体外光分离置换治疗难治性皮肤移植物抗宿主病缓解率的Meta分析

摘要/Abstract

摘要： 目的系统性评价体外光分离置换（ECP）对于糖皮质激素（激素）抵抗性、激素依赖性以及不能耐受激素不良反应等难治性移植物抗宿主病（GVHD）的治疗效果，并详细分析比较皮肤GVHD的缓解情况。方法搜集ECP治疗GVHD的研究报道，提取相关数据，应用Stata 12.0软件进行Meta分析，进行缓解率的合并分析。结果共纳入22篇文献，总计787例难治性GVHD患者。Meta分析结果显示，急性GVHD的合并完全缓解率、总体缓解率分别为57%（95%CI：47% ~ 66%）、79%（71% ~ 86%）；慢性GVHD的合并完全缓解率、总体缓解率分别为27%（21% ~ 33%）、63%（58% ~ 69%）。皮肤急性GVHD的合并完全缓解率、总体缓解率分别为77%（71% ~ 82%）、87%（82% ~ 91%）；皮肤慢性GVHD的合并完全缓解率、总体缓解率分别为39%（30% ~ 48%）、70%（63% ~ 77%）。结论 ECP治疗可作为难治性GVHD患者的一种治疗手段，尤其对于皮肤GVHD患者治疗效果较为明显。

Abstract: Cui Jing, Wang Fei Department of Dermatology, Zhongda Hospital, Southeast University, Nanjing 210009, China Corresponding author: Wang Fei, Email: ffwangfei@163.com 【Abstract】 Objective To systematically analyze therapeutic effects of extracorporeal photopheresis （ECP） on refractory steroid?resistant, ?dependent or ?intolerant graft?versus?host disease （GVHD）, to compare remission rates of skin GVHD in detail. Methods Databases were searched for studies concerning remission rates of GVHD after the treatment with ECP, and relevant data were extracted and pooled by using meta?analysis with STATA 12.0 software. Results A total of 22 literatures were reviewed, including 787 patients with refractory GVHD. Meta?analysis showed that the pooled complete remission （CR） rate and overall remission （OR） rate were 57% （95% CI: 47% - 66%） and 79% （71% - 86%） respectively in patients with acute GVHD, 27% （21% - 33%） and 63% （58% - 69%） respectively in patients with chronic GVHD, 77% （71% - 82%） and 87% （82% - 91%） in patients with acute skin GVHD, as well as 39% （30% - 48%） and 70% （63% - 77%） in patients with chronic skin GVHD. Conclusion ECP is an effective therapy for refractory GVHD, especially for skin GVHD.

崔晶王飞. 体外光分离置换治疗难治性皮肤移植物抗宿主病缓解率的Meta分析[J]. 中华皮肤科杂志, 2017, 50(4): 286-290.doi:

Jing CUI fei wang. Remission rates in patients with refractory skin graft?versus?host disease treated with extracor?poreal photopheresis: a meta?analysis [J]. Chinese Journal of Dermatology, 2017, 50(4): 286-290.doi:

