Hodgkin's Disease Research Articles

Automatic detection and segmentation of lesions in 18 F-FDG PET/CT imaging of patients with Hodgkin lymphoma using 3D dense U-Net.

The accuracy of automatic tumor segmentation in PET/computed tomography (PET/CT) images is crucial for the effective treatment and monitoring of Hodgkin lymphoma. This study aims to address the challenges faced by certain segmentation algorithms in accurately differentiating lymphoma from normal organ uptakes due to PET image resolution and tumor heterogeneity. Variants of the encoder-decoder architectures are state-of-the-art models for image segmentation. Among these kinds of architectures, U-Net is one of the most famous and predominant for medical image segmentation. In this study, we propose a fully automatic approach for Hodgkin lymphoma segmentation that combines U-Net and DenseNet architectures to reduce network loss for very small lesions, which is trained using the Tversky loss function. The hypothesis is that the fusion of these two deep learning models can improve the accuracy and robustness of Hodgkin lymphoma segmentation. A dataset with 141 samples was used to train our proposed network. Also, to test and evaluate the proposed network, we allocated two separate datasets of 20 samples. We achieved 0.759 as the mean Dice similarity coefficient with a median value of 0.767, and interquartile range (0.647-0.837). A good agreement was observed between the ground truth of test images against the predicted volume with precision and recall scores of 0.798 and 0.763, respectively. This study demonstrates that the integration of U-Net and DenseNet architectures, along with the Tversky loss function, can significantly enhance the accuracy of Hodgkin lymphoma segmentation in PET/CT images compared to similar studies.

Causal relationship between beta-2 microglobulin and B-cell malignancies: genome-wide meta-analysis and a bidirectional two-sample Mendelian randomization study.

Beta-2 microglobulin (β2M) is acknowledged as a prognostic biomarker for B-cell malignancies. However, insights into the impact of β2M on B-cell malignancy risk, and vice versa, are limited. We conducted a genome-wide meta-analysis (GWMA), bidirectional two-sample Mendelian randomization (TSMR) analysis, and pathway enrichment analysis to explore the causal relationship between β2M and B-cell malignancies and the underlying biological processes. The GWMA identified 55 lead SNPs across five genomic regions (three novel: WDR72, UMOD, and NLRC5) associated with β2M. In the UKB, genetically predicted β2M showed a positive association with diffuse large B-cell lymphoma (DLBCL; odds ratio [OR]: 1.742 per standard deviation increase in β2M; 95% confidence interval [CI]: 1.215-2.498; P = 3.00 × 10-3; FDR = 7.50× 10-3) and Hodgkin lymphoma (HL; OR: 2.270; 95% CI: 1.525-3.380; P = 5.15 × 10-5; FDR =2.58 × 10-4). However, no associations were found with follicular lymphoma (FL), chronic lymphoid leukemia (CLL), or multiple myeloma (MM). Reverse TSMR analysis revealed no association between genetically predicted B-cell malignancies and β2M. In FinnGen, β2M was found to be associated with an increased risk of DLBCL (OR: 2.098; 95% CI: 1.358-3.242; P = 8.28 × 10-4; FDR = 4.14 × 10-3), HL (OR: 1.581; 95% CI: 1.167-2.142; P = 3.13 × 10-3; FDR = 5.22 × 10-3), and FL (OR: 2.113; 95% CI: 1.292-3.455; P = 2.90 × 10-3; FDR = 5.22 × 10-3). However, no association was found with CLL or MM. Reverse TSMR analysis indicated that genetically predicted DLBCL, FL, and MM may perturb β2M levels. Pathway enrichment analysis suggested that the innate immune system represents a convergent biological process underlying β2M, DLBCL, and HL. Our findings suggested that elevated levels of β2M were associated with an increased risk of DLBCL and HL, which is potentially linked to dysfunction of the innate immune system.

Non-cryopreserved autologous peripheral blood stem cell transplantation for multiple myeloma and lymphoma in countries with limited resources: practice considerations from the Worldwide Network for Blood and Marrow Transplantation.

