Breastfeeding and the Risk of Childhood Hodgkin Lymphoma: A Systematic Review and Meta-analysis

Purpose: Numerous observational epidemiological studies have evaluated associations between breastfeedingand the risk of childhood Hodgkin lymphoma; however, the existing results are inconsistent. We thereforeconducted a systematic review and meta-analysis. Methods: Medical literature was searched in the Pubmed andEmbase databases to identify all English-language relevant studies up to April 10, 2013. Reference lists werethereafter hand-searched for additional articles. Studies that reported relative risk ratios (RRs) or odds ratios(ORs) with 95% confidence intervals (CIs) were included. This meta-analysis was conducted in accordancewith the guidelines for the meta-analysis of observational studies in epidemiology. Results: We finally included10 case-control studies in our meta-analysis, involving 1,618 childhood Hodgkin lymphoma cases and 8,181controls. Overall, we did found a borderline significant association between breastfeeding and reduced riskof childhood Hodgkin lymphoma comparing ever breastfed children to never breastfed children (pooled OR=0.79; 95%CI, 0.58-1.08; P=0.13), with limited evidence for between-study heterogeneity (P =0.12, I2 = 35.70%).Conclusion: There is limited evidence for an inverse association between breastfeeding and risk of childhoodHodgkin lymphoma.     

Smoking and Hodgkin Lymphoma Risk in Women United States

OBJECTIVE: Smoking has received little consideration as a risk factor for Hodgkin lymphoma (HL) in women, despite recent significant findings in men and gender differences in HL incidence. We investigated the association of HL with lifetime cigarette smoking and household environmental tobacco smoke (ETS) exposure in women. METHODS: In data from a population-based case-control study in women ages 19-79, we analyzed HL risk associated with self-reported smoking and household ETS exposure in 312 diagnostically re-reviewed cases and 325 random-digit dialing controls using logistic regression. Epstein-Barr virus (EBV) presence was determined in tumors of 269 cases. RESULTS: In 253 cases compared to 254 controls ages 19-44, risks of HL overall, and of nodular sclerosis and EBV-negative HL, were increased 50% with ETS exposure in childhood; for 11 cases of mixed cellularity (MC) HL, current smoking and adult ETS exposure also increased risk; for 24 cases of EBV-positive HL, risk was elevated for current smoking, greater smoking intensity and duration, and ETS exposure. In 59 cases and 71 controls ages 45-79, most smoking characteristics did not appear to affect risk. CONCLUSIONS: Apparent effects of current smoking on risks of MC HL and EBV-positive HL and of household ETS on risk of all HL in young adult females may broaden the evidence implicating tobacco smoke exposures in HL etiology.     

The Lymphoma-Associated Macrophage to Hodgkin-Reed-Sternberg Cell Ratio Is a Poor Prognostic Factor in Classic Hodgkin Lymphoma Patients

BackgroundDespite the relatively high rate of curability, approximately 20% to 30% of patients with classic Hodgkin lymphoma relapse. Hodgkin-Reed-Sternberg (HRS) cells:lymphoma-associated macrophages (LAMs) cross talk promotes tumor growth and resistance to therapy. The aim of the study was to assess the prognostic role of the LAM to HRS ratio (LHR) in lymph node biopsies using a novel automated system for scanning large sample areas.Patients and MethodsHigh-quality tissue samples obtained from 71 patients and stained with anti-CD30 and anti-CD68 were analyzed using the TissueFAXS (TissueGnostics).ResultsA high LHR was associated with inferior 5-year progression-free survival (PFS; 50.0% vs. 79.3%; P = .032) and overall survival (OS; 65.4% vs. 92.3%; P = .012). Multivariate Cox regression identified the high LHR as an unfavorable prognostic factor for PFS (hazard ratio [HR], 3.07; P = .029) and OS (HR, 4.56; P = .025).ConclusionA high LHR at diagnosis is associated with a higher risk of lymphoma progression or death. Automated image analysis is a new tool that can overcome technical limitations of by microarray samples in lymphomas with high intratumor heterogeneity.     

