Challenges and Opportunities in Lymphoma

Special Issue:

Challenges and Opportunities in Lymphoma

Akshay Nigam
Department of Radiology, Gajra Raja Medical College, Gwalior

Anupama Sharma
Department of Biochemistry and Clinical Research, Nims University, Jaipur

Girish Chandra Sharma
Department of Chemistry, Jaypee University, Anoopshahr

Sanjeev Kumar Singh
Department of Biochemistry, Gajra Raja Medical College, Gwalior

Abstract

Lymphoma involves abnormal lymphoid cell growth, often originating in lymphatic tissue, but in this case series non-Hodking’s lymphoma is visible in the extra-nodal region. This research explores different lymphoma cases, focusing on diverse presentations and utilizing modern imaging for evaluation. Four cases are detailed, involving an 18-year-old woman with tonsillar lymphoma, a 69-year-old man with ocular lymphoma, a 38-year-old lady with abdominal lymphoma, and a 30-year-old man with gastric lymphoma. All cases received adjuvant chemotherapy (RCHOP), leading to significant symptom relief after four cycles.

The discussion highlights the debate surrounding the classification of primary extranodal non-Hodgkin’s lymphoma (NHL), challenging the existing Ann Arbor classification’s applicability.

A major challenge in managing primary extranodal lymphomas is the absence of specific treatment guidelines. Evaluation criteria, defining complete response as the disappearance of all evidence of the disease, guided the study. In conclusion, this case series underscores the importance of a multidisciplinary approach in diagnosing, staging, and managing non-Hodgkin’s lymphoma. Despite challenges in defining and treating primary extranodal non-Hodgkin’s lymphoma, the study demonstrates the effectiveness of adjuvant chemotherapy in providing relief, as all the cases revealed recovery after 4 continuous cycles of chemotherapy.

Mounia Bendari
Hematology Department, Cheikh Khalifa International University Hospital, Casablanca; Faculty of Medicine, Mohammed VI University of Sciences and Health, Casablanca, Morocco. Research Entity, Mohammed VI Center for Research & Innovation, Rabat, Morocco.

Abderrahmane Elbouzidi
Hematology Department, Cheikh Khalifa International University Hospital, Casablanca; Faculty of Medicine, Mohammed VI University of Sciences and Health, Casablanca, Morocco. Research Entity, Mohammed VI Center for Research & Innovation, Rabat, Morocco.

Mariam Ahnach
Hematology Department, Cheikh Khalifa International University Hospital, Casablanca; Faculty of Medicine, Mohammed VI University of Sciences and Health, Casablanca, Morocco. Research Entity, Mohammed VI Center for Research & Innovation, Rabat, Morocco.

Said Benchekroun
Pathology Department, Cheikh Khalifa International University Hospital, Casablanca; Faculty of Medicine, Mohammed VI University of Sciences and Health, Casablanca, Morocco. Research Entity, Mohammed VI Center for Research & Innovation, Rabat, Morocco.

Abstract

Background: Mantle cell lymphoma (MCL) is a distinct subtype of Non-Hodgkin Lymphoma (NHL), it affects 5 to 8% of NHL, it is a clinically heterogeneous disease occurring within a heterogeneous patient population. The median age at time of diagnosis is over 65 years old. The incidence increased with age, and also affects man more than women with ratio of 3 to 1. Overall survivor is different according to subtype of lymphoma. Most patients present at advanced stage, and 30% present in leukemic phase.

Case report: We report a case of 60-year-old women with relapsed mantle cell lymphoma. The patient had no medical past history. The diagnosis of mantle cell lymphoma was made in 2019 revealed by anemic syndrome, the morphological and histological study of lymph node and bone marrow biopsy confirmed the mantle cell lymphoma with expression of CD19+, CD20+, CD5+, CD23-, Cyclin D1+, and KI 67 at 60%.  The PET Scan showed FDG-avid disease, the laboratory studies remarques for high level of LDH, elevated B2 microglobulin. The patient underwent R-DHAP regimen (Rituximab, Aracytine, Cisplatin, prednisone) and achieved complete remission after 2 curses, the PET Scan was negative, and the bone marrow biopsy was normal, the collect of hematopoietic stem cell was performed, and the patients received 2 other courses of RDHAP regimen. She does not benefit from autologous hematopoietic stem cell transplant (HSCT) because of severe infection of COVID19. In reality, patient had a server pneumoniae with chronic fever, she was admitted for intravenous antibiotics, all biological exam showed a high level of C- reactive protein, and high level of d-dimers, but no sign of relapse was found. The patient still febrile during 6 months. Autologous hematopoietic stem cell transplant was not realized, but she received maintenance treatment with Rituximab. One year later, the patient developed a mass under the knee with deep deterioration of general condition, relapse was suspected, the surgical biopsy was performed and histological study confirmed the relapse of mantle cell lymphoma. The aim of this case report is to describe the difficulties to manage mantle cell lymphoma associated to covid 19 infection and report the consequences of therapeutic decision.

Conclusion: Not all mantle cell lymphoma is the same, it is crucial to identify patients appropriate for aggressive treatment, autologous hematopoietic stem cell transplant improves event free survival with unclear benefit in all patients, maintenance Rituximab improves overall survivor. Minimal residual disease may guide future therapeutic decisions and help physicians manage these patients. Our patient does not receive autologous hematopoietic stem cell transplant and suffers from chronic Covid19 infection.  This association is complicated for the physician and

SEEMA DEVI
Additional Professor, State Cancer Institute, IGIMS, Patna, Bihar

Abstract

Patients presented with soft tissue lesions without any β symptoms can be a case of Primary extranodal Non- non-Hodgkins lymphoma. According to the World Health Organization classification system, there are two types of Lymphoma with various sub-types of Hodgkins Lymphoma and Non-Hodgkin Lymphoma are classified to assess the disease burden Progression and metastasis Imaging modalities are helpful. Commonest site involvement in Non-Hodgkin Lymphoma in the gastrointestinal tract (44%) followed by Head and Neck and may Involve bone (8%) and Central Nervous System 5%. Diffuse large β-Cell Lymphoma is the most common subtype representing 30%-35% of all Non-Hodgkin Lymphoma Cases. Oral and Para oral sites were involved in 2.5% of the cases. A 27-year-old Male noticed a swelling in the flank which was progressively Increasing in size one year back later it was associated with pain which reduced mobility and pain was increased during walking. Due to the advancement of diagnostic techniques, it is easy to get the radiological picture and correlation with clinical presentation and pathological reports, but these facilities are not available at various centers. Usually, patients are present in very advanced stages because of a lack of awareness about the disease, and how to proceed for diagnosis and treatment resulting in poor outcomes for these patients. This presentation and clinical funding are rare in the case of Lymphoma. This case report allows us to think of another diagnosis rather than usual.

Motoharu Shibusawa, MD
IMS group Shinmatsudo Central General Hospital, Department of Hematology, Chiba, Japan

Erika Imamine, MD
IMS group IMS Tokyo Katsushika General Hospital, Department of Cardiology, Tokyo, Japan

Abstract

Cardiovascular issues are important concerns in malignant lymphoma treatment. These issues can be broadly categorized into two groups: the invasion of malignant lymphoma into the heart and cardiovascular disease related to malignant lymphoma treatment. In terms of malignant lymphoma invasion of the heart, the presence of a heart lesion of malignant lymphoma often presents with heart-related symptoms and findings such as chest pain, heart failure, and arrhythmias. Notably, heart failure and arrhythmias can be fatal. The identification of heart lesions of malignant lymphoma will result in appropriate management and survival improvement. As for cardiovascular disease associated with malignant lymphoma treatment, the incidence and types of cardiovascular disease, management, and follow-up planning should be identified before starting treatment. This identification and plan will allow an understanding of the risk of developing cardiovascular disease and appropriate management and follow-up. In clinical practice, it is important to keep in mind that cardiac issues in patients with malignant lymphoma should be identified, assessed, and managed before initiating treatment.

Nathan Roberts, MD
 Department of Hematology and Oncology, University of Virginia Comprehensive Cancer Center, Charlottesville, VA, USA

Ifeyinwa Obiorah, MD PhD
Division of Pathology, University of Virginia Medical Center, Charlottesville, VA

Prem Batchala, MD
Division of Radiology and Medical Imaging, University of Virginia Medical Center, Charlottesville, VA, USA

Emily Ayer Ayers
Department of Hematology and Oncology, University of Virginia Comprehensive Cancer Center, Charlottesville, VA, USA

Abstract

Follicular lymphoma is the most common indolent non- Hodgkin lymphoma (NHL) and accounts for approximately 20-30% of all NHL cases in Western countries. In general, systemic therapies are not considered to be curative. Despite this, prognosis is excellent with a 5-year relative survival rate of 90% and median overall survival rates ranging from 10-20 years across numerous studies. The exact incidence of central nervous system (CNS) involvement in cases of follicular lymphoma is unknown, however retrospective data suggest an incidence of 0.2% though this likely represents an underestimation of the true incidence. The optimum treatment approach for CNS disease in follicular lymphoma is poorly defined and no randomized studies exist which prove the superiority of one approach over another. Retrospective data suggest that resection, with or without adjuvant radiation, is an effective strategy for patients with local disease limited to the CNS. In cases where synchronous systemic disease is present, treatment regimens incorporating high-dose methotrexate and bendamustine or anthracycline-based chemotherapy have demonstrated efficacy. We report a case of a 59-year-old female with stage IV follicular lymphoma with synchronous systemic and leptomeningeal involvement who achieved complete remission following treatment with bendamustine, rituximab, and intra-thecal

Methotrexate. More long-term follow up data are needed to better characterize the prognosis for patients with CNS involvement who obtain complete remission following initial therapies. Treatment selection for patients with CNS involvement should take into account the presence or absence of systemic disease, patient comorbidities and performance status, and the likelihood of transformation to a high-grade process.