Autologous peripheral blood stem cell (PBSC) transplantation is a standard treatment of multiple myeloma (MM), Hodgkin lymphoma and various subtypes of non-Hodgkin lymphoma. Cryopreservation of hematopoietic stem cells is standard practice that allows time for delivery of conditioning regimen prior to cell infusion. The aim of this Worldwide Network for Blood & Marrow Transplantation (WBMT) work was to assess existing evidence on non-cryopreserved autologous transplants through a systematic review/meta-analysis, to study feasibility and safety of this approach. We searched PubMed, Web of Science and SCOPUS for studies that utilized non-cryopreserved autologous PBSC transplantation. Identified literature was reviewed for information on mobilization, apheresis, preservation and viability, conditioning regimen, engraftment, response, and survival. Results highlight collective experience from 19 transplant centers (1686 patients), that performed autologous transplants using non-cryopreserved PBSCs. The mean of infused CD34+ was 5.6 × 106/kg. Stem cell viability at transplantation was >90% in MM and >75% in lymphomas, after a storage time of 24-144 h at +4 °C. Mean time-to-neutrophil engraftment was 12 days and 15.3 days for platelets. Pooled proportion estimates of day 100 transplant-related mortality and graft failure were 1% and 0%, respectively. Non-cryopreservation of apheresed autologous PBSCs appears feasible and safe.

Maternal and obstetric outcomes in women with pregnancy-associated haematological malignancies: an observational nationwide cohort study

Pregnancy-associated haematological malignancy is a rare event; therefore, data available to guide the treatment are scarce. We aimed to evaluate the incidence, overall survival, and maternal morbidity and mortality of women with pregnancy-associated haematological malignancies. We conducted a nationwide observational cohort study using the French National Healthcare Data System (SNDS), a health-care administrative database covering up to 99% of the French population. We included all pregnancies in France ending between Jan 1, 2012, and Dec 31, 2022. Pregnancies with terminations or miscarriages managed on an outpatient basis, and women with a history of haematological malignancies before pregnancy were excluded. A Cox proportional hazards model was used to assess overall survival, defined as the date of haematological malignancy diagnosis to either death or the end of the study follow-up, in the haematological malignancy during pregnancy group (pregnancies with a diagnosis of haematological malignancy during pregnancy) compared with the haematological malignancy post-pregnancy group (pregnancies with a diagnosis of haematological malignancy in the year following pregnancy). Severe maternal morbidity was compared in the haematological malignancy during pregnancy group versus the reference group (pregnancies without a history of haematological malignancy or a diagnosis of pregnancy-associated haematological malignancy). Births were classified as very preterm (<32 weeks of pregnancy), preterm (32-36 weeks), and term (≥37 weeks) and compared in the haematological malignancy during pregnancy group versus the reference group. Inverse probability weighting (IPW) was used for confounder adjustment, using maternal age (categorised), comorbidities, socioeconomic status, and year of delivery (as a category). Of 9 996 523 pregnancies in 5 995 235 women, 1366 pregnancy-associated haematological malignancies were identified: 413 during pregnancy (4·13 per 100 000 pregnancies) and 953 (9·53 per 100 000 pregnancies) within 12 months of the end of pregnancy (post-pregnancy). No significant differences in overall survival were observed between the haematological malignancy during and post-pregnancy groups across all types of haematological malignancy (IPW-adjusted hazard ratio 0·91 [95% CI 0·62-1·34], p=0·63), specifically for Hodgkin lymphoma (0·56 [0·07-4·53], p=0·59), aggressive B-cell non-Hodgkin lymphoma (0·52 [0·12-2·38], p=0·40), and acute leukaemia alone (0·84 [0·50-1·41], p=0·51). Severe maternal morbidity was more frequent in the haematological malignancy during pregnancy group than in the reference group (86 [26·2%] of 328 completed pregnancies vs 120 335 [1·5%] of 7 945 909 completed pregnancies; IPW-adjusted odds ratio 22·71 [95% CI 17·72-29·10], p<0·0001). We observed an increase in very preterm birth (32 [9·8%] vs 92 712 [1·2%]; IPW-adjusted odds ratio 11·90 [95% CI 7·91-17·91], p<0·0001) and preterm birth (116 [35·4%] vs 430 472 [5·4%]; 11·76 [9·34-14·81], p<0·0001) in the haematological malignancy during pregnancy group compared with the reference group. This nationwide observational study examines pregnancy-associated haematological malignancies in France, revealing no significant difference in overall survival between women diagnosed during pregnancy and post-pregnancy. Our data highlight an increased frequency of severe maternal morbidity and obstetric complications among women diagnosed during pregnancy. Notably, the study underscores the necessity for specialised care to manage these complex cases effectively. None. For the French translation of the abstract see Supplementary Materials section.

