Nodular Sclerosis Research Articles

Clinicopathological Spectrum of Hodgkin's and Non-Hodgkin's Lymphoma: A Tertiary Care Cancer Hospital Study in Pakistan.

IntroductionLymphomas are a heterogeneous group of disorders that arise primarily from lymphoid tissue and are categorized based on histological features and immunophenotypes. The distribution and frequency of different types of lymphoma vary in different parts of the world. This study aimed to document the frequency and clinicopathological characteristics of various types of lymphoma in our population to understand the ever-increasing burden of disease and formulate the optimal management and prevention plans.Materials and methodsThis study was conducted at Nuclear Medicine, Oncology and Radiotherapy Institute (NORI) from August 2015 to March 2022. A total of 300 cases of lymphoma that were diagnosed and treated at NORI were included in the study. We measured the frequency of different lymphomas and patient age, sex, and stage IV presentation at the time of diagnosis. IBM SPSS Statistics for Windows, Version 23.0 (Armonk, NY: IBM Corp.) was used to analyze the data.ResultsThree hundred patients with lymphoma were included in the study. There were more non-Hodgkin’s lymphoma (NHL) cases (n=224; 74.6%) than Hodgkin’s lymphoma (HL) cases (n=76; 25.3%). T-cell NHL was seen in 11 cases (4.8%), while B-cell NHL was found in 214 cases (95%). Diffuse large B-cell lymphoma was the predominant type (n=156; 69.3%). Among T-cell lymphomas, anaplastic T-cell lymphoma was the most common subtype (n=6; 2.6%) followed by angioimmunoblastic T-cell lymphoma (n=2; 0.8%) and T-cell lymphoblastic lymphoma (n=1; 0.4%). For classical HL, mixed cellularity was the predominant type (n=38; 50%) followed by nodular sclerosis (n=31; 40.8%), lymphocyte depleted (n=5; 6.6%), and lymphocyte rich (n=2; 2.6%). Stage IV was present in 21 HL cases (27.6%), and stage IV was seen in 67 NHL cases (29.7%) at the time of diagnosis. Most HL and NHL patients were male. Most HL cases presented in the younger age group (aged 15 to 35 years), while the largest group of NHL patients were aged 56 to 75 years.ConclusionOur population has a broad spectrum of lymphoma and its subtypes. NHL is more common than HL, and the frequency of B-cell NHL is higher than that of T-cell NHL. Approximately one-third of the patients presented in stage IV at the time of diagnosis. An awareness of clinicopathological characteristics of lymphoma in our setup would aid in diagnosis, formulating standard management plans, and prevention strategies for optimal patient outcomes.

Application of anti-programmed cell death protein 1 antibody in children with refractory or relapsed Hodgkin lymphoma

Objective: To explore the efficacy of anti-programmed cell death protein 1 (PD-1) antibody for children with refractory or relapsed Hodgkin lymphoma. Methods: Clinical data including short-term efficacy, long-term efficacy and adverse reaction of Hodgkin lymphoma children treated with anti-PD-1 antibody in Beijing Children's Hospital, Capital Medical University from December 2017 to June 2021 were analyzed retrospectively. Efficacy was evaluated as complete remission (CR), partial remission (PR), stable disease (SD), progressed disease (PD) and no response. Results: A total of 6 cases were included, including 5 males and 1 female. The age at the start of anti-PD-1 antibody treatment was 11.6 (10.2, 13.3) years, including 3 cases of mixed cellularity type, 2 cases of nodular sclerosis type, and 1 case of nodular lymphocyte-predominant type. There were 4 cases of stage Ⅳ and 2 cases of stage Ⅲ. All cases were assigned to the high-risk group, and 5 cases had B symptoms, all cases were refractory or relapsed Hodgkin lymphoma before the start of anti-PD-1 antibody treatment. Early evaluation showed that within 12 weeks of the treatment, 3 cases achieved PR and 3 cases achieved SD, while late evaluation showed that after 16 weeks of the treatment, 5 cases achieved CR and 1 case achieved PR. None of the children progressed during treatment. The follow-up time was 27 (21,41) months. Among all cases, 5 cases had event-free survival and sustained remission, 1 case had fever about 4 weeks after the drug withdrawal, finally he was confirmed to be transformed to B cell lymphoma between diffuse B cells and classic Hodgkin lymphoma. All the patients were well tolerated with anti-PD-1 antibody therapy. No adverse reactions such as high fever, chills, rash, etc. were observed during infusion. None of the patients were delayed, dose reduction or withdrawal due to adverse reactions. Two cases had reactive skin vascular hyperplasia during the treatment, without pain or itching, and they recovered on their own after stopping anti-PD-1 antibody therapy without other special treatment. Conclusion: Anti-PD-1 monoclonal antibody for children with refractory or relapsed Hodgkin lymphoma have good efficacy and tolerable side effects.

Brentuximab vedotin and association with event-free survival (EFS) in children with newly diagnosed high-risk Hodgkin lymphoma (HL): A report from the Children's Oncology Group phase 3 study AHOD1331 (NCT 02166463).

