【摘要】 目的 探討對(duì)自體造血干細(xì)胞移植（autologous hematopoietic stem cell transplantation，auto-HSCT）后復(fù)發(fā)的非霍奇金淋巴瘤患者再進(jìn)行異基因造血干細(xì)胞移植（allogeneic hematopoietic stem cell transplantation，allo-HSCT）治療的臨床療效。 方法 收集2000年1月-2010年12月難治性惡性淋巴瘤采用auto-HSCT后復(fù)發(fā)患者11例，病程27個(gè)月~6.5年。所有患者在auto-HSCT前均為復(fù)發(fā)難治性病例，auto-HSCT后，完全緩解8例，部分緩解3例，自體移植后中位復(fù)發(fā)時(shí)間15個(gè)月，患者復(fù)發(fā)后采用異基因親緣造血干細(xì)胞移植，人類(lèi)白細(xì)胞抗原（human leukocyte antigen，HLA）全相合（6/6）6例，5/6相合3例，4/6相合2例；性別相同6例，性別不同5例。預(yù)處理方案為FBC方案，即氟達(dá)拉濱30 mg/m2 1~5 d，白消安12~14 mg/kg分4 d口服，環(huán)磷酰胺120 mg/kg分2 d使用。移植物均為外周血造血干細(xì)胞加骨髓。移植物抗宿主?。╣raft-versus-host disease，GVHD）的預(yù)防：HLA全相合采用環(huán)孢素+短程甲氨蝶呤+嗎替麥考酚酯，不全相合采用抗胸腺細(xì)胞球蛋白+環(huán)孢素+短程甲氨蝶呤+嗎替麥考酚酯。 結(jié)果 11例患者全部獲得造血重建，急性GVHD發(fā)生6例（54.55%），其中Ⅰ度、Ⅱ度4例，Ⅲ度、Ⅳ度各1例；1例Ⅳ度GVHD因合并感染死亡，5例均得到有效控制；發(fā)生慢性GVHD 7例（63.64%），其中有2例急性GVHD轉(zhuǎn)為慢性，4例局限型，3例廣泛型。隨訪8個(gè)月~9年，有4例分別于移植后8、15、21、34個(gè)月疾病復(fù)發(fā)，另外6例仍生存。 結(jié)論 allo-HSCT對(duì)于auto-HSCT后復(fù)發(fā)的非霍奇金淋巴瘤患者仍是一種有效的挽救性治療手段。
【Abstract】 Objective To explore the clinical efficacy of allogeneic hematopoietic stem cell transplantation (allo-HSCT) on relapsing non-Hodgkin′s lymphoma after autologous stem cell transplantation (auto-HSCT). Methods The clinical data of 11 patients with recurrent non-Hodgkin′s lymphoma after auto-HSCT from January 2000 to December 2010 were collected, including nine males and 2 females with the median age of 39 years (13-48 years old), and the median duration of the disease was 3 years (27 months-6.5 years). All patients were relapsed or refractory cases. After auto-HSCT, complete remission was found in 8 and partial remission was in 3. The recurrence median time after auto-HSCT was 15 months. The patients underwent allo-HSCT after the recurrence of the disease. In the 11 patients, human leukocyte antigen (HLA) full matched (6/6) in 6, 5/6 matched in 3, and 4/6 matched in 2; the same gender in 6 and different gender in 5. FBC conditioning regimen: fludarabine 30 mg/m2 for 1-5 days, BU 12-14 mg/kg in 4 days of oral, CY 120 mg/kg in 2 days. Grafts are peripheral blood stem cells plus bone marrow. Prevention of graft-versus-host disease (GVHD): HLA full-matched by CsA+short-term MTX+MMF and mismatched by ATG+CsA+short-term MTX+MMF. Results All of the 11 patients received hematopoietic reconstruction, acute GVHD occurred in 6 cases (54.55%), including degree Ⅰ plus Ⅱ in 4, degree Ⅲ in 1 and degree Ⅳ in 1. One patient died of infection due to degree Ⅳ GVHD, and the rest had been effectively controlled. Chronic GVHD occurred in 7 patients (63.64%); limited type was in 4 in and extensive type was in 3. During the follow-up period of 8 months-9 years, 4 patients relapsed 8, 15, 21, and 34 months after transplantation, and the other 6 patients was still alive. Conclusion Allo-HSCT is effective on relapsing non-Hodgkin′s lymphoma after auto-HSCT.
