NCCN T细胞淋巴瘤临床实践指南2017.2版（5）
目录
T细胞幼淋巴细胞白血病（TPLL）
TPLL-1
诊断与检查
a.典型的免疫表型：CD1a-、TdT-、CD2+、sCD3+/-、cCD3+/-、CD5+、CD7++、CD52++、TCRαβ+、CD4+/CD8-(65%)、CD4+/CD8+(21%)、CD4-/CD8+(13%)。
b.少数患者可无症状且呈各异的缓慢病程。在这些合适的患者中选用观察和期待疗法是一项合理的治疗选择。
TPLL-2
有症状TPLL的治疗
c.见“治疗参考文献”（TPLL-A)。
d.根据资料显示，阿仑单抗皮下给药方式可降低药物活性，T-PLL患者应优选静脉给药方式而非皮下给药（Dearden CE, Khot A, Else M, et al.Alemtuzumab therapy in T-cell prolymphocytic leukaemia:Comparing efficacy in a series treated intravenously and a study piloting the subcutaneous route.Blood 2011;118:5799-5802）。
e.当采用阿仑单抗±嘌呤类似物治疗时，建议检测CMV再激活情况；针对疱疹病毒和卡氏肺囊虫肺炎行抗感染预防性治疗。
TPLL-A
治疗参考文献：
阿仑单抗
Dearden CE, Matutes E, Cazin B, et al. High remission rate in T-cell prolymphocytic leukemia with CAMPATH-1H. Blood 2001;98:1721-1726. Keating MJ, Cazin B, Coutre S, et al. Campath-1H treatment of T-cell prolymphocytic leukemia in patients for whom at least one prior chemotherapy regimen has failed.J Clin Oncol 2002;20:205-213.
Dearden CE, Khot A, Else M, et al. Alemtuzumab therapy in T-cell prolymphocytic leukaemia: Comparing efcacy in a series treated intravenously and a study piloting the subcutaneous route. Blood 2011;118:5799-5802.
阿仑单抗+喷司他丁
Ravandi F, Aribi A, O'Brien S, et al. Phase II study of alemtuzumab in combination with pentostatin in patients with T-cell neoplasms. J Clin Oncol 2009;27:5425-5430
FMC（氟达拉滨、米托蒽醌、环磷酰胺）继以阿仑单抗
Hopfnger G, Busch R, Pflug N, et al. Sequential chemoimmunotherapy of fludarabine, mitoxantrone, and cyclophosphamide induction followed by alemtuzumab consolidation is effective in T-cell prolymphocytic leukemia. Cancer 2013;119:2258-2267.
异基因干细胞移植
Castagna L, Nozza A, Bertuzzi A, Siracusano L, Timofeeva I, Santoro A. Allogeneic peripheral blood stem cell transplantation with reduced intensity conditioning in primary refractory prolymphocytic leukemia: graft-versus-leukemia effect without graft-versus-host disease. Bone Marrow Transplant 2001;28:1155-1156.
Kalaycio ME, Kukreja M, Woolfrey AE, et al. Allogeneic hematopoietic cell transplant for prolymphocytic leukemia. Biol Blood Marrow Transplant. 2010;16:543-547.
Murase K, Matsunaga T, Sato T, et al. Allogeneic bone marrow transplantation in a patient with T-prolymphocytic leukemia with small-intestinal involvement. Int J Clin Oncol 2003;8:391-394.
Wiktor-Jedrzejczak W, Dearden C, de Wreede L, et al. Hematopoietic stem cell transplantation in T-prolymphocytic leukemia: A retrospective study from the European Group for Blood and Marrow Transplantation and the Royal Marsden Consortium. Leukemia 2012;26:972-972.
