Phase II Trial of Fludarabine Combined With Intravenous Treosulfan and Allogeneic Hematopoietic Stem-cell Transplantation in Patients With Chemo-refractory or Previously Untreated Acute Myeloid Leukemia and Myelodysplastic Syndrome.
Inclusion Criteria:
1. Age less than physiologic 68 years.
2. Patients with AML and MDS not eligible for standard TBI- or Busulfan-based
myeloablative conditioning due to age, concurrent medical condition, or extensive
prior therapy (e.g. age > 55 years for HLA-matched sibling transplants or > 50 for
matched unrelated donor transplants, prior / concomitant pulmonary, liver, or other
organ complications).
3. This study will only include patients with chemo-refractory disease or previously
untreated active disease.
A. acute myeloid leukemias (AML) according to WHO classification (> 20% myeloblasts
in peripheral blood or bone marrow at diagnosis) in induction failure, PR, untreated
or chemo-refractory relapse. Patients must have > 10% marrow blasts at the time of
transplantation.
B. myelodysplastic syndromes (MDS) according to WHO classification (< 20% myeloblasts
in peripheral blood and bone marrow at diagnosis), indicated for allogeneic
transplantation:
- refractory anaemia with excess blasts (RAEB-1 and RAEB-2) with no prior therapy
4. Patients must have an HLA matched related or unrelated donor willing to donate either
peripheral blood stem cells or bone marrow. Matching is based on high-resolution
class I (HLA-A, -B, -C) and class II (HLA-DRB1, -DQB1) typing. The goal is to
transplant > 3 x 106 CD34+ cells per kg body weight of the recipient -
Exclusion Criteria:
1. Bilirubin > 3.0 mg/dl, transaminases > 3 times upper normal limit
2. Creatinine > 2.0 mg/dl
3. ECOG-Performance status > 2
4. Uncontrolled infection
5. Pregnancy or lactation
6. Abnormal lung diffusion capacity (DLCO < 40% predicted)
7. Severe cardiovascular disease
8. CNS disease involvement
9. Pleural effusion or ascites > 1 liter
10. Known hypersensitivity to fludarabine or treosulfan
11. Psychiatric conditions/disease that impair the ability to give informed consent or to
adequately co-operate -