7504 Background: The anti-CD30 antibody drug conjugate, Brentuximab vedotin (Bv) is approved for adults with advanced stage HL but its use has not been established in children or adolescents. We compared the efficacy and safety of Bv with doxorubicin, vincristine, etoposide, prednisone and cyclophosphamide (Bv-AVE-PC) to the standard pediatric dose intensive regimen ABVE-PC, inclusive of bleomycin. Methods: This multicenter randomized, open-label phase 3 study enrolled patients 2-21 years (yrs) with previously untreated HL, stages IIB + bulk, IIIB, IVA, IVB. Patients were randomized to 5 cycles of either ABVE-PC or Bv-AVE-PC given every 21 days with granulocyte colony-stimulating factor support. Centrally reviewed PET-CT after 2 cycles (PET2) identified slow responding lesions (SRL) defined as Deauville score > 3. Involved site radiotherapy (ISRT) was given to bulky mediastinal adenopathy and SRL. The primary objective was 3-year EFS; events include relapse/progression, second malignant neoplasm (SMN) or death. Final data cutoff was 31 December 2021. Results: 600 participants were enrolled across 151 institutions from March 2015 to August 2019; 587 were eligible. Median age was 15.6 yrs (range 3.4-21). Patient and disease characteristics were balanced across study arms. Histology was nodular sclerosing in 76.5%. Stage distribution: 20.6% IIB-bulk; 19.3% IIIB; 28.5% IVA; 31.7% IVB. At a median follow-up of 42.1 mos (0.1-80.9), 3-year EFS (95%CI) by intent-to-treat analyses was 82.5% (77.4, 86.5) with ABVE-PC and 92.1% (88.4, 94.7) with Bv-AVE-PC (HR 0.41 (0.25, 0.67), p = 0.0002). Median time to 1st event was 9.4 months for both arms but the range differs by arm (3.6-57.8 ABVE-PC; 1.3, 25.8 Bv-AVE-PC). Relapse rate was 17% following ABVE-PC and 7% with Bv-AVE-PC. One SMN is noted in each arm: thyroid cancer at 57.8 mos and acute myeloid leukemia at 20.3 mos. 3-year overall survival (95%CI) was 98.5% (96.0, 99.4) for ABVE-PC and 99.3% (97.3, 99.8) for Bv-AVE-PC (p = 0.38). PET2 SRL rates were comparable (ABVE-PC 19% vs. Bv-AVE-PC 18%, p = 0.8). As-treated ISRT receipt did not differ (ABVE-PC 55.7% vs. Bv-AVE-PC 52.7%, p = 0.69). No difference in grade 3/4 adverse events was observed; myelosuppression, reflected in a 32% incidence of > grade 3 febrile neutropenia, did not differ by arm (p = 0.67). Only 19% of patients experienced > grade 2 neuropathy by the Balis pediatric neuropathy scale, with no difference between arms (p = 0.86). Conclusions: Brentuximab vedotin with AVE-PC in a dose intensive regimen has superior efficacy to ABVE-PC for pediatric patients with high-risk HL. A 59% risk reduction in EFS was achieved with no increase in toxicity and with fewer patients receiving ISRT compared to prior pediatric trials for high-risk HL. Clinical trial information: 02166463.

A single institution cohort of patients with classical Hodgkin lymphoma treated with brentuximab vedotin plus nivolumab.

e18738 Background: Classical Hodgkin lymphoma (cHL) is a B-cell neoplasm which affects approximately 8,500 new patients annually. The initial remission rate is greater than 80%; however, 10-30% will have refractory or relapsed disease (R/R). Both Brentuximab vedotin (BV) and nivolumab (Nivo) have recently been approved for the treatment of R/R cHL. Previous studies have shown BV+Nivo to be well tolerated, with high response rates and progression free survival (PFS) in two prospective studies. However, no real-world data is available yet for this combination. Here we present clinical characteristics and outcomes of a single institution cohort of patients with cHL who received BV+Nivo. Methods: A retrospective chart review was completed of all patients with cHL who were treated with BV+Nivo at Moffitt Cancer Center between 2018 and 2021. Baseline characteristics and treatment details were obtained. PFS and overall survival (OS) were evaluated using the Kaplan-Meier curve. Results: A total of 29 patients were included in the cohort. Median follow up time was 3 months (range 1-21). 69% (n = 20) of patients were male. Histology types included unclassifiable 48.3% (n = 14), nodular sclerosis 27.6% (n = 8), lymphocyte depleted 13.8% (n = 4), and lymphocyte rich 10.3% (n = 3). 55.2% (n = 16) of patients had B symptoms at presentation. Initial stage included stage 2 (48.3%, n = 14), stage 3 (20.7%, n = 6), and stage 4 (24.1%, n = 7). 34% of the patients were primary refractory to their first line therapy. Median time from last chemo to BV+Nivo was 4.4 months (range 0.5-50 months). BV+Nivo was most often used as 2nd line therapy (51.7%, n = 15) followed by 3rd line therapy (20.7%, n = 6). One patient received BV+Nivo as first line therapy. Median number of cycles was 4 (range 1-15). The overall response rate was 65.5% (n = 19) (complete response 44.8%), and 17.2% (n = 5) had no response. Of the 15 patients receiving BV+Nivo as 2nd line therapy, 66% proceeded to autologous hematopoietic stem cell transplant. 4 patients did not proceed with transplant per their choice, and one patient could not proceed due to progressive disease. The median PFS was 21 months (95% CI: 9 months-non reached). OS was 100%. Conclusions: Here we describe the first real-world outcomes of BV+Nivo in classical Hodgkin lymphoma. In a high risk and refractory population, BV+Nivo showed excellent responses. Further studies are needed to focus on comparing the outcome to a more traditional chemotherapy based approach.

