Outcome In Hodgkin Lymphoma Research Articles

Treatment Patterns and Clinical Outcomes in Patients with Hodgkin Lymphoma from Saudi Arabia, Türkiye, and South Africa: Subgroup Analysis from the International, Multi-center, Retrospective BHOLISTIC Study.

B-HOLISTIC was a real-world, retrospective study of treatment patterns and clinical outcomes in Hodgkin lymphoma (HL) in regions outside Europe and North America. This subgroup analysis reports findings from Saudi Arabia, Türkiye, and South Africa. Patients aged ≥18 years and diagnosed with stage IIB-IV classical HL receiving frontline chemotherapy (frontline cHL) and/or relapsed/refractory HL (RRHL) from January 2010-December 2013 were assessed. The primary endpoint was progression-free survival (PFS) in patients with RRHL. Overall, 694 patients (RRHL: n=178; frontline cHL: n=653) were enrolled. Among patients with RRHL, >80% received first salvage chemotherapy. The most common first salvage regimens were etoposide, methylprednisolone, cytarabine, cisplatin (ESHAP) in Saudi Arabia (78.3%) and dexamethasone, cytarabine, cisplatin (DHAP) in Türkiye (36.1%) and South Africa (40%). Median PFS (95% confidence interval [CI]) in the RRHL group was 5.1 (3.0-15.9), 19.7 (7.5-not reached), and 5.2 (1.1- 10.1) months in Saudi Arabia, Türkiye, and South Africa, respectively. The 5-year PFS and overall survival (95% CI) rates in patients with RRHL were 33.2% (21.6-45.2) and 78.2% (65.9-86.5) in Saudi Arabia, 42.5% (29.5-54.9) and 79.4% (67.2-87.5) in Türkiye, and 13.1% (4.2-27.0) and 53% (35.5-67.8) in South Africa, respectively. This study showed that the clinical outcomes in Türkiye and Saudi Arabia were generally comparable with Western countries during the study period, although Saudi Arabia had lower PFS rates. Conversely, the clinical outcomes in South Africa were suboptimal, emphasizing the need for novel therapies and improved progression to stem cell transplantation. Additionally, these data may serve as a control group for future studies in these countries and inform clinical decision-making.

Real-world treatment outcomes for Hodgkin lymphoma in South Africa: a prospective observational study

BackgroundProspective data from sub-Saharan Africa suggests that treatment outcomes for people living with HIV (PWH) with Hodgkin lymphoma (HL) are similar to those without HIV. However, real-world data from high-resource settings and retrospective studies from sub-Saharan Africa, suggest inferior outcomes. We set out to evaluate the real-world treatment outcomes for HL in South Africa to better understand the disparate outcomes.MethodsWe established a prospective, observational cohort of newly diagnosed, adult (≥ 18 years) HL cases recruited from Chris Hani Baragwanath Academic and Netcare Olivedale Hospitals in Johannesburg, South Africa between March 2021 and March 2023. Participants were followed for up to 18 months after enrollment with data censored on December 23rd, 2023. The primary endpoint was 1-year overall survival.ResultsWe enrolled 47 participants with HL including 31 PWH and 16 HIV-negative. Advanced stage disease and B symptoms were common at time of diagnosis irrespective of HIV status. Bone marrow biopsy, performed during the work-up and evaluation of cytopenias, provided the initial diagnosis of HL in 16/31 (52%) PWH. HIV status and bone marrow involvement were associated with early mortality (within 3 months of diagnosis) and a poorer 1-year overall survival from diagnosis (HIV: 55% vs. 88%; p = 0.03; bone marrow involvement: 50% vs. 80%; p = 0.02). Among evaluable participants, those that received at least 6 cycles of chemotherapy and underwent response assessment, there was no difference between those with and without HIV.ConclusionTraditional laboratory markers of poor prognosis including anemia, lymphopenia and hypoalbuminemia were more common among PWH and those with bone marrow involvement and suggest high risk disease. A better understanding of the drivers of these aggressive presentations is warranted to ensure more PWH are able to tolerate chemotherapy.

