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 recombinant interferon alfa 2b (rIFN-a) as adjunct immunomodulatory therapy in patients with Sezary syndrome who were considered unlikely to respond to ExP alone. Six patients were treated with rIFN-a in doses ranging from 3 to 20 million units three times weekly in addition to two consecutive photopheresis treatments every 4 weeks. In addition, to better measure the effect of treatment on circulating neoplastic T-cells, cryopreserved lymphocytes were studied by two-color immunofluorescence and flow cytometry, using anti-CD4 combined with anti-CD29, anti-CD45RA, or anti-CD7. Minimal clinical improvement was observed in 4 patients 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 significant and sustained improvement did occur in 1 patient after the dose of rIFN-a was increased (20 million units TIW). Although the encountered toxicity profile from combined ExP/rIFN-a therapy was similar to that expected for ExP or comparable doses of rIFN-a given separately, treatment was discontinued in 2 patients because of adverse effects. Three antibody pairs, i.e., CD4+CD7-, CD4+CD29+, and CD4+CD45RA- subsets, appeared to be useful to monitor changes in blood Sezary cells during treatment. We conclude that the combination of ExP and low doses of rIFN-a does not appear to be effective for patients with advanced Sezary syndrome in this small patient series. However, escalation of interferon 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 with the higher doses of rIFN-a alone. Moreover, while none of the antibody pairs is unique for Sezary cells, the CD4+CD7- subset in appropriate patients provided a good objective measure of response and correlated well with visual Sezary cell counts.
Vonderheid
E C
EC
Department of Medicine, Hahnemann University, Philadelphia, Pennsylvania.
Bigler
R D
RD
Greenberg
A S
AS
Neukum
S J
SJ
Micaily
B
B
D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000032:analysis; D015415:Biomarkers / Q000032:analysis; D003131:Combined Modality Therapy; D004334:Drug Administration Schedule; D005260:Female; D005455:Fluorescent Antibody Technique; D006801:Humans; D016130:Immunophenotyping; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D017893:Photopheresis; D010865:Pilot Projects; D011994:Recombinant Proteins; D012751:Sezary Syndrome / Q000276:immunology / Q000628:therapy*; D012878:Skin Neoplasms / Q000276:immunology / Q000628:therapy*
D015703:Antigens, CD; D015415:Biomarkers; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins