Initial preclinical investigation of aclarubicin treatment in primary cutaneous T-cell lymphoma cells.

Better therapeutic agents are needed in the treatment of advanced cutaneous T-cell lymphomas. Anthracyclines, including doxorubicin, are such drugs, but they are associated with cardiotoxicity that limits treatment. Aclarubicin is an anthracycline that acts by chromatin damage only and does not show any dose-accumulated cardiotoxicity. We compared the cytotoxicity of different anthracyclines that either induce DNA breaks and/or nucleosome eviction on primary ex vivo patient material. Both cutaneous T-cell lymphoma tumor cells and normal CD4 T cells experience cytotoxicity at the same concentration of anthracyclines. Under a 2-hour pulse exposure that mimics the serum pharmacokinetics of these drugs, aclarubicin was less toxic, with an 8-20-fold lower half-maximal inhibitory concentration than those of the other anthracyclines tested, yet it demonstrated superior ex vivo cytotoxicity under T-cell activation. Aclarubicin should be considered for further preclinical and clinical evaluation in cutaneous T-cell lymphoma.