结外NK/T细胞淋巴瘤（鼻型）（NKTL）
NKTL-1
诊断与检查
a.首选在专科治疗中心接受治疗。
b.诊断活检中坏死很常见，而且很可能会延误诊断。活检样本应当包括病变的边缘，以便增加包括有活性的组织的机会。即便是在没有明显累及的区域，多次鼻咽活检也有可能是有效的检查方法。
c.见“免疫分型/基因检测在成熟B细胞和T/NK细胞淋巴瘤鉴别诊断中的应用”（见《B细胞淋巴瘤指南》)。
d.典型的NK细胞免疫表型：CD20-、CD2+、cCD3ε+ (表面CD3-)、CD4-、CD5-、CD7-/+、CD8-/+、CD43+、CD45RO+、CD56+、T细胞受体(TCR)αβ-、TCRγδ-、EBV- EBER+。TCR和Ig基因通常是生殖细胞系（NK细胞谱系）。通常表达细胞毒性颗粒蛋白（TIA1、穿孔素、颗粒酶B）。典型的T细胞免疫表型：CD2+、sCD3+、cCD3e+、CD4,5,7,8变异型、CD56+/-、EBV-EBER+、TCRαβ或γδ+、细胞毒性颗粒蛋白+。TCR基因通常呈克隆重排。
e.如果结果为阴性，则提示应进行病理鉴别诊断。
f.骨髓穿刺涂片—淋巴聚集罕见，如果EBER-1阳性，则认为受累，可能存在血球吞噬现象。
g.见NK细胞淋巴瘤预后指数（PINK）（NKTL-A）。
h.EBV病毒载量是重要的诊断，并可能用于疾病监测。结果阳性符合鼻型NK/T细胞淋巴瘤。EBV病毒血症不能正常化应被视为疾病持续的间接证据。
NKTL-2
不同分期患者的诱导治疗
a.首选在专科治疗中心接受治疗。
i.在少见的IE期鼻外型病变的情况下，可考虑行单独皮肤病灶的IFRT。
j.见“推荐治疗方案”（NKTL-B）。
NKTL-3
放疗后评估与附加治疗
a.首选在专科治疗中心接受治疗。
k.见“非霍奇金淋巴瘤卢加诺缓解标准”（LYMP-B）。
l.包括耳鼻喉科评估结果阴性。
m.如果有匹配的供者，首选异基因移植。
n.联合化疗方案（以培门冬酶为基础），见“推荐治疗方案”(NKTL-B)。
o.没有明确的数据表明同种异体或自体同源的HSCT可作为首选，治疗应个体化。
NKTL-A
危险因素与预后指数
注解：
a.Kim SJ, Yoon DH, Jaccard A, et al. A prognostic index for natural killer cell lymphoma after non-anthracycline-based treatment: a multicentre, retrospective analysis. Lancet Oncol 2016;17:389-400.
NKTL-B（2/1）
推荐治疗方案
a.见方案的的参考文献（NKTL-B 2/2）。
b.首选以培门冬酶为基础的治疗方案。然而，尚无数据表明某治疗方案优于其他方案，故应根据患者的耐受性及合并症给予个体化治疗。GELOX方案可用于不能耐受高强度化疗的患者。
NKTL-B(2/2)
推荐治疗方案的参考文献
联合化疗方案
Yamaguchi M, Kwong YL, Kim WS, et al. Phase II study of SMILE chemotherapy for newly diagnosed stage IV, relapsed, or refractory extranodal natural killer (NK)/Tcell lymphoma, nasal type: The NK-Cell Tumor Study Group Study. J Clin Oncol 2011;29:4410-4416. Jaccard A, Gachard N, Marin B, et al. Efcacy of L-asparaginase with methotrexate and dexamethasone (AspaMetDex regimen) in patients with refractory or relapsing extranodal NK/T-cell lymphoma, a phase 2 study. Blood 2011;117:1834-1839.
Gao Y, et al. Efcacy and Safety Of Pegaspargase With Gemcitabine and Oxaliplatin In Patients With Treatment -naïve, Refractory Extranodal Natural Killer/T-Cell Lymphoma: A Single-Centre Experience. Blood 2013;122:Abstract 642.
同步放化疗
Yamaguchi M, Tobinai K, Oguchi M, et al. Concurrent chemoradiotherapy for localized nasal natural killer/T-cell lymphoma: an updated analysis of the Japan clinical oncology group study JCOG0211. J Clin Oncol 2012;30:4044-4046.
Kim SJ, Kim K, Kim BS, et al. Phase II trial of concurrent radiation and weekly cisplatin followed by VIPD chemotherapy in newly diagnosed, stage IE to IIE, nasal, extranodal NK/T-cell lymphoma: Consortium for Improving Survival of Lymphoma study. J Clin Oncol 2009;27:6027-6032.
Yamaguchi M, Tobinai K, Oguchi M, et al.Phase I/II study of concurrent chemoradiotherapy for localized nasal natural killer/T-cell lymphoma: Japan Clinical Oncology Group Study JCOG0211. J Clin Oncol 2009;27:5594-5600.
Yamaguchi M, Suzuki R, Oguchi N, et al. Outcomes and prognostic factors of radiotherapy with dexamethasone, etoposide, ifosfamide, and carboplatin (RT-DeVIC) for newly diagnosed, localized extranodal NK/T-cell lymphoma, nasal type (ENKL): A cooperative study in Japan [abstract]. J Clin Oncol 2016;34: Abstract 7541.
三明治放疗
Tse E, Kwong YL. How I treat NK/T-cell lymphomas. Blood 2013;121:4997-5005.
Bi XW et al. Radiotherapy and PGEMOX/GELOX regimen improved prognosis in elderly patients with early-stage extranodal NK/T-cell lymphoma. Ann Hematol 2015;94:1525-1533.
单独放疗
Huang MJ, Jiang Y, Liu WP, et al. Early or up-front radiotherapy improved survival of localized extranodal NK/T-cell lymphoma, nasal-type in the upper aerodigestive tract. Int J Radiat Oncol Biol Phys 2008;70:166-174.
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