霍奇金淋巴瘤

患有早期霍奇金淋巴瘤 (HL) 的患者根据不存在或存在危险因素，分类为预后良好或不良。不同研究组用于区分预后良好和不良的特异性危险因素稍有不同，由德国霍奇金疾病研究组 (German Hodgkin Study Group) 所定义的危险因素较为常用，包括累及 3 个及以上淋巴结区域、红细胞沉降率 (ESR) 升高、纵膈肿块巨大和结外疾病。[28]German Hodgkin Study Group. Disease stages and risk factors. http://en.ghsg.org (last accessed 21 September 2017).http://en.ghsg.org/disease-stages

早期疾病的首选疗法为综合治疗，包括联合化疗（通常采用 ABVD [多柔比星、博来霉素、长春花碱和达卡巴嗪]），然后对受累区域进行放射疗法。[29]Laskar S, Gupta T, Vimal S, et al. Consolidation radiation after complete remission in Hodgkin's disease following six cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine chemotherapy: is there a need? J Clin Oncol. 2004;22:62-68.http://jco.ascopubs.org/cgi/content/full/22/1/62http://www.ncbi.nlm.nih.gov/pubmed/14657226?tool=bestpractice.com[30]Meyer RM, Gospodarowicz MK, Connors JM, et al. Randomized comparison of ABVD chemotherapy with a strategy that includes radiation therapy in patients with limited-stage Hodgkin's lymphoma: National Cancer Institute of Canada Clinical Trials Group and the Eastern Cooperative Oncology Group. J Clin Oncol. 2005;23:4634-4642.http://jco.ascopubs.org/cgi/content/full/23/21/4634http://www.ncbi.nlm.nih.gov/pubmed/15837968?tool=bestpractice.com[31]Noordijk EM, Thomas J, Ferme C, et al. First results of the EORTC-GELa H9 randomized trials: the H9-F trial (comparing 3 radiation dose levels) and H9-U trial (comparing 3 chemotherapy schemes) in patients with favorable or unfavorable early stage Hodgkin's lymphoma (HL). J Clin Oncol, 2005 ASCO Annual Meeting Proceedings. 2005;23(suppl):6505.[32]Straus DJ, Portlock CS, Qin J, et al. Results of a prospective randomized clinical trial of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) followed by radiation therapy (RT) versus ABVD alone for stages I, II, and IIIA nonbulky Hodgkin disease. Blood. 2004;104:3483-3489.http://bloodjournal.hematologylibrary.org/cgi/content/full/104/12/3483http://www.ncbi.nlm.nih.gov/pubmed/15315964?tool=bestpractice.com[33]Herbst C, Rehan FA, Skoetz N, et al. Chemotherapy alone versus chemotherapy plus radiotherapy for early stage Hodgkin lymphoma. Cochrane Database Syst Rev. 2011;(2):CD007110.http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD007110.pub2/fullhttp://www.ncbi.nlm.nih.gov/pubmed/21328291?tool=bestpractice.com[34]Eich HT, Diehl V, Görgen H, et al. Intensified chemotherapy and dose-reduced involved-field radiotherapy in patients with early unfavorable Hodgkin's lymphoma: final analysis of the German Hodgkin Study Group HD11 trial. J Clin Oncol. 2010;28:4199-4206.http://www.ncbi.nlm.nih.gov/pubmed/20713848?tool=bestpractice.com

