Upfront Related Donor Transplantation in Patients With Myelodisplatic Syndrome : a Phase 2 Trial

Inclusion criteria

• Age ≥ 50 and ≤ 70 years
• An HLA (Human Leukocyte Antigen) matched sibling donor or familial haplo-identical donor has been identified
• The disease fulfills at least one of the following criteria:

• Intermediate-2 or high risk according to classical International Prognostic Scoring System (IPSS)
• Intermediate-1 risk if marrow fibrosis > grade I or poor risk cytogenetics according to R IPSS or classified high or very high risk according to Revised International Prognostic Scoring System (R IPSS) or if the MDS is therapy-related neoplasm
• Usual criteria for Hematopoietic Stem Cell Transplantation (HSCT):

• Eastern Cooperative Oncology Group Score (ECOG) ≤ 2
• No severe and uncontrolled infection
• Cardiac function compatible with high dose of cyclophosphamide Left Ventricular Function (LVF) > 50%
• Adequate organ function: ASAT and ALAT ≤ 2.5N, total bilirubin ≤ 2N, creatinine clearance ≥ 30 ml/min (according to Cockroft formula)
• In case of transplantation with a haploidentical donor, absence of donor specific antibody (DSA) detected in the patient with a MFI >1000 (antibodies directed towards the distinct haplotype between donor and recipient)
• Contraception methods must be prescribed for women of childbearing age during all the study. If cyclophosphamide is used, effective contraceptive methods for men during all their participation in the study
• With health insurance coverage
• With a written informed consent signed

Exclusion criteria

• Marrow blast > 15% at time of inclusion
• MDS with excess blast >10% and NPM1 mutation or a recurrent genetic abnormality related to Acute Myeloid Leukemia (AML) (WHO 2022)
• Chemotherapy (AML like intensive chemotherapy or demethylating agent) to treat MDS at the current stage
• Disponibility of an unrelated donor 10/10 (MUD) in absence of geno-identical donor
• Patient with uncontrolled infection
• Cancer in the last 5 years (except basal cell carcinoma of the skin or "in situ" carcinoma of the cervix
• Renal failure with creatinine clearance <30ml / min (according to Cockroft formula)
• With contraindications to treatments used during the research
• Uncontrolled coronary insufficiency, recent myocardial infarction <6 month, current manifestations of heart failure, uncontrolled cardiac rhythm disorders, ventricular ejection fraction <50%
• With heart failure according to NYHA (II or more)
• Patient with seropositivity for HIV or HTLV-1 or active hepatitis B or C defined by a positive PCR Hepatitis B Virus or Hepatitis C Virus
• Yellow fever vaccine or any alive vaccine within 2 months before transplantation
• Pregnancy (β-HCG positive) or breast-feeding
• Who have any debilitating medical or psychiatric illness, which would preclude giving well understand informed consent or optimal treatment and follow-up
• Under protection by law (tutorship or curatorship)