Diagnosis Of Hodgkin Lymphoma Research Articles

Effects and outcomes of tumor lysis syndrome in patients admitted with Hodgkin and non-Hodgkin lymphoma: A National Inpatient Sample study (2019-2020).

e19032 Background: Tumor Lysis Syndrome (TLS) is a life-threatening oncologic emergency. The newer advancement in therapeutic approaches in oncology has widened the range of malignancies associated with TLS. A lot of literature on the incidence of TLS in various solid malignancies exists. However, the effects of TLS on hematological malignancies, especially Hodgkin’s Lymphoma (HL) and Non-Hodgkin’s Lymphoma (NHL) have rarely been analyzed. Our study aims to identify the impact of TLS in patients hospitalized with HL and NHL and draw a comparison between HL and NHL. Methods: We analyzed the National Inpatient Sample database from 2019 - 2020 to identify patients > 18 years old with a primary diagnosis of HL and NHL. We compared the TLS prevalence and all-cause in-hospital mortality, length of hospital stay (LOS), and total costs in patients admitted with HL and compared it with NHL. Categorical variables were compared using the chi-square test, and the t-test compared continuous variables. Multivariable regression analyses were performed adjusting for demographics, hospital-level characteristics, and relevant comorbidities. Results: Among 24,550 Hodgkin’s Lymphoma (HL) hospitalizations and 108,060 Non-Hodgkin’s Lymphoma (NHL) hospitalizations, TLS was diagnosed in 0.69% of HL patients and 0.89% of NHL patients. In-hospital mortality was significantly higher in both HL (44.1%) and NHL (28.3%) patients with TLS compared to those without TLS (HL: 4.5%, NHL: 5.1%). Multivariate regression analysis revealed that TLS presence increased the chance of mortality among both HL (OR 17.9) and NHL (OR 7.3) patients. TLS also significantly impacted secondary outcomes including Acute Kidney Injury (AKI) and Hyperkalemia in both HL and NHL patients. No statistically significant differences were found in the odds of cardiac arrhythmias between HL and NHL patients with TLS (Table). TLS was associated with longer Length of Stay and higher total hospital costs in both HL and NHL patients compared to those without TLS. Conclusions: TLS is significantly associated with increased mortality in patients with HL and NHL, more in HL compared to NHL. In patients with HL, and NHL, TLS is an independent risk factor for in-patient mortality, the longer LOS, and the total cost, thereby incurring an increased burden on healthcare resources. Our study aims to highlight the need for greater vigilance in this vulnerable group when TLS occurs. [Table: see text]

STAT3 Expression and Its Correlation with PD-L1 Expression in Non-Hodgkin's Lymphoma and Hodgkin's Lymphoma at Dr. Saiful Anwar Regional Public Hospital in Malang, Indonesian Population.

Lymphomas are malignant lymphocyte neoplasms that globally account for 10% of cancers in individuals aged <20 years. Malignant lymphomas are divided into Hodgkin's lymphoma (HL) and non-Hodgkin's lymphoma (NHL). Despite the availability of many therapeutic modalities for lymphoma, such as Brentuximab vedotin, Nivolumab, and Pembrolizumab, it is still necessary to identify appropriate strategies with minimal side effects. Immunotherapy is a promising approach, exemplified by targeting JAK/STAT3 signaling, which can inhibit tumor growth and enhance antitumor immune responses. Hence, STAT3 (signal transducer and activator of transcription 3) is a promising therapeutic target. PD-L1 (programmed death-ligand 1), an immune checkpoint molecule, is used as a frontline treatment for various cancers. This study aims to determine STAT3 expression and its correlation with PD-L1 expression in NHL and HL to serve as a basis for further research on anti-STAT3 and its combination with other therapy targets. Samples were obtained from paraffin blocks of patients with confirmed diagnoses of NHL and HL, and then immunohistochemical staining was carried out with PD-L1 and STAT3 antibodies. The collected data were then analyzed using SPSS. Among the 10 HL patients, no patients (0%) expressed STAT3, while nine patients (90%) expressed PD-L1. Among the 10 NHL patients, 1 patient (10%) expressed STAT3, while six patients (60%) expressed PD-L1. There were no significant differences in STAT3 expression and PD-L1 expression between HL patients and NHL patients. There was no correlation between STAT3 and PD-L1 expression in HL and NHL because almost all STAT3 expressions were negative. Although this study revealed no differences between STAT3 and PD-L1 expression in HL and NHL and no significant correlation between STAT3 and PD-L1 expression in HL and NHL, this may serve as the basis for understanding the role of STAT3 and PD-L1 in the regulation of HL and NHL, which may be useful for further research targeting STAT3 and PD-L1 immunotherapy in HL and NHL.

Immunohistochemistry in the therapeutic decision for Hodgkin’s lymphoma

Hodgkin's lymphoma is a highly curable malignant hemopathy in both adults and children with therapy adapted to risk factors, including both chemotherapy and radiotherapy. Through effective and curable therapeutic schemes there is a huge potential to improve the vital prognosis and the quality of life in the long term. 15-20% of patients in early stages (stages I, II) and 35-40% of those in advanced stages (III and IV) have relapses or resistance to first-line therapy. Molecular analysis of the cells facilitated the discovery that classical Hodgkin lymphoma, in the vast majority of cases, and predominantly lymphocytic lymphoma present clonal abnormalities derived from the germinal center of B cells. RS cells and their mononuclear variants – Hodgkin cells (HRS) demonstrate an antigenic expression without lineage specificity: CD 15(Leu-M1) and CD 30 (Ki-1). Immunohistochemistry helps to identify the two major categories of Hodgkin's lymphomas. The diagnosis of Hodgkin's lymphoma requires a histopathological examination on a lymph node biopsy or, more rarely, a biopsy for extranodal determination of the disease. The identification of Reed-Sternberg cells and their variants is essential for establishing the histological diagnosis of Hodgkin lymphoma. Comparative study (retrospective and prospective) of two groups of patients with Hodgkin's Lymphoma: Lot 1 – with favorable evolution; Lot 2 – refractory/relapsed/partial remission cases. Study groups – 80 patients diagnosed with classical Hodgkin's lymphoma over a 10-year period, between 2007-2017: – Lot 1-53 patients with a favorable evolution – in complete remission after the first line of treatment; – Lot 2-27 patients with unfavorable evolution (relapsed/refractory/partial remission cases).