Muhamad Alhaj Moustafa
Division of Hematology and Medical Oncology, Mayo Clinic, Jacksonville, Florida

Mario El Hayek

Abstract

Follicular lymphoma (FL) is the most common type of indolent lymphoma in the Western world, accounting for approximately 30% of lymphoma cases. FL is known for its recurrent nature, necessitating diverse treatment options. The introduction of rituximab, an anti-CD20 antibody, has greatly improved FL outcomes and paved the way for targeted therapies. In this review, we thoroughly explore the structure, mechanism of action, clinical outcomes, and side effects of currently approved monoclonal antibodies (mAb) for FL. Furthermore, we provide insights into ongoing clinical trials and emerging monoclonal antibodies that hold promise for the future of FL treatment. A comprehensive literature search was conducted using various medical databases, including ASH and ASCO publications, as well as PubMed. The clinicaltrials.gov website was used to compile a list of investigational monoclonal antibodies from ongoing clinical trials. The future of antibody-based therapy for follicular lymphoma shows great promise, with a focus on enhancing antibody efficacy, prioritizing optimized combination therapies to address treatment resistance, and evaluating bispecific antibodies as first-line therapies, all while carefully balancing risks and benefits and sequencing treatments appropriately for better disease management. These directions have the potential to establish antibodies as a central component of follicular lymphoma treatment.

Christian Gisselbrecht, MD Pr.
Hospital Saint Louis Institut d’hématologie, 1 avenue Claude Vellefaux Paris 75010 France, Lymphoma Study Association (LYSA)

Eric Van Den Neste, MD
Cliniques Universitaires UCL Saint-Luc, Brussels, Belgium; Lymphoma Study Association (LYSA)

Abstract

Diffuse large B-cell lymphoma is a highly curable disease when complete remission after immunochemotherapy is achieved. Despite a high complete remission rate, which is a prerequisite for a cure, 20–40% of patients will relapse or fail first-line therapy. Salvage chemotherapy followed by intensification with autologous stem cell transplant (ASCT) has been established as a curative treatment for relapsed chemosensitive patients under 60 years of age. The results have been somewhat disappointing, with less than 50% of patients being eligible for transplant and relapse posttransplant ranging from 60–40%. Improvements have been made with new drugs in development, immunoconjugate bispecific monoclonal antibodies, and chimeric antigen receptor technology (CAR-T). A more precise evaluation of prognostic factors with PET scans and other biological factors during treatment will allow for the design of new treatment strategies. The exceptional response rate in phase 2 achieved with the three available CARTs has now been confirmed with a longer follow-up period. At 2 years, the overall survival (OS) expectancy is 50% with a plateau on the curves. Three randomized studies compared CARTs to the standard of care with ASCT and demonstrated the superiority of CARTs. Despite this superiority, the relapse rate remains 50%, which is significantly better than the standard of care. However, major improvements in OS have not yet been achieved. A clearer definition of eligible patients should also take into account their interim pet-scan, metabolic tumour volume, relation with Ct DNA with follow-up of minimal residual disease.

A. Kaur Aminder Singh
Department of Pathology, Dayanand Medical College & Hospital, Ludhiana, Punjab, India

A. Singh, Harpreet Kaur, Bhavna Garg, Vikram Narang

Abstract

Background: Cutaneous lymphomas are a heterogeneous group of extra-nodal non-Hodgkin’s lymphomas that are characterized by a cutaneous infiltration of malignant monoclonal lymphocytes. Less frequently, these lymphomas spread from the skin to the blood or a lymph node. The incidence of primary cutaneous lymphoma has been estimated to be 1:100,000 according to the World Health Organization. Usually, these lymphomas affect adults with a median age of 50 to 60 years. T-cell lymphomas predominate over primary B-cell lymphomas of the skin. The most important subtypes of cutaneous T cell lymphomas are Mycosis fungoides, Sezary syndrome, and primary cutaneous peripheral T cell lymphomas not otherwise specified. These subtypes present different clinical, histological, and molecular features, and can follow an indolent or a very aggressive course.

Aim: The aim of this study was to analyze cutaneous lymphomas to ascertain its clinical aspects including prevalence, histopathology and immune profile.

Material and methods: A retrospective analysis of skin biopsies over a 7-year period ranging from 2016 to 2022 was done, of which 11 cases were diagnosed as cutaneous lymphomas. These cases were analyzed in detail including immune profile.

Results & conclusions: The majority of the cases out of all cutaneous lymphomas were of T cell lymphoma and only one case was of B cell type. Definitive diagnosis of CTCL requires a multidisciplinary approach.

Fatima Ezzahra Rizkou
ENT-HNS Department, Mohammed VI University Hospital Center, Marrakech, Morocco.

Yassine Jaouhari
ENT and Neck and Head Surgery Department; University Medical Center Mohammed VI. Marrakech, Morocco.

Youssef Lakhdar
ENT and Neck and Head Surgery Department; University Medical Center Mohammed VI. Marrakech, Morocco.

Othmane Benhoummad
ENT and Neck and Head Surgery Department, University Hospital of Agadir, Morocco.

Mohammed Chehbouni
ENT and Neck and Head Surgery Department; University Medical Center Mohammed VI. Marrakech, Morocco.

Omar Oulghoul
ENT and Neck and Head Surgery Department; University Medical Center Mohammed VI. Marrakech, Morocco.

Youssef Rochdi
ENT and Neck and Head Surgery Department; University Medical Center Mohammed VI. Marrakech, Morocco.

Abdelaziz Raji
ENT and Neck and Head Surgery Department; University Medical Center Mohammed VI. Marrakech, Morocco.

Mohamed Ilias Tazi
Hematology department; University Medical Center Mohammed VI. Marrakech, Morocco.

Ali Bouddounit
Anatomical Pathology Department, University Medical Center Mohammed VI. Marrakech, Morocco.

Hanane Rais
Anatomical Pathology Department, University Medical Center Mohammed VI. Marrakech, Morocco.

Abstract

Aims: Our goal was to obtain comprehensive and accurate information about primary extranodal non-Hodgkin lymphomas of the head and neck region to contribute to the advancement of medical knowledge in this field.

Materials and methods: We conducted a retrospective study of 341 patients with primary extra-nodal, non-Hodgkin lymphomas of the head and neck, over a period of 7 years from January 2016 to December 2022, in the departments of ENT and Head and Neck Surgery and Hematology, with the help of the department of anatomical pathology of the university hospital Mohammed VI of Marrakech.

Results: 341 patients, with primary extra-nodal, non-Hodgkin lymphomas of the head and neck, was included, with an average age of 57 years, and a sex ratio male/female of 2.21 . in more than half of the cases; Waldeyer’s ring was concerned; especially palatine tonsils. Type B NHL was the most frequent and involved 308 patients. Diffuse large B-cell lymphoma was the commonly observed histological type, found in 214 patients; followed by a Follicular Lymphoma and Extra-Nodal NK/T‑Cell Lymphoma, Nasal Type. Following the extension workup; patients were all staged according to the ANN ARBOR classification; with a 77.8% of them were localized stages I and II, and of the therapeutically evaluable cases, complete remission was achieved in 112 patients.

Conclusion: Our study focused on all extra-nodal localizations of NHL in the head and neck region. Due to the very heterogeneous nature of these tumors, most of the current studies are limited to a specific site of involvement. Nevertheless, our study provides an overall picture; which those specific studies can be based. The management of NHL has evolved considerably in recent years, insisting on the multidisciplinary character to a better management of these patients.

Joshua ML Casan
The Department of Clinical Haematology, The Royal Melbourne Hospital and Peter MacCallum Cancer Centre, Australia; Sir Peter MacCallum Department of Oncology, The University of Melbourne, Australia

Mary Ann Anderson
The Department of Clinical Haematology, The Royal Melbourne Hospital and Peter MacCallum Cancer Centre, Australia; The Division of Blood Cells and Blood Cancer, The Walter and Eliza Hall Institute, Australia

John F Seymour
The Department of Clinical Haematology, The Royal Melbourne Hospital and Peter MacCallum Cancer Centre, Australia; Sir Peter MacCallum Department of Oncology, The University of Melbourne, Australia

Abstract

Mantle cell lymphoma (MCL) is a rare B-cell non-Hodgkin lymphoma, and remains a clinically challenging disease entity, particularly in the relapsed setting where outcomes are poor. However, recent innovations in targeted therapeutics have expanded treatment options and demonstrate significant efficacy even in relapsed disease. MCL frequently harbours aberrations of apoptosis pathways including over-expression of the anti-apoptotic protein BCL2. Such aberrancy promotes and sustains lymphomagenesis, thus rendering MCL an attractive target for venetoclax, the highly specific, orally bioavailable inhibitor of BCL2. Pre-clinical and early clinical data of venetoclax monotherapy demonstrated high response rates in relapsed/refractory MCL, though the durability of response in high-risk patients appears modest. More recently, clinical trials deploying combination strategies that pair venetoclax with other novel agents have been undertaken, with some promising early data reported. In this article, we review the biological rationale for deploying venetoclax in MCL, as well as the emerging data from clinical trials of venetoclax monotherapy and novel combinations.

