The ratio of the absolute lymphocyte count to the absolute monocyte count is associated with prognosis in Hodgkin's lymphoma: correlation with tumor-associated macrophages

Background.

Although most patients with classical Hodgkin''s lymphoma (cHL) have a long survival duration, the current risk stratification is imperfect. A recent study suggested a prognostic role for the peripheral blood absolute lymphocyte count/absolute monocyte count (ALC/AMC) ratio at diagnosis in cHL. It is intriguing to investigate the significance of the ALC/AMC ratio in relation to tumor-associated macrophages (TAMs), yet another prognostic factor for cHL.

Methods.

We examined the prognostic impact of the ALC, AMC, and ALC/AMC ratio in 312 cHL patients (median age, 37 years) using receiver operating characteristic curve analysis for optimal cutoff values, and compared these with TAM content.

Results.

The median follow-up was 65 months (range, 0.1–245 months). On univariate analysis, a low ALC/AMC ratio (<2.9) was correlated with a poorer overall survival (OS) outcome. A subgroup analysis of patients with limited-stage disease showed that the ALC/AMC ratio was significantly correlated with the OS time. Multivariate analysis showed the ALC/AMC ratio to be an independent prognostic factor for OS outcome. A Spearman correlation test of TAM content showed a negative correlation with the ALC/AMC ratio and a positive correlation with the peripheral blood macrophage percentage.

Conclusions.

This study suggests that the ALC/AMC ratio may be a simple, inexpensive, and independent prognostic factor for OS outcome in patients with cHL and may have a role in the stratification of cHL patients in addition to the International Prognostic Score and TAM content.     

Neutrophil‐lymphocyte ratio at diagnosis is an independent prognostic factor in patients with nodular sclerosis Hodgkin lymphoma: results of a large multicenter study involving 990 patients

Several studies have demonstrated the prognostic value of neutrophil‐lymphocyte ratio (NLR) in patients with solid tumors and non–Hodgkin lymphoma. In contrast, there is only sparse data on its prognostic role in patients with classical Hodgkin lymphoma (cHL). The aim of our study was to establish whether NLR could serve as an independent prognostic factor in a cohort of 990 patients with nodular sclerosis (NS)‐cHL. After analysis of the log hazard ratio (HR) as a function of NLR, we chose the value 6 as cutoff. Patients with NLR >6 had a worse progression‐free survival and overall survival compared to those with NLR ≤6; 84% vs 75% and 92% vs 88%, at 5 years, with an HR of 1.65 and 1.82, respectively. Multivariate analysis showed that the risk remained high with HR 1.44 and HR 1.54 in progression‐free survival and overall survival, respectively. In summary, our study shows that NLR is a robust and independent prognostic parameter in NS‐cHL, both in early and advanced disease. It is inexpensive and simple to apply. Thus, we conclude that NLR, possibly in combination with the international prognostic score and absolute monocyte count, is a useful guide for physicians treating NS‐cHL patients.     

术前外周血淋巴细胞与单核细胞比值评估直肠癌预后的价值

目的:探讨直肠癌患者术前外周血淋巴细胞与单核细胞比值（LMR）与预后的关系。方法:回顾性分析2007年1月至2012年1月我院收治的85例行直肠癌根治术患者的临床资料,根据受时间依赖受试者生存曲线（ROC）将患者分为高LMR组和低LMR组。分析直肠癌患者LMR水平与临床病理特征的相关性;采用Kaplan-Meier法进行单因素生存分析,Cox风险回归模型用于多因素分析。结果:根据ROC曲线,LMR最佳临界值为4.21,其中高LMR组58例,低LMR组27例,高LMR组与低LMR组之间的脉管癌栓发生率、癌胚抗原（CEA）水平和TNM分期有统计学差异（P<0.05）;年龄、性别、病理类型、术后是否接受放化疗等方面无统计学差异（P>0.05）。单因素分析显示临床分期、术前CEA水平、脉管癌栓、LMR水平是影响直肠癌患者5年总生存率和无疾病进展生存率的危险因素（P<0.05）;高LMR组与低LMR组的5年总生存率分别为72.4%和40.7%;无疾病进展生存率分别为58.6%和25.9%;Cox多因素分析结果显示临床分期和LMR是影响直肠癌术后患者的独立预后因素。结论:LMR与直肠癌患者的术后分期相关,且LMR是直肠癌术后患者预后的独立影响因素之一,与远期生存呈正比关系,具有良好的预测价值。     

