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弥漫性大B细胞淋巴瘤一线含利妥昔单抗的化疗免疫疗法早期失败并不能预测自体造血细胞移植无效。

Early failure of frontline rituximab-containing chemo-immunotherapy in diffuse large B cell lymphoma does not predict futility of autologous hematopoietic cell transplantation.

作者信息

Hamadani Mehdi, Hari Parameswaran N, Zhang Ying, Carreras Jeanette, Akpek Görgün, Aljurf Mahmoud D, Ayala Ernesto, Bachanova Veronika, Chen Andy I, Chen Yi-Bin, Costa Luciano J, Fenske Timothy S, Freytes César O, Ganguly Siddhartha, Hertzberg Mark S, Holmberg Leona A, Inwards David J, Kamble Rammurti T, Kanfer Edward J, Lazarus Hillard M, Marks David I, Nishihori Taiga, Olsson Richard, Reddy Nishitha M, Rizzieri David A, Savani Bipin N, Solh Melhem, Vose Julie M, Wirk Baldeep, Maloney David G, Smith Sonali M, Montoto Silvia, Saber Wael, Alpdogan Onder, Cashen Amanda, Dandoy Christopher, Finke Robert, Gale Robert, Gibson John, Hsu Jack W, Janakiraman Nalini, Laughlin Mary J, Lill Michael, Cairo Mitchell S, Munker Reinhold, Rowlings Phil A, Schouten Harry C, Shea Thomas C, Stiff Patrick J, Waller Edmund K

机构信息

Center for International Blood and Marrow Transplant Research, Department of Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin.

Center for International Blood and Marrow Transplant Research, Department of Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin.

出版信息

Biol Blood Marrow Transplant. 2014 Nov;20(11):1729-36. doi: 10.1016/j.bbmt.2014.06.036. Epub 2014 Jul 5.

Abstract

The poor prognosis for patients with diffuse large B cell lymphoma (DLBCL) who relapse within 1 year of initial diagnosis after first-line rituximab-based chemo-immunotherapy has created controversy about the role of autologous transplantation (HCT) in this setting. We compared autologous HCT outcomes for chemosensitive DLBCL patients between 2000 and 2011 in 2 cohorts based on time to relapse from diagnosis. The early rituximab failure (ERF) cohort consisted of patients with primary refractory disease or those with first relapse within 1 year of initial diagnosis. The ERF cohort was compared with those relapsing >1 year after initial diagnosis (late rituximab failure [LRF] cohort). ERF and LRF cohorts included 300 and 216 patients, respectively. Nonrelapse mortality (NRM), progression/relapse, progression-free survival (PFS), and overall survival (OS) of ERF versus LRF cohorts at 3 years were 9% (95% confidence interval [CI], 6% to 13%) versus 9% (95% CI, 5% to 13%), 47% (95% CI, 41% to 52%) versus 39% (95% CI, 33% to 46%), 44% (95% CI, 38% to 50%) versus 52% (95% CI, 45% to 59%), and 50% (95% CI, 44% to 56%) versus 67% (95% CI, 60% to 74%), respectively. On multivariate analysis, ERF was not associated with higher NRM (relative risk [RR], 1.31; P = .34). The ERF cohort had a higher risk of treatment failure (progression/relapse or death) (RR, 2.08; P < .001) and overall mortality (RR, 3.75; P <.001) within the first 9 months after autologous HCT. Beyond this period, PFS and OS were not significantly different between the ERF and LRF cohorts. Autologous HCT provides durable disease control to a sizeable subset of DLBCL despite ERF (3-year PFS, 44%) and remains the standard-of-care in chemosensitive DLBCL regardless of the timing of disease relapse.

摘要

对于在基于利妥昔单抗的一线化疗免疫治疗后1年内复发的弥漫性大B细胞淋巴瘤(DLBCL)患者,其预后较差,这引发了关于自体移植(造血干细胞移植)在此种情况下作用的争议。我们比较了2000年至2011年期间2个队列中化疗敏感的DLBCL患者自体造血干细胞移植的结果,这2个队列根据从诊断开始的复发时间划分。早期利妥昔单抗治疗失败(ERF)队列包括原发性难治性疾病患者或在初始诊断后1年内首次复发的患者。将ERF队列与初始诊断1年后复发的患者(晚期利妥昔单抗治疗失败[LRF]队列)进行比较。ERF队列和LRF队列分别包括300例和216例患者。3年时,ERF队列与LRF队列的非复发死亡率(NRM)、进展/复发、无进展生存期(PFS)和总生存期(OS)分别为9%(95%置信区间[CI],6%至13%)对9%(95%CI,5%至13%)、47%(95%CI,41%至52%)对39%(95%CI,33%至46%)、44%(95%CI,38%至50%)对52%(95%CI,45%至59%)以及50%(95%CI,44%至56%)对67%(95%CI,60%至74%)。多因素分析显示,ERF与较高的NRM无关(相对风险[RR],1.31;P = 0.34)。ERF队列在自体造血干细胞移植后的前9个月内治疗失败(进展/复发或死亡)风险较高(RR,2.08;P < 0.001),总死亡率也较高(RR,3.75;P < 0.001)。在此期间之后,ERF队列和LRF队列的PFS和OS无显著差异。尽管存在ERF(3年PFS为44%),自体造血干细胞移植仍能为相当一部分DLBCL患者提供持久的疾病控制,并且无论疾病复发时间如何,仍然是化疗敏感DLBCL的标准治疗方法。

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