Long-term cause-specific mortality in adolescent and young adult Hodgkin lymphoma patients treated with contemporary regimens-A nationwide Danish cohort study.

The documented treatment-induced excess mortality in Hodgkin lymphoma (HL) has spurred important treatment changes over recent decades. This study aimed to examine mortality among young HL patients treated with contemporary strategies, including historical data comparison. This nationwide study included 1348 HL patients, diagnosed in 1995-2015 and aged 15-40 at diagnosis. Among the patients, 66.5% had Ann Arbor stage I-II and 33.5% had stage III-IV disease. With a median follow-up of 14.76 years, 139 deaths occurred, yielding a 5-year overall survival of 94.6%. Older age, advanced disease, earlier treatment periods and extensive regimens were associated with higher overall mortality risk. The cumulative risk of HL-related death showed an initial sharp rise, with a plateau at 5.3% 10-year post-diagnosis. Deaths due to cardiovascular or pulmonary diseases and second cancers initially had minimal risk, gradually reaching 1.2% and 2.0% at the 20-year mark respectively. HL cases had a 7.5-fold higher mortality hazard than the background population. This study suggests that contemporary HL treatment still poses excess mortality risk, but recent changes have notably reduced overall and cause-specific mortality compared to earlier eras. Balancing treatment efficacy and toxicity remains crucial, but our findings highlight improved outcomes with modern treatment approaches.

Longitudinal Health-Related Quality of Life Among Patients With High-Risk Pediatric Hodgkin Lymphoma Treated on the Children's Oncology Group AHOD 1331 Study.

PURPOSEThere have been no previous longitudinal assessments of health-related quality of life (HRQoL) during treatment for pediatric Hodgkin lymphoma (HL). The addition of brentuximab vedotin (BV) to a multidrug chemotherapy backbone demonstrated superior efficacy to standard chemotherapy for patients with pediatric high-risk HL in the AHOD 1331 trial. However, the impact on HRQoL is unknown.PATIENTS AND METHODSAfter treatment random assignment, 268 participants older than 11 years were enrolled in a prespecified, longitudinal, patient-reported outcomes substudy. HRQoL was assessed using the seven-item Child Health Ratings Inventories (CHRIs)-Global scale before treatment (T1) and at cycle 2 (T2), cycle 5 (T3), and end of treatment (T4). A clinically meaningful increase in HRQoL was considered 7 points on the CHRIs-Global. Multivariable linear regression estimated associations between demographic/clinical variables and HRQoL at T1. Linear mixed models estimated changes in HRQoL across the treatment arm.RESULTSParticipant characteristics were balanced by treatment arm. Ninety-three percent of participants completed the CHRIs at T1, 92% at T2, 89% at T3, and 77% at T4. At T1, female sex and fever (P < .05) were each associated with worse HRQoL. By T2, participants in the BV arm experienced a statistically and clinically significant improvement in HRQoL (β = 7.3 [95% CI, 3.2 to 11.4]; P ≤ .001), which was greater than the change in the standard arm (difference in change β = 5.1 [95% CI, -0.2 to 10.3]; P = .057). The standard arm did not experience a statistically or clinically significant increase in HRQoL until T4 (β = 9.3 [95% CI, 4.7 to 11.5]; P < .001).CONCLUSIONThese data demonstrate successful collection of serial HRQoL from youth with high-risk pediatric HL and improvement in HRQoL over the course of initial therapy, sooner and to a greater extent in the group receiving the novel agent BV.

