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4755 Donor Selection Considering Donor Age in Hematopoietic Cell Transplant Recipients 50-75 Years of Age

Program: Oral and Poster Abstracts
Session: 732. Allogeneic Transplantation: Disease Response and Comparative Treatment Studies: Poster III
Hematology Disease Topics & Pathways:
Research, Lymphoid Leukemias, ALL, Acute Myeloid Malignancies, AML, adult, elderly, Clinical Research, Diseases, registries, Lymphoid Malignancies, Myeloid Malignancies, Study Population, Human
Monday, December 12, 2022, 6:00 PM-8:00 PM

Sachiko Seo, MD, PhD1, Junya Kanda, MD, PhD2, Kenta Kono3*, Yoshihiro Inamoto, MD4, Naoyuki Uchida, MD, PhD5, Noriko Doki6, Masatsugu Tanaka7*, Masashi Sawa, MD, PhD8*, Makoto Onizuka, MD, PhD9, Yuta Katayama, MD, PhD10, Tetsuya Eto, MD, PhD11*, Ken-ichi Matsuoka, MD, PhD12, Takahiro Fukuda4*, Takahide Ara, M.D., Ph.D.13*, Yukiyasu Ozawa14*, Toshiro Kawakita15*, Keisuke Kato, MD16, Koji Uchiyama3*, Tatsuo Ichinohe17, Yoshiko Atsuta18,19* and Fumihiko Kimura, MD, PhD20

1Dokkyo Medical University,, Tochigi, Japan
2Department of Hematology and Oncology, Graduate School of Medicine, Kyoto University, Kyoto, Japan
3Dokkyo Medical University, Tochigi, Japan
4Department of Hematopoietic Stem Cell Transplantation, National Cancer Center Hospital, Tokyo, Japan
5Department of Hematology, Federation of National Public Service Personnel Mutual Aid Associations, Toranomon Hospital, Tokyo, Japan
6Hematology Division, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Tokyo, Japan
7Department of Hematology, Kanagawa Cancer Center, Yokohama, KAN, Japan
8Department of Hematology and Oncology, Anjo Kosei Hospital, Anjo, Japan
9Department of Hematology and Oncology, Tokai University School of Medicine, Isehara, Japan
10Department of Hematology, Hiroshima Red Cross Hospital and Atomic-bomb Survivors Hospital, Hiroshima, Japan
11Department of Hematology, Hamanomachi Hospital, Fukuoka, Japan
12Department of Hematology and Oncology, Okayama University Hospital, Okayama, Japan
13Department of Hematology, Hokkaido University Faculty of Medicine, Sapporo, Japan
14Department of Hematology, Japanese Red Cross Nagoya First Hospital, Nagoya, Japan
15Department of Hematology, National Hospital Organization Kumamoto Medical Center, Kumamoto, KUM, Japan
16Division of Pediatric Hematology and Oncology, Ibaraki Children's Hospital, Tsukuba, Japan
17Department of Hematology and Oncology, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan
18Department of Registry Science for Transplant and Cellular Therapy, Aichi Medical University School of Medicine, Nagakute, Japan
19Japanese Data Center for Hematopoietic Cell Transplantation, Nagoya, Japan
20Division of Hematology, Department of Internal Medicine, National Defense Medical College, Tokorozawa, Japan

Background: The number of hematopoietic cell transplantation (HCT) in older patients has been increasing. Although donor selection is a key factor for better outcomes, older patients frequently lack HLA-matched sibling donors (MSD) due to their comorbidities. Previous studies have shown that increased donor age is associated with a high mortality. In this study, we sought to identify the best donors for older patients and evaluated appropriate alternatives for MSD.

Patients and methods: For this retrospective cohort study, clinical data of donors and recipients were obtained from the registry data of the Japanese Society for Transplantation and Cellular Therapy (JSTCT). This study included 9,687 patients between the ages of 50-75 with acute leukemia or myelodysplastic syndrome who received the first HCT between 2011 and 2020 from MSD (N=1,317), 8/8 HLA-matched (HLA-A, -B, -C, and -DRB1 allele-level) unrelated donors (8/8 MUD) (N=2,341), 7/8 HLA-matched unrelated donors (7/8 MUD) (N=1,371), haploidentical related donors (HRD) (N=721), or single-unit cord blood (CB) (N=3,937). Only donors over 40 years of age were chosen to become MSD. For HRD, at least two-antigen (HLA-A, -B, -DR antigen-level) mismatched donors were included, and for CB donors, a maximum of two-antigen mismatched donors were included. Risk factors for overall mortality and other endpoints were analyzed using Cox proportional hazards models and Fine and Gray’s proportional hazards models, respectively.

