scholarly journals Cause-Specific Mortality Following Initial Chemotherapy in a Population-Based Cohort of Patients With Classical Hodgkin Lymphoma, 2000-2016

2020 ◽  
Vol 38 (35) ◽  
pp. 4149-4162
Author(s):  
Graça M. Dores ◽  
Rochelle E. Curtis ◽  
Nicole H. Dalal ◽  
Martha S. Linet ◽  
Lindsay M. Morton
Keyword(s):  
Heart Disease ◽  
Hodgkin Lymphoma ◽  
Early Stage ◽  
Cancer Registries ◽  
The United States ◽  
Population Based ◽  
Advanced Stage ◽  
Classical Hodgkin Lymphoma ◽  
Standardized Mortality Ratios

PURPOSE Mortality for patients with classical Hodgkin lymphoma (cHL) treated during an era characterized in the United States by widespread use of doxorubicin, bleomycin, vinblastine, and dacarbazine and diminishing use of radiotherapy is not well understood. PATIENTS AND METHODS We identified 20,007 individuals diagnosed with stage I/II (early) or III/IV (advanced) cHL between age 20 and 74 years treated with initial chemotherapy in US population-based cancer registries during 2000-2015 (follow-up through 2016). We used standardized mortality ratios (SMRs) to compare cause-specific relative mortality risk following cHL to that expected in the general population and estimated excess absolute risks (EARs; per 10,000 patient-years) to quantify disease-specific death burden. RESULTS We identified 3,380 deaths in the cHL cohort, including 1,321 (39%) not attributed to lymphoma. Overall, noncancer SMRs were increased 2.4-fold (95% CI, 2.2 to 2.6; observed, 559; EAR, 61.6) and 1.6-fold (95% CI, 1.4 to 1.7; observed, 473; EAR, 18.2) for advanced- and early-stage cHL, respectively, compared with the general US population. SMRs and EARs differed substantially by cause of death and cHL stage. Among the highest EARs for noncancer causes of death were those for heart disease (EAR, 15.1; SMR, 2.1), infections (EAR, 10.6; SMR, 3.9), interstitial lung disease (ILD; EAR, 9.7; SMR, 22.1), and adverse events (AEs) related to medications/drugs (EAR, 7.4; SMR, 5.0) after advanced-stage cHL and heart disease (EAR, 6.6; SMR, 1.7), ILD (EAR, 3.7; SMR, 13.1), and infections (EAR, 3.1; SMR, 2.2) after early-stage cHL. Strikingly elevated SMRs for ILD, infections, and AEs were observed < 1 year after cHL. Individuals age 60-74 years with advanced-stage cHL experienced a disproportionate excess of deaths as a result of heart disease, ILD, infections, AEs, and solid tumors. CONCLUSION Despite evolving cHL treatment approaches, patients continue to face increased nonlymphoma mortality risks from multiple, potentially preventable causes. Surveillance, early interventions, and cHL treatment refinements may favorably affect patient longevity, particularly among high-risk subgroups.

Changes In The Use Of Radiation Therapy Among Adolescents and Young Adults With Early Stage Classical Hodgkin Lymphoma: Implications For Survival and Risk Of Secondary Malignancies

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 722-722
Author(s):  
Ana Xavier ◽  
Luciano J Costa
Keyword(s):  
Young Adults ◽  
Multivariate Analysis ◽  
Radiation Therapy ◽  
Hodgkin Lymphoma ◽  
Cumulative Incidence ◽  
Early Stage ◽  
Stage I ◽  
Secondary Malignancies ◽  
Classical Hodgkin Lymphoma

