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Quản lý Lymphoma T-Cell Da Giai Đoạn Đầu Kháng Trị
Tóm tắt
Lymphoma T-Cell da (CTCL) là một nhóm heterogene của các loại lymphoma không Hodgkin, chủ yếu biểu hiện ở da. Mycosis fungoides được công nhận là loại CTCL phổ biến nhất. Bệnh nhân mắc CTCL giai đoạn đầu thường có quá trình bệnh lành tính và mãn tính. Tuy nhiên, mặc dù có nhiều lựa chọn điều trị cho CTCL giai đoạn đầu, không phải tất cả bệnh nhân đều đáp ứng với các liệu pháp cá nhân, dẫn đến tình trạng bệnh da kháng trị theo thời gian. CTCL giai đoạn đầu kháng trị đặt ra một thách thức điều trị quan trọng, vì một trong những mục tiêu điều trị chính là giữ cho bệnh khu trú ở da, từ đó ngăn ngừa tiến triển của bệnh. Rất nhiều nghiên cứu hiện tại tập trung vào việc đánh giá các liệu pháp hướng vào da đã có sẵn và các chất điều biến đáp ứng sinh học cùng với các phác đồ kết hợp của chúng, chẳng hạn như sự kết hợp của psoralen và UVA (PUVA) với interferon-α hoặc retinoids. Những phát triển mới gần đây bao gồm bexarotene đường uống, một retinoid chọn lọc thụ thể retinoid X có hoạt tính ở tất cả các giai đoạn của CTCL và đã cho thấy có hiệu quả ở những bệnh nhân mắc bệnh giai đoạn đầu kháng trị cũng như giai đoạn tiến triển. Tương tự, dạng gel bôi của bexarotene đã chứng minh là một lựa chọn điều trị quan trọng cho bệnh nhân có tổn thương kháng trị hoặc tái phát. Bexarotene đường uống và bexarotene bôi đã được FDA Hoa Kỳ chấp thuận để điều trị CTCL kháng trị. Hóa trị toàn thân thường được dành riêng cho CTCL giai đoạn tiến triển và thường không được khuyến cáo cho bệnh giai đoạn sớm, giới hạn ở da. Tuy nhiên, các nghiên cứu thăm dò gần đây cho thấy methotrexate liều thấp có thể là một liệu pháp được dung nạp tốt chung ở một nhóm bệnh nhân có CTCL giai đoạn đầu kháng trị, như doxorubicin liposome pegylated, hiện đang được nghiên cứu trong bối cảnh lâm sàng cụ thể này. Một liệu pháp gần đây khác được FDA phê duyệt là độc tố fusion interleukin-2 denileukin diftitox, hiện đã được khẳng định đóng một vai trò trong điều trị CTCL kháng trị, bao gồm bệnh đĩa rộng giai đoạn đầu. Giá trị của các tác nhân khác, chẳng hạn như tazarotene bôi, methotrexate bôi và imiquimod bôi, cùng với các phương pháp điều chỉnh miễn dịch mới bao gồm các kháng thể đơn dòng, vẫn cần được đánh giá cho CTCL giai đoạn đầu kháng trị.
Từ khóa
#Lymphoma T-Cell #CTCL #mycosis fungoides #điều trị kháng trị #bexarotene #hóa trị toàn thân #liệu pháp miễn dịchTài liệu tham khảo
Muche JM, Gellrich S, Sterry W. Treatment of cutaneous T-cell lymphomas. Semin Cutan Med Surg. 2000; 19: 142–8
Willemze R, Kerl H, Sterry W, et al. EORTC classification for primary cutaneous lymphomas: a proposal from the Cutaneous Lymphoma Study Group of the European Organization for Research and Treatment of Cancer. Blood. 1997; 90: 354–71
Jaffe ES, Harris NL, Stein H, et al. World Health Organization classification of tumours. Pathology and genetics of tumours of haematopoietic and lymphoid tissues. Lyon: IARC Press, 2001
Willemze R, Jaffe ES, Burg G, et al. WHO-EORTC classification for cutaneous lymphomas. Blood. 2005; 105: 3768–85
Smith BD, Wilson LD. Management of mycosis fungoides. Part 1: diagnosis, staging, and prognosis. Oncology (Huntingt). 2003; 17: 1281–8
Burg G, Dummer R, Haeffner A, et al. From inflammation to neoplasia: mycosis fungoides evolves from reactive inflammatory conditions (lymphoid infiltrates) transforming into neoplastic plaques and tumors [comment]. Arch Dermatol. 2001; 137: 949–52
