85 results on '"Sharat Damodar"'
Search Results
2. P1409: PHASE-2 STUDY OF VARNIMCABTAGENE AUTOLEUCEL (IMN-003A) FIRST-IN-INDIA INDUSTRY CD19-DIRECTED CAR-T WITH FRACTIONATED INFUSIONS FOR PATIENTS WITH RELAPSED REFRACTORY B CELL MALIGNANCIES: IMAGINE STUDY
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Pankaj Malhotra, Sharat Damodar, Sunil Bhat, Raja Thirumalairaj, Revathy Raj, Akshatha Nayak, Pooja Mallya, Ravi Joshi, Deepak Mb, Sudarshan Chougule, Sudeshna Dhar, Arun Kumar Mg, Pallavi Arasu, Sri Ramulu Elluru, Mohammed Manzoor Akheel, and Anil Kamat
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Diseases of the blood and blood-forming organs ,RC633-647.5 - Published
- 2023
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3. Management of B-cell lineage acute lymphoblastic leukemia: expert opinion from an Indian panel via Delphi consensus method
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Vikram Mathews, Anu Korula, Anupam Chakrapani, Dinesh Bhurani, Jina Bhattacharyya, Manju Sengar, Pankaj Malhotra, Pavan Kumar Boyella, Pawan Kumar Singh, Prasanth Ganesan, Rishi Dhawan, Sameer Melinkeri, Sharat Damodar, Tuphan Kanti Dolai, and Venkatraman Radhakrishnan
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B-cell acute lymphoblastic leukemia ,relapsed/refractory ,India ,management ,consensus ,Delphi ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
IntroductionCurrently, there are no guidelines for the management of B-cell lineage acute lymphoblastic leukemia (B-ALL) from an Indian perspective. The diagnostic workup, monitoring, and treatment of B-ALL vary among different physicians and institutes.ObjectiveTo develop evidence-based practical consensus recommendations for the management of B-ALL in Indian settings.MethodsModified Delphi consensus methodology was considered to arrive at a consensus. An expert scientific committee of 15 experts from India constituted the panel. Clinically relevant questions belonging to three major domains were drafted for presentation and discussion: (i) diagnosis and risk assignment; (ii) frontline treatment; and (iii) choice of therapy (optimal vs. real-world practice) in relapsed/refractory (R/R) settings. The questionnaire was shared with the panel members through an online survey platform. The level of consensus was categorized into high (≥ 80%), moderate (60%–79%), and no consensus (< 60%). The process involved 2 rounds of discussion and 3 rounds of Delphi survey. The questions that received near or no consensus were discussed during virtual meetings (Delphi rounds 1 and 2). The final draft of the consensus was emailed to the panel for final review.ResultsExperts recommended morphologic assessment of peripheral blood or bone marrow, flow cytometric immunophenotyping, and conventional cytogenetic analysis in the initial diagnostic workup. Berlin–Frankfurt–Münster (BFM)–based protocol is the preferred frontline therapy in pediatric and adolescent and young adult patients with B-ALL. BFM/German Multicenter Study Group for Adult Acute Lymphoblastic Leukemia–based regimen is suggested in adult patients with B-ALL. Immunotherapy (blinatumomab or inotuzumab ozogamicin) followed by allogeneic hematopoietic cell transplantation (allo-HCT) is the optimal choice of therapy that would yield the best outcomes if offered in the first salvage in patients with R/R B-ALL. In patients with financial constraints or prior allo-HCT (real-world practice) at first relapse, standard-intensive chemotherapy followed by allo-HCT may be considered. For subsequent relapses, chimeric antigen receptor T-cell therapy or palliative care was suggested as the optimal choice of therapy.ConclusionThis expert consensus will offer guidance to oncologists/clinicians on the management of B-ALL in Indian settings.
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- 2023
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4. Outcomes of patients with hematologic malignancies and COVID-19 from the Hematologic Cancer Registry of India
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Arihant Jain, Lingaraj Nayak, Uday Prakash Kulkarni, Nikita Mehra, Uday Yanamandra, Smita Kayal, Sharat Damodar, Joseph M. John, Prashant Mehta, Suvir Singh, Pritesh Munot, Sushil Selvarajan, Venkatraman Radhakrishnan, Deepesh Lad, Rajan Kapoor, Biswajit Dubashi, Ram S. Bharath, Hasmukh Jain, P. K. Jayachandran, Jeyaseelan Lakshmanan, Thenmozhi Mani, Jayashree Thorat, Satyaranjan Das, Omprakash Karunamurthy, Biju George, Manju Sengar, and Pankaj Malhotra
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Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Published
- 2022
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5. Exovesicular-Shh confers Imatinib resistance by upregulating Bcl2 expression in chronic myeloid leukemia with variant chromosomes
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Anusha, Hamza Dalal, Sitalakshmi Subramanian, Snijesh V. P., Divya A. Gowda, Krishnamurthy H., Sharat Damodar, and Neha Vyas
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Cytology ,QH573-671 - Abstract
Abstract Chronic myeloid leukemia (CML) patients with complex chromosomal translocations as well as non-compliant CML patients often demonstrate short-lived responses and poor outcomes on the current therapeutic regimes using Imatinib and its variants. It has been derived so far that leukemic stem cells (LSCs) are responsible for Imatinib resistance and CML progression. Sonic hedgehog (Shh) signaling has been implicated in proliferation of this Imatinib-resistant CD34(+) LSCs. Our work here identifies the molecular mechanism of Shh-mediated mutation-independent Imatinib resistance that is most relevant for treating CML-variants and non-compliant patients. Our results elucidate that while Shh can impart stemness, it also upregulates expression of anti-apoptotic protein—Bcl2. It is the upregulation of Bcl2 that is involved in conferring Imatinib resistance to the CD34(+) LSCs. Sub-toxic doses of Bcl2 inhibitor or Shh inhibitor (<
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- 2021
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6. Case Report of a Rare Incidence of IgH Amplification Leading to Acute Kidney Injury in a Multiple Myeloma Patient
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Sowmya Thanikachalam, Vijay Kumar Srinivasalu, K.S. Nataraj, Sharat Damodar, and Manjula Das
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multiple myeloma ,igh amplification ,acute kidney injury ,molecular cytogenetics ,heavy chain deposition ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
We present a case report of a 62-year-old male, treated for kappa light chain multiple myeloma with chemotherapy followed by autologous stem cell transplant (ASCT) in 2014. He has been in complete remission for 4 years. In 2018, he was evaluated for hypercreatinemia and acute kidney injury(AKI) with a suspicion of disease relapse; he underwent evaluation with bone marrow aspiration cytology which showed no evidence of relapse. However, careful cytogenetic analyses showed IgH amplification (14q32) which probably was the cause for AKI in the absence of any structural abnormality in the kidney. Heavy chain deposition leads to AKI in multiple myeloma, and its association with IgH amplification leading to AKI is reported here. Though heavy chain deposition leading to AKI is common, IgH amplification at chromosome level is the first case observed.
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- 2021
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7. IL-6 and IL-10 as predictors of disease severity in COVID-19 patients: results from meta-analysis and regression
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Sujan K. Dhar, Vishnupriyan K, Sharat Damodar, Shashi Gujar, and Manjula Das
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COVID-19 ,Meta-analysis ,Cytokines ,Logistic models ,Science (General) ,Q1-390 ,Social sciences (General) ,H1-99 - Abstract
Aims: SARS-CoV-2, an infectious agent behind the ongoing COVID-19 pandemic, induces high levels of cytokines such as IL-1, IL-2, IL-4, IL-6, IL-10, TNF-α, IFN-γ etc in infected individuals that play a role in the underlying patho-physiology. Nonetheless, exact association and contribution of every cytokine towards COVID-19 pathology remains poorly understood. Delineation of the roles of cytokines during COVID-19 holds the key to efficient patient management in clinics. This study performed a comprehensive meta-analysis to establish association between induced cytokines and COVID-19 disease severity to help in prognosis and clinical care. Main methods: Scientific literature was searched to identify 13 cytokines (IL-1β, IL-2, IL-2R, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12, IL-17, TNF-α and IFN-γ) from 18 clinical studies. Standardized mean difference (SMD) for selected 6 cytokines IL-2, IL-4, IL-6, IL-10, TNF-α and IFN-γ between severe and non-severe COVID-19 patient groups were summarized using random effects model. A classifier was built using logistic regression model with cytokines having significant SMD as covariates. Key findings: Out of the 13 cytokines, IL-6 and IL-10 showed statistically significant SMD across studies synthesized. Classifier with mean values of both IL-6 and IL-10 as covariates performed well with accuracy of ~92% that was significantly higher than accuracy reported in literature with IL-6 and IL-10 as individual covariates. Significance: Simple panel proposed by us with only two cytokine markers can be used as predictors for fast diagnosis of patients with higher risk of COVID-19 disease deterioration and thus can be managed well for a favourable prognosis.
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- 2021
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8. Impact of anemia and red cell indices on the diagnosis of pre-diabetes and diabetes in Indian adult population: Is there a cut-off guide for clinicians?
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Subramanian Kannan, Chinthala Jaipalreddy, Vellaichamy Muthupandi Annapandian, Bangalore Venkatraman Murali Mohan, Sharat Damodar, Kranti Shreesh Khadilkar, and Kumbenahalli Siddegowda Shivaprasad
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anemia ,concordance ,diabetes ,discordance ,hba1c ,pre-diabetes ,Diseases of the endocrine glands. Clinical endocrinology ,RC648-665 ,Diseases of the digestive system. Gastroenterology ,RC799-869 - Abstract
Background: It is well known that anemia and red cell turn over affects the HbA1c value. Iron deficiency anemia increases the HbA1c and haemolytic anemia lowers it. However, the cut-off of haemoglobin (Hb) or red-cell indices when the HbA1c value becomes unreliable is not known. Aim: We sought to find out values of HbA1c and red-cell indices where there is considerable discordance between HbA1c and plasma glucose (PG) values in the diagnosis of diabetes (DM) and pre-diabetes (Pre-DM) making HbA1c values unreliable. Methods: A cross-sectional study of 237 non-diabetic subjects who attended our out-patient division of preventive health check-up clinics, between November 2016 and December 2017. Data was collected only from relatively healthy subjects who had voluntarily opted for undergoing a preventative health check-up (including a diabetes screening). Patients were classified as concordant (fasting and 2-hr post meal glucose values are in agreement with HbA1c) and discordant (values are not in agreement with HbA1c). Results: A total of 237 patients (73% males) with mean age was 47.2±9.7 years (range 25-75) were included in the study. The HbA1c definition group had more diagnosis of DM (153 vs 96) and but lesser numbers of pre-DM (66 vs 102) compared to the PG group. Out of 237 patients, 133 (56%) showed concordance and 104 (44%) were discordant. The FPG, 2h-PPBG and HbA1c are significantly higher in the concordant group. The Hb value and MCV were significantly higher (p7% (20%). While no single Hb or MCV value could predict discordance, a RDW value >17 was consistently associated with discordance across all the HbA1c strata. Conclusion: A HbA1c below 7% is significantly influenced by red-cell turn over indices and clinicians need to perform additional testing using plasma glucose levels to confirm the presence of diabetes or pre-diabetes. In patients whose RDW >17, HbA1c should be replaced by 75gm OGTT as a test of choice for diagnosis of diabetes or pre-diabetes.
