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3609 The Comparison between BM and PBSC for the Patients with Pre-Transplant Pulmonary Dysfunction in HLA-Matched Allo-HCT: Subgroup Analysis Exploring the Impact Based on HCT FactorsClinically Relevant Abstract

Program: Oral and Poster Abstracts
Session: 732. Allogeneic Transplantation: Disease Response and Comparative Treatment Studies: Poster II
Hematology Disease Topics & Pathways:
ALL, AML, Lymphomas, Plasma Cell Disorders, Diseases, Therapies, Transplantation
Sunday, December 10, 2023, 6:00 PM-8:00 PM

Shunto Kawamura, MD1*, Masaharu Tamaki2*, Takaaki Konuma3*, Makoto Onizuka, MD, PhD4, Emiko Sakaida, MD, PhD5, Hiromi Hayashi6*, Noriko Doki, MD, PhD7, Tetsuya Nishida, MD, PhD8*, Masashi Sawa, MD, PhD9*, Hiroyuki Ohigashi10*, Takahiro Fukuda, MD, PhD11*, Jun Ishikawa12*, Ken-ichi Matsuoka, MD, PhD13*, Toshiro Kawakita, MD, PhD14*, Masatsugu Tanaka, M.D., Ph.D.15*, Fumihiko Ishimaru, MD, PhD16, Tatsuo Ichinohe, MD17, Yoshiko Atsuta, MD, PhD18,19*, Yoshinobu Kanda2,20*, Kimikazu Yakushijin, MD, PhD21, Junya Kanda22 and Hideki Nakasone, MD, PhD2,23

1Division of Hematology, Jichi Medical University Saitama Medical Center, Minuma-Ku Saitama-Shi, Saitama, Japan
2Division of Hematology, Jichi Medical University Saitama Medical Center, Saitama, Japan
3Department of Hematology/Oncology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan
4Department of Hematology/Oncology, Tokai University School of Medicine, Isehara, Japan
5Department of Hematology, Chiba University Hospital, Chiba City, Japan
6Graduate School of Medicine, Kyoto University, Kyoto, JPN
7Hematology Division, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Tokyo, Japan
8Department of Hematology, Japanese Red Cross Aichi Medical Center Nagoya Daiichi Hospital, Nagoya, Japan
9Department of Hematology and Oncology, Anjo Kosei Hospital, Anjo, Japan
10Department of Hematology, Hokkaido University Hospital, Sapporo, Japan
11Department of Hematopoietic Stem Cell Transplantation, National Cancer Center Hospital, Tokyo, Japan
12Department of Hematology, Osaka International Cancer Institute, Osaka, Japan
13Department of Hematology and Oncology, Okayama University Hospital, Okayama, Japan
14Department of Hematology, National Hospital Organization Kumamoto Medical Center, Kumamoto, Japan
15Department of Hematology, Kanagawa Cancer Center, Kanagawa, Japan
16Japanese Red Cross Kanto-Koshinetsu Block Blood Center, Tokyo, Japan
17Department of Hematology and Oncology, Research Institute For Radiation Biology and Medicine, Hiroshima, Japan
18Japanese Data Center For Hematopoietic Cell Transplantation, Nagakute, Japan
19Department of Registry Science for Transplant and Cellular Therapy, Aichi Medical University School of Medicine, Nagakute, Japan
20Division of Hematology, Department of Medicine, Jichi Medical University, Tochigi, Japan
21Department of Medical Oncology and Hematology, Kobe University Hospital, Kobe, Japan
22Department of Hematology and Oncology, Graduate School of Medicine, Kyoto University, Kyoto, Japan
23Division of Stem Cell Regulation, Center for Molecular Medicine, Jichi Medical University, Shimotsuke, Japan


Pre-transplant pulmonary dysfunction is known as an important risk factor for lung complications and subsequent non-relapse mortality (NRM) after allogeneic hematopoietic cell transplantation (allo-HCT). However, it remains unknown which cell source would be optimal for the patients with pre-transplant pulmonary dysfunction and whether the impact of cell source would differ according to recipient age, donor relation, and conditioning regimens. Therefore, we evaluated the impact of stem cell sources in patients with pre-transplant pulmonary dysfunction and in the subgroups.

