B. Kothari, P. Parab, S. Gulia, S. Rath, Sudeep Gupta
Abstract Ribociclib is a selective cyclin-dependent kinase (CDK) 4/6 inhibitor approved in combination with endocrine-based therapy for the treatment of hormone receptor-positive (HR + )/human epidermal growth factor receptor 2-negative (HER2 − ) advanced or metastatic breast cancer. It can significantly prolong the progression-free survival and improve the objective response rate compared with hormone therapy alone. However, the combined regimen results in a higher risk of adverse events, one of them being dermatological reactions. We present a case of late severe skin toxicity in a patient who had received ribociclib for 5 months. The toxicity led to severe pruritus and maculopapular and patchy rash on upper and lower extremities, which completely resolved 1 month after cessation of the drug. We conclude that ribociclib-induced skin toxicity is a noteworthy side effect that can lead to permanent cessation of this drug and is reversible. There are clinical decision dilemmas related to continuation, withholding, or switching CDK4/6 inhibitors, and benefits should be weighed against toxicities and costs.
{"title":"Ribociclib-Induced Delayed Dermatological Reaction: Case Report of a Rare Adverse Effect and Review of Literature","authors":"B. Kothari, P. Parab, S. Gulia, S. Rath, Sudeep Gupta","doi":"10.1055/s-0043-1766128","DOIUrl":"https://doi.org/10.1055/s-0043-1766128","url":null,"abstract":"Abstract Ribociclib is a selective cyclin-dependent kinase (CDK) 4/6 inhibitor approved in combination with endocrine-based therapy for the treatment of hormone receptor-positive (HR + )/human epidermal growth factor receptor 2-negative (HER2 − ) advanced or metastatic breast cancer. It can significantly prolong the progression-free survival and improve the objective response rate compared with hormone therapy alone. However, the combined regimen results in a higher risk of adverse events, one of them being dermatological reactions. We present a case of late severe skin toxicity in a patient who had received ribociclib for 5 months. The toxicity led to severe pruritus and maculopapular and patchy rash on upper and lower extremities, which completely resolved 1 month after cessation of the drug. We conclude that ribociclib-induced skin toxicity is a noteworthy side effect that can lead to permanent cessation of this drug and is reversible. There are clinical decision dilemmas related to continuation, withholding, or switching CDK4/6 inhibitors, and benefits should be weighed against toxicities and costs.","PeriodicalId":13513,"journal":{"name":"Indian Journal of Medical and Paediatric Oncology","volume":" ","pages":""},"PeriodicalIF":0.2,"publicationDate":"2023-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46197002","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Abstract Modern therapeutic protocols in acute leukemias risk stratify disease based on genetic characterization of the neoplastic cells and their response to treatment. Genetic characterization is routinely performed by cytogenetic testing of leukemic cells and is a standard component of modern risk-adapted therapy in acute lymphoblastic leukemia (ALL). High-throughput technologies like RNA sequencing have identified multiple novel subtypes in recent years. The cytogenetic strategy using GTG and fluorescent in-situ hybridization (FISH) has to be adapted to identify not only the primary principal chromosomal abnormalities but also the novel subtypes. In the review, we describe a systematic comprehensive cytogenetic strategy that integrates information from immunophenotyping, flow-based DNA ploidy, and karyotyping complemented by targeted FISH studies to identify more than 70% of genetic abnormalities described in B cell precursor ALL. The simplified strategy includes a four-probe FISH and flow ploidy strategy, ± karyotyping that identifies high risk ( KMT2A, BCR::ABL1 , hypodiploidy, iAMP21) and standard risk ( ETV6::RUNX1 and high hyperdiploid) cytogenetic groups. The extended FISH panel includes probes targeting MEF2D, ZNF384 , and CRLF2 rearrangements that are used intuitively on integrating the immunophenotyping features that characterize these entities. The strategy also includes a systematic approach to identify masked hypodiploidy integrating targeted FISH analysis directed toward identifying monosomies of chromosomes 7, 15, and 17 and flow cytometry-based DNA ploidy analysis. The recently described PH-like ALL is characterized by ABL class fusions and rearrangements of CRLF2 and JAK2 genes. FISH analysis using break-apart probes can be used to identify these aberrations. The cytogenetic approach also includes FISH analysis to identify intragenic and whole gene deletions of the IKZF1 genes that identify a subset of patients associated with high risk of treatment failure.