Results: The median donor age excluding CB was 42 years (range, 13–73). The unadjusted probability of overall survival (OS) at five years post-transplantation was highest in HCT from younger (<40 years) 8/8 MUD (48% [95% CI, 44.7%-51.2%)] followed by those from older 8/8 MUD (46% [95% CI, 42.7%-49.6%)]. The probability of OS in HCT from MSD was 43% (95% CI, 39.9%-46.0%). After adjusting for other significant factors in multivariable analysis, younger 8/8 MUD were significantly associated with a higher rate of survival (adjusted hazard ratio [aHR], 0.86; 95% CI, 0.77-0.97, P=0.012), compared to MSD (Figure), especially in patients with high-risk disease (aHR, 0.83; 95% CI, 0.71-0.97, P=0.018). On categorization of recipient age by 5 years, survival in younger 8/8 MUD was higher than that in MSD, and that trend became more apparent as recipient age increased (P for trend=0.002). On the other hand, survival in MSD was comparable to that in older 8/8 MUD, younger 7/8 MUD, and CB. Relapse rate in MSD was significantly higher than those in other donors except for HRD, while non-relapse mortality (NRM) in MSD was significantly lower except younger 8/8 or 7/8 MUD (Figure). Incidence of grades III-IV acute graft-versus-host disease (aGVHD) was significantly lower in younger 8/8 (aHR, 0.66; 95% CI, 0.50-0.86, P=0.002) or 7/8 MUD (aHR, 0.72; 95% CI, 0.52-0.98, P=0.039) than MSD. As for a graft source, no significant difference between bone marrow and peripheral blood stem cells was observed in survival.

Conclusions: Younger 8/8 MUD is the first choice as a donor source in older patients due to both low rates of relapse and NRM. The second choice is MSD, older 8/8 MUD, younger 7/8 MUD, and CB. This study will provide older patients with more opportunities to find appropriate donors in suitable timing. Reducing NRM may be a key for HLA-mismatched donors to be an alternative donor option.

Figure: Forest plots of donor groups for overall survival, relapse, and non-relapse mortality (NRM). MSD, HLA-matched sibling donors; MUD, HLA-matched unrelated donors; HRD, haploidentical related donors; CB, cord blood

Disclosures: Kanda: CSL Behring K.K.: Honoraria; MSD K.K.: Honoraria; Astellas Pharma Inc.: Consultancy, Honoraria; AbbVie Inc.: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen Pharma Inc.: Honoraria; Otsuka Pharmaceutical Co., Ltd.: Honoraria; Ono Pharma Inc.: Honoraria; Janssen Pharmaceutical K.K.: Honoraria; Megakaryon Co: Honoraria, Membership on an entity's Board of Directors or advisory committees; Kyowa Kirin Co., Ltd.: Honoraria; Sanofi K.K.: Honoraria; SymBio Pharmaceuticals, Ltd.: Membership on an entity's Board of Directors or advisory committees; DAIICHI SANKYO Co., Ltd.: Honoraria, Membership on an entity's Board of Directors or advisory committees; Sumitomo Dainippon Pharma Co., Ltd.: Honoraria; Takeda Pharmaceutical Company Limited: Honoraria; CHUGAI PHARMACEUTICAL Co., Ltd.: Honoraria; TEIJIN PHARMA LIMITED.: Honoraria; Novartis Pharma K.K.: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb Co: Honoraria; Janssen Pharmaceutical K.K.: Honoraria, Membership on an entity's Board of Directors or advisory committees; ASAHI KASEI PHARMA CORPORATION: Honoraria; asclepia: Honoraria; Otsuka Pharmaceutical Co., Ltd.: Honoraria; NIPPON KAYAKU CO.,LTD.: Honoraria; Nippon Shinyaku Co., Ltd.: Honoraria; Eisai: Research Funding. Sawa: Astellas Pharma Inc.: Honoraria; Nippon Shinyaku Co., Ltd.: Honoraria; Ono Pharmaceutical Co., Ltd.: Honoraria; Kyowa Kirin Co., Ltd.: Honoraria; Chugai Pharmaceutical Co., Ltd.: Honoraria; Pfizer Japan Inc.: Honoraria; MSD K.K.: Honoraria; Bristol-Myers Squibb K.K.: Honoraria; Asahi Kasei Pharma Corp.: Honoraria; Novartis Pharma K.K.: Honoraria; Eisai Co., Ltd.: Honoraria; Otsuka Pharmaceutical Co., Ltd.: Honoraria; Sumitomo Dainippon Pharma Co., Ltd.: Honoraria; Sanofi K.K.: Honoraria; Takeda Pharmaceutical Co., Ltd.: Honoraria; Celgene K.K.: Honoraria; Mochida Pharmaceutical Co., Ltd.: Honoraria; Shire plc: Honoraria; Mundipharma K.K.: Honoraria; AbbVie G.K.: Honoraria; CSL Behring K.K.: Honoraria; SymBio Pharmaceuticals Ltd.: Honoraria; Janssen Pharmaceutical K.K.: Honoraria; AstraZeneca K.K.: Honoraria; Daiichi Sankyo Co., Ltd.: Honoraria; GSK plc.: Honoraria. Atsuta: Kyowa Kirin Co., Ltd: Honoraria; Astellas Pharma Inc.: Honoraria; Mochida Pharmaceutical Co., Ltd.: Honoraria; Novartis Pharma KK: Honoraria; AbbVie GK: Honoraria; Meiji Seika Pharma Co, Ltd.: Honoraria.

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