Nodular Lymphocyte-predominant Hodgkin Lymphoma With Nodular Sclerosis: An Underrecognized Feature Associated With Pattern D.

Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) with unusual features, including some that can overlap morphologically with classic Hodgkin lymphoma (CHL), have been described. Herein, we describe 12 cases of NLPHL with fibrous bands and capsular fibrosis resembling, in part, nodular sclerosis (NS) CHL. Seven of 12 cases harbored Reed-Sternberg-like cells, further suggestive of CHL, but all cases lacked associated eosinophils and/or plasma cells in the background. In this cohort, all cases had areas of so-called pattern D (nodular T-cell rich) as a sole component in 7 (58%) cases or as a hybrid pattern along with pattern E (diffuse T-cell/histiocyte-rich) in 5 (42%) cases. The immunophenotype of the large neoplastic cells in these cases supported their being lymphocyte predominant cells of NLPHL, positive for CD20, CD79a, and OCT2, and negative for CD15 and CD30. However, PAX5 was weak in 9 of 11 cases similar to Hodgkin/Reed-Sternberg cells in CHL. We conclude that some cases of NLPHL are associated with fibrous bands and capsular fibrosis and resemble, in part, NS CHL. In our experience, NLPHL with NS-like features occurs in 10% to 15% of cases of NLPHL and is associated with a variant pattern (D and/or E). In addition, all patients in this cohort were not treated before biopsy, suggesting that the prominent sclerosis in these cases is inherent to disease biology. Recognition of NLPHL with NS-like features further expands the morphologic spectrum of NLPHL and helps avoid potential misdiagnosis as CHL.

The Impact of Obesity on Hodgkin's Lymphoma Patients Treated With Uniform Chemotherapy Protocol at Princess Noorah Oncology Center, National Guard Health Affairs, Jeddah, Saudi Arabia: Retrospective Matched Cohort.

BackgroundHodgkin's lymphoma (HL) is a disease that affects lymphocytes, mostly B cells, and it is commonly diagnosed by the presence of Reed-Sternberg cells. The influence of obesity on the disease course of HL is still controversial. This study’s aim was to investigate the treatment outcomes in obese patients suffering from HL and compare them to the outcomes of non-obese patients.MethodsThis study is a single-center retrospective cohort study that included 280 patients admitted between 2009 and 2020 with different subtypes of HL who received the chemotherapy regimen of Adriamycin, bleomycin, vinblastine, and dacarbazine (ABVD) at Princess Norah Oncology Center, National Guard Hospital, Jeddah, Saudi Arabia. Based on WHO criteria, the participants were divided into two groups (obese with a BMI that exceeds 30 kg/m2 versus non-obese with any BMI less than 29,9 kg/m2). All demographic data including age, gender, BMI, body surface area (BSA), and HL subtype (nodular sclerosis, mixed cellularity, lymphocyte depletion) were recorded. In addition, the presence of diabetes mellitus (DM), previous cancer, smoking, staging of HL, number of cycles of ABVD, dose intensity of ABVD, and outcomes (emergency visits, death during therapy, primary resistance, relapse) were collected from the participant files.ResultsRegarding therapy outcomes, 24.1% of obese patients were admitted to the hospital after receiving the first cycle of ABVD as compared to 75.9% of non-obese patients. However, there was no significant statistical difference between obese and non-obese patients in their hospital admission (p value=0.500). In addition, non-obese patients had a higher chance of being admitted to the hospital after receiving the chemotherapy dose with an odds ratio of 1.22 compared to obese patients. For the emergency visits, 20.8% of obese patients were admitted to ER as a complication of the chemotherapy regimen, whereas 79.3% of non-obese patients were admitted to ER after receiving the chemotherapy. The P-value was statistically not significant (0.396), but the odds of ER admissions after ABVD cycles were 1.28 times higher in non-obese patients compared to obese.ConclusionThe study outcomes showed a higher odds of hospital admission and ER admission as complications of the chemotherapy regimen in non-obese HL patients as compared to obese patients.