{"title":"Role of Cytogenetics and FISH in Laboratory Workup of B Cell Precursor Acute Lymphoblastic Leukemia","authors":"A. Dhabe, R. Islam, K. Ramakrishnan, M. Parihar","doi":"10.1055/s-0043-1766133","DOIUrl":"https://doi.org/10.1055/s-0043-1766133","url":null,"abstract":"Abstract Modern therapeutic protocols in acute leukemias risk stratify disease based on genetic characterization of the neoplastic cells and their response to treatment. Genetic characterization is routinely performed by cytogenetic testing of leukemic cells and is a standard component of modern risk-adapted therapy in acute lymphoblastic leukemia (ALL). High-throughput technologies like RNA sequencing have identified multiple novel subtypes in recent years. The cytogenetic strategy using GTG and fluorescent in-situ hybridization (FISH) has to be adapted to identify not only the primary principal chromosomal abnormalities but also the novel subtypes. In the review, we describe a systematic comprehensive cytogenetic strategy that integrates information from immunophenotyping, flow-based DNA ploidy, and karyotyping complemented by targeted FISH studies to identify more than 70% of genetic abnormalities described in B cell precursor ALL. The simplified strategy includes a four-probe FISH and flow ploidy strategy, ± karyotyping that identifies high risk ( KMT2A, BCR::ABL1 , hypodiploidy, iAMP21) and standard risk ( ETV6::RUNX1 and high hyperdiploid) cytogenetic groups. The extended FISH panel includes probes targeting MEF2D, ZNF384 , and CRLF2 rearrangements that are used intuitively on integrating the immunophenotyping features that characterize these entities. The strategy also includes a systematic approach to identify masked hypodiploidy integrating targeted FISH analysis directed toward identifying monosomies of chromosomes 7, 15, and 17 and flow cytometry-based DNA ploidy analysis. The recently described PH-like ALL is characterized by ABL class fusions and rearrangements of CRLF2 and JAK2 genes. FISH analysis using break-apart probes can be used to identify these aberrations. The cytogenetic approach also includes FISH analysis to identify intragenic and whole gene deletions of the IKZF1 genes that identify a subset of patients associated with high risk of treatment failure.","PeriodicalId":13513,"journal":{"name":"Indian Journal of Medical and Paediatric Oncology","volume":" ","pages":""},"PeriodicalIF":0.2,"publicationDate":"2023-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47551834","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
M. Maddali, A. Arunachalam, A. Kapadia, U. Kulkarni, P. Balasubramanian
Abstract The diagnostic evaluation of myeloproliferative neoplasms (MPNs) depends on the close correlation between clinical features, morphologic assessment of a trephine bone marrow biopsy, and molecular markers. Typically, MPNs have driver mutations in JAK2 , CALR , or MPL , as well as mutations in genes related to epigenetic regulation, RNA splicing, and signaling. Mutations in these genes are a hallmark of diagnostic, prognostic, and therapeutic assessment in patients with MPNs. In line with the World Health Organization classification, all myeloproliferative disorders require molecular characterization to support diagnoses or confirm entities defined by underlying molecular abnormalities. A structured molecular analysis workflow is essential for a rapid and cost-effective diagnosis of MPN. The purpose of this review is to explore the role of molecular diagnostics in the assessment of BCR::ABL1 -negative MPNs.
