Highly refractory acute myeloid leukemia.

In this study we evaluated 103 patients suffering from acute myeloid leukemia (AML) who did not respond to induction chemotherapy and defined a sub-group of patients with highly refractory disease characterized by a persistence of more than 1 G/L blast cells in the peripheral blood between days 12 and 16 of the first induction cycle. Only seven patients (one female, six males) met these criteria. Their median age was 65 years (range 41-82 years). Four had de novo AML and three secondary AML. Cytogenetic analysis was performed in six patients: complex aberrations were detected in four patients and, unexpectedly, normal karyotypes were found in the other two. Analysis of multidrug-resistance factors revealed high co-expression of P-glycoprotein (P-gp) and lung resistance protein (LRP) in all four patients with highly refractory disease tested a finding in only 6% of patients with refractory disease and 3% of patients who achieved complete remission (CR) of disease. Furthermore, patients with highly refractory AML had substantially higher leukocyte counts than patients with refractory AML or CR, although this was not significant statistically. Overall, patients with highly refractory AML are characterized by a high incidence of complex cytogenetic aberrations and marked expression of drug transporters.