Patients and methods

We performed a retrospective analysis of clinical data on 3374 allo-HCT in Japan between 2016 and 2020 using Japanese registry database. All patients had standard-risk disease and underwent their first allo-HCT from an HLA-matched donor. Their clinical outcomes were compared between peripheral blood stem cells (PBSCs) and bone marrow (BM) grafts individually in two distinct cohorts, namely the Lung-scored (LS) cohort and the normal cohort, based on the presence of lung scores determined by the Hematopoietic Cell Transplantation-specific Comorbidity Index. In addition, we conducted subgroup analyses to explore potential differences in the impact of cell sources on these outcomes according to the recipient age (≥50 or < 50), donor relation (related or unrelated), and conditioning regimens (cyclophosphamide [CY] / total body irradiation [TBI]-based myeloablative conditioning [MAC], busulfan [BU]-based MAC, or reduced-intensity conditioning [RIC]).


In the LS cohort, the 2-year overall survival (OS) tended to be higher in the BM group than that in the PBSCs group (71.9% vs 61.4%; P = 0.052). However, in the normal cohort, there was no significant difference between both the cell source types (71.6% vs 73.1%; P = 0.13). Multivariate analyses showed that PBSCs were significantly associated with inferior OS in the LS cohort (hazard ratio [HR], 1.60 [95% CI, 1.06-2.42], P = 0.026). On the other hand, cell source type did not significantly affect OS in the normal cohort (HR, 0.94 [95% CI, 0.78-1.14], P = 0.55). We also found that PBSCs were significantly associated with an increased risk of NRM in the LS cohort (HR, 1.90 [95% CI, 1.03-3.52], P = 0.041), while cell source types did not affect NRM in the normal cohort (HR, 0.85 [95% CI, 0.64-1.13], P = 0.26). PBSCs were not identified as a risk factor for relapse in both cohorts.

When we focused on the LS cohort alone, the Figure 1 summarized the impact of the use of PBSCs in the subgroups according to age, donor relation, and conditioning regimens. Briefly, the use of PBSCs exhibited a significant adverse impact on OS (HR, 3.07 [95% CI, 1.16-8.11], P = 0.024) in patients younger than 50 years old. For recipients aged 50 years or older, PBSCs were not associated with inferior OS (HR, 1.49 [95% CI, 0.91-2.42], P=0.11), although it tended to be associated with an increased risk of NRM with a borderline significance (HR, 1.94 [95% CI, 0.99-3.78], P = 0.053, Figure 1). Focusing on the subgroup stratified according to their donor relation, the use of PBSCs were not associated with inferior OS or an increased risk of NRM in both allo-HCT groups from a related donor or unrelated donor. Furthermore, focusing on the subgroups stratified according to conditioning regimens, the use of PBSCs had a significantly negative impact on OS in the subgroup with CY/TBI-based MAC (HR, 7.48 [95% CI, 2.87-19.51], P < 0.001). On the other hand, the use of PBSCs had no significant impact on OS or NRM in the subgroups of BU-based MAC or RIC. Regarding relapse incidences, the impacts of the use of PBSCs were not different in any of the individual subgroups.


The use of PBSCs were associated with inferior survival in the LS cohort, but not in the normal cohort. When we focused on the subgroups of the LS cohort alone, the use of PBSCs were associated with inferior survival in the subgroup of younger recipients or those with CY/TBI-based MAC. These patients in the LS cohort might benefit from the use of BM. These results should be validated in another registry study, and further research would be warranted for the purpose of preventing adverse impact of PBSCs or the optimal cell source selection.