Machine Learning to Predict Interim Response in Pediatric Classical Hodgkin Lymphoma Using Affordable Blood Tests.

Response assessment of classical Hodgkin lymphoma (cHL) with positron emission tomography-computerized tomography (PET-CT) is standard of care in well-resourced settings but unavailable in most African countries. We aimed to investigate correlations between changes in PET-CT findings at interim analysis with changes in blood test results in pediatric patients with cHL in 17 South African centers. Changes in ferritin, lactate dehydrogenase (LDH), erythrocyte sedimentation rate (ESR), albumin, total white cell count (TWC), absolute lymphocyte count (ALC), and absolute eosinophil count were compared with PET-CT Deauville scores (DS) after two cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine in 84 pediatric patients with cHL. DS 1-3 denoted rapid early response (RER) while DS 4-5 denoted slow early response (SER). Missing values were imputed using the k-nearest neighbor algorithm. Baseline and follow-up blood test values were combined into a single difference variable. Data were split into training and testing sets for analysis using Python scikit-learn 1.2.2 with logistic regression, random forests, naïve Bayes, and support vector machine classifiers. Random forest analysis achieved the best validated test accuracy of 73% when predicting RER or SER from blood samples. When applied to the full data set, the optimal model had a predictive accuracy of 80% and a receiver operating characteristic AUC of 89%. The most predictive variable was the differences in ALC, contributing 21% to the model. Differences in ferritin, LDH, and TWC contributed 15%-16%. Differences in ESR, hemoglobin, and albumin contributed 11%-12%. Changes in low-cost, widely available blood tests may predict chemosensitivity for pediatric cHL without access to PET-CT, identifying patients who may not require radiotherapy. Changes in these nonspecific blood tests should be assessed in combination with clinical findings and available imaging to avoid undertreatment.

PET/CT Response Assessment in Pediatric Hodgkin Lymphoma: Does Deauville Score 3 Reflect Negativity?

FDG PET is required for the staging and response evaluation of pediatric Hodgkin lymphoma. This study aimed to evaluate the outcomes of pediatric patients with Hodgkin's lymphoma based on interim PET CT assessments of early response following second-cycle chemotherapy using the Deauville score (DS). It also determines whether DS-3 is providing an adequate or inadequate response. We conducted a retrospective cohort study including 504 pediatric patients with classic Hodgkin lymphoma who were treated with chemotherapy based on the Euro-Net protocol at the Children Cancer Hospital Egypt from March 2019 till the end of October 2022. Patients with adequate response DS 1/2 and DS 3 showed nearly the same 3-year event-free survival (EFS) of 91.9% and 91.5%, respectively, compared with those patients with inadequate response DS 4/5, who showed an EFS of 80.4% ( P =0.001). Patients with a DS 3 at interim PET evaluation were considered negative as DS 1/2. Patients of DS 3 group who did not receive radiotherapy had a much worse 3-year EFS by the existence of positive B symptoms, an ESR>30, or an advanced stage. Radiation therapy did not improve the 3-year EFS in patients with an inadequate response (DS4/5) and poor prognostic characteristics. They still need more advanced treatment. DS 1/2 and DS 3 had about the same 3-year EFS, which is better than the 3-year EFS of patients with DS 4/5. Therefore, we can classify DS 3 as having negative FDG PET CT uptake.

Tattoos and Risk of Hematologic Cancer: A Population-Based Case-Control Study in Utah.

