外周血淋巴细胞绝对计数与老年DLBCL患者临床特征和R-CHOP方案化疗效果的关系

目的 探讨外周血淋巴细胞绝对计数（ALC）与老年弥漫大B细胞淋巴瘤（DLBCL）患者临床特征和R-CHOP方案化疗效果的关系。 方法 回顾性分析2017年1月～2021年2月广元市中心医院血液内科收治的老年DLBCL患者127例的相关资料,均经病理组织学确诊DLBCL且成功接受≥4个疗程R-CHOP方案化疗。依据DLBCL确诊时的ALC测定水平,将入选患者分成低ALC组（ALC＜1.0×10 9/L,n=51）和高ALC组（ALC≥1.0×10 9/L,n=76）,整理并比较两组系列临床特征指标的差异。依据化疗4个疗程后的疗效评估结果,将入选患者分成缓解组（完全缓解+部分缓解,CR+PR,n=92）和未缓解组（稳定+进展,SD+PD,n=35）,并分析ALC水平与R-CHOP方案化疗效果的相关性。 结果 低ALC组临床分期Ⅲ~Ⅳ期、IPI评分3~5分的比重明显高于高ALC组（P＜0.05）,化疗前ALC水平与IPI评分呈明显负相关（r=-0.720,P＜0.05）。低ALC组R-CHOP方案化疗缓解率明显低于高ALC组（P＜0.05）。二元Logistic回归分析显示,临床分期Ⅲ~Ⅳ期（OR=1.691,95%CI：1.147~2.540）、IPI评分3~5分（OR=2.457,95% CI：1.561~3.713）和ALC＜1.0×10 9/L（OR=1.803,95%CI：1.283~2.615）均是影响R-CHOP方案化疗效果的独立危险因素（P＜0.05）。 结论 ALC不仅与老年DLBCL患者临床分期、病情危险分层紧密相关,而且ALC降低是影响R-CHOP方案化疗效果的危险因素。     

What Determines Therapeutic Choices for Elderly Patients With DLBCL? Clinical Findings of a Multicenter Study in Portugal

BackgroundAge is a negative prognostic factor in lymphomas, and elderly patients are often undertreated because of toxicity concerns. The pattern of treatment in elderly patients with diffuse large B-cell lymphoma (DLBCL) in Portugal has not been previously described.Patients and MethodsWe conducted a multicenter retrospective study including 378 elderly patients with DLBCL receiving alkylating agent–containing regimens between 2003 and 2010. We compared the outcome of patients aged 60 to 79 years with patients > 79 years and analyzed the second group according to treatment.ResultsR-CHOP (rituximab, cyclophosphamide, doxorubicin [hydroxydaunorubicin], vincristine [Oncovin], prednisolone) was prescribed in only 60% of patients and was prescribed significantly less in patients > 79 years, despite no significant differences being found in comorbidities between the 2 age groups. Similarly, dose reductions frequently were instituted because of chronologic age and not always because of toxicity. When different regimens were compared, multivariate analysis showed an independent beneficial effect of R-CHOP in treatment outcomes. Additionally, treatment with anthracyclines and rituximab predicted a better progression-free survival (PFS) and time to progression (TTP) in patients > 79 years.ConclusionThis was the first characterization of the clinical care of elderly Portuguese patients with DLBCL. We showed that R-CHOP is effective even in patients > 79 years, emphasizing that treatment decisions based on age alone can compromise treatment efficacy and outcome in fit patients.     

