Comparative evaluation of the liposomal daunorubicin + cytarabine combination (CPX-351) versus the '7+3' combination on mucosal barrier function and intestinal microbiota

Acute myeloid leukemias (AML) are among the most frequent malignancies in elderly subjects. Age and comorbidities not only worsen leukemia characteristics in older AML patients, but also increase the risk of toxicity upon chemotherapy treatment, thus complicating the management of the patients. The biological peculiarities of these leukemic forms can determine a state of severe immunodeficiency with consequent greater susceptibility towards infectious diseases. The type and relative risk of infectious complication must be correlated to the therapies used for the treatment of acute leukemia. Indeed, the 'golden standard' therapy for the AML treatment, i.e. the '7+3' (cytarabine + daunorubicin) combination, is accompanied by significant damage to the mucous membranes, especially in the intestine, and a high percentage of infections. In 2017, a liposomal combination of cytarabine + daunorubicin (CPX-351, ratio 5:1) was approved by the FDA as first-line treatment of therapy-related or advanced AMLs, after having demonstrated a better overall survival and percentage of remissions in leukemic patients compared to the '7+3' arm. The rationale of this study is to elucidate mechanisms underlying the reduced toxicity and lower mortality of CPX-351 compared to '7+3' combination. Our working hypothesis is that the intestinal mucosal barrier, made up by the concerted action of the epithelial lining, the associated immune system and the communities of colonizing microorganisms, could be a major site for the collateral activity of the chemotherapeutic regimens and that CPX-351 has a lower impact than the '7+3' combination.