免疫抑制治疗后三个月未获血液学反应的重型/极重型再生障碍性贫血患者六个月疗效评估

Reassessing the six months prognosis of patients with severe or very severe aplastic anemia without hematological responses at three months after immunosuppressive therapy

目的再评估影响免疫抑制治疗(IST)后3个月未获血液学反应的重型/极重型再生障碍性贫血(SAA/VSAA)患者6个月疗效的因素。方法回顾性分析2017-2018年连续收治的173例初治行IST且治疗后3个月未获血液学反应的SAA/VSAA患者的临床资料, 对IST后3个月时的临床特征和血液学参数进行再评估, 通过单因素和多因素分析找出影响6个月疗效获得的相关指标。结果单因素分析结果显示IST后3个月无效患者的HGB(P=0.017)、PLT(P=0.005)、网织红细胞绝对计数(ARC)(P<0.001)、环孢素A血药浓度谷值(CsA-C0)(P=0.042)、血清可溶性转铁蛋白受体(sTfR)(P=0.003)、网织红细胞绝对计数改善值(ARC△)(P<0.001)、血清可溶性转铁蛋白受体改善值(sTfR△)(P<0.001)与IST后6个月疗效有关。多因素分析结果显示PLT<10×10^(9)/L(P=0.020)和ARC△<6.9×10^(9)/L(P<0.001)是IST后3个月未获血液学反应患者6个月疗效的危险因素。IST后6个月未获血液学反应组3年总生存率[(80.1±3.9)%对(97.6±2.6)%, P=0.002]和无事件生存率[(31.4±4.5)%对(86.5±5.3)%, P<0.001]均明显低于获得血液学反应组。结论对IST后3个月未获血液学反应的SAA/VSAA患者再评估以预测其6个月疗效非常重要;IST后3个月残存造血仍是影响预后的主要参数;ARC△可反应骨髓造血是否正在恢复及恢复的程度;IST后3个月无效患者若ARC△<6.9×10^(9)/L, 无论PLT为何值, IST后6个月的血液学反应率均较低。

Objective To reassess the predictors for response at 6 months in patients with severe or very severe aplastic anemia(SAA/VSAA)who failed to respond to immunosuppressive therapy(IST)at 3 months.Methods We retrospectively analyzed the clinical data of 173 patients with SAA/VSAA from 2017 to 2018 who received IST and were classified as nonresponders at 3 months.Univariate and multivariate logistic regression analysis were used to evaluate factors that could predict the response at 6 months.Results Univariate analysis showed that the 3-month hemoglobin(HGB)level(P=0.017),platelet(PLT)level(P=0.005),absolute reticulocyte count(ARC)(P<0.001),trough cyclosporine concentration(CsA-C0)(P=0.042),soluble transferrin receptor(sTfR)level(P=0.003),improved value of reticulocyte count(ARC△)(P<0.001),and improved value of soluble transferrin receptor(sTfR△)level(P<0.001)were related to the 6-month response.The results of the multivariate analysis showed that the PLT level(P=0.020)and ARC△(P<0.001)were independent prognostic factors for response at 6 months.If the ARC△was less than 6.9×10^(9)/L,the 6-month hematological response rate was low,regardless of the patient's PLT count.Survival analysis showed that both the 3-year overall survival(OS)[(80.1±3.9)%vs(97.6±2.6)%,P=0.002]and 3-year event-free survival(EFS)[(31.4±4.5)%vs(86.5±5.3)%,P<0.001]of the nonresponders at 6 months were significantly lower than those of the response group.Conclusion Residual hematopoietic indicators at 3 months after IST are prognostic parameters.The improved value of the reticulocyte count could reflect whether the bone marrow hematopoiesis is recovering and the degree of recovery.A second treatment could be performed sooner for patients with a very low ARC△.