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- 2019
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9. Relative quantification of BCL2 mRNA for diagnostic usage needs stable uncontrolled genes as reference.
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Nehanjali Dwivedi, Sreejeta Mondal, Smitha P K, Sowmya T, Kartik Sachdeva, Christopher Bathula, Vishnupriyan K, Nataraj K S, Sharat Damodar, Sujan K Dhar, and Manjula Das
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Medicine ,Science - Abstract
Dysregulation of BCL2 is a pathophysiology observed in haematological malignancies. For implementation of available treatment-options it is preferred to know the relative quantification of BCL2 mRNA with appropriate reference genes. For the choice of reference genes-(i) Reference Genes were selected by assessing variation of >60,000 genes from 4 RNA-seq datasets of haematological malignancies followed by filtering based on their GO biological process annotations and proximity of their chromosomal locations to known disease translocations. Selected genes were experimentally validated across various haematological malignancy samples followed by stability comparison using geNorm, NormFinder, BestKeeper and RefFinder. (ii) 43 commonly used Reference Genes were obtained from literature through extensive systematic review. Levels of BCL2 mRNA was assessed by qPCR normalized either by novel reference genes from this study or GAPDH, the most cited reference gene in literature and compared. The analysis showed PTCD2, PPP1R3B and FBXW9 to be the most unregulated genes across lymph-nodes, bone marrow and PBMC samples unlike the Reference Genes used in literature. BCL2 mRNA level shows a consistent higher expression in haematological malignancy patients when normalized by these novel Reference Genes as opposed to GAPDH, the most cited Reference Gene. These reference genes should also be applicable in qPCR platforms using Taqman probes and other model systems including cell lines and rodent models. Absence of sample from healthy-normal individual in diagnostic cases call for careful selection of Reference Genes for relative quantification of a biomarker by qPCR.BCL2 can be used as molecular diagnostics only if normalized with a set of reference genes with stable yet low levels of expression across different types of haematological malignancies.
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- 2020
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10. Incidence of early neurological complications in post allogeneic stem cell transplant patients
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Aarati Kulkarni, Prathamesh Kulkarni, Sunil Bhat, Sharat Damodar, K.S. Nataraj, Shobha Badiger, Udayshankar, and Vivek Jacob Philip
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Pediatrics ,RJ1-570 - Published
- 2017
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11. Haploidentical haematopoeitic stem cell transplants (Hsct) in paediatric acute leukemia
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Sohini Chakraborty, Shobha Badiger, Sharat Damodar, and Sunil Bhat
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Pediatrics ,RJ1-570 - Published
- 2017
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12. Hematopoietic stem cell transplantation in thalassemia. A single center experience from India
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Waseem Iqbal, Sonamani Ngangbam, Shobha Badiger, Sharat Damodar, K.S. Nataraj, B.R. Prathip, and Sunil Bhat
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Pediatrics ,RJ1-570 - Published
- 2016
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13. Low relapse rates in TCR α/β and CD 19 depleted graft in haplo-identical stem cell transplantation for pediatric acute leukemia
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Sonamani Ngangbam, Waseem Iqbal, Shobha Badiger, Sharat Damodar, K.S. Nataraj, B.R. Prathip, and Sunil Bhat
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Pediatrics ,RJ1-570 - Published
- 2016
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14. Clinical experience of granulocyte transfusion therapy in management of neutropenia related infections in a tertiary care center
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Sohini Chakraborty, Ruchi Chaudhary, Waseem Iqbal, Sonamani Ngangbam, Shobha Badiger, Tadele Hailu, B.R. Prathip, Sharat Damodar, K.S. Nataraj, and Sunil Bhat
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Pediatrics ,RJ1-570 - Published
- 2016
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15. Outcome in allogeneic T cell depleted haplo-identical transplantation with TCR α/β and CD 19 depletion in pediatric patients: A single-center experience from South India
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Sonamani Ngangbam, Waseem Iqbal, Shobha Badiger, Sharat Damodar, K.S. Nataraj, B.R. Prathip, Nedun Cherian, and Sunil Bhat
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Pediatrics ,RJ1-570 - Published
- 2016
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16. Allogeneic stem cell transplant in a patient with aplastic anemia with bacteremia and candidemia
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Sharat Damodar
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aplastic anemia ,transplant ,sepsis ,Diseases of the blood and blood-forming organs ,RC633-647.5 - Published
- 2008
17. Fludrabine Treosulfan Conditioning Regimen Appears Safe and Effective in Patients with Acute Myeloid Leukemia(AML) and Myelodysplastic Syndrome (MDS) Undergoing Allogenic Hematopoietic Stem Cell Transplantation (HSCT)
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Chitresh Yadav, Sharat Damodar, Rahul Bhargava, Nikhil Krishna Haridas, Ganesh S Jaishetwar, Mobin Paul, Bharath Ram S, Akshatha Nayak, Monisha Harimadhavan, Rohit Mangal, Manoj Unni, Rema Ganapathy, Rashmi Suresh Yawalkar, Shreya Gopal Agrawal, Ullas Mony, Nivedhitha Kartha, and Neeraj Sidharthan
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Immunology ,Cell Biology ,Hematology ,Biochemistry - Published
- 2022
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18. Case Report of a Rare Incidence of IgH Amplification Leading to Acute Kidney Injury in a Multiple Myeloma Patient
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Sharat Damodar, Sowmya Thanikachalam, Vijay Kumar Srinivasalu, Manjula Das, and K.S. Nataraj
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0301 basic medicine ,medicine.medical_specialty ,medicine.medical_treatment ,Case Report ,urologic and male genital diseases ,Immunoglobulin light chain ,lcsh:RC254-282 ,Gastroenterology ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,medicine ,igh amplification ,Multiple myeloma ,Chemotherapy ,Kidney ,urogenital system ,business.industry ,heavy chain deposition ,Incidence (epidemiology) ,Acute kidney injury ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,medicine.disease ,female genital diseases and pregnancy complications ,multiple myeloma ,030104 developmental biology ,medicine.anatomical_structure ,acute kidney injury ,Oncology ,030220 oncology & carcinogenesis ,molecular cytogenetics ,Bone marrow ,Stem cell ,business - Abstract
We present a case report of a 62-year-old male, treated for kappa light chain multiple myeloma with chemotherapy followed by autologous stem cell transplant (ASCT) in 2014. He has been in complete remission for 4 years. In 2018, he was evaluated for hypercreatinemia and acute kidney injury(AKI) with a suspicion of disease relapse; he underwent evaluation with bone marrow aspiration cytology which showed no evidence of relapse. However, careful cytogenetic analyses showed IgH amplification (14q32) which probably was the cause for AKI in the absence of any structural abnormality in the kidney. Heavy chain deposition leads to AKI in multiple myeloma, and its association with IgH amplification leading to AKI is reported here. Though heavy chain deposition leading to AKI is common, IgH amplification at chromosome level is the first case observed.
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- 2021
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- View/download PDF
19. Exovesicular-Shh confers Imatinib resistance by upregulating Bcl2 expression in chronic myeloid leukemia with variant chromosomes
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Hamza Yusuf Dalal, Divya A. Gowda, Anusha, Sharat Damodar, Neha Vyas, Sitalakshmi Subramanian, H Krishnamurthy, and V. P. Snijesh
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Cancer Research ,Immunology ,CD34 ,Antineoplastic Agents ,Chromosomal translocation ,Article ,Cellular and Molecular Neuroscience ,Downregulation and upregulation ,Leukemia, Myelogenous, Chronic, BCR-ABL Positive ,hemic and lymphatic diseases ,Antineoplastic Combined Chemotherapy Protocols ,Chromosomes, Human ,Humans ,Medicine ,Hedgehog Proteins ,Sonic hedgehog ,lcsh:QH573-671 ,Protein Kinase Inhibitors ,neoplasms ,Chronic myeloid leukaemia ,biology ,Imatinib resistance ,business.industry ,lcsh:Cytology ,Veratrum Alkaloids ,Myeloid leukemia ,Imatinib ,Cell Biology ,Up-Regulation ,Gene Expression Regulation, Neoplastic ,Thiazoles ,Cancer therapeutic resistance ,Proto-Oncogene Proteins c-bcl-2 ,Drug Resistance, Neoplasm ,Imatinib Mesylate ,Neoplastic Stem Cells ,Cancer research ,biology.protein ,Stem cell ,K562 Cells ,business ,medicine.drug - Abstract
Chronic myeloid leukemia (CML) patients with complex chromosomal translocations as well as non-compliant CML patients often demonstrate short-lived responses and poor outcomes on the current therapeutic regimes using Imatinib and its variants. It has been derived so far that leukemic stem cells (LSCs) are responsible for Imatinib resistance and CML progression. Sonic hedgehog (Shh) signaling has been implicated in proliferation of this Imatinib-resistant CD34(+) LSCs. Our work here identifies the molecular mechanism of Shh-mediated mutation-independent Imatinib resistance that is most relevant for treating CML-variants and non-compliant patients. Our results elucidate that while Shh can impart stemness, it also upregulates expression of anti-apoptotic protein—Bcl2. It is the upregulation of Bcl2 that is involved in conferring Imatinib resistance to the CD34(+) LSCs. Sub-toxic doses of Bcl2 inhibitor or Shh inhibitor (<
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- 2021
20. Response, Peak and Persistence of Varnimcabtagene Autoleucel (IMN-003A), First-in-India Industry CD19-Directed CAR-T Cell Therapy, with Fractionated Infusions for Patients with Relapsed and/or Refractory B Cell Malignancies: Early Results (IMAGINE Study)