Christopher K. Williams, MD FRCPC
Department of Hematology, College of Medicine, University of Ibadan, Nigeria; Department of Medical Oncology, British Columbia Cancer Agency, Vancouver, Canada; Department of Medicine, University of British Columbia, Vancouver, Canada

Abstract

The African environment has for millennia been dominated by rampant agents of infections, of which malaria is among the best known, virtually uncontrolled, and associated with lifelong human struggles, ameliorarated by measures as socioeconomicaly affordable. This has led to the emergence of a variety of genetic aberrations, some of which are deleterious, resulting in major disease dysparities, including benign ones like sickle cell disease, and malignancies like the leukaemias, lymphomas, and breast cancer. They include the reduced incidence and the absence of its peak in acute lymphoblastic leukaemia in the first quinquennium of Nigerian children, which is otherwise typically seen in the children of high-income countries. Conversely is the observation in acute myelogenous leukaemia, with its chloroma-associated variant and its incidence peaking in the second quinquennium. This epidemiology is akin to the recent observation of acute myelogenous leukemia among sickle cell disease patients among the people of African descent in California, USA. Chloroma-associated acute myelogenous leukemia, and Burkitt lymphoma are linked with low socioeconomic status, an epidemiological feature that is shared with triple negative breast cancer patients in West Africa and the women of African descent in the United States. While a role for the malaria-associated genetic aberration underlying the Duffy null genotype is confirmed in the diversity of the triple negative breast cancer in the women of West Africa and those of African descent in the United States, it is conceivable, but not yet established in acute myelogenous leukemia. The zoonosis-linked human T-cell lymphotropic virus type 1 infection is associated with at least 17% of non-BL-non-Hodgkin lymphoma in form of its sentinel disease, the adult T-lymphoma/leukemia, but unexpicably much lower than the 50-60% of other major endemic zones of Japan and the African descendants of the Caribeean. This report describes the clinical, laboratory, and epidemiological features of leukemia and lymphoma cases diagnosed between 1982 and 1984 in the city of Ibadan, Nigeria, some of the features of which are reminiscent of the observations of Ludwig Gross’s experiments on environmental influences, such as malnutrition and infections, on animal leukemogenesis. These events are the consequences of the primordial pressures that have shaped human genetics and pathophysiology. Evidence provided in this study, indicating association of increasing socioeconomic status with increasing frequency of the c-ALL subtype, is indicative of the prospects for leukemogenesis of acute lymphoblastic leukemia and its epidemiology in Nigerians. Some findings reported here indicate the influence of the African genetic ancestry in the etiology of acute myelogenous leukemia, while socioecomic status is linked to the etiology of childhood acute lymphoblastic leukemia, as well as a variant of chronic lymphocytic leukemia, and the chloroma-associated acute myelogenous leukemia. These observations are suggestive of the existence of pathways to etiological discoveries in the leukemias. Observations reviewed in this paper reflect examples of changes that have occurred over the past 200 years in the societal perception of health challenges among the new-found communities of colonial Africa and the Americas – from the reductionistic connotations such as in the “virgin-soil theory” – towards that of social determinants of health.

Dr. Linu Abraham Jacob
Professor and Head, Department of Medical oncology, Kidwai Memorial Institute of Oncology, Dr. M. H. Marigowda road, Bengaluru Karnataka India

Dr Dayanand Sagar P
Senior resident, Department of Medical oncology, Kidwai Memorial Institute of Oncology, Dr. M. H. Marigowda road, Bengaluru Karnataka India

Dr. Animesh Gupta
Senior Resident, Department of Medical oncology, Kidwai Memorial Institute of Oncology, Dr. M. H. Marigowda road, Bengaluru Karnataka India

Dr Priya D
Associate Professor, Department of Pathology, Kidwai Memorial Institute of Oncology, Dr. M. H. Marigowda road, Bengaluru Karnataka India

Dr. M C Suresh Babu
Professor, Department of Medical oncology, Kidwai Memorial Institute of Oncology, Dr. M. H. Marigowda road, Bengaluru Karnataka India

Dr. Lokesh K N
Associate Professor, Department of Medical oncology, Kidwai Memorial Institute of Oncology, Dr. M. H. Marigowda road, Bengaluru Karnataka India

Dr. A H Rudresha
Associate Professor, Department of Medical oncology, Kidwai Memorial Institute of Oncology, Dr. M. H. Marigowda road, Bengaluru Karnataka India

Dr. Rajeev L K
Associate Professor, Department of Medical oncology, Kidwai Memorial Institute of Oncology, Dr. M. H. Marigowda road, Bengaluru Karnataka India

Dr. Smitha C Saldanha
Associate Professor, Department of Medical oncology, Kidwai Memorial Institute of Oncology, Dr. M. H. Marigowda road, Bengaluru Karnataka India

Abstract

Lymphomatoid papulosis (LyP) is a rare skin disease which is characterised by chronic, recurrent self-healing papulo-nodular skin lesions. It is classified under the group of primary cutaneousCD30+ve lymphoproliferative disorders. It is important to diagnose LyP as it is usually associated with other malignant lymhoproliferative disorders like mycosis fungoides, cutaneous or systemic anaplastic large cell lymphoma and Hodgkin’s lymphoma. LyP associated malignancies may occur before, concurrent with or after the onset of LyP. In most of the cases previously described, Hodgkin’s disease has developed after, or concurrently with, the onset of LyP. Here we report a case of LyP that developed 5 years after the onset and therapy for Hodgkin’s lymphoma.

David Tucker
Royal Cornwall Hospital NHS Trust

Cristina M. Thiebaud

Abstract

The management of non-Hodgkin lymphoma (NHL), including refractory and relapsed high grade and low-grade NHL has been significantly improved in recent years with the development of cellular therapies which harness the powerful anti-cancer effects of the immune system. These include the ground-breaking and now established technology of chimeric antigen receptor cell therapy as well as the promising new range of bispecific monoclonal antibody therapies. This article will give a summary of the currently available cellular and bi-specific antibody therapies for the treatment of NHL in licenced use and clinical trials, including an overview of their proven efficacy and characteristic side-effect profiles which distinguish them from conventional immunochemotherapy.  The relative strengths and weaknesses of these comparable therapies will also be discussed together with consideration of where they may fit into the treatment sequence of NHL in the future.  The article will also address the challenges of delivering these innovative technologies in different healthcare settings and how they may alter the future of therapy for patients with this form of cancer.

Noah Giese
Department of Academic Medicine, Houston Methodist Hospital, 6550 Fannin St, Smith 1001, Houston, TX 77030 Houston, TX, USA.

Shubham Adroja
Houston Methodist Neal Cancer Center, Houston Methodist Hospital, 6445 Main Street, Outpatient Center, 24th Floor, Houston, TX 77030, USA.

Hala Hassanain
Department of Academic Medicine, Houston Methodist Hospital, 6550 Fannin St, Smith 1001, Houston, TX 77030 Houston, TX, USA.

Meera Khosla
Department of Academic Medicine, Houston Methodist Hospital, 6550 Fannin St, Smith 1001, Houston, TX 77030 Houston, TX, USA.

Jacqueline Rios
Department of Academic Medicine, Houston Methodist Hospital, 6550 Fannin St, Smith 1001, Houston, TX 77030 Houston, TX, USA.

Sai Ravi Pingali
Houston Methodist Neal Cancer Center, Houston Methodist Hospital, 6445 Main Street, Outpatient Center, 24th Floor, Houston, TX 77030, USA.

Ethan A Burns, MD.
Department of Academic Medicine, Houston Methodist Hospital, 6550 Fannin St, Smith 1001, Houston, TX 77030 Houston, TX, USA; Houston Methodist Neal Cancer Center, Houston Methodist Hospital, 6445 Main Street, Outpatient Center, 24th Floor, Houston, TX 77030, USA.

Abstract

Diffuse Large B-cell Lymphoma (DLBCL) is classically a disease of older individuals. However, varying definitions of “older” age, underrepresentation in clinical trials, and significant patient heterogeneity requires a highly personalized treatment approach. Older patients often have comorbidities leading to decreased tolerance with standard of care therapies; however, predictive tools such as the simplified Comprehensive Geriatric Assessment may help tailor treatments accordingly. Several approaches have been introduced to augment therapeutic tolerance in the front-line setting, including prephase therapies, attenuation of current standard of care chemoimmunotherapy dosing, or alternative chemotherapeutic agents when prohibitive comorbidities such as cardiovascular disease are present. In the relapsed and refractory disease setting antibody-based therapies have improved outcomes and demonstrated therapeutic tolerance in older patients. Cellular therapies and bone marrow transplantation remain options for fit patients who are eligible and should be considered. The aim of this review is to focus on patient assessment and treatment recommendations in older patients with DLBCL.

Ruben Reinhard
University Center for Plastic, Reconstructive, Aesthetic and Hand Surgery, University Hospital Regensburg, Germany

Niklas Biermann
University Center for Plastic, Reconstructive, Aesthetic and Hand Surgery, University Hospital Regensburg, Germany

Britta Kuehlmann
Division of Plastic, Reconstructive Surgery, Department of Surgery, Stanford University, USA

Lukas Prantl
University Center for Plastic, Reconstructive, Aesthetic and Hand Surgery, University Hospital Regensburg, Germany

Abstract

Background: Breast implant–associated anaplastic large cell lymphoma (BIA ALCL) is a rare indolent yet lethal disease. Recently the WHO accepted it as an individual new entity. Since then national and international registries have attempted to collect epidemiological data, but incidence rates vary strongly. The aim of this article is to provide an update on the status of the national BIA-ALCL registries and identify pitfalls alongside the current collection and diagnostic algorhythm.

Methods: A systematic review of the literature was performed and epidemiological data from national registries were compared. Furthermore a case report of a false positive diagnosis was added and the pitfalls alongside the diagnostic algorhythm was worked out.