Elevated preoperative neutrophil/lymphocyte ratio is associated with poor prognosis in soft-tissue sarcoma patients

Background:

Recent data indicate that tumour microenvironment, which is influenced by inflammatory cells, has a crucial role in cancer progression and clinical outcome of patients. In the present study, we investigated the prognostic relevance of preoperative neutrophil/lymphocyte (N/L) ratio on time to tumour recurrence (TTR) and overall survival (OS) in soft-tissue sarcoma (STS) patients who underwent curative surgical resection.

Methods:

In all, 260 STS patients were included in this retrospective study. Kaplan–Meier curves and multivariate Cox proportional models were calculated for TTR and OS.

Results:

In univariate analysis, elevated N/L ratio was significantly associated with decreased TTR (hazard ratio (HR), 2.32; 95% confidence interval (CI), 1.30–4.14; P=0.005) and remained significant in the multivariate analysis (HR, 1.98; 95%CI, 1.05–3.71; P=0.035). Patients with elevated N/L ratio showed a median TTR of 77.9 months. In contrast, patients with low N/L ratio had a median TTR of 99.1 months. Regarding OS, elevated N/L ratio was also significantly associated with decreased survival in univariate analysis (HR, 2.90; 95%CI, 1.82–4.61; P=0.001) and remained significant in multivariate analysis (HR, 1.88; 95%CI, 1.14–3.12; P=0.014).

Conclusion:

In conclusion, our findings suggest that an elevated preoperative N/L ratio predicts poor clinical outcome in STS patients and may serve as a cost-effective and broadly available independent prognostic biomarker.     

Comorbidity assessment to determine prognosis in older adult patients with classical Hodgkin lymphoma

The clinical management of older adult patients with Hodgkin lymphoma (HL) remains a major challenge. The aim of this study was to evaluate the impact of comorbidity assessment according to a standardized approach, the Cumulative Illness Rating Scale (CIRS), on prognosis in patients with classical HL aged 60 years and older. We studied 76 consecutive older adult patients with HL (median age 69 y, range 60-84) who had been treated in our institution between 1999 and 2018. Comorbidity was assessed at diagnosis according to CIRS. Anthracycline-containing chemotherapy with curative intent was administered in 59 (78%) patients. We identified 41 (54%) patients with at least one severe comorbidity rated on CIRS grade ≥ 3. Patients with severe comorbidity were more likely to have advanced-stage disease (P = .003), to have an International Prognostic Score (IPS) > 3 (P = .03), and to not receive anthracycline-containing chemotherapy (P = .008). The probability of overall survival (OS) at 3 years was 88% (95% CI, 71%-95%) in patients without severe comorbidities, while it was only 46% (95% CI, 29%-62%) in patients with a comorbidity CIRS grade ≥ 3 (P = .0001). The impact of comorbidity on prognosis was also evident when restricting the analysis to patients treated with anthracycline-containing therapy. The 3-year OS was 93% (95% CI, 76%-98%) (P = .004) in patients without severe comorbidity and 72% (95% CI, 47%-87%) in patients with severe comorbidity (P = .004). In a multivariate analysis, presence of comorbidity, but not age, was a significant factor for OS. Therefore, we conclude that a significant proportion of older adult patients with HL has severe comorbidity on the CIRS scale, which impacts more importantly than age on prognosis.     