Graft Failure Incidence, Risk Factors, and Outcomes in Patients Undergoing Non-Myeloablative Allogeneic Hematopoietic Cell Transplantation Using Post-Transplant Cyclophosphamide

Graft failure (GF) is a major complication of allogeneic hematopoietic cell transplantation (alloHCT) that results in significant morbidity and mortality. Post-transplant cyclophosphamide (PTCy)-based graft-versus-host disease (GVHD) prophylaxis has emerged as an effective regimen across the spectrum of donor-match settings, but few studies have investigated the characteristics of GF in the setting of PTCy-based GVHD prophylaxis. The objective was to detail the incidence, clinical features, risk factors, and outcomes for patients with primary graft failure (PGF) and secondary graft failure (SGF). In this retrospective study at a single institution, 958 consecutive patients undergoing first nonmyeloablative (NMA) alloHCT with PTCy-based GVHD prophylaxis were analyzed. PGF was defined as a failure to achieve an ANC ≥ 500 cells/m3 by day 30 of transplant in the absence of residual disease. SGF was defined as complete loss of donor chimerism after initial engraftment. The incidences of PGF and SGF were 3.8% (n = 37) and 1.8% (n = 17), respectively. Neither PGF nor SGF were associated with HLA disparity. In a multivariate analysis, risk factors for PGF in this cohort included age ≥ 65 (OR 2.4, 95% CI 1.2 to 4.8, P = .0120), an underlying diagnosis of MDS, MPN, or MDS/MPN overlap (OR 2.8, 95% CI 1.4 to 5.7, P = .0050), post-transplant viremia with HHV-6 (OR 2.9, 95% CI 1.5 to 5.7, P = .0030), and low CD34+ dose (OR 0.7, 95% CI 0.5 to 0.9, P = .0080). Patients with PGF had poor overall survival, driven primarily by a high rate of nonrelapse mortality (59% at 36 months). SGF was associated with use of a bone marrow graft source and a diagnosis of Hodgkin lymphoma. Patients with SGF had excellent clinical outcomes with only one of seventeen patients experiencing relapse and relapse-related mortality. The incidence of PGF and SGF in patients receiving NMA conditioning and PTCy is low and is not impacted by HLA disparities between donors and recipients. PGF is more common in recipients with age ≥ 65, a diagnosis of MDS, MPN, or MDS/MPN-overlap, post-transplant HHV-6 viremia, and low CD34+ cell dose. Low total nucleated cell dose is also a risk factor for PGF in patients receiving a bone marrow graft source. Patients who experience PGF have poor outcomes due to high rates of nonrelapse mortality, whereas patients who experience SGF have excellent long-term outcomes.

Safety, efficacy, and affordability of ABVD for Hodgkin lymphoma in Malawi: a prospective cohort study

ABVD (doxorubicin, bleomycin, vinblastine, and dexamethasone) is a proven, curative regimen for Hodgkin lymphoma (HL). Prospective data describing HL treatment in sub-Saharan Africa are limited. We aimed to fill this knowledge gap, using data from Malawi. We report a prospective observational cohort of HL (aged 15) from a single, tertiary referral centre in Malawi. We enrolled patients with pathologicially confirmed Hodgkin lymphoma between June 1, 2013, and Dec 31, 2021 with follow-up censored on May 31, 2022. Patients were treated with ABVD and concurrent antiretroviral therapy if HIV-positive and were followed up for 5 years. The primary outcome was overall survival; secondary outcomes included progression-free survival, response assessment, and adverse events. Microcosting of HL diagnosis, treatment, and follow-up was embedded. We enrolled 38 patients with a median age of 27 years (interquartile range 19-46); eleven (28%) were HIV-positive. Of 35 patients treated with ABVD, 24 (71%) had stage III/IV, nine (26%) unfavourable limited stage, and two (6%) favourable limited stage. Among HIV-infected individuals, mean CD4 count at HL diagnosis was 179cells/uL and ten (91%) had HIV RNA < 400 copies/mL. Grade 3/4 neutropenia occurred in 24 (68%) patients and caused treatment delay in 16 (46%). Of ten deaths, seven were due to HL, two possible treatment-related toxicity, and one uncertain. 2-year overall survival was 82% (95% CI 70-96%) and 2-year progression-free survival was 64% (95% CI 50-83%). PFS appeared better for HIV-positive patients (HR 0.23 (95% CI 0.05-1.02)) after controlling for stage and performance status (p=0.05). We estimated $2708 (2022 USD) for HL diagnosis, treatment, and follow-up in our cohort. Our findings suggest that treatment with ABVD is safe, efficacious, and affordable for HL in Malawi. Outcomes are worse than in high-income countries due to HL progression. Future studies are needed to understand outcome inequities and to assess efficacy of therapies for patients with relapsed or refractory HL in Malawi. National Institutes of Health, Lineberger Comprehensive Cancer Center.

Lymphocyte Level at Diagnosis in Hodgkin lymphoma: Could It be an Indicator of the Stage at Initial Diagnosis?