Current Immunotherapy Progress in the Hodgkin Lymphoma

Hodgkin lymphoma, a distinctive cancer affecting the lymphatic system, poses challenges in treatment due to its unique characteristics and the limitations of traditional therapies. This essay delves into the potential of immunotherapy to transform the landscape of treatment for Hodgkin lymphoma. Furthermore, the essay analyses case studies to illustrate the efficacy of these approaches. It presents an overview of the underlying principles, as well as specific immunotherapeutic approaches, such as checkpoint inhibitors, monoclonal antibodies, and CAR-T cell therapy, and their mechanisms. Immunotherapy offers a targeted and personalized alternative to conventional chemotherapy and radiation, presenting promising results in clinical trials. Clinicians manage subtleties in immune-related toxicity and response assessment as the field develops. The goal of immunotherapy research in the initial phases of treatment is to increase cure rates while lowering long-term dangers. Ongoing research and advancements, including checkpoint blockade studies, offer hope for refining treatment approaches and optimizing outcomes in Hodgkin lymphoma. This essay emphasizes the significance of immunotherapy in providing effective and less toxic alternatives, heralding a new era in Hodgkin lymphoma treatment.

Prognostic Impact of Serum β2-Microglobulin Levels in Hodgkin Lymphoma Treated with ABVD or Equivalent Regimens: A Comprehensive Analysis of 915 Patients.

The significance of serum beta-2 microglobulin (sβ2m) in Hodgkin lymphoma (HL) is controversial. We analyzed 915 patients with HL, who were treated with ABVD or equivalent regimens with or without radiotherapy. Sβ2m levels were measured by a radioimmunoassay (upper normal limit 2.4 mg/L). Sequential cutoffs (1.8-3.0 by 0.1 mg/L increments, 3.5 and 4.0 mg/L) were tested along with ROC analysis. The median sβ2m levels were 2.20 mg/L and were elevated (>2.4 mg/L) in 383/915 patients (41.9%). Higher sβ2m was associated with inferior freedom from progression (FFP) at all tested cutoffs. The best cutoff was 2.0 mg/L (10-year FFP 83% vs. 70%, p = 0.001), which performed better than the 2.4 mg/L cutoff ("normal versus high"). In multivariate analysis, sβ2m > 2.0 mg/L was an independent adverse prognostic factor in the whole patient population. In multivariate overall survival analysis, sβ2m levels were predictive at 2.0 mg/L cutoff in the whole patient population and in advanced stages. Similarly, sβ2m > 2.0 mg/L independently predicted inferior HL-specific survival in the whole patient population. Our data suggest that higher sβ2m is an independent predictor of outcome in HL but the optimal cutoff lies within the normal limits (i.e., at 2.0 mg/L) in this predominantly young patient population, performing much better than a "normal versus high" cutoff set at 2.4 mg/L.

Quality Analysis of Radiation Therapy for Hodgkin Lymphoma in the HD 16/17 Trials: A Final Report By the Reference Radiation Oncology Panel of the German Hodgkin Study Group

