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Purine analogues [fludarabine monophosphate (FAMP); deoxycoformycin and 2-chlorodeoxyadenosine) and extracorporeal photochemotherapy (ECP) have been suggested to be active agents in advanced cutaneous T-cell lymphoma (CTCL) patients. To explore further the clinical efficacy and safety of FAMP monochemotherapy in advanced CTCL and to evaluate if the sequential association of ECP to FAMP in selected patients may improve the response rate (RR) and/or lengthen the remission duration. Forty-four CTCL patients [17 Sézary syndrome (SS); 26 mycosis fungoides (MF), stage IIB–IV or with peripheral blood involvement; one MF associated with lymphomatoid papulosis (LyP)] were enrolled in this pilot cohort study. All the patients received FAMP 25 mg m−2 5 days monthly; 19 patients (43·2%) underwent ECP after FAMP was discontinued. The majority of patients with erythrodermic CTCL or peripheral blood involvement underwent the combined FAMP–ECP schedule. After a median follow-up of 4·2 years, the overall FAMP RR was 29·5% (13/44); a higher RR was obtained in SS (35·3%) than in MF patients (25·9%). According to the treatment group, the RR of the FAMP–ECP group (63·2%) was significantly higher than that of the FAMP monotherapy group (24%; P = 0·021). No statistically significant difference was found in time-to-progression (TTP) or survival by therapy group, even if the TTP of the patients treated with the FAMP–ECP combination therapy was higher (median 13 vs. 7 months). A decrease or a normalization in the CD4+CD26– circulating subset was observed in responding patients, paralleling the reduction in the circulating Sézary cells. FAMP confirms its clinical activity as a single agent in SS; conversely, FAMP results do not compare favourably with other therapeutic approaches for advanced stage MF patients. The sequential association of ECP after FAMP seems to increase the RR, even if future randomized studies are needed to confirm these results. [ABSTRACT FROM AUTHOR]