Abstract Background Early stage classical Hodgkin lymphoma (HL) is a highly curable disease with the combined use of chemotherapy and radiation therapy (RT). There has been a recent trend to abandon RT, driven mostly by concerns of development of secondary malignancies (SMN). However, it is unknown whether the omission of RT in adolescents and young adults (AYA) with early stage HL affects survival and the risk of developing SMN. Methods We used data from the National Cancer Institute's Surveillance Epidemiology and End Results program (SEER-13) to determine the overall survival (OS) and the risk of SMN among AYA with early stage HL treated or not with radiation therapy. Inclusion criterion was the diagnosis of stage I or II HL in the period of 1995-2010 as first malignant neoplasm among patients age 13 to 40 years. Patients with less than 6 months of follow up and patients with unknown use of RT were excluded. Follow up was updated to the end of 2012 (November 2012 submission). Cases were divided in two “eras”, 1995-2002 and 2003-2010, with the latter being expected to reflect changes in the use of RT. The impact of the era, RT, age, race, gender, and stage on survival were accessed utilizing multivariate analysis. Cumulative incidence of SMN among early stage HL survivors was calculated using a competing risk model, treating death from any cause in absence of SMN as the competing risk. Results A total of 5,336 early stage HL cases were included in the analysis with median follow up of 89 months (range 7-191). Median age of patients was 27 years, 2,459 (46%) were male, 1,327 (24.8%) had stage I, 512 (9.7%) had classical HL non otherwise specified, 4,231 (79.2%) had nodular sclerosing HL, 442 (8.3%), had mixed-cellularity HL, 130 (2.4%) had lymphocyte-rich HL, and 21 (0.4%) had lymphocyte depleted HL. Most patients were white (4,438; 83.2%), 513 (9.6%) black, 337 (6.4%) other ethnicity, and 44 (0.8%) unknown. There where 2,793 patients in the 1995-2002 era and 2,542 patients in the 2003-2010 era. Radiation was included in the initial treatment of 1,659 (59.4%) patients in the former and 1,351 (53%) patients in the latter era (P<0.001). Factors associated with use of RT were earlier era, white race and stage II HL. Within the 1995-2002 era, there was a trend towards better survival among patients treated with RT (5-year survival 95.0% vs. 93.6%, P=0.058). In the 2003-2010 cohort survival was superior among patients treated with RT (5-year survival 97.3% vs. 95.9%, P=0.008). In multivariate analysis, diagnosis of HL in the 1995-2002 era (HR=1.73, 95% C.I. 1.31-2.28, P < 0.001), black race (HR= 2.18, 95% C.I. 1.63-2.91, P <0.001), male sex (HR=1.55, 97% C.I. 1.24-1.93, P < 0.001), and omission of RT (HR=1.31, 95% C.I. 1.05-1.64, P=0.017) were associated with higher mortality. The cumulative incidence of SMN was not significantly different between patients treated or not with radiation, while the risk of death was higher among patients not treated with RT (Figure). Conclusion There has been a reduction in utilization of RT among AYA with early stage HL in the US. Omission of RT was associated with increased overall mortality but no reduction in incidence of SMN and should not be adopted outside clinical trials. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Five-year follow-up of brentuximab vedotin combined with ABVD or AVD for advanced-stage classical Hodgkin lymphoma

Blood ◽  
2017 ◽  
Vol 130 (11) ◽  
pp. 1375-1377 ◽  
Author(s):  
Joseph M. Connors ◽  
Stephen M. Ansell ◽  
Michelle Fanale ◽  
Steven I. Park ◽  
Anas Younes
Keyword(s):  
Hodgkin Lymphoma ◽  
Brentuximab Vedotin ◽  
Advanced Stage ◽  
Classical Hodgkin Lymphoma

An Immunohistochemical Score Based On CD68 and FOXP3 Expression In the Tumour Microenvironment at Diagnosis Defines Prognostic Groups In Both Early and Advanced Stage Classical Hodgkin Lymphoma

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 750-750 ◽  
Author(s):  
Paul Greaves ◽  
Andrew James Clear ◽  
David Andrew Owen ◽  
Finlay Macdougall ◽  
Andrew Wilson ◽  
...  
Keyword(s):  
Hodgkin Lymphoma ◽  
Early Stage ◽  
Prognostic Significance ◽  
Automated Image Analysis ◽  
Advanced Stage ◽  
Classical Hodgkin Lymphoma ◽  
Early Stage Disease ◽  
Stage Disease ◽  
Prognostic Groups ◽  
Good Risk