The lower peripheral blood lymphocyte/monocyte ratio assessed during routine follow-up after standard first-line chemotherapy is a risk factor for predicting relapse in patients with diffuse large B-cell lymphoma

A specific predictor during routine follow-up to ascertain risk for relapse after standard first-line chemotherapy in non-Hodgkin's lymphoma (NHL) has not been identified, although blood counts, lactate dehydrogenase (LDH) and imaging studies, such as computed tomography (CT) scans or positron emission tomography, have been recommended. Therefore, we studied the absolute lymphocyte count/absolute monocyte count ratio (ALC/AMC ratio) as a marker of poststandard first-line chemotherapy for predicting relapse in patients with diffuse large B-cell lymphoma (DLBCL). 220 consecutive DLBCL patients, originally diagnosed, treated with CHOP or R-CHOP and followed up at two institutions. ALC/AMC ratio was obtained at the time of confirmed relapse or last follow-up. Patients at the time of confirmed relapse (n = 163) had a lower ALC/AMC ratio compared with those at last follow-up (n = 57) (P < 0.001). ALC/AMC ratio at the time of confirmed relapse was a strong predictor for relapse with an area under the curve = 0.813 (P < 0.001). The sensitivity and specificity for ALC/AMC ratio at the time of confirmed relapse or at last follow-up were 68.1% and 87.7%, respectively, and the relative risk of relapse with an ALC/AMC ratio < 2.8 at the time of confirmed relapse or at last follow-up was 1.845 with an odds ratio of 15.247 (95% cumulative incidence: 6.473–35.916) after CHOP or R-CHOP in DLBCL. Patients with an ALC/AMC ratio (<2.8) had a higher cumulative hazard rate of relapse compared with an ALC/AMC ratio (≥2.8) (P < 0.001). This study suggests that the lower ALC/AMC ratio can be used as a marker to assess risk of DLBCL relapse during routine follow-up after standard first-line chemotherapy.     

Tumor microenvironment composition in pediatric classical Hodgkin lymphoma is modulated by age and Epstein-Barr virus infection

Classical Hodgkin lymphoma (cHL) is characterized by a small number of neoplastic cells in a background of reactive cells. Children and adults differ in constitution and functionality of the immune system and it is possible that there may be age-related differences in tumor microenvironment composition in cHL. One hundred children with pediatric cHL were studied. Tumor-infiltrating lymphocytes were analyzed by immunohistochemistry (IHC) and image analysis. Epstein-Barr virus (EBV) status was determined by EBER-specific in situ hybridization and IHC. Results were analyzed in the context of age-group, histological characteristics and clinical follow-up. EBV-status was not associated with age-group. Children<10 years and EBV+ cases were characterized by a more intense T cell infiltrate, exhibiting a cytotoxic/Th1 profile, characterized by higher numbers of CD3+, CD8+, TIA1+ and TBET+ lymphocytes. Extranodal disease (p=0.016) and high number of GranzymeB+ lymphocytes (p=0.04) were independently associated with reduced progression-free survival (PFS). Yet, in EBV+ cases, improved outcome was observed in cases with low numbers of FOXP3+ lymphocytes (p=0.046), FOXP3/CD8 ratio<1 (p=0.021) and TBET/CMAF ratio<1 (p=0.017). By contrast, in EBV- cases, poor survival was observed in cases with extranodal disease (p=0.028), MC subtype (p=0.009) and high numbers of TIA1+ (p=0.044) and GranzymeB+ (p=0.04) lymphocytes. The results suggest that in EBV+ cHL an effective immune response directed against viral or tumor antigens may be triggered in the tumor microenvironment and that physiological and age-related changes of the immune system may also modulate the tumor microenvironment in pediatric cHL.     