The HD 16 and 17 trials by the German Hodgkin Study Group (GHSG) have evaluated the use of consolidative radiotherapy (RT) in early-favorable and -unfavorable stage Hodgkin lymphoma (HL), respectively (1, 2). Quality of RT planning and execution is pivotal for treatment outcome in HL with protocol violations jeopardizing prognosis (3). Consequently, the present work aims at a decisive analysis of quality and dosimetry in the modern era. Random samples of 100 involved-field RT (IFRT) plans in HD16 and 176 plans in HD17 (134 involved-node RT (INRT) and 42 IFRT) were selected for analysis. Evaluation was performed systematically by the reference radiation oncology panel using pre-chemotherapy imaging, recommendation by the reference radiation oncology and RT planning imaging and graded as "correct", "minor" or "major deviation", respectively. RT doses to the target volume and organs at risks (OAR) were analyzed using dose-volume histograms. Median RT doses were 20 Gy (19.8 Gy-21.6 Gy) in HD16 and 30 Gy in HD17 (IFRT: 18-30.6 Gy, INRT: 14 Gy-40 Gy). Overall, 84.0%, 69.0%, and 76.1% of RT series in HD16, the IFRT-group of HD17 and the INRT-group of HD17, respectively, were planned correctly. The main reason for major deviation was an insufficient coverage of an involved region (11 %-14.3 %). There was no significant difference in quality between IFRT and INRT in HD17 (p = 0.418 for any deviations; p = 0.466 for major deviations). In comparison to previous GHSG studies in the respective stages, a significant increase in correct RT-series (p<0.001) and decrease in major deviations (p<0.001) occurred. However, doses to OAR varied individually with median values of 4.3 Gy (0.2 Gy-9.2 Gy), 4.7 Gy (0.2 Gy-15.2 Gy) and 3.8 Gy (0.0 Gy-16.0 Gy) for mean doses to the right lung, left lung and heart in HD16, respectively. Correspondingly, values were 9.8 Gy (0.3 Gy-20.0 Gy), 10.5 Gy (0.2 Gy-26.5 Gy) and 13.1 Gy (0.5 Gy-30.4 Gy) for mean doses to the right lung, left lung and heart in HD17, respectively. The size of the planning target volume decreased significantly with INRT compared to IFRT (median values: 1163.1 ml vs. 1464.3 ml; p = 0.043). However, only some OAR-parameters (V25 of the right and left lung, respectively, thyroid and spinal cord) showed significant differences between INRT and IFRT in HD17. The use of intensity-modulated techniques in HD 17 resulted in an increase in V5 and V10 of the lungs with a concomitant decrease in V20-V30. Quality of RT in the planning and treatment of HL has improved significantly with the latest GHSG study generation. Future analyses will focus on a further individualization of treatment fields.

POSTER: HL-456 A Retrospective Analysis of Impact of EBV Status on Outcomes in Hodgkin Lymphoma

POSTER: HL-456 A Retrospective Analysis of Impact of EBV Status on Outcomes in Hodgkin Lymphoma

HL-456 A Retrospective Analysis of Impact of EBV Status on Outcomes in Hodgkin Lymphoma

HL-456 A Retrospective Analysis of Impact of EBV Status on Outcomes in Hodgkin Lymphoma

Advances and Clinical Outcomes in Hodgkin Lymphoma in the Era of Novel Therapies

Hodgkin lymphoma (HL) is traditionally considered one of the hematological malignancies with the highest rate of cure, ranging from 70 to 90% depending on the disease and patient features [...].

Influence of Sociodemographic Determinants on the Hodgkin Lymphoma Baseline Characteristics in Long Survivors Patients Enrolled in the Prospective Phase 3 Trial AHL2011.

Whereas numerous studies on several cancers describe the link between social conditions and disease severity, little is known about the social and demographic characteristics of Hodgkin lymphoma (HL) patients. At diagnosis, 10-15% of the patients in the advanced stages have a well-known poor outcome owing to their chemoresistance, but the determinants of the more advanced stages remain elusive. The objective of the present study was to decipher the potential impact of social disparities on the disease features at diagnosis and analyze how the sociodemographic patient features could impact the HL outcome of patients with advanced-stage HL enrolled in the AHL2011 trial. This ancillary study was conducted on a cohort of patients from French centers that had recruited more than five patients in the phase III AHL2011 study (NCT0135874). Patients had to be alive at the time of the ancillary study and had to have given their consent to answer the questionnaire. Pre-treatment data (age, gender, stage, B symptoms, IPS), the treatment received, the responses to PET-CT, and the presence of serious adverse events (serious adverse events-SAEs) were all extracted from the AHL2011 trial database. Sociodemographic data-marital status, living area, level of education, socio-professional category, and professional situation-were extracted from the questionnaires. The population density at the point of diagnosis was determined based on ZIP Code, and the distance from the reference medical center was then calculated by the road network. Baseline PET acquisition was performed before any treatment. PET images at baseline were centrally reviewed. The total metabolic tumor volume (TMTV) at the baseline was calculated using a 41% SUVmax cutoff for each lesion. Progression-free survival was defined as the time from randomization to the first progression, relapse, or death from any cause or the last follow-up. The data cutoff for the analyses presented here was 31 October 2017. The progression-free survival was analyzed on an intention-to-treat basis. Among the 823 patients enrolled in the AHL2011 study, the questionnaire was sent to 394 patients, of whom 232 (58.9%) responded. At the time of HL diagnosis, 61.9% (N = 143) of patients declared that they were not socially isolated, 38.1% (N = 88) that they were single, 163 (71.2%) had a professional activity, and 66 (28.8%) were inactive owing to unemployment, retirement, or sick leave. Of the patients, 31.1% (N = 71) lived in a rural region, compared to 68.9% (N = 157) that lived in an urban region. The residence ZIP Code at the time of HL diagnosis was available for 163 (70%). Sociodemographic characteristics did not influence the presence of usual prognostic factors (ECOG, B symptoms, bulky mass, IPS) except for professional activity, which was associated with more frequent low IPS (0-2) (79 (48.5%) active versus 20 (30.3%) inactive patients; p = 0.012). Likewise, no correlation was observed between TMTV and sociodemographic characteristics. However, the TMTV quartile distribution was different according to the living area, with the two upper quartiles being enriched with patients living in a rural area (p = 0.008). Moreover, a negative correlation between the average number of the living area's inhabitants and TMTV (R Pearson = -0.29, p = 0.0004) was observed. This study focused on sociodemographic parameters in advanced-stage HL patients and shows that professional activity is associated with more favorable disease features (low IPS), while patients living in rural or low-populated areas are more likely to have an unfavorable HL presentation with a high tumor burden (high TMTV). These data suggest that some patient sociodemographic characteristics might impact either access to medical care or environmental exposure, leading to a higher frequency of unfavorable presentations. Further prospective sociodemographic studies are necessary to confirm these preliminary results.

