The prognostic value of cytogenetics is reinforced by the kind of induction/consolidation therapy in influencing the outcome of acute myeloid leukemia - analysis of 848 patients

We studied the impact of cytogenetics and kind of induction/consolidation t herapy on 848 adult acute myeloid leukemia (AML) patients (age 15-83). The patients received three types of induction/consolidation regimen: standard (daunorubicin and cytosine arabinoside (3/7)3 two cycles); intensive (idaru bicin, cytosine arabinoside and etoposide (ICE), plus mitoxantrone and inte rmediate-dose Ara-C (NOVIA)); and low-dose (low-dose cytosine arabinoside). CR patients under 60 years of age, if an HLA-identical donor was available received allogeneic stem cell transplantation (allo-SCT); otherwise, as pa rt of the program, they underwent autologous (auto)SCT. CR rates significan tly associated with 'favorable' (inv(l6), 1(8;21)), 'intermediate' ('no abn ormality', abn(11q23), +8, del(7q)) and 'unfavorable' (del (5q), -7, abn(3) (q21q26), 1(6;9), 'complex' (more than three unrelated cytogenetic abnormal ities)) karyotypes (88% vs 65% vs 36%, respectively; P = 0.0001). These tre nds were confirmed in all age groups. On therapeutic grounds, intensive ind uction did not determine significant increases of CR rates in any of the co nsidered groups, with respect to standard induction. Low-dose induction was associated with significantly lower CR rates. Considering disease-free sur vival (DFS), multivariate analysis of the factors examined (including karyo type grouping) showed that only age >60 years significantly affected outcom e. However, in cases where intensive induction was adopted,'favorable' kary otype was significantly related to longer DFS (P = 0.04). This was mainly d ue to the favorable outcome of 1(8;21) patients treated with intensive indu ction. Patients receiving allo-SCT had significantly longer DFS (P = 0.005) ; in particular, allo-SCT significantly improved DFS in the 'favorable' and 'intermediate' groups (P = 0.04 and P = 0.048, respectively). In conclusio n our study could provide some guidelines for AML therapy: (1) patients in the 'favorable' karyotype group seem to have a longer DFS when treated with an intensive induction/consolidation regimen, adopted before auto-SCT inst ead of standard induction; this underlines the importance of reinforcement of chemotherapy, not necessarily based on repeated high dose AraC cycles. A llo SCT, independently of induction/consolidation therapy, should be consid ered an alternative treatment; (2) patients in the 'intermediate' karyotype group should receive allo-SCT; (3) patients in the 'unfavorable' karyotype group should be treated using investigational chemotherapy, considering th at even allo-SCT cannot provide a significantly longer DFS, but only a tren d to a better prognosis.