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472 Conditioning Intensity in Patients Aged > 50 Years Undergoing Allogeneic Hematopoietic Cell Transplantation for Myelodysplastic Syndrom: A Study on Behalf of the Chronic Malignancies Working Party of the EBMT

Program: Oral and Poster Abstracts
Type: Oral
Session: 721. Allogeneic Transplantation: Conditioning Regimens, Engraftment and Acute Toxicities: Novel Conditioning Regimens for Myeloid Malignancies
Sunday, December 10, 2023: 10:15 AM

Noureddine Henoun Loukili1*, Luuk Gras Sr., MD, PhD2*, Linda Koster3*, Didier Blaise, MD, PhD4, Tobias Gedde-Dahl, MD5*, Johan Maertens, MD, PhD6*, Regis Peffault De Latour7,8,9,10,11,12,13,14,15*, Henrik Sengeloev16*, Stephan Mielke, MD17, Patrice Chevallier, MD18, Jakob R. Passweg, MD, MS19, Jenny Louise Byrne, MD, PhD20*, Urpu Salmenniemi21*, Anne Sirvent, MD22*, Denis Guyotat, MD23*, Simona Sica24*, Liesbeth C. de Wreede, PhD25*, Francesco Onida, MD26*, Christoph Scheid27*, Carmelo Gurnari, MD28,29, Joanna Drozd-Sokolowska, MD, PhD30*, Kavita Raj, MD, PhD31, Marie Robin, MD32*, Donal P McLornan, MD, PhD31* and Ibrahim Yakoub-Agha, MD, PhD33*

1CHU de Lille, Univ Lille, INSERM U1286, Infinite, 59000, Lille, AL, France
2EBMT Statistical Unit, Leiden, Netherlands
3EBMT Leiden Study Unit, Leiden, Netherlands
4Institut Paoli Calmettes, Marseille, FRA
5Oslo University Hospital, Oslo, NOR
6Department of Hematology, University Hospitals Leuven, Leuven, Belgium
7French Référence Center for Aplastic Anemia and Paroxysmal Nocturnal Hemoglobinuria, Paris, France
8BMT Unit, Assistance Publique Hôpitaux de Paris, Université Paris Cité, Paris, France
9Hematology and Transplantation Unit, Hôpital Saint Louis, AP-HP, Paris, France
10Saint-Louis Hospital, Paris, France
11Hôpital Saint-Louis,, Paris, France
12Hopital St. Louis, Department of Hematology - BMT, Paris, France
13Hôpital Saint-Louis, Hematology Department, AP-HP, Paris, France
14Hôpital Saint-Louis, Paris, France
15French Reference Center for Aplastic Anemia and Paroxysmal Nocturnal Hemoglobinuria, Paris, France
16Rigshospitalet, Copenhagen, Denmark
17Department of Cellular Therapy and Allogeneic Stem Cell Transplantation, Karolinska Institute & University Hospital, Stockholm, Stockholms Laen, Sweden
18CHU De NANTES, Nantes Cedex 1, France
19Department of Hematology University Hospital of Basel, Basel, Switzerland
20Nottingham University, Nottingham, ENG, GBR
21Turku University Hospital, Turku, FIN
22CHU Montpellier, Montpellier, France
23Institut de Cancerologie Lucien Neuwirth, CHU Saint Etienne, Saint Etienne, FRA
24Sezione di Ematologia, Dipartimento di Scienze Radiologiche ed Ematologiche, Università Cattolica del Sacro Cuore, Rome, Italy
25Department of Biomedical Data Sciences, Leiden University Medical Center, Leiden, Netherlands
26Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico - University of, Milan, Italy
27University of Cologne, Cologne, Germany
28Department of Translational Hematology and Oncology Research, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH
29Department of Biomedicine and Prevention, University of Rome Tor Vergata, Rome, Italy
30Central Clinical Hospital, The Medical University of Warsaw, Warsaw, Poland
31University College London Hospitals NHS Trust, London, United Kingdom
32Hopital Saint-Louis, Paris, France
33CHU de Lille, Univ Lille, INSERM U1286, Infinite, 59000, LILLE, FRA


Myelodysplastic syndromes (MDS) affect mainly older individuals, with a median age > 70 years. Reduced intensity conditioning (RIC) is usually used for MDS patients undergoing allo-HCT to balance the toxicity of myeloablative conditioning (MAC), particularly in the more elderly or those with multiple comorbidities. In addition, the clinicians subjective opinion/ experience remains a major guide in choosing the intensity of conditioning. The majority of studies comparing RIC and MAC reported a higher cumulative incidence (CI) of relapse (RP) and lower non-relapse mortality (NRM) in the RIC groups. However, the impact of conditioning intensity on outcome after allo-HCT remains controversial. To gain more insight into the impact of conditioning on outcomes following allo-HCT for MDS, we evaluated RIC versus MAC in MDS patients aged > 50 years in a large EBMT cohort.