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Sunil Bhat, Sharat Damodar, Pooja Mallya, Akshatha Nayak, Ravi Joshi, Bharath Ram S, Sudarshan Chougule, Deepak MB, Gopinadh Jakka, Sudeshna Dhar, Anne Roshan Joseph, Arun Kumar MG, Murugan Palanisamy, Jeetendra Kumar, Melina Soares, Pallavi Arasu, Sri Ramulu Elluru, Mohammed Manzoor Akheel, and Anil Kamat
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Immunology ,Cell Biology ,Hematology ,Biochemistry - Published
- 2022
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21. Induction Related Mortality Score in Acute Myeloid Leukemia: Prospective Validation Study (pRISM) of the Hematology Cancer Consortium (HCC)
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Smita Kayal, Hasmukh Jain, Lingaraj Nayak, Jayashree Thorat, Jina Bhattacharyya, Damodar Das, Sewali Deka Talukdar, Dinesh Bhurani, Rayaz Ahmed, Narendra Agrawal, Dubashi Biswajit, Prasanth Ganesan, Chandran K. Nair, Vineetha Raghavan, Manuprasad A, Uday Kulkarni, Sushil Selvarajan, Jayachandran PK, Parathan Karunakaran, Sadashivudu Gundeti, Kundan Mishra, Sharat Damodar, Bharath Ram S, Atul Sharma, Suvir Singh, M. Joseph John, Gaurav Prakash, Smitha Carol Saldanha, Chepsy C Philip, Prashant Mehta, Thenmozhi Mani, Om Prakash, Marimuthu S, Jeyaseelan Lakshmanan, Manju Sengar, Vikram Mathews, and Rajan Kapoor
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Immunology ,Cell Biology ,Hematology ,Biochemistry - Published
- 2022
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22. Early Results from a Phase-2 Study of Varnimcabtagene Autoleucel (IMN-003A), a First-in-India Industry CD19-Directed CAR-T Cell Therapy with Fractionated Infusions for Patients with Relapsed and/or Refractory B Cell Malignancies (IMAGINE Study)
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Sharat Damodar, Sunil Bhat, Akshatha Nayak, Pooja Mallya, Bharath Ram S, Ravi Joshi, Deepak MB, Sudarshan Chougule, Anne Roshan Joseph, Gopinadh Jakka, Sudeshna Dhar, Arun Kumar MG, Murugan Palanisamy, Sri Ramulu Elluru, Mohammed Manzoor Akheel, Arun Anand, and Anil Kamat
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Immunology ,Cell Biology ,Hematology ,Biochemistry - Published
- 2022
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23. Quantification of Liver Iron Overload: Correlation of MRI and Liver Tissue Biopsy in Pediatric Thalassemia Major Patients Undergoing Bone Marrow Transplant
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Shobha Badiger, Varun Bafna, K.S. Nataraj, Sunil Bhat, Vimal Raj, Sharat Damodar, and Vellaichamy M Annapandian
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Bone marrow transplant ,medicine.medical_specialty ,Liver Iron Concentration ,Hematology ,medicine.diagnostic_test ,business.industry ,Thalassemia ,Magnetic resonance imaging ,medicine.disease ,Gastroenterology ,In vivo ,Liver tissue ,Internal medicine ,Biopsy ,medicine ,Original Article ,business - Abstract
Determination of the magnitude of body iron stores helps to identify individuals at risk of iron-induced organ damage in Thalassemia patients. The most direct clinical method of measuring liver iron concentration (LIC) is through chemical analysis of needle biopsy specimens. Here we present a noninvasive method for the measurement of LIC in vivo using magnetic resonance imaging (MRI). Twenty-three pediatric Thalassemia major patients undergoing bone marrow transplantation at our centre were studied. All 23 patients had MRI T2* and R2* decay time for evaluation of LIC on a 1.5 Tesla MRI system followed by liver tissue biopsy for the assessment of iron concentration using an atomic absorption spectrometry. Simultaneously, serum ferritin levels were measured by enzymatic assay. We have correlated biopsy LIC with liver T2* and serum ferritin values with liver R2*. Of the 23 patients 11 were males, the mean age was 8.3 ± 3.7 years. The study results showed a significant correlation between biopsy LIC and liver T2* MRI (r = 0.768; p
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- 2020
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24. Prophyactic Platelet Transfusion in Stable Dengue Fever Patients: Is It Really Necessary?
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Prashantha, B., Varun, S., Sharat, Damodar, Murali Mohan, B. V., Ranganatha, R., Shivaprasad, and Naveen, Manchal
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- 2014
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25. Safety and efficacy of intravenous immunoglobulin (Flebogamma® 10% DIF) in patients with immune thrombocytopenic purpura
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Chirag Shah, Paul Pinciaro, Maria Esperança Aragonés, Karen Rucker, Gladis Barrera, Jaume Ayguasanosa, Sharat Damodar, Vijay Ramanan, Chieh-Lin 'Kathy' Fu, Shashikant Apte, Giraldo Kato, Marcela Torres, Joseph M John, Jordi Navarro-Puerto, and Cecil Ross
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0301 basic medicine ,medicine.medical_specialty ,Immunology ,Gastroenterology ,03 medical and health sciences ,0302 clinical medicine ,Immune system ,hemic and lymphatic diseases ,Internal medicine ,medicine ,Immunology and Allergy ,In patient ,Platelet ,Adverse effect ,End point ,biology ,business.industry ,medicine.disease ,Thrombocytopenic purpura ,Flebogamma ,030104 developmental biology ,Oncology ,030220 oncology & carcinogenesis ,biology.protein ,Antibody ,business - Abstract
Aim: To evaluate the safety and efficacy of 10% intravenous immunoglobulin (IVIG; Flebogamma® 10% DIF) in individuals with chronic immune thrombocytopenic purpura (ITP). Patients & methods: Patients aged 3–70 years, diagnosed with chronic ITP, received 1 g/kg IVIG over two consecutive days. Results: 64 evaluable patients (51 adults, 13 children) with chronic ITP received IVIG. The primary efficacy end point (increased platelet counts from ≤20 × 109/l to ≥50 × 109/l by day 8) was achieved by 81.3% of patients; mean time to response was 1.7 days (all responders). Adverse events, mostly mild or moderate, were reported in 59 patients (92.2%). Conclusion: Flebogamma® 10% DIF administered over two consecutive days was safe and effective in adults and children with chronic ITP.
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- 2019
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26. Mobilization of backup autologous peripheral stem cells in pediatric thalassemia patients: A single center experience
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Pooja P. Mallya, Shobha Badiger, null Prathip, Ravi Joshi, Sharat Damodar, null Santhosh, null Shwetha, null Swathi, null Monika, null Gayatri, and Sunil Bhat
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Oncology ,Pediatrics, Perinatology and Child Health ,Hematology - Published
- 2021
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27. Relative quantification of BCL2 mRNA for diagnostic usage needs stable uncontrolled genes as reference
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Sreejeta Mondal, Christopher Bathula, Nehanjali Dwivedi, Smitha P K, Sujan K. Dhar, Kartik Sachdeva, Nataraj K S, Manjula Das, Vishnupriyan K, Sharat Damodar, and Sowmya T
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0301 basic medicine ,Physiology ,Gene Expression ,Datasets as Topic ,Hematologic Cancers and Related Disorders ,0302 clinical medicine ,Bone Marrow ,Reference genes ,Immune Physiology ,Gene expression ,Medicine and Health Sciences ,RNA-Seq ,Statistical Data ,Regulation of gene expression ,Multidisciplinary ,Hematology ,Genes, Essential ,Statistics ,Genomics ,Research Assessment ,Reference Standards ,Gene Expression Regulation, Neoplastic ,Oncology ,Proto-Oncogene Proteins c-bcl-2 ,030220 oncology & carcinogenesis ,Hematologic Neoplasms ,Physical Sciences ,Medicine ,Biomarker (medicine) ,Transcriptome Analysis ,Research Article ,medicine.medical_specialty ,Systematic Reviews ,Science ,Immunology ,Computational biology ,Biology ,Research and Analysis Methods ,Real-Time Polymerase Chain Reaction ,03 medical and health sciences ,Diagnostic Medicine ,Internal medicine ,Cell Line, Tumor ,TaqMan ,medicine ,Genetics ,Cancer Detection and Diagnosis ,Biomarkers, Tumor ,Animals ,Humans ,RNA, Messenger ,Gene ,Cancers and Neoplasms ,Biology and Life Sciences ,Computational Biology ,Molecular diagnostics ,Genome Analysis ,Disease Models, Animal ,030104 developmental biology ,Immune System ,Leukocytes, Mononuclear ,Feasibility Studies ,Genome Expression Analysis ,Mathematics - Abstract
Dysregulation of BCL2 is a pathophysiology observed in haematological malignancies. For implementation of available treatment-options it is preferred to know the relative quantification of BCL2 mRNA with appropriate reference genes. For the choice of reference genes-(i) Reference Genes were selected by assessing variation of >60,000 genes from 4 RNA-seq datasets of haematological malignancies followed by filtering based on their GO biological process annotations and proximity of their chromosomal locations to known disease translocations. Selected genes were experimentally validated across various haematological malignancy samples followed by stability comparison using geNorm, NormFinder, BestKeeper and RefFinder. (ii) 43 commonly used Reference Genes were obtained from literature through extensive systematic review. Levels of BCL2 mRNA was assessed by qPCR normalized either by novel reference genes from this study or GAPDH, the most cited reference gene in literature and compared. The analysis showed PTCD2, PPP1R3B and FBXW9 to be the most unregulated genes across lymph-nodes, bone marrow and PBMC samples unlike the Reference Genes used in literature. BCL2 mRNA level shows a consistent higher expression in haematological malignancy patients when normalized by these novel Reference Genes as opposed to GAPDH, the most cited Reference Gene. These reference genes should also be applicable in qPCR platforms using Taqman probes and other model systems including cell lines and rodent models. Absence of sample from healthy-normal individual in diagnostic cases call for careful selection of Reference Genes for relative quantification of a biomarker by qPCR.BCL2 can be used as molecular diagnostics only if normalized with a set of reference genes with stable yet low levels of expression across different types of haematological malignancies.
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- 2020
28. Impact of anemia and red cell indices on the diagnosis of pre-diabetes and diabetes in Indian adult population: Is there a cut-off guide for clinicians?