引用本文： 蘇毅,易海,付利,范方毅,孫浩平,劉陽(yáng)陽(yáng),鄧濤,王譯,何光翠,賴思含,王淋,劉一嵐. 異基因造血干細(xì)胞移植治療自體造血干細(xì)胞移植后復(fù)發(fā)的非霍奇金淋巴瘤臨床觀察. 華西醫(yī)學(xué), 2011, 26(12): 1780-1782. doi: 復(fù)制
| 1. | Zelenetz AD, Abramson JS, Advani RH, et al. Non-Hodgkin′s Lymphomas[J]. J Natl Compr Canc Netw, 2011, 9(5): 484-560. |
| 2. | 蘇毅, 鄭華金, 趙月華, 等. 自體外周血造血干細(xì)胞移植治療難治性非霍奇金淋巴瘤的臨床療效[J]. 中國(guó)腫瘤臨床, 2001, 28(11): 835-837. |
| 3. | 蘇毅, 范方毅, 易海, 等. 負(fù)載自體腫瘤抗原的DC-CIK細(xì)胞聯(lián)合自體造血干細(xì)胞移植治療難治性淋巴瘤的臨床研究[J]. 中國(guó)輸血雜志, 2009, 22(10): 802-805. |
| 4. | 周穎, 陳寶安, 趙剛. 急性GVHD的治療研究新進(jìn)展[J]. 中國(guó)實(shí)驗(yàn)血液學(xué)雜志, 2010, 18(1): 238-241. |
| 5. | Peniket AJ, Ruiz de Elvira MC, Taghipour G, et al. An EBMT registry matched study of allogeneic stem cell transplants for lymphoma: allogeneic transplantation is associated with a lower relapse rate but a higher procedure-related mortality rate than autologous transplantation[J]. Bone Marrow Transplantation, 2003, 31(8), 667-678. |
| 6. | 王健民, 吳濤. 造血干細(xì)胞移植預(yù)處理研究現(xiàn)狀[J]. 內(nèi)科理論與實(shí)踐, 2010, 5(1): 4-8. |
| 7. | Slavin S, Nagler A, Naparstek E, et al. Nonmyeloablative stem cell transplantation and cell therapy as an alternative to conventional bone marrow transplantation with lethal cytoreduction for the treatment of malignant and nonmalignant hematologic diseases[J]. Blood, 1998, 91(3): 756-763. |
| 8. | 黃寧, 葛林阜, 馬煥文, 等. FBC方案預(yù)處理進(jìn)行異基因造血干細(xì)胞移植的臨床研究[J]. 中國(guó)腫瘤生物治療雜志, 2005, 12(2): 150-151. |
| 9. | 蘇毅, 范方毅, 易海, 等. 化療聯(lián)合半相合供者淋巴細(xì)胞輸注治療難治性非霍奇金淋巴瘤實(shí)驗(yàn)及臨床研究[J]. 西南國(guó)防醫(yī)藥, 2010, 20(10): 1070-1073. |
| 10. | Bloor AJ, Thomson K, Chowdhry N, et al. High response rate to donor lymphocyte infusion after allogeneic stem cell transplantation for indolent non-Hodgkin lymphoma[J]. Biol Blood Marrow Transplant, 2008, 14(1): 50-58. |
| 11. | Calvo-Villas JM, Martin A, Conde E, et al. Effect of addition of rituximab to salvage chemotherapy on outcome of patients with diffuse large B-cell lymphoma relapsing after an autologous stem-cell transplantation[J]. Ann Oncol, 2010, 21(9): 1891-1897. |
| 12. | Gisselbrecht C, Glass B, Mounier N, et al. Salvage regimens with autologous transplantation for relapsed large B-cell lymphoma in the rituximab era[J]. Ann Oncol, 2010, 28(27): 4184-4190. |
- 1. Zelenetz AD, Abramson JS, Advani RH, et al. Non-Hodgkin′s Lymphomas[J]. J Natl Compr Canc Netw, 2011, 9(5): 484-560.
- 2. 蘇毅, 鄭華金, 趙月華, 等. 自體外周血造血干細(xì)胞移植治療難治性非霍奇金淋巴瘤的臨床療效[J]. 中國(guó)腫瘤臨床, 2001, 28(11): 835-837.
- 3. 蘇毅, 范方毅, 易海, 等. 負(fù)載自體腫瘤抗原的DC-CIK細(xì)胞聯(lián)合自體造血干細(xì)胞移植治療難治性淋巴瘤的臨床研究[J]. 中國(guó)輸血雜志, 2009, 22(10): 802-805.
- 4. 周穎, 陳寶安, 趙剛. 急性GVHD的治療研究新進(jìn)展[J]. 中國(guó)實(shí)驗(yàn)血液學(xué)雜志, 2010, 18(1): 238-241.
- 5. Peniket AJ, Ruiz de Elvira MC, Taghipour G, et al. An EBMT registry matched study of allogeneic stem cell transplants for lymphoma: allogeneic transplantation is associated with a lower relapse rate but a higher procedure-related mortality rate than autologous transplantation[J]. Bone Marrow Transplantation, 2003, 31(8), 667-678.
- 6. 王健民, 吳濤. 造血干細(xì)胞移植預(yù)處理研究現(xiàn)狀[J]. 內(nèi)科理論與實(shí)踐, 2010, 5(1): 4-8.
- 7. Slavin S, Nagler A, Naparstek E, et al. Nonmyeloablative stem cell transplantation and cell therapy as an alternative to conventional bone marrow transplantation with lethal cytoreduction for the treatment of malignant and nonmalignant hematologic diseases[J]. Blood, 1998, 91(3): 756-763.
- 8. 黃寧, 葛林阜, 馬煥文, 等. FBC方案預(yù)處理進(jìn)行異基因造血干細(xì)胞移植的臨床研究[J]. 中國(guó)腫瘤生物治療雜志, 2005, 12(2): 150-151.
- 9. 蘇毅, 范方毅, 易海, 等. 化療聯(lián)合半相合供者淋巴細(xì)胞輸注治療難治性非霍奇金淋巴瘤實(shí)驗(yàn)及臨床研究[J]. 西南國(guó)防醫(yī)藥, 2010, 20(10): 1070-1073.
- 10. Bloor AJ, Thomson K, Chowdhry N, et al. High response rate to donor lymphocyte infusion after allogeneic stem cell transplantation for indolent non-Hodgkin lymphoma[J]. Biol Blood Marrow Transplant, 2008, 14(1): 50-58.
- 11. Calvo-Villas JM, Martin A, Conde E, et al. Effect of addition of rituximab to salvage chemotherapy on outcome of patients with diffuse large B-cell lymphoma relapsing after an autologous stem-cell transplantation[J]. Ann Oncol, 2010, 21(9): 1891-1897.
- 12. Gisselbrecht C, Glass B, Mounier N, et al. Salvage regimens with autologous transplantation for relapsed large B-cell lymphoma in the rituximab era[J]. Ann Oncol, 2010, 28(27): 4184-4190.