The Effects of Social Vulnerability on the Prognosis and Outcomes of Hodgkin's Lymphoma in Adults across the United States

Introduction: Hodgkin's Lymphoma (HL) is a common presentation of lymphoma in the United States, representing 10% of all newly diagnosed lymphomas or around 8540 cases annually. With an estimated 5-year survival of 88%, HL generally follows a more indolent course compared to other hematologic malignancies, necessitating patients with HL receiving longer follow up care. Therefore, social determinants of health (SDoH) have ample opportunity to impact care; individual SDoH factors, such as race or lower socioeconomic status (SES), have already been identified as contributing poorer prognosis. However, SDoH is realistically multifaceted and combining multiple factors of SDoH to assess HL outcomes has not yet been well characterized. Here, we compare aggregated SDoH encapsulated by the social vulnerability index, a tool created by the Centers for Disease Control (CDC) using census data, to determine how SDoH impacts prognosis and outcomes in patients with HL. Methods: All adult patients with HL as tracked in the Surveillance, Epidemiology, and End Results (SEER) Program were geographically matched to determine social vulnerability using the Social Vulnerability Index (SVI) at the time of diagnosis. Extranodal HL manifestations were excluded as this was a much rarer form with a different presentation. SVI dynamically weights 15 SDoH considerations into 4 themed domains, including SES, minority status & language, household composition & disability, and housing type & transportation, at the census tract, or county level in sparsely populated areas, to provide a percentile rank ranging from 0 (least vulnerable) to 1 (most vulnerable) across the United States. HL patients were grouped into equivalently sized relative-SVI quintiles based on actual SVI scores ranging from lowest to highest vulnerability. Data was analyzed for HL months surveyed and then patients lost to follow up were excluded to assess mortality in HL months survival for the established quintiles as seen in figure 1. Univariate linear regressions were used to determine significance. Similar methodologies and analyses were also conducted for the 4 SVI domains. Results: Overall, 49366 individuals were identified in SEER (113±105 months), with 17597 of those individuals included in months survival analysis (76±96 months). All groups were statistically significant (P<0.001) with both overall and SVI domains demonstrating decreasing months surveyed or survival with increasing social vulnerability. Additionally, as seen in table 1, a 31.2% decrease in months surveyed and a 48.9% decreased in months survival was noted for overall SVI when comparing the highest vulnerability (most negative SDoH profile) to the lowest vulnerability quintile (most positive SDOH profile). Substantial decreases were also seen in SES (34.3%, 35.2%), minority status & language (13.7%, 21.8%), household composition & disability (15.8%, 18.8%), and housing type & transportation (22.5%, 36.5%) for months surveyed and months survival respectively between the two groups. Conclusion: Higher overall SVI scores and specific social vulnerability domain scores correlated with statistically decreased months surveyed and months survival in patients with HL. Furthermore, the size of difference noted between high and low vulnerability groups in both categories indicate the substantial role SDoH has in both patient follow up and mortality and may suggest differing impact across various SDoH domains. Despite established management for HL, consequential health disparities are clearly still present affecting multiple avenues of care. With such a large and encompassing data set, greater power and statistical certainty can be generated. This work highlights the need for specific initiatives to target SDoH in HL to bridge the gap in providing equitable treatment for all. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Treatment pathways and clinical outcomes in Hodgkin lymphoma outside Europe and North America: results from the international, multicenter, retrospective, B-HOLISTIC study