海南省恶性淋巴瘤危险因素病例对照研究

[目的]探讨海南省恶性淋巴瘤发病的危险因素。[方法]调查156例经病理确诊的恶性淋巴瘤患者和106例同性别、年龄相差上下不超过5岁的健康人。数据采用条件Logistic回归单因素和多因素逐步同归分析。[结果]与恶性淋巴瘤发病相关的因素有：乙型肝炎病毒感染（OR=1．851，95％可信区间1．075～3．189），慢性炎症持续时间（OR=1．794，95％可信区间1．416～2．273），经济状况（OR=0．401，95％可信区间0．243～0．660）。[结论]乙型肝炎病毒感染及慢性炎症持续时间长可增加患恶性淋巴瘤的危险性；而经济状况好则为保护因素。     

Association between insurance and socioeconomic status and risk of advanced stage Hodgkin lymphoma in adolescents and young adults

BACKGROUND:

Hodgkin lymphoma (HL) is one of the most common types of cancer among adolescents and young adults (AYAs) in the United States. Unfortunately, a greater percentage of AYAs are presenting with an advanced stage of disease at the time of diagnosis compared with their younger counterparts.

METHODS:

The objective of the current study was to examine the association between possible barriers and characteristics (including gender, race, birthplace, marital status, socioeconomic status [SES], and insurance status) that may increase the risk of advanced stage HL at the time of diagnosis in a large cohort of AYA patients with HL from the California Cancer Registry (7343 incident cases of HL diagnosed from 1988‐2006, between ages 15 years‐40 years).

RESULTS:

AYAs with advanced stage HL were more likely to be male, of Hispanic or black race/ethnicity, foreign born, single, of lower SES, and uninsured or to have only public health insurance (P < .05). Multivariate logistic regression analysis demonstrated that there was a significant increase in the odds of having advanced HL in males (odds ratio [OR], 1.57; 95% confidence interval [95% CI], 1.42‐1.74 [P < .0001]), those with the lowest SES (OR, 1.47; 95% CI, 1.23‐1.75 [P = .0003]), those without health insurance (OR, 1.76; 95% CI, 1.34‐2.31 [P < .0001]), and those with public health insurance (OR, 1.45; 95% CI, 1.23‐1.71 [P < .0001]).

CONCLUSIONS:

A strong association was found between male gender, lower SES, and lack of health insurance and advanced stage HL at the time of diagnosis in AYAs (See editorial on pages 000–000, this issue.) Cancer 2012. © 2012 American Cancer Society.     

The Triple Positivity for EBV,PD-1, and PD-L1 Identifies a Very High Risk Classical Hodgkin Lymphoma

BackgroundThe programmed death receptor (PD-1) and ligand (PD-L1) pathway act by suppressing the antitumor response in chronic Hodgkin lymphoma (cHL). In this study, we aimed to investigate the effect of PD-1, PD-L1, and Epstein-Barr virus (EBV) positivity on prognosis at the initial diagnosis of cHL.Material and MethodsThirty-six patients with cHL were retrospectively analyzed. PD-L1 staining was performed for RS cells and tumor microenvironment in the biopsy materials of cases. The presence of EBV was investigated by EBER (EBV-encoded RNA) method in tumor cell. P < .05 was accepted as significant.ResultsThe presence of advanced-stage disease, B symptoms, intermediate or high-risk international prognostic index (IPS), and extranodal involvement were found to be related to both PD-L1 positivity and EBV positivity in RS cells. PD-L1 positivity in RS cells was also associated with EBV positivity. There were 6 (16.7%) triple-positive (EBV⁺, RS-PD-L1⁺, mic-PD-1⁺) patients. All of these patients had advanced-stage disease, B symptoms at the time of diagnosis, and intermediate-high IPS score, and 4 of 6 patients had extranodal involvement. This group also had significantly shortened overall survival compared with others (38.4 months vs. 67.9 months P = .024).ConclusionOur data suggest that there is correlation between PD-L1 positivity and EBV positivity in tumor RS cells that are also associated with extranodal involvement, intermediate and high IPS score, presence of B symptoms, and advanced-stage disease. In addition, we identified a group of triple-positive (EBV⁺, RS-PD-L1⁺, mic-PD-1⁺) cHL patients who have a very high-risk disease.     

