Stasi R, Zinzani L, Galieni P, Lauta V M, Damasio E, Dispensa E, Dammacco F, Tura S, Papa G
Department of Hematology, University of Rome Tor Vergata, Italy.
Cancer. 1994 Sep 15;74(6):1792-800. doi: 10.1002/1097-0142(19940915)74:6<1792::aid-cncr2820740623>3.0.co;2-f.
This study explores the ability of the combined detection of soluble IL-2 receptor (sIL-2r) and interleukin-10 (IL-10) to predict treatment failure in patients with aggressive non-Hodgkin's lymphoma (NHL) and to evaluate the modifications in cytokine measurements induced by the therapeutic administration of recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF).
Serum levels of sIL-2r and IL-10 were measured serially in 93 patients with newly diagnosed aggressive NHL treated with four courses of a multiagent chemotherapy regimen. GM-CSF was administered subcutaneously in 39 of these patients from day +5 to day +18 after each chemotherapy course.
Pretreatment levels of sIL-2r were greatly elevated in patients with NHL compared with control subjects (P < 0.001), significantly correlating with the Ann Arbor stage (P < 0.001) and beta 2-microglobulin (beta 2-m) concentrations (r = 0.552, P = 0.004). IL-10 was detected in 37 patients at diagnosis, with no correlation with clinicohematologic parameters, and was not detected in the control sample (P < 0.001). Cytokine and receptor levels progressively declined to normal ranges in responding patients, whereas they remained elevated in nonresponders. During administration of GM-CSF, the authors observed an increase of sIL-2r, whereas lower elevations were recorded for IL-10. However, on completion of the induction treatment, cytokine/receptor levels were comparable in patients with the same type of response, whether or not they had received GM-CSF. In the five patients who were investigated at relapse, the levels of sIL-2r, beta 2-m, and lactic dehydrogenase were found to be elevated. IL-10 concentrations were high in three of these patients: two already had detectable levels at presentation, whereas one tested positive only on recurrence. No single parameter was associated with response to therapy, but the combination of elevated IL-10 and sIL-2r concentrations greater than 3000 U/ml resulted in a subset of eight patients who failed induction chemotherapy (P < 0.001). In addition, six of eight patients with high IL-10 and beta 2-m concentrations greater than 3.3 mg/l had an unfavorable outcome (P = 0.003). A multivariate regression model was used to identify sIL-2r (P = 0.004) and beta 2-m (P = 0.043) as the covariates that amplified the prognostic ability of IL-10.
sIL-2r and IL-10 measurements provide valuable information for better management of patients with NHL as markers to monitor disease activity and as prognostic indicators.
本研究探讨联合检测可溶性白细胞介素-2受体（sIL-2r）和白细胞介素-10（IL-10）对侵袭性非霍奇金淋巴瘤（NHL）患者治疗失败的预测能力，并评估重组人粒细胞-巨噬细胞集落刺激因子（GM-CSF）治疗性给药诱导的细胞因子测量变化。
对93例新诊断的侵袭性NHL患者进行多药化疗方案四个疗程治疗，连续检测其血清sIL-2r和IL-10水平。其中39例患者在每个化疗疗程后第5天至第18天皮下注射GM-CSF。
与对照组相比，NHL患者治疗前sIL-2r水平显著升高（P < 0.001），与Ann Arbor分期（P < 0.001）和β2-微球蛋白（β2-m）浓度显著相关（r = 0.552，P = 0.004）。37例患者在诊断时检测到IL-10，与临床血液学参数无关，对照组样本中未检测到（P < 0.001）。有反应的患者细胞因子和受体水平逐渐降至正常范围，而无反应者则持续升高。在GM-CSF给药期间，作者观察到sIL-2r升高，而IL-10升高幅度较小。然而，诱导治疗结束时，无论是否接受GM-CSF，相同反应类型患者的细胞因子/受体水平相当。在复发时接受调查的5例患者中，发现sIL-2r、β2-m和乳酸脱氢酶水平升高。其中3例患者IL-10浓度较高：2例在初诊时已有可检测水平，而1例仅在复发时检测呈阳性。没有单一参数与治疗反应相关，但IL-10升高且sIL-2r浓度大于3000 U/ml的组合导致8例患者诱导化疗失败（P < 0.001）。此外，8例IL-10升高且β2-m浓度大于3.3 mg/l的患者中有6例预后不良（P = 0.003）。使用多变量回归模型确定sIL-2r（P = 0.004）和β2-m（P = 0.043）为增强IL-10预后能力的协变量。
sIL-2r和IL-10测量可为NHL患者的更好管理提供有价值的信息，作为监测疾病活动的标志物和预后指标。