参考文献 41

［1］	刘萍, 张建中. 皮肤移植物抗宿主病［J］.中华皮肤科杂志, 2013, 46（10）: 764⁃767. DOI: 10.3760/cma.j.issn.0412⁃4030. 2013.10.029.
［2］	Schwartz J, Winters JL, Padmanabhan A, et al. Guidelines on the use of therapeutic apheresis in clinical practice⁃evidence⁃based approach from the Writing Committee of the American Society for Apheresis: the sixth special issue［J］. J Clin Apher, 2013, 28（3）: 145⁃284. DOI: 10.1002/jca.21276.
［3］	Winters JL. American Society for Apheresis guidelines on the use of apheresis in clinical practice: practical, concise, evidence⁃based recommendations for the apheresis practitioner［J］. J Clin Apher, 2014, 29（4）: 191⁃193. DOI: 10.1002/jca.21334.
［4］	Dall′Amico R, Montini G, Murer L, et al. Extracorporeal photo⁃chemotherapy after cardiac transplantation: a new therapeutic approach to allograft rejection［J］. Int J Artif Organs, 2000, 23（1）: 49⁃54.
［5］	张天嵩, 钟文昭, 李博. 实用循证医学方法学［M］. 长沙: 中南大学出版社, 2014: 349⁃352
［6］	Apisarnthanarax N, Donato M, Korbling M, et al. Extracorporeal photopheresis therapy in the management of steroid⁃refractory or steroid⁃dependent cutaneous chronic graft⁃versus⁃host disease after allogeneic stem cell transplantation: feasibility and results［J］. Bone Marrow Transplant, 2003, 31（6）: 459⁃465. DOI: 10.1038/sj.bmt.1703871.
［7］	Berger M, Pessolano R, Albiani R, et al. Extracorporeal photo⁃pheresis for steroid resistant graft versus host disease in pediatric patients: a pilot single institution report［J］. J Pediatr Hematol Oncol, 2007, 29（10）: 678⁃687. DOI: 10.1097/MPH. 0b013e31814d66f5.
［8］	Calore E, Calo A, Tridello G, et al. Extracorporeal photochemo⁃therapy may improve outcome in children with acute GVHD［J］. Bone Marrow Transplant, 2008, 42（6）: 421⁃425. DOI: 10.1038/bmt.2008.174.
［9］	Perotti C, Del Fante C, Tinelli C, et al. Extracorporeal photo⁃chemotherapy in graft⁃versus⁃host disease: a longitudinal study on factors influencing the response and survival in pediatric patients［J］. Transfusion, 2010, 50（6）: 1359⁃1369. DOI: 10.1111/j.1537⁃2995.2009.02577.x.
［10］	Couriel DR, Hosing C, Saliba R, et al. Extracorporeal photo⁃chemotherapy for the treatment of steroid⁃resistant chronic GVHD［J］. Blood, 2006, 107（8）: 3074⁃3080. DOI: 10.1182/blood⁃2005⁃09⁃3907.
［11］	Dignan FL, Aguilar S, Scarisbrick JJ, et al. Impact of extracor⁃poreal photopheresis on skin scores and quality of life in patients with steroid⁃refractory chronic GVHD［J］. Bone Marrow Transplant, 2014, 49（5）: 704⁃708. DOI: 10.1038/bmt.2014.21.
［12］	Ayyildiz E, Arslan O, Topcuoglu P, et al. The effect of extra⁃corporeal photoimmunotherapy （ECP） on serum TNF⁃a level in chronic graft versus host disease （GvHD）［J］. Transfus Apher Sci, 2007, 36（1）: 79⁃85. DOI: 10.1016/j.transci.2006.06.007.
［13］	Calore E, Marson P, Pillon M, et al. Treatment of acute graft⁃versus⁃host disease in childhood with extracorporeal photoche⁃motherapy/photopheresis: the padova experience［J］. Biol Blood Marrow Transplant, 2015, 21（11）: 1963⁃1972. DOI: 10.1016/j.bbmt.2015.07.007.
［14］	Foss FM, DiVenuti GM, Chin K, et al. Prospective study of extracorporeal photopheresis in steroid⁃refractory or steroid⁃resistant extensive chronic graft⁃versus⁃host disease: analysis of response and survival incorporating prognostic factors［J］. Bone Marrow Transplant, 2005, 35（12）: 1187⁃1193. DOI: 10.1038/sj.bmt.1704984.
