Bexarotene treatment of late-stage mycosis fungoides and Sézary syndrome: development of extracutaneous lymphoma in 6 patients.

Bexarotene is a retinoid drug that is approved for the treatment of cutaneous T-cell lymphoma. We report 6 cases in which the initiation of bexarotene therapy for cutaneous T-cell lymphoma was temporally associated with the progression of internal disease despite improvement in cutaneous signs and symptoms. It is possible that bexarotene contributed to this progression. Although bexarotene therapy may alleviate symptoms and signs of cutaneous T-cell lymphoma, careful surveillance of lymph nodes and solid organs during treatment is advised.

Extracorporeal photopheresis and adjuvant aerosolized granulocyte-macrophage colony-stimulating factor for Sézary syndrome.

Encouraged by preliminary phase 1 studies of aerosolized granulocyte-macrophage colony-stimulating factor (GM-CSF, sargramostim) in the treatment of patients with melanoma and other malignancies, we treated a 72-year-old patient with Sézary syndrome, using alternate-week cycles of aerosolized GM-CSF in combination with monthly cycles of extracorporeal photopheresis (ECP). Sézary syndrome, one of the more aggressive forms of cutaneous T-cell lymphoma, is a devastating and highly symptomatic form of non-Hodgkin lymphoma in which malignant clones of mature helper CD4 T cells, containing large, convoluted nuclei known as Sézary cells, circulate in the blood and infiltrate skin. Extracorporeal photopheresis, an immunomodulatory therapy, has become a primary treatment for patients with Sézary syndrome. This pheresis-based therapy combines psoralen and ultraviolet A radiation as systemic photochemotherapy to induce immune responses. However, the activity and efficacy of ECP vary considerably. To our knowledge this is the first patient with Sézary syndrome treated with adjuvant aerosolized GM-CSF combined with ECP. It produced clinical improvement and decreased the number of circulating Sézary cells in a previously ECP-refractory patient.

Sustained remission of Sézary syndrome.

Sézary syndrome, an aggressive form of cutaneous T-cell lymphoma, is a devastating, highly symptomatic form of non-Hodgkin lymphoma. Malignant clones of mature helper CD4 T cells containing large, convoluted nuclei known as Sézary cells circulate in the blood and infiltrate the skin. Clinical features include exfoliative erythroderma, generalized lymphadenopathy, alopecia, onychodystrophy, palmoplantar hyperkeratosis, and ectropion. Patients often have severe pruritus, burning sensations, pain, bleeding from excoriations, and disfigurement. Extracorporeal photopheresis, an immunomodulatory therapy, has become a primary therapy for these patients. This pheresis-based therapy uses psoralen and ultraviolet A radiation-mediated photochemotherapy to induce immune responses. The effects of extracorporeal photopheresis vary considerably. We report sustained remission (2 years) in a patient with Sézary syndrome. Previously he had received extracorporeal photopheresis and interferon alfa-2b injections. He is the only one of 55 patients with Sézary syndrome treated at Mayo Clinic (Rochester, Minnesota, USA) to achieve sustained remission on extracorporeal photopheresis alone.

Oral bexarotene in a therapy-resistant Sézary syndrome patient: observations on Sézary cell compartmentalization.

BACKGROUND: A 63-year-old man with therapy-resistant Sézary syndrome was enrolled in a multicenter trial of oral bexarotene for advanced-stage cutaneous T-cell lymphoma (CTCL). METHODS: Monthly evaluations for efficacy and side-effects were conducted and documented. RESULTS: Gradual improvement in erythema, pruritus, and scale was noted during the initial 16-week trial period and treatment was extended to 40 weeks. From week 20 to week 40, the erythroderma continued to improve and the lymph node burden decreased, but the absolute Sézary cell count inversely increased. By week 40, intractable pruritus and erythroderma abruptly recurred, and bexarotene was discontinued. CONCLUSIONS: Bexarotene is well tolerated and can be efficacious in patients with Sézary syndrome. Shifting of Sézary cells between different compartments was noted. Further studies on the interaction between the skin, lymph nodes, and peripheral blood compartments during bexarotene treatment in this subset of patients with CTCL are needed.

Contribution of sexually transmitted diseases and socioeconomic factors to perinatal mortality in rural Ghana.