预后良好疾病采用 2 个周期的 ABVD，然后采用 20 Gy 放射进行治疗，而不良预后的疾病则通常使用 4 个周期的 ABVD，然后 30 Gy 放射进行治疗。[34]Eich HT, Diehl V, Görgen H, et al. Intensified chemotherapy and dose-reduced involved-field radiotherapy in patients with early unfavorable Hodgkin's lymphoma: final analysis of the German Hodgkin Study Group HD11 trial. J Clin Oncol. 2010;28:4199-4206.http://www.ncbi.nlm.nih.gov/pubmed/20713848?tool=bestpractice.com[35]Engert A, Plütschow A, Eich HT, et al. Reduced treatment intensity in patients with early-stage Hodgkin's lymphoma. N Engl J Med. 2010;363:640-652.http://www.nejm.org/doi/full/10.1056/NEJMoa1000067http://www.ncbi.nlm.nih.gov/pubmed/20818855?tool=bestpractice.com[36]Behringer K, Goergen H, Hitz F, et al. Omission of dacarbazine or bleomycin, or both, from the ABVD regimen in treatment of early-stage favourable Hodgkin's lymphoma (GHSG HD13): an open-label, randomised, non-inferiority trial. Lancet. 2015;385:1418-1427.http://www.ncbi.nlm.nih.gov/pubmed/25539730?tool=bestpractice.com在有预后良好的早期疾病的老年患者中，4 个周期的 ABVD 未能改善缓解率，但这种治疗方法会导致严重毒性的风险较高，包括博来霉素诱发的肺脏毒性。[37]Böll B, Goergen H, Behringer K, et al. Bleomycin in older early-stage favorable Hodgkin lymphoma patients: analysis of the German Hodgkin Study Group (GHSG) HD10 and HD13 trials. Blood. 2016;127:2189-2192.http://www.bloodjournal.org/content/127/18/2189.long?sso-checked=truehttp://www.ncbi.nlm.nih.gov/pubmed/26834240?tool=bestpractice.com

强化化疗为：先进行 2 个周期的 BEACOPP 剂量递增方案（博来霉素、依托泊苷、多柔比星、环磷酰胺、长春新碱、丙卡巴肼和泼尼松龙）化疗，随后再进行 2 个周期的 ABVD 化疗和放疗。该疗法可改善高风险患者的肿瘤控制，但毒性较大，继发性急性白血病的风险也较高。[38]von Tresckow B, Plütschow A, Fuchs M, et al. Dose-intensification in early unfavorable Hodgkin's lymphoma: final analysis of the German Hodgkin study group HD14 trial. J Clin Oncol. 2012;30:907-913.http://jco.ascopubs.org/content/30/9/907.longhttp://www.ncbi.nlm.nih.gov/pubmed/22271480?tool=bestpractice.com[68]Franklin J, Eichenauer DA, Becker I, et al. Optimisation of chemotherapy and radiotherapy for untreated Hodgkin lymphoma patients with respect to second malignant neoplasms, overall and progression-free survival: individual participant data analysis. Cochrane Database Syst Rev. 2017;(9):CD008814.http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD008814.pub2/fullhttp://www.ncbi.nlm.nih.gov/pubmed/28901021?tool=bestpractice.com

诱导化疗起效后，针对起初的累及部位进行局部放疗。没有必要对继发的累及部位进行放疗，当单独采用放疗时，才需要对继发的累及部位进行放疗。[77]Engert A, Schiller P, Josting A, et al. Involved-field radiotherapy is equally effective and less toxic compared with extended-field radiotherapy after four cycles of chemotherapy in patients with early-stage unfavorable Hodgkin's lymphoma: results of the HD8 trial of the German Hodgkin's Lymphoma Study Group. J Clin Oncol. 2003;21:3601-3608.http://www.ncbi.nlm.nih.gov/pubmed/12913100?tool=bestpractice.com[78]Zittoun R, Audebert A, Hoerni B, et al. Extended versus involved fields irradiation combined with MOPP chemotherapy in early clinical stages of Hodgkin's disease. J Clin Oncol. 1985;3:207-214.http://www.ncbi.nlm.nih.gov/pubmed/3838188?tool=bestpractice.com[79]Bonadonna G, Bonfante V, Viviani S, et al. ABVD plus subtotal nodal versus involved-field radiotherapy in early-stage Hodgkin's disease: long-term results. J Clin Oncol. 2004;22:2835-2841.http://jco.ascopubs.org/cgi/content/full/22/14/2835http://www.ncbi.nlm.nih.gov/pubmed/15199092?tool=bestpractice.com