Kempf W, Kettelhack N, Duvic M, et al. Topical and systemic retinoid therapy for cutaneous T-cell lymphoma. Hematol Oncol Clin North Am. 2003; 17: 1405–19
Dummer R, Michie SA, Kell D, et al. Expression of bel-2 protein and Ki-67 nuclear proliferation antigen in benign and malignant cutaneous T-cell infiltrates. J Cutan Pathol. 1995; 22: 11–7
Weinstock MA, Gardstein B. Twenty-year trends in the reported incidence of mycosis fungoides and associated mortality. Am J Public Health. 1999; 89: 1240–4
Demierre MF, Foss FM, Koh HK. Proceedings of the International Consensus Conference on Cutaneous T-Cell Lymphoma (CTCL) Treatment Recommendations. Boston, Massachusetts, Oct. 1 and 2, 1994. J Am Acad Dermatol. 1997; 36: 460–6
Bunn Jr PA, Lamberg SI. Report of the Committee on Staging and Classification of Cutaneous T-Cell Lymphomas. Cancer Treat Rep. 1979; 63: 725–8
Knobler E. Current management strategies for cutaneous T-cell lymphoma. Clin Dermatol. 2004; 22: 197–208
Sausville EA, Eddy JL, Makuch RW, et al. Histopathologic staging at initial diagnosis of mycosis fungoides and the Sezary syndrome: definition of three distinctive prognostic groups. Ann Intern Med. 1988; 109: 372–82
Foss F. Mycosis fungoides and the Sezary syndrome. Curr Opin Oncol. 2004; 16: 421–8
Zackheim HS, Amin S, Kashani-Sabet M, et al. Prognosis in cutaneous T-cell lymphoma by skin stage: long-term survival in 489 patients. J Am Acad Dermatol. 1999; 40: 418–25
van Doom R, van Haselen CW, van Voorst Vader PC, et al. Mycosis fungoides: disease evolution and prognosis of 309 Dutch patients. Arch Dermatol. 2001; 136: 504–10
Kim YH, Chow S, Varghese A, et al. Clinical characteristics and long-term outcome of patients with generalized patch and/or plaque (T2) mycosis fungoides. Arch Dermatol. 1999; 135: 26–32
Kaye FJ, Bunn PA, Steinberg SM, et al. A randomized trial comparing combination electron-beam radiation and chemotherapy with topical therapy in the initial treatment of mycosis fungoides. N Engl J Med. 1989; 321: 1784–90
Dummer R, Haffner AC, Hess M, et al. A rational approach to the therapy of cutaneous T-cell lymphomas. Onkologie. 1996; 19: 226–30
Zackheim HS, Kashani-Sabet M, Amin S. Topical corticosteroids for mycosis fungoides: experience in 79 patients. Arch Dermatol. 1998; 134: 949–54
Zackheim HS. Treatment of patch-stage mycosis fungoides with topical corticosteroids. Dermatol Ther. 2003; 16: 283–7
Dummer R, Kempf W, Hess Schmid M, et al. Therapy of cutaneous lymphoma: current practice and future developments. Onkologie. 2003; 26: 366–72
Apisamthanarax N, Talpur R, Duvic M. Treatment of cutaneous T cell lymphoma. Am J Clin Dermatol. 2002; 3: 193–215
Smith BD, Wilson LD. Management of mycosis fungoides. Part 2: treatment. Oncology (Huntingt). 2003; 17: 1419–28
Kim YH, Martinez G, Varghese A, et al. Topical nitrogen mustard in the management of mycosis fungoides: update of the Stanford experience. Arch Dermatol. 2003; 139: 165–73
Zackheim HS, Epstein Jr EH, Crain WR. Topical carmustine (BCNU) for cutaneous T cell lymphoma: a 15-year experience in 143 patients. J Am Acad Dermatol. 1990; 22: 802–10
Zackheim HS. Topical carmustine (BCNU) in the treatment of mycosis fungoides. Dermatol Ther. 2003; 16: 299–302
Zhang C, Duvic M. Retinoids: therapeutic applications and mechanisms of action in cutaneous T-cell lymphoma. Dermatol Ther. 2003; 16: 322–30
Zhang C, Hazarika P, Ni X, et al. Induction of apoptosis by bexarotene in cutaneous T-cell lymphoma cells: relevance to mechanism of therapeutic action. Clin Cancer Res. 2002; 8: 1234–40