MO608: INV-202, A CB1 Receptor Blocker, Reduces Renal Injury in A Murine Model of Streptozotocin (STZ)-Induced Type-1 Diabetes

Abstract BACKGROUND AND AIMS Renal diseases remain a burden for Public Health and chronic kidney disease (CKD) affects several millions of individuals worldwide. Diabetic Nephropathy (DN) is the most frequent consequence of diabetes and is characterized by an increase in urinary albumin excretion and progressive loss of renal function associated with glomerular basement membrane thickening, mesangial expansion, nodular glomerular sclerosis and tubulointerstitial fibrosis. To date, there are few treatments that can prevent its progression. Indeed, current therapeutic approaches including RAAS blockers, SGLT2 inhibitors or both approaches combined do not fully abrogate DN progression. A growing body of experimental evidence suggests that modulation of the endocannabinoid system, and in particular its type 1 receptor (CB1R), may be a therapeutic tool in the management of CKD and more particularly DN. CB1R blockade represents a potential therapeutic modality in the fight against obesity, diabetes and their metabolic sequelae. In kidney, CB1R inhibition promotes a reduction in albuminuria, renal fibrosis and preserves renal function in both obesity-induced and diabetic nephropathy in mice mainly through a direct action of CB1R in podocytes and/or proximal tubules. INV-202 is a peripherally acting Cannabinoid receptor-1 (CB1r) inverse agonist that is under clinical development for the treatment of diseases associated with diabetes and metabolic syndrome. Here we report the effects of INV-202 on renal function and associated parameters in a preclinical model of diabetic nephropathy. METHOD Twelve weeks after the initiation of diabetes using streptozotocin, C57BL6/J mice (8 per treatment group) were randomized to receive a daily oral dose of INV-202, 0.3 mg/kg and 3 mg/kg or vehicle for 4 weeks. Five mice not treated with STZ were used as a nondiabetic control. At the end of treatment, animals were sacrificed. Urinary albumin-to-creatinine ratio (ACR), renal matrix remodelling, glomerular filtration and interstitial fibrosis were assessed in addition to glucose levels, body weight and organ weights. RESULTS After 28 days of treatment, there was no significant effect on hyperglycemia or body weight with either dose of INV-202. Renal and hepatic weights were reduced while heart weight was unaffected. This remained true when normalizing for tibial length. Compared with vehicle-treated diabetic mice, INV-202-challenged mice displayed a marked decrease in many clinical features of DN such as albuminuria, albumin-to-creatinine ratio, urinary urea, loss of glomerular filtration rate and renal hypertrophy. Interestingly, we also found an improvement in both podocyte and proximal tubular cells morphology and health markers that were likely responsible for the improvement previously mentioned. In addition, INV-202 led to a downregulation of the angiotensin II receptor expression as well as a reduced urinary excretion, suggesting an inhibitory effect of this compound on the angiotensin II-mediated renal dysfunction in the context of DN. Furthermore, INV-202 also led to a drastic reduction in renal inflammation and oxidative stress markers that are known to be highly involved in the pathogenesis of DN. Finally, despite the limitation of our model in regard to interstitial fibrosis development, we could observe a marked anti-fibrotic effect of INV-202. CONCLUSION Treatment with INV-202 reduced the progression of nephropathy in STZ-induced diabetic mice. Improvements in kidney size, function and histology, with corresponding gene expression, were noted with both doses of INV-202. Further work to explore the effect of INV-202 in humans is warranted.

Impact on the survival of neutrophil-lymphocyte ratio, platelet-lymphocyte ratio, and monocyte-lymphocyte ratio on prognosis in children with Hodgkin lymphoma.

Objectives:To evaluate the clinical utility of the recently described absolute neutrophil counts to absolute lymphocyte counts ratio (NLR), absolute platelet counts to absolute lymphocyte counts ratio (PLR), and absolute monocyte counts to absolute lymphocyte counts ratio (MLR) on prognosis in children with Hodgkin lymphoma (HL).Methods:We retrospectively evaluated the clinical characteristics, laboratory features (lymphocyte counts, NLR, PLR, and MLR), treatment, and results of 52 children with HL in the Department of Pediatric Hematology and Oncology, Selcuk University, konya, Turkey, from January 2006 until December 2021.Results:The patients included 27 (51.9%) females and 25 (48.1%) males. The age of the patients ranged between 3-17.5 years old (median: 9 years). There were 22 patients in stage II, 24 in stage III, and 6 in stage IV. The most prevalent histopathological subgroup was the nodular sclerosing type (53.8%). The 5-year overall survival rate was 93.7%. The overall survival rate differed based on lymphocyte counts (p<0.0001), NLR (p=0.018), and PLR (p=0.009). However, none of the prognostic factors in the univariate analysis were not prognostic risk factors (p>0.05) in the multivariate analysis.Conclusion:Lymphocyte counts, NLR, and PLR may be useful markers for determining the outcomes in children with HL.

