Dreger P, Martin S, Kuse R, Sonnen R, Glass B, Kröger N, Parwaresch R, Kneba M, Schmitz N, Haas R
Second Department of Medicine, University of Kiel, Germany.
Hematol J. 2000;1(2):87-94. doi: 10.1038/sj.thj.6200007.
The purpose of this analysis was to investigate if early sequential high-dose therapy with autologous stem cell transplantation (ASCT) can improve the poor prognosis of patients with disseminated mantle cell lymphoma (MCL).
A joint analysis of two parallel single center studies was performed. Both were characterized by a sequential high-dose therapy consisting of an intensive chemotherapy ('HAM' or 'Dexa-BEAM') for mobilization of peripheral blood stem cells and induction of minimal disease followed by a total body irradiation-containing myeloablative regimen and ASCT. Forty-six patients with reference panel-confirmed stage III/IV MCL were included. Thirty-four patients were accrued to the protocol immediately after diagnosis ('upfront ASCT' group). These 34 patients received a standard first-line regimen prior to mobilization. The remaining 12 patients were put on the protocol later during the course of their disease ('delayed ASCT' group).
All patients were in remission after mobilization chemotherapy and proceeded to ASCT; there were no exclusions due to poor response, poor mobilization, or patient refusal. With a follow-up of 24 (2-73) months post transplant, the event-free and overall survival probabilities at 2 years were 77 and 100% for the upfront ASCT group compared to 30% (P=0.0007) and 54% (P=0.0016) for the delayed ASCT group. Event-free and overall survival tended to be longer in the upfront ASCT group than in the delayed ASCT group also if calculated from initial diagnosis (76 and 93% vs 42 and 63%, respectively, at 4 years after diagnosis; median follow-up 35 months), although this was not statistically significant. Besides timing of ASCT, only spleen size was identified as an independent predictor of survival by univariate and multivariate analysis.
ASCT is not curative but may improve the prognosis of patients with MCL if performed as part of an intensive first-line treatment strategy. In contrast, the benefits of this approach for salvaging individuals with relapsed disease appear to be limited.
本分析的目的是研究自体干细胞移植(ASCT)的早期序贯大剂量疗法能否改善弥漫性套细胞淋巴瘤(MCL)患者的不良预后。
对两项平行的单中心研究进行联合分析。两项研究均采用序贯大剂量疗法,包括强化化疗(“HAM”或“Dexa-BEAM”)以动员外周血干细胞并诱导微小疾病,随后是含全身照射的清髓方案和ASCT。纳入了46例经参考标准确诊为III/IV期MCL的患者。34例患者在诊断后立即进入方案(“ upfront ASCT”组)。这34例患者在动员前接受了标准的一线方案。其余12例患者在病程后期进入方案(“延迟ASCT”组)。
所有患者在动员化疗后均缓解并进行了ASCT;没有因反应差、动员不佳或患者拒绝而被排除。移植后随访24(2 - 73)个月, upfront ASCT组2年时的无事件生存率和总生存率分别为77%和100%,而延迟ASCT组分别为30%(P = 0.0007)和54%(P = 0.0016)。即使从初始诊断计算, upfront ASCT组的无事件生存率和总生存率也倾向于比延迟ASCT组长(诊断后4年时分别为76%和93%对42%和63%;中位随访35个月),尽管这无统计学意义。除了ASCT的时机外,单因素和多因素分析仅将脾脏大小确定为生存的独立预测因素。
ASCT不能治愈,但如果作为强化一线治疗策略的一部分进行,可能会改善MCL患者的预后。相比之下,这种方法对挽救复发疾病患者的益处似乎有限。