Verrucous presentation in patients with mycosis fungoides

Mycosis fungoides is a potentially fatal skin condition whose variable clinical appearance may mimic a variety of benign, inflammatory dermatoses, making it a diagnostic challenge. Three patients with mycosis fungoides, treated with multiple approved topical and systemic therapies, presented with acquired verrucous lesions on the extremities. The verrucous presentation of mycosis fungoides is one of the many atypical forms of the disease, with a paucity of documented cases in the medical literature. Although rare, verrucous and hyperkeratotic lesions in mycosis fungoides may increase the risk of considerable diagnostic delay if clinicians do not maintain a high degree of suspicion in cases of acquired verrucous lesions in the appropriate clinical setting.     

Extracorporeal Photopheresis for the Treatment of Cutaneous T-Cell Lymphoma

Journal of Cutaneous Medicine and Surgery -     

Multicenter photopheresis intervention trial in early-stage mycosis fungoides

PurposeTo demonstrate the efficacy of the UVAR XTS Photopheresis System and evaluate health-related quality of life in patients with early-stage mycosis fungoides (MF).Patients and MethodsExtracorporeal photopheresis was administered 2 days every 4 weeks for 6 months. Patients with partial responses by skin weighted assessment continued for 6 months; nonresponders added oral bexarotene and/or interferon α. Health-related quality of life was assessed at baseline and every 3 months with 3 validated tools.ResultsNineteen patients with early-stage MF (7 men, 12 women; 16 white, 3 African Americans) with median age of 63.5 years (range, 46-85 years) participated. Their stages were IA (n = 3), IB (n = 14), and IIA (n = 2). The overall response rate for extracorporeal photopheresis (ECP) alone, was 42% (8/19; including 7 partial response, 1 complete response), with a median of 12 ECP sessions (range, 3-32) given over a median of 12 months (3-32 months) and with an overall duration of response of 6.5 months (range, 1-48 months). Seven patients with stable disease at 3 months received additional bexarotene (3/5; 1 complete response) or bexarotene plus interferon α (1/2), and 4 (57%) of 7 responded. Treatment-related adverse effects were limited to those expected with interferon (fatigue, nausea, vomiting, and diarrhea), or with hypertriglyceridemia and bexarotene. Trends in health-related quality of life indicated an improvement in emotional scores over time.ConclusionsECP is effective for patients with early-stage MF alone or in combination with biologic response modifiers with low toxicity and improved quality of life.     

Optimizing bexarotene therapy for cutaneous T-cell lymphoma

BACKGROUND: Bexarotene (Targretin oral capsules), the first RXR-selective retinoid "rexinoid" approved for all stages of cutaneous T-cell lymphoma (CTCL), had a response rate (RR) of 45% at the optimal dose of 300 mg/m(2) per day in 2 multicenter trials. With hypertriglyceridemia reported at 79%, bexarotene is often administered with lipid-lowering agents (LLAs). Statins (inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductase) may modulate class II major histocompatibility class expression and T-cell responses. OBJECTIVE: We attempted to optimize the clinical response to bexarotene by controlling dose-limiting hypertriglyceridemia and combining bexarotene with other active agents. METHODS: We prospectively evaluated 70 patients with CTCL at M. D. Anderson Cancer Center who were treated with oral bexarotene as monotherapy or in combination with other active agents. RESULTS: Fifty-four patients receiving bexarotene monotherapy achieved an overall RR of 48%. Thirteen had stage IA-IIA disease (RR = 53%, 1 complete response [CR]); 41 had stage IIB-IVB disease (RR = 46%, 2 CRs). Forty-two (77%) of these also required one or more LLAs: atorvastatin (n = 29, RR 43%), atorvastatin plus fenofibrate (n = 10, RR 90%), or gemfibrozil (n = 3, RR 33%). Gemfibrozil was discontinued because it increased bexarotene and triglyceride levels. Patients taking 2 LLAs had a significantly higher RR of 90% during monotherapy than those taking one or no LLAs (P <.0001). Forty of 54 patients (74%) received thyroid hormone replacement to normalize thyroxine levels. Four patients receiving monotherapy have complete CRs of >3 years' duration and received maintenance dosing. Sixteen patients with advanced disease treated with bexarotene (225-750 mg/d) in combination with other CTCL therapies achieved an overall RR of 69% (11/16) with concomitant statin therapy. Bexarotene was safely combined with psoralen ultraviolet A (PUVA) plus interferon alfa (IFN-alpha) (n = 2, RR = 50%), with extracorporeal photopheresis (ECP) (n = 8, RR = 75%, 1 CR), with ECP/IFN-alpha (n = 4, RR =50%), with ECP/IFN-alpha/PUVA (n = 1, RR = 100%), and with IFN-alpha/PUVA/topical nitrogen mustard (n = 1, RR = 100%). Two patients receiving IFN-alpha had slight leukopenia, but rhabdomyolysis associated with multiple LLAs did not occur. CONCLUSION: This single-center study supports the safety and efficacy of bexarotene as both a monotherapy and a combination therapy for CTCL. Long durable CRs may be achieved with oral monotherapy. Use of statins with bexarotene may also increase RRs by permitting higher doses to be administered without interruption, by modulating the immune response, or both. When bexarotene is combined with other active CTCL therapies, higher RRs were achieved in patients with advanced disease, without unacceptable side effects.     