Individualised Estimation of Quality-adjusted Survival Benefit and Cost-effectiveness of Proton Beam Therapy in Intermediate-stage Hodgkin Lymphoma

AimsRadiotherapy for Hodgkin lymphoma leads to the irradiation of organs at risk (OAR), which may confer excess risks of late effects. Comparative dosimetry studies show that proton beam therapy (PBT) may reduce OAR irradiation compared with photon radiotherapy, but PBT is more expensive and treatment capacity is limited. The purpose of this study is to inform the appropriateness of PBT for intermediate-stage Hodgkin lymphoma (ISHL).Materials and methodsA microsimulation model simulating the course of ISHL, background mortality and late effects was used to estimate comparative quality-adjusted life years (QALYs) lived and healthcare costs after consolidative pencil beam scanning PBT or volumetric modulated arc therapy (VMAT), both in deep-inspiration breath-hold. Outcomes were compared for 606 illustrative patients covering a spectrum of clinical presentations, varying by two age strata (20 and 40 years), both sexes, three smoking statuses (never, former and current) and 61 pairs of OAR radiation doses from a comparative planning study. Both undiscounted and discounted outcomes at 3.5% yearly discount were estimated. The maximum excess cost of PBT that might be considered cost-effective by the UK's National Institute for Health and Care Excellence was calculated.ResultsOAR doses, smoking status and discount rate had large impacts on QALYs gained with PBT. Current smokers benefited the most, averaging 0.605 undiscounted QALYs (range –0.341 to 2.171) and 0.146 discounted QALYs (range –0.067 to 0.686), whereas never smokers benefited the least, averaging 0.074 undiscounted QALYs (range –0.196 to 0.491) and 0.017 discounted QALYs (range –0.030 to 0.086). For the gain in discounted QALYs to be considered cost-effective, PBT would have to cost at most £4812 more than VMAT for current smokers and £645 more for never smokers. This is below preliminary National Health Service cost estimates of PBT over photon radiotherapy.ConclusionIn a UK setting, PBT for ISHL may not be considered cost-effective. However, the degree of unquantifiable uncertainty is substantial.     

Ethnic variations in diagnosis, treatment, socioeconomic status, and survival in a large population-based cohort of elderly patients with non-Hodgkin lymphoma

BACKGROUND.

There is a lack of research on ethnic disparities in survival among patients with non‐Hodgkin lymphoma (NHL), although these disparities have been documented for patients with many other tumors.

METHODS.

A retrospective cohort of 13,321 patients diagnosed with incident NHL at age ≥65 years from 1992 to 1999 were identified from the Surveillance, Epidemiology, and End Results (SEER)‐Medicare linked database with 11 years of follow‐up. Of these patients, 11,868 were Caucasians, 533 were African Americans, and 920 were other ethnicities. A time‐to‐event Cox regression model was used to examine the relative risk of all‐cause and disease‐specific mortality.

RESULTS.

A larger proportion (72.2%) of African Americans were in the poorest quartile of socioeconomic status as measured by the poverty level compared with 21.8% of Caucasians, and 43.2% of African Americans received chemotherapy compared with 52.4% of Caucasians (P < .01). Hazard ratio of all‐cause and NHL‐specific mortality increased significantly with age, advanced stage, higher comorbidity scores, and poorer socioeconomic status. Patients receiving either chemotherapy or radiotherapy or both were significantly less likely to die. After taking into account differences in treatment, comorbidity, and socioeconomic status, there was no statistically significant difference in the risk of all‐cause (hazard ratio, 0.97; 95% confidence interval, 0.88‐1.08) and disease‐specific mortality (hazard ratio, 1.07; 95% confidence interval, 0.92‐1.25) between African Americans and Caucasians.

CONCLUSIONS.

The risk of mortality in patients with NHL was associated with socioeconomic status and was reduced in patients receiving chemotherapy. No significant differences in the risk of mortality were observed between African Americans and Caucasians after controlling for factors such as treatment and socioeconomic status. Cancer 2008. © 2008 American Cancer Society.     

Risk factors for impaired gonadal function in female Hodgkin lymphoma survivors: final analysis of a retrospective multicenter joint study from Italian and Brazilian Institutions

Hodgkin lymphoma (HL) is one of the most common types of cancer in the young and one of the most curable forms of cancer. Therefore, there has been an increasing interest in the study of long‐term morbidities. The aims of the present study were to evaluate the prevalence and risk factors for impaired gonadal function in a retrospective cohort of 238 HL female survivors from Italy and Brazil and to analyse the role of oral contraceptives (OC) and GnRH‐analogues. Besides data collection from HL databases, a specific questionnaire was administered to collect data on gonadal function. The median age at diagnosis was 25 years and the median follow‐up was 7 years. Overall, 25% of the patients developed impaired gonadal function. Older age at diagnosis, front‐line therapies containing alkylating agents and more than one treatment were independent risk factors, whereas the use of OC or GnRH‐a reduced independently the risk of impaired gonadal function. The fertility rate among fertile survivors was low when compared with the general population. We confirmed that older age, type of front‐line chemotherapy and a higher number of therapies are associated with gonadal function impairment in terms of infertility and premature menopause in female HL survivors. Also, the use of GnRH‐a or OC was independently identified as a protective factor. Further prospective studies are needed to better understand the barriers to parenthood in HL survivors. Copyright © 2012 John Wiley & Sons, Ltd.     

