Janikova Andrea, Bortlicek Zbynek, Campr Vit, Kopalova Natasa, Benesova Katerina, Hamouzova Michaela, Belada David, Prochazka Vit, Pytlik Robert, Vokurka Samuel, Pirnos Jan, Duras Juraj, Mocikova Heidi, Mayer Jiri, Trneny Marek
Department of Internal Medicine-Hematology and Oncology, Masaryk University and University Hospital Brno, Brno, Czech Republic.
Department of Hematology and Oncology, University Hospital Brno and Masaryk University Brno, Jihlavska 20, 625 00, Brno, Czech Republic.
Ann Hematol. 2018 Apr;97(4):669-678. doi: 10.1007/s00277-017-3218-0. Epub 2018 Jan 9.
The aim of this study is to assess the incidence, risk factors, and outcome of biopsy-proven transformation in follicular lymphoma (FL) patients in the rituximab era. Transformation was analyzed in 1233 patients with initially diagnosed FL grades 1-3A, identified between 2002 and 2012 in the prospectively maintained Czech Lymphoma Study Group database. Only patients with histologically proven transformation (HT) were included. HT occurred in 58 cases at a median of 3.0 years from the initial FL diagnosis; the HT rate was 4% at 5 years. Transformation occurred most frequently at the first relapse (84% patients). Median OS from the HT was 2.5 years (95% CI 0.4-4.6) and 6-year OS with HT was shorter compared to all FLs (60 vs. 83.9%; 95% CI). A bulky tumor (≥ 10 cm), increased lactate dehydrogenase, age ≥ 60 years, and International Prognostic Index (intermediate/high risk), but not Follicular Lymphoma International Prognostic Index, were associated with transformation (p < 0.05). In the first line, 70% of patients received rituximab (including 36% rituximab maintenance), 57% CHOP-like regimens, and 2.6% of patients were treated with fludarabine-based therapy, whereas 11% of patients were watched only. The patients treated with R-CHOP in the first line (n = 591) showed the transformation rate at 5 years of 4.23% (95% CI 2.52-5.93); subsequent rituximab maintenance (n = 276) vs. observation (n = 153) was associated with a lower transformation rate (p.033; HR 3.29; CI 1.10-9.82). The transformation rate seems to be lower than in previous series, which may be influenced by broad use of rituximab, but prognosis of HT developed during therapy continues to be poor.
本研究旨在评估利妥昔单抗时代滤泡性淋巴瘤（FL）患者经活检证实的转化的发生率、危险因素及转归。对2002年至2012年间在前瞻性维护的捷克淋巴瘤研究组数据库中最初诊断为1-3A级FL的1233例患者的转化情况进行了分析。仅纳入组织学证实有转化（HT）的患者。HT发生于58例患者，自最初FL诊断起的中位时间为3.0年；5年时HT发生率为4%。转化最常发生于首次复发时（84%的患者）。HT后的中位总生存期为2.5年（95%CI 0.4-4.6），与所有FL相比，HT患者的6年总生存期较短（60%对83.9%；95%CI）。巨大肿瘤（≥10cm）、乳酸脱氢酶升高、年龄≥60岁和国际预后指数（中/高风险），而非滤泡性淋巴瘤国际预后指数，与转化相关（p<0.05）。一线治疗中，70%的患者接受利妥昔单抗治疗（包括36%的利妥昔单抗维持治疗），57%的患者接受类CHOP方案治疗，2.6%的患者接受基于氟达拉滨的治疗，而11%的患者仅接受观察。一线接受R-CHOP治疗的患者（n=591）5年时的转化率为4.23%（95%CI 2.52-5.93）；后续利妥昔单抗维持治疗（n=276）与观察（n=153）相比，转化率较低（p=0.033；HR 3.29；CI 1.10-9.82）。转化率似乎低于先前系列研究，这可能受利妥昔单抗广泛应用的影响，但治疗期间发生HT的预后仍然较差。