Results: The comparison of national registries revealed significant differences in the collected data. Mean start of the registries was 2014, median 2015. Reporting of BIA-ALCL cases is mandatory except in two countries. Capture rates vary between 0-100%. Incidence rates range from 0.0 up to 8.9 per million implant years. The number of deaths does not correlate with the number of implants or the total population. The very same strains of CD30 can be interpreted differently.

Conclusion: Comparing epidemiologic data revealed significant differences among national registries. In particular, non-published sales data of breast implants and non-mandatory recording of the disease lead to an overall underreporting of cases. Therefore, the incidence rates still cannot be compared uniformly. Furthermore the definition of CD30 straining intensity should be standardized and adjusted in the guidelines.

David Tucker
Royal Cornwall Hospital NHS Trust

Cristina M. Thiebaud

Abstract

The management of non-Hodgkin lymphoma (NHL), including refractory and relapsed high grade and low-grade NHL has been significantly improved in recent years with the development of cellular therapies which harness the powerful anti-cancer effects of the immune system. These include the ground-breaking and now established technology of chimeric antigen receptor cell therapy as well as the promising new range of bispecific monoclonal antibody therapies. This article will give a summary of the currently available cellular and bi-specific antibody therapies for the treatment of NHL in licenced use and clinical trials, including an overview of their proven efficacy and characteristic side-effect profiles which distinguish them from conventional immunochemotherapy.  The relative strengths and weaknesses of these comparable therapies will also be discussed together with consideration of where they may fit into the treatment sequence of NHL in the future.  The article will also address the challenges of delivering these innovative technologies in different healthcare settings and how they may alter the future of therapy for patients with this form of cancer.

Dhanya Mohan
Department of Neprology, Dubai hospital, Dubai, United Arab Emirates

Amna Khalifa Alhadari
Department of Neprology, Dubai hospital, Dubai, United Arab Emirates

Dileep Kumar
Department of Neprology, Dubai hospital, Dubai, United Arab Emirates

Sima Abdolla Nejad
Department of Neprology, Dubai hospital, Dubai, United Arab Emirates

Rahaf Mohamad Wardeh
Department of Internal Medicine, Dubai hospital, Dubai, United Arab Emirates

Batool Khan
Dubai Medical College for Girls, Dubai, United Arab Emirates

Madheeha Mahmood
Dubai Medical College for Girls, Dubai, United Arab Emirates

Zuha Fathima
Dubai Medical College for Girls, Dubai, United Arab Emirates

Mohammed Railey
Department of Neprology, Dubai hospital, Dubai, United Arab Emirates

Abstract

Cryoglobulinemic vasculitis presents with systemic vasculitis including vasculitic rash, fever, peripheral neuropathy, and, in rare cases renal involvement. This could be secondary to infections like hepatitis C, malignancies like myeloma, Non Hodgkin’s lymphoma and chronic lymphocytic leukemia. We encountered a patient who presented with fever, anemia, purpuric skin rash and acute kidney injury due to acute glomerulonephritis with nephritic picture and fluid overload that required hemodialysis.Investigations revealed hemolytic anemia, cryoglobulinemia, proliferative glomerulonephritis with Ig M intra-capillary deposits and hyaline thrombi. Bone marrow biopsy clinched the diagnosis of Chronic lymphocytic B cell lymphoma with CD 20 positivity. Treatment was instituted with Rituximab and Bendamustine. Plasmapheresis was done for hyperviscosity syndrome. With treatment, hemodialysis could be discontinued after 10 weeks and renal functions recovered partially with serum creatinine settling at 1.5 mg/dl. We present this case to highlight the presentation of chronic lymphocytic leukemia with cryoglobulinemic vasculitis that presented with purpura and rapidly progressive renal failure that required dialysis.

Noah Giese
Department of Academic Medicine, Houston Methodist Hospital, 6550 Fannin St, Smith 1001, Houston, TX 77030 Houston, TX, USA.

Shubham Adroja
Houston Methodist Neal Cancer Center, Houston Methodist Hospital, 6445 Main Street, Outpatient Center, 24th Floor, Houston, TX 77030, USA.

Hala Hassanain
Department of Academic Medicine, Houston Methodist Hospital, 6550 Fannin St, Smith 1001, Houston, TX 77030 Houston, TX, USA.

Meera Khosla
Department of Academic Medicine, Houston Methodist Hospital, 6550 Fannin St, Smith 1001, Houston, TX 77030 Houston, TX, USA.

Jacqueline Rios
Department of Academic Medicine, Houston Methodist Hospital, 6550 Fannin St, Smith 1001, Houston, TX 77030 Houston, TX, USA.

Sai Ravi Pingali
Houston Methodist Neal Cancer Center, Houston Methodist Hospital, 6445 Main Street, Outpatient Center, 24th Floor, Houston, TX 77030, USA.

Ethan A Burns, MD.
Department of Academic Medicine, Houston Methodist Hospital, 6550 Fannin St, Smith 1001, Houston, TX 77030 Houston, TX, USA; Houston Methodist Neal Cancer Center, Houston Methodist Hospital, 6445 Main Street, Outpatient Center, 24th Floor, Houston, TX 77030, USA.

Abstract

Diffuse Large B-cell Lymphoma (DLBCL) is classically a disease of older individuals. However, varying definitions of “older” age, underrepresentation in clinical trials, and significant patient heterogeneity requires a highly personalized treatment approach. Older patients often have comorbidities leading to decreased tolerance with standard of care therapies; however, predictive tools such as the simplified Comprehensive Geriatric Assessment may help tailor treatments accordingly. Several approaches have been introduced to augment therapeutic tolerance in the front-line setting, including prephase therapies, attenuation of current standard of care chemoimmunotherapy dosing, or alternative chemotherapeutic agents when prohibitive comorbidities such as cardiovascular disease are present. In the relapsed and refractory disease setting antibody-based therapies have improved outcomes and demonstrated therapeutic tolerance in older patients. Cellular therapies and bone marrow transplantation remain options for fit patients who are eligible and should be considered. The aim of this review is to focus on patient assessment and treatment recommendations in older patients with DLBCL.

Peter Vajdovich
Department of Clinical Pathology and Oncology, University of Veterinary Medicine, 1078, István u. 2., Budapest, Hungary

Bernadett Szabó
Department of Clinical Pathology and Oncology, University of Veterinary Medicine, 1078, István u. 2., Budapest, Hungary

Noémi Tarpataki
Department of Internal Medicine, University of Veterinary Medicine, 1078, István u. 2., Budapest, Hungary

Judit Jakus
Department of Clinical Pathology and Oncology, University of Veterinary Medicine, 1078, István u. 2., Budapest, Hungary

Abstract

Purpose: Oxidative stress is a contributor in the development of neoplasms. OS is involved in multidrug resistance, adverse events, and outcome.

Methods: Forty- two dogs with lymphoma have been included in the study, 30 of which were treated by Cyclophosphamide – Hydroxyldaunorubicin® (doxorubicin) – Oncovin® (vincristine) – Prednisolone (CHOP)-based protocol. Tumor samples were excised for histopatholgy, immunophenotyping, Ki67%, and biochemical analyses. Thiobarbituric acid reactive substances (TBARS), reduced and oxidized glutathione (GSH, GSSG), glutathione peroxidase (GSH-Px), Cu-Zn-superoxide dismutase (SOD), ferric reducing ability (FRAP), vitamin-C, -E, retinyl palmitate and trans-retinol in red blood cell hemolysates, lymph node homogenates, and blood plasma have been measured. The results were correlated with the outcome of the chemotherapy.

Results: Median overall survival time (OST), relapse-free period (RFP) were 862 and 280 days, respectively, with adverse effects in 18 cases.

Plasma GSH levels increased with age (dogs from 1 to 6 years vs 9 to 13 years, p = 0.0385). Lymph node FRAP levels were higher in samples with higher Ki67%, and plasma GSH/GSSG ratio was lower in dogs with increased OST and RFP. Plasma retinyl palmitate levels were lower in dogs with increased RFP. Overall survival time was increased with lower lymph node TBARS (cut off: 53 nmol/mg protein), GHS-Px (cut off: 16 U/mg protein), and higher plasma all-trans-retinol (cut off: 4 mg/ml). Relapse-free period was increased with lower lymph node TBARS (cut off: 53 nmol/mg protein), lower FRAP (cut off: 6 µmol/mg) and higher SOD (cut off: 70 U/mg protein). During chemotherapy a gradual increase in plasma vitamin E and C concentrations was detected, while GSH and GSSG showed a decrease before adverse events.

Conclusion: Although oxidative stress parameters varied, some parameters, i.e. TBARS, GSH-Px, SOD, FRAP measured in lymph node samples, and plasma all-trans retinol might be used as prognostic indices.

Chutika Srisuttiyakorn, M.D.
1 Division of Dermatology, Department Of Medicine, Phramongkutklao Hospital, Bangkok, Thailand

Patcharasiri Bocam, M.D.
1 Division of Dermatology, Department Of Medicine, Phramongkutklao Hospital, Bangkok, Thailand

Abstract

Background: Hypopigmented mycosis fungoides (MF) is a variant of primary cutaneous T-cell lymphoma. Although the prognosis of hypopigmented mycosis fungoides is excellent, the diagnosis is usually missed.