Linfoma de Hodgkin (LH). Historia de un éxito a lo largo de 50 años

Hodgkin Lymphoma (HL) is a rare B-origin lymphoma that accounts for approximately 10% of all lymphomas. HL is made up of two different entities: on the one hand, the Classical Hodgkin Lymphoma (CHL), consisting of the histological forms of predominantly lymphocytic, nodular sclerosis, mixed cellularity and lymphocytic depletion and, on the other, the Nodular Lymphocyte-Predominant Hodgkin Lymphoma (NLPHL). During the last 50 years, we have seen a move from a monovalent therapy – with a 5-10% survival probability at 5 years – to a combination chemotherapy and a therapeutic approach aimed at reducing the treatment toxicity while maintaining a high probability of cure even in advanced cases. The curative role of radiotherapy in patients with localized Hodgkin’s lymphomas has been observed for about a century. New agents such as Brentuximab and PD-1 antibodies have recently proven to be efficient in recurrent cases and their incorporation to the first line is being studied. Likewise, the role of autologous haematopoietic stem cell transplantation after salvage chemotherapy in first relapse and the role of allogeneic transplantation and the use of anti-CD30 CAR T-cell therapy in relapsed or refractory Hodgkin’s lymphoma are discussed.

Management of basal cell carcinoma: our experience at tertiary care institute

Background: Basal cell carcinoma (BCC) is a slow growing, locally invasive and most common skin cancer. Its etiology is mostly linked to exposure to U.V. rays in sunlight. Diagnosis is mostly clinical and wide local excision is main treatment modality.Methods: The study was conducted on 50 cases of BCC diagnosed at Sri Guru Ramdas University of Health Sciences during a study period extending from January 2013 to January 2021. In the present study various variables associated with BCC i.e. age, gender, size, site, and histopathology were studies.Results: The present study was conducted on 50 patients of BCC. Total number of males was 32 (64%) and there were 18 (36%) females. Mean age of patients presented with BCC was 65 years and SD=14.054. It was observed that most common site of lesion was infra orbital region 12 (24%). Size of lesion varied from 1 to 3 cm and wide local excision with flap was most commonly performed procedure at our Institute. Nodular sclerosing was observed to be the most common histopathological type accounted for 35 (70%) of total cases.Conclusions: BCC is a common surface malignancy amenable to early detection and potential cure. Infra orbital region is most common site and nodular sclerosing is most common histopathological type. Wide local excision remains the heart of treatment.

CHOLESTATIC JAUNDICE AS A CLINICAL PRESENTATION OF HODGKIN’S LYMPHOMA IN A 20-YEAR-OLD SAUDI MALE PATIENT, A CASE REPORT

Background: Hodgkin lymphoma (HL) represents approximately 10% of lymphomas and is curable in most, but not all, patients. It has a bimodal incidence, although it most commonly presents in young adults. Presentation with mediastinal, cervical, and supraclavicular involvement is particularly common for the nodular sclerosing subtype. Patients may also present with B symptoms, although that is more commonly seen in elderly patients with more advanced disease. Pruritus may also be a presenting symptom. The diagnosis is established with a lymph node biopsy specimen showing Reed-Sternberg cells, malignant cells that originate from germinal center B cells and are seen in an inammatory inltrate. Case Report: We report a case of a 20 years old Saudi male presented to our emergency department with jaundice without clinical lymphadenopathy, accompanied with laboratory investigations that is showing intrahepatic cholestasis. The patient was admitted initially to evaluate the causes of jaundice that he has mainly by investigating hepatic and post-hepatic diseases. Months later, he has developed palpable lymphadenopathy. Surgical excisional biopsy result concluded that the patient is having Hodgkin's lymphoma. Conclusion:Although it is thought to be an uncommon cause of intrahepatic cholestatic, lymphomas should be considered in evaluating a patient who came with similar presentation.

Real-World Outcomes of Hodgkin Lymphoma: A Multi-Centric Registry From India.

BackgroundHodgkin’s lymphoma (HL) is one of the most curable malignancies with a 5-year survival of over 80%. Most published literature from low-middle income countries comes from single institute experience.MethodologyThe OncoCollect Lymphoma group registry was set up in 2017 and has 9 major participating sites across India. Data of newly diagnosed classical HL (CHL) patients, treated between 2011 and 2017, were collected using OncoCollect software. The clinical features, subtypes, prognostic stratification, treatment patterns, response to first-line treatment, and 5-year outcomes were analyzed. All statistical analysis was done using Microsoft R Open statistical software linked to OncoCollect software.ResultsThere were 939 newly diagnosed CHL patients with a median age of 38 (range, 18–99) years at presentation. The male-to-female ratio was 2.07:1. Histological subtypes included mixed cellularity, CHL (MC, CHL), nodular sclerosis, CHL (NS, CHL), lymphocyte-rich, CHL (LR, CHL), and lymphocyte-depleted, CHL (LD, CHL), in 60.60%, 26.94%, 9.80%, and 2.66%, respectively. At presentation, 50.43% had B symptoms and 53.35% had advanced disease. 29.71% of advanced-stage patients had high Hodgkin IPI score. 79% and 21% of patients received 1st-line treatment with chemotherapy alone or combined modality treatment with chemotherapy and radiotherapy. The most common first-line chemotherapy was ABVD-based regimen (94.68%). The overall response rate was 93.48%. Complete response rates among early-stage favorable and unfavorable risk groups were 92.73% and 86.79%, and those among advanced-stage low- and high-risk groups were 76.64% and 69.78%, respectively. The median relapse-free follow-up duration was 51 months (IQR 22–69). A significant difference was found in 5-year EFS between the early- and advanced-stage disease 83.53% and 73.55% (p = 0.00087), respectively. Similarly, significant difference was found in EFS among early-stage patients treated with a combination of 4-cycle chemotherapy and radiotherapy vs. chemotherapy alone 88.57% and 66.33% (p = 0.0042), respectively.ConclusionsIn this large cohort from India, survival of patients with HL was comparable to the developed world. With a median follow-up of 51 months, the 5-year EFS and OS of all patients were 78.24% and 83.63%, respectively.