Abstract Abstract 750 The non-malignant immune infiltrate comprises the bulk of pathologic tissue in classical Hodgkin lymphoma (CHL). This microenvironment has the potential to induce both malignant cell suppression and support. Increased macrophage infiltration assessed by CD68 expression has been shown to confer adverse prognostic significance (Steidl et al. N Engl J Med, 2010; 362:875-85) while increased FOXP3 expressing T cells are beneficial in this disease (Tzankov et al. Haematologica, 2008; 93: 193–200). However no histological score routinely leads to modification of treatment. Assessing outcomes by the parameters of overall survival (OS), disease specific survival (DSS) and freedom from first line treatment failure (FFTF) at 5 years in a cohort of patients treated at St Bartholomew's Hospital (Barts), London we developed a prognostic score based upon expression of both FOXP3 and CD68 in the CHL microenvironment which defined poor and good risk groups in both early (Stages I and IIA) and advanced stage disease, including a 'poor risk' early stage group with 25% FFTF and a ‘good risk' advanced stage group with 90% FFTF. Immunohistochemical analysis was performed on tissue microarrays (TMAs) from previously untreated patients' diagnostic lymph node biopsies in whom clinical outcome was available. From all 1056 adult patients with HL diagnosed at Barts between 1972 and 2005, high quality formalin-fixed paraffin-embedded tissue was available for 122 (12%), with characteristics representative of the whole group. Median age of the 122 patients was 30 (range 18–80) years, 35% female, 71% advanced stage with median follow up 16.5 (range 2–40) years. Triplicate cores were made from areas of high cellularity, containing malignant cells and avoiding fibrotic, acellular portions, arrayed onto glass slides and stained immunohistochemically for FOXP3 or CD68. Absolute and proportional numbers of FOXP3+ nuclei and CD68+ cell bodies were counted across all intact cores using an automated image analysis system (Ariol), confirmed by expert histopathologists, and means calculated and corrected to a single high powered field (hpf). Recursive partitioning was used to generate optimal cutoff values discriminating prognostic groups and comparisons performed by the chi-square test. Using cutoffs of <5%, 5–15% and >15% to define low, intermediate and high CD68 density, 3 prognostic groups were defined, the favourable group having the lowest CD68+ density. OS for low, intermediate and high groups were 89%, 80% and 65% respectively (p=0.02), with FFTF 82%, 64% and 29% (p=0.001). Prognostic significance was maintained in subgroups presenting with advanced stage (FFTF 73%, 63% and 33%, p=0.03), as well as early stage disease (FFTF 92%, 70% and 20%, p=0.01). Using cutoffs of <12.5, 12.5–50 and >50 nuclei/hpf to define low, intermediate and high FOXP3+ cell density, 3 prognostic groups were defined, the favourable group having the highest FOXP3+ density. OS for low, intermediate and high groups were 68%, 80% and 94% respectively (p=0.006), with FFTF 50%, 62%, and 84% (p=0.002). Prognostic significance was maintained for both advanced (FFTF: 48%, 60% and 72%, p=0.04) and early stage disease (FFTF: 57%, 67% and 100%, p=0.04). A combined ‘FOXP3/CD68 score' derived from the patient's prognostic group for both markers, for which suitable cores were available on 98 patients, further improved the predictive value of each individually (See Figure). In this model, favourable, intermediate and unfavourable groups had 5 year FFTF of 93%, 62% and 47% (p=0.0002), DSS 93%, 82% and 63% (p=0.03) and OS 93%, 82% and 59% (p=0.002). The score retained prognostic significance for 5 year FFTF and OS in the subgroup of patients presenting with advanced (FFTF: 90%, 59% and 46%, p=0.008; OS: 90%, 80% and 54%, p=0.004) as well as early stage disease (FFTF: 100%, 71% and 25%, p=0.005; OS: 100%, 82% and 75%, trend only, p=ns). We conclude that FOXP3 and CD68 are important independent factors, which in combination have considerable predictive power and will now be validated prospectively. Disclosures: No relevant conflicts of interest to declare.

NIVOLUMAB PLUS DOXORUBICIN, VINBLASTINE AND DACARBAZINE FOR NEWLY DIAGNOSED ADVANCED-STAGE CLASSICAL HODGKIN LYMPHOMA: CHECKMATE 205 COHORT D 2-YEAR FOLLOW-UP

2019 ◽  
Vol 37 ◽  
pp. 146-147 ◽  
Author(s):  
S. Ansell ◽  
R. Ramchandren ◽  
E. Domingo-Domènech ◽  
A. Rueda ◽  
M. Trněný ◽  
...  
Keyword(s):  
Hodgkin Lymphoma ◽  
Advanced Stage ◽  
Newly Diagnosed ◽  
Classical Hodgkin Lymphoma

Final Report of a Phase-II Study of Rituximab Plus ABVD for Patients with Newly Diagnosed Advanced Stage Classical Hodgkin Lymphoma.: Results of Long Follow up and Comparison to Institutional Historical Data.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1680-1680 ◽  
Author(s):  
Amanda R Copeland ◽  
Yumei Cao ◽  
Michelle Fanale ◽  
Luis Fayad ◽  
Peter McLaughlin ◽  
...  
Keyword(s):  
Hodgkin Lymphoma ◽  
Historical Data ◽  
Stage Iii ◽  
Advanced Stage ◽  
Newly Diagnosed ◽  
Classical Hodgkin Lymphoma ◽  
Bulky Disease ◽  
Long Term Follow Up

