Section of Hematopathology, Department of Immunology and Pathology, Washington University School of Medicine, St. Louis, Missouri.
Division of Public Health Sciences, Department of Surgery, Washington University School of Medicine, St. Louis, Missouri.
Biol Blood Marrow Transplant. 2017 Dec;23(12):2199-2204. doi: 10.1016/j.bbmt.2017.08.022. Epub 2017 Aug 26.
Cell-of-origin determination has emerged as an important prognostic factor for patients initially diagnosed with diffuse large B cell lymphoma (DLBCL). Specifically, the nongerminal center B cell-like (non-GCB) subtype, composed predominantly of the activated B cell-like (ABC) molecular subtype, has been shown to portend poor prognosis because of its more aggressive nature and resistance to standard cyclophosphamide, hydroxydaunorubicin, oncovin, prednisone (CHOP)-like chemotherapy compared with the GCB subtype. The recurrent MyD88 L265P mutation, present in 29% of ABC DLBCL, was reported as an independent poor prognostic factor for patients with newly diagnosed DLBCL. For patients whose disease relapses or is refractory to first-line chemotherapy, high-dose chemotherapy with autologous stem cell transplantation (ASCT) is frequently offered as salvage therapy. However, the impact of MyD88 mutation status on post-ASCT outcome has not been reported. Here, we retrospectively analyzed, with up to 20 years of follow-up, 165 patients who underwent ASCT for relapsed/refractory DLBCL at our institution. We found that MyD88 mutation status did not correlate with overall survival (OS), post-ASCT OS, or progression-free survival (PFS). Patients with non-GCB subtype had significantly worse OS from initial diagnosis and after ASCT. Notably, high International Prognostic Index score was predictive of poor pre- and post-transplant PFS and post-transplant OS.
细胞起源的确定已成为初始诊断为弥漫性大 B 细胞淋巴瘤(DLBCL)患者的重要预后因素。具体而言,非生发中心 B 细胞样(non-GCB)亚型,主要由激活 B 细胞样(ABC)分子亚型组成,由于其更具侵袭性和对标准环磷酰胺、阿霉素、长春新碱、泼尼松(CHOP)样化疗的耐药性,预示着预后不良,而非 GCB 亚型。在 29%的 ABC DLBCL 中存在的反复 MyD88 L265P 突变被报道为新诊断为 DLBCL 患者的独立不良预后因素。对于疾病复发或对一线化疗耐药的患者,高剂量化疗联合自体干细胞移植(ASCT)常作为挽救治疗。然而,MyD88 突变状态对 ASCT 后结局的影响尚未报道。在这里,我们回顾性分析了在我们机构接受 ASCT 治疗的 165 例复发性/难治性 DLBCL 患者,随访时间长达 20 年。我们发现 MyD88 突变状态与总生存期(OS)、ASCT 后 OS 或无进展生存期(PFS)无关。非 GCB 亚型患者从初始诊断和 ASCT 后 OS 显著更差。值得注意的是,国际预后指数评分高预测移植前和移植后 PFS 和移植后 OS 不良。