Breneman D, Duvic M, Kuzel T, et al. Phase 1 and 2 trial of bexarotene gel for skin-directed treatment of patients with cutaneous T-cell lymphoma. Arch Dermatol. 2002; 138: 325–32
Heald P, Mehlmauer M, Martin AG, et al. Topical bexarotene therapy for patients with refractory or persistent early-stage cutaneous T-cell lymphoma: results of the phase III clinical trial. J Am Acad Dermatol. 2003; 49: 801–15
Apisarnlhanarax N, Talpur R, Ward S, et al. Tazarotene 0.1% gel for refractory mycosis fungoides lesions: an open-label pilot study. J Am Acad Dermatol. 2004; 50: 600–7
Demierre MF, Vachon L, Ho V, et al. Phase 1/2 pilot study of methotrexate-laurocapram topical gel for the treatment of patients with early-stage mycosis fungoides. Arch Dermatol. 2003; 139: 624–8
Dummer R, Urosevic M, Kempf W, et al. Imiquimod induces complete clearance of a PUVA-resistant plaque in mycosis fungoides. Dermatology. 2003; 207: 116–8
Deeths MJ, Chapman JT, Dellavalle RP, et al. Treatment of patch and plaque stage mycosis fungoides with imiquimod 5% cream. J Am Acad Dermatol. 2005; 52: 275–80
Baron ED, Stevens SR. Phototherapy for cutaneous T-cell lymphoma. Dermatol Ther. 2003; 16: 303–10
Girardi M, Knobler R, Edelson R. Selective immunotherapy through extracorporeal photochemotherapy: yesterday, today, and tomorrow. Hematol Oncol Clin N Am. 2003; 17: 1391–403
Zic JA. The treatment of cutaneous T-cell lymphoma with photopheresis. Dermatol Ther. 2003; 16: 337–46
Krueger JG, Wolfe JT, Nabeya RT, et al. Successful ultraviolet B treatment of psoriasis is accompanied by a reversal of keratinocyte pathology and by selective depletion of intraepidermal T cells. J Exp Med. 1995; 182: 2057–68
Herrmann JJ, Roenigk Jr HH, Honigsmann H. Ultraviolet radiation for treatment of cutaneous T-cell lymphoma. Hematol Oncol Clin N Am. 1995; 9: 1077–88
Ramsay DL, Lish KM, Yalowitz CB, et al. Ultraviolet-B phototherapy for early-stage cutaneous T-cell lymphoma. Arch Dermatol. 1992; 128: 931–3
Resnik KS, Vonderheid EC. Home UV phototherapy of early mycosis fungoides: long-term follow-up observations in thirty-one patients. J Am Acad Dermatol. 1993; 29: 73–7
Hofer A, Cerroni L, Kerl H, et al. Narrowband (311-nm) UV-B therapy for small plaque parapsoriasis and early-stage mycosis fungoides. Arch Dermatol. 1999; 135: 1377–80
Clark C, Dawe RS, Evans AT, et al. Narrowband TL-01 phototherapy for patch-stage mycosis fungoides. Arch Dermatol. 2001; 136: 748–52
Diederen PV, van Weelden H, Sanders CJ, et al. Narrowband UVB and psoralen-UVA in the treatment of early-stage mycosis fungoides: a retrospective study. J Am Acad Dermatol. 2003; 48: 215–9
Herrmann JJ, Roenigk HH, Hurria A, et al. Treatment of mycosis fungoides with photochemotherapy (PUVA): long-term follow-up. J Am Acad Dermatol. 1995; 33: 234–42
Mostow EN, Neckel SI, Oberhelman L, et al. Complete remissions in psoralen and UV-A (PUVA)-refractory mycosis fungoides-type cutaneous T-cell lymphoma with combined interferon-alfa and PUVA. Arch Dermatol. 1993; 129: 747–52
Wolf P, Fink-Puches R, Cerroni L, et al. Photodynamic therapy for mycosis fungoides after topical photosensitization with 5-aminolevulinic acid. J Am Acad Dermatol. 1994; 31: 678–80
Leman JA, Dick DC, Morton CA. Topical 5-ALA photodynamic therapy for the treatment of cutaneous T-cell lymphoma. Clin Exp Dermatol. 2002; 27: 516–8
Yoo EK, Rook AH, Elenitsas R, et al. Apoptosis induction of ultraviolet light A and photochemotherapy in cutaneous T-cell lymphoma: relevance to mechanism of therapeutic action. J Invest Dermatol. 1996; 107: 235–42