Information on Hodgkin lymphoma (HL) is mostly limited to Europe and North America. This real-world, retrospective study assessed treatment pathways and clinical outcomes in adults with stage IIB–IV classical HL receiving frontline treatment (n = 1598) or relapsed/refractory HL (RRHL, n = 426) in regions outside Europe and North America between January 2010 and December 2013. The primary endpoint was progression-free survival (PFS) in the RRHL group. Among patients with RRHL, 89.0% received salvage chemotherapy; most common regimen was etoposide, methylprednisolone, cytarabine, cisplatin (ESHAP; 26.3%). Median PFS in the RRHL group was 13.2 months (95% confidence interval [CI]: 9.9–20.2) and was longer in patients with vs. without stem cell transplantation (SCT; 20.6 vs. 7.5 months; p = 0.0071). This large-scale study identified a lower PFS for RRHL in the rest of the world compared with Europe and North America, highlighting the need for novel targeted therapies and SCT earlier in the treatment continuum. Clinical trial registration: NCT03327571.

P069: Characterisation of influencing parameters on oocyte quality preservation in a cohort of Hodgkin lymphoma patients

Background: Hodgkin lymphoma (HL) is the most frequent lymphoma in the young population. The standard of treatment is chemotherapy including alkylating agents known to affect fertility. Fertility preservation is usually proposed before treatment with oocyte cryopreservation as a reference. In different cohorts of healthy women, some factors are well known to have an impact on oocyte quality preservation such as age, anti-Müllerian hormone (AMH), body mass index (BMI). German Hodgkin Study Group (GHSG) distinguishes 3 prognostic groups: early, intermediate, advanced stages (respectively defined GHSG I, II, III in our study). In literature, the parameters influencing fertility preservation outcomes in HL are not clear, namely HL’s stage and inflammation. In this study we evaluated the impact of HL’s stage using GHSG criteria on fertility preservation outcomes. Methods: We performed a retrospective study on 79 women, with newly diagnosed and previously untreated HL who underwent oocyte cryopreservation between 2012 and 2021. The patients were extracted from a cohort of fertility observatory in Lille University Hospital. The primary outcome was the number of metaphase 2 oocyte retrieved (M2). Estradiol level at the ovulation induction and the ratio of M2/follicles >15mm were secondary outcomes. We compared fertility outcomes between two groups: early and intermediate stage (GHSG I+II) and advanced stage (GHSG III). We evaluated in univariate and multivariate analyses the following factors: AMH, BMI, use of hormonal contraception, age and C reactive protein (CRP). Results: The two groups (GHSG I-II and GHSG III) were comparable. In univariate analyses, AMH was the only statistically significant factor regarding the number of M2 (p<0,0001) and Estradiol level (p<0,0001). In multivariate analysis, GHSG score was not statistically significant concerning Estradiol level (p=0,5) contrary to AMH level (p<0,0001). Conclusion: In our study, AMH level is doubtlessly a factor impacting the quality of oocyte preservation. HL’s stage and inflammation do not seem to affect fertility preservation outcomes in the whole cohort. These results, based on the largest cohort of HL patients evaluating HL’s risk groups provide important information about expected cryopreservation outcomes. According to this study, oocyte cryopreservation should be considered even for patients with advanced HL’s stage.

