ASH：针对年轻霍奇金淋巴瘤患者的新评分系统
       据美国血液病学会(ASH)年会上报告的一项研究，一种名为儿童霍奇金国际预测评分(CHIPS)的简单系统可在年轻霍奇金淋巴瘤患者中识别预计无事件生存率低于80%的亚群。

      该研究由罗德岛州普罗维登斯Hasbro儿童医院儿童血液/肿瘤科主任Cindy L. Schwartz医生和儿童肿瘤组的同事完成，他们对1,721例年龄不足21岁并参加AHOD0031研究的中危霍奇金淋巴瘤患者进行了评估。AHOD0031是一项Ⅲ期剂量强化治疗研究，在770例随机或分配到接受[相同治疗4个周期的阿霉素、博莱霉素、长春新碱、依托泊苷、强的松和环磷酰胺(ABVE-PC) 以及21 Gy 局限野放射治疗(IFRT)]的患者中，依据其早期应答调整治疗。根据Schwartz医生的观点，将快速早期应答定义为ABVE-PC治疗2个周期后CT显示二维肿瘤缩减超过60%；完全应答定义为CT显示二维肿瘤缩减超过80%，且核医学显像的异常消失。在2次追加ABVE-PC治疗后达到完全应答的快速应答患者随机接受21 Gy放射治疗。缓慢早期应答患者在4次ABVE-PC治疗和21 Gy放射治疗之外，随机接受地塞米松、依托泊苷、顺铂和阿糖胞苷(DECA)治疗。

       结果显示，使用Cox回归分析和多变量预测模型，研究者确定了4个无事件生存的预测因素：Ⅳ期疾病[危险比(HR)，1.6]、纵膈淋巴结病(HR，1.7)、白蛋白低于3.5 g/dl(HR，1.8)和发热(HR，2.5)。因为危险比相似，研究者设计了CHIPS评分，对于4个不利的预测因素各评1分。使用这种方法，他们确定了CHIPS评分为0或1的患者的无事件生存率为90%，CHIPS评分为2的患者为78%，CHIPS评分为3的患者为62%(因为该研究中纳入的是中危疾病患者，无一患者的CHIPS评分为4)。研究者根据上述结果确定，预计中危疾病患者中有22%的患者无事件生存率低于80%。


研究摘要

The Childhood Hodgkin International Prognostic Score (CHIPS) for Predicting Event Free Survival in Pediatric and Adolescent Hodgkin Lymphoma


Purpose
To develop a method for predicting Event Free Survival (EFS) in Hodgkin Lymphoma (HL) using clinical factors known at diagnosis. 
Background:  Although early response as measured by CT and/or PET scan has proven useful in the allocation of patients to therapy (eg. eliminating radiation or augmenting chemotherapy) (D Friedman, ASH 2010), stratification at diagnosis may allow earlier modification of treatment approach.   The International Prognostic Score (D. Hasenclever, N Engl J Med, 1998) has been used effectively in adults with advanced stage disease, but includes predictors that may not be applicable to the pediatric and adolescent population.  1721 patients with intermediate risk HL (excludes IA and IIA without bulk disease and IIIB/IVB) were treated on AHOD0031, a Children’s Oncology Group study using a dose dense, response based algorithm. 770 patients who were randomized or assigned to receive the same treatment (4 ABVE-PC and IFRT) serve as the basis for this report.


Methods
Patients  <21 years with intermediate risk HL were eligible for COG AHOD0031.  The study evaluated the tailoring of treatment by early response to 2 ABVE-PC.  Rapid early response (RER) was a 2-dimensional tumor reduction of >60% after 2 cycles of ABVE-PC.   Complete response (CR) was a >80% 2-diminsional reduction by CT, and resolution of nuclear imaging abnormalities.   RER who achieved CR after 2 additional ABVE-PC were randomized to +/- 21Gy.  Slow early responders (SER) were randomized to +/- DECA in addition to the 4 ABVE-PC/21 Gy.    


Cox regression analysis was used to evaluate potential predictors of EFS (gender, age, race, stage, mediastinal mass, B symptoms, hemoglobin, sedimentation rate, albumen, histology).   Continuous variables were dichotomized by clinical significance or quartiles of the population.  Multivariable predictive modeling was performed using univariate predictors with a p<0.25.  In instances of collinearity, the most robust variable was used.  A stepwise selection algorithm was used to identify predictors with a p<0.15.   


Results
Four predictors (stage 4, large mediastinal adenopathy, albumen<3.5 and fever) were identified as predictive of adverse EFS.   Since the Hazard Ratios were similar, the CHIPS (Childhood Hodgkin IPS) score was devised that gave 1 point for each of the 4 adverse predictors.  EFS based on score was found to predict an excellent outcome of nearly 90% for those with CHIPS 0 or 1 (N=589) vs. 78% or 62% for those with CHIPS 2 or 3 respectively (N= 141 and 32).


Conclusion
The CHIPS score identifies a subset of patients accounting for 22% of an intermediate risk population who are predicted to have an EFS <80%.  Early augmentation of therapy may improve outcome for this cohort.   After  further validation of this approach in historical cohorts, future studies will evaluate the utility of the CHIPS in additional cohorts of newly diagnosed patients.

学习