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Blood, 18 June 2009, Vol. 113, No. 25, pp. 6338-6341. Prepublished online as a Blood First Edition Paper on April 23, 2009; DOI 10.1182/blood-2009-03-210989.
Submitted March 18, 2009
Department of Dermatology, Columbia Presbyterian Medical Center, New York, NY, United States * Corresponding author; email: alexander_marneros{at}yahoo.com.
Pralatrexate is a novel antifolate, which shows increased anti-tumor activity in human tumor xenograft studies in mice as compared to methotrexate. We investigated the effects of pralatrexate in a patient with adult T-cell lymphoma/leukemia (ATLL) with significant skin involvement. Atypical lymphocytes in epidermal Pautrier microabscesses were positive for HTLV-1. After the patient presented with leukemic conversion and with worsening of an erythematous generalized papular rash, he received one dose of pralatrexate. Within one week his skin developed innumerable small erosions limited to the areas of the papular rash, sparing unaffected skin. Here we present in vivo evidence that pralatrexate-induced erosions in skin affected by ATLL are a manifestation of apoptosis of tumor cells infiltrating the epidermis and are not due to cytotoxicity by pralatrexate on keratinocytes. This distinction is critical and may profoundly influence the clinical decision to continue pralatrexate treatment. Pralatrexate-induced skin erosions may indicate response to treatment.
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