HL-100 Outcomes of Patients With Hodgkin Lymphoma During a Period of Drug Shortage in Lebanon: A Single-Center Experience

Hodgkin lymphoma (HL) represents two-thirds of all lymphomas diagnosed in Lebanon. Due to the COVID-19 pandemic and the unprecedented financial crisis, shortages of oncology drugs are now common in Lebanon. The shortage of conventional agents has created remarkable challenges for both HL patients and health care providers. We lack studies that document the outcome of HL in Lebanon during this period. To determine the outcome of HL patients treated in Lebanon during the period of drug shortages. This retrospective study included 52 HL patients diagnosed between October 2019 and December 2021 at Hôtel Dieu de France Hospital in Lebanon. Patients had classical or nodular lymphocyte-predominant subtypes. The treatment patterns, frequency of incomplete protocols, missing agents, and response to first-line treatment were analyzed. A total of 52 patients were reviewed with a median age of 35 years (range, 15-85 years); 52% were male. In this study, 65% of patients had B symptoms at diagnosis, 70% had no comorbidities, 64% had an advanced stage, 60% had bulky disease, and 90% had low- to intermediate-risk disease according to the International Prognostic Score. The nodular sclerosing subtype was the most common histological subtype (77%). The ABVD regimen was offered to 85% of patients and radiotherapy was offered to 10%. Eleven patients (22%) did not receive the full treatment per protocol due to drug shortage: 8 patients (15%), 2 patients (4%), and 1 patient (2%) had missing bleomycin, dacarbazine, and vinblastine, respectively. Of these patients, 6 (54%) received treatment without the missing agent, 4 (36%) imported the medication from an external source at their own expense, and 1 (9%) was switched to another protocol. Among 11 patients who did not receive proper therapy, the rates of complete response, partial response, stable disease, and progressive disease were 70%, 15%, 5%, and 10%, respectively. In this single-institution study from Lebanon, the outcomes of patients with HL treated during an unprecedented crisis and drugs shortage were comparable to those of previous reports. This emphasizes the resilience of the Lebanese population and adaptability despite hard conditions.

The Outcome of Hodgkin Lymphoma With Reference to Prognostic Markers.

Objectives: This study aimed to determine the impact of prognostic markers on the outcomes of Hodgkin lymphoma.Methods: It is a cross-sectional, single-center study. A total of 60 patients diagnosed with Hodgkin lymphoma were recruited for the study over five years between 2016 to 2020. The study setting was the National Institute of Blood and Bone Marrow Transplant in Pakistan. The Statistical Package for Social Sciences (SPSS) version 23 (IBM Corp., Armonk, NY, USA) was used for statistical analysis.Results: In the study population, 63.3% of the patients were male (38/60), and 36.7% were female (22/60). Hodgkin lymphoma was divided into four stages: stage I (18.3%), stage II (18.3%), stage III (46.7%), and stage IV (16.7%). Patients in stage III had a higher value of hemoglobin (Hb) than in other stages of the disease. The erythrocyte sedimentation rate was high in 56.7% of stage III patients than in patients of the other stages. The lactate dehydrogenase (LDH) levels were not under the normal range in 51.6% of patients. Only 20% of patients in stage III had LDH values within the normal range, whereas 26.6% did not.Conclusion: There was a significant impact of prognostic factors on the survival of patients with Hodgkin lymphoma.

The prognostıc significance of blood counts in patients with hodgkin lymphoma.

The aim of the study was to examine the demographic, clinical features, treatment responses, and outcomes of Hodgkin lymphoma (HL) patients and to investigate the factors affecting their survival. A retrospective analysis was made of patients diagnosed with HL in our department between 2009 and 2019. Treatment regimen, treatment response, and follow-up times were recorded for all patients. Using these data, complete response (CR) rates, overall survival (OS), and progression-free survival (PFS) were calculated. The effects of parameters on survival were investigated with Cox regression analysis. Evaluation was made of 60 patients with a median age of 33.5 years [18.0-80.0] and mean follow-up duration of 29.34 ± 23.64 months. Median OS and PFS could not be reached with a mean OS of 85.6 months, and PFS of 71.7 months at the final visit. Only initial leukocyte and neurophil count were determined to have a statistically significant impact on survival (OR = 1.004; P = 0.031 vs OR = 0.996; P = 0.036). In HL patients, in addition to the many prognostic scoring systems, leukocyte and neutrophil count can be used as an independent prognostic parameter. Patients with higher leukocyte and lower neutrophil counts at the time of diagnosis should be managed more carefully.