Abstract Abstract 1680 Poster Board I-706 We previously reported (Wedgwood et al, ASH, 2007) improvement in event free survival (EFS) using Rituximab+ABVD (RABVD) in newly diagnosed patients with advanced stage classical Hodgkin lymphoma (HL) when compared to the previously published historical data from the International Prognostic Score (IPS) project using standard ABVD (Hasenclever et. Al, NEJM, 1998). The purpose of this report is to provide a final update on the EFS with long term follow up of patients who received RABVD. In addition, because of the potential difference in the EFS reported by the IPS project and a single institution results, we provide a new analysis comparing our RABVD data to that of historical data from our institution. After IRB approval, we conducted a retrospective data analysis on patients with advanced HL treated at our center with ABVD from February 1996 to May 2006. Information was collected for the IPS factors: age, stage, gender, hemoglobin, white blood cell count, albumin, and lymphocyte count. 104 consecutive patients who met the eligibility criteria for the RABVD study were identified, and were evaluable for response with at least 2 year follow up. Median age was 35 years old, 48 were female and 56 male. 23 (22%) had stage II disease, 12 of these with bulky disease, 45 (43%) stage III and 36 (35%) with stage IV. 65 (63%) had IPS 0-2 and 39 (37%) had IPS >2. The institutional 5-year EFS for ABVD patients regardless of IPS was 66%. For those with IPS 0-2 the institutional EFS was 71% compared with 74% reported by the IPS project. The institutional 5 year EFS for patients treated with ABVD with IPS >2 was 55%, compared with 55% reported by the IPS project. With a median of 5 year follow up (6-94 months) the projected EFS for RABVD is 87% which is significantly better than institutional results with ABVD (p=0.0036). Improvement in EFS was observed with RABVD in patients with IPS 0-2 (EFS 89% vs. 71%, p=0.0248); and those with IPS >2 (80% vs. 55%; p=0.0532). In conclusion, this long term follow up data confirms the superiority of RABVD to ABVD in patients with advanced stage classical HL in all risk groups. This data serves as the rationale for a multicenter randomized trial comparing ABVD with RABVD in newly diagnosed patients with classical HL with stage III and IV and IPS >2. The study is currently enrolling patients. Disclosures Off Label Use: Rituximab in Hodgkin lymphoma. Younes:Genentech: Honoraria, Research Funding.

scholarly journals Gonadal Function and Fertility in Survivors After Hodgkin Lymphoma Treatment Within the German Hodgkin Study Group HD13 to HD15 Trials

2013 ◽  
Vol 31 (2) ◽  
pp. 231-239 ◽  
Author(s):  
Karolin Behringer ◽  
Horst Mueller ◽  
Helen Goergen ◽  
Indra Thielen ◽  
Angelika Diana Eibl ◽  
...  
Keyword(s):  
Menstrual Cycle ◽  
Hodgkin Lymphoma ◽  
Recovery Time ◽  
Early Stage ◽  
Study Group ◽  
Advanced Stage ◽  
Male Survivors ◽  
German Hodgkin Study Group ◽  
The Impact

Purpose To optimize fertility advice in patients with Hodgkin lymphoma (HL) before therapy and during survivorship, information on the impact of chemotherapy is needed. Therefore, we analyzed gonadal functions in survivors of HL. Patients and Methods Women younger than age 40 and men younger than 50 years at diagnosis in ongoing remission at least 1 year after therapy within the German Hodgkin Study Group HD13 to HD15 trials for early- and advanced-stage HL were included. Hormone parameters, menstrual cycle, symptoms of hypogonadism, and offspring were evaluated. Results A total of 1,323 (55%) of 2,412 contacted female and male survivors were evaluable for the current analysis (mean follow-up, 46 and 48 months, respectively). Follicle-stimulating hormone, anti-Müllerian hormone, and inhibin B levels correlated significantly with therapy intensity (P < .001). Low birth rates were observed in survivors after advanced-stage treatment within the observation time (women, 6.5%; men, 3.3%). Regular menstrual cycle was reported by more than 90% of female survivors of early-stage HL (recovery time mostly ≤ 12 months). After six to eight cycles of bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone, menstrual activity was strongly related to age (< v ≥ 30 years: 82% v 45%, respectively; P < .001; prolonged recovery time). Thirty-four percent of women age ≥ 30 years suffered severe menopausal symptoms (three- to four-fold more frequently than expected). In contrast, male survivors had mean levels of testosterone within the normal range and reported no increased symptoms of hypogonadism. Conclusion The present analysis in a large group of survivors of HL provides well-grounded information on gonadal toxicity of currently used treatment regimens and allows risk-adapted fertility preservation and comprehensive support during therapy and follow-up.