Patients and methods

This was a registry-based retrospective multicenter study that included MDS patients above 50 years, who received a first allo-HCT following RIC or MAC conditioning between 2014 - 2018 and had data on IPSS-R at allo-HCT and RIC/MAC conditioning available. Data collected included disease features, patient, donor and transplantation characteristics. Patients with ex vivo T-cell depletion were excluded. Variables with missing values ≤35% were handled with multiple imputation. OS, DFS, RP and NRM were compared using the Log-rank and Gray’s test for CI, and (cause-specific) Cox proportional hazard models for multivariable analyses (MVA). A conditional logistic regression after propensity score matching (PSM) was also performed for potential risk confounders.


Among the 1393 included patients (from 121 centres), 922 (66%) were men and the median age at allo-HCT was 62.8 (IQR:58.2-66.9) years. The majority of patients (n=884; 64.3%) had RAEB. The IPSS-R was recorded as very low/low (n=598, 43%), intermediate (n=352, 25%) and high/very high (n=443, 32%). Cytogenetic risk score was very good/good (n=932, 66.9%), intermediate (n=250, 17.9%) and poor/very poor (n=211, 15.1%). Karnofsky index was ≥ 90 in 916 pts (69.3%) and HCT-CI ≥ 3 in 292 pts (27.3%). Disease status at transplant was recorded as complete remission (n=486, 34.9%), untreated/stable disease (n=544, 39.0%), and progressive disease (n=310, 22.3%). Donor was HLA-matched (related/unrelated) (n=989, 71.1%), unrelated HLA-mismatched (n=286, 20.5%) or familial HLA haplo-identical donor (n=153, 10.9%). Source of SC was BM (n=112, 8.0%) and PB (n=1255, 90.0%). A RIC regimen was used in 1053 (75.5%) patients. In vivo T-cell depletion with anti-thymocyte globulin (ATG) was used in 941 pts (67.5%).

Median time of follow up was 27.9 months (IQR: 26.4-30.6). Median rate of OS in RIC vs MAC group was 54.2(95% CI: 33.5-NA) vs 46.2(95% CI: 32.6-69.4), p=0.84; median rate of DFS was 28.4(95% CI: 19.4-58) vs 28.0 (95% CI: 22.5-39.1), respectively, p=0.64. Cumulative incidence rate of RP and NRM for RIC vs MAC regimen at 36 months were 31.2% vs 29.7% and 29.9% vs 30.4%, respectively (Figure 1). Both in univariable and MVA we did not observe a significant (> 0.05) association between the conditioning regimen on the outcomes. Similar results were obtained using PSM to control potential confounders (such as age, source of SC, stage of disease, HCT-CI, cytogentic risk score, neutrophile and platelet counts and sAML) and conditional logistic regression analysis (Table1).


To our knowledge, this is the largest retrospective cohort study that highlights a lack of association between RIC/MAC regimen and outcomes in MDS patients undergoing allo-HCT. Our results are in line with the recent published systematic review and metanalysis where evidence for using a one conditioning regimen over another remains weak [1,2].

1) Rashidi et al. Biology of Blood and Marrow Transplantation. 2020; 26:138-141.

2) Akbar et al. Blood.2020; 136:40-41.

Disclosures: Peffault De Latour: Jazz Pharmaceuticals: Honoraria. Chevallier: Immedica Pharma: Honoraria; Takeda: Honoraria; Sanofi: Honoraria; Mallinckrodt Pharmaceuticals: Honoraria; Incyte: Honoraria, Research Funding; Servier: Honoraria. Salmenniemi: Astra Zeneca: Membership on an entity's Board of Directors or advisory committees; Immedia Pharma AB: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; Viatris: Consultancy. McLornan: UK ALL RIC TRIAL - DSM board: Other: participation on a data safety monitoring board or advisory board; Novartis: Honoraria; Abbvie: Honoraria; Jazz Pharma: Honoraria; EBMT Scientific Council Member: Other: Chair of EBMT CMWP; Imago Biosciences: Research Funding. Yakoub-Agha: Kite, a Gilead Company: Honoraria, Other: travel support; Janssen: Honoraria; Novartis: Honoraria; Bristol Myers Squibb: Honoraria.

*signifies non-member of ASH