Murashige Naoko, Kami Masahiro, Mori Shin-ichiro, Katayama Yuta, Kobayashi Kazuhiko, Onishi Yasushi, Hori Akiko, Kishi Yukiko, Hamaki Tamae, Tajima Kinuko, Kanda Yoshinobu, Tanosaki Ryuji, Takaue Yoichi
Hematopoietic Stem Cell Transplantation Unit, The National Cancer Center Hospital, Tokyo, Japan.
Am J Hematol. 2008 Aug;83(8):630-4. doi: 10.1002/ajh.21197.
To investigate clinical features of acute graft-versus-host disease (GVHD) following reduced intensity stem-cell transplantation (RIST), we retrospectively investigated medical records of 65 patients with hematologic malignancies who underwent RIST from a matched related donor. Preparative regimen comprised fludarabine 30 mg/m(2) (n = 53) or cladribine 0.11 mg/kg (n = 12) for 6 days plus busulfan 4 mg/kg for 2 days. Twelve patients received rabbit antithymocyte globulin 2.5 mg/kg/day for 2-4 consecutive days. Grade II to IV acute GVHD was diagnosed in 36 patients (55%). Its median onset was day 58 (range, 17-109), while it was bimodal, peaking day 15-29 (early-onset GVHD, n = 18) and day 75-89 days (late-onset GVHD, n = 18). Variables that were more common in early-onset GVHD than late-onset GVHD included skin rash (89% vs. 61%) and noninfectious fevers (33% vs. 11%). Desaturation, pulmonary infiltrates and hyperbilirubinemia (>2.0 mg/dL) were more common in late-onset GVHD (6% vs. 22%, 0% vs. 17%, and 6% vs. 33%, respectively). All of the patients with early-onset GVHD given corticosteroid responded to it, while 5 of the 18 patients with late-onset GVHD failed to respond it. Patients with either early-onset or late-onset GVHD tended to have better progression-free survival (PFS) than those without it; however, there was no significant difference in PFS between patients with early-onset GVHD and those with late-onset GVHD. This study suggests that several etiologies might have contributed to the development of acute GVHD following RIST.
为研究减低剂量干细胞移植(RIST)后急性移植物抗宿主病(GVHD)的临床特征,我们回顾性调查了65例接受来自匹配相关供者RIST的血液系统恶性肿瘤患者的病历。预处理方案包括氟达拉滨30mg/m²(n = 53)或克拉屈滨0.11mg/kg(n = 12),连用6天,加白消安4mg/kg,连用2天。12例患者连续2 - 4天接受兔抗胸腺细胞球蛋白2.5mg/kg/天治疗。36例患者(55%)被诊断为Ⅱ - Ⅳ级急性GVHD。其发病中位时间为第58天(范围17 - 109天),呈双峰分布,在第15 - 29天达到高峰(早发型GVHD,n = 18)和第75 - 89天达到高峰(晚发型GVHD)。早发型GVHD比晚发型GVHD更常见的变量包括皮疹(89%对61%)和非感染性发热(33%对11%)。低氧血症、肺部浸润和高胆红素血症(>2.0mg/dL)在晚发型GVHD中更常见(分别为6%对22%、0%对17%、6%对33%)。所有接受皮质类固醇治疗的早发型GVHD患者均有反应,而18例晚发型GVHD患者中有5例对此无反应。早发型或晚发型GVHD患者的无进展生存期(PFS)往往比无GVHD的患者更好;然而,早发型GVHD患者和晚发型GVHD患者的PFS之间没有显著差异。本研究表明,几种病因可能促成了RIST后急性GVHD的发生。