［15］	Bertani G, Santoleri L, Ferri U, et al. Response of steroid⁃refractory chronic graft⁃versus⁃host disease to extracorporeal photopheresis correlates with the dose of CD3+ lymphocytes har⁃vested during early treatment cycles［J］. Transfusion, 2016, 56（2）: 505⁃510. DOI: 10.1111/trf.13369.
［16］	Gonzalez Vicent M, Ramirez M, Sevilla J, et al. Analysis of clinical outcome and survival in pediatric patients undergoing extracorporeal photopheresis for the treatment of steroid⁃refractory GVHD［J］. J Pediatr Hematol Oncol, 2010, 32（8）: 589⁃593. DOI: 10.1097/MPH.0b013e3181e7942d.
［17］	Gonzalez⁃Vicent M, Ramirez M, Perez A, et al. Extracorporeal photochemotherapy for steroid⁃refractory graft⁃versus⁃host disease in low⁃weight pediatric patients. Immunomodulatory effects and clinical outcome［J］. Haematologica, 2008, 93（8）: 1278⁃1280. DOI: 10.3324/haematol.12688.
［18］	Greinix HT, Knobler RM, Worel N, et al. The effect of intensified extracorporeal photochemotherapy on long⁃term survival in patients with severe acute graft⁃versus⁃host disease［J］. Haematologica, 2006, 91（3）: 405⁃408.
［19］	Halle P, Paillard C, D′Incan M, et al. Successful extracorporeal photochemotherapy for chronic graft⁃versus⁃host disease in pediatric patients［J］. J Hematother Stem Cell Res, 2002, 11（3）: 501⁃512. DOI: 10.1089/15258160260090960.
［20］	Jagasia M, Greinix H, Robin M, et al. Extracorporeal photo⁃pheresis versus anticytokine therapy as a second⁃line treatment for steroid⁃refractory acute GVHD: a multicenter comparative analysis［J］. Biol Blood Marrow Transplant, 2013, 19（7）: 1129⁃1133. DOI: 10.1016/j.bbmt.2013.04.018.
［21］	Kanold J, Merlin E, Halle P, et al. Photopheresis in pediatric graft⁃versus⁃host disease after allogeneic marrow transplantation: clinical practice guidelines based on field experience and review of the literature［J］. Transfusion, 2007, 47（12）: 2276⁃2289. DOI: 10.1111/j.1537⁃2995.2007.01469.x.
［22］	Merlin E, Paillard C, Rochette E, et al. Extracorporeal photo⁃chemotherapy as second⁃ or first⁃line therapy of acute GVHD?［J］. Bone Marrow Transplant, 2010, 45（5）: 963⁃965. DOI:10.1038/bmt.2009.271.
［23］	Messina C, Locatelli F, Lanino E, et al. Extracorporeal photo⁃chemotherapy for paediatric patients with graft⁃versus⁃host disease after haematopoietic stem cell transplantation［J］. Br J Haematol, 2003, 122（1）: 118⁃127.
［24］	Perfetti P, Carlier P, Strada P, et al. Extracorporeal photopheresis for the treatment of steroid refractory acute GVHD［J］. Bone Marrow Transplant, 2008, 42（9）: 609⁃617. DOI: 10.1038/bmt.2008.221.
［25］	Tsirigotis P, Kaloyannidis P, Papalexandri A, et al. Extracorporeal photopheresis in the treatment of chronic graft⁃versus⁃host disease. The Hellenic experience: a study by the Hellenic association of hematology［J］. Transfus Apher Sci, 2012, 46（2）: 173⁃180. DOI: 10.1016/j.transci.2011.09.001.
［26］	Rubegni P, Cuccia A, Sbano P, et al. Role of extracorporeal photochemotherapy in patients with refractory chronic graft⁃versus⁃host disease［J］. Br J Haematol, 2005, 130（2）: 271⁃275. DOI:10.1111/j.1365⁃2141.2005.05586.x.