Jones GW, Hoppe RT, Glatstein E. Electron beam treatment for cutaneous T-cell lymphoma. Hematol Oncol Clin N Am. 1995; 9: 1057–76
Chinn DM, Chow S, Kim YH, et al. Total skin electron beam therapy with or without adjuvant topical nitrogen mustard or nitrogen mustard alone as initial treatment of T2 and T3 mycosis fungoides. Int J Radial Oncol Biol Phys. 1999; 43: 951–8
Hoppe RT. Mycosis fungoides: radiation therapy. Dermatol Ther. 2003; 16: 347–54
Jones GW, Kacinski BM, Wilson LD, et al. Total skin electron radiation in the management of mycosis fungoides: consensus of the European Organization for Research and Treatment of Cancer (EORTC) Cutaneous Lymphoma Project Group. J Am Acad Dermatol. 2002; 47: 364–70
Dummer R. Immunomodulators in the treatment of cutaneous lymphomas. Expert Opin Biol Ther. 2002; 2: 279–86
Rook AH, Kuzel TM, Olsen EA. Cytokine therapy of cutaneous T-cell lymphoma: interferons, interleukin-12, and interleukin-2. Hematol Oncol Clin N Am. 2003; 17: 1435–48
Rook AH, McGinnis KS, Richardson SK, et al. The use of cytokines, fusion proteins and antibodies to treat cutaneous T-cell lymphoma. Dermatol Ther. 2003; 16: 331–6
Jumbou O, N’Guyen JM, Tessier MH, et al. Long-term follow-up in 51 patients with mycosis fungoides and Sezary syndrome treated by interferon-alfa. Br J Dermatol. 1999; 140: 427–31
Olsen EA. Interferon in the treatment of cutaneous T-cell lymphoma. Dermatol Ther. 2003; 16: 311–21
Olsen EA, Bunn PA. Interferon in the treatment of cutaneous T-cell lymphoma. Hematol Oncol Clin N Am. 1995; 9: 1089–107
Lundin J, Osterborg A. Therapy for mycosis fungoides. Curr Treat Options Oncol. 2004; 5: 203–14
Thomsen K, Hammar H, Molin L, et al. Retinoids plus PUVA (RePUVA) and PUVA in mycosis fungoides, plaque stage: a report from the Scandinavian Mycosis Fungoides Group. Acta Derm Venereol. 1989; 69: 536–8
Duvic M, Hymes K, Heald P, et al. Bexarotene is effective and safe for treatment of refractory advanced-stage cutaneous T-cell lymphoma: multinational phase II–III trial results. J Clin Oncol. 2001; 19: 2456–71
Duvic M, Martin AG, Kim Y, et al. Phase 2 and 3 clinical trial of oral bexarotene (Targretin capsules) for the treatment of refractory or persistent early-stage cutaneous T-cell lymphoma. Arch Dermatol. 2001; 137: 581–93
Talpur R, Ward S, Apisarnthanarax N, et al. Optimizing bexarotene therapy for cutaneous T-cell lymphoma. J Am Acad Dermatol. 2002; 47: 672–84
Rook AH, Wood GS, Yoo EK, et al. Interleukin-12 therapy of cutaneous T-cell lymphoma induces lesion regression and cytotoxic T-cell responses. Blood. 1999; 94: 902–8
Rook AH, Zaki MH, Wysocka M, et al. The role for interleukin-12 therapy of cutaneous T cell lymphoma. Ann N Y Acad Sci. 2001; 941: 177–84
Lenihan DJ, Alencar AJ, Yang D, et al. Cardiac toxicity of alemtuzumab in patients with mycosis fungoides/Sezary syndrome. Blood. 2004; 104: 655–8
Kuzel TM. Systemic chemotherapy for the treatment of mycosis fungoides and Sezary syndrome. Dermatol Ther. 2003; 16: 355–61
Zinzani P, Baliva G, Magagnoli M, et al. Gemcitabine treatment in pretreated cutaneous T-cell lymphoma: experience in 44 patients. J Clin Oncol. 2001; 18: 2603–6
Kurzrock R, Pilat S, Duvic M. Pentostatin therapy of T-cell lymphomas with cutaneous manifestations. J Clin Oncol. 1999; 17: 3117–21
Foss F. Activity of pentostatin (Nipent) in cutaneous T-cell lymphoma: single-agent and combination studies. Semin Oncol. 2001; 27: 58–63
Quaglino P, Fierro MT, Rossotto GL, et al. Treatment of advanced mycosis fungoides/Sezary syndrome with fludarabine and potential adjunctive benefit to subsequent extracorporeal photochemotherapy. Br J Dermatol. 2004; 150: 327–36
