Immune recovery after fludarabine-cyclophosphamide-rituximab treatment in B-chronic lymphocytic leukemia: implication for maintenance immunotherapy
Immune recovery after fludarabine-cyclophosphamide-rituximab treatment in B-chronic lymphocytic leukemia: implication for maintenance immunotherapy
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DOI：
10.1038/leu.2010.89
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发表时间：
2010-07-01
期刊：
影响因子：
11.4
通讯作者：
Quillet-Mary, A.
中科院分区：
文献类型：
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作者：
Ysebaert, L.;Gross, E.;Quillet-Mary, A.
用氟达拉滨-环磷酰胺-利妥昔单抗(FCR)治疗30例慢性B细胞白血病患者，观察治疗结束(EOT)至36个月(M36)免疫细胞计数(NK细胞、CD_4、CD_8、T-γ和单核细胞)的变化。此外，在治疗开始、EOT和M12时，还检测了非白血病外周血淋巴细胞的细胞毒性(PBL/CTC)以及依赖于美妥昔单抗(RTX)的PBL/CTC。这些参数与FCR后使用四色流式细胞术监测血液中微小残留病(MRD)水平相关。FCR导致了所有T细胞群的严重和持续的耗竭，其中T-Gamma增量受影响最大，而NK细胞相对保留。在FCR后，基础和白介素2刺激的非白血病PBL/CTC对CLL细胞系MEC-2的杀伤作用均增加。免疫恢复参数与MRD进展情况之间没有相关性，除了FCR后CD4(+)计数较高的患者经历了快速的MRD进展。M12的MRD预测临床复发。有限的数据显示，在慢性粒细胞白血病患者中，RTX介导的LBL/CTC对自体B细胞的杀伤活性
Thirty B-cell chronic lymphocytic leukemia patients were treated with fludarabine-cyclophosphamide-rituximab (FCR) and immune cell counts (natural killer (NK) cells, CD4, CD8, T gamma delta and monocytes) were monitored from the end of treatment (EOT) up to 36 months (M36). Moreover, nonleukemic peripheral blood lymphocyte cytotoxicity (PBL/CTC) as well as rituximab (RTX)-dependent PBL/CTC was also measured at the initiation of therapy, EOT and M12. These parameters were correlated with post-FCR monitoring of the minimal residual disease (MRD) level in blood using a four-color flow cytometry technique. FCR induced a profound and sustained depletion of all T-cell populations, T gamma delta being the most affected, whereas NK cells were relatively preserved. Both basal and interleukin-2-stimulated nonleukemic PBL/CTC against MEC-2, a CLL cell line, increased during the post-FCR period. There was no correlation between immune recovery parameters and MRD progression profile, except that patients with high post-FCR CD4(+) counts experienced rapid MRD progression. MRD at M12 predicts clinical relapse. The limited data show RTX-mediated LBL/CTC activity against autologous B-cell cells in individuals with