The main objective of the study is to improve the response rate (complete and partial remission) at 12 months after diagnosis of chronic Chronic Graft Versus Host Disease (GVHD) and treatment with the combination of ciclosporine, prednisone and Rituximab as first line treatment.

Inclusion Criteria:

• Adult patients (≥18 years) who have received a first allogeneic stem cell transplantation for a hematological disease

• Confirmed diagnosis of first episode of chronic GVHD requiring systemic immunosuppressive therapy. Chronic GVHD diagnosis is defined according to the NIH Working Group Consensus. Chronic GVHD diagnosis will be based on the evaluation of the severity of the different clinical manifestations including :

  1. Ocular, oral and mucosal symptoms,
  2. Performance status evaluation,
  3. Pulmonary function evaluation,
  4. Cutaneous evaluation measured by the percentage of extension of manifestations of liche-noid or sclerodermatous aspects, eventually confirmed with a biopsy whenever possible,
  5. Evaluation of the musculoskeletal manifestations, especially the amplitude of the rele-vant articulations,
  6. Evaluation of liver involvement (Total bilirubin, Transaminases, Phosphatase alcalines and Gamma GT).

• Any source of hematopoietic stem cells is authorized.

• Any category of conditioning regimen prior to allo-SCT is authorized.

• Any type of stem cell donors is authorized.

• Signed informed consent.

• Any prior GVHD prophylaxis previously used is accepted.

• Absence of contra-indications to the use of Rituximab.

• Subjects affiliated with an appropriate social security system.

• Women who are of childbearing potential must have a negative serum pregnancy test and agree to use a medically acceptable method of contraception throughout the study and for 3 months following the end of the study.

Exclusion Criteria:

• Patient developing acute GVHD (whether early or "late onset" form)
• A "limited" form of chronic GVHD not requiring systemic immunosuppressive therapy
• Treatment with prednisone (or equivalent) at doses higher than 1 mg/kg/day at the time of enrollment.
• GVHD occurring following donor lymphocytes infusion (DLI)
• Not the first episode of chronic GVHD needing systemic immunosuppressive therapy
• Neutropenia <500/µL
• Second allogeneic stem cell transplant
• Uncontrolled systemic infection which in the opinion of the investigator is associated with an increased risk of the patient's death within 1 month after the start of therapy
• Severe neurological or psychiatric disorders
• Denied informed consent
• Pregnancy