{"title":"A Review on the Role of Molecular Genetics in the Diagnostic Workup of BCR::ABL1 -Negative Myeloproliferative Neoplasms","authors":"M. Maddali, A. Arunachalam, A. Kapadia, U. Kulkarni, P. Balasubramanian","doi":"10.1055/s-0043-1766138","DOIUrl":"https://doi.org/10.1055/s-0043-1766138","url":null,"abstract":"Abstract The diagnostic evaluation of myeloproliferative neoplasms (MPNs) depends on the close correlation between clinical features, morphologic assessment of a trephine bone marrow biopsy, and molecular markers. Typically, MPNs have driver mutations in JAK2 , CALR , or MPL , as well as mutations in genes related to epigenetic regulation, RNA splicing, and signaling. Mutations in these genes are a hallmark of diagnostic, prognostic, and therapeutic assessment in patients with MPNs. In line with the World Health Organization classification, all myeloproliferative disorders require molecular characterization to support diagnoses or confirm entities defined by underlying molecular abnormalities. A structured molecular analysis workflow is essential for a rapid and cost-effective diagnosis of MPN. The purpose of this review is to explore the role of molecular diagnostics in the assessment of BCR::ABL1 -negative MPNs.","PeriodicalId":13513,"journal":{"name":"Indian Journal of Medical and Paediatric Oncology","volume":" ","pages":""},"PeriodicalIF":0.2,"publicationDate":"2023-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47814824","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hiba Siddiqui, Shubham Garg, P. Julka, A. Chaturvedi, Sharan Choudhri, R. Arora
Abstract Introduction and Objective Health care professionals (HPs) have been at the forefront facing the pressures and uncertainties of the COVID-19 pandemic, and thus have a higher psychological vulnerability. The incidence of psychological distress, which can negatively affect an HP's work efficiency and long-term well-being, has not been studied in depth in India. Materials and Methods A multicentric study was conducted using the digital means of communication across Max Healthcare between June and August 2020. HPs in the department of oncology, including doctors, nurses, and other support staff, were invited to voluntarily participate in the self-administered online survey. A total of 87 HPs in oncology (41 doctors, 28 nurses, and 18 in other fronts) were assessed using the 12-item General Health Questionnaire (GHQ-12). Outcome of interest was psychological distress (defined as a GHQ-12 score >15). Results The overall incidence of psychological distress among HPs in oncology during the COVID-19 pandemic was 17.20%. Significantly higher levels of psychological distress were observed among HPs with a history of psychiatric illness ( p = 0.003), and among HPs with a work experience of less than 10 years ( p = 0.017). Conclusion The COVID-19 pandemic had a significant impact on the psychological well-being of HPs in India. This study implicated the recognition of the psychological well-being of HPs in oncology as an unmet need during the COVID-19 pandemic, further recommending efforts toward increasing accessibility of mental health services for them.
{"title":"Impact of the COVID-19 Pandemic on the Psychological Well-Being of Health Care Professionals in India","authors":"Hiba Siddiqui, Shubham Garg, P. Julka, A. Chaturvedi, Sharan Choudhri, R. Arora","doi":"10.1055/s-0043-1764368","DOIUrl":"https://doi.org/10.1055/s-0043-1764368","url":null,"abstract":"Abstract Introduction and Objective Health care professionals (HPs) have been at the forefront facing the pressures and uncertainties of the COVID-19 pandemic, and thus have a higher psychological vulnerability. The incidence of psychological distress, which can negatively affect an HP's work efficiency and long-term well-being, has not been studied in depth in India. Materials and Methods A multicentric study was conducted using the digital means of communication across Max Healthcare between June and August 2020. HPs in the department of oncology, including doctors, nurses, and other support staff, were invited to voluntarily participate in the self-administered online survey. A total of 87 HPs in oncology (41 doctors, 28 nurses, and 18 in other fronts) were assessed using the 12-item General Health Questionnaire (GHQ-12). Outcome of interest was psychological distress (defined as a GHQ-12 