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低剂量病灶内重组干扰素-α2b 治疗蕈样肉芽肿。

Low-Dose Intralesional Recombinant Interferon-α2b in the Treatment of Mycosis Fungoides.

机构信息

Yale School of Medicine, New Haven, CT.

Department of Dermatology, Yale School of Medicine, New Haven, CT.

出版信息

Yale J Biol Med. 2020 Mar 27;93(1):41-44. eCollection 2020 Mar.

Abstract

Mycosis fungoides (MF), the most common form of cutaneous T-cell lymphoma (CTCL), is characterized by malignant CD4+ skin-homing T-cells that drive formation of cutaneous patches, plaques, and/or tumors. MF's known immunogenicity makes it an ideal candidate for local immunotherapy. Recombinant human leukocyte interferon-α2 (rIFN-α2) has well-established immunomodulatory, antiproliferative, and antitumor effects; and relatively low levels of endogenous IFN-α have been observed within MF lesions. As a systemic therapy delivered via subcutaneous (SC) or intramuscular (IM) injection, rIFN-α2 has previously shown efficacy against MF. Due to high levels of toxicity associated with the systemic dosing required for improvement of disease, rIFN-α2 has had limited use in the treatment of MF. For these reasons, we sought to deliver rIFN-2 as a local immunotherapy, and herein describe two cases of MF successfully managed with intralesional injections of low-dose rIFN-α2. With limited reporting in the medical literature, intralesional injection of rIFN-α2 has shown efficacy, but with high frequency of associated systemic side effects. Towards a better tolerated, localized immunotherapy, we initiated treatment in two MF patients with low dose (0.5 MU) rIFN-α2 per injection that led to marked responses, and subsequent dosing to 1.0 MU ultimately led to complete resolution of the treated lesions without the generalized side effects observed with systemic administration of rIFN-α2. These cases suggest that low-dose intralesional rIFN-α2 may be an efficacious and well-tolerated local immunotherapy for early stage MF, providing a therapeutic option for the management of chronic, recalcitrant lesions.

摘要

蕈样肉芽肿(MF),最常见的皮肤 T 细胞淋巴瘤(CTCL)形式,其特征是恶性 CD4+皮肤归巢 T 细胞,驱动皮肤斑块、斑块和/或肿瘤的形成。MF 的已知免疫原性使其成为局部免疫治疗的理想候选者。重组人白细胞干扰素-α2(rIFN-α2)具有良好的免疫调节、抗增殖和抗肿瘤作用;并且在 MF 病变内观察到相对低水平的内源性 IFN-α。作为通过皮下(SC)或肌肉内(IM)注射给予的全身治疗,rIFN-α2 以前已显示对 MF 有效。由于与改善疾病所需的全身剂量相关的毒性水平高,rIFN-α2 在 MF 的治疗中使用有限。出于这些原因,我们试图将 rIFN-2 作为局部免疫疗法进行递送,并且在此描述了两例成功用低剂量 rIFN-α2 进行病变内注射治疗的 MF 病例。由于在医学文献中报告有限,rIFN-α2 的病变内注射已显示出疗效,但与相关的全身性副作用的高频率相关。为了实现更好耐受的局部免疫疗法,我们开始对两名 MF 患者用低剂量(0.5 MU)rIFN-α2 进行治疗,每次注射导致明显反应,随后增加剂量至 1.0 MU,最终导致治疗病变完全消退,而没有观察到全身性副作用与 rIFN-α2 的全身给药相关。这些病例表明,低剂量病变内 rIFN-α2 可能是早期 MF 的有效且耐受良好的局部免疫疗法,为管理慢性、难治性病变提供了一种治疗选择。

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