Objective: The study aimed to identified the prevalence of patients with hypopigmented mycosis fungoides presenting hypopigmentation in Phramongkutklao Hospital, Bangkok, Thailand. We also reported the characteristic of hypopigmented mycosis fungoides among patients presenting hypopigmentation and compared clinical presentations between patients with a diagnosis of hypopigmented mycosis fungoides and patients with other diagnoses

Materials and Methods: We conducted a retrospective among 56 patients presenting hypopigmentation and receiving skin biopsies at Division of Dermatology, Department of Medicine, Phramongkutklao Hospital, Bangkok, Thailand between January 2016 to December 2021. The data parameters including demographic data, clinical manifestations (symptoms, size and morphology of the lesions, e.g., scale, margin, erythema, atrophy, mottled hypopigmentation, involved body surface area and distribution, histopathologic reports, special stains, final diagnosis, further investigations, treatments, follow-up duration and result of the treatments were recorded.

Results: The prevalence of hypopigmented mycosis fungoides among patient presenting with hypopigmentation was 16.1%. Compared with patients with other diagnoses, patients with hypopigmented mycosis fungoides usually had lesions with ill-defined margins (P-value=0.045) and presence of atrophy lesion (P-value=0.023).

Conclusion: The prevalence of hypopigmented mycosis fungoides involved 16.1% of patients presenting hypopigmentation. The presence of ill-defined margins and atrophic lesions led to suspected hypopigmented MF in our study. This data could be useful in epidemiologic information and might be adapted when choosing lesions for biopsy to diagnose MF.

Tyler R. Harrison
Department of Communication Studies, University of Miami, Coral Gable, Florida, USA

Jessica Wendorf Muhamad
School of Communication, Florida State University, Tallahassee, Florida, USA

Ekaterina Malova
Simon Business School, University of Rochester, Rochester, New Yor, USA

Abstract

Objective: This paper provides a review of current knowledge and trends in research on firefighters cancer risks and risk reduction efforts and calls for future research focused on European and international firefighters to understand and reduce occupational cancer risk.

Cancer incidence: Firefighters face increased occupational cancer risk.  Firefighting has been linked with multiple types of cancer, including bladder, colorectal, brain and central nervous system, non-Hodgkin’s lymphoma, skin melanoma, and prostate and testicular cancer, with several others types of cancer being found at increased rates.

Cancer risks: Increased occupational cancer risk is, in part, related to carcinogenic exposures at fire events and improper use and cleaning of personal protective equipment (PPE), with role and years in service increasing risk.

Risk Perception: Research on efforts to reduce cancer risk are growing, and include examination of firefighter knowledge, attitudes, norms, and behaviors toward decontamination, screening, and healthy eating. Many firefighters report high perceived susceptibility and severity of cancer risk, and identify fire scene exposures, contaminated gear, diet, sleep disruption, chemical exposure from cleaning products, and barriers to medical care as contributing to increased risk.

Risk Reduction: Firefighters have strong desire to reduce cancer risk and report generally favorable attitudes toward decontamination practices and proper gear use, but face barriers to reducing those risks, including lack of knowledge, occupational needs, organizational culture, policy, and lack of resources. Behavioral interventions to reduce cancer risk through decontamination efforts and dietary change have demonstrated positive results, however there is a dearth of research on these efforts, especially with European and international firefighters.

Future Directions: Future research should focus on understanding European and international firefighters’ knowledge, attitudes, and behaviors toward cancer risk reduction, the impact of the built environment on cancer risk (station layout, clean cabs), improved efforts at tracking exposures, use of new technology and virtual reality in training to reduce cancer risk, and improved understanding of firefighter cancer risk by medical professionals.

Dr. Linu Abraham Jacob, Professor and Head
Department of Medical oncology; Kidwai Memorial Institute of Oncology, Dr. M. H. Marigowda road, Bengaluru Karnataka India

Dr. Animesh Gupta, Senior resident
Department of Medical oncology; Kidwai Memorial Institute of Oncology, Dr. M. H. Marigowda road, Bengaluru Karnataka India

Dr. Kanika Sharma
Department of Medical Oncology; MAX Super Specialty Hospital, Mohali Punjab

Dr. M C Suresh Babu, Professor
Department of Medical oncology; Kidwai Memorial Institute of Oncology, Dr. M. H. Marigowda road, Bengaluru Karnataka India

Dr. Lokesh K. N., Associate Professor
Department of Medical oncology; Kidwai Memorial Institute of Oncology, Dr. M. H. Marigowda road, Bengaluru Karnataka India

Dr. A H Rudresha, Associate Professor
Department of Medical oncology; Kidwai Memorial Institute of Oncology, Dr. M. H. Marigowda road, Bengaluru Karnataka India

Dr. Rajeev L. K.,, Associate Professor
Department of Medical oncology; Kidwai Memorial Institute of Oncology, Dr. M. H. Marigowda road, Bengaluru Karnataka India

Dr. Smitha C. Saldanha, Associate Profesor
Department of Medical oncology; Kidwai Memorial Institute of Oncology, Dr. M. H. Marigowda road, Bengaluru Karnataka India

Dr. Usha Amirtham, Professor and Head
Department of Pathology; Kidwai Memorial Institute of Oncology, Dr. M. H. Marigowda road, Bengaluru Karnataka India

Abstract

PURPOSE – Diffuse Large B-Cell Lymphoma can be subclassified into the prognostically distinct groups of GCB and non-GCB using the immunohistochemical Hans algorithm. However, in real life, patients classified as GCB show differing outcomes even when treated with the same chemotherapy regimen. CD10 is a GCB marker, while MUM1 is a non-GCB marker, but Hans algorithm classifies CD10+ MUM1+ patients as GCB DLBCL. We explored whether CD10+ MUM1+ GCB DLBCL patients had different outcomes compared to rest of the GCB DLBCL patients.

METHODS – In this study, we retrospectively analyzed the clinical records of 427 DLBCL patients treated with standard chemo-immunotherapy at Kidwai Memorial Institute of Oncology, Bengaluru from 2013 to 2019. The clinical characteristics, response rate and overall survival of CD10+ MUM1+ GCB group was compared with MUM1-ve GCB group and non-GCB group.

RESULTS – Among the patients studied, 187 (43%) patients were of GCB subtype, whereas 240 (57%) patients belonged to the non-GCB subtype. Additionally, 61 (14.3%) patients were of the CD10+ MUM1+ GCB immune-phenotype. No significant differences could be demonstrated in the clinical characteristics of CD10+ MUM1+ GCB and MUM1- GCB patients. Patients with CD10+ MUM1+ GCB subtype exhibited a significantly inferior response rate compared to those with MUM1- GCB subtype (81% versus 92%; p=0.04). Although, both non-GCB and CD10+ MUM1+ GCB subtypes displayed diminished overall survival in comparison to MUM1- GCB patients, (non-GCB = 33 months, CD10+ MUM1+ GCB = 33 months and MUM1-ve GCB = 40.4 months, p = 0.21) it did not reach statistical significance

CONCLUSION – CD10+ MUM1+ GCB patients may be prognostically more similar to non-GCB patients, as suggested by the inferior response rates and numerically inferior OS comp

Mukund Tinguria
Department of Pathology and Laboratory Medicine Brantford General Hospital 200 Terrace Hill Street Brantford, Ontario Postal Code – N3R 1G9 Canada

Abstract

Celiac disease (CD) is an immune mediated disorder characterised by intolerance to glutens in certain grains like whet, barley, and rye. The exposure to gliadin protein component in the susceptible individuals leads to an inflammatory reaction damaging small bowel mucosa with progressive disappearance of intestinal villi. The damaged intestinal mucosa leads to malabsorption. The usual symptoms of celiac disease include diarrhea, steatorrhea, weight loss, fatigue, and abdominal pain. Diagnosis is based on clinical features, duodenal biopsy, elevated levels of anti-gliadin antibodies and response to gluten free diet. Contrary to common belief, celiac disease is a protein systemic disease rather than merely a pure digestive alteration. Celiac disease is closely associated with genes that code HLA -II antigens mainly of DQ2 and DQ8 classes, production of disease specific antibodies (i.e., endomysial antibodies), multiorgan involvement, comorbidity with other autoimmune diseases (shared autoimmunity), familial aggregation, and immune system dysregulation.

The clinical presentation of celiac disease can be variable. In mild form, patients can be almost asymptomatic whereas in the most severe form, the patients are at increased risk of life-threatening complications. Celiac disease has a well-known association with other autoimmune diseases such as autoimmune liver diseases (autoimmune hepatitis, primary biliary cirrhosis, primary sclerosing cholangitis), diabetes mellitus, autoimmune thyroid diseases, skin diseases such as dermatitis herpetiformis, rheumatoid arthritis, systemic lupus erythematosus, Sjogren’s syndrome, psoriasis, sarcoidosis, immune thrombocytopenic purpura, and pancreatitis. In addition, celiac disease may be associated with rare but potentially serious complications such as, collagenous sprue, ulcerative jejunoileitis, refractory celiac disease (RCD), enteropathy associated T-cell lymphoma, small bowel adenocarcinoma (SBA), hyposplenism, and cavitating mesenteric lymph node syndrome (CMLNS). The present article describes clinicopathologic features of these rare but serious complications of celiac disease.