对于没有较大肿块的患者来讲，也可考虑仅采用联合化疗（例如：4-6 个周期的 ABVD）。[39]Connors JM. The case for chemotherapy alone for limited-stage Hodgkin's lymphoma. Oncologist. 2012;17:1011-1013.http://theoncologist.alphamedpress.org/content/17/8/1011.longhttp://www.ncbi.nlm.nih.gov/pubmed/22807512?tool=bestpractice.com[40]Hill-Kayser CE, Plastaras JP, Tochner Z, et al. The case for combined-modality therapy for limited-stage Hodgkin's disease. Oncologist. 2012;17:1006-1010.http://theoncologist.alphamedpress.org/content/17/8/1006.longhttp://www.ncbi.nlm.nih.gov/pubmed/22807513?tool=bestpractice.com该疗法与综合疗法相比，肿瘤控制率稍低，但生存率相似。[41]Meyer RM, Gospodarowicz MK, Connors JM, et al. ABVD alone versus radiation-based therapy in limited-stage Hodgkin's lymphoma. N Engl J Med. 2012;366:399-408.http://www.nejm.org/doi/full/10.1056/NEJMoa1111961#t=articlehttp://www.ncbi.nlm.nih.gov/pubmed/22149921?tool=bestpractice.com[42]Raemaekers JM, André MP, Federico M, et al. Omitting radiotherapy in early positron emission tomography-negative stage I/II Hodgkin lymphoma is associated with an increased risk of early relapse: clinical results of the preplanned interim analysis of the randomized EORTC/LYSA/FIL H10 trial. J Clin Oncol. 2014;32:1188-1194.http://jco.ascopubs.org/content/32/12/1188.longhttp://www.ncbi.nlm.nih.gov/pubmed/24637998?tool=bestpractice.com

评估在早期霍奇金淋巴瘤 (HL) 中根据 PET 调整方法的研究目的在于使用中期 PET 结果以识别可以安全规避放射治疗的患者。在一项针对IA 或 IIA 期且无较大肿瘤的患者的研究中，将经过 3 个周期的 ABVD 疗法后 PET 阴性的患者随机分配至接受放射巩固或不再进一步治疗。其中，仅使用化疗的患者观察到有临床意义的肿瘤控制率，所以如果想要避免放射，这一结果让此治疗选择颇具吸引力。[43]Radford J, Illidge T, Counsell N, et al. Results of a trial of PET-directed therapy for early-stage Hodgkin's lymphoma. N Engl J Med. 2015;372:1598-1607.http://www.nejm.org/doi/full/10.1056/NEJMoa1408648#t=articlehttp://www.ncbi.nlm.nih.gov/pubmed/25901426?tool=bestpractice.com其他研究也发现了相似的结果。[42]Raemaekers JM, André MP, Federico M, et al. Omitting radiotherapy in early positron emission tomography-negative stage I/II Hodgkin lymphoma is associated with an increased risk of early relapse: clinical results of the preplanned interim analysis of the randomized EORTC/LYSA/FIL H10 trial. J Clin Oncol. 2014;32:1188-1194.http://jco.ascopubs.org/content/32/12/1188.longhttp://www.ncbi.nlm.nih.gov/pubmed/24637998?tool=bestpractice.com [ ]How does positron emission tomography-adapted therapy as first-line treatment affect outcomes in people with early-stage Hodgkin lymphoma?http://cochraneclinicalanswers.com/doi/10.1002/cca.758/full显示答案

ABVD（博来霉素）治疗方案最严重的迟发性影响为肺毒性。与 MOPP（氮芥、长春新碱、丙卡巴肼和泼尼松龙）治疗方案相比，该方案导致的不孕和急性白血病发病率都较低。