score >15). Results The overall incidence of psychological distress among HPs in oncology during the COVID-19 pandemic was 17.20%. Significantly higher levels of psychological distress were observed among HPs with a history of psychiatric illness ( p = 0.003), and among HPs with a work experience of less than 10 years ( p = 0.017). Conclusion The COVID-19 pandemic had a significant impact on the psychological well-being of HPs in India. This study implicated the recognition of the psychological well-being of HPs in oncology as an unmet need during the COVID-19 pandemic, further recommending efforts toward increasing accessibility of mental health services for them.","PeriodicalId":13513,"journal":{"name":"Indian Journal of Medical and Paediatric Oncology","volume":" ","pages":""},"PeriodicalIF":0.2,"publicationDate":"2023-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48557462","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Abstract The role of hematopathologists in the diagnosis of acute leukemia (AL) starts with the morphological examination of either peripheral blood smear or bone marrow. The morphological hallmark for the myeloblast includes “Auer rods” and “Phi bodies.” The addition of cytochemical stains such as myeloperoxidase, Sudan Black B, periodic acid-Schiff stain, nonspecific esterase, and Perls' stain acts as an important adjunct to the morphological classification in the resource-constrained settings. The recent World Health Organization classification still endorses the utility of morphology which requires the presence of either ≥ 20% lymphoblasts or myeloblasts/or its equivalents (monoblasts, promonocytes, or megakaryoblasts) and integrates it with the clinical features, immunophenotyping (IP), and molecular genetics for making the diagnosis of AL. Morphology can give clue to the specific diagnosis of acute myeloid leukemia (AML) with t(8:21), t(15:17), t(16:16), or inv(16) and this diagnosis can be made irrespective of blasts count if such translocations are demonstrated by molecular tests. There are some interesting findings such as blasts with “hand-mirror” morphology, nuclear cleavage, prominent cytoplasmic vacuoles, pseudo-Chediak-Higashi granules, cup-like nucleus, and other dysplastic features helping in differentiating lymphoid and myeloid leukemias. Transient abnormal myelopoiesis in Down syndrome and hypoplastic AL can be picked up on morphological examination. Bone marrow biopsy would be greatly beneficial and complementary to aspirate smears and is required for diagnosing exact cellularity, topography of cells, dyspoiesis, myelonecrosis, gelatinous marrow transformation, myelofibrosis, and IP can be performed using immunohistochemistry. Morphological examination in AL is not only helpful for diagnosis but also useful for predicting the prognosis in posttherapy cases, AML with myelodysplasia-related changes, therapy-related myeloid neoplasms, and mixed phenotype AL. Hematogones, blastoid mantle cell lymphoma, high grade B cell lymphoid with blastoid morphology, Burkitt leukemia, prolymphocytes in prolymphocytic leukemia, hairy cell leukemia variant, plasmablasts especially in plasmablastic leukemia, or plasma cell leukemia can mimic AL and IP is useful in these situations. Hence, morphology should be considered as a kind of “gold-standard” starting point for the analysis of AL cases. Morphological examination cannot be replaced and advanced tests cannot be used as surrogate for morphology.
{"title":"Role of Morphology in the Diagnosis of Acute Leukemias: Systematic Review","authors":"M. Sekar, Manasa Raj, P. Manivannan","doi":"10.1055/s-0043-1764369","DOIUrl":"https://doi.org/10.1055/s-0043-1764369","url":null,"abstract":"Abstract The role of hematopathologists in the diagnosis of acute leukemia (AL) starts with the morphological examination of either peripheral blood smear or bone marrow. The morphological hallmark for the myeloblast includes “Auer rods” and “Phi bodies.” The addition of cytochemical stains such as myeloperoxidase, Sudan Black B, periodic acid-Schiff stain, nonspecific esterase, and Perls' stain acts as an important adjunct to the morphological classification in the resource-constrained settings. The recent World Health Organization classification still endorses the utility of morphology which requires the presence of either ≥ 20% lymphoblasts or myeloblasts/or