R-CHOP方案与CHOP方案治疗初治弥漫性大B细胞淋巴瘤的临床研究

为比较利妥昔单克隆抗体联合标准CHOP方案与标准CHOP方案治疗初治CD20阳性的弥漫慢大B细胞淋巴瘤（DLBCL）患者的疗效和安全性，采用同期（2003年7月至2006年12月）非随机对照的前瞻性研究方法，将69例在我院住院的初治DLBCL患者分为R—CHOP组和CHOP组，其中CHOP组36例，R—CHOP组33例，比较两组的完全缓解率、生存期及不良反应情况。结果显示：R—CHOP组23例（69．7％）获完全缓解（CR），部分缓解（PR）6例（18.2％），总有效率为88．5％，高于CHOP组；CHOP组17例（47．2％）获CR，11例（30．6％）获PR，总有效率77．8％（P=0.049）。尤其在男性、AnnArbor Ⅲ—Ⅳ和IPI3—5分的患者中，R—CHOP方案的CR率明显高于CHOP方案，且差异具有统计学意义（P=0．017、P=0．005和P=0．000）。R—CHOP组预计的平均生存时间（OS）为45．7个月，长于CHOP组的35．2个月，但经Log—Rank检验，差异无统计学意义（P=0．145）；R—CHOP组预计的平均无疾病进展生存时间（PFS）为38．5个月，长于CHOP组的24．6个月，经Log—Rank检验，差异有统计学意义（P=0.017）。R—CHOP组的不良反应主要为发热等输注相关的不良反应，而骨髓抑制情况与CHOP组类似：结论：利妥昔单克隆抗体联合CHOP方案治疗CD20阳性的DLBCL与单纯CHOP方案相比，能显著提高疗效，同时并不增加化疗的毒副反应。     

减低剂量利妥昔单抗联合CHOP方案治疗老年弥漫性大B细胞淋巴瘤的疗效观察

目的 观察减低剂量利妥昔单抗+环磷酰胺+多柔比星+长春新碱+泼尼松(R-CHOP)方案与减低剂量环磷酰胺+多柔比星+长春新碱+泼尼松(CHOP)方案治疗老年弥漫性大B细胞淋巴瘤(DLBCL)的临床疗效及不良反应.方法 选取2007年1月至2013年6月,四川省医学科学院·四川省人民医院血液科收治的老年DLBCL患者66例为研究对象.全部患者均经组织病理学及免疫组织化学检测,且均符合《世界卫生组织造血及淋巴组织肿瘤分类(2008年版)》中关于DLBCL的诊断标准,明确诊断为DLBCL.本研究纳入标准:①符合DLBCL的诊断标准;②年龄＞60岁;③Ann Arbor临床分期为Ⅱ～Ⅳ期.排除标准:①患者入院前已接受其他药物或手术治疗;②患者在本次入院前已合并严重的肝、肾疾病,以及恶性肿瘤等严重系统性疾病;③患者对本次治疗应用的药物有变态反应史.采用简单随机法将66例老年DLBCL患者分为2组,分别为减低剂量R-CHOP方案化疗组(n=27)与减低剂量CHOP方案化疗组(n=39).66例初治老年DLBCL患者66例应用减低剂量CHOP或R-CHOP方案进行化疗,每例患者治疗至少3个周期评估疗效,能够耐受减低剂量R-CHOP或CHOP方案的老年DLBCL患者,行化疗4～6个周期,即1个疗程.对老年DLBCL患者进行近期治疗反应的评估,并随访观察总生存(OS)率,无进展生存(PFS)率及无事件生存(EFS)率.并观察老年DLBCL患者接受减低剂量CHOP或R-CHOP方案进行化疗后的不良反应.本研究遵循的程序符合四川省医学科学院·四川省人民医院人体试验委员会所制定的伦理学标准,得到该委员会批准,征得受试对象的知情同意,并与之签署临床研究知情同意书.两组患者年龄、性别构成比等一般临床资料比较,差异均无统计学意义(P＞0.05).结果 ①减低剂量R-CHOP方案化疗组27例老年DLBCL患者中,1例患者因合并症而终止化疗,其余26例患者化疗后的完全缓解(CR)率为69.2％(18/26),部分缓解(PR)率为19.2％(5/26),总缓解(OR)率为88.5％(23/26).减低剂量CHOP方案化疗组39例老年DLBCL患者中,1例患者化疗1个周期后猝死,1例化疗后因合并症而终止化疗,其余37例患者化疗后的CR率为43.2％(16/37),PR率为21.6％(8/37),OR率为64.7％(24/37).减低剂量R-CHOP方案化疗组CR率、OR率均高于减低剂量CHOP化疗方案组,且差异有统计学意义(x2=4.15、4.49,P＜0.05);但两组患者PR率相比,差异却无统计学意义(x2=0.05;P＞0.05).②本组中位随访时间为42个月,随访率为95.5％.减低剂量R-CHOP方案化疗组可评估的26例老年DLBCL患者的3年PFS率为53.8％(14/26),3年EFS率为57.7％(15/26),3年OS率为80.8％(21/26).减低剂量CHOP方案化疗组可评估的37例老年DLBCL患者的3年PFS率为51.4％(19/37),3年EFS率为51.4％(19/37),3年OS率为56.8％(21/37).减低剂量R-CHOP方案化疗组老年DLBCL患者3年OS率高于减低剂量CHOP方案化疗组患者,且差异有统计学意义(x2=3.96,P＜0.05);两组患者3年PFS率、3年EFS率相比,差异却均无统计学意义(x2=0.04、0.25,P＞0.05).③两组老年DLBCL患者接受减低剂量CHOP或R-CHOP方案进行化疗后常见化疗相关不良反应为粒细胞计数减低、血小板计数减低、贫血、合并感染、胃肠道反应、肝功能异常、心脏不良反应.减低剂量R-CHOP方案组与减低剂量CHOP方案化疗组不良反应率分别为38.5％(10/26)与40.5％(15/37),两者相比,差异无统计学意义(P＞0.05).结论与减低剂量CHOP化疗方案相比,减低剂量R-CHOP化疗方案可以提高老年DLBCL患者的OR率、CR率、并提高OS率,可作为初治老年DLBCL患者的化疗方案之一.     