Background: Despite the existence of standard risk classification systems and effective treatment approaches, 34% to 37% of advanced-stage Hodgkin lymphomas (HLs) either relapse or progress. Our goal in our study was to show the relationship between initial lymphocyte count and stage while examining their effects on prognosis. The initial lymphocyte count, which is proven in advanced-stage patients, could be an important factor in terms of showing the prognosis in the early stage. Materials and Methods: Our study included 190 patients diagnosed with HL in our hospital between January 2010 and September 2020. HL subtypes, diagnosis stages, presence of bulky or mediastinal masses, lymphadenopathy areas, and demographic data of patients, such as age and sex. The aim was to obtain a cutoff in the statistical analysis performed to explore the relationship between lymphocyte level and stage, which is the main hypothesis of the study. Results: Of the 190 patients evaluated, 77 were female (40.5%) and 113 were male (59.5%). To obtain a cutoff in terms of lymphocyte level and stage relationship, a value of 2380/mm3 and below was found to be associated with stage 3-4 disease with a sensitivity of 86.44% and a specificity of 33.3% (AUC: 0.613 (0.539-0.682), p<0.007). Conclusion: This result can be improved in combination with conventional imaging methods used for staging purposes. Further studies may shed light on staging and especially the diagnosis of advanced-stage disease with high sensitivity.

PET-FDG response in alcohol induced chest pain with Hodgkin lymphoma

We present a case of alcohol induced pain in the setting of a mediastinal mass with significant lymphadenopathy. A diagnosis of Hodgkin lymphoma (HL) was made. The alcohol induced pain resolved, correlating with post-chemotherapy treatment response on positron emission tomography/ computed tomography (PET/CT) imaging. The incidences and possible causes of alcohol induced pain are reviewed. The use of PET/CT imaging is discussed in relation to decision making for management of lymphoma.

Трудности диагностики лимфомы Ходжкина у ребенка с бронхиальной астмой

Hodgkin's lymphoma (HL) is a B-cell malignant lymphoproliferative disease. It is characterized by the presence of giant Reed-Berezovsky- Sternberg cells, which can be detected by microscopy of affected lymph nodes. The incidence of HL in the Russian Federation is 2.2 per 100,000 per year, and it ranks 26th among other malignancies worldwide. The disease has two peaks, occurring at the ages of 15–19 years and after 50 years. Men are slightly more commonly affected than women. Young patients with HL are predominantly women, while older patients are predominantly men. The etiology of HL remains unclear. Clinically, the disease is characterized by asymptomatic lymph node enlargement, intoxication, intermittent fever, and, in patients with massive mediastinal involvement, chest pain, cough, dyspnea, and symptoms of superior vena cava syndrome. The article discusses the prevalence, specifics of treatment, and association with allergic diseases, and describes a 13-year-old child with nodular sclerosis classic Hodgkin's lymphoma. KEYWORDS: Hodgkin's lymphoma, nodular sclerosis, allergic disease, asthma, lymphoproliferative disease, differential diagnosis. FOR CITATION: Belykh N.A., Chernenko A.P., Mikhaylova Yu.V., Piznyur I.V. Challenges in the diagnosis of Hodgkin lymphoma in a child with asthma. Russian Medical Inquiry. 2024;8(3):176–182 (in Russ.). DOI: 10.32364/2587-6821-2024-8-3-9.

Epidemiologic Associations Between Inflammatory Bowel Disease and Hodgkin Lymphoma or Multiple Sclerosis

Background and AimsEpidemiologic evidence suggests that Hodgkin lymphoma (HL) and multiple sclerosis (MS) share a common set of risk factors with Crohn’s disease (CD) and ulcerative colitis (UC). It was hypothesized that such shared risk factors would lead to similar geographic distributions of these 4 diagnoses and to their concurrence in identical patients. MethodsAll subjects with HL, MS, CD, or UC were identified in the complete Inpatient Standard Analytic File of the Centers for Medicare and Medicaid Services (CMS) from 2018. In a cross-sectional study, we evaluated whether the frequencies of HL, MS, CD, and UC occurrence among different US states were statistically correlated with each other. In a case-control study, the observed concurrences of each 2 of 4 diagnoses were compared with their expected frequencies in the overall Medicare population by calculating odds ratios (OR) with their 95% confidence intervals (CI). ResultsThe total CMS population comprised 6,462,321 unique patients, of whom 8,027 presented with HL, 42,934 with MS, 40,623 with CD, and 32,521 with UC. Statistically significant positive correlations (r) with p<0.001 were found between HL and MS (r=0.50), HL and CD (0.46), HL and UC (0.68), MS and CD (0.66), MS and UC (0.72), CD and UC (0.68). Any inflammatory bowel disease (IBD) was significantly associated with a diagnosis of concurrent HL (OR: 1.22, 95%CI: 1.01-1.48) or MS (1.35, 1.25-1.46). ConclusionsThe epidemiologic associations of IBD with HL or MS may reflect on a common pathway in the etiology or pathogenesis of these diseases.

Real-World Multicenter Study of PD-1 Blockade in HIV-Associated Hodgkin Lymphoma across the United States

