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2438 Does a Change in IPSS-R between Diagnosis and Transplant Have an Impact on Transplant Outcome in Patients with MDS? a Retrospective Analysis from the EBMT Chronic Malignancies Working Party

Program: Oral and Poster Abstracts
Session: 732. Clinical Allogeneic Transplantation: Results: Poster II
Hematology Disease Topics & Pathways:
Biological, Diseases, Therapies, MDS, Clinically relevant, Myeloid Malignancies, transplantation
Sunday, December 6, 2020, 7:00 AM-3:30 PM

Christof Scheid, MD1, Dirk-Jan Eikema2*, Riitta Niittyvuopio3*, Johan Maertens4*, Jakob Passweg5*, Didier Blaise, MD6, Jennifer Byrne, FRCP, FRCPath, PhD7*, Nicolaus Kröger8*, Martin Bornhäuser, MD9*, Patrice Chevallier, MD, PhD10, Jean-Henri Bourhis11*, Jan J. Cornelissen, MD, PhD12, Henrik Sengeloev13*, Jürgen Finke Sr., MD, PhD14, John A Snowden, MD, PhD15*, Tobias Gedde-Dahl16*, Denis Guyotat, MD, PhD17*, Urs Schanz, MD18, Amit Patel, PhD19*, Linda Koster2*, Liesbeth C. de Wreede, PhD20*, Patrick J Hayden, MD21, Francesco Onida, MD22, Marie Robin23* and Ibrahim Yakoub-Agha24

1Department I of Internal Medicine and Center of Integrated Oncology Cologne Bonn, University of Cologne, Cologne, Germany
2EBMT Data Office Leiden, Department of Medical Statistics and Bioinformatics, Leiden University Medical Center, Leiden, Netherlands
3Helsinki Hospital, HELSINKI, FIN
4University Hospital Gasthuisberg, Leuven, Belgium
5Hematology, University Hospital Basel, Basel, Switzerland
6Institut Paoli Calmettes, Marseille, France
7Centre for Clinical Haematology, Nottingham University Hospitals Trust, Nottingham, ENG, United Kingdom
8University Hospital Eppendorf, Hamburg, Germany
9University Cancer Center (UCC), University Hospital Carl Gustav Carus, Technical University Dresden, Dresden, Germany
10Hematology Clinic, CHU Nantes, Nantes, France
11Gustave Roussy, Villejuif, France
12Department of Hematology, Erasmus MC Cancer Institute, Rotterdam, Netherlands
13Rigshospitalet, Copenhagen, Denmark
14University of Freiburg, Freiburg, Germany, Dept. of Hematology, Oncology and Stem Cell Transplantation,, Freiburg, Germany
15Department of Haematology, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, United Kingdom
16Department of Hematology, Oslo University Hospital, Rikshospitalet and Institute of Clinical Medicine, University of Oslo, Oslo, Norway
17Hematology department, Lucien Neuwirth Cancer Institute, Saint-Priest-en-Jarez, France
18Department of Medical Oncology and Hematology, University Hospital Zurich, Zurich, Switzerland, Zurich, Switzerland
19The Christie NHS Foundation Trust, Manchester, UK, Manchester, United Kingdom
20LUMC, Dept. Medical Statistics & Bioinformatics, Leiden, Netherlands
21Department of Haematology, St. James's Hospital, Dublin, Ireland
22BMT Center - Hematology Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico - University of Milan, Milano, Italy
23Hopital Saint Louis, Paris, FRA
24Univ Lille, CHU de Lille, INFINITE, INSERM U1286, 59000 Lille, LILLE, France

IPSS-R is a well established prognostic factor for transplant outcome in patients with MDS, irrespective whether it is assessed at diagnosis or at transplant. However it is unclear how a change in IPSS-R, e.g. by reducing bone marrow blasts through therapy, would potentially affect transplant results. In particular the decision to treat patients before transplant or perform an upfront allogeneic transplantation can so far not be based on evidence.

We did a registry search based in the MDS quality initiative conducted by EBMT to identify transplanted patients with MDS and sufficient data to calculate IPSS-R at diagnosis and before transplant. The search was limited to patients reveiving a first allogeneic stem cell transplantation in the period 2005 -2018.

1482 patients were identified. Median age at alloHCT was 59 (interquartile range 51-64) years, 60% were male. Donors were related in 36%, graft source was PBSC in 85% of cases. Conditioning was standard dose in 33% and reduced intensity in 67%.

IPSS-R both at diagnosis and at transplant had a significant impact on OS and RFS after alloHCT. To investigate the effect of a change in IPSS-R between diagnosis and transplant we constructed 3 subgroups: stable IPSS-R, improved IPSS-R, worsened IPSS-R. A change in IPSS-R was noted in 77.5% of patients with prior chemotherapy, 72% with prior HMA and 59.8% of untreated patients. Univariate analysis showed no significant difference in OS or RFS in patients with stable IPSS-R compared to improved or worsened IPSS-R. In patients treated with chemotherapy before transplant OS and RFS was significantly worse with worsened IPSS-R, while this effect was not found in patient treated with hypomethylating agents (HMA) or untreated patients. The same analysis was performed regarding the difference in bone marrow blasts and the cytogenetics score: OS and RFS after transplant were significantly worse with increased blasts (p=0.04 and p=0.001) and a worsened cytogenetic score before transplant (both p<0.001). While worsened IPSS-R, blast count or cytogenetic score had a negative impact on transplant outcome, the improvement of these parameters showed no positive effect on either OS or RFS in the total cohort or in the subgroups of untreated patients, after chemotherapy or after HMA treatment.

In this retrospective analysis from a large cohort of patients with MDS we found that worsening of IPSS-R, blast count or cytogenetic score had a negative prognostic impact in chemotherapy-treated patients, while only worsened blast count and cytogenetics were significant negative factors in HMA-treated or untreated patients. Conversely we did not find a positive effect of improved IPSS-R, decreased blasts or improved cytogenetics in any of the subgroups of treated or untreated patients. Thus for MDS patients receiving an allogeneic transplantation our results provide no clear signal that prior therapy is able to improve transplant outcome.

Disclosures: Scheid: Novartis: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; BMS: Honoraria; Amgen: Honoraria; Takeda: Honoraria, Research Funding. Blaise: Jazz Pharmaceuticals: Honoraria. Chevallier: Incyte Corporation: Honoraria. Yakoub-Agha: Celgene: Honoraria; Novartis: Honoraria; Gilead/Kite: Honoraria, Other: travel support; Janssen: Honoraria; Jazz Pharmaceuticals: Honoraria.

*signifies non-member of ASH