Abstract Recent studies have demonstrated promising outcomes of the first-line anaplastic lymphoma kinase-tyrosine kinase inhibitor (ALK-TKI) “crizotinib” in patients with locally advanced and metastatic lung cancers with high expression of the fusion protein “EML4-ALK.” High drug resistance, however, restricts the therapeutic advantages of ALK-TKIs in patients with nonsmall cell lung cancer (NSCLC). The contemporary literature documents limited treatment approaches for patients with NSCLC relapse or nonresponsiveness to second-/third-generation ALK-TKIs. We hereby provide a descriptive analysis of five NSCLC cases treated with crizotinib, ceritinib, and alectinib for a median duration of 54 months. The outcomes indicate a profound therapeutic response in patients receiving 4th and subsequent line of treatment with crizotinib. The crizotinib retreatment actively reduced patient resistance to the ALK-TKIs by reversing the mesenchymal epithelial transition amplification. The results from this case series also emphasize the possible role of next-generation sequencing in determining therapeutic resistance and transforming the treatment paradigm for NSCLC. Partial response was observed in the patients after 6 months of crizotinib readministration. This is possibly the first case series reporting crizotinib rechallenge in patients of ALK positive NSCLC who failed on subsequent ALK-TKIs and multiple lines of chemotherapies.
{"title":"Clinical Outcomes of Crizotinib Readministration in Patients with Nonsmall Cell Lung Cancer with Anaplastic Lymphoma Kinase Rearrangement: Case Report and Review of Literature","authors":"Prasanta Kumar Parida","doi":"10.1055/s-0043-1777040","DOIUrl":"https://doi.org/10.1055/s-0043-1777040","url":null,"abstract":"Abstract Recent studies have demonstrated promising outcomes of the first-line anaplastic lymphoma kinase-tyrosine kinase inhibitor (ALK-TKI) “crizotinib” in patients with locally advanced and metastatic lung cancers with high expression of the fusion protein “EML4-ALK.” High drug resistance, however, restricts the therapeutic advantages of ALK-TKIs in patients with nonsmall cell lung cancer (NSCLC). The contemporary literature documents limited treatment approaches for patients with NSCLC relapse or nonresponsiveness to second-/third-generation ALK-TKIs. We hereby provide a descriptive analysis of five NSCLC cases treated with crizotinib, ceritinib, and alectinib for a median duration of 54 months. The outcomes indicate a profound therapeutic response in patients receiving 4th and subsequent line of treatment with crizotinib. The crizotinib retreatment actively reduced patient resistance to the ALK-TKIs by reversing the mesenchymal epithelial transition amplification. The results from this case series also emphasize the possible role of next-generation sequencing in determining therapeutic resistance and transforming the treatment paradigm for NSCLC. Partial response was observed in the patients after 6 months of crizotinib readministration. This is possibly the first case series reporting crizotinib rechallenge in patients of ALK positive NSCLC who failed on subsequent ALK-TKIs and multiple lines of chemotherapies.","PeriodicalId":13513,"journal":{"name":"Indian Journal of Medical and Paediatric Oncology","volume":"25 12","pages":""},"PeriodicalIF":0.2,"publicationDate":"2023-12-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139151696","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. Nlemadim, T. Ugbem, Gabriel Unimke Udie, Godwin Cletus Omini, Eghomwanre Davis Izekor, O. F. Adedokun, Ekaete Joseph Asuquo, M. M. Meremikwu, F. Odey
Abstract Pediatric-type follicular lymphoma (PFL) is a rare, nonaggressive, slow-growing (indolent), non-Hodgkin lymphoma that is typically seen in males as a localized disease with excellent outcomes. It is largely different from follicular lymphoma (FL). Few published studies on PFL are case series in developed nations. We report on a patient with advanced PFL, a 14-year-old female with 5-year history of neck swellings, abdominal distension for a month, and pericardial effusion, among others. The swellings waxed and waned; and involved all the peripheral lymph nodes. Tuberculosis (TB) GeneXpert and human immunodeficiency virus (HIV) screening were negative. She received anti-TB drugs prior to presentation in our hospital where nodal histopathology showed effaced architecture with diffuse follicles and abundant blastoid cells as well as negative CD5 and BCL2, and positive CD10 and CD20. Diagnosis of PFL (stage 3) was made. She completed six courses of cyclophosphamide, doxorubicin, vincristine, and prednisolone and is well 9 months after therapy. The PFL usually presents with stage 1 or 2 disease unlike in the index female case that was also complicated by effusion and ascites due to late presentation. It responded to chemotherapy and has not reoccurred; in contrast to classic FL and reactive follicular hyperplasia (RFH) which should be differentiated from PFL. Although RFH can be caused by TB or HIV, they are not causes of malignant lymphadenopathy. Physicians should be aware of PFL which may present in high clinical stages, but still retain its good prognosis, for the purposes of counseling.