Background: Despite a 5 to 20-fold higher risk of Hodgkin lymphoma (HL) in people with HIV (PWH) than the general population, PWH were excluded from clinical trials that led to the approval of anti-PD-1 agents (PD-1) in HL. PD-1 have overall response rates (ORR) of 65-70% in the general population and are used in all lines of HL therapy. Several prospective and retrospective studies have shown PD-1 are safe in PWH, but they remain underutilized in HIV-associated HL (HIV-HL) where data are limited. Methods: Patients (pts) with HIV-HL were identified from the retrospective, international database, “Cancer Therapy using Checkpoint inhibitors in PWH-International (CATCH-IT)” consortium, that is maintained at the Dana-Farber Cancer Institute (DFCI) and approved by DFCI and local institutional review boards. Pts who received either nivolumab or pembrolizumab, alone or in combination with other agents were included. Records were reviewed for demographics, HL and HIV characteristics, and treatment data. Safety was evaluated by the occurrence of immune-related adverse events (irAEs) per Common Terminology Criteria for Adverse Events (CTCAE) v5.0. Response to treatment was evaluated using descriptive statistics, and immune reconstitution was measured by changes in CD4 + T cell counts (CD4) from prior to end of PD-1 therapy via paired t-tests. ORR was defined as the proportion of pts with partial or complete response (PR/CR) per the 2014 Lugano classification for HL. Duration of response (DOR) was defined as the time from the date of the first CR or PR to the date of progressive disease (PD) or death. Progression-free survival (PFS) was defined as the time from PD-1 initiation to disease progression, death, or censored on the date of the last follow-up. Overall survival (OS) was defined as the time from PD-1 initiation to death or censored at the last follow-up. DOR, PFS, and OS were evaluated by Kaplan-Meier methodology. Results: We identified 23 pts with HIV-HL from 12 institutions in the United States: 20 cisgender men, 3 cisgender women; 10 Black,10 White, and 10 Hispanic; median age 48 years [interquartile range (IQR): 36-58]. At HL diagnosis, 19 (83%) pts had advanced stage disease, and in 20 pts where EBV status of the tumor was known, all were positive. Nine (39%) pts had primary refractory disease. The median number of prior systemic therapies was 2 (IQR: 1-3). One pt had PD-1 as 1 st-line therapy, 6 had PD-1 as 2 nd-line therapy, and 16 had PD-1 as ≥3 rd-line therapy. Fourteen (61%) pts received doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) as 1 st-line therapy. Two pts had prior autologous stem cell transplant (ASCT). At the time of PD-1 initiation, 22 pts (96%) had advanced stage disease, 17 (46%) had extranodal disease, and the median ECOG performance status was 1 (IQR: 0-2). Seventeen (74%) pts received PD-1 monotherapy, 5 (22%) received nivolumab + brentuximab vedotin, and 1 received nivolumab + ifosfamide, carboplatin, and etoposide. Four pts had uncontrolled HIV at the time of PD-1 initiation (HIV viral load range=10,000-2,000,000 copies/mL). All pts received antiretroviral therapy during treatment. Median baseline CD4 was 155 cells/µL (IQR: 66-297) and CD8 was 429 cells/µL (IQR: 158-716). Median CD4 and CD8 increased to 310 and 653 cells/µL at the end of PD-1 treatment (P=0.0084, P=0.32). The median number of PD-1 cycles was 6 (IQR: 4-21). Three (13%) pts had irAEs (all grade 3): hypothyroidism, autoimmune pancreatitis, and pneumonitis. None required PD-1 discontinuation. The ORR was 83% in the overall cohort. Sixteen pts (70%) had CR, 3 (13%) PR, and 4 (17%) PD as best response. Among the 19 pts with CR or PR, the median DOR was 19.7 months; 8 had PD after initial response and 11 had ongoing CR at data cut-off. Ten pts received consolidation with ASCT after PD-1, 6 of whom had received PD-1 at ≥3 rd line treatment. All pts who received ASCT had ongoing CR at data cut-off. Median PFS was 21.2 months in the overall cohort. Among pts with CD4 &amp;lt;200 and &amp;gt;200 cells/µL, PFS was not statistically different (17.3 vs 29 months; P=0.95). At data cut-off, 17 pts (74%) were alive and 6 (26%) had died due to HIV-HL. Median OS was 23.6 months in the overall cohort. Conclusion: In HIV-HL, PD-1 blockade was safe, had a high ORR and CR rate, and allowed for immune reconstitution in pts across a wide range of CD4 counts and HIV viral loads. These data add to the evidence that anti-PD-1 agents are effective in PWH and should be used in HIV-HL.

Long-Term Cause-Specific Mortality in Hodgkin Lymphoma Patients - a Nationwide Danish Cohort Study

Introduction: The documented treatment-induced excess mortality in Hodgkin lymphoma (HL) has led to significant changes in treatment regimens aimed at maintaining efficacy while reducing toxicity. These modifications include the replacement of alkylator-based regimens with anthracycline-based combinations and the adoption of highly conformal radiotherapy. Danish and Nordic radiation oncologists were pioneers in implementing these changes nationwide 10-15 years earlier than most other nations. These early adaptations make Danish HL data uniquely valuable for assessing long-term mortality in a cohort where modern treatment regimens have been implemented nationwide throughout the entire study period. The impact of these treatment modifications on mortality risk in HL survivors remains unclear, therefore, this study aims to assess cause-specific mortality among HL patients treated with contemporary strategies. Methods: This nationwide, unselected study included all HL patients in Denmark aged 15-40 years at diagnosis and treated between 1995 and 2015. Patients were followed from diagnosis until emigration, death, or the study end. HL cases were identified through meticulous individual record reviews of medical records, national registries, and pathology data. Disease-specific death due to HL was the primary outcome, with other cause-specific mortality as a competing risk. Cox proportional hazard models assessed factors influencing overall survival and cause-specific survival. A landmark analysis was conducted to compare the risk of death between the study population and the national background population. Results: Among 1,348 included HL patients, 66.5% had Ann Arbor stage I-II at the time of diagnosis. During 18,731 person-years of follow-up, 139 deaths occurred, resulting in a 5-year overall survival rate of 94.6% (95% CI 93.4-95.8). Factors associated with higher overall mortality risk included older age, advanced disease stage at diagnosis, earlier treatment periods, and exposure to intensive treatment regimens. Causes of death included: HL (71 cases), cardiovascular disease (9 cases), second malignancies (19 cases including 3 hematologic malignancies), bone-marrow transplant-related complications (9 cases), acute treatment-related toxicity (&amp;lt;5 cases), pulmonary diseases (&amp;lt;5 cases), other diseases not related to HL (11 cases), and deaths related to accidents, poisoning or suicide (7 cases). The cumulative risk of mortality due to HL steeply increased over the first 10 years, reaching a plateau at 5.3% at the 10-year mark. Cumulative risk of death due to cardiovascular or pulmonary disease and second cancers had a gradual increase around 10 years after HL diagnosis, but only reached 1.2% and 2.0%, respectively, at the 20-year mark. The cumulative risk of death due to other causes had a slower rise, reaching 2.5% 15 years after diagnosis. Stratifying the cumulative cause-specific risk of death into HL and other causes, we found an initial sharp increase in cumulative risk of death due to HL in the first year after diagnosis, which was surpassed by the risk of death from other causes by 17.8 years of follow-up, with a cumulative risk of death of 5.72%. HL cases had a 7.5-fold higher hazard of mortality compared to the background population. Conclusion: Despite the implementation of contemporary treatment regimes, HL patients still face higher mortality compared to the general population. In the initial years after diagnosis, most deaths are disease-specific, while the risk of mortality due to possible treatment-related late effects gradually increases after 10 years. However, our findings demonstrate a markedly lower overall risk of mortality and cause-specific mortality among HL patients exposed to contemporary treatment, compared to the risk reported in earlier studies among patients from earlier treatment eras (Aleman, B. et al. Long-term cause-specific mortality of patients treated for Hodgkin's disease. J Clin Oncol21 2003, 3431-3439). Furthermore, we observe a remarkably low overall and cause-specific risk of death due to possible treatment-related late effects. The treatment of HL remains a balance between efficacy and toxicity in the individual patient, but our results suggest that recent changes in treatment strategies have led to a distinct reduction in the risk of fatal long-term toxicity and have improved HL-specific survival.