BACKGROUND: The infant mortality rate is higher in sub-Saharan Africa than in other developing regions. The purpose of this study was to evaluate the association of sexually transmitted diseases (STDs) and socioeconomic and obstetric factors with perinatal mortality in rural Ghana. METHODS: Perinatal mortality data were collected from 154 patient records of the outpatient and inpatient gynecology department of a rural Ghanaian setting in 1997. All women attended the antenatal care unit of the hospital at least once before delivery, where they were screened for common STDs, including syphilis, gonorrhea, and trichomoniasis. Patients' socioeconomic characteristics and previous obstetric complications were recorded. RESULTS: The rate of perinatal mortality at the Holy Family Hospital in the Berekum district of Ghana was 13.7% in 1997 (154 of 1123 documented births). Characteristics of mothers whose infants died in the perinatal period and who had attended antenatal care at least once were as follows: prior obstetric complications, 108 patients (70.1%); average age, 25 years (range: 16-42 years); average number of previous sexual partners, three; prevalence of STDs, including gonorrhea, trichomoniasis, or syphilis, 83 patients (53.8%); history of other chronic diseases, 13 patients (8.5%); and illiteracy, 66 patients (42.8%). The number of previous sexual partners and illiteracy were higher in the STD-positive women. CONCLUSIONS: Sexually transmitted diseases and previous obstetric complications seemed to contribute considerably to perinatal mortality in rural Ghana.

Effect of insulin-dependent diabetes mellitus on response to extracorporeal photopheresis in patients with Sézary syndrome.

BACKGROUND: Extracorporeal photopheresis (ECP) has become a primary therapy for selected forms of cutaneous T-cell lymphoma, especially Sézary syndrome. Variability in response of patients with Sézary syndrome to ECP has been reported. OBJECTIVE: Our purpose was to determine whether underlying medical conditions influence the efficacy of ECP in patients with Sézary syndrome. METHODS: We retrospectively reviewed the medical records of 55 patients with Sézary syndrome who received ECP between 1987 and 2000. Efficacy criteria included decrease in Sézary cell count, erythroderma, lymphadenopathy, organomegaly, and pruritus. RESULTS: Thirty-four patients responded well and 10 patients responded partially to ECP; 11 patients had no response. Nine patients with no response to ECP had insulin-dependent diabetes mellitus (IDDM). IDDM was documented in only 2 patients with a good response and in no patients with a partial response to ECP. CONCLUSION: Patients with Sézary syndrome and IDDM typically respond poorly to the standard ECP treatment regimen.

Treatment of late-stage Sézary syndrome with 2-Chlorodeoxyadenosine.

BACKGROUND: 2-Chlorodeoxyadenosine (2-CdA), a purine adenosine analog, is safe and effective chemotherapy for patients with hairy cell leukemia and low-grade lymphomas. Adverse effects include neutropenia, lymphocytopenia, and infectious complications. Our objective was to evaluate the efficacy of 2-CdA (2-6 seven-day cycles) in the treatment of late-stage, recalcitrant Sézary syndrome. METHODS: Retrospective review of medical records of six patients with Sézary syndrome who had received 2-CdA cycles at Mayo Clinic, Rochester between March 1995 and March 2000. Variables assessed from the records included improvement in global appearance, extent of erythroderma, size of lymph nodes, pruritus, and leukocyte, lymphocyte, and absolute Sézary cell counts. RESULTS: Two patients, both with stage III Sézary syndrome, whose previous treatment consisted of only two modalities, responded well to the treatment, with moderate to total clearing of erythroderma and pruritus associated with a significant decrease in Sézary cell counts. The other four patients had only a partial response (one patient) or no response (three patients) to 2-CdA. The mortality rate was 50%. All three patients died of Staphylococcus aureus sepsis. However, only one patient was receiving 2-CdA treatment when he died. The other two patients died 8 and 9 weeks after the last 2-CdA cycle. This high mortality rate is attributed to infectious complications after 2-CdA treatment in patients with recalcitrant disease. CONCLUSION: 2-Chlorodeoxyadenosine shows efficacy in stage III Sézary syndrome, but it also carries a substantial risk of septic complications and mortality. It can be used if no other suitable alternatives are available. Caution should be exercised in all these patients regarding skin care and avoidance of infections or sepsis.