{"title":"Advanced Pediatric-Type Follicular Lymphoma, Consequences of a Late Presentation in a Resource-Poor Setting: Case Report and Literature Review","authors":"A. Nlemadim, T. Ugbem, Gabriel Unimke Udie, Godwin Cletus Omini, Eghomwanre Davis Izekor, O. F. Adedokun, Ekaete Joseph Asuquo, M. M. Meremikwu, F. Odey","doi":"10.1055/s-0043-1777042","DOIUrl":"https://doi.org/10.1055/s-0043-1777042","url":null,"abstract":"Abstract Pediatric-type follicular lymphoma (PFL) is a rare, nonaggressive, slow-growing (indolent), non-Hodgkin lymphoma that is typically seen in males as a localized disease with excellent outcomes. It is largely different from follicular lymphoma (FL). Few published studies on PFL are case series in developed nations. We report on a patient with advanced PFL, a 14-year-old female with 5-year history of neck swellings, abdominal distension for a month, and pericardial effusion, among others. The swellings waxed and waned; and involved all the peripheral lymph nodes. Tuberculosis (TB) GeneXpert and human immunodeficiency virus (HIV) screening were negative. She received anti-TB drugs prior to presentation in our hospital where nodal histopathology showed effaced architecture with diffuse follicles and abundant blastoid cells as well as negative CD5 and BCL2, and positive CD10 and CD20. Diagnosis of PFL (stage 3) was made. She completed six courses of cyclophosphamide, doxorubicin, vincristine, and prednisolone and is well 9 months after therapy. The PFL usually presents with stage 1 or 2 disease unlike in the index female case that was also complicated by effusion and ascites due to late presentation. It responded to chemotherapy and has not reoccurred; in contrast to classic FL and reactive follicular hyperplasia (RFH) which should be differentiated from PFL. Although RFH can be caused by TB or HIV, they are not causes of malignant lymphadenopathy. Physicians should be aware of PFL which may present in high clinical stages, but still retain its good prognosis, for the purposes of counseling.","PeriodicalId":13513,"journal":{"name":"Indian Journal of Medical and Paediatric Oncology","volume":" 35","pages":""},"PeriodicalIF":0.2,"publicationDate":"2023-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138961099","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}
Vina D Dave, Aekta Shah, B. Parambil, Poonam Panjwani, S. Qureshi, M. Ramadwar
Abstract Inflammatory myofibroblastic tumor (IMT) is an intermediate-grade neoplasm of myofibroblastic lineage occurring due to a cytogenetic clonal abnormality of chromosome 2p23. Pediatric renal IMTs are rare and infant renal IMTs are almost anecdotal. We herein report a 1-year-old female child who presented with a firm mass in the right lumbar region. Biopsy, and later, surgical resection revealed a tumor composed of spindle cells with intermixed plasma cells. On immunohistochemistry (IHC), the lesional cells were positive for smooth muscle actin and anaplastic lymphoma kinase (ALK). A diagnosis of IMT was made based on morphology and IHC. Diagnosis of renal IMTs become challenging especially in a tiny biopsy wherein clear cell sarcoma of kidney, Wilms tumor with predominant mesenchymal component, congenital mesoblastic nephroma, and metanephric stromal tumor are the differential diagnoses in this age group. Renal IMTs generally have better prognosis as compared to extrarenal IMTs. Approximately, 50 to 60% of these tumors harbor ALK gene rearrangement as demonstrated by positivity for ALK IHC. ALK inhibitors like crizotinib or ceritinib can be given for advanced metastatic tumors.
