Clinical Drug Experience Knowledgebase

Criteria

Inclusion Criteria:

Age less than physiologic 68 years.
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).

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

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:

Bilirubin > 3.0 mg/dl, transaminases > 3 times upper normal limit
Creatinine > 2.0 mg/dl
ECOG-Performance status > 2
Uncontrolled infection
Pregnancy or lactation
Abnormal lung diffusion capacity (DLCO < 40% predicted)
Severe cardiovascular disease
CNS disease involvement
Pleural effusion or ascites > 1 liter
Known hypersensitivity to fludarabine or treosulfan
Psychiatric conditions/disease that impair the ability to give informed consent or to adequately co-operate -