Trial Information

Phase II Study of Early Allogeneic Blood Stem Cell Transplantation During Induction-Chemotherapy Induced Aplasia in High-Risk Acute Myeloid Leukemia

Only patients with newly-diagnosed AML are eligible for this prospective study. An immediate
donor-search, either within the family or in volunteer donor registries, will be performed
at diagnosis irrespective of the expected risk profile. All patients will receiv at least
one cycle of IC. Inclusion criteria for early allogeneic transplantation are either poor
risk cytogenetics and/or bad response to the first cycle of IC defined by more than 10%
marrow blasts on day 15. If a patient meets one of those criteria they could enter the early
allogeneic HSCT trial after providing informed consent. DNA-based HLA-typing of donor and
recipient will be performed using high resolution (4 digits) for HLA - A, B, DRB1 and DQB1
and intermediate resolution (2 digits) for HLA- C.

During IC-induced aplasia after the 1st or 2nd cycle a fludarabine-based reduced intensity
conditioning therapy will be started if a donor is available. All patients receive
fludarabine 30 mg/m2 i.v. daily for five days (day- 6 to -2) and melphalan 150 mg/m² on
day-2. Antithymocyte globulin (ATG Fresenius 10 mg/kg/day day -5 to -2, total dose 40 mg/kg,
Fresenius, Bad Homburg, Germany) will be applied after transplantation from unrelated or HLA
mismatched family donors. PBSC grafts will be preferred. As immunosuppression cyclosporin A
(CsA) is either administered intravenously at a dose of 3 mg/kg/day or given at an
bioequivalent amount of the oral formulation in two divided doses starting on the day before
blood stem cell infusion (day -1). The dose of CsA is adjusted to maintain blood levels
between 150 and 250 ng/ml. Starting on day 50, oral CsA administration will be tapered by 5%
weekly if GVHD was inactive. Acute and chronic GvHD will be treated with prednisone, CsA or
tacrolimus.