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3953 Impact of Specific Adverse Cytogenetic Features on Outcomes after Allogeneic Hematopoietic Cell Transplantation in Myelodysplastic Syndrome with Very Poor Risk Cytogenetics: A Study from the Chronic Malignancies Working Party of EBMT

Program: Oral and Poster Abstracts
Session: 732. Allogeneic Transplantation: Disease Response and Comparative Treatment Studies: Poster III
Hematology Disease Topics & Pathways:
Biological, Adults, Clinically Relevant, Diseases, Therapies, Myeloid Malignancies, Study Population, Transplantation
Monday, December 13, 2021, 6:00 PM-8:00 PM

Xavier Poiré, MD, PhD1*, Diderik-jan Eikeman2*, Linda Koster3*, Johan A. Maertens, MD, PhD4*, Jan J. Cornelissen, MD, PhD5, Nathalie Fegueux, MD6*, Jennifer Byrne7*, Urpu Salmenniemi, MD8*, Goda Choi, MD PhD MBA9, Patrice Chevallier, MD10, Francesca A Kinsella, PhD, MRCP11*, Thomas Schroeder, MD12*, Yves Beguin, MD, PhD13, Didier Blaise14, Jean-Henri Bourhis, M.D.15, Jurgen H.E. Kuball, MD, PhD16, Hendrik Veelken, MD, PhD17, Jakob R. Passweg, MD, MS18, Arancha Bermudez Rodriguez, MD19*, Micha Srour, MD20*, Patrick John Hayden, BA21, Francesco Onida, MD22, Christof Scheid23, Marie Robin, MD, PhD24 and Ibrahim Yakoub-Agha25

1Section of Hematology, Cliniques Universitaires St-Luc, Brussels, Brussels, Belgium
2EBMT Statistical Unit, Leiden, Netherlands
3EBMT Data Office, Leiden, Netherlands
4Deptartment of Hematology, University Hospital Gasthuisberg, University of Leuven, Leuven, Belgium
5Department of Hematology, Erasmus MC Cancer Institute, University Medical Center Rotterdam, Rotterdam, Netherlands
6Département d’Hématologie Clinique, CHU Lapeyronie Montpellier, Montpellier, France
7Centre for Clinical Haematology, Nottingham University, Nottingham, ENG, United Kingdom
8Stem Cell Transplantation Unit, Helsinki University Hospital Comprehensive Cancer Center, Helsinki, Finland
9Dept. of Hematology, University Medical Center Groningen (UMCG),University of Groningen, Groningen, Netherlands
10Hematology, Hôpital Hôtel Dieu, Nantes, France
11Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, ENG, United Kingdom
12Hematology, Uniklinik Dusseldorf, Duesseldorf, Germany
13Hematology Dpt, CHU Liege, University of Liege, Liege, Belgium
14Department of Hematology, Institut Paoli Calmettes, Marseille, France
15Department of Hematology, Gustave Roussy Cancer Center, Villejuif, France
16Department of Hematology, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands
17Department of Hematology, Leiden University Medical Center, Leiden, Netherlands
18Hematology, University Hospital Basel, Basel, Switzerland
19Servicio de Hematología-Hemoterapia, Hospital U. Marqués de Valdecilla, Santander, Spain
20Hematologie CHRU de Lille, Lille, France
21Department of Haematology, Trinity College Dublin, St.James Hospital, Dublin, Ireland
22Hematology Unit, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy
23University of Cologne, Cologne, Germany
24Hopital Saint-Louis, Paris Cedex 10, France
25Centre Hospitalier Universitaire de Lille LIRIC, INSERM U1286, Université de Lille, Lille, France

INTRODUCTION: Myelodysplastic Syndrome (MDS) is a heterogenous disease which is almost incurable without an allogeneic hematopoietic cell transplantation (allo-HCT). Within the revised international scoring system (R-IPSS), MDS with poor and very poor cytogenetics have a much worse outcome after allo-HCT. The very poor cytogenetic subgroup refers to patients harboring more than 3 abnormalities and is therefore a highly heterogenous group. We have shown in acute myeloid leukemia (AML) that beyond complex karyotype, specific adverse cytogenetic features such as 7q abnormalities (abn7q), 5q abnormalities (abn5q), 17p abnormalities (abn17p) and monosomal karyotype (MK) worsen the outcomes after allo-HCT. We have therefore retrospectively reviewed MDS with very poor cytogenetics and studied the impact of adverse cytogenetic features on outcomes after transplant.