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Sharat Damodar, K. S. Shivaprasad, Kranti Khadilkar, Subramanian Kannan, Bangalore Venkatraman Murali Mohan, Vellaichamy M Annapandian, and Chinthala Jaipalreddy
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concordance ,medicine.medical_specialty ,endocrine system diseases ,Anemia ,Endocrinology, Diabetes and Metabolism ,Concordance ,hba1c ,030209 endocrinology & metabolism ,lcsh:Diseases of the endocrine glands. Clinical endocrinology ,03 medical and health sciences ,0302 clinical medicine ,Endocrinology ,pre-diabetes ,Diabetes mellitus ,Internal medicine ,medicine ,030212 general & internal medicine ,discordance ,lcsh:RC799-869 ,Meal ,lcsh:RC648-665 ,Red Cell ,diabetes ,RED-CELL INDICES ,business.industry ,nutritional and metabolic diseases ,medicine.disease ,anemia ,Iron-deficiency anemia ,Original Article ,lcsh:Diseases of the digestive system. Gastroenterology ,Cut-off ,business - Abstract
Background: It is well known that anemia and red cell turn over affects the HbA1c value. Iron deficiency anemia increases the HbA1c and haemolytic anemia lowers it. However, the cut-off of haemoglobin (Hb) or red-cell indices when the HbA1c value becomes unreliable is not known. Aim: We sought to find out values of HbA1c and red-cell indices where there is considerable discordance between HbA1c and plasma glucose (PG) values in the diagnosis of diabetes (DM) and pre-diabetes (Pre-DM) making HbA1c values unreliable. Methods: A cross-sectional study of 237 non-diabetic subjects who attended our out-patient division of preventive health check-up clinics, between November 2016 and December 2017. Data was collected only from relatively healthy subjects who had voluntarily opted for undergoing a preventative health check-up (including a diabetes screening). Patients were classified as concordant (fasting and 2-hr post meal glucose values are in agreement with HbA1c) and discordant (values are not in agreement with HbA1c). Results: A total of 237 patients (73% males) with mean age was 47.2±9.7 years (range 25-75) were included in the study. The HbA1c definition group had more diagnosis of DM (153 vs 96) and but lesser numbers of pre-DM (66 vs 102) compared to the PG group. Out of 237 patients, 133 (56%) showed concordance and 104 (44%) were discordant. The FPG, 2h-PPBG and HbA1c are significantly higher in the concordant group. The Hb value and MCV were significantly higher (p7% (20%). While no single Hb or MCV value could predict discordance, a RDW value >17 was consistently associated with discordance across all the HbA1c strata. Conclusion: A HbA1c below 7% is significantly influenced by red-cell turn over indices and clinicians need to perform additional testing using plasma glucose levels to confirm the presence of diabetes or pre-diabetes. In patients whose RDW >17, HbA1c should be replaced by 75gm OGTT as a test of choice for diagnosis of diabetes or pre-diabetes.
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- 2019
29. Itolizumab in Indian Patients with Chronic Gvhd: an Update
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Aditi Shah, Bharath Ram, Shilpa Prabhu, and Sharat Damodar
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Transplantation ,Molecular Medicine ,Immunology and Allergy ,Cell Biology ,Hematology - Published
- 2022
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30. Covid-19 Infection in Hematological Malignancies: Registry Data from India
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Sharat Damodar, Jayashree Thorat, Arihant Jain, Smita Kayal, Om Prakash, Lingaraj Nayak, Jeyaseelan Lakshmanan, Hasmukh Jain, Uday Yanamandra, Biju George, Deepesh Lad, Bharath Ram S, Pankaj Malhotra, Rajan Kapoor, Joseph M John, Satyaranjan Das, Pritesh Naresh Munot, Suvir Singh, Sushil Selvarajan, Prashant Mehta, Jayachandran Pk, Uday Kulkarni, Venkatraman Radhakrishnan, Nikita Mehra, Biswajit Dubashi, and Thenmozhi Mani
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Pediatrics ,medicine.medical_specialty ,903.Health Services Research-Myeloid Malignancies ,Coronavirus disease 2019 (COVID-19) ,business.industry ,Immunology ,Medicine ,Registry data ,Cell Biology ,Hematology ,business ,Biochemistry - Abstract
Background: The impact of COVID-19 pandemic has been highly heterogeneous across the globe and different regions within the country. The differences in the outcome of these patients is related to their demographic profile, genetics, socio-economic conditions, and government health policies. Prior to the COVID-19 pandemic, the Healthcare Access and Quality (HAQ) Index for hematological malignancies (HAQ index Methods: Ten tertiary referral hospitals across India reported the demographic, clinical, laboratory, treatment, and outcomes of COVID-19 infection in patients with hematological malignancies. The registry was retrospective from March 21, 2020, and prospective from November 1, 2020, till March 20, 2021. Risk factors associated with severity and mortality were evaluated using the penalised logistic regression and Cox proportional hazards model. Findings: Data from 565 patients was included in this study. Among these, 429 (76%) patients were hospitalized, 186 (33%) patients had moderate/severe COVID-19.There were 116 (20.5%) non-survivors at a mean follow up of 147 (95% CI : 142-153) days. Age >60 years (HR 2·55, 1·23 - 5·27), diagnosis of acute myeloid leukemia (HR 2·85, 1·58 - 5·13), interruption or alteration of anticancer therapy (HR 2·78, 1·65 - 4·68), and post hematopoietic cell transplant status (HR 3·68, 1·82 - 7·45) predicted mortality. In contrast, increasing age [20-40 years (OR 2·54, 1·32 - 4·90), 41-60 years (OR 3·51, 1·84 - 6·71), >60 years (OR 6·04, 3·01 - 12·10), comorbidities such as diabetes mellitus (OR 1·89, 1·18 - 3·04), hypertension (OR 1·94, 1·17 - 3·19), diagnosis of AML (OR 3·70, 2·06 - 6·67), indolent non-hodgkin lymphoma (OR 3·20, 1·68 - 6·09), multiple myeloma (OR 2·88, 1·64 - 5·05), malignancy not being in remission (OR 1·71, 1·12 - 2·60)were significantly associated with severe COVID-19 on univariate analysis. Of these, only increasing age [20-40 years (OR 2·60 (1·31 - 5·15), 40-60 years (OR 3·44, 1.60 - 7·41), more than 60 years (OR 5·70, 2·43 - 13·35)] , AML (OR 2·73, 1·45 - 5·12), and malignancy not being in remission (OR 1·85, 1·18 - 2·89) were significantly associated with severe COVID-19 on multivariable analysis Conclusion: The overall mortality from COVID-19 infection of the entire cohort was 20.5%; the mortality was 46.2% in patients who had moderate to severe disease COVID-19 illness. Similar to previous studies, age, diagnosis of acute myeloid leukemia and a post stem cell transplant status was associated with mortality. In addition, interruption or de-escalation of anticancer therapy during Covid-19 infection was identified as an important factor associated with higher mortality on follow up in the current study. References 1. Measuring performance on the Healthcare Access and Quality Index for 195 countries and territories and selected subnational locations: a systematic analysis from the Global Burden of Disease Study 2016. Lancet (London, England)2018; 391(10136): 2236-71.Lee AJX, Purshouse K. COVID-19 and cancer registries: learning from the first peak of the SARS-CoV-2 pandemic. Br J Cancer 2021; 124(11): 1777-84. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.
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- 2021
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31. Acquired and Inherited Thrombophilia Testing in Patients with Chronic Thromboembolic Pulmonary Hypertension: Value of Testing in an Academic Health Center
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Karthick R G, Monisha Harimadhavan, Devi Prasad Shetty, Shilpa Prabhu, Sharat Damodar, and Bharath Ram S
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Pediatrics ,medicine.medical_specialty ,business.industry ,Immunology ,Cell Biology ,Hematology ,Biochemistry ,Medicine ,Chronic thromboembolic pulmonary hypertension ,In patient ,Center (algebra and category theory) ,business ,Inherited thrombophilia ,Value (mathematics) - Abstract
Introduction Chronic thromboembolic pulmonary hypertension (CTEPH) is classed as group 4 in the present classification of pulmonary hypertension. The pathophysiology of CTEPH is complex, mainly is a consequence of prior acute pulmonary embolism with failure of thrombi to resolve and the recent recognition of added small vessel changes which impacts long-term outcomes even after surgical management. The role of thrombophilia testing in this condition has been debated. Hence, we here analyzed the utility of thrombophilia testing in CTEPH from a center in a developing country. Methods This is a single institution (Narayana Health City, Bangalore); retrospective study including patients ≥ 18 years of age who underwent thrombophilia workup in a diagnosis of CTEPH from January 2019 till July 2021. Tests done to evaluate thrombophilia included factor V Leiden; prothrombin F20210A mutation; MTHFR gene mutation; Protein C, S, and antithrombin deficiency; lupus anticoagulant, anti-beta2 glycoprotein I (IgM and IgG) and anticardiolipin antibody (IgM and IgG); hyperhomocysteinemia and anti-nuclear antibody testing (ANA-IF). The study was approved by the ethics committee of the institute and was carried out in accordance with the principles of the declaration of Helsinki. Results and discussion The study included 56 patients with a median age of 37 years (range 23-50), and 36 (64%) were males. Patients with recurrent venous thrombosis included 37 (66%), with the majority having thrombosis at 2 sites (53%; 22 patients with associated deep vein thrombosis). A family history of thrombosis was present in 4 patients. The majority of patients received vitamin K antagonists (76%), with the rest receiving direct oral anticoagulants (DOAC). Among the tests sent for acquired thrombophilia, ANA-IF and antiphospholipid antibody (APLA) were most frequently evaluated (94%). ANA-IF and APLA tests were positive in 5.6% and 30.1%, respectively. Among the APLA tests, Anti-beta2 glycoprotein I (IgM or IgG) was the most commonly detected antibody (13/46), followed by anticardiolipin antibody (IgG or IgM) (9/43) and lupus anticoagulant (7/40). Double and triple positive APLA were present in 3 and 4 patients, respectively. Homocysteine levels were high in 93.7% though only 16 patients were tested in this cohort. Among the tests for inherited thrombophilia, genetic tests (factor V Leiden, prothrombin F20210A mutation, and MTHFR gene mutation) were tested in only ~50%. Twenty-three percent were positive for heterozygous MTHFR followed by MTHFR compound heterozygous (10%) and heterozygous factor V Leiden heterozygous (10%). Antithrombin III, protein C, and S were tested in ~30% of patients. Antithrombin III was low in only 1 patient, with protein C and S assays being normal in all the patients. The cost analysis was calculated, showed a median of $364 (₹ 27,055) was spent per person on thrombophilia workup. The median cost incurred per patient for inherited thrombophilia workup was $232 (₹ 17,300) and for acquired thrombophilia was $132 (₹ 9814), respectively. Conclusion This single-institution study on thrombophilia workup in CTEPH patients reveals that APLA was the most commonly performed test with high positivity rates of 30.1%. Among the inherited thrombophilia, the positivity rate of MTHFR mutation was highest (33.3%), with other tests having a low positivity rate (0-10%). Hence, we would recommend APLA testing in all patients with CTEPH considering its high positivity and clinical utility. Testing for other thrombophilias should be pursued judiciously especially in economically restrictive settings. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.