参考当地专科医生治疗方案作为剂量指导。

治疗的目标是痊愈。常规治疗方法为联合化疗： ABVD 治疗方案（阿霉素、博来霉素、长春花碱和达卡巴嗪）或高剂量 BEACOPP 治疗方案（博来霉素、依托泊苷、阿霉素、环磷酰胺、长春新碱、丙卡巴肼和泼尼松龙）[44]Hoskin PJ, Lowry L, Horwich A, et al. Randomized comparison of the Stanford V regimen and ABVD in the treatment of advanced Hodgkin's Lymphoma: United Kingdom National Cancer Research Institute Lymphoma Group Study ISRCTN 64141244. J Clin Oncol. 2009;27:5390-5396.http://www.ncbi.nlm.nih.gov/pubmed/19738111?tool=bestpractice.com[45]Federico M, Luminari S, Iannitto E, et al; HD2000 Gruppo Italiano per lo Studio dei Linfomi Trial. ABVD compared with BEACOPP compared with CEC for the initial treatment of patients with advanced Hodgkin's lymphoma: results from the HD2000 Gruppo Italiano per lo Studio dei Linfomi Trial. J Clin Oncol. 2009;27:805-811.http://www.ncbi.nlm.nih.gov/pubmed/19124807?tool=bestpractice.com[46]Skoetz N, Will A, Monsef I, et al. Comparison of first-line chemotherapy including escalated BEACOPP versus chemotherapy including ABVD for people with early unfavourable or advanced stage Hodgkin lymphoma. Cochrane Database Syst Rev. 2017;(5):CD007941.http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD007941.pub3/fullhttp://www.ncbi.nlm.nih.gov/pubmed/28541603?tool=bestpractice.com对于晚期霍奇金淋巴瘤患者，BEACOPP 剂量递增疗法是 ABVD 方案的有效替代治疗方案，但毒性较大，继发性急性白血病的风险也较高。[67]Engert A, Diehl V, Franklin J, et al. Escalated-dose BEACOPP in the treatment of patients with advanced-stage Hodgkin's lymphoma: 10 years of follow-up of the GHSG HD9 study. J Clin Oncol. 2009;27:4548-4554.http://www.ncbi.nlm.nih.gov/pubmed/19704068?tool=bestpractice.com[68]Franklin J, Eichenauer DA, Becker I, et al. Optimisation of chemotherapy and radiotherapy for untreated Hodgkin lymphoma patients with respect to second malignant neoplasms, overall and progression-free survival: individual participant data analysis. Cochrane Database Syst Rev. 2017;(9):CD008814.http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD008814.pub2/fullhttp://www.ncbi.nlm.nih.gov/pubmed/28901021?tool=bestpractice.com对有较大肿块的晚期霍奇金淋巴瘤 (HL) 患者使用巩固性放疗存在争议；然而，数据显示，对治疗终末 PET 扫描阴性的患者来说，可能无需这一疗法。[53]Engert A, Haverkamp H, Kobe C, et al. Reduced-intensity chemotherapy and PET-guided radiotherapy in patients with advanced stage Hodgkin's lymphoma (HD15 trial): a randomised, open-label, phase 3 non-inferiority trial. Lancet. 2012;379:1791-1799.http://www.ncbi.nlm.nih.gov/pubmed/22480758?tool=bestpractice.com[48]Aleman BM, Raemaekers JM, Tirelli U, et al. Involved-field radiotherapy for advanced Hodgkin's lymphoma. N Engl J Med. 2003;348:2396-2406.http://content.nejm.org/cgi/content/full/348/24/2396http://www.ncbi.nlm.nih.gov/pubmed/12802025?tool=bestpractice.com[49]DeVita VT Jr. Hodgkin's disease - clinical trials and travails. N Engl J Med. 2003;348:2375-2376.http://www.ncbi.nlm.nih.gov/pubmed/12802021?tool=bestpractice.com[50]Fabian CJ, Mansfield CM, Dahlberg S, et al. Low-dose involved field radiation after chemotherapy in advanced Hodgkin disease. A Southwest Oncology Group randomized study. Ann Intern Med. 1994;120:903-912.http://www.ncbi.nlm.nih.gov/pubmed/8172436?tool=bestpractice.com[51]Prosnitz LR. Consolidation radiotherapy in the treatment of advanced Hodgkin's disease: is it dead? Int J Radiat Oncol Biol Phys. 2003;56:605-608.http://www.ncbi.nlm.nih.gov/pubmed/12788163?tool=bestpractice.com[81]Johnson PW, Sydes MR, Hancock BW, et al. Consolidation radiotherapy in patients with advanced Hodgkin's lymphoma: survival data from the UKLG LY09 randomized controlled trial (ISRCTN97144519). J Clin Oncol. 2010;28:3352-3359.http://www.ncbi.nlm.nih.gov/pubmed/20498402?tool=bestpractice.com

对于霍奇金淋巴瘤晚期患者来讲，其治疗方案一般为6–8个疗程的 ABVD 化疗。ABVD（博来霉素）治疗方案最严重的迟发性影响为肺毒性。与 MOPP（氮芥、长春新碱、丙卡巴肼和泼尼松龙）治疗方案相比，该方案导致的不孕和急性白血病发病率都较低。

高剂量 BEACOPP 治疗方案一般是6个疗程。[53]Engert A, Haverkamp H, Kobe C, et al. Reduced-intensity chemotherapy and PET-guided radiotherapy in patients with advanced stage Hodgkin's lymphoma (HD15 trial): a randomised, open-label, phase 3 non-inferiority trial. Lancet. 2012;379:1791-1799.http://www.ncbi.nlm.nih.gov/pubmed/22480758?tool=bestpractice.com