its equivalents (monoblasts, promonocytes, or megakaryoblasts) and integrates it with the clinical features, immunophenotyping (IP), and molecular genetics for making the diagnosis of AL. Morphology can give clue to the specific diagnosis of acute myeloid leukemia (AML) with t(8:21), t(15:17), t(16:16), or inv(16) and this diagnosis can be made irrespective of blasts count if such translocations are demonstrated by molecular tests. There are some interesting findings such as blasts with “hand-mirror” morphology, nuclear cleavage, prominent cytoplasmic vacuoles, pseudo-Chediak-Higashi granules, cup-like nucleus, and other dysplastic features helping in differentiating lymphoid and myeloid leukemias. Transient abnormal myelopoiesis in Down syndrome and hypoplastic AL can be picked up on morphological examination. Bone marrow biopsy would be greatly beneficial and complementary to aspirate smears and is required for diagnosing exact cellularity, topography of cells, dyspoiesis, myelonecrosis, gelatinous marrow transformation, myelofibrosis, and IP can be performed using immunohistochemistry. Morphological examination in AL is not only helpful for diagnosis but also useful for predicting the prognosis in posttherapy cases, AML with myelodysplasia-related changes, therapy-related myeloid neoplasms, and mixed phenotype AL. Hematogones, blastoid mantle cell lymphoma, high grade B cell lymphoid with blastoid morphology, Burkitt leukemia, prolymphocytes in prolymphocytic leukemia, hairy cell leukemia variant, plasmablasts especially in plasmablastic leukemia, or plasma cell leukemia can mimic AL and IP is useful in these situations. Hence, morphology should be considered as a kind of “gold-standard” starting point for the analysis of AL cases. Morphological examination cannot be replaced and advanced tests cannot be used as surrogate for morphology.","PeriodicalId":13513,"journal":{"name":"Indian Journal of Medical and Paediatric Oncology","volume":" ","pages":""},"PeriodicalIF":0.2,"publicationDate":"2023-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42052154","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
A. Saha, Sneha Kakoty, Kazoomi Patel, V. Rai, Jyoti Sawhney, Nainesh Menat
Abstract Introduction: Chronic myelomonocytic leukemia (CMML) is a rare clonal hematopoietic neoplasm with a prevalence of 1.05 to 1.94 cases per 1,00,000 population. There are multiple prognostic scoring system used in practice for CMML, which include both cytogenetic and next-generation sequencing based. Objective This study assesses the clinicohematological profile of CMML patients, along with comparison of three widely used prognostic scoring systems for CMML (CMML-specific prognostic scoring system, MD Anderson prognostic score, Mayo prognostic model). Materials and Methods : This study is an 8-year retrospective study. All relevant data had been retrieved and reviewed by the authors. Inclusion and exclusion criteria: All the cases that were diagnosed before 2016 as per 2008 criteria were reclassified, (2) all the cases that were positive for the mutations associated with myeloproliferative neoplasms were excluded, and (3) cases with more than or equal to 20% blast/blast equivalents were excluded. A univariate analysis was done followed by a multivariate analysis for all the parameters constituting each scoring system. Lastly, a receiver operating characteristic curve was plotted for all the three scoring systems. Result : There were total 23 patients, with a median age of 63 years and a male to female ratio of 2.3:1. Cytogenetic aberration and genetic mutation were observed in 6 and 3 cases, respectively. The median overall survival (OS) was 48 months and the median leukemia-free survival was 12 months. Post-multivariate analysis, the parameters with significant impact on OS were absolute monocyte count more than 10 × 10^9/L, myeloid precursors in peripheral blood, hemoglobin less than 10g/dL, platelet less than 100 × 10^9/L, hemoglobin less than 12g/dL, and absolute lymphocyte count more than 2.5 × 10^9/L. Conclusion : To summarize, we discovered CPSS to be a better prognostic tool for a setup like ours, since molecular investigations are not always readily available for each case. More such researches are needed in the near future so that we can design better prognostic tools and see for their usefulness in real life.