Disclosures: Kawamura: Nippon Shinyaku: Speakers Bureau. Tamaki: Chugai Pharmaceutical: Honoraria. Sakaida: Pfizer: Consultancy, Speakers Bureau; Otsuka: Consultancy; Ohara: Consultancy; Human Life Cord Japan: Consultancy; Chugai: Research Funding; Kyowa-Kirin: Research Funding; Takeda: Speakers Bureau; Janssen: Speakers Bureau; Novartis: Consultancy, Speakers Bureau; Bristol Myers Squibb: Consultancy, Research Funding, Speakers Bureau. Hayashi: Sanofi: Honoraria. Doki: Janssen Pharmaceutical K.K.: Honoraria; Novartis Pharma K.K.: Honoraria. Sawa: Sanofi: Honoraria; Janssen: Honoraria. Tanaka: Astellas Phrama: Speakers Bureau; Chugai Pharmaceutical: Speakers Bureau; Daiichi Sankyo: Speakers Bureau; Kyowa-Kirin: Speakers Bureau; MSD: Speakers Bureau; Otsuka Pharmaceutical: Speakers Bureau; Pfizer: Speakers Bureau; Sumitomo Pharma: Speakers Bureau; Asahi Kasei Pharma: Speakers Bureau; Abbvie: Speakers Bureau. Atsuta: Meiji Seika Pharma Co, Ltd.: Honoraria; Otsuka Pharmaceutical Co., Ltd: Speakers Bureau; JCR Pharmaceuticals Co., Ltd.: Consultancy; Novartis Pharma KK: Speakers Bureau; CHUGAI PHARMACEUTICAL CO., LTD.: Speakers Bureau. Kanda: Human Life CORD: Speakers Bureau; Sumitomo Pharma: Research Funding, Speakers Bureau; Amgen: Speakers Bureau; Takeda Pharmaceutical: Research Funding, Speakers Bureau; Meiji Seika Pharma: Speakers Bureau; Asahi Kasei Pharma: Research Funding, Speakers Bureau; Daiichi Sankyo: Research Funding, Speakers Bureau; Saitama Hokeni Kyokai: Speakers Bureau; MSD: Speakers Bureau; Kyowa Kirin: Research Funding, Speakers Bureau; Janssen Pharmaceutical: Speakers Bureau; Sanofi: Speakers Bureau; Pfizer: Speakers Bureau; Chugai Pharmaceutical: Research Funding, Speakers Bureau; Novartis: Speakers Bureau; Bristol Myers Squibb: Speakers Bureau; Otsuka Pharmaceutical: Research Funding, Speakers Bureau; AstraZeneca: Speakers Bureau; Japan Blood Products Organization: Research Funding, Speakers Bureau; CSL Behring: Speakers Bureau; AbbVie: Research Funding, Speakers Bureau; Towa Pharma: Speakers Bureau; Precision: Speakers Bureau; Eisai: Research Funding, Speakers Bureau; Nippon Shinyaku: Speakers Bureau; FUJIFILM Wako Pure Chemical: Speakers Bureau; Shionogi Pharma: Research Funding; Wakunaga Pharmaceutical: Speakers Bureau; Alexion Pharma: Speakers Bureau; Taiho Pharmaceutical: Research Funding; Nippon Kayaku: Research Funding; JCR Pharmaceuticals: Research Funding. Yakushijin: Janssen Pharmaceutical: Honoraria; Novartis: Honoraria; Asahi Kasei Pharma: Honoraria; Otsuka Pharmaceutical: Honoraria; Pfizer: Honoraria; Jazz Pharmaceuticals: Honoraria; Nippon Shinyaku: Honoraria; Astrazeneca: Honoraria; Chugai Pharmaceutical: Research Funding. Kanda: CHUGAIIGAKU CO., LTD.: Honoraria; TERUMO CORPORATION: Honoraria; DAIICHI SANKYO Co., Ltd.: Honoraria; Astellas Pharma Inc.: Honoraria; Kyowa Kirin Co., Ltd.: Honoraria; Wakunaga Pharmaceutical Co., Ltd.: Honoraria; Bristol-Myers Squibb Co: Honoraria; Novartis Pharma K.K.: Honoraria; ASAHI KASEI PHARMA CORPORATION: Honoraria; Takeda Pharmaceutical Company Limited: Honoraria; Amgen Pharma Inc.: Honoraria; Nippon Shinyaku Co., Ltd.: Honoraria; Otsuka Pharmaceutical Co., Ltd.: Honoraria; CSL Behring K.K.: Honoraria; NIPPON KAYAKU CO. LTD.: Honoraria; MSD K.K.: Honoraria; asclepia: Honoraria; AbbVie Inc.: Honoraria; Megakaryon Co: Consultancy; Sanofi K.K.: Honoraria; CHUGAI PHARMACEUTICAL Co., Ltd.: Honoraria; Janssen Pharmaceutical K.K.: Honoraria; Fujimoto Pharmaceutical Corporation.: Honoraria; Eisai: Research Funding. Nakasone: Takeda Pharmaceutical: Honoraria; Sanofi: Honoraria; Chugai Pharmaceutical: Honoraria; Eisai: Honoraria; Meiji Seika Pharma: Honoraria; Novartis: Honoraria; Pfizer: Honoraria; Bristol-Myers Squibb: Honoraria; Otsuka Pharmaceutical: Honoraria; Nippon Shinyaku: Honoraria.

*signifies non-member of ASH