Comparison of Hemanext ONE® System and Conventional Red Blood Cell Transfusion

Inclusion Criteria:

• Male or female aged 18 or older

• Patients with a documented diagnosis of a haematological malignancy requiringchronic transfusions.

• If MDS patient, Have low risk or intermediate risk MDS per either IPSS-R (https://www.mds-foundation.org/ipss-r-calculator/) or IPSS-M (IPSS-M RiskCalculator (mds-risk-model.com))

• If MDS patient, a bone marrow aspirate completed within the 6 months prior to studyenrolment, and which did not show progression to higher risk MDS

• Have RBC transfusion dependence (at least 2 RBC units /8 weeks during the last 16weeks)

• Baseline RBC transfusion threshold of 9 g/dL

• ECOG (Eastern Cooperative Oncology Group) performance status < 3

• Have signed the informed consent form and are willing to comply with the studyvisits and procedures

• If on Iron Chelation Therapy, have been on a stable dose for ≥3 months prior toscreening

Exclusion Criteria:

• Have a life expectancy of less than 1 year

• Have palpable splenomegaly (more than 3 cm below the mid clavicular line)

• Have other associated causes of anemia (including auto-immune hemolysis or activehemorrhage, or progression to acute leukemia)

• If prescribed erythropoiesis affecting disease modifying agents (e.g. G-CSF,erythropoietin), have not been on a stable dose for 90 days

• Is currently taking Luspatercept or other investigational erythropoiesis affectingdisease modifying agent

• Have severe renal insufficiency with creatinine clearance (MDRD or CKD EPI) below 30ml/min

• Have lung disease with hypoxia or oxygen-dependent

• Have severe coronary artery disease (including unstable angina or recent myocardialinfraction) or severe heart failure (left ventricular ejection fraction less than 30%)

• Have a history of cancer active in the previous 3 years, except local cervix cancer,or basal cell cutaneous carcinoma

• Have a history of allo-immunization other than rhesus Kell that cannot be managed bythe local blood bank

• Are a female of child-bearing potential that is pregnant, planning to becomepregnant in the next 14 months or breastfeeding

• Are a patient under guardianship or curatorship

• Are currently participating in another interventional study evaluating anerythropoiesis affecting disease modifying agent