In this study, treosulfan is evaluated for conditioning in allogenic stem cell transplantation. The procedure and the follow-up are the same as in standard allogenic transplant.

The donor is unrelated (identical HLA). The graft is haematological peripheral blood stem cell.

The conditioning with reduced intensity is: fludarabine (from day -6 to day -2), treosulfan (from day -6 to day -4) and thymoglobuline (from day -2 to day -1).

Inclusion Criteria:

• AGE: >= 18 years and <= 65 years

• Patients with a too high transplant-related mortality (TRM) after standard transplantation (multiple myeloma, chronic lymphoid leukemia, non Hodgkin's lymphoma, myelodysplasia)

• Patients with visceral contra-indication for standard transplantation:

  • cardiac: myocardiopathy; forced expiratory volume (FEV) < 50%;
  • respiratory: abnormal carbon monoxide diffusing capacity (DLCO);
  • renal: creatinine clearance < 50ml/min;
  • hepatic: transaminases and bilirubin > 2 upper normal limit;
  • infectious: controlled fungal infection.

• Karnofsky score >= 70%

• Unrelated donor HLA identical (ABC, DRB1; DQB1)

• Signed informed consent

Diagnosis :

Chronic myelogenous leukemia (CML):

• In first chronic phase, resistant to interferon with or without aracytine or refractory or resistant to Glivec
• In complete response (CR) or in 2nd partial response (PR) after being in blastic phase

Multiple myeloma (MM):

• Relapse after autograft if the therapeutic response was evaluated to 50%

Non-Hodgkin's lymphoma (NHL):

• Mantle cell lymphoma after first relapse but in case of chemosensitivity ≥ 50% except for high grade lymphoma
• In 2nd CR or PR chemosensitive in response ≥ 50% after autograft

Chronic lymphocytic leukemia (CLL):

• In 2nd CR or PR or in response ≥ 50% after autograft or in 2nd relapse after 2 lines of treatment but in case of chemosensitivity ≥ 50%

Acute myeloid leukemia (AML):

• In 2nd CR or in 1st CR for high risk criteria [high risk criteria defined by: LAM 7; leukocytes > 30,000/mm3; chromosomal abnormalities: t(6,9); abnormalities of 11q23, 17p, 11q, 20q, 21q, -5, del(5q), -7/del7q, del 9q et inv 3q]

Acute lymphoblastic leukemia (ALL):

• In 2nd CR or in 1st CR if high risk criteria patients who are defined by chromosomal abnormalities t(9,22); t(1,19); t(4,11); abnormalities of 11q23

Myelodysplastic syndromes (MDS):

• Patients without prior chemotherapy, with intermediate or high International Prognostic Scoring System (IPSS) score and blast cells < 1% in bone marrow (BM)
• CR or PR after chemotherapy for patients with 20 to 30% of blast cells in BM
• Secondary AML patients with a response to chemotherapy (< 30% blasts in BM and < 5% of blast cells in blood)

For all:

• Adequate contraception in female patients of child bearing potential