Approximately one-third of US adults have a tattoo, and the prevalence is increasing. Tattooing can result in long-term exposure to carcinogens and inflammatory and immune responses. We examined tattooing and risk of hematologic cancers in a population-based case-control study with 820 cases diagnosed 2019-2021 and 8200 frequency-matched controls, ages 18-79 years. We calculated odds ratios (OR) and 95% confidence intervals (CI) using multivariable-adjusted logistic regression models. The prevalence of tattooing was 22% among Hodgkin lymphoma (HL) cases, 11% among non-Hodgkin lymphoma (NHL) cases, 16% among myeloid neoplasm cases, and 15% among controls. Though there were no clear patterns of associations between ever receiving a tattoo and risk of HL, NHL, or myeloid neoplasms overall, in analyses restricted to ages 20-60 years, ever receiving a tattoo (OR 2.06 [95% CI 1.01, 4.20]) and receiving a tattoo 10+ years prior (OR 2.64 [95% CI 1.23, 5.68]) were associated with an aggregated group of rarer mature B-cell NHLs. We also observed elevated risks for a 10+ year latency for myelodysplastic syndromes and chronic myeloid leukemia (OR 1.48 [95% CI 0.40, 5.41], and OR 1.24 [95% CI 0.45, 3.43], respectively). Though estimates were imprecise, we found some suggestive evidence that tattooing may be associated with an increased risk of certain hematologic cancer subtypes. With an estimated 46% prevalence of tattooing in US individuals ages 30-49, additional studies are needed to understand the degree to which these exposures may be associated with hematologic cancer risk.

Development and validation of a hierarchical approach for lymphoma classification using immunohistochemical markers.

Accurate lymphoma classification is critical for effective treatment and immunohistochemistry is a cost-effective and time-saving approach. Although several machine learning algorithms showed effective results, they focused on a specific task of classification but not the whole classification workflow, thus impractical to be applied in clinical settings. Thus, we aim to develop an effective and economic machine learning-assisted system that can streamline the lymphoma differential diagnostic workflow using EBER insitu hybridization and immunohistochemical markers. We included pathological reports diagnosed as lymphomas from two cancer centers (Sun Yat-sen University Cancer Center and Peking University Cancer Hospital & Institute). We proposed a hierarchical approach that mimicked the human diagnostic process and employed simplified panels of markers to perform a series of interpretable classification. The diagnostic accuracy for lymphoma pathological subtypes and the markers saving ratio were investigated in both temporal independent population and external medical center. A total of 14,927 patients and corresponding immunohistochemical results from two cancer centers were included. The proposed system had high discriminative ability for differentiating lymphoma pathological subtypes (measured by mean AUC in three validation cohorts, non-Hodgkin and Hodgkin lymphoma: 0.959; non-Hodgkin subtypes: 0.983; B-lymphoma subtypes: 0.868; T-lymphoma subtypes: 0.962; DLBCL subtypes: 0.957). In addition, the system's well selected characteristics can contribute to the development of agreement on panels of markers for differential diagnosis and help minimize cost of immunohistochemical marker techniques (measured by marker saving ratio compared to real clinical settings, internal primary-stage cohort: 16.45% saved, p < 0.001; internal later-stage cohort: 21.73% saved, p < 0.001; external cohort: 3.67% saved, p < 0.001). Machine learning-based hierarchical system using EBER insitu hybridization and IHC markers was developed, which could streamline the workflow by sequentially determining each lymphoma pathological subtype. The proposed system proved to be effective and cost-saving in independent and external validation, thus could be adopted affordably in future clinical practice.

Adherence to guideline-recommended cardiac screening in Medicaid-enrolled survivors of childhood cancer: A report from the Childhood Cancer Survivor Study (CCSS).

