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非清髓性干细胞移植是难治性或复发性霍奇金淋巴瘤的有效治疗方法:一项西班牙前瞻性合作方案的结果

Nonmyeloablative stem cell transplantation is an effective therapy for refractory or relapsed hodgkin lymphoma: results of a spanish prospective cooperative protocol.

作者信息

Alvarez Iván, Sureda Anna, Caballero Maria D, Urbano-Ispizua Alvaro, Ribera Josep M, Canales Miguel, García-Conde Javier, Sanz Guillermo, Arranz Reyes, Bernal Maria T, de la Serna Javier, Díez José L, Moraleda José M, Rubió-Félix Daniel, Xicoy Blanca, Martínez Carmen, Mateos Marivi V, Sierra Jorge

机构信息

Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.

出版信息

Biol Blood Marrow Transplant. 2006 Feb;12(2):172-83. doi: 10.1016/j.bbmt.2005.09.009.

Abstract

We report the results of reduced-intensity conditioning allogeneic stem cell transplantation (allo-RIC) in patients with advanced Hodgkin lymphoma (HL). Forty patients with relapsed or refractory HL were homogeneously treated with an RIC protocol (fludarabine 150 mg/m(2) intravenously plus melphalan 140 mg/m(2) intravenously) and cyclosporin A and methotrexate as graft-versus-host disease (GVHD) prophylaxis. Twenty-one patients (53%) had received >2 lines of chemotherapy, 23 patients (58%) had received radiotherapy, and 29 patients (73%) had experienced treatment failure with a previous autologous stem cell transplantation. Twenty patients (50%) were allografted in resistant relapse, and 38 patients received hematopoietic cells from an HLA-identical sibling. Five patients (12%) died from early transplant-related mortality (before day +100 after allo-RIC). One-year transplant-related mortality was 25%. Acute GVHD developed in 18 patients (45%). Chronic GVHD developed in 17 (45%) of the 31 evaluable patients. The response rate 3 months after the allo-RIC was 67% (21 [52%] complete remissions and 6 [15%] partial remissions). Eleven patients received donor lymphocyte infusions (DLIs) for disease relapse. The response rate after DLI was 54% (3 complete remissions and 3 partial remissions). Overall survival (OS) and progression-free survival (PFS) were 48% +/- 10% and 32% +/- 10% at 2 years, respectively. Refractoriness to chemotherapy was the only adverse prognostic factor for both OS (63% +/- 12% versus 35% +/- 13%; P = .05) and PFS (55% +/- 16% versus 10% +/- 9%; P = .006). For patients with failure of a prior autologous hematopoietic stem cell transplantation, results were especially good for those who experienced late relapses (>/=12 months: 2-year OS and PFS were 75% +/- 16% and 70% +/- 18%, respectively). These data suggest that allo-RIC is feasible in heavily pretreated HL patients and has an acceptable early transplant-related mortality. Results are better in patients allografted in sensitive disease. Both responses observed after the development of GVHD and DLI may suggest a graft-versus-HL effect. Allo-RIC has to be considered an effective therapeutic approach for patients who have had treatment failure with a previous autologous hematopoietic stem cell transplantation.

摘要

我们报告了晚期霍奇金淋巴瘤(HL)患者接受减低强度预处理异基因干细胞移植(allo-RIC)的结果。40例复发或难治性HL患者均接受了RIC方案(静脉注射氟达拉滨150mg/m²加静脉注射美法仑140mg/m²),并使用环孢素A和甲氨蝶呤预防移植物抗宿主病(GVHD)。21例患者(53%)接受过超过2线化疗,23例患者(58%)接受过放疗,29例患者(73%)既往自体干细胞移植治疗失败。20例患者(50%)在耐药复发时接受了异基因移植,38例患者接受了来自HLA匹配同胞的造血细胞。5例患者(12%)死于早期移植相关死亡率(allo-RIC后第100天之前)。1年移植相关死亡率为25%。18例患者(45%)发生急性GVHD。31例可评估患者中有17例(45%)发生慢性GVHD。allo-RIC后3个月的缓解率为67%(完全缓解21例[52%],部分缓解6例[15%])。11例患者因疾病复发接受了供体淋巴细胞输注(DLI)。DLI后的缓解率为54%(完全缓解3例,部分缓解3例)。2年总生存率(OS)和无进展生存率(PFS)分别为48%±10%和32%±10%。化疗难治性是OS(63%±12%对35%±13%;P = 0.05)和PFS(55%±16%对10%±9%;P = 0.006)的唯一不良预后因素。对于既往自体造血干细胞移植失败的患者,那些晚期复发(≥12个月)的患者结果尤其好(2年OS和PFS分别为75%±16%和70%±18%)。这些数据表明,allo-RIC在经过大量预处理的HL患者中是可行的,并且具有可接受的早期移植相关死亡率。在敏感疾病中接受异基因移植的患者结果更好。GVHD和DLI后观察到的缓解可能提示移植物抗HL效应。对于既往自体造血干细胞移植治疗失败的患者,allo-RIC必须被视为一种有效的治疗方法。

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