Effect of cefoperazone adjuvant therapy on the response to the remission induction regimen in patients with acute myeloid leukemia

Abstract EN

Cefoperazone is an antibiotic that is frequently prescribed at a dose of 1-2g i.v.

every 12 hours in many situations.

At the same time, it was reported to reverse P-glycoprolein (P-gp) mediated multiple drug resistance (MDR) in vitro.

We investigated whether the same effect could be achieved in acute myeloid leukemia (AML) in vivo. We divided newly diagnosed AML patients into those with P-gp overexpression which is defined as staining with a P-gp monoclonal antibody in ≥ 20% of the peripheral mononuclear cells and those with low P-gp expression.

We found that 47.5% of AML patients had P-gp overexpression at diagnosis.

We compared the response to the standard remission induction therapy in patients with P-gp over expression and those with low P-gp expression at Diagnosis.

Patients with P-gp overexpression had a lower rate of achievement of complete remission (CR).

The response to treatment in a subset of patients with P-gp overexpression and treated concomitantly with cefoperazone at a dose of 1g i.v.

every 12 hours was similar to patients treated without cefoperazone.

In all the groups tested, the percentage of cells stained with the P-gp monoclonal antibody increased after as compared to before therapy reflecting a treatment induced increase in the percentage of P-gp expressing stem cells in the bone marrow.

In conclusion: cefoperazone at a dose of 1g i.v.

every 12 hours failed to modulate MDR in AML patients.

The effect of higher doses should be investigated.