Multiplex Immunofluorescence reveals specific subsets of immune cell populations expressing CD137/TNFRSF9 as predictors of unfavorable outcomes in Hodgkin Lymphoma

The tumor microenvironment (TME) is a crucial determinant of tumor growth, progression, and resistance to chemotherapy in cancer, with classical Hodgkin's lymphoma (cHL) being one of the most representative examples. The major component of the tumor mass in cHL is a rich and vast immune microenvironment, comprising a diverse repertoire of cell populations, many of which remain unknown. The specific contribution of the different functional cell subsets in the TME, such as T lymphocytes, monocytic populations, or dendritic cells, is also undiscovered. Currently, around 30% of advanced-disease patients or some atypical cases of primary refractory tumors do not respond to treatment or relapse shortly afterwards. Response predicting features of TME have been recently identified, which suggest a rationale for alternative therapeutic strategies. All existing evidence indicates that HRS cells actively coordinate and remodel their complex TME and that its diverse components influence the therapeutic response in cHL patients. The sensitivity of current technology enables analysis of specific functional phenotypes in the TME as diagnostic and predictive biomarkers. One example is the quantitative dissection of the TME with in situ multispectral imaging using formalin-fixed, paraffin-embedded (FFPE) tissues, with which we could analyze simultaneously CD68, CD137, CD30, CD3, PDL1, and PD1 markers to identify specific cell subsets. Remarkably, some cell populations expressing CD137 were associated with unfavorable responses in cHL patients, such as the activated monocytic cells (CD68+ CD137+), the tumor-reactive T cells (CD3+ CD137+), and the tumor CD30+ CD137+ PDL1+ cell subset. By contrast, the CD3+ CD137- T-cell population was associated with better prognosis, suggesting that CD137 could be a new prognostic marker in cHL for poor outcomes. Moreover, some cell subsets that could not be studied until now due to the lack of appropriate technology were found to be more abundant in the first stages of the disease, whereas others were less abundant than in stage IV. For instance, we could study exhausted T cells (CD3+ PD-L1+ PD-1+) and other related cells that were largely unexplored in cHL. Finally, these findings were validated with independent series of patient samples, including immunohistochemical studies with specific antibodies and gene-expression analysis.

Nomogram model and risk score predicting overall survival and guiding clinical decision in patients with Hodgkin’s lymphoma: an observational study using SEER population-based data

IntroductionThis study developed a prognostic nomogram of Hodgkin lymphoma (HL) for purpose of discussing independent risk factors for HL patients with Surveillance, Epidemiology and End Results (SEER) database.MethodsWe collected data...

HL-342: Clinical Profile, Prognostic Factors, and Outcomes of Hodgkin Lymphoma: A Retrospective Study

HL-342: Clinical Profile, Prognostic Factors, and Outcomes of Hodgkin Lymphoma: A Retrospective Study

Are Absolute Monocyte Count and The Lymphocyte-Monocyte Ratio (LMR) Valid Prognostic Factors In Classical Hodgkin Lymphoma? An Evaluation Based On Data From 1079 Patients