{"title":"Renal Inflammatory Myofibroblastic Tumor in an Infant: Case Report with Review of Literature","authors":"Vina D Dave, Aekta Shah, B. Parambil, Poonam Panjwani, S. Qureshi, M. Ramadwar","doi":"10.1055/s-0043-1777041","DOIUrl":"https://doi.org/10.1055/s-0043-1777041","url":null,"abstract":"Abstract Inflammatory myofibroblastic tumor (IMT) is an intermediate-grade neoplasm of myofibroblastic lineage occurring due to a cytogenetic clonal abnormality of chromosome 2p23. Pediatric renal IMTs are rare and infant renal IMTs are almost anecdotal. We herein report a 1-year-old female child who presented with a firm mass in the right lumbar region. Biopsy, and later, surgical resection revealed a tumor composed of spindle cells with intermixed plasma cells. On immunohistochemistry (IHC), the lesional cells were positive for smooth muscle actin and anaplastic lymphoma kinase (ALK). A diagnosis of IMT was made based on morphology and IHC. Diagnosis of renal IMTs become challenging especially in a tiny biopsy wherein clear cell sarcoma of kidney, Wilms tumor with predominant mesenchymal component, congenital mesoblastic nephroma, and metanephric stromal tumor are the differential diagnoses in this age group. Renal IMTs generally have better prognosis as compared to extrarenal IMTs. Approximately, 50 to 60% of these tumors harbor ALK gene rearrangement as demonstrated by positivity for ALK IHC. ALK inhibitors like crizotinib or ceritinib can be given for advanced metastatic tumors.","PeriodicalId":13513,"journal":{"name":"Indian Journal of Medical and Paediatric Oncology","volume":"40 10","pages":""},"PeriodicalIF":0.2,"publicationDate":"2023-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138595214","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 Measurable/minimal residual disease (MRD) status is the most relevant predictor of clinical outcome in hematolymphoid neoplasms, including acute myeloid leukemia (AML). In contrast to acute lymphoblastic leukemia, multiple myeloma, or chronic lymphocytic leukemia, etc., AML is a widely heterogeneous neoplasm with poor clinical outcomes. Multicolor flow cytometry (MFC) is a powerful technology with high sensitivity, rapid results, cost-effectiveness, and easy availability. It is routinely used for diagnosing and MRD monitoring in many hematological neoplasms. However, MFC-based MRD monitoring in AML is complex and challenging. It requires a refined approach, a wide panel of markers, and adequate training and experience. This review focuses on the panel design, processing details, template design, analysis approach, and recent updates in MFC-based MRD monitoring in AML. It further describes the normal distribution and maturation patterns of various sublineages among hematological progenitors and their utility in studying AML MRD.
