Czuczman M S, Grillo-López A J, McLaughlin P, White C A, Saleh M, Gordon L, LoBuglio A F, Rosenberg J, Alkuzweny B, Maloney D
Department of Hematologic Oncology and Bone Marrow Transplantation, Roswell Park Cancer Institute, Buffalo, New York 14263, USA.
Ann Oncol. 2001 Jan;12(1):109-14. doi: 10.1023/a:1008395214584.
Patients who were PCR-positive for B-cell leukemia-lymphoma 2 (bcl-2) gene rearrangement [t(14;18)] were evaluated for responses to rituximab alone or combined with CHOP.
Patients had relapsed or refractory low-grade or follicular non-Hodgkin's lymphoma (IWF: A-D). The single-agent trial used 375 mg/m2 weekly x 4; combination therapy included six cycles of CHOP and six 375 mg/m2 infusions of rituximab. Bcl-2 analyses of bone marrow (BM) and peripheral blood (PB) samples at base-line and following therapy were performed using a PCR assay.
In the single-agent trial, of 70 patients whose peripheral blood (PB) was bcl-2 positive at baseline, 36 became bcl-2-negative, 13 remained positive, and 21 varied between positive and negative. The overall response rates (ORRs) were 72%, 31%, and 57%, respectively. Twelve of twenty-two patients with repeat bone marrow (BM) samples were bcl-2-negative three months post-treatment. Of 18 patients in the combination trial, 8 were bcl-2 positive in PB and/or BM. All of seven patients positive in PB at baseline and six of seven patients positive in BM were negative at the end of therapy; all patients responded to treatment (100% ORR).
Rituximab, alone or combined with CHOP, eradicated bcl-2 positive cells from PB and BM in over half of the patients treated and was associated with a high overall clinical response rate. The impact on disease-free and overall survival awaits long-term follow up.
对B细胞白血病-淋巴瘤2（bcl-2）基因重排[t(14;18)]呈聚合酶链反应（PCR）阳性的患者，评估其对单独使用利妥昔单抗或联合CHOP方案的反应。
患者患有复发性或难治性低度或滤泡性非霍奇金淋巴瘤（国际工作分类：A-D）。单药试验采用375mg/m²每周1次，共4周；联合治疗包括6个周期的CHOP方案以及6次375mg/m²的利妥昔单抗输注。使用PCR检测法对基线期及治疗后的骨髓（BM）和外周血（PB）样本进行bcl-2分析。
在单药试验中，70例基线期外周血bcl-2阳性的患者中，36例变为bcl-2阴性，13例仍为阳性，21例呈阳性和阴性交替变化。总体缓解率（ORR）分别为72%、31%和57%。22例有重复骨髓样本的患者中，12例在治疗后3个月时bcl-2阴性。联合试验的18例患者中，8例外周血和/或骨髓bcl-2阳性。基线期外周血阳性的7例患者以及骨髓阳性的7例患者中的6例，在治疗结束时均为阴性；所有患者对治疗均有反应（ORR为100%）。
利妥昔单抗单独使用或联合CHOP方案，在超过半数接受治疗的患者中清除了外周血和骨髓中的bcl-2阳性细胞，并与较高的总体临床缓解率相关。对无病生存期和总生存期的影响有待长期随访。