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- 2021
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32. Interim Analysis of a Prospective Study of Itolizumab for Treatment of Chronic Graft VS Host Disease Following Haematopoietic Stem Cell Transplantation
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Sharat Damodar, K.S. Nataraj, Bharath Ram, Shilpa Prabhu, and Aditi Shah
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Oncology ,Transplantation ,medicine.medical_specialty ,business.industry ,Itolizumab ,Cell Biology ,Hematology ,Interim analysis ,Haematopoiesis ,Internal medicine ,medicine ,Molecular Medicine ,Immunology and Allergy ,Stem cell ,Prospective cohort study ,business ,Host disease ,medicine.drug - Published
- 2021
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33. Donor-to-Recipient ABO Mismatch Does Not Impact Outcomes of Allogeneic Hematopoietic Cell Transplantation Regardless of Graft Source
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Daniel J. Weisdorf, Sharat Damodar, Celalettin Ustun, Ryan Shanley, and Margaret L. MacMillan
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Oncology ,medicine.medical_treatment ,Graft vs Host Disease ,Transplants ,Pure red cell aplasia ,Hematopoietic stem cell transplantation ,Umbilical cord ,0302 clinical medicine ,Bone Marrow ,hemic and lymphatic diseases ,Child ,Graft Survival ,Hematopoietic Stem Cell Transplantation ,Hematology ,Middle Aged ,Fetal Blood ,Survival Rate ,Treatment Outcome ,surgical procedures, operative ,medicine.anatomical_structure ,Blood Group Incompatibility ,Child, Preschool ,030220 oncology & carcinogenesis ,Adult ,congenital, hereditary, and neonatal diseases and abnormalities ,medicine.medical_specialty ,Adolescent ,Platelet Engraftment ,Red-Cell Aplasia, Pure ,Article ,ABO Blood-Group System ,Young Adult ,03 medical and health sciences ,Internal medicine ,ABO blood group system ,parasitic diseases ,medicine ,Humans ,Transplantation, Homologous ,Aged ,Transplantation ,Neutrophil Engraftment ,business.industry ,Infant ,medicine.disease ,biological factors ,Immunology ,Peripheral Blood Stem Cells ,Bone marrow ,business ,030215 immunology - Abstract
The impact of ABO mismatch has been studied on various hematopoietic cell transplant (HCT) outcomes, including neutrophil and platelet engraftment, pure red cell aplasia, acute and chronic graft-versus-host disease (GVHD), nonrelapse mortality (NRM), and overall survival (OS). Yet conflicting results have been reported. However, the impact of ABO mismatch on transplant outcomes with various graft types has not been carefully investigated. We analyzed the impact of various graft sources and type of ABO mismatch on transplant outcomes for 1502 patients who underwent HCT at the University of Minnesota between 2000 and 2014: 312 receiving marrow (BM), 475 filgrastim-mobilized blood (peripheral blood stem cell [PBSC]), and 715 umbilical cord blood (UCB) grafts. Neutrophil engraftment by day 28 was marginally less frequent in the bidirectional ABO mismatched transplants receiving UCB, whereas ABO matching had no influence on engraftment in the BM or PBSC cohorts. ABO mismatch led to no significant differences in platelet engraftment irrespective of stem cell source. We observed a modest but not significantly lower incidence of grades II/IV acute GVHD in the bidirectional ABO mismatched transplants in the UCB and the PBSC cohorts but not in the BM group. We found a higher incidence of chronic GVHD in the PBSC group, but it was not significantly lower in the minor ABO mismatched transplants. The incidence of chronic GVHD was similar in the major ABO mismatched transplants receiving BM. We found no significant difference in the OS and NRM between ABO matched and ABO mismatched transplants within each of the 3 graft source groups. Multivariable analysis adjusting for other relevant factors confirmed that ABO match status did not significantly influence the outcomes of either engraftment, acute or chronic GVHD or NRM. We conclude that ABO mismatch does not influence the outcomes of allogeneic HCT, regardless of stem cell source.
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- 2017
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34. Prevalence of Genetic Abnormalities in Patients with Multiple Myeloma and Its Clinical Relevance in a Developing Country like India
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Aditi Shah, Sundareshan T S, K.S. Nataraj, Bharath Ram S, Shilpa Prabhu, Sharat Damodar, Hamza Yusuf Dalal, and Shiva Kumar Komaravelli
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medicine.medical_specialty ,education.field_of_study ,medicine.diagnostic_test ,business.industry ,Incidence (epidemiology) ,Immunology ,Population ,Induction chemotherapy ,Cell Biology ,Hematology ,Biochemistry ,Chemotherapy regimen ,Internal medicine ,Medicine ,Population study ,Hyperdiploidy ,Lost to follow-up ,business ,education ,Genetic testing - Abstract
Introduction Multiple myeloma (MM) is a malignancy involving terminally differentiated plasma cells. Its incidence in India is about 0.7/1,00,000 population amounting to about 6,800 new cases a year A number of genomic aberrations are associated with MM, most of which confer prognostic significance. Cytogenetic abnormalities are a part of R-ISS score for prognostication which stratifies presence of del(17p), t(4;14) or t(14;16) as stage 3, mSMART is another risk stratification tool which divides MM into high risk and standard risk groups based on genetic aberrations. Hence it is evident that determining the genetic abnormality in MM is important. however, due to limited resources genetic testing is not routinely done and the data in the Indian population is limited. Objective: To estimate the prevalence of molecular cytogenetic abnormalities by Fluorescent in situ hybridization (FISH) analysis in patients with MM and to assess the co-relation with response to induction chemotherapy, relapse and overall survival. Material and Methods: 64 patients were included from January 2016 to December 2019 and followed up till June 2020. Interphase FISH study was performed either at diagnosis or at relapse, on bone marrow aspirate with panel of probes consisting of CKS1B (1q21-22), CDKN2C (1p32.3), D13S319 (13q14.2/13q34), IGH (14q32.33), p53 (17p13.1) and trisomy (5p15/9q22/15q22) (trisomies are considered as hyperdiploidy in this study). Plasma cell purification techniques were not applied prior to FISH analysis. Patients were divided into 2 risk groups; 1) high risk group with presence of del17p, del13q, amplification 1q, del1p and two or more aberrations with either of these and 2) standard risk group with presence of hyperdiploidy or no genetic abnormality. There was no difference in chemotherapy regimen between the 2 groups; 46 (71.8%) received bortezomib-thalidomide-dexamethasone, 10 (15.6%) received bortezomib-cyclophosphamide-dexamethasone, 2(3.1%) received bortezomib-lenalidomide-dexamethasone, 1(1.5%) received daratumumab-bortezomib-dexamethasone and 5(7.8%) received 2 drug chemotherapy. Patients who did not complete minimum follow up of 6 months either due to death or lost to follow up were excluded from the study. Institutional Ethics Committee's approval was taken. Results: Mean age of the population was 60.33 years and male to female ratio was 1.65. 46.87%, 28.13% and 25% of the study population were in the age group of ≤ 60, 61 - 65 and ≥66 years respectively. 12.3%, 43.8% and 43.8% were in R ISS stage 1, 2 and 3 respectively. FISH analysis was done on 61 out of 64 patients (remaining 3 were excluded due to hemodilute bone marrow sample). 22 (36.1%) patients had abnormal genetic aberration on FISH analysis with 10 (16.39%) having two or more abnormalities. The frequency of genetic aberrations was as follows; amplification 1q (13/61, 21.31%), del13q (9/61, 14.75%), hyperdiploidy (7/61, 11.47%), del17p (4/61, 6.55%), IgH rearrangement (3/61, 4.91%), and del1p (1/61, 1.6%). All 3 patients with IgH rearrangement had associated one or more high-risk genetic aberration and hence were included in high risk group. 31.1% of the patients were high risk and 68.9% were standard risk. The response to induction chemotherapy, incidence of relapse, time to 1st relapse and total number of relapses are shown in (table;1) and there was no significant difference between high risk and standard risk group. Overall survival in standard risk group at 2 and 5 years was 89.6% ± 5.8% and 78.6% ± 13.9% and in high risk group was 60.7% ± 13.2% and 29.5% ± 23.1% respectively (p value: 0.762). Overall survival was significantly lower in age group ≥66 years as compared to age group ≤ 60 years and 61 - 65 years (p value 0.001) and it was also significantly lower in R ISS stage 3 as compared to R ISS stage 1 and 2 (p value 0.006). Conclusion: More than one third patients of MM (36.1%) showed genetic abnormality, amplification 1q being the most frequent. Overall survival was significantly lower in older age group and R ISS stage 3 patients. Response to induction chemotherapy and relapse rate were similar in high and standard risk groups. Although overall survival was lower in high risk group, it was statistically not significant. This study highlights the importance of FISH analysis for disease stratification and prognostication which should be routinely practiced. Disclosures No relevant conflicts of interest to declare.
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- 2020
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35. Hematopoietic Stem Cell Transplant Outcomes in Patients with Acute Myeloid Leukemia from a Tertiary Care Center in South Inida
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Shobha Badiger, P. Vasundhara, Sharat Damodar, Sunil Bhat, K.S. Nataraj, Vellaichamy M Annapandian, and Shilpa Prabhu
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Transplantation ,medicine.medical_specialty ,business.industry ,Incidence (epidemiology) ,medicine.medical_treatment ,Myeloid leukemia ,Hematopoietic stem cell ,Hematology ,Hematopoietic stem cell transplantation ,Tertiary care ,surgical procedures, operative ,medicine.anatomical_structure ,Internal medicine ,medicine ,Sibling ,Stem cell ,business - Abstract
Background Allogenic hematopoietic stem cell transplantation (allo-HSCT) is one of the best therapies for acute myeloid leukemia (AML) and a proven post-remission therapy for intermediate and high-risk AML. The best HSCT source seems to be a matched sibling donor (MSD), but in the absence of one, a readily available haplo-identical donor provides an equally high cure rate. This is of relevance in a developing country like India as the cost of an unrelated donor is usually unaffordable. We present our experience from a single centre. Methods We analysed retrospective data of 122 AML patients who have undergone HSCT between Jan-2012 to Jun-2019 at our centre. Fludarabine + Busulfan or Fludarabine + Melphalan based conditioning regimen were used in MSD transplant and John Hopkins's protocol was followed in haploidentical HSCT. Cyclosporine + methotrexate was used as GVHD prophylaxis in MSD and unrelated donor group and cyclophosphamide + tacrolimus + mycophenolate was used for haploidentical post-transplant. Day 100 Survival, overall survival, incidence of GVHD and CMV reactivation was computed. Results Out of 122 patients, 69 (56.6%) were males, the mean age was 29.05±20.13 (range, 1 -74) years. Peripheral blood stem cell (99%) was the predominant graft source with majority of matched sibling donor (MSD; 54.1%) compared to Haplo-identical donors (30%). Figure 1 shows the demographic and clinical details of the study patients. The incidence of acute GVHD (40.9% vs 32.6%; p=0.372) and chronic GVHD (16.7% vs 15.2%; p=0.837) are similar in MSD and Haplo transplantation. There were 25 (38%) deaths in MSD and 23 (50%) deaths haplo-identical transplantation (p=0.245). The day-100 survival and overall survival function is significantly better in MSD transplantation (p Conclusion Our study showed comparable outcomes in MSD and Haplo-identical transplant with respect to incidence of GVHD and mortality. However, the survival function is better with MSD transplantation. Haplo-identical transplant is a feasible option in case of non-availability of MSD, due to ease of donor availability and strong motivation from the family donor to donate the stem cells.
