Dose-range Finding Treosulfan-based Conditioning

Inclusion Criteria:

1. Patients with a haematological chemosensitive malignancy indicated for an allogeneic transplantation, but presenting an increased toxicity risk for classical (high-dose busulfan or standard-dose total body irradiation) conditioning therapies (remission criteria ref. to Appendix L):

   * CML in first or subsequent chronic phase
   * NHL in 2nd CR/PR, chemosensitive PR after autologous transplantation ; CLL in 2nd or subsequent CR/PR
   * Relapsed Morbus Hodgkin (MH) after autologous transplantation
   * Multiple Myeloma (MM) stage II and III according to Durie and Salmon
   * AML in 2nd CR/PR or high-risk AML in 1st CR/PR

   High-risk defined for example by the following:
   * Cytogenetics: -5/5q, -7/7q, del(5q), abnormalities of 3q, complex karyotype (\> 3 abnormalities), or
   * PR after 1 cycle of induction therapy
   * ALL in 2nd CR/PR or high-risk ALL in 1st CR/PR

   High-risk defined as follows:
   * Leukocytes \> 3000/µl (B-Linage) or \> 100000/µl (T-Linage);
   * Pro-B-ALL, pre-T-ALL
   * Cytogenetics: t(9;22)/BCR-ABL; t(4;11)/ALL1-AF
   * MDS (patients without prior chemotherapy may be included)
2. Availability of an HLA-identical sibling donor (MRD) or HLA-identical unrelated donor (MUD) or one mismatch (out of the 6 standard markers) sibling donor (1 misMRD):

   • HLA-identity defined by the following markers: A, B, DRB1. DQB1 must be recorded.
3. Age \> 18 years
4. Karnofsky Index \> 80 %
5. Adequate contraception in female patients of child-bearing potential
6. Co-operative behavior of individual patients
7. Written informed consent

Exclusion Criteria:

1. Completely chemotherapy-resistant disease
2. Severe cardiac insufficiency, severe cardio-vascular or other severe concomitant diseases
3. Symptomatic malignant involvement of the CNS
4. Active infectious disease
5. HIV-positive or active hepatitis infection
6. Impaired liver function (Bilirubin \> 1.5 x upper normal limit; Transaminases \> 3.0 x upper normal limit)
7. Impaired renal function (Creatinine-clearance \< 60 ml/min; Serum Creatinine \> 1.5 x upper normal limit).
8. Pleural effusion or ascites \> 1.0 L
9. Pregnancy or lactation
10. Known hypersensitivity to fludarabine and/or treosulfan
11. Parallel participation in another experimental drug trial