Distinctive patterns of marrow involvement by classic Hodgkin lymphoma are clues for diagnosis and subtyping.

Classic Hodgkin lymphoma (CHL) is a lymphoid neoplasm deriving from B cells in a rich inflammatory background. There are four histological subtypes with different epidemiological features. Bone marrow involvement by CHL is infrequent, and subtyping CHL from the bone marrow is not suggested as there might be discordant histopathology between the primary tumors and bone marrow specimens. In this study, we aimed to identify the histopathological features of bone marrow involved by CHL and tried to correlate these features with their subtypes. Among the 23 recruited cases, the frequencies of mixed cellularity (MC; 48%, 11/23) and nodular sclerosis (NS; 44%, 10/23) were similar. There were two patterns of marrow involvement: pattern A (fibrous), space-occupying lesions with alternating hypo- and hypercellular areas against a fibrotic background with dilated sinusoids and pattern B (histiocyte-rich), ill-defined granuloma-likelesions in which histiocytes merged with normal hematopoietic and inflammatory cells. Pattern A was more frequent in patients with CHL-NS than CHL-MC (100% vs. 18.2%; p < 0.001). Diagnostic Hodgkin cells and Reed-Sternberg (HRS) cells were identified in all cases, while HRS variant lacunar cells were occasionally discovered, particularly in the CHL-NS subtype (NS 100% vs. MC 9%; p < 0.001). The frequency of EBV association was higher in MC (64%) than that in NS (36%) subtype, but not statistically significant. Of the two patterns of marrow involvement, pattern A was more commonly associated with the NS subtype and less frequently associated with EBV. Recognizingthe patterns of marrow involvement is important for diagnosis and may contribute to the subtyping of CHL.

Occurrence and Severity of Adverse Reactions of Immune Checkpoint Inhibitors (PD-1 and PD L1) Based on Mordovian Dispensary Data Analysis

Background: Recently, a novel therapeutic technique has been revealed to recruit PDL1 and PD1 inhibitors to promote and enhance the cytotoxic T cell activity in combating the tumor. But unfortunately, several followed patients who didn’t tolerate the drug appeared unfavorable autoimmune side effects, such as anemia, pneumonitis, hepatitis, colitis, in addition to fatigue/ asthenia, decreased appetite, nausea, cough, dyspnea, constipation. Aim: To assess the severity of the adverse reactions of PD-1 and PD-L1 inhibitors in treating patients with positive PD-1 or PD-L1; non-small cell lung cancer patients (NSCLCs), small cell lung cancer (SCLC), nodular sclerosis Hodgkin lymphoma, classic Hodgkin's lymphoma, gastric cancer, renal cell carcinoma, caecal carcinoma, buccal mucosa carcinoma, nasopharyngeal carcinoma, laryngopharynx cancer, bladder cancer, cervical cancer, and melanoma. Materials and Methods: The study data was collected and analyzed randomly from the period of January 2019 to November 2020 from the Mordovian oncological dispensary. The data are collected from the electronic archive of the hospital. Then, we followed up with the patients for the same period, and we recorded the presented adverse reactions. The patients received anti-tumor drug; PD-L1/PD-L inhibitors (Atezolizumab; 1200mg, Pembrolizumab; 200mg, and Nivolumab; 240mg or 3 mg/kg) every 21 or 14 days they got IV infusion of PD-1 and/or PD-L1 inhibitors. After the progression and metastasis of the tumor, the patients received a combination of chemotherapy prior to the immunotherapy. Results: The analyzed data have shown 7.14% of the studied patients (n=28) have developed adverse reactions that ranged from mild to moderate severity (anemia and biochemical tests deviation). Conclusion: These clinical findings supported the moderate risk of developing life-threatening adverse reactions after administration of immune checkpoint inhibitors (Nivolumab, Pembrolizumab, Atezolizumab) to patients with advanced-stage tumors. The patients who were treated with PD-1 inhibitors developed less severe adverse reactions than patients who were treated with PD-L1 inhibitors. The adverse reaction severity depends on the period of administration and the type of the treated tumor, which consequently determines the dose of immunotherapy. Also, the aggressiveness of the autoimmune reactions depends on the patient's immune state and its reactivity.

