title: Pralatrexate-induced tumor cell apoptosis in the epidermis of a patient with HTLV-1 adult T-cell lymphoma/leukemia causing skin erosions.
abstract: Pralatrexate is a novel antifolate, which shows increased antitumor activity in human tumor xenograft studies in mice compared with methotrexate. We investigated the effects of pralatrexate in a patient with adult T-cell lymphoma/leukemia 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 adult T-cell lymphoma/leukemia are a manifestation of apoptosis of tumor cells infiltrating the epidermis and are not the result of 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.
authors.affiliation: Department of Dermatology, Columbia Presbyterian Medical Center, New York, NY, USA. alexander_marneros@yahoo.com
authors.forename: Alexander G
authors.initials: AG
authors.lastname: Marneros
authors.forename: Marc E
authors.initials: ME
authors.lastname: Grossman
authors.forename: David N
authors.initials: DN
authors.lastname: Silvers
authors.forename: Sameera
authors.initials: S
authors.lastname: Husain
authors.forename: Gerard J
authors.initials: GJ
authors.lastname: Nuovo
authors.forename: Barbara
authors.initials: B
authors.lastname: MacGregor-Cortelli
authors.forename: Ellen
authors.initials: E
authors.lastname: Neylon
authors.forename: Molly
authors.initials: M
authors.lastname: Patterson
authors.forename: Owen A
authors.initials: OA
authors.lastname: O'Connor
authors.forename: Jasmine M
authors.initials: JM
authors.lastname: Zain
mesh_terms: D000328:Adult; D000630:Aminopterin / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology* / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects*; D001706:Biopsy; D003520:Cyclophosphamide / Q000008:administration & dosage; D003937:Diagnosis, Differential; D018450:Disease Progression; D004317:Doxorubicin / Q000008:administration & dosage; D003875:Drug Eruptions / Q000175:diagnosis; D004817:Epidermis / Q000187:drug effects* / Q000473:pathology; D005047:Etoposide / Q000008:administration & dosage; D005076:Exanthema / Q000139:chemically induced* / Q000175:diagnosis; D005493:Folic Acid Antagonists / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000188:drug therapy / Q000473:pathology* / Q000532:radiotherapy; D008297:Male; D011241:Prednisone / Q000008:administration & dosage; D011994:Recombinant Proteins; D014750:Vincristine / Q000008:administration & dosage; D015215:Zidovudine / Q000008:administration & dosage
chemical_list: C418863:10-propargyl-10-deazaaminopterin; D000964:Antimetabolites, Antineoplastic; D005493:Folic Acid Antagonists; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D015215:Zidovudine; D014750:Vincristine; D005047:Etoposide; D004317:Doxorubicin; D003520:Cyclophosphamide; D000630:Aminopterin; D011241:Prednisone