由斯坦福大学提出的斯坦福V疗法（阿霉素、长春新碱、氮芥 长春花碱、博来霉素、 依托泊苷和泼尼松龙）治疗疗程为12周（预后良好的早期霍奇金淋巴瘤为 8 周）以及化疗药物（氮芥、阿霉素和博来霉素）累积剂量水平低。美国合作研究组并不能够证明斯坦福V方案优于 ABVD 方案。但是，肺病或其他疾病患者，需要减少博来霉素用量，可采用斯坦福 V 方案。[47]Gordon LI, Hong F, Fisher RI, et al. Randomized phase III trial of ABVD versus Stanford V with or without radiation therapy in locally extensive and advanced-stage Hodgkin lymphoma: an intergroup study coordinated by the Eastern Cooperative Oncology Group (E2496). J Clin Oncol. 2013;31:684-691.http://www.ncbi.nlm.nih.gov/pubmed/23182987?tool=bestpractice.com[82]Bartlett NL, Rosenberg SA, Hoppe RT, et al. Brief chemotherapy, Stanford V, and adjuvant radiotherapy for bulky or advanced-stage Hodgkin's disease: a preliminary report. J Clin Oncol. 1995;13:1080-1088.http://www.ncbi.nlm.nih.gov/pubmed/7537796?tool=bestpractice.com

巩固放疗 (30-36 Gy) 是斯坦福V疗法中不可分割的组成部分。

有数据表明，在有新近诊断出的晚期疾病（II-IV 期）的患者中，临时 PET 扫描（在 2 个周期的 ABVD 之后）有助于作出有关化疗升级或降级的决定，[52]Johnson P, Federico M, Kirkwood A, et al. Adapted treatment guided by interim PET-CT scan in advanced Hodgkin's lymphoma. N Engl J Med. 2016;374:2419-2429.http://www.nejm.org/doi/full/10.1056/NEJMoa1510093#t=articlehttp://www.ncbi.nlm.nih.gov/pubmed/27332902?tool=bestpractice.com而且化疗后的 PET 反应可指导是否需要进行巩固性放疗。[53]Engert A, Haverkamp H, Kobe C, et al. Reduced-intensity chemotherapy and PET-guided radiotherapy in patients with advanced stage Hodgkin's lymphoma (HD15 trial): a randomised, open-label, phase 3 non-inferiority trial. Lancet. 2012;379:1791-1799.http://www.ncbi.nlm.nih.gov/pubmed/22480758?tool=bestpractice.com

剂量指南参见本地的专科医生协议。

大部分结节性淋巴细胞为主霍奇金淋巴瘤 (NLPHD) 患者处于疾病 I 期，累及的部位为外周淋巴结区域，如：腹股沟、腋窝以及颈部等。早期 NLPHD 的整体预后都非常好。由于该亚型罕见，故缺乏相关前瞻性研究。大型回顾性研究表明单独使用放疗对累及区域进行治疗后，其预后良好，因此目前推荐的治疗方法为单独放疗。[54]Nogova L, Reineke T, Eich HT, et al. Extended field radiotherapy, combined modality treatment or involved field radiotherapy for patients with stage IA lymphocyte-predominant Hodgkin's lymphoma: a retrospective analysis from the German Hodgkin Study Group (GHSG). Ann Oncol. 2005;16:1683-1687.http://annonc.oxfordjournals.org/cgi/content/full/16/10/1683http://www.ncbi.nlm.nih.gov/pubmed/16093276?tool=bestpractice.com推荐剂量为 30–36 Gy。对于所有放疗方案，可查看当地剂量指南相关规定。

对于晚期结节性淋巴细胞为主型霍奇金淋巴瘤患者，其治疗方案为联合化疗法，可伴有或不伴有巩固性放疗。

对于霍奇金淋巴瘤晚期患者来讲，其治疗方案一般为 6–8 个疗程的 ABVD 化疗（阿霉素、博来霉素、长春碱和达卡巴嗪）。ABVD（博来霉素）治疗方案最严重的迟发性影响为肺毒性。与 MOPP（氮芥、长春新碱、丙卡巴肼和泼尼松龙）治疗方案相比，该方案导致的不孕和急性白血病发病率都较低。