scholarly journals Lymphoproliferative malignancies in patients with neurofibromatosis 1

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Christina Bergqvist ◽  
François Hemery ◽  
Arnaud Jannic ◽  
Salah Ferkal ◽  
Pierre Wolkenstein
Keyword(s):  
General Population ◽  
Medical History ◽  
Hodgkin Lymphoma ◽  
Incidence Rate ◽  
Population Based ◽  
Neurofibromatosis 1 ◽  
Population Based Study ◽  
Non Hodgkin Lymphoma ◽  
History Of

AbstractNeurofibromatosis 1 (NF1) is an inherited, autosomal-dominant, tumor predisposition syndrome with a birth incidence as high as 1:2000. A patient with NF1 is four to five times more likely to develop a malignancy as compared to the general population. The number of epidemiologic studies on lymphoproliferative malignancies in patients with NF1 is limited. The aim of this study was to determine the incidence rate of lymphoproliferative malignancies (lymphoma and leukemia) in NF1 patients followed in our referral center for neurofibromatoses. We used the Informatics for Integrated Biology and the Bedside (i2b2) platform to extract information from the hospital’s electronic health records. We performed a keyword search on clinical notes generated between Jan/01/2014 and May/11/2020 for patients aged 18 years or older. A total of 1507 patients with confirmed NF1 patients aged 18 years and above were identified (mean age 39.2 years; 57% women). The total number of person-years in follow-up was 57,736 (men, 24,327 years; women, 33,409 years). Mean length of follow-up was 38.3 years (median, 36 years). A total of 13 patients had a medical history of either lymphoma or leukemia, yielding an overall incidence rate of 22.5 per 100,000 (0.000225, 95% confidence interval (CI) 0.000223–0.000227). This incidence is similar to that of the general population in France (standardized incidence ratio 1.07, 95% CI 0.60–1.79). Four patients had a medical history leukemia and 9 patients had a medical history of lymphoma of which 7 had non-Hodgkin lymphoma, and 2 had Hodgkin lymphoma. Our results show that adults with NF1 do not have an increased tendency to develop lymphoproliferative malignancies, in contrast to the general increased risk of malignancy. While our results are consistent with the recent population-based study in Finland, they are in contrast with the larger population-based study in England whereby NF1 individuals were found to be 3 times more likely to develop both non-Hodgkin lymphoma and lymphocytic leukemia. Large-scale epidemiological studies based on nationwide data sets are thus needed to confirm our findings.

scholarly journals Joint association between education and polygenic risk score for incident coronary heart disease events: a longitudinal population-based study of 26 203 men and women

2021 ◽  
pp. jech-2020-214358
Author(s):  
Pekka Martikainen ◽  
Kaarina Korhonen ◽  
Aline Jelenkovic ◽  
Hannu Lahtinen ◽  
Aki Havulinna ◽  
...  
Keyword(s):  
Coronary Heart Disease ◽  
Heart Disease ◽  
Risk Score ◽  
Density Lipoprotein ◽  
Population Based ◽  
Polygenic Risk Score ◽  
Genome Wide ◽  
Increased Risk ◽  
Region Of Residence

BackgroundGenetic vulnerability to coronary heart disease (CHD) is well established, but little is known whether these effects are mediated or modified by equally well-established social determinants of CHD. We estimate the joint associations of the polygenetic risk score (PRS) for CHD and education on CHD events.MethodsThe data are from the 1992, 1997, 2002, 2007 and 2012 surveys of the population-based FINRISK Study including measures of social, behavioural and metabolic factors and genome-wide genotypes (N=26 203). Follow-up of fatal and non-fatal incident CHD events (N=2063) was based on nationwide registers.ResultsAllowing for age, sex, study year, region of residence, study batch and principal components, those in the highest quartile of PRS for CHD had strongly increased risk of CHD events compared with the lowest quartile (HR=2.26; 95% CI: 1.97 to 2.59); associations were also observed for low education (HR=1.58; 95% CI: 1.32 to 1.89). These effects were largely independent of each other. Adjustment for baseline smoking, alcohol use, body mass index, igh-density lipoprotein (HDL) and total cholesterol, blood pressure and diabetes attenuated the PRS associations by 10% and the education associations by 50%. We do not find strong evidence of interactions between PRS and education.ConclusionsPRS and education predict CHD events, and these associations are independent of each other. Both can improve CHD prediction beyond behavioural risks. The results imply that observational studies that do not have information on genetic risk factors for CHD do not provide confounded estimates for the association between education and CHD.

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