{"title":"Monitoring Measurable/Minimal Residual Disease in Acute Myeloid Leukemia: Multiparametric Flow Cytometry-Based Approach","authors":"P. Tembhare","doi":"10.1055/s-0043-1772203","DOIUrl":"https://doi.org/10.1055/s-0043-1772203","url":null,"abstract":"Abstract Measurable/minimal residual disease (MRD) status is the most relevant predictor of clinical outcome in hematolymphoid neoplasms, including acute myeloid leukemia (AML). In contrast to acute lymphoblastic leukemia, multiple myeloma, or chronic lymphocytic leukemia, etc., AML is a widely heterogeneous neoplasm with poor clinical outcomes. Multicolor flow cytometry (MFC) is a powerful technology with high sensitivity, rapid results, cost-effectiveness, and easy availability. It is routinely used for diagnosing and MRD monitoring in many hematological neoplasms. However, MFC-based MRD monitoring in AML is complex and challenging. It requires a refined approach, a wide panel of markers, and adequate training and experience. This review focuses on the panel design, processing details, template design, analysis approach, and recent updates in MFC-based MRD monitoring in AML. It further describes the normal distribution and maturation patterns of various sublineages among hematological progenitors and their utility in studying AML MRD.","PeriodicalId":13513,"journal":{"name":"Indian Journal of Medical and Paediatric Oncology","volume":"47 1","pages":"554 - 565"},"PeriodicalIF":0.2,"publicationDate":"2023-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139233523","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":"Approach to Diagnosis of BCR::ABL1 -Negative Myeloproliferative Neoplasms","authors":"Manali Satiza, A. Purohit","doi":"10.1055/s-0043-1769489","DOIUrl":"https://doi.org/10.1055/s-0043-1769489","url":null,"abstract":"","PeriodicalId":13513,"journal":{"name":"Indian Journal of Medical and Paediatric Oncology","volume":"46 1","pages":"585 - 591"},"PeriodicalIF":0.2,"publicationDate":"2023-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139229285","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 A new understanding of acute myeloid leukemia as a varied group of unique biologic entity has emerged, as a result of the identification of various chromosomal aberrations and their association with clinical prognosis and diagnosis. Following induction treatment, cytogenetic examination can establish the presence of any residual malignant cells, it's recurrence, clonal evolution if any, or the formation of novel abnormalities. The G-banded karyotype has been the gold standard method for detecting all of these aberrations for years. The capacity to examine the entire genome through karyotype analysis quickly enabled the detection of deletions, duplications, and structural rearrangements across every chromosome, and the more frequent ones were associated with particular aberrant clinical symptoms. Fluorescence in situ hybridization (FISH) is a sensitive technology that aids in differential diagnosis or therapeutic planning and provides rapid results. Furthermore, the combination of cytogenetic and molecular profiling enables a more precise evaluation of disease prognosis, diagnosis, classification, risk stratification, and patient treatment. Interphase FISH analysis, in conjunction with G-banded chromosomal analysis, can be used as a major testing tool for the evaluation of hematological neoplasms. For accurate and consistent descriptions of genomic changes identified by karyotyping and FISH, a specified terminology is necessary. The International System for Human Cytogenomic Nomenclature is the main source and provides instructions for documenting cytogenetic and molecular findings in laboratory reports. This review discusses the two methods, karyotyping and FISH, their advantages and limitations, sample requirements, various FISH probes that are used, nomenclature for results reporting, and the necessary quality control measures.
摘要 由于发现了各种染色体畸变及其与临床预后和诊断的关系，人们对急性髓性白血病这一独特的生物实体有了新的认识。在诱导治疗后，细胞遗传学检查可以确定是否存在残留的恶性细胞、是否复发、是否有克隆进化或形成新的异常。多年来，G 带核型一直是检测所有这些畸变的黄金标准方法。通过核型分析检查整个基因组的能力使我们很快就能检测出每条染色体上的缺失、重复和结构重排，其中较常见的与特定的异常临床症状有关。荧光原位杂交（FISH）是一种灵敏的技术，有助于鉴别诊断或制定治疗计划，并能快速得出结果。此外，细胞遗传学和分子图谱分析相结合，可以更精确地评估疾病预后、诊断、分类、风险分层和患者治疗。相间 FISH 分析与 G 带染色体分析相结合，可作为评估血液肿瘤的主要检测工具。为了准确、一致地描述核型和 FISH 发现的基因组变化，必须使用特定的术语。国际人类细胞基因组命名系统》（International System for Human Cytogenomic Nomenclature）是主要的术语来源，它为在实验室报告中记录细胞遗传学和分子学结果提供了指导。本综述讨论了核型分析和 FISH 这两种方法、它们的优点和局限性、样本要求、使用的各种 FISH 探针、结果报告术语以及必要的质量控制措施。
