Low-Dose Antithymocyte Globulin for Graft-versus-Host-Disease Prophylaxis in Matched Unrelated Allogeneic Hematopoietic Stem Cell Transplantation
Low-Dose Antithymocyte Globulin for Graft-versus-Host-Disease Prophylaxis in Matched Unrelated Allogeneic Hematopoietic Stem Cell Transplantation
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DOI：
10.1016/j.bbmt.2017.08.007
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发表时间：
2017-12-01
影响因子：
4.3
通讯作者：
Kekre, Natasha
中科院分区：
文献类型：
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作者：
Bryant, Adam;Mallick, Ranjeeta;Kekre, Natasha
移植物抗宿主病（GVHD）是异基因造血干细胞移植（alloHCT）中发病率和死亡率的主要原因。用抗胸腺细胞球蛋白（ATG）预防性体内T细胞耗竭与许多alloHCT环境中GVHD率降低相关。尽管进行了数十年的临床研究，但尚未确定最佳的ATG剂量。我们了解到，与匹配的相关供体（MRD）alloHCT相比，匹配的非相关供体（MUD）的GVHD发生率更高，在我们的机构，MUD alloHCT接受者在我们的标准MRD GVHD预防方案中加入了低剂量的Thymoglobulin（总剂量，2.5 mg/kg; Genzyme-Sanofi，剑桥，MA）。在这项回顾性队列研究中，我们通过比较ATG暴露（MUD）和未暴露（MRD）alloHCT受体的GVHD和其他临床HCT结局，评估了HCT后我们独特的低剂量ATG策略的有效性。这项回顾性单中心研究纳入了2009年至2014年在渥太华医院因任何恶性适应症接受移植的所有Ha患者。MUD患者除了标准GVHD预防之外，还接受了2天内给予的总剂量为2.5mg/kg的兔ATG（胸腺球蛋白）（在干细胞输注前第-2天为0.5mg/kg;在干细胞输注前第-1天为2.0mg/kg）。评估的主要结局是急性和慢性GVHD的发生率，定义为新发GVHD，需要系统性免疫抑制治疗，分别小于或大于100天。次要结局包括疾病复发和生存。ATG暴露（MUD）和未暴露（MRD）队列分别有110例和77例患者。基线时，队列间移植时的中位年龄、性别、疾病适应症或风险指数、移植物来源、预处理方案或强度无显著差异。高比例的7/8错配供体移植（13%对3%，P= 0.02）和较高的中位CD 34（+）剂量（7.9对4.9 × 10（8）细胞; P
Graft-versus-host disease (GVHD) is a leading cause of morbidity and mortality in allogeneic hematopoietic stem cell transplantation (alloHCT). Prophylactic in vivo T cell depletion with antithymocyte globulin (ATG) has been associated with decreased GVHD rates in many alloHCT settings. Despite decades of clinical study, optimal ATG dosing has not been established. Understanding that higher rates of GVHD are observed with matched unrelated donor (MUD) versus matched related donor (MRD) alloHCT, at our institution MUD alloHCT recipients have historically had low-dose Thymoglobulin (total dose, 2.5 mg/kg; Genzyme-Sanofi, Cambridge, MA) added to our standard MRD GVHD prophylaxis regimen. In this retrospective cohort study we assessed post-HCT the effectiveness of our uniquely low-dose ATG strategy by comparing ATG exposed (MUD) and unexposed (MRD) alloHCT recipients for GVHD and other clinical HCT outcomes. This retrospective single center study included all Ha patients transplanted for any malignant indication at The Ottawa Hospital from 2009 to 2014. MUD patients received rabbit ATG (Thymoglobulin) at a total dose of 2.5 mg/kg given over 2 days (.5 mg/kg on day -2; 2.0 mg/kg on day -1 before stem cell infusion) in addition to standard GVHD prophylaxis. Primary outcomes assessed were incidence of acute and chronic GVHD, defined as new-onset GVHD requiring systemic immunosuppressive therapy at less or more than 100 days, respectively. Secondary outcomes included disease relapse and survival. There were 110 and 77 patients in the ATG exposed (MUD) and unexposed (MRD) cohorts, respectively. At baseline there were no significant differences in median age at transplant, sex, disease indication or risk index, graft source, conditioning regimen, or intensity between cohorts. A higher proportion of 7/8 mismatched donor transplants (13% versus 3%, P=.02) and a higher median CD34(+) dose (7.9 versus 4.9 x 10(8) cells; P