上海 2012年8月9日 訊 /生物谷BIOON/ --根據(jù)一篇于2012年8月6日在線發(fā)表在Journal of Clinical Oncology期刊上的研究論文,，患有血液惡性腫瘤的病人接受來自HLA錯(cuò)配的非親緣供者(HLA-mismatched unrelated donor, MMUD)的低強(qiáng)度預(yù)處理(reduced-intensity conditioning, RIC)的造血干細(xì)胞移植(hematopoietic stem cell transplantation, HSCT)之后,，短期預(yù)防性的基于硼替佐米(bortezomib)的治療以便降低移植物抗宿主病(graft-versus-host disease, GVHD)的發(fā)病率，可能能夠給他們帶來益處,。
來自美國哈佛醫(yī)學(xué)院達(dá)納-法伯癌癥研究所(Dana-Farber Cancer Institute)的研究員John Koreth博士和同事們開展一項(xiàng)前瞻性I/II期臨床試驗(yàn),。這項(xiàng)臨床試驗(yàn)涉及45名接受過MMUD RIC HSCT的病人。
這45名臨床試驗(yàn)參與者隨后接受短期的GVHD預(yù)防治療,，即在接受外周血干細(xì)胞輸注和甲氨蝶呤(methotrexate)和他克莫司(tacrolimus)治療之后的第一天,、第四天和第七天服用硼替佐米。
研究人員發(fā)現(xiàn),，在180天之后,，二到四級GVHD的累積性發(fā)病率(cumulative incidence)為22%，而一年的慢性GVHD累積性發(fā)病率為29%,。2年后，病人腫瘤復(fù)發(fā)的死亡率為38%,，而沒有腫瘤復(fù)發(fā)的死亡率為11%,。2年后，病人的無惡化存活率(progression-free surviva)和總存活率(overall survival)分別為51%和64%,。沒有腫瘤復(fù)發(fā)的死亡率,、急性GVHD和慢性GVHD發(fā)病率以及存活率都與那些同時(shí)接受HLA匹配的RIC HSCT病人相類似。
論文作者們寫道,，“總之,，對接受HLA錯(cuò)配的RIC移植的病人而言，短期的基于硼替佐米的GVHD預(yù)防治療似乎是安全的和有效的,，因?yàn)檫@會(huì)提高他們的存活率,。重要的是,，基于硼替佐米的MMUD移植獲得的臨床結(jié)果能夠與HLA匹配的移植相比擬，而且還伴隨著多種免疫重建參數(shù)的改善,。”(生物谷：Bioon.com)
本文編譯自Bortezomib beneficial in graft-versus-host disease prophylaxis
doi: 10.1200/JCO.2012.42.0984
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Bortezomib-Based Graft-Versus-Host Disease Prophylaxis in HLA-Mismatched Unrelated Donor Transplantation
John Koreth⇓, Kristen E. Stevenson, Haesook T. Kim, Sean M. McDonough, Bhavjot Bindra, Philippe Armand, Vincent T. Ho, Corey Cutler, Bruce R. Blazar, Joseph H. Antin, Robert J. Soiffer, Jerome Ritz and Edwin P. Alyea III
Purpose HLA-mismatched unrelated donor (MMUD) hematopoietic stem-cell transplantation (HSCT) is associated with increased graft-versus-host disease (GVHD) and impaired survival. In reduced-intensity conditioning (RIC), neither ex vivo nor in vivo T-cell depletion (eg, antithymocyte globulin) convincingly improved outcomes. The proteasome inhibitor bortezomib has immunomodulatory properties potentially beneficial for control of GVHD in T-cell-replete HLA-mismatched transplantation. Patients and Methods We conducted a prospective phase I/II trial of a GVHD prophylaxis regimen of short-course bortezomib, administered once per day on days +1, +4, and +7 after peripheral blood stem-cell infusion plus standard tacrolimus and methotrexate in patients with hematologic malignancies undergoing MMUD RIC HSCT. We report outcomes for 45 study patients: 40 (89%) 1-locus and five (11%) 2-loci mismatches (HLA-A, -B, -C, -DRB1, or -DQB1), with a median of 36.5 months (range, 17.4 to 59.6 months) follow-up. Results The 180-day cumulative incidence of grade 2 to 4 acute GVHD was 22% (95% CI, 11% to 35%). One-year cumulative incidence of chronic GVHD was 29% (95% CI, 16% to 43%). Two-year cumulative incidences of nonrelapse mortality (NRM) and relapse were 11% (95% CI, 4% to 22%) and 38% (95% CI, 24% to 52%), respectively. Two-year progression-free survival and overall survival were 51% (95% CI, 36% to 64%) and 64% (95% CI, 49% to 76%), respectively. Bortezomib-treated HLA-mismatched patients experienced rates of NRM, acute and chronic GVHD, and survival similar to those of contemporaneous HLA-matched RIC HSCT at our institution. Immune recovery, including CD8+ T-cell and natural killer cell reconstitution, was enhanced with bortezomib. Conclusion A novel short-course, bortezomib-based GVHD regimen can abrogate the survival impairment of MMUD RIC HSCT, can enhance early immune reconstitution, and appears to be suitable for prospective randomized evaluation.
