Paper: Prognostic Impact of Transfusions Intensity on Survival and Development of Thrombocytopenia in Newly Diagnosed Lower-Risk MDS Patients Participating in the European Leukemianet EU-MDS Registry

Myelodysplastic Syndromes – Clinical Studies
Oral and Poster Abstracts
637. Myelodysplastic Syndromes – Clinical Studies: Poster I

Hall A, Level 2 (Orange County Convention Center)

Louise De Swart, MD¹^*, Tom Johnston, PhD²^*, Alexandra Smith³^*, Pierre Fenaux, MD, PhD⁴, Argiris Symeonidis, MD, PhD⁵, Jaroslav Cermak, MD, Ph.D.⁶, Eva Hellström-Lindberg, MD, PhD⁷^*, Guillermo Sanz, MD, PhD⁸, Reinhard Stauder, MD, MSc⁹^*, Luca Malcovati, MD¹⁰^*, Ulrich Germing, MD¹¹^*, Gerwin Huls, MD, PhD¹²^*, Mette Skov Holm¹³^*, Moshe Mittelman, MD¹⁴, Krzysztof Madry¹⁵^*, Aurelia Tatic, MD¹⁶^*, Antonio Medina Almeida¹⁷^*, Aleksandar Savic¹⁸, Sophie Park, MD, PhD¹⁹, Odile Beyne-Rauzy, MD, PhD²⁰^*, Raphaël Itzykson, MD, PhD²¹, Corine van Marrewijk¹^*, David Bowen, MD, PhD²² and Theo de Witte, MD, PhD²³

¹Hematology, Radboudumc, Nijmegen, Netherlands
²University of York, York, United Kingdom
³Epidemiology and Cancer Statistics Group, University of York, York, United Kingdom
⁴University Paris 7 Diderot, Hôpital Saint-Louis, Paris, France
⁵Hematology, University of Patras Medical School, Patras, Greece
⁶Department of Clinical Hematology, Institute of Hematology and Blood Transfusion, Prague, Czech Republic
⁷Center for Hematology and Regenerative Medicine, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden
⁸Servicio de Hematologia, Hospital Universitario La Fe, Valencia, Spain
⁹Department of Internal Medicine V (Hematology and Oncology), Innsbruck Medical University, Innsbruck, Austria
¹⁰Department of Hematology Oncology, Fondazione IRCCS Policlinico San Matteo, Pavia, Pavia, Italy
¹¹Department of Hematology, Oncology, and Clinical Immunology, Heinrich-Heine-University Duesseldorf, Duesseldorf, Germany
¹²Department of Hematology, Radboud university medical center, Nijmegen, Netherlands
¹³Dept of Hematology, Aarhus University Hospital, Aarhus, Denmark
¹⁴Tel Aviv Sourasky Medical Center, Tel Aviv, Israel
¹⁵Hematology Oncology and Internal Medicine, Warszawa Medical University, Warszawa, Poland
¹⁶Center of Hematology and Bone Marrow Transplantation, Fundeni Clinical Institute, Bucharest, Romania
¹⁷Instituto Português de Oncologia de Lisboa,, Serviço de Hematologia,, Lisbon, Portugal
¹⁸Clinic of Hematology, Clinical Center of Vojvodina, Novi Sad, Serbia
¹⁹Cochin Hospital, University Paris 5, Paris, France
²⁰Service de medecine Interne, CHU Purpan, Toulouse, France
²¹Hematology Department, Saint-Louis Hospital, University Paris 7, Paris, France
²²St. James's Institute of Oncology, Leeds Teaching Hospitals, Leeds, United Kingdom
²³Nijmegen Center for Molecular Life Sciences, Dep. of Tumor Immunology, Radboud University of Nijmegen Medical Centre, Nijmegen, Netherlands

Background The outcome of lower-risk MDS patients with red blood cell transfusions (RBCT) dependency is inferior to that of RBCT independent patients, but whether the intensity of RBCT is important for prognosis is unknown. The EUMDS Registry is a non-interventional, observational longitudinal study enrolling patients with lower-risk MDS from 142 sites in 17 countries as described elsewhere (1). The EUMDS registry has accrued 1,902 patients as of July 21, 2015. We hypothesized that RBCT intensity is an independent prognostic factor for survival.