Fertility and Gonadal Function after First-Line Treatment with Nivolumab-AVD in Hodgkin Lymphoma Patients: An Analysis from the Phase II GHSG Nivahl Trial

Background: First-line treatment of patients with classical Hodgkin lymphoma (HL) with anti-PD1 antibodies in combination with AVD chemotherapy is highly effective across risk-groups. Based on encouraging phase II and ongoing phase III trials, anti-PD1 based first-line treatment may hence soon become a first-line treatment option. To date, no data on fertility and gonadal function after anti-PD1 based first-line HL treatment is available. Herein, we present data on pregnancies and gonadal function in patients treated within the randomized GHSG phase II NIVAHL trial. Methods: NIVAHL enrolled 109 patients aged 18-60 years with first diagnosis of early-stage unfavorable HL to receive either fully concomitant (4xN-AVD; group A) or sequential (4xN, 2xN-AVD, 2xAVD; group B) nivolumab-based 1st-line treatment, each followed by 30Gy involved-site radiotherapy (IS-RT). The primary and final analyses showed excellent efficacy and an acceptable safety profile after 1- and 3-years of follow up; details were previously published (Bröckelmann et al. JAMA Oncol 2020 &amp; JCO 2023). Data on pregnancies and births as well as sexual hormones prior, during and after treatment were collected via standardized case report forms. The cohort for this descriptive analysis included women &amp;lt;40 and men &amp;lt;50 years of age. Results: A total of 87 patients (55% female, 51% treatment group A) with a median age of 25 (range 18-49) were eligible for this analysis. Patient characteristics were well balanced between treatment groups and patients presented predominantly with stage IIA disease (75.3%) and presence of the risk factors ≥3 nodal areas (75%), elevated ESR (44%) and bulky mediastinal disease (20.2%). Cryopreservation prior start of treatment was performed in 39.6% of female and 74.4% of male patients. With a median follow-up (FU) of 41 months, a total of 11 pregnancies were documented (12.6%; 9 in female patients, 2 in partners of male patients). These resulted in 8 documented live births (2 abortions, 1 missing info), with none using assisted reproductive techniques. In female patients, median hormone levels remained relatively stable from baseline to 12-24 months of FU for FSH (4.7 -&amp;gt; 4.3 U/l), LH (6 -&amp;gt; 7.2 U/l) and AMH (2.3 -&amp;gt; 2.8 ug/l) while an increase of estradiol was observed (53.6 -&amp;gt; 102 ng/l). Similar trajectories of largely stable hormone levels were observed when stratifying female patients by age groups (i.e. 18-29 and 30-39 years). Women ≥30 years presented higher median FSH (6.1 vs 4.7 U/l) and lower estradiol values (48.8 vs 53.6 ng/l) compared to younger women at baseline, however, presented with similar median FSH levels at 12-24 months of FU (4.2 and 4.4 U/l, respectively). In male patients, hormone levels also remained stable from baseline to 12-24 months of FU for FSH (4.2 -&amp;gt; 4.2 U/l), LH (4.1 -&amp;gt; 3.9 U/l), testosterone (4 -&amp;gt; 5.6 ug/l) and inhibin B (159.4 -&amp;gt; 180 ng/l). More detailed analyses regarding hormonal trajectories of individual patients and stratifications by treatment group are ongoing and will be presented at the meeting. Conclusion: This analysis of pregnancies, births and sex hormones after first-line HL treatment with N-AVD indicates preserved gonadal function in the majority of both female and male patients.

Quality of Life with Nivolumab and AVD First-Line Treatment in Hodgkin Lymphoma: Patient-Reported Outcomes from the Phase II GHSG Nivahl Trial