Anjum Siddiqui
Dr. Anjum Siddiqui, Senior Resident, Department of Medicine, LHMC & Smt.SK Hospital, New Delhi

Aparna Agrawal
Director Professor, Department of Medicine, LHMC& Smt S.K Hospital, New Delhi

Praveen Kumar
Director Professor, Department of Paediatrics, LHMC& Kalawati Saran Children’s Hospital, New Delhi

Lekhraj Hemraj Ghotekar
Head of Department and Director Professor, Department of Medicine, LHMC& Smt S.K Hospital, New Delhi

Sanjana Taneja
MBBS, Lady Hardinge Medical College and associated Hospitals, New Delhi

Abstract

Gluten, in genetically susceptible individuals induces an immune mediated enteropathy called Celiac disease (CD). It is an established cause of malabsorption, with the worldwide prevalence being 1% in the general population. It is found across all age groups, from infants to the elderly with 20% patients being diagnosed in the seventh decade of life. It has varying clinical presentations ranging from silent asymptomatic forms which are diagnosed during screening to life threatening forms with severe malabsorption to atypical presentations, with the symptom spectrum extending beyond the gastrointestinal tract which are more common in adults. High index of suspicion, robust screening and testing, followed by strict adherence to gluten free diet is a must to curb and cure the disease. Patients tend to face difficulties not only during diagnosis, but also with compliance and availability of a gluten free diet, in addition to significant economic and psychosocial burden, which is more predominant in developing countries. Screening of high-risk groups like first-degree relatives of celiac disease, patients with severe malnutrition, other autoimmune diseases, refractory anaemia and irritable bowel syndrome should be done to enhance case detection. In low middle income countries, judicious resource utilisation takes precedence, hence, tackling a multifactorial disease such as celiac disease becomes challenging. Repeated follow ups, awareness among patients and doctors, encouragement, availability of testing and dietary counselling is necessary for management of the disease in such settings. Improving sanitation and feeding practices may also play role in decreasing incidence, considering childhood GI infections are a well-established risk factor. Increased availability of serological tests (IgA/IgG anti-tTG, anti -EMA and anti-DGP), biopsy, genetic testing and other newer modalities under research have improved the diagnostic accuracy. Poor compliance increases the risk of GI malignancy, non-Hodgkin’s lymphoma, Hepatocellular carcinoma and MALToma. Hence adherence is a must to prevent complications. A wide variety of treatment modalities are being evaluated to bring into force alternative strategies for management. Only providing gluten free diet is often not sufficient for improvement of nutritional status in patients with CD. Hence, micronutrient supplementation should also be encouraged to meet the unmet needs.

Arthur Edward Frankel
Department of Medicine, West Palm Beach VA Medical Center, West Palm Beach, FL

Tazio Capozzola, Mr.
Immunology graduate student, The Scripps Research Institute, La Jolla, CA, USA

Raiees Andrabi, PhD
Investigator, The Scripps Research Institute, La Jolla, CA, USA

Chul Ahn, PhD
Division of Biostatistics, Department of Population and Data Sciences, University of Texas Southwestern Medical School, Dallas,TX, USA

Wan-ting He, PhD
Scientist , The Scripps Research Institute, La Jolla, CA, USA

Dennis R. Burton, Dr.
Laboratory Chief, The Scripps Research Institute, La Jolla, CA, USA

Abstract

Immunocompromised cancer patients are at significant risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. A method to identify those patients at highest risk is needed so that prophylactic measures may be employed. Serum antibodies to SARS-CoV-2 spike protein are important markers of protection against COVID-19 disease. We evaluated total and neutralizing antibody levels pre and post third booster vaccine and compared responses among different cancer-bearing and healthy veterans. This as a prospective, single site, comparative cohort observational trial. The setting was the West Palm Beach VA Medical Center cancer center. All veterans received a third SARS-CoV-2 mRNA booster. The main outcomes were anti-SARS-CoV-2 spike IgG and neutralizing antibodies to wild-type, and B.1.617, BA1, BA2, and BA4/5 variants were measured. Disease type and therapy, COVID-19 infection, and anti-CD20 antibody treatments were documented. The third mRNA vaccine booster increased the mean blood anti-spike IgG five-fold. The second anti-spike level was equal or greater than the first in 129/140 veterans. All the groups except the myeloma group, had post-booster antibody levels significantly higher than pre-booster with 4-fold, 12-fold, 4-fold, 6-fold and 3.5-fold increases for the control, solid tumor, CLL, B cell lymphoma and all B cell malignancy cohorts. The myeloma set showed only a non-significant 1.7-fold increase. Recently anti-CD20 antibody-treated patients were shown to have approximately 200-fold less anti-S IgG production after vaccine booster than other patients. There was a 2.5-fold enhancement of wild-type virus mean neutralizing antibodies after a third mRNA booster and mean neutralization of Delta and Omicron variants increased 2.2, 6.5, 7.7, and 6.2-fold versus pre-boost levels. B cell malignancies failed to show increased post-booster neutralization. The third SARS CoV-2 booster increased total anti-spike IgG and neutralizing antibodies for most subjects. Veterans with B cell malignancies particularly myeloma and those receiving anti-CD20 monoclonal antibodies had the weakest humoral responses. Neutralizing antibody responses to Omicron variants were less than for wild-type virus. A subset of patients without humoral immunity post-booster should be considered for prophylactic antibody or close monitoring.

Victor E. Reyes
University of Texas Medical Branch at Galveston

Abstract

Pylori is perhaps the most prevalent human pathogen worldwide and infects almost half of the world’s population. Despite the decreasing prevalence of infection overall, it is significant in developing countries. Most infections are acquired in childhood and persist for a lifetime unless treated. Children are often asymptomatic and often develop a tolerogenic immune response that includes T regulatory cells and their products, immunosuppressive cytokines, such as interleukin (IL)-10, and transforming growth factor-β (TGF-β). This contrasts to the gastric immune response seen in H. pylori-infected adults, where the response is mainly inflammatory, with predominant Th1 and Th17 cells, as well as, inflammatory cytokines, such as TNF-α, IFN-γ, IL-1, IL-6, IL-8, and IL-17. Therefore, compared to adults, infected children generally have limited gastric inflammation and peptic ulcer disease. H. pylori surreptitiously subverts immune defenses to persist in the human gastric mucosa for decades. The chronic infection might result in clinically significant diseases in adults, such as peptic ulcer disease, gastric adenocarcinoma, and mucosa-associated lymphoid tissue lymphoma. This review compares the infection in children and adults and highlights the H. pylori virulence mechanisms responsible for the pathogenesis and immune evasion.

Jan S. Moreb
Hematology, Transplantation and Cellular Therapy, Novant Health Cancer Institute, Winston Salem, NC

Amanda Edwards
Hematology, Transplantation and Cellular Therapy, Novant Health Cancer Institute, Winston Salem, NC

Savannah Perry
Hematology, Transplantation and Cellular Therapy, Novant Health Cancer Institute, Winston Salem, NC

James Dugan
Hematology, Transplantation and Cellular Therapy, Novant Health Cancer Institute, Winston Salem, NC

Raymond Thertulien
Hematology, Transplantation and Cellular Therapy, Novant Health Cancer Institute, Charlotte, NC

Kathleen Elliott
Hematology, Transplantation and Cellular Therapy, Novant Health Cancer Institute, Winston Salem, NC

Alan P Skarbnik
Hematology, Transplantation and Cellular Therapy, Novant Health Cancer Institute, Charlotte, NC

Kimberly Ward
Hematology, Transplantation and Cellular Therapy, Novant Health Cancer Institute, NC

Abhishek R. Chilkulwar
Hematology, Transplantation and Cellular Therapy, Novant Health Cancer Institute, Charlotte, NC

Patricia L Kropf
Hematology, Transplantation and Cellular Therapy, Novant Health Cancer Institute, Charlotte, NC

Franklin Chen
Hematology, Transplantation and Cellular Therapy, Novant Health Cancer Institute, Winston Salem, NC

Abstract

COVID 19 infection had significant impact, including high mortality rate, in immunosuppressed patients including patients with hematological malignancies undergoing hematopoietic stem cell transplantation. This retrospective study describes the characteristics and outcomes of COVID 19 infection in autologous stem cell transplantation (ASCT) recipients. The time period for the study was Feb 2020 to Feb 2022. During that time 29 patients (28%) out of 102 ASCT recipients became infected with COVID 19 diagnosed by PCR test. 22 and 7 were multiple myeloma (MM) and lymphoma (Ly) patients, respectively.  Infection rate was 30.5% among MM patients and 23% among Ly patients. Median age was 59 years, 16 were females, 45% were Caucasians. Eight patients had infection prior to first ASCT, and one prior to second ASCT. Nine developed the infection within 12 months post ASCT. 6 patients had 2nd episode of infection within 8-20 months from 1st episode, only one patient required hospitalization. One MM patient contracted the infection from his relatives while in the hospital undergoing ASCT. He was one of total of 3 deaths from COVID infection. All 3 patients had significant comorbidities including 2 on dialysis and the 3rd had chronic kidney failure stage 3B, all were MM patients within < 1 year from ASCT. Two of them were vaccinated with the primary shots but no boosters. Overall, 8 patients were hospitalized due to COVID infection, 7 had multiple comorbidities and 6 had low absolute lymphocyte counts (ALC). Sixteen patients were noted to have low ALC around the time of infection, 5 were Ly patients. Seven patients had no symptoms, only 3 of them were vaccinated. Overall, 12 were vaccinated at the time of infection. 10 patients received monoclonal antibodies after they became positive for COVID. Evusheld was given to 2 patients. Other treatments used mainly in hospitalized patients include dexamethasone, remdesivir, and fresh frozen plasma. In conclusion, our patient population seems to have done better than published reports with about 10% mortality from COVID infection. Comorbidities, especially advanced renal failure, and low ALC may have contributed to worse morbidity and mortality outcomes.