Methods We first assessed the impact of RBCT intensity in the first year post-diagnosis (1yrPD) on progression-free survival among the 1034 patients who survived at least 1yrPD and had potential for a further year of follow-up. Secondly, we developed a longitudinal model of platelet counts throughout follow-up for 1660 patients in the registry with potential for at least one year follow-up.

Results Among the 1034 patients, 323 patients had died: 67 after progression to higher-risk MDS/AML and 256 without progression. A further 41 surviving patients had progressed to AML. The overall 5-year survival was 52%. In a proportional hazards regression model (Table), the risk of death or progression increased in a non-linear fashion with age at diagnosis (p<0.001). The risk of death was increased in the intermediate IPSS-R risk group compared to low risk. Patients with RARS and 5q- syndrome had a better outcome compared to RCMD. Increased RBCT intensity in 1yrPD (Table, Figure) was strongly associated with an increased risk of death (p<0.001).

In the 1660 patients no significant decline in platelet counts was observed (0.16x10⁹ platelets/l average monthly decline, p=0.16) among patients who were not RBC transfused at any time during follow-up. However platelet counts of patients receiving RBCT declined more quickly (p<0.0001) at an average rate of 1.14x10⁹platelets/l/month. Among the 920 RBCT dependent patients, lower platelet counts were associated with receiving more RBCT units in the preceding six months. 185 Patients had at least 2 observations both before and after becoming RBCT dependent, defined as 1^st RBCT. 50% of these patients had a decreasing trend of platelets prior to their 1^st RBCT and 67% had a decreasing slope of platelets after their 1^st RBCT. In the control group of RBC untransfused patients, decreasing slopes of platelets occurred in around 50% of the patients throughout the whole observation period of 4 visits. Logistic regression of the risk of having a post-1^st RBCT decreasing trend in platelets showed that transfused patients were at a greater risk (OR=1.7, 95% CI: 1.1-2.7) of having a post-1^st RBCT decreasing trend in platelets than untransfused patients.

Conclusion These multivariate regression models including age, sex, country, IPSS and WHO classification showed that more intensive RBCT treatment is associated with poor prognosis and a more rapid decline of platelets. This indicates that the intensity of RBCT should be incorporated in the regular prognostic scoring systems and the choice of therapeutic interventions.

(1): De Swart L et al. Br J Haematol 2015; 170: 372-83.

Disclosures: Fenaux: NOVARTIS: Honoraria , Research Funding ; CELGENE: Honoraria , Research Funding ; JANSSEN: Honoraria , Research Funding ; AMGEN: Honoraria , Research Funding . Hellström-Lindberg: Celgene Corporation: Research Funding . Sanz: JANSSEN CILAG: Honoraria , Research Funding , Speakers Bureau . Mittelman: Roche: Research Funding ; Novartis Pharmaceuticals Corporation: Research Funding ; GlaxoSmithKline: Research Funding ; Johnson & Johnson: Research Funding , Speakers Bureau ; Celgene: Research Funding , Speakers Bureau ; Amgen: Research Funding . Almeida: Bristol Meyer Squibb: Speakers Bureau ; Shire: Speakers Bureau ; Celgene: Consultancy ; Novartis: Consultancy . Park: Hospira: Research Funding ; Novartis: Membership on an entity’s Board of Directors or advisory committees , Research Funding ; Celgene: Research Funding . Itzykson: Oncoethix: Research Funding . de Witte: Novartis: Research Funding .

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1677 Prognostic Impact of Transfusions Intensity on Survival and Development of Thrombocytopenia in Newly Diagnosed Lower-Risk MDS Patients Participating in the European Leukemianet EU-MDS Registry