{"title":"Role of Cytogenetics and Fluorescence In Situ Hybridization in the Laboratory Workup of Acute Myeloid Leukemias","authors":"H. Jain, D. Shetty","doi":"10.1055/s-0043-1768052","DOIUrl":"https://doi.org/10.1055/s-0043-1768052","url":null,"abstract":"Abstract A new understanding of acute myeloid leukemia as a varied group of unique biologic entity has emerged, as a result of the identification of various chromosomal aberrations and their association with clinical prognosis and diagnosis. Following induction treatment, cytogenetic examination can establish the presence of any residual malignant cells, it's recurrence, clonal evolution if any, or the formation of novel abnormalities. The G-banded karyotype has been the gold standard method for detecting all of these aberrations for years. The capacity to examine the entire genome through karyotype analysis quickly enabled the detection of deletions, duplications, and structural rearrangements across every chromosome, and the more frequent ones were associated with particular aberrant clinical symptoms. Fluorescence in situ hybridization (FISH) is a sensitive technology that aids in differential diagnosis or therapeutic planning and provides rapid results. Furthermore, the combination of cytogenetic and molecular profiling enables a more precise evaluation of disease prognosis, diagnosis, classification, risk stratification, and patient treatment. Interphase FISH analysis, in conjunction with G-banded chromosomal analysis, can be used as a major testing tool for the evaluation of hematological neoplasms. For accurate and consistent descriptions of genomic changes identified by karyotyping and FISH, a specified terminology is necessary. The International System for Human Cytogenomic Nomenclature is the main source and provides instructions for documenting cytogenetic and molecular findings in laboratory reports. This review discusses the two methods, karyotyping and FISH, their advantages and limitations, sample requirements, various FISH probes that are used, nomenclature for results reporting, and the necessary quality control measures.","PeriodicalId":13513,"journal":{"name":"Indian Journal of Medical and Paediatric Oncology","volume":"1 1","pages":"543 - 553"},"PeriodicalIF":0.2,"publicationDate":"2023-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139229944","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}
S. Devaraj, S. Panda, Gourab Arun, Adyakinkar Panda, D. Mohapatra, L. Moharana, Spoorthy Kolluri, S. Kilaru, S. Mohanty, Ghanashyam Biswas
Abstract Anaplastic lymphoma kinase inhibitors (ALKi) are the standard of care for metastatic ALK-rearranged nonsmall cell lung cancer (NSCLC). Though most patients respond well to ALK, seldom there are instances where the disease progresses rapidly. Here, we present a case of a 41-years-old male diagnosed as NSCLC with ALK rearrangement. Despite being started on first- and second-generation ALK-targeted therapy, he had rapid disease progression ultimately succumbing to the disease within 3 months of diagnosis. We suspect that our patient has a variant of ALK, making him resistant to both first- and second-line targeted therapy. Subjecting such nonresponders to next-generation sequencing and identifying the variants might help to recognize a subset of patients among ALK+ NSCLC who will need intense monitoring and early institution of other therapies for a better outcome.
{"title":"Primary Resistance to ALK Inhibitors in a Patient with Nonsmall Cell Lung Cancer with ALK Rearrangement: A Case Report with Review of Literature","authors":"S. Devaraj, S. Panda, Gourab Arun, Adyakinkar Panda, D. Mohapatra, L. Moharana, Spoorthy Kolluri, S. Kilaru, S. Mohanty, Ghanashyam Biswas","doi":"10.1055/s-0043-1776704","DOIUrl":"https://doi.org/10.1055/s-0043-1776704","url":null,"abstract":"Abstract Anaplastic lymphoma kinase inhibitors (ALKi) are the standard of care for metastatic ALK-rearranged nonsmall cell lung cancer (NSCLC). Though most patients respond well to ALK, seldom there are instances where the disease progresses rapidly. Here, we present a case of a 41-years-old male diagnosed as NSCLC with ALK rearrangement. Despite being started on first- and second-generation ALK-targeted therapy, he had rapid disease progression ultimately succumbing to the disease within 3 months of diagnosis. We suspect that our patient has a variant of ALK, making him resistant to both first- and second-line targeted therapy. Subjecting such nonresponders to next-generation sequencing and identifying the variants might help to recognize a subset of patients among ALK+ NSCLC who will need intense monitoring and early institution of other therapies for a better outcome.","PeriodicalId":13513,"journal":{"name":"Indian Journal of Medical and Paediatric Oncology","volume":"24 1","pages":""},"PeriodicalIF":0.2,"publicationDate":"2023-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139228860","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}