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- 2020
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36. Haematopoietic Stem Cell Transplant Outcomes in Patients with Thalassemia Major from a Tertiary Care Center in South India
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Shobha Badiger, Sunil Bhat, Annapandian Vm, Sharat Damodar, and K.S. Nataraj
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Transplantation ,medicine.medical_specialty ,Neutrophil Engraftment ,Cyclophosphamide ,Platelet Engraftment ,business.industry ,Thalassemia ,Hematology ,medicine.disease ,Fludarabine ,surgical procedures, operative ,medicine.anatomical_structure ,Graft-versus-host disease ,hemic and lymphatic diseases ,Internal medicine ,medicine ,Bone marrow ,business ,Busulfan ,medicine.drug - Abstract
Background Hematopoietic stem cell transplant (HSCT) is widely used as a gene replacement therapy in Thalassemia patients for decades. Survival probabilities after HSCT have increased considerably with advancements in graft versus host disease (GVHD) preventive strategies and conditioning regimens. Here we report our HSCT experience in patients with Thalassemia major, with different graft sources, in terms of transplant outcomes such as neutrophil and platelet engraftment, acute and chronic graft versus host disease (GVHD), thalassemia free survival and overall survival. Methods We analysed the data of 164 Thalassemia patients who have undergone HSCT between Jan-2012 to Jun-2019 at our centre. We evaluated the demographic and clinical characteristics of patients, graft source on the HSCT outcomes, such as engraftment, graft versus host disease, day-100 survival, thalassemia-free survival and overall survival. Results Out of 164 patients, 100 (61%) were males, the mean age was 9.47±4.41 (range, 1 -24) years. Peripheral blood stem cell (50%) and bone marrow (47%) are the respective graft sources with predominant matched sibling donor transplants (60.4%). One third of the patients received Fludarabine/Busulfan/Cyclophosphamide based conditioning regimen. Twenty-eight percent of the patients developed acute GVHD (grades I-IV) and 7.3% developed chronic GVHD. The average time to neutrophil engraftment was 14 (range, 8-24) days and platelet engraftment was 18 (range, 8-72) days. The average time to neutrophil engraftment and platelets engraftment did not significantly differ between the HLA-donor type (Figure 1). There were 26 deaths (15.9%) and 7 (4.3%) graft rejections during the follow-up. Infections are the major cause of deaths. The day 100 survival was 89%, the overall survival was 84% and the thalassemia free survival was 74.4%. Conclusion HSCT with various preparative regimens, GVHD preventive strategies, and varied graft sources is certainly a unique curative option for the Thalassemia major patients in the developing world. The survival after HSCT in Thalassemia patients are similar regardless of stem cell source, donor-HLA type (Figure 2) and GVHD (Figure 3). However, the incidence of GVHD is more with matched unrelated donors.
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- 2020
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37. A Prospective Observational Multi-institutional Study on Invasive Fungal Infections Following Chemotherapy for Acute Myeloid Leukemia (MISFIC Study): A Real World Scenario from India
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Kavitha M Lakshmi, Sharat Damodar, Narendra Agrawal, Gaurav Prakash, Radhe Shyam, Pankaj Malhotra, Shashi Apte, Manju Sengar, Aby Abraham, Biju George, Anu Korula, Vikram Mathews, K.S. Nataraj, Ajay K. Sharma, Dinesh Bhurani, Hari Menon, Anup J. Devasia, Jose Easow, Tulika Seth, Alka Khadwal, Sanjeevan Sharma, and Rayaz Ahmed
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medicine.medical_specialty ,Chemotherapy ,Posaconazole ,Hematology ,business.industry ,Incidence (epidemiology) ,medicine.medical_treatment ,Induction chemotherapy ,Myeloid leukemia ,030204 cardiovascular system & hematology ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,medicine ,Observational study ,Original Article ,Prospective cohort study ,business ,030215 immunology ,medicine.drug - Abstract
We performed a prospective multi-centre observational study to understand the incidence of IFI in patients with AML in India with use of anti-fungal prophylaxis. All patients with AML receiving either induction chemotherapy or salvage chemotherapy between November 2014 and February 2016 were included in this prospective observational study from 10 Indian centres. IFI was defined as per the revised EORTC-MSG criteria. Data on type of chemotherapy used, type of anti-fungal prophylaxis used, time to neutrophil recovery, incidence of IFI and survival were collected. Two hundred patients (118 male and 82 females) with a median age of 35 years (range: 2–66) were recruited. One hundred and eighty-six (93%) had newly diagnosed acute myeloid leukemia (AML) while 14 (7%) had relapsed disease. IFI occurred in 53 patients (26.5%) with proven or probable IFI occurring in 17 (8.5%). Use of posaconazole prophylaxis (p = 0.027) was the only factor found to be associated with a reduced incidence of IFI. The overall survival (OS) at 6 weeks and 3 months respectively was similar among patients who had IFI (83.0 ± 5.2%; 81.0 ± 5.4%) as compared to those without IFI (84.4 + 3.0%; 81.4 ± 3.2%). This prospective study reveals a high incidence of IFI in patients undergoing chemotherapy for AML in India. The use of posaconazole prophylaxis was associated with a significantly lower incidence of IFI. Optimal strategies to prevent IFI need to be studied.
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- 2019
38. Summary of the Highlights of 2019 ASTCT Meeting by iNDUS BMT Group at Chennai, India
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Biju George, Jose Easow, Neeraj Sidharthan, Sharat Damodar, Vikram Mathews, Sunil Bhat, Tapan Saikia, Dharma Choudhary, Satya Prakash Yadav, Ajay K. Sharma, Tulika Seth, Joseph M John, Velu Nair, Chezian Subhash, Pankaj Malhotra, Dinesh Bhurani, Revathy Raj, Soniya Nityanand, Lalit Kumar, Rayaz Ahmed, and Rahul Bhargava
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business.industry ,Indus ,Library science ,Developing country ,Hematology ,Review Article ,030204 cardiovascular system & hematology ,Transplantation ,03 medical and health sciences ,0302 clinical medicine ,surgical procedures, operative ,Medicine ,business ,030215 immunology - Abstract
This article summarises the main highlights of the abstracts presented at the annual meeting of American Society of Transplantation and Cellular Therapy (ASTCT). The highlights of ASTCT meeting were organised by iNDUS BMT group in Chennai, India. The purpose of the highlight meeting was to educate the students about the latest research in the field of hematopoietic stem cell transplantation and its applicability for the developing country perspective.
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- 2019
39. IL-6 and IL-10 as predictors of disease severity in COVID-19 patients: results from meta-analysis and regression
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Sharat Damodar, Manjula Das, Shashi Gujar, Vishnupriyan K, and Sujan K. Dhar
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0301 basic medicine ,Oncology ,medicine.medical_specialty ,medicine.medical_treatment ,Disease ,Logistic regression ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,medicine ,lcsh:Social sciences (General) ,lcsh:Science (General) ,Interleukin 6 ,Multidisciplinary ,biology ,business.industry ,COVID-19 ,Random effects model ,Regression ,Logistic models ,Meta-analysis ,030104 developmental biology ,Cytokine ,Strictly standardized mean difference ,biology.protein ,Cytokines ,lcsh:H1-99 ,business ,030217 neurology & neurosurgery ,lcsh:Q1-390 ,Research Article - Abstract
Aims SARS-CoV-2, an infectious agent behind the ongoing COVID-19 pandemic, induces high levels of cytokines such as IL-1, IL-2, IL-4, IL-6, IL-10, TNF-α, IFN-γ etc in infected individuals that play a role in the underlying patho-physiology. Nonetheless, exact association and contribution of every cytokine towards COVID-19 pathology remains poorly understood. Delineation of the roles of cytokines during COVID-19 holds the key to efficient patient management in clinics. This study performed a comprehensive meta-analysis to establish association between induced cytokines and COVID-19 disease severity to help in prognosis and clinical care. Main methods Scientific literature was searched to identify 13 cytokines (IL-1β, IL-2, IL-2R, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12, IL-17, TNF-α and IFN-γ) from 18 clinical studies. Standardized mean difference (SMD) for selected 6 cytokines IL-2, IL-4, IL-6, IL-10, TNF-α and IFN-γ between severe and non-severe COVID-19 patient groups were summarized using random effects model. A classifier was built using logistic regression model with cytokines having significant SMD as covariates. Key findings Out of the 13 cytokines, IL-6 and IL-10 showed statistically significant SMD across studies synthesized. Classifier with mean values of both IL-6 and IL-10 as covariates performed well with accuracy of ~92% that was significantly higher than accuracy reported in literature with IL-6 and IL-10 as individual covariates. Significance Simple panel proposed by us with only two cytokine markers can be used as predictors for fast diagnosis of patients with higher risk of COVID-19 disease deterioration and thus can be managed well for a favourable prognosis., COVID-19, Meta-Analysis, Cytokines, Logistic Models.
