Russell James A, Turner A Robert, Larratt Loree, Chaudhry Ahsan, Morris Donald, Brown Christopher, Quinlan Diana, Stewart Douglas
Alberta Blood and Bone Marrow Transplant Program and Departments of Medicine and Oncology, Foothills Hospital, Calgary, Alberta, Canada.
Biol Blood Marrow Transplant. 2007 Mar;13(3):299-306. doi: 10.1016/j.bbmt.2006.10.017.
Because pretransplantation anti-thymocyte globulin (ATG) seems to reduce graft-versus-host-disease (GVHD) and treatment-related mortality (TRM) after unrelated donor bone marrow transplantation (BMT), we investigated this agent in matched related donor (MRD) blood cell transplantation (BCT). Fifty-four adults receiving rabbit ATG, cyclosporine A, and methotrexate with myeloablative conditioning and undergoing first MRD BCT were matched for disease and stage with 54 patients not given ATG. Most ATG-treated patients had fludarabine with oral (7) or i.v. busulfan (46) with total body irradiation (TBI) in 10. Control patients largely received TBI with VP16 (28) or oral busulfan with cyclophosphamide (15) or fludarabine (7). The ATG was given at a total dose of 4.5 mg/kg over 3 d, finishing on day 0. Rates of acute GVHD (aGVHD) grade II-IV, aGVHD grade III-IV, and chronic GVHD (cGVHD) were 19 +/- 5% versus 32 +/- 6% (P = .1), 6 +/- 3% versus 13 +/- 5% (P = NS), and 55 +/- 8% versus 96 +/- 3% (P = .002) in the ATG and control groups, respectively. Patients given ATG had fewer sites involved by cGVHD compared with the control group (mean 2.1 +/- 0.2 versus 2.8 +/- 0.2, P = .04). Non-relapse mortality (NRM) with and without ATG, respectively, was 4 +/- 3% versus 17 +/- 5% at 100 d and 9 +/- 4% versus 34 +/- 7% at 4 yr (P = .002). Deaths were GVHD related in 3 ATG-treated patients versus 14 controls (P = .007). Despite a trend to more relapse with ATG (43 +/- 7% versus 22 +/- 7% at 4 yr, P = 0.05), survival was 66 +/- 7% in the patients given ATG versus 50 +/- 7% in the controls (P = 0.046). This study indicates that myeloablative regimens incorporating fludarabine and oral or i.v. busulfan with pretransplantation ATG given to recipients undergoing MRD BCT may result in less cGVHD, lower TRM, and probably improved quality of life in survivors compared with previous protocols.
由于移植前抗胸腺细胞球蛋白（ATG）似乎可降低无关供者骨髓移植（BMT）后移植物抗宿主病（GVHD）和治疗相关死亡率（TRM），我们在匹配的相关供者（MRD）血细胞移植（BCT）中对该药物进行了研究。54例接受兔ATG、环孢素A和甲氨蝶呤并进行清髓性预处理且接受首次MRD BCT的成年患者，在疾病和分期方面与54例未给予ATG的患者进行了匹配。大多数接受ATG治疗的患者使用氟达拉滨联合口服（7例）或静脉注射白消安（46例），其中10例接受全身照射（TBI）。对照组患者大多接受TBI联合VP16（28例）或口服白消安联合环磷酰胺（15例）或氟达拉滨（7例）。ATG的总剂量为4.5mg/kg，在3天内给予，于第0天结束。ATG组和对照组的急性GVHD（aGVHD）II-IV级、aGVHD III-IV级和慢性GVHD（cGVHD）发生率分别为19±5%对32±6%（P = 0.1）、6±3%对13±5%（P = 无显著性差异）和55±8%对96±3%（P = 0.002）。与对照组相比，接受ATG治疗的患者cGVHD累及的部位更少（平均2.1±0.2对2.8±0.2，P = 0.04）。有或无ATG情况下的非复发死亡率（NRM），在100天时分别为4±3%对17±5%（P = 0.002），在4年时分别为9±4%对34±7%（P = 0.002）。3例接受ATG治疗的患者死于GVHD相关原因，而对照组为14例（P = 0.007）。尽管使用ATG后复发趋势更明显（4年时为43±7%对22±7%，P = 0.05），但接受ATG治疗的患者生存率为66±7%，而对照组为50±7%（P = 0.046）。本研究表明，与既往方案相比，在接受MRD BCT的受者中，采用含氟达拉滨和口服或静脉注射白消安并联合移植前ATG的清髓方案可能导致cGVHD减少、TRM降低，且可能改善幸存者的生活质量。