METHODS: We selected MDS patients who underwent allo-HCT between 2001 and 2018 from a matched related or unrelated donor, for whom a full cytogenetic report was available in the EBMT registry. We then stratified them according to the presence of abn7q, abn5q, abn17p, MK and the number of abnormalities (≤5, 6-9 and ≥10). Graft-versus-host disease (GvHD) and relapse-free survival (GRFS) was defined as survival without grade II-IV acute GvHD, extensive chronic GvHD or relapse.

RESULTS: A total of 154 patients were identified in the registry. One hundred twenty-three patients (81%) had MDS with excess of blasts and 4 (3%) had secondary AML. Median age was 59 years (interquartile range (IQR), 51-64) and the median follow-up was 38 months (95% confidence interval (CI), 34-60). The time from diagnosis to allo-HCT was a median of 6 months (IQR, 4-8). Two thirds of patients received a reduced-intensity conditioning regimen (N = 103, 67%) and 87 patients had a matched unrelated donor (57%). Almost all patients were in first complete remission at time of transplant (N= 149, 97%). Regarding specific cytogenetic features, 87 patients had abn7q (57%), 99 abn5q (64%), 59 abn17p (38%) and 120 MK (78%) with considerable overlap between groups.

The 2-year overall survival (OS) and progression-free survival (PFS) was 34% (95% CI 26-42%) and 24% (95% CI 17-31%), respectively. The 2-year cumulative incidence of relapse and non-relapse mortality (NRM) was 59% (95% CI 51-67%) and 18% (95% CI 12-24%), respectively. The cumulative incidence of grade II-IV acute GvHD and chronic GvHD was 33% (95% CI 25-40%) and 44% (95% CI 36-53%) by day 100 and 2 years respectively. The 2-year GRFS was 12% (95% CI 6-17%). The presence of abn5q was associated with a significantly decreased PFS of 17% (95% CI 9-25%) versus 36% (95% CI 23-49%); p=0.05) and GRFS (6% (95% CI 1-11%) versus 23% (95% CI 11-34%); p=0.04). The presence of abn7q was associated with significantly increased NRM (25% (15-34%) versus 9% (2-16%); p=0.02) which did not translate into OS. There were no specific cytogenetic features that had an independent impact on the cumulative incidence of relapse, but age over 55 years did increase the relapse risk (<55: 45% (95% CI 31-59%); 55-65: 65% (95% CI 54-77%); >65: 66% (95% CI 50-83%); p=0.03). A continuous effect was also observed (per decade increase: HR=1.24, 95%CI 1.02-1.52; p=0.03). Patients with an interval of more than 6 months from diagnosis to allo-HCT had almost double the OS (45% (95% CI 32-58%)) compared to patients with an interval less than 6 months (27% (95% CI 17-37%); p=0.04), however a continuous effect was not observed.

CONCLUSION: MDS with very poor cytogenetics according to R-IPSS is a very bad group with dismal outcomes after allo-HCT. Within this high-risk group, specific adverse cytogenetic features such as the number of abnormalities, abn7q, abn5q, abn17p or MK did not stratify outcomes further, except for abn5q which was associated with a decreased PFS. Our results might be explained in part by the low number patients and by the over-representation of adverse features within this cohort. Despite that, advancing age was associated with increased relapse. Whilst allo-HCT remains the best therapeutic option for this very high-risk patient group, efforts should focus on post-transplant preemptive intervention strategies to prevent relapse.

Disclosures: Byrne: Incyte: Honoraria. Schroeder: Celgene: Honoraria, Other: Travel support, Research Funding. Blaise: Jazz Pharmaceuticals: Honoraria. Hayden: Jansen, Takeda: Other: Travel, Accomodation, Expenses; Amgen: Honoraria. Scheid: Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Abbvie: Honoraria; Roche: Consultancy; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees. Yakoub-Agha: Jazz Pharmaceuticals: Honoraria.

*signifies non-member of ASH