56 Background: Childhood cancer survivors face increased risks of heart failure and myocardial dysfunction associated with cancer treatment exposure. Children’s Oncology Group (COG) guidelines recommend periodic cardiac screening for survivors exposed to anthracycline or radiation. However, the extent of adherence to cardiac screening among Medicaid-enrolled survivors—a group typically characterized by socioeconomic disadvantages—remains unclear. Additionally, as Medicaid expansion under the Affordable Care Act has occurred in most, but not all states, cardiac screening adherence may vary based on survivors' state of residence. Methods: Data from the CCSS were linked to administrative Medicaid insurance claims from 2015 to 2019. We included at-risk survivors (i.e., received radiation to chest or heart, total body irradiation, and/or anthracyclines), aged 18-64 years, continuously covered by Medicaid during 2015-2019, and without a history of grade 3-4 cardiovascular conditions by 2019 to ensure the identified cardiac tests were for screening purposes. Our primary outcome assessed adherence to COG guidelines (V4.0) based on age- and therapy dose-specific frequency of cardiac testing (i.e., echocardiogram, multigated acquisition scan, or magnetic resonance imaging) during the study period. Multivariable logistic models assessed sociodemographic, clinical, and policy-related factors associated with adherence, with adjusted probability differences (i.e., marginal effects [MEs]) reported. Results: We identified 1,062 survivors at risk of cardiovascular conditions, with 57.0% female, 52.8% young adults (ages 18-39 years), and 72.8% non-Hispanic White. During 2015-2019, 285 (26.8%) survivors received any cardiac test, and 102 (9.6%) adhered to COG guideline-based frequency of cardiac testing. In multivariable models, survivors residing in states that expanded Medicaid in 2014 and later has 4.3 percentage points (ppts, 95% CI=0.58.1, p =0.025) and 6.1 ppts (95% CI=0.611.6, p =0.031) increased likelihood of adhering to guideline-based frequency of cardiac testing respectively compared to states that did not. Compared to leukemia survivors, the likelihood of adhering to guideline-based frequency of cardiac testing was higher in survivors of central nervous system tumors (ME=7.6 ppt, 95% CI=2.712.6, p =0.002), Hodgkin lymphoma (ME=10.7 ppt, 95% CI=1.320.1, p =0.026), and non-Hodgkin lymphoma (ME=9.4, 95% CI=1.017.8, p =0.028). Conclusions: Adherence to risk-based cardiac testing is low among Medicaid-enrolled survivors of childhood cancer, and associated with residence in a Medicaid expansion state and cancer type. Policy reforms toward improving affordable, continuous health insurance coverage are important means to increase adherence to guideline-based cardiac tests among survivors.

Radiological follow-up of osteonecrosis lesions in children and adolescents with Hodgkin lymphoma.

Osteonecrosis (ON) is a common complication of glucocorticoid-based Hodgkin lymphoma (HL) treatment, but the natural evolution and prognosis of ON lesions remain poorly understood. We describe the radiological evolution of ON lesions identified in a Nordic population-based cohort of paediatric HL patients. Magnetic resonance images of suspected ON lesions were centrally reviewed to confirm ON diagnosis and grade the ON lesions according to the Niinimäki classification. The study included 202 ON lesions in 46 patients, of which 77 were joint lesions. Follow-up images were available for 146/202 lesions, with a mean follow-up time of 28 months. During follow-up, 71% of the lesions remained stable, 26% improved or resolved, and 3% progressed. A higher ON grade at diagnosis was associated with a lower likelihood of spontaneous resolution. The likelihood for resolution of ON decreased by 50% for each year of added patient age, when adjusted for sex, ON location, and symptoms. Hip ON showed less spontaneous improvement compared with other joints, and the risk for surgery was 13-fold in hip ON. Grades 3-4 joint ON has the potential to either progress or resolve, warranting follow-up in patients with severe symptoms. Research on secondary prevention should be directed at grade 3-4 joint ON.

Recurrent Hypercalcemia in a Patient with Hodgkin Lymphoma with Concurrent Elevated Parathyroid Hormone-Related Peptide (PTHrP) and Vitamin D

Recurrent Hypercalcemia in a Patient with Hodgkin Lymphoma with Concurrent Elevated Parathyroid Hormone-Related Peptide (PTHrP) and Vitamin D

Elevated serum magnesium levels prompt favourable outcomes in cancer patients treated with immune checkpoint blockers

