Hematology/Oncology, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire, USA.
Drugs. 2010 Feb 12;70(3):273-86. doi: 10.2165/11532190-000000000-00000.
Cutaneous T-cell lymphomas (CTCLs) are a rare group of mature T-cell lymphomas presenting primarily in the skin. The most common subtypes of CTCL are mycosis fungoides and its leukaemic variant Sézary's syndrome. Patients with early-stage disease frequently have an indolent clinical course; however, those with advanced stages have a shortened survival. For the treating physician, the question of how to choose a particular therapy in the management of CTCL is important. These diseases span the disciplines of dermatology, medical oncology and radiation oncology. Other than an allogeneic stem cell transplant, there are no curative therapies for this disease. Hence, many treatment modalities need to be offered to the patient over the course of their life. An accepted treatment approach has been to delay traditional chemotherapy, which can cause excessive toxicity without durable benefit. More conservative treatment strategies in the initial management of CTCL have led to the development of newer biological and targeted therapies. These therapies include biological immune enhancers such as interferon alpha and extracorporeal photopheresis that exert their effect by stimulating an immune response to the tumour cells. Retinoids such as bexarotene have been shown to be effective and well tolerated with predictable adverse effects. The fusion toxin denileukin diftitox targets the interleukin-2 receptor expressed on malignant T cells. Histone deacetylase inhibitors such as vorinostat and romidepsin (depsipeptide) may reverse the epigenetic states associated with cancer. Forodesine is a novel inhibitor of purine nucleoside phosphorylase and leads to apoptosis of malignant T cells. Pralatrexate is a novel targeted antifolate that targets the reduced folate carrier in cancer cells. Lastly, systemic chemotherapy including transplantation is used when rapid disease control is needed or if all other biological therapies have failed. As response rates to most of the biological agents used to treat CTCL are 25-30%, it is also reasonable to consider clinical trials with novel agents if one or two front-line therapies have failed, especially before considering chemotherapy. CTCL is largely an incurable disease with significant morbidity and more active agents are needed.
皮肤 T 细胞淋巴瘤（CTCL）是一组罕见的成熟 T 细胞淋巴瘤，主要发生在皮肤。CTCL 最常见的亚型是蕈样真菌病及其白血病变体塞扎里综合征。早期疾病患者的临床病程通常呈惰性；然而，晚期患者的生存期较短。对于治疗医生来说，在 CTCL 治疗中如何选择特定的治疗方法是一个重要的问题。这些疾病跨越了皮肤科、肿瘤内科和放射肿瘤学的领域。除了异基因干细胞移植，这种疾病没有治愈的方法。因此，在患者的一生中需要向他们提供许多治疗方法。一种被接受的治疗方法是延迟传统的化疗，因为它可能会导致过度的毒性而没有持久的益处。在 CTCL 的初始管理中采用更为保守的治疗策略，导致了新的生物和靶向治疗方法的发展。这些治疗方法包括生物免疫增强剂，如干扰素α和体外光化学疗法，通过刺激对肿瘤细胞的免疫反应来发挥作用。贝沙罗汀等类视黄醇已被证明是有效的，并且具有可预测的不良反应，具有良好的耐受性。融合毒素 denileukin diftitox 靶向表达在恶性 T 细胞上的白细胞介素-2 受体。组蛋白去乙酰化酶抑制剂，如伏立诺他和罗米地辛（depsipeptide），可能逆转与癌症相关的表观遗传状态。氟达拉滨是一种新型嘌呤核苷磷酸化酶抑制剂，导致恶性 T 细胞凋亡。普拉曲沙是一种新型靶向叶酸类似物，靶向癌细胞中的还原叶酸载体。最后，当需要快速控制疾病或如果所有其他生物治疗都失败时，使用全身化疗包括移植。由于大多数用于治疗 CTCL 的生物制剂的反应率为 25-30%，因此如果一种或两种一线治疗失败，特别是在考虑化疗之前，考虑使用新型药物的临床试验也是合理的。CTCL 是一种基本无法治愈的疾病，具有很高的发病率，需要更有效的药物。
