risk-adapted therapy for adult acute myeloid leukemia.

Conditions: Leukemia, Myelocytic, Acute

Summary: in a protocol of treatment of aml used in 1994 for adults with aml up to the age of 50 years, the spanish cetlam group showed a complete remission rate 75 % using the combination of daunorubicin (60 mg/m2, 3 days) plus conventional dose cytarabine (100mg/m2/day in continuous infusion during 7 days) and etoposide (100mg/m2 iv/day 3 days). if idarubicin (10 mg/m2, 3 days) was administered instead of daunorubicin, the complete remission (cr) rate in adults up to 60 years was 75%. to improve the proportion of crs and to decrease relapse rate appearing in 50% of patients, the phase ii aml-99 trial includes intermediate dose-cytarabine during induction and risk-adapted post remission treatment based on the improvement in prognostic characterization of aml and the implementation of novel transplantation techniques.

induction chemotherapy: idarubicin (12mg/m2/day intravenous), intermediate-dose cytarabine (500mg/m2/12h, intravenous) and etoposide (100mg/m2/day, intravenous) in 3+7+3 schedule. this induction therapy is repeated if complete remission (cr) is not achieved after the first course of treatment. consolidation therapy: mitoxantrone (12mg/m2/day, intravenous, days 4, 5 and 6) and intermediate-dose cytarabine (500mg/m2/12h from day 1 to 6). risk-stratification according to cytogenetics, courses to cr and availability of an hla-identical sibling: * patients in the favorable cytogenetics group \[t(8;21), inv(16) or t(16;16)\] are treated with high-dose cytarabine (3g/m2/12h, intravenous, days 1, 3 and 5). * patients in intermediate cytogenetics group (normal karyotype and a single course to achieve the cr) receive an autologous peripheral blood stem cell (pbsc) transplant, regardless of having an hla-identical sibling. * the remaining patients are considered in the high-risk group and are treated with autologous or allogeneic pbsc transplantation depending on the availability of a sibling donor. in allotransplants, cd34+ cell selection of hematopoietic cells is performed.

Eligibility criteria:
inclusion criteria: * patients with newly diagnosed aml, classified by fab criteria * age not superior to 60 years * verbal informed consent for the chemotherapy and written for the mobilization and stem cell transplantation exclusion criteria: * patients treated previously for its aml with other chemotherapy different from hydroxyurea * acute promyelocytic leukemia (m3) * chronic myeloid leukemia in blastic crisis * leukemias appearing after other myeloproliferative processes * leukemias surviving after myelodysplastic syndromes with more than 6 months of evolution * presence of other neoplastic disease in activity * secondary aml which had appeared after cured malignancies (for instance hodgkin disease) and those who are still exposed to alkylant agents or radiation * renal and hepatic abnormal function with creatinine values and/or bilirubin two times higher than the normal threshold, except when this alteration could be attributed to the leukemia * patients with a fraction of ejection very low (inferior to 40%), symptomatic cardiac insufficiency or both * patients with a grave concomitant neurological or psychiatric disease * positivity of hiv (donor and/or receptor)

Keywords: primary aml risk-adapted treatment hematopoietic transplantation cd34+ cell selection