斯坦福 V 疗法（阿霉素、长春新碱、氮芥、长春花碱、博来霉素、 依托泊苷和泼尼松龙）的治疗疗程为12周（预后良好的早期霍奇金淋巴瘤为 8 周）以及化疗药物（氮芥、阿霉素和博来霉素）累积剂量水平低。[82]Bartlett NL, Rosenberg SA, Hoppe RT, et al. Brief chemotherapy, Stanford V, and adjuvant radiotherapy for bulky or advanced-stage Hodgkin's disease: a preliminary report. J Clin Oncol. 1995;13:1080-1088.http://www.ncbi.nlm.nih.gov/pubmed/7537796?tool=bestpractice.com巩固放疗 (30-36 Gy) 是斯坦福V疗法中不可分割的组成部分。

剂量指南参见本地的专科医生协议。

对于复发性霍奇金淋巴瘤必须进行个体化管理。治疗的目的，至少在开始治疗时是治愈。推荐的疗法有多种并应根据不同的因素进行选择，包括先前采取的一线治疗选择（单独采用放射疗法、单独化疗或综合疗法）、患者年龄、医学共病、首次缓解的持续时间以及复发时所处的阶段等。对于某些患者来讲，单独放疗或单独化疗都有可能是适合的。[55]Josting A, Nogova L, Franklin J, et al. Salvage radiotherapy in patients with relapsed and refractory Hodgkin's lymphoma: a retrospective analysis from the German Hodgkin Lymphoma Study Group. J Clin Oncol. 2005;23:1522-1529.http://jco.ascopubs.org/cgi/content/full/23/7/1522http://www.ncbi.nlm.nih.gov/pubmed/15632410?tool=bestpractice.com

对于多数化疗或综合治疗失败的患者，首选治疗方式是先行高剂量的化疗（对于符合条件的患者，可联合使用放疗），随后进行自体干细胞移植 (ASCT)。[56]Linch DC, Winfield D, Goldstone AH, et al. Dose intensification with autologous bone-marrow transplantation in relapsed and resistant Hodgkin's disease: results of a BNLI randomised trial. Lancet. 1993;341:1051-1054.http://www.ncbi.nlm.nih.gov/pubmed/8096958?tool=bestpractice.com[57]Schmitz N, Pfistner B, Sextro M, et al. Aggressive conventional chemotherapy compared with high-dose chemotherapy with autologous haemopoietic stem-cell transplantation for relapsed chemosensitive Hodgkin's disease: a randomised trial. Lancet. 2002;359:2065-2071.http://www.ncbi.nlm.nih.gov/pubmed/12086759?tool=bestpractice.com[58]Baetz T, Belch A, Couban S, et al. Gemcitabine, dexamethasone and cisplatin is an active and non-toxic chemotherapy regimen in relapsed or refractory Hodgkin's disease: a phase II study by the National Cancer Institute of Canada Clinical Trials Group. Ann Oncol. 2003;14:1762-1767.http://annonc.oxfordjournals.org/content/14/12/1762.longhttp://www.ncbi.nlm.nih.gov/pubmed/14630682?tool=bestpractice.com[59]Moskowitz CH, Nimer SD, Zelenetz AD, et al. A 2-step comprehensive high-dose chemoradiotherapy second-line program for relapsed and refractory Hodgkin disease: analysis by intent to treat and development of a prognostic model. Blood. 2001;97:616-623.http://bloodjournal.hematologylibrary.org/content/97/3/616.longhttp://www.ncbi.nlm.nih.gov/pubmed/11157476?tool=bestpractice.com[60]Santoro A, Magagnoli M, Spina M, et al. Ifosfamide, gemcitabine, and vinorelbine: a new induction regimen for refractory and relapsed Hodgkin's lymphoma. Haematologica. 2007;92:35-41.http://www.haematologica.org/content/92/1/35.longhttp://www.ncbi.nlm.nih.gov/pubmed/17229633?tool=bestpractice.com移植前氟脱氧葡萄糖 (FDG) PET 检查对于移植后的结果具有高度预测性，因而，PET 检查结果达到正常水平是移植前挽救治疗的目标。[83]Moskowitz CH, Matasar MJ, Zelenetz AD, et al. Normalization of pre-ASCT, FDG-PET imaging with second-line, non-cross-resistant, chemotherapy programs improves event-free survival in patients with Hodgkin lymphoma. Blood. 2012;119:1665-1670.http://bloodjournal.hematologylibrary.org/content/119/7/1665.longhttp://www.ncbi.nlm.nih.gov/pubmed/22184409?tool=bestpractice.com