［27］	Salvaneschi L, Perotti C, Zecca M, et al. Extracorporeal photo⁃chemotherapy for treatment of acute and chronic GVHD in childhood［J］. Transfusion, 2001, 41（10）: 1299⁃1305.
［28］	Johnson ML, Farmer ER. Graft⁃versus⁃host reactions in dermatology［J］. J Am Acad Dermatol, 1998, 38（3）: 369⁃392; quiz 393⁃396. DOI: 10.1016/S0190⁃9622（98）70495⁃5.
［29］	Peñas PF, Fernández⁃Herrera J, García⁃Diez A. Dermatologic treatment of cutaneous graft versus host disease［J］. Am J Clin Dermatol, 2004, 5（6）: 403⁃416. DOI: 10.2165/00128071⁃200405060⁃00005.
［30］	Peñas PF, Zaman S. Many faces of graft⁃versus⁃host disease［J］. Australas J Dermatol, 2010, 51（1）: 1⁃10; quiz 11. DOI: 10.1111/j.1440⁃0960.2009.00577.x.
［31］	Ballester⁃Sánchez R, Navarro⁃Mira M, Sanz⁃Caballer J, et al. Review of Cutaneous Graft⁃vs⁃Host Disease［J］. Actas Dermosifiliogr, 2016, 107（3）: 183⁃193. DOI: 10.1016/j.ad.2015. 10.003.
［32］	Kuzmina Z, Stroncek D, Pavletic SZ. Extracorporeal photo⁃pheresis as a therapy for autoimmune diseases［J］. J Clin Apher, 2015, 30（4）: 224⁃237. DOI: 10.1002/jca.21367.
［33］	Pileri A, Raone B, Raboni R, et al. Generalized morphea suc⁃cessfully treated with extracorporeal photochemotherapy （ECP）［J］. Dermatol Online J, 2014, 20（1）: 21258.
［34］	Prasad VK, Kernan NA, Heller G, et al. DNA typing for HLA⁃A and HLA⁃B identifies disparities between patients and unrelated donors matched by HLA⁃A and HLA⁃B serology and HLA⁃DRB1［J］. Blood, 1999, 93（1）: 399⁃409.
［35］	Ferrara GB, Bacigalupo A, Lamparelli T, et al. Bone marrow transplantation from unrelated donors: the impact of mismatches with substitutions at position 116 of the human leukocyte antigen class I heavy chain［J］. Blood, 2001, 98（10）: 3150⁃3155. DOI: 10.1182/blood.V98.10.3150.
［36］	Flomenberg N, Baxter⁃Lowe LA, Confer D, et al. Impact of HLA class I and class II high⁃resolution matching on outcomes of unrelated donor bone marrow transplantation: HLA⁃C mismatching is associated with a strong adverse effect on transplantation outcome［J］. Blood, 2004, 104（7）: 1923⁃1930. DOI: 10.1182/blood⁃2004⁃03⁃0803.
［37］	Bross DS, Tutschka PJ, Farmer ER, et al. Predictive factors for acute graft⁃versus⁃host disease in patients transplanted with HLA⁃identical bone marrow［J］. Blood, 1984, 63（6）: 1265⁃1270.
［38］	Kollman C, Howe CW, Anasetti C, et al. Donor characteristics as risk factors in recipients after transplantation of bone marrow from unrelated donors: the effect of donor age［J］. Blood, 2001, 98（7）: 2043⁃2051. DOI: 10.1182/blood.V98.7.2043.
［39］	Anasetti C, Logan BR, Lee SJ, et al. Peripheral⁃blood stem cells versus bone marrow from unrelated donors［J］. N Engl J Med, 2012, 367（16）: 1487⁃1496. DOI: 10.1056/NEJMoa1203517.
［40］	Jagasia M, Arora M, Flowers ME, et al. Risk factors for acute GVHD and survival after hematopoietic cell transplantation［J］. Blood, 2012, 119（1）: 296⁃307. DOI: 10.1182/blood⁃2011⁃06⁃364265.
［41］	Flowers ME, Inamoto Y, Carpenter PA, et al. Comparative analysis of risk factors for acute graft⁃versus⁃host disease and for chronic graft⁃versus⁃host disease according to National Institutes of Health consensus criteria［J］. Blood, 2011, 117（11）: 3214⁃3219. DOI: 10.1182/blood⁃2010⁃08⁃302109.