EXTRACORPOREAL PHOTOPHERESIS AND RECOMBINANT INTERFERON ALFA-2B IN SEZARY-SYNDROME - USE OF DUAL MARKER LABELING TO MONITOR THERAPEUTIC RESPONSE

The purpose of this pilot study was to evaluate the role of recombinan t interferon alfa 2b (rIFN-alpha) as adjunct immunomodulatory therapy in patients with Sezary syndrome who were considered unlikely to respo nd to ExP alone. Six patients were treated with rIFN-a in doses rangin g from 3 to 20 million units three times weekly in addition to two con secutive photopheresis treatments every 4 weeks. In addition, to bette r measure the effect of treatment on circulating neoplastic T-cells, c ryopreserved lymphocytes were studied by two-color immunofluorescence and flow cytometry, using anti-CD4 combined with anti-CD29, anti-CD45R A, or anti-CD7. Minimal clinical improvement was observed in 4 patient s treated with low doses of rIFN-a (3 to 5 million units TIW), and the response was sustained in only 1 patient. However, a clinically signi ficant and sustained improvement did occur in 1 patient after the dose of rIFN-a was increased (20 million units TIW). Although the encounte red toxicity profile from combined ExP/rIFN-a therapy was similar to t hat expected for ExP or comparable doses of rIFN-a given separately, t reatment was discontinued in 2 patients because of adverse effects. Th ree antibody pairs, i.e., CD4+CD7-, CD4+CD29+, and CD4+CD45RA- subsets , appeared to be useful to monitor changes in blood Sezary cells durin g treatment. We conclude that the combination of ExP and low doses of rIFN-a does not appear to be effective for patients with advanced Seza ry syndrome in this small patient series. However, escalation of inter feron dose may be beneficial as shown in one patient, but it cannot be discerned whether the response was due to a combination of therapies, or whether the same therapeutic response would have been achieved wit h the higher doses of rIFN-a alone. Moreover, while none of the antibo dy pairs is unique for Sezary cells, the CD4+CD7- subset in appropriat e patients provided a good objective measure of response and correlate d well with visual Sezary cell counts.