Clofarabine is known to have a stronger anti-tumor effect than Fludarabine and has shown its efficacy in treating aggressive acute leukemias. In addition, evidence is that it is well-tolerated with manageable side effects especially in elderly patients. Thus, replacing Fludarabine with Clofarabine in a reduced intensity transplant regimen may provide a regimen with increased anti-tumor activity without adding significant risks of toxicity.The purpose of this study is to evaluate the efficacy and the safety of clofarabine in combination with IV busulfan and ATG as the backbone of a reduced intensity conditioning regimen for allogeneic stem cell transplantation for the treatment of patients with high-risk MDS/AML or ALL not eligible to conventional or standard myeloablative allo-SCT.

Inclusion Criteria:

• Age 18 to 65
• For patients younger than 50 years, cons-indication for the use of a standard myeloablative conditioning (history of hematopoietic stem cell transplantation autologous or allogeneic, or the presence of co-morbidities or medical history making prohibitive in terms toxicity using chemotherapy and / or high dose radiotherapy as judged by the referring physician) - MDS, ALL or AML at high risk, WHO THE biphenotypic-Score <2
• Any primary diagnosis of high-risk MDS/AML or ALL eligible for a treatment by reduced intensity conditioning (RIC) allogeneic hematopoietic stem cell transplantation (allo-SCT)
• Suitable donor available (related or matched unrelated)
• Cardiac: LV Ejection Fraction ≥ 50% by MUGA or Echocardiogram.
• Pulmonary: FEV1 and FVC ≥ 50% predicted, and DLCO (corrected for hemoglobin) ≥ 50% of predicted
• Adequate renal and hepatic function
• Performance status: Karnofsky ≥ 70%
• Informed consent signed by patient prior to enrolment

Exclusion Criteria:

• Age <18
• Age >65
• Known hypersensitivity to clofarabine or excipients- Other hematologic malignancies than ALL, AML and MDS
• Patients with prior standard allogeneic HSCT with grade > 2 aGvHD
• Prior standard allogeneic transplantation if < 2 months
• Contra-indication to one of the drug of the RIC regimen .
• Patient with > 3 treatment lines prior to inclusion
• Pregnant or lactating females
• Patient HIV+, Hep B+, Hep C+- Uncontrolled systemic infection
• Performance Status Score ECOG > 2- Known central nervous system involvement with AML or ALL- Uncontrolled active infection of any kind or bleeding
• Any other severe concurrent disease, or have a history of serious organ dysfunction or disease involving the heart, kidney, liver or other organ system that may place the patient at undue risk to undergo the agents included in the conditioning regimen.
• For patients younger than 50 years, possibly indicating a standard myeloablative conditioning