外周血绝对单核细胞计数、血小板与绝对淋巴细胞计数比值在原发鼻腔NK/T细胞淋巴瘤中的预后分析

背景与目的:NK/T细胞淋巴瘤(natural killer/T-cell lymphoma,NKTCL)为恶性淋巴瘤中较少见的一种类型,其在临床表现及整体疗效上差别较大,目前尚无确切的危险分层指导预后.该研究旨在探索治疗前外周血绝对单核细胞计数(absolute monocyte count,AMC)、血小板与绝对淋巴细胞计数比值(platelet-lymphocyte ratio,PLR)在原发鼻腔NKTCL预后中的意义,为患者提供更确切的危险分层,从而选择恰当的治疗方案改善预后.方法:收集天津医科大学肿瘤医院2008年1月—2013年12月初诊的132例原发鼻腔NKTCL患者的临床资料.回顾性分析治疗前外周血AMC、PLR与患者5年总生存率(overall survival,OS)及无进展生存率(progression-free survival,PFS)之间的关系.患者预后的影响因素采用单因素分析和Cox比例风险模型多因素分析.结果:治疗前外周血AMC、PLR在原发鼻腔NKTCL患者的预后分层中均具有重要作用.AMC小于0.5×109个/L组患者的预后明显优于AMC大于等于0.5×109个/L组,PLR小于150组患者的预后优于PLR大于等于150组(P<0.05).根据分期、ECOG评分标准、AMC、PLR这4个独立危险因素,我们试图建立了一个新的预后模式,将所有患者分为3个不同危险组,结果发现3个组的5年OS及PFS差异有统计学意义(P<0.05).结论:外周血AMC、PLR与原发鼻腔NKTCL患者的预后明显相关.由分期、ECOG评分标准、AMC、PLR这4个独立危险因素组成的新的预后模式可能较国际预后指数(International Prognostic Index,IPI)及韩国预后指数(Korean Prognostic Index,KPI)更确切方便、更经济实用.     

中性粒细胞与淋巴细胞比值对弥漫性大B细胞淋巴瘤预后判断的意义北大核心

目的:探讨中性粒细胞/淋巴细胞比值(neutrophil to lymphocyte ratio,NLR)对初治前弥漫性大B细胞淋巴瘤(diffuse large B cell lymphoma,DLBCL)患者预后的意义。方法:回顾性分析2010年1月至2019年10月,新疆医科大学附属肿瘤医院收治的165例初治DLBCL患者,确定了NLR(>2.77)在预后预测中的最佳临界值,采用Log-rank检验和Cox回归模型进行分析,评价治疗前NLR对无进展生存期(progression free survival time,PFS)和总生存期(overall survival rate,OS)的影响。结果:在入选的165例患者中,有67例患者治疗前NLR升高(>2.77),NLR升高与PFS和OS较短的患者明显相关(P<0.001和P=0.003)。多变量分析进一步表明,NLR>2.77是PFS的独立预测因子。结论:治疗前NLR升高提示DLBCL患者预后不良。     

中性粒细胞/淋巴细胞比值血小板/淋巴细胞比值与TACE治疗肝癌患者预后的相关性

  目的  本研究探讨中性粒细胞与淋巴细胞比值（neutrophil to lymphocyte ratio,NLR）和血小板与淋巴细胞比值（platelet to lymphocyte ratio,PLR）与接受肝动脉栓塞化疗（transarterial chemoembolization,TACE）肝癌（hepatocellular carcinoma,HCC）患者术后生存期的相关性。  方法  回顾性分析2007年1月至2015年6月中山大学肿瘤防治中心肝胆胰科确诊为肝癌并行TACE治疗的216例患者。研究患者依照NLR和PLR的界值分成两组。分析并比较NLR和PLR在不同随访时间点的受试者工作曲线（ROC）下面积。单因素和多因素分析用于评价NLR和PLR与TACE术后肝癌患者预后的相关性。  结果  本研究中位随访时间为431.1 d。全体研究对象1、2、3年生存率分别为61.3%、44.2%和40.5%。中位生存时间为410.5 d。术前NLR＜1.77组和术前NLR≥1.77组1、2、3年生存率分别为81.6%、63.0%、45.7%和43.1%、27.0%、19.3%,差异具有统计学意义（P < 0.001）。术前PLR < 94.62组和术前PLR≥94.62组1、2、3年生存率分别为62.7%、47.0%、37.0%和46.8%、29.0%、18.5%,差异具有统计学意义（P=0.002）。多因素分析显示NLR≥1.77与TACE术后肝癌患者较差预后相关,是肝癌患者TACE治疗后的危险因素。  结论  TACE介入术前HCC患者的NLR水平,作为系统炎症的一个反应指标,是影响其预后的危险因素。      

