Sustained remission of Sézary syndrome

ARTICLE

Cutaneous T-cell lymphoma represents a group of low-grade, non-Hodgkin lymphomas, including Sézary syndrome and mycosis fungoides and its variants [1, 2]. Sézary syndrome is the leukemic and most aggressive subtype of cutaneous T-cell lymphoma and is associated with a poor prognosis [1, 2]. The clinical features of Sézary syndrome include exfoliative erythroderma, pruritus, generalized lymphadenopathy, alopecia, onychodystrophy, palmoplantar hyperkeratosis, and ectropion [1-3]. Various therapies are available for managing patients with Sézary syndrome, including extracorporeal photopheresis (ECP), interferon alfa, and newer chemotherapeutic agents such as nucleoside analogues, bexarotene (Targretin), and denileukin diftitox (Ontak) [4-8].

ECP is an immunomodulatory therapy. The instrument used (Therakos, Exton, PA, USA) integrates initial discontinuous leukapheresis with subsequent exposure to ultraviolet light in a single apparatus. The procedure involves pooling 240 ml of leukocyte-enriched blood with 300 ml of the patient's plasma (removed 2 hrs after ingestion of 50 mg of methoxypsoralen) and 200 ml of normal saline, yielding a final hematocrit of 6.4% (mean saline) and containing 5 to 10% of the number of lymphocytes in the patient's bloodstream. The total volume is then passed as a 1-mm film through a 6-chambered disposable sterile cassette to expose blood to ultraviolet A energy delivered by a fluorescent source. The entire amount is then returned to the patient [9].

The treatment of erythrodermic cutaneous T-cell lymphoma with ECP was first described by Edelson et al. in 1987 [10]. Data demonstrating the efficacy in enhancing survival of patients with Sézary syndrome remain controversial, and remission is rare [11-18]. Findings indicate that patients with normal CD8 levels and diminished CD4/CD8 ratios at the initiation of therapy have a higher response rate [19]. The mechanisms for action of ECP are also incompletely understood. In evaluating the activity of a related modality of photochemotherapy, psoralen ultraviolet A, Johnson et al. [20], as well as Yoo et al. [21], found evidence of induction of apoptosis of circulating T cells from patients with Sézary syndrome who were undergoing ECP therapy.

In the patient reported herein, clinical, histologic, and laboratory evidence of cutaneous T cell lymphoma and Sézary syndrome disappeared while the patient was receiving monthly treatment with ECP. Response to treatment was evaluated according to the following criteria: extent of red and scaling skin, lymph node size, absolute leukocyte count, and absolute Sézary cell count.

Case report

An 82-year-old white man presented to Mayo Clinic (Rochester, MN, USA) in April 1997 with an 18-month history of exfoliative erythroderma (Fig. 1A). Physical examination revealed palmoplantar hyperkeratosis (Fig. 2A), ectropion, and bilateral inguinal lymphadenopathy. A skin biopsy showed mononuclear cell infiltrate with atypia. Analysis of blood smears (an average of 2 samples on 2 consecutive days) showed an absolute Sézary cell count of 1,660, with a CD4/CD8 ratio of 4:1. Gene rearrangement studies from peripheral blood, tissue, and bone marrow showed clonal gene rearrangements in the peripheral blood. Sézary syndrome was diagnosed.

In April 1997 the patient began receiving a course of 15 million units of interferon alfa-2b (5 times 3 million units), injected subcutaneously; fludarabine (2-chlorodeoxyadenosine) was added later but was soon stopped because of adverse side effects. Because there was no response to interferon alone, monthly treatment with ECP was begun in July 1997. Because of nausea, fatigue, flu-like symptoms, and a 20-pound weight loss since the initiation of interferon, interferon was stopped in September 1998.

During the following 6 months, the patient's erythroderma resolved and the Sézary cell count decreased. The frequency of ECP treatment was changed from monthly to once every 3 months; ECP was stopped in July 1999. The patient has remained in remission (Figs. 1B and 2B). Biopsies have been interpreted as showing nonspecific dermatitis. Sézary cell counts have ranged from undetectable to 450 mg/dl, never exceeding 1,000 mg/dl. The gene rearrangement of the peripheral blood repeated in April 2000 and showed no evidence of a peripheral blood clone.

Comment

Sézary syndrome is a debilitating, malignant T-cell lymphoproliferative disorder of CD4 T cells involving skin, blood, and lymph nodes. The disease has been associated with a poor prognosis [3]. Newer approaches to control Sézary syndrome include bexarotene (Targretin), denileukin diftitox (Ontak), combination chemotherapy, and interferon alfa-2b [8]. Unfortunately, these treatments have been largely palliative rather than curative [11-18].

In a study of 115 patients being treated for Sézary syndrome at M.D. Anderson Cancer Center (Houston, TX, USA), actuarial median survival ranged from 2.5 years to more than 13 years [22]. In a cohort of 62 patients in Italy, median survival time was 31 months (range, 1 month to at least 15.7 years), and the 5-year survival rate was 33.5% [9].

Our experience with ECP in the treatment of Sézary syndrome has shown that therapy is typically prolonged, with slow clinical response, and control of disease is often lost over time. Sustained remission of disease occurred in this patient. Of 102 patients with Sézary syndrome followed at our institution between 1965 and 2000, remission occurred in only 2 patients. One is the patient reported herein. (The other patient, whose case will be reported separately, had remission for 18 months after treatment with 2-chlorodeoxyadenosine but died of squamous cell carcinoma of the lungs.) Remission of Sézary syndrome also has been reported to occur after treatment with systemic chemotherapy and bone marrow transplantation [23, 24] and ECP/2-chlorodeoxyadenosine [15-19, 25-27].

Complete remissions of cutaneous T-cell lymphoma (but not the Sézary variant) after treatment with ECP and other therapy have occurred in European and United States trials [15-19]. We note that the patient described is the only one of 55 patients with Sézary syndrome treated exclusively with ECP at our institution who achieved sustained complete remission of the disease. The role of ECP in improving survival in patients with Sézary syndrome is a subject of ongoing study.

CONCLUSION

REFERENCES

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