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- 2021
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40. A Novel Clinical Risk Factor Based Scoring System to Predict the Severity of Acute Graft Versus Host Disease and Steroid Response in Resource Constrained Settings
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Hamza Yusuf Dalal, Shilpa Prabhu, Monisha Harimadhavan, Bharath Ram S, Shiva Kumar Komaravelli, Aditi Shah, Sharat Damodar, and Nataraj K S
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Scoring system ,business.industry ,medicine.medical_treatment ,Immunology ,Resource constrained ,Cell Biology ,Hematology ,Bioinformatics ,Biochemistry ,Steroid ,Acute graft versus host disease ,medicine ,business ,Clinical risk factor - Abstract
INTRODUCTION Acute Graft-versus-host disease (aGVHD) is a common complication of allogeneic hematopoietic cell transplantation (HCT), affecting about 50% of transplants. Grading of aGVHD can serve a variety of purposes, including retrospective assessment of peak severity, real-time assessment of severity at prespecified time points, and determination of the need for treatment. But several problems hamper the application of grading systems to predict outcomes among patients with aGVHD: (1) Assignment of a peak GVHD score is done retrospectively; clinicians cannot use the current grading system for peak score in real-time1. (2) The systems do not account for the time to the response after treatment1. (3) Assignment of grade IV GVHD is often used to indicate that GVHD caused a death, irrespective of the severity. In this situation, the grading reflects the outcome and cannot be used to predict the outcome1. Recently serum biomarkers have emerged as an additional potential measurement of acute GVHD severity. The Mount Sinai Acute GVHD International Consortium (MAGIC) Group, has validated MAGIC algorithm probability (MAP) that combines two GI biomarkers (ST2 and REG3α) into a single value. The MAP predicts response to treatment, GVHD severity. But in resource-limited settings, like transplant centers in India lack testing features. In this study we have developed a risk scoring based on clinical and easily available biochemical parameters to predict the severity of aGVHD. AIMS AND OBJECTIVES To predict the aGVHD severity at the onset based on risk factor score. To assess the steroid response in different risk groups MATERIAL AND METHODS The study included patients who underwent allogeneic HCT at Narayana hrudayalaya hospital, between January 2015 and April 2020 and developed acute GVHD within 100 days of transplant. After taking institutional ethics committee approval, data were collected from medical records. Baseline patient characteristics are mentioned in table 1. The following parameters were analyzed as risk factors for the development of severe GVHD (MAGIC grade 3 and 4): 1. Age >18 yrs, 2. MDR organisms in baseline stool culture, 3. HCT comorbidity index >1, 4. Peripheral blood as a source of stem cells, 5. Female to male transplants, 6. Myeloablative regimens, 7. Suboptimal GVHD prophylaxis, 8. CD34 dose > 6 x 106/kg, 9. Grade 3/4 mucositis 10. Early-onset GVHD (within 28 days), 11. Albumin level at the onset of GVHD, 12. Albumin drop from baseline3, and 13. Bloodstream infection. Risk factors with a p-value of 8). The following outcomes were assessed in each group; severity of GVHD (Grade I/II vs Grade III/IV) and response to steroids. RESULTS Out of 148 patients, 35.5% of Group 1, 56.5% of Group 2 patients and 85.5% of Group 3 patients developed Grade 3 or 4 GVHD respectively (P-value 8 to predict Grade 3/4 GVHD is 85.4%, negative predictive value is 50.6%, sensitivity is 50.5%, and specificity is 85.5%. From Group 1 and 2, only 30% of patients were steroid non responders, while 55.3% of Group 3 patients are steroid non responders (P-value - 0.04). CONCLUSION Traditional GVHD scoring systems reflect the outcome and cannot be used to predict the outcome. Various biomarker-based scoring systems are helpful in this situation, but in resource-limited settings, it might not be easily feasible. Clinical scoring systems like risk factor-based scoring systems are very helpful, which can predict the severe GVHD at early time points leading to management decisions such as upfront initiation of aggressive treatments and earlier introduction of second-line agents. References Leisenring WM, et al. An acute graft-versus-host disease activity index to predict survival after hematopoietic cell transplantation with myeloablative conditioning regimens. Blood. 2006;108(2):749-55. 2.Rashidi A, et al. Peritransplant Serum Albumin Decline Predicts Subsequent Severe Acute Graft-versus-Host Disease after Mucotoxic Myeloablative Conditioning. Biol Blood Marrow Transplant. 2016;22(6):1137-41. Disclosures No relevant conflicts of interest to declare.
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- 2020
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41. Safety and efficacy of intravenous immunoglobulin (Flebogamma
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Shashikant, Apte, Jordi, Navarro-Puerto, Sharat, Damodar, Vijay, Ramanan, Joseph, John, Giraldo, Kato, Cecil, Ross, Chirag, Shah, Marcela, Torres, Chieh-Lin 'Kathy', Fu, Karen, Rucker, Paul, Pinciaro, Gladis, Barrera, Maria Esperança, Aragonés, and Jaume, Ayguasanosa
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Adult ,Blood Platelets ,Male ,Purpura, Thrombocytopenic, Idiopathic ,Adolescent ,Immunoglobulins, Intravenous ,Middle Aged ,Leukocyte Count ,Young Adult ,Treatment Outcome ,Child, Preschool ,Humans ,Female ,Child ,Aged - Abstract
To evaluate the safety and efficacy of 10% intravenous immunoglobulin (IVIG; FlebogammaPatients aged 3-70 years, diagnosed with chronic ITP, received 1 g/kg IVIG over two consecutive days.64 evaluable patients (51 adults, 13 children) with chronic ITP received IVIG. The primary efficacy end point (increased platelet counts from ≤20 × 10Flebogamma
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- 2018
42. Comparison of Diagnostic Yield of a FISH Panel Against Conventional Cytogenetic Studies for Hematological Malignancies: A South Indian Referral Laboratory Analysis Of 201 Cases
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Vishal, Ashok, Ramya, Ranganathan, Smitha, Chander, Sharat, Damodar, Sunil, Bhat, Nataraj K, S, Satish Kumar, A, Sachin Suresh, Jadav, Mahesh, Rajashekaraiah, and Sundareshan, T S
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Chromosome Aberrations ,fungi ,India ,Prognosis ,Chromosomal aberration ,cytogenetics ,Asian People ,Hematologic Neoplasms ,Karyotyping ,Cytogenetic Analysis ,Humans ,hematological malignancies ,Referral and Consultation ,fluorescence in situ hybridization ,In Situ Hybridization, Fluorescence ,Research Article - Abstract
Objectives: Genetic markers are crucial fort diagnostic and prognostic investigation of hematological malignancies (HM). The conventional cytogenetic study (CCS) has been the gold standard for more than five decades. However, FISH (Fluorescence in Situ Hybridization) testing has become a popular modality owing to its targeted approach and the ability to detect abnormalities in non-mitotic cells. We here aimed to compare the diagnostic yields of a FISH panel against CCS in HMs. Methods: Samples of bone marrow and peripheral blood for a total of 201 HMs were tested for specific gene rearrangements using multi-target FISH and the results were compared with those from CCS. Results: Exhibited a greater diagnostic yield with a positive result in 39.8% of the cases, as compared to 17.9% of cases detected by CCS. Cases of chronic lymphocytic leukaemia (CLL) benefited the most by FISH testing, which identified chromosomal aberrations beyond the capacity of CCS. FISH was least beneficial in myelodysplastic syndrome (MDS) where the highest concordance with CCS was exhibited. Acute lymphocytic leukaemia (ALL) demonstrated greater benefit with CCS. In addition, we found the following abnormalities to be most prevalent in HMs by FISH panel testing: RUNX1 (21q22) amplification in ALL, deletion of D13S319/LAMP1 (13q14) in CLL, CKS1B (1q21) amplification in multiple myeloma and deletion of EGR1/RPS14 (5q31/5q32) in MDS, consistent with the literature. Conclusions: In conclusion, FISH was found to be advantageous in only a subset of HMs and cannot completely replace CCS. Utilization of the two modalities in conjunction or independently should depend on the indicated HM for an optimal approach to detecting chromosomal aberrations.
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- 2017
43. Haploidentical Stem Cell Transplantation With TCR Alpha/Beta and CD19 Depletion in a Case of Unstable Hemoglobin Disease
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Karunakumar Kumar, Shobha Badiger, Sunil Bhat, and Sharat Damodar
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Transplantation ,biology ,business.industry ,Receptors, Antigen, T-Cell, alpha-beta ,Antigens, CD19 ,Hematopoietic Stem Cell Transplantation ,Graft vs Host Disease ,Infant ,Unstable hemoglobin disease ,CD19 ,Hemoglobinopathies ,03 medical and health sciences ,0302 clinical medicine ,030220 oncology & carcinogenesis ,Immunology ,Transplantation, Haploidentical ,biology.protein ,Medicine ,TcR alpha-beta ,Humans ,Female ,Stem cell ,business ,030215 immunology - Published
- 2017
44. A Prospective Analysis of the Genomic Landscape of Patients with Acute Myeloid Leukemia and Its Impact on Clinical Outcomes - Data from a Tertiary Care Center in India
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Mukesh Chawla, Shoba Badiger, Shilpa Prabhu, K.S. Nataraj, Aditi Shah, Bharathram S, Amarnadh Polisetty, Vedam L Ramprasad, Shivakumar Komaravelli, Coral Miriam K, Vidya Veldore, Sunil Bhat, Hamza Yusuf Dalal, and Sharat Damodar
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Oncology ,education.field_of_study ,NPM1 ,medicine.medical_specialty ,Myeloid ,business.industry ,Genetic heterogeneity ,Immunology ,Population ,Induction chemotherapy ,Cell Biology ,Hematology ,Disease ,Biochemistry ,Chemotherapy regimen ,Regimen ,medicine.anatomical_structure ,Internal medicine ,medicine ,education ,business - Abstract
BACKGROUND : Clinical Phenotype and outcomes of patients with Acute myeloid leukemia (AML) in the Indian subcontinent differs from published literature. A younger age at diagnosis and higher induction mortality complicate AML management in India(1). Metaphase Karyotyping represents the backbone of prognostication and risk stratification in AML. Optimal treatment strategies for the cohort of Cytogenetically normal AML are still under evaluation. Applications of Next generation Sequencing (NGS) techniques in AML have unravelled the genetic heterogeneity of this disease. Whole genome sequencing has identified many novel mutations leading to tremendous improvements in diagnosis and risk stratification. Development of therapies targeting these genetic alterations is enabling a gradual shift from non-specific approaches to personalised therapy tailored to an individual patient's genome. This will undoubtedly translate to better clinical outcomes for this disease, with otherwise poor prognosis. Whole genome sequencing is still in a nascent stage in Indian settings with no published literature on genomics in AML till date. We aimed to study the genomic landscape of AML in the Indian population and to co-relate this with clinical outcomes over the course of 1 year. METHODS: We recruited 34 newly diagnosed patients with AML who presented to our Centre (Mazumdar Shaw Medical Centre, Narayana Health City, Bangalore, India) between November 2017 and May 2018. Clinical and laboratory details of all patients were recorded. Bone marrow and paired peripheral blood samples were drawn before initiating therapy. Whole genome sequencing and Exome capture was done for each sample using Ilumina HiSeq platform. Patients were risk stratified as per ELN 2017 and treated as per NCCN guidelines. Patients were followed up prospectively for one year from initial diagnosis. Genetic results were stratified according to gene function and analysed with respect to predefined clinical outcomes (remission status post induction, relapse rates, progression free and overall survival). RESULTS: Amongst the 34 study participants, 5 patients failed QC during sequencing and were de-recruited. Hence 29 patients were available for final analysis. Median age of patients was 42 years with 13 patients (44.8%) less than 40 years of age.18 patients (60%) had normal cytogenetics at baseline.17 patients (58%) were classified as intermediate risk and 6 patients each as Standard and high risk, as per ELN 2017. 22 patients (79.3%) patients received standard Induction chemotherapy (3+7 regimen) while 6 patients received hypomethylating agents. Overall CR rate following induction at Day 28 was 50% and Induction mortality was 21.42%. 6 patients underwent an Allogenic Stem cell transplant. A total of 96 mutations (47 driver and 49 VUS mutations) in 123 genes were identified. The average number of Driver mutations was 1.48 per patient. IDH genes were the most frequently mutated Driver genes followed by FLT3 mutations. Frequency of NPM1 mutations was significantly low (17.25%). Highest frequency of VUS mutations was seen in the ETV6, ATM and CBLC genes. Highest frequency of somatic mutations were identified in the genes encoding for myeloid transcription factors and DNA methylation. Average driver mutations showed significant co-relation to Age (> 60 years) and high burden of Bone marrow blasts (>30%). An updated risk stratification incorporating mutation analysis findings resulted in re-stratification of 8 intermediate risk patients into high risk. 2 patients with detectable FLT3 ITD mutation by NGS were negative by PCR. Choice of consolidation therapy and Driver mutation status were found to show statistically significant association with both Event free survival and Overall survival at 1 year. Increased driver mutation burden was associated with increased refractoriness to chemotherapy and poor EFS and OS. Mutations in Tumour suppressor genes, were associated with suboptimal treatment outcomes and poor survival. CONCLUSIONS Genomic landscape of AML in Indian patients shows significant differences from published literature. This may hold clues to the differing biological characteristics of AML seen in this population. Genome based risk stratification and tailored therapy needs to be adapted into the management of AML. This data provides valuable insights into developing therapeutic strategies for Indian patients. Disclosures No relevant conflicts of interest to declare.