The diffuse large B-cell lymphoma – where do we stand now in everyday clinical practice

Background

Due to superior results observed with the addition of rituximab into treatment of patients with the diffuse large B-cell lymphoma (DLBCL),the R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone) regimen and its variants became the standard initial treatment of these patients. However, the treatment recommendations are based on results of clinical studies while the conditions of routine treatment are far different from the ones in clinical studies. The aim of this retrospective study was therefore to compare the treatment results of routinely treated patients with the DLBCL to results reported by some larger studies.

Patients and methods

Two hundred and ninety five patients with the DLBCL were treated between 2004 and 2008 according to the then protocol with R-CHOP or R-CHOP-like regimens at the Institute of Oncology Ljubljana. Treatment response was evaluated according to Cheson’s criteria and the disease-free and overall survival by means of Kaplan Meier survival curves.

Results

Response to treatment in our evaluation diverged from the reported one predominately in the low risk group (international prognostic index [IPI] categorisation) and in the very good prognosis group (revised international prognostic index (R-IPI) categorisation). The determined complete response (CR) rates in other IPI and R-IPI groups were generally within expectations. Also in the disease-free survival the largest discrepancy occurred in the low-risk patient group (3 year disease-free survival rate of 75%) and in the very good prognosis group (4 year disease-free survival rate of 59%). In all other IPI risk groups, the disease-free survival at 3 years (low intermediate risk 76%, high intermediate risk group 57%, and high risk group 53%) agreed very well with the quoted ones. Slightly worse was the compliance of the 4 year disease-free survival rates (72% in the good prognosis and 51% in the poor prognosis group) with the results from the literature. The 3 year overall survival rates (low risk patients 87%, high intermediate risk 61% and high risk patients 51%) were somewhat worse than the reported ones in all IPI subgroups except in the low intermediate risk group (82%). On the other hand, the 4 year overall survival rates of the R-IPI categories (94% in the very good prognosis group, 80% in the good prognosis group, 56% in the poor prognosis group) were much better correlated with the data from the literature.

Conclusions

In total, the treatment outcomes of routinely treated patient with the DLBCL at our institute are quite encouraging when compared to results of some larger studies. There are probably no dilemmas about how to treat young good prognosis patients and patients aged over 60 years at present. However, the 5 year overall survival rate of 76% for the young poor prognosis group is unsatisfying and needs to be improved. At present, quite a few studies are underway to clarify which of the regimens will perform best in this population.