IntroductionThere is an increasing amount of data showing that both host immunity and tumor microenvironment play an essential role in determining the clinical course in patients with Hodgkin lymphoma (HL) and may also influence their response to therapy. Some investigators have considered the absolute lymphocyte count (ALC) as a surrogate bio-marker of tumor-infiltrating lymphocytes reflecting systemic host immunity, while the absolute monocyte count (AMC) is regarded as a surrogate bio-marker of tumor-associated macrophages reflecting the tumor microenvironment. For many years lymphopenia has been considered as a negative factor predicting poor outcome in HL. Recently monocytosis and the lymphocyte-monocyte ratio (LMR= ALC/AMC), which combines these two surrogate bio-markers, have also been shown to be useful prognostic parameters in HL, particularly in terms of progression free survival (PFS). AimsThe aim of the present study was to verify whether AMC and LMR are indeed valid prognostic parameters in HL, utilizing a large cohort of patients with the disease. Materials and MethodsWe collected data from 1079 patients with classical Hodgkin's lymphoma (cHL) enrolled in different clinical trials of “Gruppo Italiano Studio Linfomi (GISL)” during 1988-2007. Previously we had evaluated a database of 371 patients with cHL and examined different AMC and LMR cut-off levels using the maximum log rank test and c-Harell (area under the curve). We identified AMC of 600/mm3 and LMR of 3.5, as optimal cut-off values. ResultsPatients in our current study had the following characteristics: median age 32 years (range 17-71), 51% males, 15% stage IV disease, 74% with International Prognostic Score (IPS) 0-2, 72% nodular sclerosis and 18% mixed cellularity; 43% were treated with ABVD and 29% with BEACOPP/BEACOPP-like regimens. Radiotherapy (RT) was administered to 66% of cases. Median follow-up was 6.8 years (range 0.1-19), and 5-years and 10-years overall survival (OS) was 89 and 83%, respectively; 5-years PFS was 79%. In an earlier evaluation the 10-years PFS for patients with AMC >600/mm3 and LMR <3.5 was significantly worse, compared to the group with AMC <600/mm3 and LMR >3.5 (p-value: 0.032 and 0.005). However now after applying the same cut-off values to the larger database, we found no statistical differences in PFS ,and both threshold values for AMC (600/mm3) and LMR (3.5) lost their prognostic power. Using the same statistical methods for the cohort of 1079 patients, we found different cut-off values for AMC and LMR, that were equally effective in splitting different survival patterns. For AMC the value of 750/mm3 (26% of patients with AMC >750/mm3), and for LMR a ratio of 1.5 (19% of patients with LMR <1.5) revealed a difference in PFS which was statistically significant (p-value 0.003 and 0.001, respectively), as shown in Figure 1. In multivariate analysis after adjusting by IPS, RT and type of chemotherapy regimen administered, AMC and LMR maintained their prognostic significance for PFS (HR 1.37, p 0.022 and 1.37, p 0.037). After interaction with IPS (Figure 2) LMR showed an uniform pattern within the two risk -groups (overall: HR=1.42, p 0.019; IPS 0-2: HR=1.34, p 0.181; IPS 3-7: HR=1.49, p 0.048). [Display omitted] [Display omitted] ConclusionsOur study of 1079 patients confirms that peripheral monocyte and lymphocyte counts have an important prognostic impact in cHL. The cut off-values we used, although different from those utilized previously, were able to distinguish patients with different PFS. The cut-offs reported in the literature vary according to the different authors and the various sets of patients examined. At present we feel there is still a clear need to finally establish definitive and more appropriate cut-off levels that can be used for all future studies. In order to achieve this goal, it is essential to study an even larger series of patients within the framework of an international collaborative study. Disclosures:No relevant conflicts of interest to declare.

Discordant PET Findings and a High Relapse Rate Characterize Hispanics With Hodgkin's Lymphoma Treated With ABVD.

Population-based studies on Hodgkin's lymphoma (HL) have shown reduced survival in Hispanics and non-Hispanic Blacks compared with non-Hispanic Whites. To better understand the factors contributing to this outcome discrepancy, we retrospectively reviewed the charts of patients with HL diagnosed and treated at a single institution located along the Texas-Mexico border. We performed a retrospective chart review of all patients with HL treated at our institution over an 8-year period (2011-2018). The International Prognostic Score was calculated for all patients and results of positron-emission tomography (PET) scans (interim and end of treatment) were also recorded. Variables analyzed included tumor-related findings (stage, subtype of HL), treatment history (chemotherapy regimen including number of cycles, dose intensity and radiation treatments) and neutrophil to lymphocyte ratio. Quantitative variables were described using median, interquartile range, minimum and maximum observations. Categorical variables were described using frequency and proportions. Kaplan-Meier curves were used to show relapse-free survival. A total of 24 patients were treated in the time frame, of whom 23 were Hispanic. All were treated with doxorubicin, bleomycin, vinblastine and dacarbazine (ABVD) or an ABVD-like regimen. Dose intensity for chemotherapy exceeded 90%. After a median follow-up of 43 months, the relapse rate was 45.8%. Positive and negative predictive values for interim PET (0% and 50%) and end of therapy PET (80% and 58%) were suboptimal to allow for a PET-adapted therapeutic approach. Hispanics have a high relapse rate following ABVD which is not fully explained by universally accepted prognostic factors. Performance of PET scan in predicting outcomes of HL needs to be further studied and optimized before adopting a PET-adapted treatment paradigm for underserved Hispanic populations.