{"title":"An Assessment of the Three Popular Prognostic Scoring Systems for Chronic Myelomonocytic Leukemia (CMML) in an Indian Context","authors":"A. Saha, Sneha Kakoty, Kazoomi Patel, V. Rai, Jyoti Sawhney, Nainesh Menat","doi":"10.1055/s-0043-1766130","DOIUrl":"https://doi.org/10.1055/s-0043-1766130","url":null,"abstract":"Abstract Introduction: Chronic myelomonocytic leukemia (CMML) is a rare clonal hematopoietic neoplasm with a prevalence of 1.05 to 1.94 cases per 1,00,000 population. There are multiple prognostic scoring system used in practice for CMML, which include both cytogenetic and next-generation sequencing based. Objective This study assesses the clinicohematological profile of CMML patients, along with comparison of three widely used prognostic scoring systems for CMML (CMML-specific prognostic scoring system, MD Anderson prognostic score, Mayo prognostic model). Materials and Methods : This study is an 8-year retrospective study. All relevant data had been retrieved and reviewed by the authors. Inclusion and exclusion criteria: All the cases that were diagnosed before 2016 as per 2008 criteria were reclassified, (2) all the cases that were positive for the mutations associated with myeloproliferative neoplasms were excluded, and (3) cases with more than or equal to 20% blast/blast equivalents were excluded. A univariate analysis was done followed by a multivariate analysis for all the parameters constituting each scoring system. Lastly, a receiver operating characteristic curve was plotted for all the three scoring systems. Result : There were total 23 patients, with a median age of 63 years and a male to female ratio of 2.3:1. Cytogenetic aberration and genetic mutation were observed in 6 and 3 cases, respectively. The median overall survival (OS) was 48 months and the median leukemia-free survival was 12 months. Post-multivariate analysis, the parameters with significant impact on OS were absolute monocyte count more than 10 × 10^9/L, myeloid precursors in peripheral blood, hemoglobin less than 10g/dL, platelet less than 100 × 10^9/L, hemoglobin less than 12g/dL, and absolute lymphocyte count more than 2.5 × 10^9/L. Conclusion : To summarize, we discovered CPSS to be a better prognostic tool for a setup like ours, since molecular investigations are not always readily available for each case. More such researches are needed in the near future so that we can design better prognostic tools and see for their usefulness in real life.","PeriodicalId":13513,"journal":{"name":"Indian Journal of Medical and Paediatric Oncology","volume":"44 1","pages":"422 - 427"},"PeriodicalIF":0.2,"publicationDate":"2023-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48846056","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Abstract Hypereosinophilia (HE) can be caused by a wide variety of non-hematologic (secondary or reactive) and hematologic (primary, clonal) disorders. Diagnosing hypereosinophilia/hypereosinophilic syndrome (HE/HES) is challenging due to the complex nature of disease manifestations and numerous underlying etiologies. Knowing that only rare cases are clonal, it is wise to rule out reactive conditions and proceed with molecular and other advanced tools. The exclusion of secondary causes needs a detailed clinical evaluation followed by a wide range of serological and imaging investigations. Once reactive eosinophilia has been ruled out, the diagnosis of primary HE/HES is made using a combination of morphologic examination of the blood and bone marrow, conventional cytogenetics, fluorescent in situ hybridization, flow-cytometry, and T-cell clonality evaluation to look for histopathologic or clonal evidence of an underlying hematological disorder. The accurate diagnosis of clonal eosinophilia-causing myeloid and lymphoid neoplasms and the identification of numerous gene rearrangements significantly enhance patient outcomes, because a proportion of these patients (such as PDGFRA and PDGFRB rearrangements) responds well to tyrosine kinase inhibitors. Considering the complex etiopathologies, the cost of testing, and the time involved, the workup needs to be tailored according to the urgency of the situation and the resources available. In urgent situations with organ damage, it is crucial to initiate appropriate management without waiting for the results of investigations. In contrast, in a resource-limited situation, it is acceptable to employ step-by-step rather than comprehensive testing to rule out the most common causes first. Here, we discuss various laboratory investigations employed in diagnosing HE/HES, highlighting their importance in different situations.