Cytomegalovirus seropositivity is significantly associated with mycosis fungoides and Sézary syndrome

Although mycosis fungoides (MF) may arise through persistent antigen stimulation, cytomegalovirus (CMV) is not a known risk factor. To study the incidence of seropositivity to viral infections, we compared MF and Sézary Syndrome (SS) patients to healthy bone marrow donors and other historical control groups. Baseline screening serologies at baseline were performed on 116 biopsy-proven MF/SS patients at MD Anderson Cancer Center from 1992 to 2001 and on healthy bone marrow donors evaluated by the transplant service from 1988 to 2001. Antibodies to HTLV-I/II, HIV-1, EBV, and CMV were measured using standard enzyme-linked immunosorbent (ELISA) and membrane enzyme immunoassay (MEIA) assays. One hundred thirteen (97.4%) of all MF/SS patients had positive CMV IgG serologies at initial presentation. Early- and late-stage patients' seropositivity rates were significantly higher than healthy bone marrow donor controls (chi(2).05(df=1) = 71.79). By stage, 98.1% of early-stage MF patients (IA, IB, IIA; 52/53) and 96.8% of late-stage MF and SS patients (IIB-IVB; 61/63) were seropositive compared with healthy bone marrow donors whose seropositivity rate was 57.3% (757/1322). Because the rate of CMV seropositivity increases with age, a subset of cutaneous T-cell lymphoma (CTCL) patients 55 years or younger were compared to age-matched healthy donor controls; their seropositivity rate for CMV was also significantly higher (chi(2).05 05(df=1) = 20.4). EBV titers were positive by serology in 13 patients who were examined prospectively. CMV seropositivity is highly associated with MF and SS, even in the earliest stages of the disease, and is significantly higher than that of healthy and immunocompromised controls.     

Treatment of refractory peripheral T-cell lymphoma with denileukin diftitox (ONTAK)

Peripheral T-cell lymphomas (PTCLs) are an uncommon and heterogeneous group of well-differentiated, post-thymic T-cell malignancies that can present in the skin as cutaneous T-cell lymphomas. In general, their prognosis is poor, and specific therapy is not well defined. We report the successful treatment of a patient with relapsed, refractory PTCL who after failing 13 standard single and multiple chemotherapy regimens and experimental agents had a dramatic prolonged response to diftitoxin denileukin (ONTAK). This fusion protein, composed of diphtheria toxin coupled to interleukin-2, is approved for cutaneous T-cell lymphomas, including mycosis fungoides, and should be considered for treatment of the rare subset of peripheral T-cell lymphomas.     

Overall survival in erythrodermic cutaneous T-cell lymphoma: an analysis of prognostic factors in a cohort of patients with erythrodermic cutaneous T-cell lymphoma

Background The most common cutaneous T‐cell lymphomas (CTCLs) are mycosis fungoides and Sézary syndrome. Aim To determine whether blood stage and other prognostic variables affect overall survival (OS) in CTCL. Methods We studied retrospectively 1197 CTCL patients seen at the M.D. Anderson Cancer Center since 1987. Results We identified 124 (10.3%) patients with erythrodermic CTCL (E‐CTCL), 63% of whom had positive gene rearrangements in skin and 19 of whom had no evidence of hematologic involvement. The median age at diagnosis was 63 years (range, 26–90 years); the male to female ratio was 1.3 : 1. OS curves were estimated by the Kaplan–Meier method and compared using log‐rank tests. The median OS in all 124 E‐CTCL patients was 5.1 years (range, 0.4–18.6 years) regardless of the cause of death or blood involvement. Patients were stratified by the H0–H4 staging system with manual or flow cytometric determination of Sézary cell counts (Russell‐Jones R, Whittaker SJ. Sézary syndrome: diagnostic criteria and therapeutic options. Semin Cutan Med Surg 2000; 19 : 100–108). The median OS was 7.6 years for H0–H2 (< 1000 Sézary cells/L) (n = 23), 5.4 years for H3 (≥ 1000 to ≤ 10,000 Sézary cells/L) (n = 79), and 2.4 years for H4 (≥ 10,000 Sézary cells/L) (n = 22) (P = 0.011). Treatment with systemic steroids, age, serum lactate dehydrogenase, and white blood cell count ≥ 20,000 µL were significant prognostic factors, but large cell transformation, T‐cell receptor gene rearrangement, tumor–node–metastasis stage, treatments, and CD4 : CD8 ratio were not. In multivariate analysis, advanced age and elevated lactate dehydrogenase were the strongest predictors of a poor prognosis. Conclusions Serum LDH and age were the strongest predictive factors for OS in E‐CTCL.