BackgroundMagnesium deficiency influences the activation and cytotoxicity of immune cells. Nevertheless, whether serum magnesium levels influence the clinical outcomes of immune checkpoint blockers (ICBs) treatment still remains ambiguous. There is an urgent need for clinical research to elucidate the relationship between serum magnesium levels and the outcomes of ICB therapy. Such insights could offer new perspectives on immunotherapy for cancer. MethodsA multi-center retrospective study involving in pan-cancer patients treated with ICBs at three large cancer centers from August 2012 to May 2023 was conducted. The primary objective was to assess the correlation between serum magnesium levels and therapeutic response in patients receiving ICBs, and further evaluate the associations between serum magnesium levels and progression-free survival (PFS) and overall survival (OS). ResultsA total of 1441 patients treated with ICBs, including 1042 with lung cancer, 270 with esophageal cancer, and 129 with Hodgkin lymphoma, were enrolled in this study. We found that patients with elevated serum magnesium levels exhibited a favourable response to ICBs treatment. The optimal cut-off point for serum magnesium level (0.79 mmol/L) was applied for stratifying patients into distinct groups. In the three tumor cohorts, patients in high magnesium level group (Mg2+ ≥ 0.79 mmol/L) had longer PFS and OS than those in low magnesium level group (Mg2+ < 0.79 mmol/L). Univariate and multivariate analyses confirmed that the serum Mg2+ level serves as an independent prognostic factor for cancer patients receiving ICBs therapy. ConclusionOur multi-center study demonstrated that among patients receiving ICBs therapy, those with elevated serum magnesium levels exhibit significantly better clinical outcomes than those with low serum magnesium levels. Further prospective validation studies are needed to confirm these findings.

Outcomes of Surgical Valve Replacements for Radiation-Induced Valvulopathy

Objective(s)Cancer patients who receive radiation therapy to the thorax often develop radiation-induced heart disease (RIHD) decades later. Prior chest radiation is associated with elevated perioperative risk of complications and mortality following cardiac surgery. Whether the type of valve (mechanical vs. bioprosthetic) used affects outcomes in patients with RIHD is unknown. MethodsThis retrospective review analyzed the characteristics and post-operative outcomes of patients with a prior history of chest radiation for Hodgkin or non-Hodgkin lymphoma who underwent surgical valve replacement at a single institution between 2000 and 2021. Both 30-day peri-operative outcomes and long-term survival were assessed. ResultsMechanical valve patients tended to be younger, have more valves replaced, and have undergone prior coronary artery bypass grafting (CABG) than bioprosthetic valve recipients. Valve type alone did not alter perioperative complications or overall survival. Median survival was 11.0 years in mechanical and 10.9 years in bioprosthetic valve patients (P = 0.930). Twelve patients underwent valve reinterventions (6 mechanical, 6 bioprosthetic), and three underwent transplant. Single valve (AV or MV) recipients fared better with median survival of 13.3 years compared to 6.2 years in those who underwent combined AVR+MVR (P<0.0001). ConclusionsPatients with RIHD who undergo surgical valve replacement have similarly suboptimal short- and long-term outcomes regardless of mechanical vs. bioprosthetic valve type. Those who required combined aortic and mitral valve replacement had especially high 10-year overall mortality. Further investigation in a larger dataset including transcatheter approaches is warranted.

P16-6 Challenges in managing refractory classical Hodgkin lymphoma in a developing country

P16-6 Challenges in managing refractory classical Hodgkin lymphoma in a developing country

S4527 A Post-Transplant Immunosuppression Complication: EBV-Positive Classic Hodgkin Lymphoma PTLD Mimicking as Cholangiocarcinoma

S4527 A Post-Transplant Immunosuppression Complication: EBV-Positive Classic Hodgkin Lymphoma PTLD Mimicking as Cholangiocarcinoma

Long-term efficacy and safety of dose-dense and dose-intense ABVD without consolidation radiotherapy in patients with advanced Hodgkin lymphoma: A 15-year follow-up of the ABVDDD-DI phase II study.

