Graft-Versus-Host Disease and Graft-Versus-Tumor Effects After Allogeneic Hematopoietic Cell Transplantation
Graft-Versus-Host Disease and Graft-Versus-Tumor Effects After Allogeneic Hematopoietic Cell Transplantation
复制标题
DOI：
10.1200/jco.2012.45.0247
复制
发表时间：
2013-04-20
影响因子：
45.3
通讯作者：
Sandmaier, Brenda M.
中科院分区：
文献类型：
--
作者：
Storb, Rainer;Gyurkocza, Boglarka;Sandmaier, Brenda M.
我们设计了一种最小强度预处理方案，用于因年龄、严重合并症或既往接受过大剂量异基因造血细胞移植（HCT）而无法耐受高强度方案的晚期恶性血液病患者的异基因造血细胞移植（HCT）。该方案允许最纯粹的评估移植物抗肿瘤（GVT）的影响，除了调节和移植物抗宿主病（GVHD）不增加的方案相关toxicity.Patients和MethodsPatients接受低剂量全身照射+/-氟达拉滨HCT前从HLA匹配的相关（n = 611）或无关（n = 481）供体，随后给予吗替麦考酚酯和钙调磷酸酶抑制剂以帮助移植和控制GVHD。中位患者年龄为56岁（范围：7 - 75岁）。45%的患者合并症评分>= 3。中位随访时间为5年（范围，0.6至12.7年）。结果根据疾病的风险，合并症，和GVHD，持久缓解被认为是在45%至75%的患者，5年生存率范围从25%至60%。5年时，非复发死亡率（NRM）为24%，复发死亡率为34.5%。大多数NRM是GVHD的结果。与GVHD相关的NRM相关的最重要因素是严重的合并症和无关供体的移植物。大多数复发发生在免疫系统受损的早期。无关和相关移植后GVT效应相当。慢性GVHD，而不是急性GVHD，进一步增加GVT效应。增加NRM.ConclusionAllogeneic HCT依赖于GVT的影响是可行的，并导致相当数量的恶性肿瘤的治愈与慢性GVHD相关的潜在利益被超过。改善的结果可能来自HCT后早期控制恶性肿瘤进展和有效预防GVHD的方法。临床肿瘤学杂志31：1530-1538。(C)2013年美国临床肿瘤学会
PurposeWe designed a minimal-intensity conditioning regimen for allogeneic hematopoietic cell transplantation (HCT) in patients with advanced hematologic malignancies unable to tolerate high-intensity regimens because of age, serious comorbidities, or previous high-dose HCT. The regimen allows the purest assessment of graft-versus-tumor (GVT) effects apart from conditioning and graft-versus-host disease (GVHD) not augmented by regimen-related toxicities.Patients and MethodsPatients received low-dose total-body irradiation +/- fludarabine before HCT from HLA-matched related (n = 611) or unrelated (n = 481) donors, followed by mycophenolate mofetil and a calcineurin inhibitor to aid engraftment and control GVHD. Median patient age was 56 years (range, 7 to 75 years). Forty-five percent of patients had comorbidity scores of >= 3. Median follow-up time was 5 years (range, 0.6 to 12.7 years).ResultsDepending on disease risk, comorbidities, and GVHD, lasting remissions were seen in 45% to 75% of patients, and 5-year survival ranged from 25% to 60%. At 5 years, the nonrelapse mortality (NRM) rate was 24%, and the relapse mortality rate was 34.5%. Most NRM was a result of GVHD. The most significant factors associated with GVHD-associated NRM were serious comorbidities and grafts from unrelated donors. Most relapses occurred early while the immune system was compromised. GVT effects were comparable after unrelated and related grafts. Chronic GVHD, but not acute GVHD, further increased GVT effects. The potential benefit associated with chronic GVHD was outweighed by increased NRM.ConclusionAllogeneic HCT relying on GVT effects is feasible and results in cures of an appreciable number of malignancies. Improved results could come from methods that control progression of malignancy early after HCT and effectively prevent GVHD. J Clin Oncol 31:1530-1538. (C) 2013 by American Society of Clinical Oncology