Prognostic significance of CD163- and CD68-expressing macrophages in nodular sclerosis Hodgkin lymphoma

The objective of the study was to determine the clinical and morphological criteria and prognostic significance of CD163- and CD68-expressing macrophages in formalin-fixed paraffin-embedded (FFPE) lymph node samples of nodular sclerosis Hodgkin lymphoma.Materials and methods. We have studied clinical and laboratory characteristics and treatment results of 52 patients with newly diagnosed nodular sclerosis Hodgkin lymphoma. The treatment efficacy was assessed after 2–4 courses of chemotherapy by positron emission tomography combined with computed tomography scan (PET-CT) according to the Deauville scale.Results. In FFPE lymph node samples, differences in the localization and relative number of CD163-positive macrophages in patients of both study groups were determined. Morphometric counting of CD68-positive cells did not reveal statistically significant intergroup differences. The threshold of CD163-positive cells has been established. The relationship between the CD68 expression level and the response to frontline therapy was not revealed. The ratio of tumorassociated macrophages in each patient was assessed by the CD163/CD68 index. The threshold of the index was determined, which allows predicting the course of nodular sclerosis Hodgkin lymphoma.Conclusion. The following parameters could be used as additional morphological criteria for predicting the response to frontline therapy in patients with nodular sclerosis Hodgkin lymphoma: tissue distribution pattern and quantitative calculation of macrophage-histiocytic microenvironment subpopulation composition. The results could be used to risk group stratification of patients with nodular sclerosis Hodgkin lymphoma in order to predict the response to initial phase of therapy, as well as to determine personalized treatment approaches.

Epstein-Barr Virus in Childhood and Adolescent Classic Hodgkin Lymphoma in a French Cohort of 301 Patients.

The aim was to analyze the role of Epstein-Barr virus (EBV) in the bioclinical characteristics of patients treated for classic Hodgkin lymphoma (cHL) in France. Biopathologic data of 301 patients treated for a cHL in/or according to the EuroNet PHL-C1 trial between November 2008 and February 2013 were centrally reviewed. Median age at diagnosis was 14 (3 to 18) years and the F/M ratio 0.86, 0.47 before 10 years and 0.9 from 11 to 18. CHL subtypes were nodular sclerosis for 266/301 (88%) patients, mixed cellularity for 22/301 (7%), lymphocyte rich for 2/301 (1%), and 11/301 were unclassified. EBV positivity by in situ hybridization was observed for 68/301 (23%) patients, significantly associated with mixed cellularity subtype and male sex, particularly overrepresented in boys below 10 years: 15/23 (65%) versus 28/139 among other male patients (20%). EBV viral load was detectable in 22 of 108 (22%) tested cases and was overrepresented in EBV cHL (13/28) versus non-EBV cHL (9/80) patients. Detailed semiquantitative histologic analysis showed a high number of B-cell residual follicles in EBV cHL relative to EBV-negative HL. Distribution of EBV cHL in children and adolescents is associated with young age and male sex, suggesting a specific physiopathology and may require a differential therapeutic approach.

Killer Cell Immunoglobulin-Like Receptor Haplotype B Modulates Susceptibility to EBV-Associated Classic Hodgkin Lymphoma.

Tumor cells of classic Hodgkin lymphoma (cHL) are derived from antigen presenting B cells that are infected by Epstein Barr virus (EBV) in ~30% of patients. Polymorphic Killer cell immunoglobulin-like receptors (KIRs) expressed on NK cells interact with human leukocyte antigen (HLA) class I and play a key role in immune surveillance against virally infected cells and tumor cells. We investigated the effect of KIR types on cHL susceptibility overall (n=211) and in EBV-stratified subgroups using the Dutch GoNL cohort as controls (n=498). The frequency of the KIR haplotype B subgroup was significantly different between EBV+ and EBV− cHL patients (62% vs. 77%, p=0.04) and this difference was more pronounced in nodular sclerosis (NS) cHL (49% vs. 79%, p=0.0003). The frequency of KIR haplotype B subgroup was significantly lower in EBV+ NS cHL compared to controls (49% vs. 67%, p=0.01). Analyses of known KIR – HLA interaction pairs revealed lower carrier frequencies of KIR2DS2 – HLA-C1 (29% vs. 46%, p=0.03) and KIR2DL2 – HLA-C1 (29% vs. 45%, p=0.04) in EBV+ NS cHL patients compared to controls. Carriers of the KIR haplotype B subgroup are less likely to develop EBV+ NS cHL, probably because of a more efficient control over EBV-infected B cells.