免疫治疗药物也可用于复发性或难治性经典型霍奇金淋巴瘤患者。本妥昔单抗是一种靶向 CD30 的单克隆抗体-药物偶联物，在有高复发风险的患者中（例如初始治疗无效的患者，初始治疗后 12 个月内复发的患者，或伴淋巴结外病变的患者），可用作 ASCT 术后的维持治疗。[61]Moskowitz CH, Nademanee A, Masszi T, et al. Brentuximab vedotin as consolidation therapy after autologous stem-cell transplantation in patients with Hodgkin's lymphoma at risk of relapse or progression (AETHERA): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2015;385:1853-1862.http://www.ncbi.nlm.nih.gov/pubmed/25796459?tool=bestpractice.com或者，可以在 ASCT 治疗失败后使用本妥昔单抗。其也可以用于不适合 ASCT 的患者，但是只有在已经尝试过两种或更多种多药化疗方案的情况下才可以使用。[62]Younes A, Gopal AK, Smith SE, et al. Results of a pivotal phase II study of brentuximab vedotin for patients with relapsed or refractory Hodgkin's lymphoma. J Clin Oncol. 2012;30:2183-2189.http://jco.ascopubs.org/content/30/18/2183.longhttp://www.ncbi.nlm.nih.gov/pubmed/22454421?tool=bestpractice.com

使用 ASCT 和本妥昔单抗均无效的患者可以考虑用纳武单抗治疗。纳武单抗是一种单克隆抗体，可靶向并阻断程序性死亡-1 (PD-1) 信号传导通路。对纳武单抗的临床研究表明，在已经接受过广泛预处理的霍奇金淋巴瘤患者中，客观缓解率＞65%，其中许多患者之前的 ASCT 治疗无效，并在使用本妥昔单抗后病情复发或对其无效。[63]Ansell SM, Lesokhin AM, Borrello I, et al. PD-1 blockade with nivolumab in relapsed or refractory Hodgkin's lymphoma. N Engl J Med. 2015;372:311-319.http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4348009/http://www.ncbi.nlm.nih.gov/pubmed/25482239?tool=bestpractice.com[64]Younes A, Santoro A, Shipp M, et al. Nivolumab for classical Hodgkin's lymphoma after failure of both autologous stem-cell transplantation and brentuximab vedotin: a multicentre, multicohort, single-arm phase 2 trial. Lancet Oncol. 2016;17:1283-1294.http://www.sciencedirect.com/science/article/pii/S147020451630167Xhttp://www.ncbi.nlm.nih.gov/pubmed/27451390?tool=bestpractice.com派姆单抗是另一种可靶向并阻断程序性死亡-1 (PD-1) 信号传导通路的单克隆抗体。在美国，派姆单抗可以用于既往经过三线或更前线治疗之后复发的霍奇金淋巴瘤患者。在欧洲，派姆单抗可用于经 ASCT 和本妥昔单抗（类似于纳武单抗）治疗无效的患者，以及不适合 ASCT 且本妥昔单抗治疗无效的患者。对派姆单抗的临床研究报告称，在使用本妥昔单抗治疗无效的复发性或难治性疾病患者中，其总缓解率为 65%。[65]Armand P, Shipp MA, Ribrag V, et al. Programmed death-1 blockade with pembrolizumab in patients with classical Hodgkin lymphoma after brentuximab vedotin failure. J Clin Oncol. 2016 Jun 27 [Epub ahead of print].http://www.ncbi.nlm.nih.gov/pubmed/27354476?tool=bestpractice.com

在自体移植后复发的患者中，异体移植疗法的作用可能有限，但是否应采用该疗法仍有争议。[66]Anderlini P, Champlin RE. Reduced intensity conditioning for allogeneic stem cell transplantation in relapsed and refractory Hodgkin lymphoma: where do we stand? Biol Blood Marrow Transplant. 2006;12:599-602.http://www.ncbi.nlm.nih.gov/pubmed/16737932?tool=bestpractice.com