Incidence and epidemiology of non‐Hodgkin lymphoma and risk of second malignancy among 22 466 survivors in Israel with 30 years of follow‐up

Previous studies have shown an increase risk of second malignancies after non‐Hodgkin's lymphoma (NHL), which is probably related to a combination of factors including genetic predisposition, molecular background, host immunological status and therapy administered. Here, we determined the incidence of NHL and risk of second solid tumours and haematological malignancies among survivors of NHL diagnosed in Israel during 1980–2011. Data were collected from the records of the Israeli National Cancer Registry. The total cohort of 24 666 NHL‐patients included 22 601 Jews and 2065 Arabs. Median age of diagnosis for Jews was 61.3 years and 48.2 for Arab patients. Of the Jews with NHL, 11 265 (50%) were of European–American origin, 5005 (22%) Asian or African and 6114 (27%) were born in Israel. Second cancers were recorded in 2010 NHL survivors, 1918 Jews and 92 Arabs, representing a rate of 8.5%, and 4.5% o, respectively. Second malignancies in all recorded sites were more frequent than in the general population, with a standardized incidence ratio (SIR) of 1.28 for Jewish men, 1.25 for Jewish women, 1.73 for Arab men and 1.98 for Arab women. This higher risk was even more pronounced for the 309 cases with secondary haematological malignancies (secondary haematological malignancies of 1.97, 1.81, 4.48 and 4.15, respectively). Our findings show that there is an increased risk of second malignancies occurring after diagnosis of NHL in Israel, particularly for haematological malignancies such as leukaemia and NHL. The differences we report in the incidence of NHL and the types of second malignancies occurring among Jews and Arabs suggest that ethnicity and genetic susceptibility may be important relevant risk factors. Copyright © 2016 John Wiley & Sons, Ltd.     

Neutrophil/lymphocyte ratio is associated with survival in synovial sarcoma

Background

Synovial sarcoma is a rare malignant soft tissue tumor, more common in adolescents and young adults and entails a poor prognosis. Several good prognostic factors have been well established such as age less than 25, size less than 5?cm and absence of a poorly differentiated component. Inflammation has a well-established role in tumor proliferation and survival. The aim of this study was to investigate the prognostic significance of the neutrophil/lymphocyte ratio (NLR) in a large cohort of synovial sarcoma patients.

Pretransplantation [18‐F]fluorodeoxyglucose positron emission tomography scan predicts outcome in patients with recurrent Hodgkin lymphoma or aggressive non‐Hodgkin lymphoma undergoing reduced‐intensity conditioning followed by allogeneic stem cell transplantation

BACKGROUND:

The use of positron emission tomography (PET) scanning in Hodgkin lymphoma (HL) and aggressive non‐Hodgkin lymphoma (HG‐NHL) has recognized prognostic value in patients who are receiving chemotherapy or undergoing autologous stem cell transplantation (SCT). In contrast, the role of PET before reduced‐intensity conditioning (RIC) and followed by allogeneic SCT has not been investigated to date.

METHODS:

PET was used to assess 80 patients who had chemosensitive disease (34 patients with HG‐NHL and 46 patients with HL) before they underwent allogeneic SCT: 42 patients had negative PET studies, and 38 patients had positive PET studies. Patients underwent allograft from matched related siblings (n = 41) or alternative donors (n = 39).