{"title":"Laboratory workup of Hypereosinophilia","authors":"Durgadevi Sundaresan, S. Sreedharanunni","doi":"10.1055/s-0043-1761261","DOIUrl":"https://doi.org/10.1055/s-0043-1761261","url":null,"abstract":"Abstract Hypereosinophilia (HE) can be caused by a wide variety of non-hematologic (secondary or reactive) and hematologic (primary, clonal) disorders. Diagnosing hypereosinophilia/hypereosinophilic syndrome (HE/HES) is challenging due to the complex nature of disease manifestations and numerous underlying etiologies. Knowing that only rare cases are clonal, it is wise to rule out reactive conditions and proceed with molecular and other advanced tools. The exclusion of secondary causes needs a detailed clinical evaluation followed by a wide range of serological and imaging investigations. Once reactive eosinophilia has been ruled out, the diagnosis of primary HE/HES is made using a combination of morphologic examination of the blood and bone marrow, conventional cytogenetics, fluorescent in situ hybridization, flow-cytometry, and T-cell clonality evaluation to look for histopathologic or clonal evidence of an underlying hematological disorder. The accurate diagnosis of clonal eosinophilia-causing myeloid and lymphoid neoplasms and the identification of numerous gene rearrangements significantly enhance patient outcomes, because a proportion of these patients (such as PDGFRA and PDGFRB rearrangements) responds well to tyrosine kinase inhibitors. Considering the complex etiopathologies, the cost of testing, and the time involved, the workup needs to be tailored according to the urgency of the situation and the resources available. In urgent situations with organ damage, it is crucial to initiate appropriate management without waiting for the results of investigations. In contrast, in a resource-limited situation, it is acceptable to employ step-by-step rather than comprehensive testing to rule out the most common causes first. Here, we discuss various laboratory investigations employed in diagnosing HE/HES, highlighting their importance in different situations.","PeriodicalId":13513,"journal":{"name":"Indian Journal of Medical and Paediatric Oncology","volume":" ","pages":""},"PeriodicalIF":0.2,"publicationDate":"2023-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43568570","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Abstract Detection of measurable residual disease (MRD) is of significant value in the management of acute myeloid leukemia (AML) patients. Along with multicolor flowcytometry (MFC), molecular techniques form an integral tool in AML MRD detection. Multiple studies have reiterated the role of molecular MRD evaluation in AML at defined timepoints during the course of therapy, helping in risk stratification, prediction of relapse, and as guide for pre-emptive therapy. The latest World Health Organization (WHO) classification (WHO-HEME5) has refined the classification of AML bringing forth newer entities defined by molecular abnormalities, especially fusions. AML is a clonally heterogeneous disease characterized by a spectrum of multiple molecular abnormalities including gene mutations and fusions. Accordingly, the molecular methods employed are also diverse and need robust technical standardization in clinical laboratories. Real-time quantitative polymerase chain reaction (PCR), digital PCR, and next-generation sequencing (NGS) are the major molecular platforms for AML MRD. The European LeukemiaNet (ELN) MRD Working Party consensus document recently updated in 2021 for the first time has reflected on the technical recommendations for NGS MRD in AML and stressed the value of an integrated approach. It is, therefore, desirable for physicians, scientists, and pathologists alike to thoroughly understand these molecular methods for appropriate utilization and interpretation. In this article, we discuss the various facets of molecular methods for MRD detection in AML including technical requirements, advantages, drawbacks, and applications.