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- 2019
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45. Is Heparin Induced Thrombocytopenia Expert Probability (HEP) Scoring System Superior to 4T'S Scoring in the Diagnosis of Heparin Induced Thrombocytopenia? a Prospective Observational Study from a Tertiary Care Cardiac Centre in India
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Shilpa Prabhu, Sharat Damodar, Hamza Yusuf Dalal, K.S. Nataraj, Amarnadh Polisetty, and Devi Prasad Shetty
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medicine.medical_specialty ,Receiver operating characteristic ,business.industry ,Incidence (epidemiology) ,medicine.medical_treatment ,Immunology ,Area under the curve ,Subgroup analysis ,Cell Biology ,Hematology ,Perioperative ,medicine.disease ,Biochemistry ,Internal medicine ,Heparin-induced thrombocytopenia ,medicine ,Population study ,Renal replacement therapy ,business - Abstract
Heparin-induced thrombocytopenia (HIT) is a drug-induced thrombocytopenia that results in thrombotic complications rather than bleeding.In many countries like India, the availability of functional assay for diagnosing HIT is unavailable. But with the utility of scoring systems the probability of HIT can be assessed and can guide the intervention required. Presently there are two well characterised and easily calculated scoring systems, which are the commonly used 4T scoring system and newly designed HEP score, to overcome some of the limitations of 4T`s scoring system. The 4Ts score has a negative predictive value (NPV) approaching 100%, but is limited by modest positive predictive value (PPV) and significant inter-observer variability.In this study we are comparing the two scoring systems and their relevance in the Indian scenario in patients undergoing cardiac intervention, receiving heparin. METHODS: - We recruited 100 patients with suspected HIT, for whom antibody testing was orderedat our centre (Narayana Health City, Bangalore, India) between November 2017 and May 2018. - Data were collected at baseline diagnosis in the form of clinical and laboratory data. 4T`s score and the HEP score was calculated based on the above details before the availability of antibody test. - HIT antibody testing was done using ID-PaGIA Heparin/pF4 Antibody Test Kit with control. In this 10 millilitre of serum is pippeted into the upper chamber of the appropriate microtube. Incubate the ID card at room temperature for 5mins at room temperature (18-25oc). Later centrifuge the ID-card for 10mins in the ID-centrifuge then read and records the results. - Patients were followed up daily till the discharge and complete blood picture including WBC count, development of any adverse effects including renal failure, sepsis, intra-arterial device insertion, bleeding was noted. - Area under the curve (AUC) for the receiver operating curve (ROC) of HEP and 4T scores was calculated and p value was obtained based on these curves. RESULTS: - 37 patients were HIT antibody positive out of 100 patients with suspected HIT from a patient population of 26430, who received heparin. The overall incidence of HIT in our institute is 0.14% (37/26430). - Out of the 100 suspected patients 37 were proven to have HIT by using ID-PaGIA Heparin/PF4 rapid gel agglutination assay. In this series, 91% patients had undergone cardiothoracic surgery forming the majority. Two-thirds of the study population was in the age group (41-70years). Males (61%) are more in the study than females (39%).The percentage of HIT positivity was more in females (43.5) than males (32.7%). - In 87 patients who received UFH, who presented with thrombocytopenia during their perioperative period, 30 were proven to have HIT (34.4%).We also observed during that the total leucocyte count at the nadir of platelet was higher in thr HIT positive group. However, it was not statistically significant (p-0.283) - Out of 100 patients with suspected HIT 49% expired. Of the 37 cases proven to have HIT 20 patients expired (54%). There was no statistically significant association between the occurrence of HIT and mortality ( p-value =0.438). - In this study, the areas under the curve for predicting HIT by 4T score was more than HEP score (0.754 and 0.66) with P value-0.093. As the HEP score was not superior to 4T score we have evaluated 2 subgroup analysis. - Among 36 subjects with the intra-arterial device (included in HEP score), 12 were positive for HIT (33.3%). Area under the Curve for the 4T score (0.698) was higher than that for HEP score (0.599) although the difference was not statistically significant(p-0.3906) - In this study, the incidence of renal replacement therapy (not included in HEP score)was 43%. In this patient population, 46% (n=20) are HIT positive. Among subjects on RRT, 4T score (814) had higher Area under the curve compared to HEP score (0.607) in the diagnosis of HIT positivity and the difference was statistically significant (p value 0.035). CONCLUSION The newly diagnosed HEP scoring system, which includes additional causes of thrombocytopenia was not superior to the 4T's score in this study. The inclusion of intra-arterial device in the HEP score did not make a difference in prediction of HIT. Conversely the 4T score was superior to HEP score in the evaluation of the subset of patients on renal replacement therapy, a significant cause of thrombocytopenia, which was not included in the scoring system. Disclosures No relevant conflicts of interest to declare.
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- 2019
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46. Retrospective analysis of pediatric haplo -identical hematopoietic stem cell transplantation with TCR αβ and CD 19 depletion
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Ravi, Joshi, primary, Archana, M.V., additional, Shobha, Badiger, additional, Vasundhara, P., additional, Sharat, Damodar, additional, Nataraj, K.S., additional, Pooja, Mallya, additional, Mohammad, Salmaan, additional, Mohan, Reddy, additional, and Sunil, Bhat, additional
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- 2019
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47. Haploidentical haematopoeitic stem cell transplants (Hsct) in paediatric acute leukemia
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Sharat Damodar, Shobha Badiger, Sunil Bhat, and Sohini Chakraborty
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Oncology ,medicine.medical_specialty ,Acute leukemia ,business.industry ,Internal medicine ,Pediatrics, Perinatology and Child Health ,medicine ,lcsh:RJ1-570 ,lcsh:Pediatrics ,Hematology ,Stem cell ,business - Published
- 2017
48. HLA match likelihoods for Indian patients seeking unrelated donor transplantation grafts: a population-based study
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Pankaj Malhotra, Sunil Parekh, Dolly Daniels, Sharat Damodar, Saranya Narayan, Daniel J. Weisdorf, Periathiruvadi Srinivasan, Soo Young Yang, Raghu Rajagopal, Sandip Shah, H. Sudarshan Ballal, Navin Khattry, Martin Maiers, Michael Halagan, Latha Jagannatthan, Nezih Cereb, Sangeeta Joshi, Ranjana W. Minz, and Joy John Mammen
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medicine.medical_specialty ,education.field_of_study ,Hla haplotypes ,business.industry ,Population ,Hematology ,Human leukocyte antigen ,Surgery ,Population based study ,Transplantation ,Unrelated Donor ,Match rate ,Genetic model ,medicine ,education ,business ,Demography - Abstract
Summary Background For patients who do not have a suitable human leukocyte antigen (HLA)-matched family donor, unrelated donor registries of adult volunteers and banked umbilical cord blood (UCB) units provide the potential for successful haemopoietic stem-cell transplantation. The size and genetic composition of such registries determines the proportion of patients who will be able to find a suitable match. We aimed to assess the proportion of positive matches for Indian patients. Methods Using HLA data from ten existing donor and UCB registries and clinical transplant centres in India, we built population-based genetic models for 14 Indian regions to model Indian registry growth to predict the likelihood of identifying a suitable donor—either an adult donor or UCB—for Indian patients. We computed ranking tables of the top ten haplotypes in each regional group and compared these with four US samples from the National Marrow Donor Program (NMDP) registry. Findings The mean proportion of individuals who would have a 10/10 adult donor match within India ranged from 14·4% with a registry size of 25 000 to 60·6% with a registry size of 1 000 000. Only when donor registries increased to 250 000 did the match rate within India exceed that found by searching the US-NMDP registry combined with an Indian registry of 25 000 donors. The proportion of matches increased logarithmically with increased registry size ( R 2 =0·993). For a UCB registry size of 25 000, 96·4% of individuals would find a 4/6 match; however, only 18·3% would have a 6/6 match. Interpretation Serial match modelling and follow-up comparisons can identify the relative and progressively greater value of an India-based donor registry and UCB banking network to serve the Indian population. Understanding regional HLA haplotype diversity could guide registry growth and maximise benefit to patients. Similar modelling could guide planning for the needs of other ethnically distinct populations. Funding University of Minnesota and the Indian Council for Medical Research.
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- 2016
49. Outcomes of Myeloablative Haplo-Identical Hematopoietic Stem Cell Transplant in Pediatric Patients with TCR α/β and CD 19 Depletion
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B.R. Prathip, Sonamani Ngangbam, K.S. Nataraj, Nedun Chezhian, Sunil Bhat, Shobha Badiger, Tadele Hailu, Ruchi Chaudhary, Waseem Iqbal, Sharat Damodar, and Sohini Chakraborty
- Subjects
Transplantation ,business.industry ,T-cell receptor ,Hematopoietic stem cell ,Hematology ,Haplo identical ,03 medical and health sciences ,0302 clinical medicine ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Cancer research ,Medicine ,business ,030215 immunology - Published
- 2017
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50. Assessment of Quality of Life in Myeloma Patients Post Autologous Stem Cell Transplant- A Single Centre Experience in South India
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Shoba Badiger, Sunil Bhat, Suresh Karanth, Sharat Damodar, Prathip Kumar, and K.S. Nataraj
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Cancer Research ,medicine.medical_specialty ,Single centre ,Quality of life (healthcare) ,Oncology ,business.industry ,medicine ,Hematology ,Stem cell ,Intensive care medicine ,business ,Surgery - Published
- 2017
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