Deepak Kumar Mishra, Indranil Dey, Rakesh Demde, S. Vinarkar, M. Parihar
Abstract Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm caused by the BCR::ABL1 fusion gene, which results from a reciprocal translocation between chromosome 9 and 22 t(9;22)(q34;q11). The use of tyrosine kinase inhibitor (TKI) against the chimeric BCR::ABL1 fusion protein has led to a paradigm shift in CML patient outcomes. Despite generational advancements in TKI, a fraction of patients harbor residual disease or exhibit resistance to TKI. The importance of disease monitoring and detection of resistance mechanisms has gained prominence with increasing knowledge about disease evolution. In the past, cytogenetic techniques such as karyotyping and fluorescence in situ hybridization were widely utilized for monitoring disease and prognostication. These techniques had various challenges related to limited sensitivity in minimal residual disease (MRD) monitoring; however, their importance still holds in the detection of additional chromosomal aberrations and in cases with cryptic insertions, variants, and masked Philadelphia chromosome. Molecular genetics has evolved significantly from the past to the present times for MRD monitoring in CML patients. Qualitative reverse transcription polymerase chain reaction (RQ-PCR) can be performed at diagnosis to detect the BCR::ABL1 transcript, while quantitative RQ-PCR is the most widely used and well-standardized MRD monitoring method. The DNA-based assays demonstrated high sensitivity and specificity, with many efforts directed toward making the laborious step of BCR::ABL1 breakpoint characterization less tedious to increase the utility of DNA-based MRD approach in the future. Flow cytometric–based approaches for the detection of the BCR::ABL1 fusion protein have been under trial with a scope of becoming a more robust and convenient methodology for monitoring in the future. Upcoming techniques such as digital PCR and ultra-deep sequencing next-generation sequencing (UDS-NGS) have shown promising results in residual disease monitoring and detection of resistance mutations. Novel MRD monitoring systems that are independent of BCR::ABL1 fusion such as the detection of CD26+ leukemic stem cells and microRNA mutations are the future of residual disease monitoring, which can go up to the level of a single cell. In this review, we tried to discuss the evolution of most of the above-mentioned techniques encompassing the pros, cons, utility, and challenges for MRD monitoring and detection of TKI resistance mutations.
{"title":"Disease Response Assessment Modalities in Chronic Myeloid Leukemia: Past, Present, and Future","authors":"Deepak Kumar Mishra, Indranil Dey, Rakesh Demde, S. Vinarkar, M. Parihar","doi":"10.1055/s-0043-1771186","DOIUrl":"https://doi.org/10.1055/s-0043-1771186","url":null,"abstract":"Abstract Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm caused by the BCR::ABL1 fusion gene, which results from a reciprocal translocation between chromosome 9 and 22 t(9;22)(q34;q11). The use of tyrosine kinase inhibitor (TKI) against the chimeric BCR::ABL1 fusion protein has led to a paradigm shift in CML patient outcomes. Despite generational advancements in TKI, a fraction of patients harbor residual disease or exhibit resistance to TKI. The importance of disease monitoring and detection of resistance mechanisms has gained prominence with increasing knowledge about disease evolution. In the past, cytogenetic techniques such as karyotyping and fluorescence in situ hybridization were widely utilized for monitoring disease and prognostication. These techniques had various challenges related to limited sensitivity in minimal residual disease (MRD) monitoring; however, their importance still holds in the detection of additional chromosomal aberrations and in cases with cryptic insertions, variants, and masked Philadelphia chromosome. Molecular genetics has evolved significantly from the past to the present times for MRD monitoring in CML patients. Qualitative reverse transcription polymerase chain reaction (RQ-PCR) can be performed at diagnosis to detect the BCR::ABL1 transcript, while