{"title":"Molecular MRD Assessment in Acute Myeloid Leukemias","authors":"Shivangi Harankhedkar, N. Patkar","doi":"10.1055/s-0043-1762921","DOIUrl":"https://doi.org/10.1055/s-0043-1762921","url":null,"abstract":"Abstract Detection of measurable residual disease (MRD) is of significant value in the management of acute myeloid leukemia (AML) patients. Along with multicolor flowcytometry (MFC), molecular techniques form an integral tool in AML MRD detection. Multiple studies have reiterated the role of molecular MRD evaluation in AML at defined timepoints during the course of therapy, helping in risk stratification, prediction of relapse, and as guide for pre-emptive therapy. The latest World Health Organization (WHO) classification (WHO-HEME5) has refined the classification of AML bringing forth newer entities defined by molecular abnormalities, especially fusions. AML is a clonally heterogeneous disease characterized by a spectrum of multiple molecular abnormalities including gene mutations and fusions. Accordingly, the molecular methods employed are also diverse and need robust technical standardization in clinical laboratories. Real-time quantitative polymerase chain reaction (PCR), digital PCR, and next-generation sequencing (NGS) are the major molecular platforms for AML MRD. The European LeukemiaNet (ELN) MRD Working Party consensus document recently updated in 2021 for the first time has reflected on the technical recommendations for NGS MRD in AML and stressed the value of an integrated approach. It is, therefore, desirable for physicians, scientists, and pathologists alike to thoroughly understand these molecular methods for appropriate utilization and interpretation. In this article, we discuss the various facets of molecular methods for MRD detection in AML including technical requirements, advantages, drawbacks, and applications.","PeriodicalId":13513,"journal":{"name":"Indian Journal of Medical and Paediatric Oncology","volume":"1 1","pages":""},"PeriodicalIF":0.2,"publicationDate":"2023-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"57980308","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Abstract Purpose We describe the challenges faced and lessons learnt over three decades of a childhood cancer survivorship program in India. Methods We provide a descriptive analysis of the challenges and barriers faced in running this program, our strategies in management, and detail the stages of development of holistic support system. Results The profile of late effects in our cohort of survivors is notable for the high prevalence of psychosocial issues and metabolic syndrome. Major difficulties faced were transitioning of patients to survivorship care and attrition to follow-up, which were overcome to an extent by ensuring constant communication/rapport-building, updated databases, and peer support groups. Collaborations with nonprofit organizations and other donors have enabled financial, psychosocial, educational, and vocational rehabilitation. Conclusions It is feasible to establish and sustain a survivorship program in a large-volume center in low- and medium-income country. Understanding the unique spectrum of late effects and establishing a holistic support system go a long way in ensuring the long-term physical and mental health and psychosocial concerns of childhood cancer survivors. Decentralization, development of a strong national networks, capacity building, and incorporation of sustainable technology should be priorities in survivorship care.
{"title":"The Care of Childhood Cancer Survivors in India: Challenges and Solutions","authors":"M. Prasad, S. Goswami, P. Kurkure","doi":"10.1055/s-0043-1761262","DOIUrl":"https://doi.org/10.1055/s-0043-1761262","url":null,"abstract":"Abstract Purpose We describe the challenges faced and lessons learnt over three decades of a childhood cancer survivorship program in India. Methods We provide a descriptive analysis of the challenges and barriers faced in running this program, our strategies in management, and detail the stages of development of holistic support system. Results The profile of late effects in our cohort of survivors is notable for the high prevalence of psychosocial issues and metabolic syndrome. Major difficulties faced were transitioning of patients to survivorship care and attrition to follow-up, which were overcome to an extent by ensuring constant communication/rapport-building, updated databases, and peer support groups. Collaborations with nonprofit organizations and other donors have enabled financial, psychosocial, educational, and vocational rehabilitation. Conclusions It is feasible to establish and sustain a survivorship program in a large-volume center in low- and medium-income country. Understanding the unique spectrum of late effects and establishing a holistic support system go a long way in ensuring the long-term physical and mental health and psychosocial concerns of childhood cancer survivors. Decentralization, development of a strong national networks, capacity building, and incorporation of sustainable technology should be priorities in survivorship care.","PeriodicalId":13513,"journal":{"name":"Indian Journal of Medical and Paediatric Oncology","volume":"1 1","pages":""},"PeriodicalIF":0.2,"publicationDate":"2023-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41683594","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"One World, One Life","authors":"S. Mullapally","doi":"10.1055/s-0042-1760323","DOIUrl":"https://doi.org/10.1055/s-0042-1760323","url":null,"abstract":"","PeriodicalId":13513,"journal":{"name":"Indian Journal of Medical and Paediatric Oncology","volume":" ","pages":""},"PeriodicalIF":0.2,"publicationDate":"2023-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42559099","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
京公网安备 11010802042870号
京ICP备2023020795号-1
扫码关注我们
求助内容：
应助结果提醒方式：