Background: First-line treatment of patients with classical Hodgkin lymphoma (HL) with anti-PD1 antibodies in combination with AVD chemotherapy is highly effective across risk-groups. Based on encouraging phase II and ongoing phase III trials, anti-PD1 based first-line treatment may hence soon become a first-line treatment option. To date, no patient-reported outcome (PRO) data is available in this setting, which is crucial to comprehensively evaluate relative benefits of these novel treatment approaches. Herein, we present the preplanned PRO analysis of quality of life (QoL), fatigue and life situation of HL patients treated within the randomized GHSG phase II NIVAHL trial. Methods: NIVAHL enrolled 109 patients aged 18-60 years with first diagnosis of early-stage unfavorable HL to receive either fully concomitant (4xN-AVD; group A) or sequential (4xN, 2xN-AVD, 2xAVD; group B) nivolumab-based 1st-line treatment, each followed by 30Gy involved-site radiotherapy (IS-RT). The primary and final analyses showed excellent efficacy and an acceptable safety profile after 1- and 3-years of follow up; details were previously published (Bröckelmann et al. JAMA Oncol 2020 &amp; JCO 2023). Patients providing separate informed consent reported QoL and Fatigue by the EORTC QLQC30 questionnaire in addition to key sociodemographic data including employment status at baseline and after systemic treatment, radiotherapy and 1- and 3-years of follow-up (FU), respectively. Data were analyzed descriptively and time-to-recovery (TTR) calculated for resolution of fatigue (TTR-F, event defined as first documentation of a fatigue score &amp;lt;30 after end-of-treatment (EOT)) and return to work (TTR-W, event defined as first documentation of employment after EOT). Results: A total of 99 patients provided a median of 4 questionnaires per patient (range 1-11), with the vast majority (85%) providing baseline and at least one questionnaire during FU. Mean fatigue score was 22 points higher (95% confidence interval, CI 16.1-27.9) than the age- and sex-matched German reference population at baseline, worsened during treatment (+38.2, 95%CI 31.4-44.9) but improved over the course of FU (1-year +10.2, 95%CI 3.7-16.6) to normal values at 3-year FU (-3.4, 95%CI -10.7 to 3.9), without any differences between treatment groups. Similar trajectories were observed for global health status/QoL as well as the different functional and symptom scales. While improvement beyond baseline (79.6, 95%CI 76.5-82.7) was observed, global health status/QoL did not improve to age- and sex-matched reference values at 1- (87.2, 95%CI 83.2-91.2) and 3-year FU (92, 95%CI 87.8-96.2). Multiple regression analysis showed a significant effect of baseline score (ß 0.28-0.56) and age (ß 0.23-0.34) but not sex (p&amp;gt;0.2 each) on cognitive, emotional and social functional scales as well as fatigue at 1-year of FU. At 3-years of FU the effect of age remained significant (ß 0.48-0.66) for all functional or symptom scales except resolution of dyspnea, while baseline scores had no significant effect. More detailed analysis of the different QLQ-C30 scales is ongoing and will be presented at the meeting. Median TTR-F and TTR-W were 12.8 (95%CI 7.3-20.3) and 3.8 months (95%CI 1.4-8.0) after EOT, respectively. Cox regression analysis for TTR-F showed significant effect of baseline fatigue (HR 0.99, p=0.03) but not sex (HR 1.71, p=0.09) or age (HR 0.98, p=0.14). For TTR-W, Cox regression did not show significant effects of baseline fatigue (HR 1, p=0.93) or age (HR 0.99, p=0.69) but a trend for faster return to work in male patients (HR 1.82, p=0.06). Conclusion: This first ever analysis of PROs after anti-PD1 based first-line HL treatment with N-AVD indicates substantial improvement of functional and symptom scales as well as global health status/QoL at last FU compared to baseline. Baseline status and age have a significant effect for improvement of functioning and symptoms at 1-year of FU. Importantly, while substantial fatigue is present at baseline, relevant improvement with resolution to age- and sex-matched reference values is observed and recovery is influenced by baseline fatigue score.

The role of radiotherapy in patients with refractory Hodgkin's lymphoma after treatment with brentuximab vedotin and/or immune checkpoint inhibitors

BackgroundApproximately 10%–30% of patients with Hodgkin's lymphoma (HL) experience relapse or refractory (R/R) disease after first-line standard therapy. Brentuximab vedotin (BV) and immune checkpoint inhibitors (ICIs) have important roles in the salvage treatment of R/R HL. However, subsequent treatment for HL refractory to BV and/or ICI treatment is challenging. MethodsWe retrospectively analyzed patients in two institutions who had R/R HL, experienced BV or ICI treatment failure, and received radiotherapy (RT) thereafter. The overall response rate (ORR), duration of response (DOR), progression-free survival (PFS), and overall survival (OS) were analyzed. ResultsOverall, 19 patients were enrolled. First-line systemic therapy comprised doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD, 84.2%); AVD plus ICIs (10.5%); and bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP, 5.3%). After first-line therapy, 15 (78.9%) and four patients (21.1%) had refractory disease and relapsed, respectively. After R/R HL diagnosis, six (31.6%), two (10.5%), and 11 (57.9%) patients received BV and ICIs concurrently, BV monotherapy, and ICI monotherapy, respectively. All patients received intensity-modulated RT (n = 12, 63.2%) or volumetric modulated arc therapy (VMAT; n = 7, 36.8%). The ORR as well as the complete response (CR) rate was 100%; the median DOR to RT was 17.2 months (range, 7.9–46.7 months). Two patients showed progression outside the radiation field; one patient had extensive in-field, out-of-field, nodal, and extranodal relapse. With a median follow-up time of 16.2 months (range, 9.2–23.2 months), the 1-year PFS and OS were 84.4% and 100%, respectively. PFS was associated with extranodal involvement (P = 0.019) and gross tumor volume (P = 0.044). All patients tolerated RT well without adverse events of grade ≥ 3. ConclusionRT is effective and safe for treating HL refractory to BV or ICIs and has the potential to be part of a comprehensive strategy for HL.

Relation between coronary artery calcium score and cardiovascular events in Hodgkin lymphoma survivors: a cross-sectional matched cohort study

Abstract Introduction Long-term survival after Hodgkin lymphoma (HL) has improved significantly over the past years, due to enhanced treatment options. Thoracic radiotherapy is still one of the corner stones of HL treatment, but is associated with increased risk of cardiovascular events. As HL is often diagnosed at young age, long-term follow-up including screening for coronary artery disease (CAD) is recommended. Purpose This study aims to evaluate the presence and distribution of coronary artery calcium in relation to cardiovascular events in HL patients treated with thoracic radiotherapy compared to a non-cancer control group. Methods Consecutive HL patients treated with thoracic radiotherapy, who underwent evaluation for asymptomatic CAD with coronary computed tomography angiography (CCTA) &amp;gt; 10 years after irradiation between 2002 and 2022 were included. HL patients were matched 1:1 to non-cancer patients on gender, age, cardiovascular risk factors and statin use. Differences in coronary artery calcium score (CACS), stenosis severity and cardiovascular events between the two groups were compared. Results The total study population consisted of 194 patients of whom 97 patients had a prior HL diagnosis and 97 patients had no history of cancer. Elevated CACS was seen in 50.5% of the HL patients (N=49) and 30.9% of the control patients (N=30). HL survivors had an odds ratio of 2.28 [95% CI: 1.22 – 4.28] for having a CACS &amp;gt; 0 compared to the matched non-cancer population (p=0.006). Distribution pattern of coronary calcium differed significantly with the prevalence of a CACS above the 90th percentile (17.5% in HL survivors versus 4.7% in the matched population, p=0.005). Also coronary artery stenosis was more prevalent in the HL population than in the control population (39.2% versus 15.5% respectively, p=&amp;lt;0.001). Nine HL patients experienced an event during the follow-up period including two patients with a CACS of zero. No events were observed in the control population. Conclusion This study shows that in a matched study population, HL survivors have a higher prevalence of a CACS &amp;gt; 0 and an increased risk of cardiovascular events after thoracic irradiation compared to a matched non-cancer control group.Distribution of CACS percentiles