RESULTS:

At the time of the last follow‐up, 48 patients were alive (60%), and 32 had died. The 3‐year cumulative incidence of nonrecurrence mortality and disease recurrence was 17% and 40%, respectively. The cumulative incidence of disease recurrence was significantly lower in the PET‐negative patients (25% vs 56%; P = .007), but there was no significant difference between the patients with or without chronic graft‐versus‐host disease (P = .400). The patients who had negative PET studies before undergoing allogenic SCT also had significantly better outcomes in terms of 3‐year overall survival (76% vs 33%; P = .001) and 3‐year progression‐free survival (73% vs 31%; P = .001). On multivariate analysis, overall survival was influenced by PET status (hazard ratio [HR], 3.35), performance status (HR, 5.15), and type of donor (HR, 6.26 for haploidentical vs sibling; HR, 1.94 for matched unrelated donor vs sibling).

CONCLUSIONS:

The current results indicated that PET scanning appears to be an accurate tool for assessing prognosis in patients who are eligible for RIC allografting. Cancer 2010. © 2010 American Cancer Society.     

Multicenter phase II study of nivolumab in Japanese patients with relapsed or refractory classical Hodgkin lymphoma

Overexpression of programmed death‐1 (PD‐1) ligands contributes to an immunosuppressive microenvironment. Nivolumab is a PD‐1‐blocking antibody that inhibits the PD‐1 pathway and showed good efficacy in several types of malignancy. This phase II study examined the efficacy and safety of nivolumab in 17 Japanese patients with refractory/relapsed classical Hodgkin lymphoma previously treated with brentuximab vedotin. Sixteen patients were included in efficacy analyses and 17 in safety analyses. The primary endpoint was the centrally assessed objective response rate (ORR). The study was commenced in March 2015. We report data obtained at a cutoff of 16 March 2016, at which time 11 patients were still receiving nivolumab. The median (range) duration of treatment and follow‐up were 7.0 (1.4–10.6) months and 9.8 (6.0–11.1) months, respectively. All 17 patients had previously received brentuximab vedotin. The ORR was 81.3% (95% confidence interval [CI]: 54.4–96.0%; 13/16 patients), with complete remission and partial remission in 4 and 9 patients, respectively. The overall survival (OS) and progression‐free survival (PFS) rates at 6 months were 100 and 60.0% (95% CI: 31.8–79.7%), respectively; the median OS and PFS were not reached. The most common adverse events (AE) were pyrexia (41.2%), pruritus (35.3%), rash (35.3%) and hypothyroidism (29.4%). Four patients (23.5%) experienced grade 3 or 4 AE, but most AE were of grade 1 or 2. In conclusion, nivolumab is a potentially effective and tolerable treatment option for Japanese patients with relapsed/refractory classical Hodgkin lymphoma previously treated with brentuximab vedotin.     

术前外周血淋巴细胞与单核细胞比值（LMR）早期预测甲状腺乳头状癌复发的价值

目的:探讨术前外周血淋巴细胞与单核细胞比值（LMR）早期预测甲状腺乳头状癌复发的价值。方法:回顾性收集429例甲状腺乳头状癌患者的临床资料。采用受试者工作曲线（ROC）确定术前LMR预测PTC复发的最佳截断值,根据最佳截断值将患者分为低LMR组和高LMR组,比较两组患者间临床特征及复发率的差异。采用Kaplan-Meier法绘制生存曲线,并进行Log-rank检验。使用Cox回归比例风险模型进行单因素及多因素分析,确定与PTC复发相关的危险因素。结果:术前LMR预测PTC复发的最佳截断值为5.246 6。低LMR组患者的复发率明显高于高LMR组（11% vs 2%,P=0.000）。多因素分析显示术前LMR＜5.246 6（P=0.006）及肿瘤多灶性（P=0.039）是预测PTC复发的独立危险因素。结论:术前LMR对早期预测PTC复发具有一定价值,临床实践中可将其作为复发危险度分层的补充,联合应用以提高预测的准确性。     

Primary nodular lymphocyte predominant Hodgkin lymphoma of the palate: A rare incidence which was also associated with progressive transformation of germinal centres of cervical lymph node

Primary manifestation of nodular lymphocyte predominant Hodgkin lymphoma in oral cavity is very rare. We are describing such a case which was associated with progressive transformation of germinal centres in a cervical lymph node.