quantitative RQ-PCR is the most widely used and well-standardized MRD monitoring method. The DNA-based assays demonstrated high sensitivity and specificity, with many efforts directed toward making the laborious step of BCR::ABL1 breakpoint characterization less tedious to increase the utility of DNA-based MRD approach in the future. Flow cytometric–based approaches for the detection of the BCR::ABL1 fusion protein have been under trial with a scope of becoming a more robust and convenient methodology for monitoring in the future. Upcoming techniques such as digital PCR and ultra-deep sequencing next-generation sequencing (UDS-NGS) have shown promising results in residual disease monitoring and detection of resistance mutations. Novel MRD monitoring systems that are independent of BCR::ABL1 fusion such as the detection of CD26+ leukemic stem cells and microRNA mutations are the future of residual disease monitoring, which can go up to the level of a single cell. In this review, we tried to discuss the evolution of most of the above-mentioned techniques encompassing the pros, cons, utility, and challenges for MRD monitoring and detection of TKI resistance mutations.","PeriodicalId":13513,"journal":{"name":"Indian Journal of Medical and Paediatric Oncology","volume":"7 1","pages":"592 - 601"},"PeriodicalIF":0.2,"publicationDate":"2023-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139232635","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}
Mehak Sehgal, A. Dhua, V. Jain, P. Goel, Dev Yadav, S. Agarwala
The coronavirus pandemic has had a signi fi cant impact on our daily life and led to a surge in digitization and utilization of resources available on the Internet. 1 This shifting trend is also re fl ected in health care and medicine, where apart from general medical anxiety due to the pandemic, the public relied on information technology for addressing their medical concerns. Pediatric solid tumors often cause a degree of anxiety and stress among parents of the affected children. 2 With growing access to the Internet, parents of children diagnosed with cancer often resort to using its resources for fi nding further information related to their child ’ s diagnosis and prognosis. We sought to evaluate the pre-and postpan-demic interest in the information on pediatric solid tumors available on the Internet by the public. Google Trends is a powerful, freely accessible tool that provides information on Internet search data and gives access toalargelyun fi lteredsampleofactualsearchrequestsmadeto Google. 3 Google Trends was used to conduct search for terms from the parents ’ perspective after a diagnosis of an extracranial pediatric solid tumor for their child. Three common tumors used were “ Wilms Tumor, ” “ Neuroblastoma, ” and “ Hepatoblastoma. ” The search terms list consisted of “ Wilms Tumor, ” “ Wilms Tumor Survival Rate, ” “ Wilms Tumor Symptoms, ” “ Wilms Tumor Treatment, ” “ Neuroblastoma, ” “ Neuro-blastoma Survival Rate, ” “ Neuroblastoma Symptoms, ”
{"title":"Determining the Trend of Public Interest in Pediatric Solid Tumors: A Pre- and Post-COVID Pandemic Analysis","authors":"Mehak Sehgal, A. Dhua, V. Jain, P. Goel, Dev Yadav, S. Agarwala","doi":"10.1055/s-0043-1776710","DOIUrl":"https://doi.org/10.1055/s-0043-1776710","url":null,"abstract":"The coronavirus pandemic has had a signi fi cant impact on our daily life and led to a surge in digitization and utilization of resources available on the Internet. 1 This shifting trend is also re fl ected in health care and medicine, where apart from general medical anxiety due to the pandemic, the public relied on information technology for addressing their medical concerns. Pediatric solid tumors often cause a degree of anxiety and stress among parents of the affected children. 2 With growing access to the Internet, parents of children diagnosed with cancer often resort to using its resources for fi nding further information related to their child ’ s diagnosis and prognosis. We sought to evaluate the pre-and postpan-demic interest in the information on pediatric solid tumors available on the Internet by the public. Google Trends is a powerful, freely accessible tool that provides information on Internet search data and gives access toalargelyun fi lteredsampleofactualsearchrequestsmadeto Google. 3 Google Trends was used to conduct search for terms from the parents ’ perspective after a diagnosis of an extracranial pediatric solid tumor for their child. Three common tumors used were “ Wilms Tumor, ” “ Neuroblastoma, ” and “ Hepatoblastoma. ” The search terms list consisted of “ Wilms Tumor, ” “ Wilms Tumor Survival Rate, ” “ Wilms Tumor Symptoms, ” “ Wilms Tumor Treatment, ” “ Neuroblastoma, ” “ Neuro-blastoma Survival Rate, ” “ Neuroblastoma Symptoms, ”","PeriodicalId":13513,"journal":{"name":"Indian Journal of Medical and Paediatric Oncology","volume":"22 S1","pages":""},"PeriodicalIF":0.2,"publicationDate":"2023-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139253037","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}