The impact of cancer and quality of life for post‐treatment non‐Hodgkin lymphoma survivors

Objective: Recent work suggests that perceptions of the impact of cancer on survivors' lives are associated with physical and mental health and quality of life (QOL) outcomes. This study examines the association between the Impact of Cancer Version 2 Scales (IOCv2) and these outcomes in a large sample of survivors of adult non‐Hodgkin lymphoma (NHL). Methods: Participants completed a mailed survey to assess physical and mental health (SF‐36), cancer‐specific QOL (FACT‐G) and perceived impact of cancer (IOCv2). Hierarchical multiple regression models, in which demographic, clinical, psychosocial and IOCv2 measures were added sequentially, were employed to evaluate their contribution to explain variance in SF‐36 and FACT‐G scores. Results: A total of 652 post‐treatment NHL survivors participated. Survivors with comorbidities and negative appraisals of life threat and treatment intensity reported worse physical and mental health and QOL (all p<0.05). After controlling for demographic and clinical characteristics, younger respondents reported better physical but worse mental health and QOL (all p<0.01). Lower IOCv2 Negative Impact (all p<0.001) and higher Positive Impact (all p<0.05) scores were associated with better physical and mental health and QOL after controlling for demographic, clinical and psychosocial characteristics. Conclusions: Findings suggest that perceptions of cancer's impact on survivors' lives may influence or be influenced by health status and functioning and QOL. Longitudinal research is needed to establish causality, which could lead to the development of interventions targeting survivors' impact of cancer concerns, and ultimately to the enhancement of overall health and QOL. Copyright © 2010 John Wiley & Sons, Ltd.     

Administration of brentuximab vedotin to a Hodgkin lymphoma patient with liver dysfunction due to vanishing bile duct syndrome resulting in a partial response without any severe adverse events

Vanishing bile duct syndrome (VBDS) is a rare hepatic disorder which leads to liver failure as a result of progressive destruction of the intrahepatic bile ducts. There are no treatment modalities for VBDS itself and severe hepatic dysfunction restricts the treatment of underlying diseases. We safely treated a case of classic Hodgkin lymphoma (HL) with VBDS using brentuximab vedotin (BV). The patient was treated with 5 cycles of reduced BV and a partial metabolic response was obtained. Moreover, a standard dose of BV for another 5 cycles was accomplished with minimal adverse events. Our experience indicates that BV could be a treatment option for classic HL with VBDS.     

Lack of evidence of disease contamination in ovarian tissue harvested for cryopreservation from patients with Hodgkin lymphoma and analysis of factors predictive of oocyte yield

Ovarian cryopreservation is a promising technique to preserve fertility in women with Hodgkin lymphoma (HL) treated with chemotherapy. Thus, the aim of this study was to examine harvested ovarian tissue for subclinical involvement by HL by morphology/immunohistochemistry, and to define patient and treatment factors predictive of oocyte yield. This was a retrospective analysis of 26 ovarian tissue samples harvested for cryopreservation from women with HL. Histology, immunohistochemistry and follicle density (number mm(-3)) was examined. Disease status and preharvest chemotherapy details were obtained on 24 patients. The median age was 22 years (range 13-29). Seven of 24 patients had infradiaphragmatic disease at time of harvest. Nine of 20 patients had received chemotherapy preharvest (ABVD (Adriamycin), Bleomycin, Vinblastine and Dacarbazine) = 7, other regimens = 2). The seven receiving ABVD showed no difference in follicle density compared to patients not receiving treatment (n = 14); (median = 1555 vs 1620 mm3 P = 0.97). Follicle density measurement showed no correlation with patient age (R2 = 0.0001, P = 0.99). There was no evidence of HL involvement in the 26 samples examined (95% CI = 0-11%). In conclusion, subclinical involvement of HL has not been identified in ovarian tissue, even when patients have infradiaphragmatic disease. Furthermore, the quality of tissue harvested does not appear to be adversely affected by patient's age or prior ABVD chemotherapy.