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供者淋巴细胞输注和二次移植作为减轻强度移植后复发骨髓纤维化的挽救治疗。

Donor lymphocyte infusions and second transplantation as salvage treatment for relapsed myelofibrosis after reduced-intensity allografting.

机构信息

Department of Stem Cell Transplantation, University Cancer Centre Hamburg, Hamburg, Germany.

出版信息

Br J Haematol. 2012 Oct;159(2):172-81. doi: 10.1111/bjh.12013. Epub 2012 Aug 22.

Abstract

Thirty myelofibrosis patients (21 males, nine females) with relapse (n = 27) or graft-rejection (n = 3) after dose-reduced allografting underwent a salvage strategy including donor lymphocyte infusions (DLIs) and/or second allogeneic haematopoietic stem cell transplantation (HSCT). Twenty-six patients received a median number of three (range, 1-5) DLIs in a dose-escalated mode starting with a median dose of 1·2 × 10(6) (range, 0·003-8 × 10(6) ) up to median dose of 40 × 10(6) T-cells/kg (range, 10-130 × 10(6) ). 10/26 patients (39%) achieved complete response (CR) to DLIs. Acute (grade II-IV) and chronic graft-versus-host (GvHD) disease occurred in 12% and 36% cases. Thirteen non-responders to DLI and four patients who did not receive DLI due to graft-rejection or acute transformation of the blast phase underwent a second allogeneic HSCT from alternative (n = 15) or the same (n = 2) donor. One patient (6%) experienced primary graft-failure and died. Acute (II-IV) and chronic GvHD were observed in 47% and 46% of patients. Overall responses after second HSCT were seen in 12/15 patients (80%: CR: n = 9, partial response: n = 3). The 1-year cumulative incidence of non-relapse mortality for recipients of a second allograft was 6%, and the cumulative incidence of relapse was 24%. After a median follow-up of 27 months, the 2-year overall survival and progression-free survival for all 30 patients was 70% and 67%, respectively. In conclusion, our two-step strategy, including DLI and second HSCT for non-responding or ineligible patients, is an effective and well-tolerated salvage approach for patients relapsing after reduced-intensity allograft after myelofibrosis.

摘要

30 例骨髓纤维化患者(男 21 例,女 9 例)在减剂量异体移植后发生复发(n=27)或移植物排斥(n=3),采用包括供者淋巴细胞输注(DLIs)和/或第二次同种异体造血干细胞移植(HSCT)的挽救策略。26 例患者以剂量递增模式接受中位数为 3 次(范围 1-5 次)的 DLI,起始剂量中位数为 1.2×10(6)(范围 0.003-8×10(6)),直至 T 细胞中位数剂量为 40×10(6)/kg(范围 10-130×10(6))。26 例患者中的 10 例(39%)对 DLI 有完全缓解(CR)。12%和 36%的患者发生急性(Ⅱ-Ⅳ级)和慢性移植物抗宿主病(GvHD)。13 例对 DLI 无反应的非应答者和 4 例因移植物排斥或原始细胞危象而未接受 DLI 的患者接受了来自替代(n=15)或相同(n=2)供体的第二次同种异体 HSCT。1 例患者(6%)出现原发性移植物失败并死亡。47%和 46%的患者出现急性(Ⅱ-Ⅳ级)和慢性 GvHD。第二次 HSCT 后的总反应见于 15 例患者中的 12 例(80%:CR:n=9,部分反应:n=3)。第二次同种异体移植受者的 1 年非复发死亡率累积发生率为 6%,复发率为 24%。在中位随访 27 个月后,所有 30 例患者的 2 年总生存率和无进展生存率分别为 70%和 67%。总之,我们的两步策略包括 DLI 和对无反应或不合格患者的第二次 HSCT,是一种有效且耐受良好的挽救策略,适用于骨髓纤维化患者在减剂量异体移植后复发。

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