Puckrin Robert, Kinzel Megan, Stewart Douglas, Chaudhry Ahsan, Jamani Kareem, Storek Jan
University of Calgary, Calgary, Alberta, Canada; Alberta Health Services, Calgary, Alberta, Canada.
University of Calgary, Calgary, Alberta, Canada.
Transplant Cell Ther. 2025 Mar;31(3):176.e1-176.e8. doi: 10.1016/j.jtct.2024.12.024. Epub 2025 Jan 5.
Multiple factors have been described to influence the risk of acute or chronic graft-versus-host disease (aGVHD or cGVHD) after allogeneic hematopoietic cell transplantation (HCT), including underlying chronic myeloid leukemia (CML) and high-dose total body irradiation (TBI). However, the impact of the underlying disease or low-dose TBI on the risk of GVHD in the modern era has not been determined. The objective of this study was to determine risk factors for GVHD in the modern era in the setting of antithymocyte globulin (ATG)-based GVHD prophylaxis. This retrospective study included 1219 patients with hematologic malignancy who underwent first peripheral blood allogeneic HCT using myeloablative fludarabine and busulfan conditioning ± low-dose total body irradiation, along with ATG, cyclosporine, and methotrexate as GVHD prophylaxis. The adjusted cumulative incidence of GVHD was compared between patient subgroups using multivariable competing risks regression. When disregarding the underlying disease, risk factors for grade 2-4 aGVHD were donor type other than matched sibling donor (non-MSD) and lack of low-dose TBI (non-TBI). Risk factors for grade 3-4 aGVHD were non-MSD, non-TBI, and CMV donor negative/recipient positive serostatus (D-R+). Risk factors for moderate-severe cGVHD were ≤9/10 HLA match, non-male/male donor/recipient sex, and non-TBI. In models including the underlying disease, additional significant risk factors were chronic lymphocytic leukemia (CLL) for grade 2 to 4 aGVHD (sub-hazard ratio over acute myeloid leukemia [SHR] 3.16, 95% CI 1.97-5.08, P < .001); CLL and acute lymphoblastic leukemia (ALL) for grade 3-4 aGVHD (SHR for CLL 3.54, 95% CI 1.54-8.17, P = .003 and SHR for ALL 2.26, 95% CI 1.26-4.04, P = .006); and myelofibrosis (MF) for moderate-severe cGVHD (SHR 2.14, 95 CI 1.34-3.41, P = .001). In the modern era when using ATG for GVHD prophylaxis, newly identified risk factors include CLL and non-TBI for grade 2-4 aGVHD; CLL, ALL, and non-TBI for grade 3-4 aGVHD; and MF and non-TBI for moderate-severe cGVHD. These findings, if confirmed in a separate cohort, should be taken into consideration when tailoring the prophylaxis and monitoring of GVHD.
已有多种因素被描述为会影响异基因造血细胞移植（HCT）后急性或慢性移植物抗宿主病（aGVHD或cGVHD）的风险，包括潜在的慢性髓性白血病（CML）和高剂量全身照射（TBI）。然而，在现代，潜在疾病或低剂量TBI对GVHD风险的影响尚未确定。本研究的目的是确定在基于抗胸腺细胞球蛋白（ATG）的GVHD预防方案下，现代GVHD的风险因素。这项回顾性研究纳入了1219例血液系统恶性肿瘤患者，这些患者接受了首次外周血异基因HCT，采用氟达拉滨和白消安进行清髓预处理±低剂量全身照射，同时使用ATG、环孢素和甲氨蝶呤进行GVHD预防。使用多变量竞争风险回归比较患者亚组之间GVHD的调整累积发病率。在不考虑潜在疾病的情况下，2-4级aGVHD的风险因素是除匹配同胞供体（非MSD）以外的供体类型以及缺乏低剂量TBI（非TBI）。3-4级aGVHD的风险因素是非MSD、非TBI以及巨细胞病毒供体阴性/受体阳性血清学状态（D-R+）。中度至重度cGVHD的风险因素是≤9/10 HLA匹配、非男性/男性供体/受体性别以及非TBI。在纳入潜在疾病的模型中，其他显著风险因素包括：2至4级aGVHD的慢性淋巴细胞白血病（CLL）（相对于急性髓性白血病的亚危险比[SHR]为3.16，95%可信区间为1.97-5.08，P <.001）；3-4级aGVHD的CLL和急性淋巴细胞白血病（ALL）（CLL的SHR为3.54，95%可信区间为1.54-8.17，P =.003，ALL的SHR为2.26，95%可信区间为1.26-4.04，P =.006）；以及中度至重度cGVHD的骨髓纤维化（MF）（SHR为2.14，95%可信区间为1.34-3.41，P =.001）。在现代使用ATG进行GVHD预防时，新发现的风险因素包括：2-4级aGVHD的CLL和非TBI；3-4级aGVHD的CLL、ALL和非TBI；以及中度至重度cGVHD的MF和非TBI。如果在另一个队列中得到证实，这些发现应在制定GVHD的预防和监测方案时予以考虑。
