Red Blood Cell Transfusion Burden in Myelodysplastic Syndromes (MDS) with Ring Sideroblasts (RS): A Retrospective Multicenter Study By the Groupe Francophone Des Myélodysplasies (GFM)
Authors: Jouzier Claire , Cherait Amina , Cony-Makhoul Pascale , Thepot Sylvain , Cluzeau Thomas , Stamatoulas Bastard Aspasia , Peterlin Pierre , Guerci Bresler Agnes , Dimicoli-Salazar Sophie , Pica Gian-Matteo , Cheze Stephane , Santana Clémence , Chermat Fatiha , Fenaux Pierre , Park Sophie 
Published: November 2020

Background: MDS-RS are associated with a low risk of Acute Myeloid Leukemia (AML) progression and prolonged survival in most cases, but recurring anemia whose treatments, including Erythropoiesis Stimulating Agent (ESA), Lenalidomide, hypomethylating agents (HMAs), Luspatercept, and experimental drugs generally have transient effect and/or are not widely available. MDS-RS patients thus eventually have regular Red Blood Cells (RBC) transfusion dependency (TD) associated with mean low hemoglobin levels, and chronic anemia responsible for reduced quality of life, cardiovascular complications, and iron overload with organ dysfunction. We performed a retrospective observational study to describe transfusion characteristics and costs, along with clinical events, in a French population of RBC TD MDS-RS patients.
Methods: Adult RBC-TD patients with MDS-RS from 12 hematology departments of the GFM were included. The number of RBC concentrates transfused was assessed over the last 6 months (during which no other treatment than transfusions was received), and patients categorized in low transfusion burden (LTB: 3 to 7 RBC/16 weeks) and high transfusion burden (HTB: ≥8 RBC concentrates /16 weeks). Data about iron chelation, full time hospitalization (differing from day care facility stays for programmed transfusions), causes of hospitalization, treatment of anemia before inclusion and transfusion costs was collected.
Results: 100 patients MDS-RS were included, with a median time from diagnosis of 5 years (1 to 21 years). Median age was 78 years (57 to 99). Patients had received a median of 2 lines of treatment (including an ESA in 97% of them). 21% had LTB and 79% HTB. HTB patients had a longer disease duration, more frequent iron chelation (82% versus 50% in LTB patients, p=0.0052) and higher serum ferritin at inclusion (median 1958 µg/l versus 1176 µg/l, p=0.03).
During the 6-month study period, 22% of the patients required full time hospitalization (in addition to day care facility for transfusions), including 25% of patients with HTB and 15% with LTB, and 43% during overall disease follow-up. Causes of full time hospitalization (figure) were symptomatic anemia (41%), general condition degradation (5%) or cardiac disease (8%), to both of which anemia potentially contributed, infection (23%), bleeding (8%), pulmonary (2%), 13% for other reasons. 15 HTB patients versus 1 LTB patient were hospitalized for symptomatic anemia.
The 6-months average transfusion costs, including cost of the day care facility for RBC transfusion, transportation to and from the hospital, lab tests and iron chelation were $21459/patient, excluding costs of full-time hospitalization for complications. The average cost in HTB and LTB patients was $22829 and $7586/patient, respectively.
Conclusion: Most MDS-RS patients currently become RBC-TD, often during several years, and most have high transfusion burden. The average cost of RBC transfusions and iron chelation was $21459/ 6 months. During this short observation time, 22% of the patients required full time hospitalization, due to complications of anemia in at least 50% of the cases, which also increased costs (comparison with rates of hospitalization in an age and sex matched general population will be presented). Poor quality of life associated with chronic anemia should also be taken into account in those RBC-TD patients. Widely available treatments, capable of avoiding RBC transfusion dependence and improving mean hemoglobin levels, are required in those MDS-RS patients.

Disclosures
Cony-Makhoul: BMS: Speakers Bureau; Incyte Biosciences: Speakers Bureau; BMS: Consultancy; Novartis: Consultancy; Pfizer: Consultancy. Thepot:astellas: Honoraria; novartis: Honoraria; sanofi: Honoraria; celgene: Honoraria. Cluzeau:Celgene: Membership on an entity's Board of Directors or advisory committees; Jazz Pharma: Consultancy, Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; Agios: Membership on an entity's Board of Directors or advisory committees; Menarini: Consultancy; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Astellas: Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees. Stamatoulas Bastard:Takeda: Consultancy; Pfizer: Other: TRAVEL, ACCOMMODATIONS, EXPENSES; Celgene: Honoraria. Fenaux:Jazz: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; Abbvie: Honoraria, Research Funding; BMS: Honoraria, Research Funding. Park:Pfizer: Other: Travel expenses; Takeda: Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Membership on an entity's Board of Directors or advisory committees.