Risk of Therapy-Related Acute Myeloid Leukemia (t-AML) in Adolescent and Young Adults Cancer Patients Treated with Chemotherapy with or without Radiotherapy: A National Population-Based Cohort Study Using SEER Registry

INTRODUCTION The risk of treatment-related acute myeloid leukemia (t-AML) in adolescents and young adults (AYA) with first cancers treated with chemotherapy with or without radiation is not well characterized. We analyzed Surveillance, Epidemiology and End Result (SEER) data for the past 45-years (1975-2020) to identify the overall risk of t-AML in treated AYA cancer patients (pts) and by index cancer sites as well as latency periods. METHOD We analyzed NCI's SEER-8 registries. ICD-O-3/WHO-2008 codes were used to identify pts with index cancer types between the ages of 15-39 years (AYA), treated with either chemotherapy or radiotherapy, and with a subsequent diagnosis of acute myeloid leukemia (AML) at least one year after index cancer, between January 1975 and December 2020. The risk of t-AML was estimated by standardized incidence ratio (SIR), defined as the ratio of observed t-AML-cases in the AYA-with-cancer, to the expected number of AML-cases in the matched general US population. A reference rate file for AML incidence in age, gender, race and calendar-year matched US population is available in SEERStat software. A Poisson distribution of observed t-AML was assumed for the calculation of 95% confidence intervals (CIs). A P-value &amp;lt;.05 was considered statistically significant. We stratified the risk of t-AML for index cancer types with ten or more pts, by attained-calendar-years, and latency at multiple time intervals (Table-1) from index cancer diagnosis. RESULT Among 102,879 AYA cancer pts eligible for analysis, 236 pts developed t-AML with SIR of 6.19 (95%CI: 5.43-7.04, P &amp;lt;.05) with excess risk of 1.46 per-10000 person-years (pyrs). (Table-1). We stratified risk for index cancer types with at least ten patients developing t-AML, these included breast, Hodgkin lymphoma (HL), non-Hodgkin lymphoma (NHL), testicular, thyroid, bone and joint, and soft tissue including heart. As a general trend, risk of t-AML was highest during 1-3 years after index cancer diagnosis compared to subsequent latency periods. However, risk for t-AML was significantly greater than the matched-general US population even after 20-40 years of breast cancer, HL, and NHL (Table-1). When stratified by attained calendar-year periods (1975-1985, 1986-1995, 1996-2005, 2006-2015, 2016-2020), risk for t-AML was higher than general population in all time periods. However, overall SIR was comparatively lower for recent time periods, particularly lowest during 2016-2020 [SIR: 3.49 (2.51-4.72, P &amp;lt;.05)]. Notably, the highest risk for t-AML in 2016-2020 was observed with index cancer of soft tissue including heart [SIR: 10.12 (1.23-36.57), P &amp;lt;.05]. CONCLUSION In this study spanning between 1975-2020, we observed the risk of t-AML trending down among AYA in recent years, albeit higher than the age matched general population. The risk of t-AML remained significantly elevated even after 20-40 from diagnosis of breast cancer, HL and NHL. Since these pts likely received radiation and older (higher intensity) chemotherapy based-regimens, it is essential to analyze the long-term impact of newer therapies for these cancers and assess the risk of t-AML in future studies.

CD20low/CD68high a Promising Microenvironnement Profile Identifying Classical Hodgkin Lymphoma Patients with Poor Outcome a Lysa Study