Foss FM, Ihde DC, Linnoila IR, et al. Phase II trial of fludarabine phosphate and interferon alfa-2a in advanced mycosis fungoides/Sezary syndrome. J Clin Oncol. 1994; 12: 2051–9
Fung MA, Murphy MJ, Hoss DM, et al. Practical evaluation and management of cutaneous lymphoma. J Am Acad Dermatol. 2002; 46: 325–57
Aviles A, Neri N, Fernandez R, et al. Nasal NK/T-cell lymphoma with disseminated disease treated with aggressive combined therapy. Med Oncol. 2003; 20: 13–7
Kuzel TM, Junghans R, Foss FM. Novel agents for cutaneous T-cell lymphoma. Hematol Oncol Clin N Am. 2003; 17: 1459–66
Zackheim HS, Kashani-Sabet M, Hwang ST. Low-dose methotrexate to treat erythrodermic cutaneous T-cell lymphoma: results in twenty-nine patients. J Am Acad Dermatol. 1996; 34: 626–31
Zackheim HS, Kashani-Sabet M, McMillan A. Low-dose methotrexate to treat mycosis fungoides: a retrospective study in 69 patients. J Am Acad Dermatol. 2003; 49: 873–8
Sarris AH, Phan A, Duvic M, et al. Trimetrexate in relapsed T-cell lymphoma with skin involvement. J Clin Oncol. 2002; 20: 2876–80
Wollina U, Graefe T, Katie K. Treatment of relapsing or recalcitrant cutaneous T-cell lymphoma with pegylated liposomal doxorubicin. J Am Acad Dermatol. 2001; 42: 40–6
Wollina U, Graefe T, Kaatz M. Pegylated doxorubicin for primary cutaneous T-cell lymphoma: a report on ten patients with follow-up. J Cancer Res Clin Oncol. 2001; 127: 128–34
Wollina U, Dummer R, Brockmeyer NH, et al. Multicenter study of pegylated liposomal doxorubicin in patients with cutaneous T-cell lymphoma. Cancer. 2003; 98: 993–1001
Foss FM, Waldmann TA. Interleukin-2 receptor-directed therapies for cutaneous lymphomas. Hematol Oncol Clin N Am. 2003; 17: 1449–58
Olsen E, Duvic M, Frankel A, et al. Pivotal phase III trial of two dose levels of denileukin diftitox for the treatment of cutaneous T-cell lymphoma. J Clin Oncol. 2001; 19: 376–88
Foss FM, Bacha P, Osann KE, et al. Biological correlates of acute hypersensitivity events with DAB(389)IL-2 (denileukin diftitox, ONTAK) in cutaneous T-cell lymphoma: decreased frequency and severity with steroid premedication. Clin Lymphoma. 2001; 1: 298–302
Gorgun G, Foss F. Immunomodulatory effects of RXR rexinoids: modulation of high-affinity IL-2R expression enhances susceptibility to denileukin diftitox. Blood. 2002; 100: 1399–403
Foss F, Demierre MF, Divenuti G. A phase-1 trial of bexarotene and denileukin diftitox in patients with relapsed or refractory cutaneous T-cell lymphoma. Blood. 2005; 106: 454–7
Duvic M, Apisarnthanarax N, Cohen DS, et al. Analysis of long-term outcomes of combined modality therapy for cutaneous T-cell lymphoma. J Am Acad Dermatol. 2003; 49: 35–49
Kuzel TM, Roenigk Jr HH, Samuelson E, et al. Effectiveness of interferon alfa-2a combined with phototherapy for mycosis fungoides and the Sezary syndrome. J Clin Oncol. 1995; 13: 257–63
Stadler R, Otte HG, Luger T, et al. Prospective randomized multicenter clinical trial on the use of interferon-2a plus acitretin versus interferon-2a plus PUVA in patients with cutaneous T-cell lymphoma stages I and II. Blood. 1998; 92: 3578–81
Huber MA, Kunzi-Rapp K, Staib G, et al. Management of refractory early-stage cutaneous T-cell lymphoma (mycosis fungoides) with a combination of oral bexarotene and psoralen plus ultraviolet A bath therapy. J Am Acad Dermatol. 2004; 50: 475–6
Singh F, Lebwohl MG. Cutaneous T-cell lymphoma treatment using bexarotene and PUVA: a case series. J Am Acad Dermatol. 2004; 51: 570–3