Department of Internal Medicine III, University Medical Center Regensburg, Regensburg, Germany.
Department of Nephrology, University Medical Center Regensburg, Regensburg, Germany.
Transplant Cell Ther. 2023 Dec;29(12):772.e1-772.e10. doi: 10.1016/j.jtct.2023.09.016. Epub 2023 Sep 28.
Chronic graft-versus-host disease (cGVHD) is the leading cause of late nonrelapse mortality (NRM) after allogeneic hematopoietic stem cell transplantation (alloHSCT) and defined by 8 diagnostic target organs. Recently, provisional criteria for atypical manifestations of cGVHD that include manifestations in nonclassic organs as well as atypical manifestations in National Institutes of Health (NIH)-defined organs, were proposed by a NIH task force. Little is known about the incidence, risk factors, and impact on survival of atypical cGVHD, however. The aim of the present study was to analyze these parameters in a sequential patient population. We retrospectively screened 623 patients who underwent alloHSCT at the University Medical Center Regensburg between January 2008 and December 2020 for atypical cGVHD manifestations, applying the provisional NIH taskforce criteria. A total of 102 patients (16.4%) met the criteria, representing 25% of all cGVHD cases, and 14 patients (2.2%) had only atypical cGVHD. The most frequent manifestations were immune-mediated cytopenias (24.5%), renal cGVHD (13.7%) and (poly)serositis (13.7%). Multivariate analysis identified prior acute GVHD (odds ratio [OR], 2.28 and 2.93) and infusion of donor lymphocytes (OR, 1.77 for both) as risk factors for classic cGVHD and atypical cGVHD, whereas total body irradiation was an independent risk factor for atypical cGVHD manifestations only (OR, 1.76). Compared to patients without cGVHD, those with atypical and NIH-defined cGVHD showed similarly better overall survival (P = .034 and < .001) and low relapse-related mortality (P < .001 for both). NRM was significantly increased by atypical GVHD, but not by NIH-defined cGVHD (P = .019 and .10), which was driven only by a few atypical organ manifestations (eg, renal, restrictive lung disease, peripheral neuropathy), whereas others did not contribute to NRM (eg, thyroid gland, musculoskeletal, pancreas). In summary, atypical cGVHD is more common than previously estimated and has both similarities with and differences from NIH-defined cGVHD. In particular, the increased NRM and a subset of patients with only atypical cGVHD point to the urgent need to capture these manifestations in cGVHD cohorts, including analysis of treatment outcomes.
慢性移植物抗宿主病（cGVHD）是异基因造血干细胞移植（alloHSCT）后晚期非复发相关死亡率（NRM）的主要原因，其由 8 个诊断靶器官定义。最近，NIH 工作组提出了 cGVHD 不典型表现的临时标准，这些表现包括非经典器官的表现以及 NIH 定义的器官中的不典型表现。然而，对于不典型 cGVHD 的发生率、危险因素和对生存的影响知之甚少。本研究的目的是在连续的患者人群中分析这些参数。我们回顾性筛选了 2008 年 1 月至 2020 年 12 月在雷根斯堡大学医学中心接受 alloHSCT 的 623 例患者，应用 NIH 工作组的临时标准，评估不典型 cGVHD 表现。共有 102 例患者（16.4%）符合标准，占所有 cGVHD 病例的 25%，14 例患者（2.2%）仅有不典型 cGVHD。最常见的表现是免疫介导的血细胞减少症（24.5%）、肾 cGVHD（13.7%）和（多）浆膜炎（13.7%）。多变量分析发现，急性移植物抗宿主病（GVHD）（比值比 [OR]，2.28 和 2.93）和供者淋巴细胞输注（OR，2 次均为 1.77）是经典 cGVHD 和不典型 cGVHD 的危险因素，而全身照射是不典型 cGVHD 表现的独立危险因素（OR，1.76）。与无 cGVHD 的患者相比，有不典型和 NIH 定义的 cGVHD 的患者的总体生存率（P=0.034 和 <0.001）和低复发相关死亡率（P<0.001）相似。不典型 GVHD 显著增加 NRM，但 NIH 定义的 cGVHD 则没有（P=0.019 和 0.10），这仅由少数不典型器官表现驱动（如肾、限制性肺病、周围神经病），而其他表现则不导致 NRM（如甲状腺、肌肉骨骼、胰腺）。总之，不典型 cGVHD 比以前估计的更为常见，并且与 NIH 定义的 cGVHD 既有相似之处，也有不同之处。特别是，增加的 NRM 和一小部分仅有不典型 cGVHD 的患者表明迫切需要在 cGVHD 队列中捕获这些表现，包括对治疗结果的分析。