Introduction Although progression free survival and overall survival of patients with Hodgkin lymphoma (HL) has improved in the past 10 years, 15 % of patients will fail to conventional therapy and die of their lymphoma. The search of new prognostic factors for identifying these high risk patients at diagnosis of HL remains challenging in PET-guided strategies developed to improve the outcome HL patients while reducing treatment toxicity The aim of this study was therefore to assess the impact of baseline tumor microenvironnement in a large cohort of HL patients prospectively treated with upfront escalated BEACOPP in a randomized phase III clinical trial evaluating a PET-driven strategy (AHL 2011, NCT01358747) and to compare its prognostic value with other clinicopathological markers. Material and Methods Tumoral material was collected from HL patients prospectively enrolled in the AHL2011 study from LYSA centers in France and Belgium. The AHL2011 study was designed to evaluate in 16-60y HL patients with Ann Arbor stage III, IV or high risk IIB, a de-escalade PET-driven strategy after 2 cycles of BEACOPPesc (PET2) randomly compared to a standard treatment not driven by PET delivering 6 cycles of BEACOPPesc. The AHL2011 strategy was shown to safely guide treatment of advanced HL patients allowing using ABVD in early responders to BEACOPPesc (PET2 negative) reducing toxicities without impairing disease control (Casasnovas et al, Lancet Oncol 2019, JCO 2022). The tumor microenvironnement (TME) was analyzed on formalin fixed paraffin embedded diagnostic tissue biopsy obtained before treatment by morphological evaluation on standard staining on whole slides (% polynuclear eosinophils, % lymphocytes, % plasmocytes, % histiocytes), and immunohistochemistry (IHC) scoring (score 0-1-2-3) for CD20, CD3, CD4, CD8, CD68-TAMs (tumor-associated macrophages), CD163 (n=680) and EBERS (n= 634). Additional staining were done on Tissue microarray (TMA n=409) for PD-1, PD-L1, TIM3, GATA3, CD45R0, TBET and were centrally reviewed. Computational analysis was used for the TMA analysis using Tissu Studio software (Definiens). For each marker, a H-score was calculated (stained cells x 1, 2 or 3 according to the intensity of staining divided by the total number of cells x100) Results 680 patients were included on the whole slides analyses and 409 for those on the TMA analyses. Patients included had similar characteristics to the remaining patients of AHL2011 not included here. Among all the microenvironnement biomarkers tested only CD20 and CD68 had prognosis value. In univariate analysis, high CD20 H-score was associated with a favorable PFS (HR=0.43, 95%CI 0.22-0.86), while patients having high CD68 H-score had unfavorable PFS (HR=2.29, 95%CI 1.29-4.05). Then, the patients with a combined CD20 low/CD68high TME (n= 239, 47%) had a significant lower PFS compared to other groups (HR=2.46, 95%CI 1.48-4.09; p=0.004) (figure 1). In multivariate analysis including all relevant variables (Bulky disease / IPS / TMTV (total metabolic volume) / PET2 /PET4 / combination CD20 CD68 / % of tumor cells /EBV status / B symptoms), only High TMTV &amp;gt;220ml (HR = 2.09, p =0.017), PET4 positivity (HR= 7.06 ; p &amp;lt; 0.0001) and the CD20 low/CD68high profile (HR=1.95, p=0.025) had an independant prognosis value on PFS. Patients harboring both a TME depleted in CD20 and enriched in CD68, had peculiarities. Indeed, they had significantly more B symptoms (78.2% vs 64.2%, p&amp;lt;0.001), higher median TMTV (270 vs 163ml, p&amp;lt;0.001), were more frequently EBERs positive (23.6 vs 12.7%, p=0.002), had more frequently lymphopenia (38.5 vs 18.2%, p&amp;lt;0.001) and high IPS (69.2 vs 53%, p&amp;lt;0.001). Finally, patients with a CD20low/CD68high profile, had a higher median tumor cells PD-L1 H-score compared to other patients (39.7 vs 7.4, p&amp;lt;0.001). Conclusion Altogether these results demonstrate in a large PET-guided phase III trial (AHL2011), the interest of analyzing CD20 and CD68 expressions within the tumor microenvironnement to better evaluate the risk of treatment failure prior to therapy in patients with advanced HL. The prognosis value of the CD20/CD68 profile is independant of those of the baseline PET metrics (TMTV), and the early reponse to treatment. The enrichment of highly positive PD-L1 tumor cells in patients with CD20 low/CD68high TME suggests that PD-1 blockers could be a good therapeutic option in frontline treatment of this poor prognosis group.

Hodgkin lenfoma hastalarında maksimum tümör çapı ve 18F-FDG PET/BT görüntüleme durumunun genel sağkalıma etkisi

Aims: This research aims to determine the impact of maximum tumor diameter and FDG PET CT status at the time of diagnosis on survival outcomes and to identify prognostic factors that influence treatment response and survival. &#x0D; Methods: 239 patients with a diagnosis of Hodgkin lymphoma participated in the study. Clinical characteristics, treatment responses, and prognostic factors influencing survival were retrospectively analyzed from patient medical records.&#x0D; Results: There were 136 (56.9%) male patients and 103 (43.1%) female patients, who participated in the study. Of these patients, 202 (84.5%) survived, while 37 (15.5%) died during the study period. When surviving patients and non-survivor patients were compared, the deceased patients had a higher mean age (p = 0.003), a higher prevalence of spleen involvement and B symptoms (p = 0.011 and p = 0.001, respectively), lower albumin levels (p = 0.008), higher beta-2 microglobulin levels (p = 0.001), and more bone marrow involvement (p = 0.006). A fourfold increase in mortality was seen in patients with beta-2 microglobulin levels &gt; 2920 mg/L, and a 3.188-fold increase in mortality was seen in patients with spleen involvement.&#x0D; Conclusion: In conclusion, beta-2 microglobulin &gt; 2920 mg/L, the presence of spleen involvement, the presence of relapse, and the presence of progressive or refractory disease in FDG PET CT were significant prognostic factors for 1st, 3rd, and 5th-year survival rates in patients with Hodgkin lymphoma. In addition, there was no correlation between survival rate and maximum tumor diameter as measured by FDG-PET or CT.

Concurrence of inflammatory bowel disease with multiple sclerosis or Hodgkin lymphoma.

Epidemiologic evidence suggests that Hodgkin lymphoma (HL) and multiple sclerosis (MS) share a common set of risk factors with Crohn's disease (CD) and ulcerative colitis (UC). It was hypothesized that such shared risk factors would lead to clustering of the 4 diagnoses in the same patients. All patients with HL, MS, CD, or UC were identified in the veterans population from 2016-2020 and the Medicare population from 1986 to 1989. In a case-control study, the observed concurrences amongst these 4 diagnoses were compared with their expected frequencies in the overall veterans or Medicare population during the same time period by calculating odds ratios (OR) with their 95% confidence intervals (CI). The study included 6 million veterans and 35 million Medicare patients. In the veterans population, inflammatory bowel disease (IBD) was significantly associated with a concurrent diagnosis of HL (OR: 1.40, 95% CI: 1.15-1.71) and MS (1.34, 1.19-1.50). In the Medicare population, IBD was also significantly associated with HL (1.84, 1.07-3.17) and MS (2.31, 1.59-3.35). Similar trends were observed in CD or UC when analyzed separately in both datasets. In the veterans population, adjustment for the potentially confounding influence of ethnicity, sex, and age left all OR values largely unaffected and statistically significant. The concurrence of IBD with HL or MS could reflect on a common pathway in the etiology or pathogenesis of these 4 diseases.

Elevated serum TARC levels precede classic Hodgkin lymphoma diagnosis by several years

AbstractTumor cells in classic Hodgkin lymphoma produce high quantities of the thymus- and activation-related chemokine (TARC). We measured TARC levels in prediagnostic serum samples and found strikingly increased values in the vast majority of patients, as early as 6 years before diagnosis.