Composite Classic Hodgkin Lymphoma and Follicular Lymphoma

Composite classic Hodgkin lymphoma and follicular lymphoma (CHLFL) is a rare and poorly characterized entity. Herein, we report the clinicopathologic features of 22 cases of CHLFL from 3 institutions and we assess 27 additional cases reported in the literature. In our cohort (n=22), patients with CHLFL had a median age of 61 years and an equal male to female incidence. Most cases (95%) arose de novo with the remaining patients having a history of non-Hodgkin lymphoma. CHLFL always involved lymph nodes (100%) and most cases (95%) revealed 2 distinct areas separately diagnostic for CHL and FL. The CHL component represented a variable proportion of the overall neoplasm (5% to 90%) and was either mixed cellularity (82%) or nodular sclerosis (18%) type. The Hodgkin/Reed-Sternberg cells expressed CD30 (100%), PAX5 (100%), CD15 (62%), BCL6 (47%), BCL2 (29%), and EBER (25%), in a polymorphous inflammatory background typical of CHL. The FL component was low-grade in 55%, grade 3A in 36%, and grade 3B in 9% of cases. All 3 cases investigated by cytogenetic methods for a clonal relationship between the CHL and FL components were clonally related. These clinicopathologic features of our cohort are similar to those of cases reported in the literature. The 5-year overall survival in combined patients with CHLFL (n=49) was 48%, comparable to CHL but worse than FL in the elderly. In summary, CHLFL is a rare entity that most often occurs in older adults, involves lymph nodes, and most commonly presents de novo. In the small number of cases assessed, the CHL and FL components are usually clonally related suggesting that the CHL and FL components may share a common progenitor B-cell, likely a mutated germinal center B-cell.

Prognostic Value of the Degree of Tumor Tissue Infiltration by CD15-Positive Granulocytes in Nodular Sclerosis Classical Hodgkin’s Lymphoma

Nodular sclerosis classical Hodgkin’s lymphoma (NSCHL) is one of the most common malignant lymphoproliferative diseases among younger people. The tumor is considered to be potentially curable. However, despite successful application of standard treatment methods, primary resistance and relapses occur. At present, many researchers focus on studying the value of tumor microenvironment in the prognosis of the course and progression of classical Hodgkin’s lymphoma (cHL), aiming at identifying new therapeutic targets. The present paper shows that the relative count of CD15-positive granulocytes in patients with favorable course of the disease is significantly lower than in therapy-refractory patients. The threshold of tumor microenvironment cells expressing CD15 was 8 %. The data obtained provide the basis for determining prognostic value of CD15-positive granulocytes in NSCHL and presenting this cell pool as a potential therapeutic target.

Survival by age in paediatric and adolescent patients with Hodgkin lymphoma: a retrospective pooled analysis of children's oncology group trials

Adolescents with Hodgkin lymphoma have worse disease outcomes than children. Whether these differences persist within clinical trials is unknown. We examined survival, by age, in patients receiving response-adapted therapy for Hodgkin lymphoma on Children's Oncology Group (COG) trials. Patients (aged 1-21 years) diagnosed with classical Hodgkin lymphoma and enrolled between Sept 23, 2002, and Jan 19, 2012, on one of three phase 3 COG trials in the USA and Canada were eligible for inclusion. The three COG trials were defined by risk group according to Ann Arbor stage, B-symptoms, and bulk (AHOD0431 [low risk; NCT00302003], AHOD0031 [intermediate risk; NCT00025259], or AHOD0831 [high risk; NCT01026220]). The outcomes of this study were event-free survival (death, relapse, or subsequent neoplasm) and overall survival. Cox proportional hazards models estimated survival, adjusting for disease and treatment factors both overall and in patients with mixed cellularity or non-mixed cellularity (nodular sclerosing and not-otherwise-specified) disease. Of 2155 patients enrolled on the three trials, 1907 (88·4%; 968 [50·8%] male and 939 [49·2%] female; 1227 [64·3%] non-Hispanic White) were included in this analysis. After a median follow-up of 7·4 years (IQR 4·3-10·2), older patients (aged ≥15 years) had worse unadjusted 5-year event-free survival (80% [95% CI 78-83]) than did younger patients (aged <15 years; 86% [83-88]; HR 1·38 [1·11-1·71]; p=0·0038). Older patients also had worse unadjusted 5-year overall survival than did younger patients (96% [95% CI 95-97] vs 99% [98-99]; HR 2·50 [1·41-4·45]; p=0·0012). In patients with non-mixed cellularity histology, older patients had a significantly increased risk of having an event than did younger patients with the same histology (HR 1·32 [1·03-1·68]; p=0·027). Older patients with mixed cellularity had significantly worse 5-year event-free survival than did younger patients in unadjusted (77% [95% CI 65-86] for older patients vs 94% [88-97] for younger patients; HR 2·93 [1·37-6·29]; p=0·0039) and multivariable models (HR 3·72 [1·56-8·91]; p=0·0032). Overall, older patients were more likely to die than younger patients (HR 3·08 [1·49-6·39]; p=0·0025). Adolescents (≥15 years) treated on COG Hodgkin lymphoma trials had worse event-free survival and increased risk of death compared with children (<15 years). Our findings highlight the need for prospective studies to examine tumour and host biology, and to test novel therapies across the age spectrum. National Institutes of Health, St Baldrick's Foundation, and Lymphoma Research Foundation.