A Mallum
Department of Radiotherapy and Oncology, University of KwaZulu-Natal, Durban 4041, South Africa; Department of Oncology, Inkosi Albert Luthuli Central Hospital, Durban 4091, South Africa

F A Barry
Johns Hopkins University School of Medicine, Baltimore, Maryland, MD 21205, USA

M B Tendwa
South Africa Health Product Regulatory Authority, Pretoria, South Africa

A O Joseph
NSIA-LUTH Cancer Treatment Center, Lagos University Teaching Hospital, Lagos 100254, Nigeria

L Keno
Johns Hopkins University School of Medicine, Baltimore, Maryland, MD 21205, USA

K M Graef
BIO Ventures for Global Health, Seattle, WA 98121, USA

S Kibudde
Uganda Cancer Institute, Kampala, Uganda

H Li
Johns Hopkins University School of Medicine, Baltimore, Maryland, MD 21205, USA

A Ajose
NSIA-LUTH Cancer Treatment Center, Lagos University Teaching Hospital, Lagos 100254, Nigeria

E Lugina
Ocean Road Cancer Institute, Dar Es Salaam 3592, Tanzania

M T Ngoma
Ocean Road Cancer Institute, Dar Es Salaam 3592, Tanzania

J D Kisukari
Ocean Road Cancer Institute, Dar Es Salaam 3592, Tanzania

K Awusi
Uganda Cancer Institute, Kampala, Uganda

S O Adeneye
NSIA-LUTH Cancer Treatment Center, Lagos University Teaching Hospital, Lagos 100254, Nigeria

T Mkhize
Department of Radiotherapy and Oncology, University of KwaZulu-Natal, Durban 4041, South Africa; Department of Oncology, Inkosi Albert Luthuli Central Hospital, Durban 4091, South Africa

A Alabi
NSIA-LUTH Cancer Treatment Center, Lagos University Teaching Hospital, Lagos 100254, Nigeria

I El Hamamsi
NSIA-LUTH Cancer Treatment Center, Lagos University Teaching Hospital, Lagos 100254, Nigeria

M A Mseti
Ocean Road Cancer Institute, Dar Es Salaam 3592, Tanzania

A Studen
University of Ljubljana, Faculty of Mathematics and Physics, Ljubljana 1000, Slovenia; Jožef Stefan Institute, Ljubljana 1000, Slovenia

J Lehmann
Department of Radiation Oncology, Calvary Mater Newcastle, Newcastle, NSW 2298, Australia; Institute of Medical Physics, The University of Sydney, Sydney, NSW 2006, Australia; School of Information and Physical Sciences, University of Newcastle, Newcastle, NSW, Australia

W Swanson
Department of Radiation Oncology, Weill Cornell Medicine, New York, NY 10065, USA

K Wijesooriya
Department of Radiation Oncology, University of Virginia School of Medicine, Charlottesville, Virginia

S Avery
Department of Radiation Oncology, Perelman Center for Advanced Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA

M S Huq
Department of Radiation Oncology, UPMC Hillman Cancer Center, Pittsburgh, PA 15232, USA

L Incrocci
Department of Radiotherapy, Erasmus MC, Rotterdam, Netherlands

W Ngwa
Johns Hopkins University School of Medicine, Baltimore, Maryland, MD 21205, USA; Brigham and Women’s Hospital, Dana-Farber Cancer Institute, Harvard Medical School, Boston, USA

T A Ngoma
Ocean Road Cancer Institute, Dar Es Salaam 3592, Tanzania; Department of Clinical Oncology, Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania

Abstract

Cancer presents an escalating challenge in Sub-Saharan Africa (SSA), necessitating strategic interventions grounded in regionally relevant evidence-based medicine. Informed decision-making is critical to formulate effective strategies for cancer prevention, diagnosis, funding, and treatment within the SSA population. The aim of this study is to highlight ongoing clinical trials in SSA, emphasizing the continuous initiatives aimed at filling existing knowledge gaps. Further, the study seeks to assess whether SSA is progressing or stagnating in the global landscape of cancer research. A comprehensive review of research papers and online registries on clinical trials was executed, focusing on English-language journal articles retrieved from the PubMed database. Additionally, a quantitative, web-based, retrospective review was conducted on registered cancer studies in SSA over the past decade (2000-2023) from ClinicalTrials.gov and the Pan African Clinical Trials Registry (PACTR) databases. The review resulted in the inclusion of 71 articles from PubMed, alongside 104 and 140 clinical trials from ClinicalTrials.gov and PACTR databases, respectively. Aggregate findings from PubMed and clinical trial databases revealed that East Africa is the predominant contributor (37%) to cancer clinical trials, whereas Central Africa exhibited the lowest contribution (4%). Notably, PubMed indicated a predominant focus on cervical cancer in clinical trials. Between 2000 and 2015, less than 4% of global cancer clinical trials listed on ClinicalTrials.gov were performed in SSA; in subsequent years, there was an observable increase in the percentage of total trials performed in SSA. Analyses of funding sources revealed that 45% and 32% of clinical trials in SSA were supported by the United States and the United Kingdom, respectively. In the last two decades, the formation of entities like the African Consortium for Cancer Clinical Trials, spearheaded by BIO Ventures for Global Health in partnership with African ministries of health, cancer hospitals, private industry, research institutions, and global oncology experts, contributed to increasing the effective implementation of multicenter clinical trials in Africa. Noteworthy instances, such as the Burkitt’s lymphoma and HypoAfrica studies, serve as examples of the results arising from these collaborative initiatives, reflecting substantial progress within SSA’s cancer research landscape.

Chutika Srisuttiyakorn, M.D.
Division of Dermatology, Department Of Medicine, Phramongkutklao Hospital, Bangkok, Thailand

Patcharasiri Bocam, M.D.
Division of Dermatology, Department Of Medicine, Phramongkutklao Hospital, Bangkok, Thailand

Abstract

Background: Hypopigmented mycosis fungoides (MF) is a variant of primary cutaneous T-cell lymphoma. Although the prognosis of hypopigmented mycosis fungoides is excellent, the diagnosis is usually missed.

Objective: The study aimed to identified the prevalence of patients with hypopigmented mycosis fungoides presenting hypopigmentation in Phramongkutklao Hospital, Bangkok, Thailand. We also reported the characteristic of hypopigmented mycosis fungoides among patients presenting hypopigmentation and compared clinical presentations between patients with a diagnosis of hypopigmented mycosis fungoides and patients with other diagnoses

Materials and Methods: We conducted a retrospective among 56 patients presenting hypopigmentation and receiving skin biopsies at Division of Dermatology, Department of Medicine, Phramongkutklao Hospital, Bangkok, Thailand between January 2016 to December 2021. The data parameters including demographic data, clinical manifestations (symptoms, size and morphology of the lesions, e.g., scale, margin, erythema, atrophy, mottled hypopigmentation, involved body surface area and distribution, histopathologic reports, special stains, final diagnosis, further investigations, treatments, follow-up duration and result of the treatments were recorded.

Results: The prevalence of hypopigmented mycosis fungoides among patient presenting with hypopigmentation was 16.1%. Compared with patients with other diagnoses, patients with hypopigmented mycosis fungoides usually had lesions with ill-defined margins (P-value=0.045) and presence of atrophy lesion (P-value=0.023).

Conclusion: The prevalence of hypopigmented mycosis fungoides involved 16.1% of patients presenting hypopigmentation. The presence of ill-defined margins and atrophic lesions led to suspected hypopigmented MF in our study. This data could be useful in epidemiologic information and might be adapted when choosing lesions for biopsy to diagnose MF.

Mukund Tinguria, MD, FRCP, FCAP
Department of Pathology and Laboratory Medicine, Brantford General Hospital, 200 Terrace Hill Street. Brantford, Ontario, Postal Code – N3R 1G9, Canada.

Abstract

Celiac disease (CD) is an immune mediated disorder characterized by intolerance to glutens in certain grains like wheat, barley, and rye. The gliadin exposure in susceptible individuals leads to an inflammatory reaction with damage to the small intestinal mucosa with villous blunting, atrophy and ultimate disappearance of intestinal villi. The damaged intestinal villi lead to malabsorption.

The development of celiac disease (CD) is determined by both environmental and genetic factors. The gluten in the grains represents an environmental factor. In addition to this environmental factor, CD development involves genetic predisposition as most CD patients possess human leucocyte antigen (HLA) DQ2 and/or HLA-DQ8. The complex interplay of multiple genetic and environmental factors determines the development of CD.

Small bowel mucosal biopsies remain gold standard for the diagnosis of CD because of variation in the clinical findings and serologic testing. Histologic examination of small intestine also helps to monitor the course of disease, response to treatment, and in detecting potential complications of celiac disease such as enteropathy associated T-cell lymphoma, adenocarcinoma, and concurrent intestinal diseases.

There has been significant development in understanding the pathophysiology, pathogenesis, and diagnosis of celiac disease. The present review summarizes the important development in CD in last few years with special emphasis on etiopathogenesis, pathophysiology, and pathologic features of CD. Better understanding of these features is not only important for correct diagnosis but also results in better patient management and would pave a way for future research of this overly complex disease characterized by complex interaction of environmental, genetic as well as immunologic mechanisms.

Tyler R. Harrison
Department of Communication Studies, University of Miami, Coral Gable, Florida, USA

Jessica Wendorf Muhamad
School of Communication, Florida State University, Tallahassee, Florida, USA

Ekaterina Malova
Simon Business School, University of Rochester, Rochester, New Yor, USA

Abstract

Objective: This paper provides a review of current knowledge and trends in research on firefighters cancer risks and risk reduction efforts and calls for future research focused on European and international firefighters to understand and reduce occupational cancer risk.

Cancer incidence: Firefighters face increased occupational cancer risk.  Firefighting has been linked with multiple types of cancer, including bladder, colorectal, brain and central nervous system, non-Hodgkin’s lymphoma, skin melanoma, and prostate and testicular cancer, with several others types of cancer being found at increased rates.

