM

Guru Subramanian Guru Murthy, MD1*, Soyoung Kim2,3*, Zhen-Huan Hu, MPH4*, Noel Estrada-Merly, MS5*, Ryotaro Nakamura, M.D.6, Betul Oran, MD, MS7, Bart L. Scott, MD8, Ronald Sobecks, MD9 and Wael Saber, MD, MS10

1Medical College of Wisconsin, Milwaukee, WI
2Center for International Blood and Marrow Transplant Research, Department of Medicine, Medical College of Wisconsin, Milwaukee, WI
3Division of Biostatistics, Institute for Health and Society, Medical College of Wisconsin, Milwaukee, WI
4CIBMTR (Center for International Blood and Marrow Transplant Research), Department of Medicine, Medical College of Wisconsin, Milwaukee, WI
5CIBMTR (Center for International Blood and Marrow Transplant Research) Medical College of Wisconsin, Milwaukee, WI
6Department of Hematology and Hematopoietic Cell Transplantation, City of Hope National Medical Center, Duarte, CA
7Stem Cell Transplantation and Cellular Therapy, The University of Texas, MD Anderson Cancer Center, Houston, TX
8Fred Hutchinson Cancer Research Center, Seattle, WA
9Taussig Cancer Institute, Department of Hematology and Medical Oncology, Cleveland Clinic, Cleveland, OH
10CIBMTR, Medical College of Wisconsin, Milwaukee, WI


When older MDS patients present for allo-HCT, HLA-identical sibling donors who are eligible to donate are usually the preferred choice. The age of the HLA-identical sibling donor is likely to be advanced as well. However, the choice between an older HLA-identical sibling donor and younger HLA-matched unrelated donor remains unclear.


Using the center for international blood and marrow transplant research (CIBMTR) database, we identified adults aged ≥50 years with MDS who underwent allo-HCT from older HLA-identical sibling donor (age ≥50) or younger 8/8 (HLA-A, -B, -C and -DRB1) well matched unrelated donor (MUD) (age ≤ 35) between the years 2011-2017. In prior studies, compared to older MUD, allo-HCT from MUD younger than age 35 was associated with superior outcomes (Shaw BE et al. BBMT 2018, Kollman C et al. Blood 2016, CIBMTR internal data). Hence, in the current analysis, the MUD arm was restricted to those aged ≤35. Key exclusion criteria were allo-HCT from mismatched unrelated donor, haploidentical donor, cord blood donor and ex-vivo T-cell depleted grafts. Overall survival (OS), disease free survival (DFS), non-relapse mortality (NRM), relapse, acute and chronic graft versus host disease (GVHD) were evaluated. Survival analysis was done using Kaplan-Meier method and significant predictors were evaluated using Cox-proportional hazard regression method. Multivariate regression model included main effect (donor age group) and covariates (patient age, gender match, CMV match, disease subtype, R-IPSS at HCT, comorbidities score (HCT-CI), Karnofsky performance status, prior therapy, interval between diagnosis and transplant, conditioning intensity, stem cell source, GVHD prophylaxis, ATG/campath use, transplant year, and center affect). Fine and Gray (F-G) model for competing risks was used for analysis of NRM and relapse.


Of 1761 patients who met the study criteria, 646 patients received allo-HCT from older HLA-identical sibling and 1115 patients from younger MUD. Cohorts were similar for age, sex, Karnofsky performance status, HCT-CI, R-IPSS at HCT, time from diagnosis to transplant, prior therapy, graft type and conditioning intensity. Notable differences between donor groups included donor age (HLA identical sibling donor- median age 61.3 years vs. MUD- median age 25.2 years) and use of ATG/campath (HLA identical sibling donor 14% vs MUD 37%). In multivariable analysis, there was a significant difference in DFS (p=0.01) but not OS (p=0.14) among donor groups. Compared to MUD ≤35 years, DFS was inferior in HLA identical sibling donor age ≥60 but not in HLA-identical sibling donor age 50-59 (Table 1) (Figure 1A). In multivariate analysis using Fine and Gray model, the risk of relapse was significantly higher in patients receiving allo-HCT from HLA-identical sibling donor compared to MUD≤35 (Table 1, figure 1B). There was no significant difference in NRM between HLA-identical sibling donors and MUD ≤35 (overall p=0.07, table 1). HLA-identical sibling donor cohort was associated with lower risk of acute GVHD (p<0.001) and chronic GVHD (overall p=0.007) as compared to MUD ≤35 cohort (table 1). Results were consistent across all subgroups.


Our results demonstrate a superior DFS that is mediated by superior disease control for MDS patients undergoing allo-HCT from younger MUD compared to older HLA-identical sibling donors. Our results should inform donor selection algorithms for older MDS patients undergoing allo-HCT.

Disclosures: Nakamura: Alexion: Other: Support on a meeting presentation; Kadmon Corporation: Other: Advisory board meeting; Kyowa-Kirin: Other: Support on a meeting presentation; Merck: Other: advisory board meeting; Magenta Therapeutics: Other: Advisory board meeting; Viracor: Consultancy; Celgene: Other: Support on seminar; NapaJen Pharma: Consultancy. Oran: Celgene: Consultancy; ASTEX: Research Funding; Arog Pharmaceuticals: Research Funding. Scott: BMS, Novartis: Research Funding; Alexion, Incyte, Novartis, Regeneron: Consultancy; Agios, BMS: Honoraria.

*signifies non-member of ASH