Reshma R. Balachandran, Vishesha V. Adhvaryu, Shalaka Joshi, Mukta Ramadwar, Ameya Bindu, Prakash Nayak
Abstract Primary, nonmidline, extragonadal germ cell tumors are rare. Numerous hypotheses have been proposed regarding their origin. There is lack of consensus regarding their appropriate management. We report a case of an immature teratoma arising of the left palm. A 36-year-old lady presented with a recurrent left palm swelling. Histopathological features with immunohistochemical evaluation were characteristic of an immature teratoma. Alpha-fetoprotein (AFP) and lactate dehydrogenase (LDH) were elevated. She received preoperative chemotherapy with bleomycin, etoposide, cisplatin (BEP) followed by wide excision of the palm lesion and reconstruction with free latissimus dorsi flap. Postoperatively, two more cycles of BEP were given. Eight months later, she presented with large left axillary mass which showed metastatic deposits of immature teratoma on trucut biopsy. AFP and LDH were mildly elevated. On staging fluorodeoxyglucose-positron emission tomography (FDG-PET), there were no distant metastases. She received two cycles of vinblastine, ifosfamide, and cisplatin (VeIP). Postchemotherapy FDG-PET showed good metabolic response; however, the mass remained morphologically stable. Complete resection of the axillary mass was achieved with resection of a segment of axillary vein and end-to-end reanastomosis. At 12 months of follow-up the patient is disease free. This is the first report of axillary metastases in immature teratoma of the upper extremity. Axilla is a possible site of lymph node metastases in extremity teratoma. Primary extragonadal germ cell tumor should be managed with complete surgical resection and chemotherapy.
{"title":"Primary, Nonmidline, Extragonadal, Immature Teratoma of the Palm with Axillary Nodal Metastasis: A Rare Case Report and Review of Literature","authors":"Reshma R. Balachandran, Vishesha V. Adhvaryu, Shalaka Joshi, Mukta Ramadwar, Ameya Bindu, Prakash Nayak","doi":"10.1055/s-0043-1776343","DOIUrl":"https://doi.org/10.1055/s-0043-1776343","url":null,"abstract":"Abstract Primary, nonmidline, extragonadal germ cell tumors are rare. Numerous hypotheses have been proposed regarding their origin. There is lack of consensus regarding their appropriate management. We report a case of an immature teratoma arising of the left palm. A 36-year-old lady presented with a recurrent left palm swelling. Histopathological features with immunohistochemical evaluation were characteristic of an immature teratoma. Alpha-fetoprotein (AFP) and lactate dehydrogenase (LDH) were elevated. She received preoperative chemotherapy with bleomycin, etoposide, cisplatin (BEP) followed by wide excision of the palm lesion and reconstruction with free latissimus dorsi flap. Postoperatively, two more cycles of BEP were given. Eight months later, she presented with large left axillary mass which showed metastatic deposits of immature teratoma on trucut biopsy. AFP and LDH were mildly elevated. On staging fluorodeoxyglucose-positron emission tomography (FDG-PET), there were no distant metastases. She received two cycles of vinblastine, ifosfamide, and cisplatin (VeIP). Postchemotherapy FDG-PET showed good metabolic response; however, the mass remained morphologically stable. Complete resection of the axillary mass was achieved with resection of a segment of axillary vein and end-to-end reanastomosis. At 12 months of follow-up the patient is disease free. This is the first report of axillary metastases in immature teratoma of the upper extremity. Axilla is a possible site of lymph node metastases in extremity teratoma. Primary extragonadal germ cell tumor should be managed with complete surgical resection and chemotherapy.","PeriodicalId":13513,"journal":{"name":"Indian Journal of Medical and Paediatric Oncology","volume":" 12","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135141171","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}
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