Study Testing Two Conditioning Regimen With a Single Prophylaxis of GVHD by Cyclophosphamide and Methotrexate Post-transplant in Patients Eligible for Matched-donor Allograft Transplantation

Inclusion Criteria:

• Age: ≥ 18 and ≤ 70 years old

• Patient with hematologic malignancy

• Indication for HSC allograft with attenuated conditioning

• Pluripotent stem cell (PSC) engraftment

• Availability of a 10/10 familial or non-familial HLA compatible donor

• Consent to the protocol

• ECOG <=2

• Woman of childbearing age with negative pregnancy test and on highly effectivecontraception during treatment and for a period of 12 months after stopping MTX andCY

• Man of childbearing age with highly effective contraception during treatment and fora period of 6 months after stopping MTX and CY and a period of 12 months afterstopping MTX and CY if TBF conditioning regimen arm

• Negative Hepatitis B, C, HIV serologies

• Social security affiliation

Exclusion Criteria:

• History of allograft

• Patient eligible for myeloablative conditioning (MAC)

• Bone marrow transplant

• Other progressive cancerous disease, or antecedent of cancer in the last five years,with the exception of a carcinoma of the skin or a carcinoma in situ of the uterinecole treated and in remission.

• Progressive psychiatric condition

• Pregnant or breastfeeding woman,

• Woman or man of childbearing age with lack of effective contraception

• Serious and uncontrolled concomitant infection

• Cardiac: systolic ejection fraction < 50% by transthoracic ultrasound or by isotopicmethod (isotope gamma angiography), NYHA II, III or IV heart failure, activerhythmic, valvular or ischemic heart disease or anteriority

• Respiratory with EFR: DLCOc <40% of theoretical

• Renal: creatinine clearance < 50 ml/min (assessment with MDRD method)

• Urological: active urinary tract infection, history of acute urothelial toxicity dueto cytotoxic chemotherapy or radiotherapy, known obstruction of urinary flow,pre-existing hemorrhagic cystitis

• Hepatic: transaminases greater than 5 times normal or bilirubin greater than 2 timesnormal

• Person protected by law (major under guardianship, curatorship or legal protection)

• Vaccination against yellow fever in the last year

• Known or suspected hypersensitivity to rabbit proteins as well as to the activesubstance and excipients of all investigational and ancillary drugs administeredduring the study,

• Contraindication to any of the investigational or adjuvant drugs administered duringthe study

• Patient not speaking French