We demonstrated that dose-densified and dose-intensified ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine; ABVDDD-DI) was safe and effective. Here, we present a post hoc long-term analysis of the 82 patients enrolled in the original study. The median observation time was 175 months (IQR 159-197). At 15 years, progression-free and overall survival rates were 81.2% (95% CI, 69.9%-88.7%) and 92.7% (95% CI, 82.6%-97.0%), respectively. Four patients with multiple cardiovascular risk factors experienced delayed G3 cardiac events. The cumulative incidence of second malignancies at 20 years was 6.1%. Fertility and childbearing potential were unaffected. Data support an ongoing benefit for ABVDDD-DI without uneven late toxicities.

Circulating Tumor DNA Sequencing for Biologic Classification and Individualized Risk Stratification in Patients With Hodgkin Lymphoma.

Current clinical challenges in Hodgkin lymphoma (HL) include difficult-to-treat relapsed/refractory disease and considerable long-term toxicities of treatment. Since clinical risk factors lack discriminatory power, intensity of therapy is mainly based on tumor burden. Exploring HL genetics and tumor microenvironment (TME) might provide valuable insights for improved risk stratification. In this study, we applied circulating tumor DNA sequencing to 243 patients obtained from pivotal German Hodgkin Study Group trials to identify subtypes of HL. Independent validation of the subtypes was performed in 96 patients treated in the EuroNet-PHL-C2 study. Outcome differences of subtypes were assessed in an event-enriched clinical validation cohort comprising 72 patients from the HD21 trial, using a refined, validated, and clinically feasible assay. We propose a biologic classification of HL consisting of three distinct subtypes: inflammatory immune escape HL is characterized by frequent copy-number variations including immune escape variants such as high-level amplifications of the PD-L1 locus and an inflammatory TME. Virally-driven HL is associated with Epstein-Barr virus and/or human herpesvirus 6 and an inflammatory TME with neutrophils and macrophages, while the tumor mutational burden (TMB) is low. Oncogene-driven HL is defined by a high TMB, recurrent mutations in oncogenic drivers such as TNFAIP3, ITPKB, and SOCS1, and a cold TME. A refined and validated assay version aiming at clinically feasible risk stratification showed significant progression-free survival differences between subtypes. In addition, assessment of minimal residual disease (MRD) allowed for the detection of patients at very high risk of relapse within the subtypes. We propose a clinically feasible, noninvasive method for individualized risk stratification and MRD monitoring in patients with HL on the basis of circulating tumor DNA sequencing.

CORRELATION OF T-CELL LYMPHOMA SUBTYPES WITH ANEMIA AT DR MOHAMMAD HOESIN HOSPITAL PALEMBANG 2018-2022

Lymphoma is divided into Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL). Among NHL T-cell lymphoma is a rare malignancy of T cells, accounts for 12% of all NHL cases, it is further classified into 53 subtypes by WHO. T-cell lymphoma generally have worse prognosis than those B cells. In 2020 there were 16.125 new cases in Indonesia with 9.024 deaths for all ages and genders. Anemia occurs in some cases of lymphoma, which will make the prognosis of lymphoma worse. This study aims to determine the relationship between T-cell lymphoma subtype and anemia. This observational analytic study utilized a cross-sectional design conducted at the Department of Anatomic Pathology Faculty of Medicine Sriwiaya University/Dr. Mohammad Hoesin Palembang Hospital (RSMH) and the central laboratory of RSMH. The samples from this study were all patients who were diagnosed histopathologically and immunohistochemically as T cell lymphoma at RSMH Palembang from 2018 to 2022. Among 38 samples, T-cell lymphoma predominated in the age group &lt;55 years (73,7%), male gender (73,7%), extranodal location (73,7%), and ENKTCL, nasal subtype (55,3%). Anemia occurred in 60,5% cases and most often it is mild anemia (60,9%). There was no significant correlation between T-cell lymphoma subtype and anemia status (*p = 0.178) and T-cell lymphoma subtype and anemia degree (*p = 0.342). It can be concluded that there is no significant correlation between the T-cell lymphoma subtype and anemia.