Hess Georg, Flohr Thomas, Kolbe Karin, Bonn Sarah, Schuler Martin, Derigs Hans Günter, Huber Christoph
Department of Haematology/Oncology, Johannes Gutenberg University, Langenbeckstr. 1, 55131, Mainz, Germany.
Ann Hematol. 2006 Nov;85(11):769-79. doi: 10.1007/s00277-006-0157-6. Epub 2006 Aug 1.
To better define the role of rituximab in salvage and high-dose therapy (HDT) for relapsed or refractory non-Hodgkin's lymphoma (NHL), patients treated before the implementation of rituximab in salvage and HDT (n = 57, control group) were compared with patients with rituximab included in this procedure (n = 36, study group). All patients had been antibody-naive at this point, and analyses were performed separately for 22 and 31 patients with aggressive, and 14 and 26 patients with indolent NHL, respectively. All patients received two courses of salvage therapy, predominantly dexamethasone, BCNU, etoposide, cytosine arabinoside, melphalan. Conditioning regimens included BCNU, etoposide, cytosine arabinoside, melphalan; BCNU, etoposide, cytosine arabinoside, cyclophosphamide or total body irradiation and cyclophosphamide, with rituximab added for patients in the study group. Despite the absence of differences in stem cell collection, haematopoietic recovery was delayed in patients with aggressive NHL treated in the study group: median days to absolute neutrophil count more than 0.5 x 10(9)/l, 11 vs 10 (p = 0.01), and platelets more than 20 x 10(9)/l, 14 vs 11 (p = 0.0005), with an increased requirement for platelet transfusions. No similar observations were made in indolent lymphoma patients. Remission rates were superior for patients with aggressive NHL in the study group. With a median follow-up of 7.25 and 4.5 years, this resulted in an improvement in OS at 4.5 years: 67 vs 45% (95% confidence interval, 47-87% vs 28-64%; p = 0.0468). For patients with indolent lymphoma, no comparable benefit was detectable. Our data support the use of rituximab in HDT for patients with aggressive NHL. For patients with indolent NHL, only longer follow-up and/or randomized trials may help to fully determine the impact of rituximab on the outcome after HDT.
为了更好地明确利妥昔单抗在复发或难治性非霍奇金淋巴瘤（NHL）的挽救治疗及大剂量治疗（HDT）中的作用，将在挽救治疗及HDT中应用利妥昔单抗之前接受治疗的患者（n = 57，对照组）与在此治疗过程中纳入利妥昔单抗的患者（n = 36，研究组）进行比较。此时所有患者均未接受过抗体治疗，分别对22例侵袭性NHL患者和31例惰性NHL患者，以及14例侵袭性NHL患者和26例惰性NHL患者进行了分析。所有患者均接受了两个疗程的挽救治疗，主要药物为地塞米松、卡莫司汀（BCNU）、依托泊苷、阿糖胞苷、美法仑。预处理方案包括BCNU、依托泊苷、阿糖胞苷、美法仑；BCNU、依托泊苷、阿糖胞苷、环磷酰胺，或全身照射及环磷酰胺，研究组患者在此基础上加用利妥昔单抗。尽管在干细胞采集方面没有差异，但研究组中接受治疗的侵袭性NHL患者造血恢复延迟：绝对中性粒细胞计数超过0.5×10⁹/L的中位天数，分别为11天和10天（p = 0.01），血小板计数超过20×10⁹/L的中位天数，分别为14天和11天（p = 0.0005），血小板输注需求增加。在惰性淋巴瘤患者中未观察到类似情况。研究组中侵袭性NHL患者的缓解率更高。中位随访时间分别为7.25年和4.5年，这导致4.5年时总生存期有所改善：分别为67%和45%（95%置信区间，47 - 87%对28 - 64%；p = 0.0468）。对于惰性淋巴瘤患者，未发现类似的获益。我们的数据支持在HDT中对侵袭性NHL患者使用利妥昔单抗。对于惰性NHL患者，只有更长时间的随访和/或随机试验可能有助于充分确定利妥昔单抗对HDT后结局的影响。