Cancer risks: Increased occupational cancer risk is, in part, related to carcinogenic exposures at fire events and improper use and cleaning of personal protective equipment (PPE), with role and years in service increasing risk.

Risk Perception: Research on efforts to reduce cancer risk are growing, and include examination of firefighter knowledge, attitudes, norms, and behaviors toward decontamination, screening, and healthy eating. Many firefighters report high perceived susceptibility and severity of cancer risk, and identify fire scene exposures, contaminated gear, diet, sleep disruption, chemical exposure from cleaning products, and barriers to medical care as contributing to increased risk.

Risk Reduction: Firefighters have strong desire to reduce cancer risk and report generally favorable attitudes toward decontamination practices and proper gear use, but face barriers to reducing those risks, including lack of knowledge, occupational needs, organizational culture, policy, and lack of resources. Behavioral interventions to reduce cancer risk through decontamination efforts and dietary change have demonstrated positive results, however there is a dearth of research on these efforts, especially with European and international firefighters.

Future Directions: Future research should focus on understanding European and international firefighters’ knowledge, attitudes, and behaviors toward cancer risk reduction, the impact of the built environment on cancer risk (station layout, clean cabs), improved efforts at tracking exposures, use of new technology and virtual reality in training to reduce cancer risk, and improved understanding of firefighter cancer risk by medical professionals.

Dr. Linu Abraham Jacob, Professor and Head
Department of Medical oncology; Kidwai Memorial Institute of Oncology, Dr. M. H. Marigowda road, Bengaluru Karnataka India

Dr. Animesh Gupta, Senior resident
Department of Medical oncology; Kidwai Memorial Institute of Oncology, Dr. M. H. Marigowda road, Bengaluru Karnataka India

Dr. Kanika Sharma
Department of Medical Oncology; MAX Super Specialty Hospital, Mohali Punjab

Dr. M C Suresh Babu, Professor
Department of Medical oncology; Kidwai Memorial Institute of Oncology, Dr. M. H. Marigowda road, Bengaluru Karnataka India

Dr. Lokesh K. N., Associate Professor
Department of Medical oncology; Kidwai Memorial Institute of Oncology, Dr. M. H. Marigowda road, Bengaluru Karnataka India

Dr. A H Rudresha, Associate Professor
Department of Medical oncology; Kidwai Memorial Institute of Oncology, Dr. M. H. Marigowda road, Bengaluru Karnataka India

Dr. Rajeev L. K.,, Associate Professor
Department of Medical oncology; Kidwai Memorial Institute of Oncology, Dr. M. H. Marigowda road, Bengaluru Karnataka India

Dr. Smitha C. Saldanha, Associate Profesor
Department of Medical oncology; Kidwai Memorial Institute of Oncology, Dr. M. H. Marigowda road, Bengaluru Karnataka India

Dr. Usha Amirtham, Professor and Head
Department of Pathology; Kidwai Memorial Institute of Oncology, Dr. M. H. Marigowda road, Bengaluru Karnataka India

Abstract

PURPOSE – Diffuse Large B-Cell Lymphoma can be subclassified into the prognostically distinct groups of GCB and non-GCB using the immunohistochemical Hans algorithm. However, in real life, patients classified as GCB show differing outcomes even when treated with the same chemotherapy regimen. CD10 is a GCB marker, while MUM1 is a non-GCB marker, but Hans algorithm classifies CD10+ MUM1+ patients as GCB DLBCL. We explored whether CD10+ MUM1+ GCB DLBCL patients had different outcomes compared to rest of the GCB DLBCL patients.

METHODS – In this study, we retrospectively analyzed the clinical records of 427 DLBCL patients treated with standard chemo-immunotherapy at Kidwai Memorial Institute of Oncology, Bengaluru from 2013 to 2019. The clinical characteristics, response rate and overall survival of CD10+ MUM1+ GCB group was compared with MUM1-ve GCB group and non-GCB group.

RESULTS – Among the patients studied, 187 (43%) patients were of GCB subtype, whereas 240 (57%) patients belonged to the non-GCB subtype. Additionally, 61 (14.3%) patients were of the CD10+ MUM1+ GCB immune-phenotype. No significant differences could be demonstrated in the clinical characteristics of CD10+ MUM1+ GCB and MUM1- GCB patients. Patients with CD10+ MUM1+ GCB subtype exhibited a significantly inferior response rate compared to those with MUM1- GCB subtype (81% versus 92%; p=0.04). Although, both non-GCB and CD10+ MUM1+ GCB subtypes displayed diminished overall survival in comparison to MUM1- GCB patients, (non-GCB = 33 months, CD10+ MUM1+ GCB = 33 months and MUM1-ve GCB = 40.4 months, p = 0.21) it did not reach statistical significance

CONCLUSION – CD10+ MUM1+ GCB patients may be prognostically more similar to non-GCB patients, as suggested by the inferior response rates and numerically inferior OS compared to other GCB patients. This needs further confirmation in prospective studies.

Mukund Tinguria
Department of Pathology and Laboratory Medicine Brantford General Hospital 200 Terrace Hill Street Brantford, Ontario Postal Code – N3R 1G9 Canada

Abstract

Celiac disease (CD) is an immune mediated disorder characterised by intolerance to glutens in certain grains like whet, barley, and rye. The exposure to gliadin protein component in the susceptible individuals leads to an inflammatory reaction damaging small bowel mucosa with progressive disappearance of intestinal villi. The damaged intestinal mucosa leads to malabsorption. The usual symptoms of celiac disease include diarrhea, steatorrhea, weight loss, fatigue, and abdominal pain. Diagnosis is based on clinical features, duodenal biopsy, elevated levels of anti-gliadin antibodies and response to gluten free diet. Contrary to common belief, celiac disease is a protein systemic disease rather than merely a pure digestive alteration. Celiac disease is closely associated with genes that code HLA -II antigens mainly of DQ2 and DQ8 classes, production of disease specific antibodies (i.e., endomysial antibodies), multiorgan involvement, comorbidity with other autoimmune diseases (shared autoimmunity), familial aggregation, and immune system dysregulation.

 

The clinical presentation of celiac disease can be variable. In mild form, patients can be almost asymptomatic whereas in the most severe form, the patients are at increased risk of life-threatening complications. Celiac disease has a well-known association with other autoimmune diseases such as autoimmune liver diseases (autoimmune hepatitis, primary biliary cirrhosis, primary sclerosing cholangitis), diabetes mellitus, autoimmune thyroid diseases, skin diseases such as dermatitis herpetiformis, rheumatoid arthritis, systemic lupus erythematosus, Sjogren’s syndrome, psoriasis, sarcoidosis, immune thrombocytopenic purpura, and pancreatitis. In addition, celiac disease may be associated with rare but potentially serious complications such as, collagenous sprue, ulcerative jejunoileitis, refractory celiac disease (RCD), enteropathy associated T-cell lymphoma, small bowel adenocarcinoma (SBA), hyposplenism, and cavitating mesenteric lymph node syndrome (CMLNS). The present article describes clinicopathologic features of these rare but serious complications of celiac disease.

Anjum Siddiqui
Dr. Anjum Siddiqui, Senior Resident, Department of Medicine, LHMC & Smt.SK Hospital, New Delhi

Aparna Agrawal
Director Professor, Department of Medicine, LHMC& Smt S.K Hospital, New Delhi

Praveen Kumar
Director Professor, Department of Paediatrics, LHMC& Kalawati Saran Children’s Hospital, New Delhi

Lekhraj Hemraj Ghotekar
Head of Department and Director Professor, Department of Medicine, LHMC& Smt S.K Hospital, New Delhi

Sanjana Taneja
MBBS, Lady Hardinge Medical College and associated Hospitals, New Delhi

Abstract

Gluten, in genetically susceptible individuals induces an immune mediated enteropathy called Celiac disease (CD). It is an established cause of malabsorption, with the worldwide prevalence being 1% in the general population. It is found across all age groups, from infants to the elderly with 20% patients being diagnosed in the seventh decade of life. It has varying clinical presentations ranging from silent asymptomatic forms which are diagnosed during screening to life threatening forms with severe malabsorption to atypical presentations, with the symptom spectrum extending beyond the gastrointestinal tract which are more common in adults. High index of suspicion, robust screening and testing, followed by strict adherence to gluten free diet is a must to curb and cure the disease. Patients tend to face difficulties not only during diagnosis, but also with compliance and availability of a gluten free diet, in addition to significant economic and psychosocial burden, which is more predominant in developing countries. Screening of high-risk groups like first-degree relatives of celiac disease, patients with severe malnutrition, other autoimmune diseases, refractory anaemia and irritable bowel syndrome should be done to enhance case detection. In low middle income countries, judicious resource utilisation takes precedence, hence, tackling a multifactorial disease such as celiac disease becomes challenging. Repeated follow ups, awareness among patients and doctors, encouragement, availability of testing and dietary counselling is necessary for management of the disease in such settings. Improving sanitation and feeding practices may also play role in decreasing incidence, considering childhood GI infections are a well-established risk factor. Increased availability of serological tests (IgA/IgG anti-tTG, anti -EMA and anti-DGP), biopsy, genetic testing and other newer modalities under research have improved the diagnostic accuracy. Poor compliance increases the risk of GI malignancy, non-Hodgkin’s lymphoma, Hepatocellular carcinoma and MALToma. Hence adherence is a must to prevent complications. A wide variety of treatment modalities are being evaluated to bring into force alternative strategies for management. Only providing gluten free diet is often not sufficient for improvement of nutritional status in patients with CD. Hence, micronutrient supplementation should also be encouraged to meet the unmet needs.

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