25 results on '"Joseph M. John"'
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2. R.M.S. bite corrector: A novel appliance for the correction of mandibular prognathism in growing children-Part one: Skeletal and dental changes
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Rajmohan Shetty, Joseph M. John, Amitha M. Hegde, and Amina Usman
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General Medicine ,General Biochemistry, Genetics and Molecular Biology - Abstract
Introduction and Aim: Mandibular prognathism is one of the most challenging conditions in clinical dental practice. No appliance has yet been introduced to manage this strenuous condition. Hence, a modified appliance, R.M.S. (removable acrylic splint) bite corrector was fabricated combining the principles of three conventional appliances. The aim was to evaluate the skeletal and dental changes following R.M.S bite corrector in growing children with mandibular prognathism, using lateral cephalograms. Materials and Methods: Twenty children between the age group 9 - 13 years, presenting with class III malocclusion with prognathic mandible were selected. R.M.S bite corrector was fabricated, which consist of reverse twin block with RME (Rapid Maxillary Expansion) incorporated in the upper block. Hooks integrated in the molar region of the upper block, and between the lateral incisors and canines in the lower block. A gradual increasing force was delivered by engaging intraoral intermaxillary elastics. After 10 months, skeletal, dental, and dentoalveolar parameters and linear measurements of jaw bases were compared using pre- and post-operative lateral cephalograms. Results: After 10 months, skeletal changes included a significant retrusion of the mandible and maxillary protraction. Dental changes comprised of an increase in proclination of maxillary and mandibular incisors, which was not significant. A significant increase in the length of the maxillary base, non-significant change in the linear measurements of the mandibular base and ramal length leading to relocation of the mandible in a relatively new position with better esthetics. Conclusion: Desirable skeletal and dental changes were observed following R.M.S. bite correction.
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- 2022
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3. Real World Data on Unique Challenges and Outcomes of Older Patients with AML from Resource Limited Settings: Indian Acute Leukemia Research Database (INwARD) of the Hematology Cancer Consortium (HCC)
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Suvir Singh, Sharon Lionel, Hasmukh Jain, Lingaraj Nayak, Sushil Selvarajan, Prasanna Samuel, Rayaz Ahmed, Narendra Agrawal, Pavitra DS, Poojitha Byreddy, Joseph M John, Kundan Mishra, Suman Kumar, Mobin Paul, Latha Abraham, Smita Kayal, Prasanth Ganesan, Chepsy C Philip, Damodar Das, Sreeraj Vasudevan, Prashant Mehta, Jayachandran PK, Vineetha Raghavan, Stalin Chowdary Bala, Bharath Ram S, Swaratika Majumdar, Akhil Rajendra, Om Prakash, Barath U, Bhausaheb Bagal, Aby Abraham, Rajan Kapoor, Dinesh Bhurani, Manju Sengar, and Vikram Mathews
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Immunology ,Cell Biology ,Hematology ,Biochemistry - Published
- 2022
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4. 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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5. 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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6. 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
7. Patient blood management in India - Review of current practices and feasibility of applying appropriate standard of care guidelines. A position paper by an interdisciplinary expert group
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Anil Handoo, Vijay Vohra, Klaus Görlinger, Ajay Gandhi, Anil Karlekar, Jyoti Kotwal, Anjali Rani, Joseph M John, Sukesh C. Nair, Shweta Singh, Shashikant Apte, Anjan Trikha, Yatin Mehta, Aseem K Tiwari, Poonam Malhotra Kapoor, and Gajendra Gupta
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medicine.medical_specialty ,Blood management ,Review Article ,thromboelastometry ,blood transfusion ,coagulopathy ,Patient safety ,Pharmacy and materia medica ,Anesthesiology ,Intensive care ,Health care ,patient safety ,Medicine ,RD78.3-87.3 ,Pharmacology (medical) ,General Pharmacology, Toxicology and Pharmaceutics ,hemostasis testing ,patient blood management ,Modalities ,business.industry ,Bleeding ,Perioperative ,medicine.disease ,RS1-441 ,point-of-care testing ,Anesthesiology and Pain Medicine ,Position paper ,Medical emergency ,hemorrhage ,business - Abstract
In a developing country like India, with limited resources and access to healthcare facilities, dealing with massive hemorrhage is a major challenge. This challenge gets compounded by pre-existing anemia, hemostatic disorders, and logistic issues of timely transfer of such patients from peripheral hospitals to centers with adequate resources and management expertise. Despite the awareness amongst healthcare providers regarding management modalities of bleeding patients, no uniform Patient Blood Management (PBM) or perioperative bleeding management protocols have been implemented in India, yet. In light of this, an interdisciplinary expert group came together, comprising of experts working in transfusion medicine, hematology, obstetrics, anesthesiology and intensive care, to review current practices in management of bleeding in Indian healthcare institutions and evaluating the feasibility of implementing uniform PBM guidelines. The specific intent was to perform a gap analysis between the ideal and the current status in terms of practices and resources. The expert group identified interdisciplinary education in PBM and bleeding management, bleeding history, viscoelastic and platelet function testing, and the implementation of validated, setting-specific bleeding management protocols (algorithms) as important tools in PBM and perioperative bleeding management. Here, trauma, major surgery, postpartum hemorrhage, cardiac and liver surgery are the most common clinical settings associated with massive blood loss. Accordingly, PBM should be implemented as a multidisciplinary and practically applicable concept in India in a timely manner in order to optimize the use the precious resource blood and to increase patients' safety.
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- 2021
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8. Systemic and primary cutaneous anaplastic large cell lymphoma: Clinical features, morphological spectrum, and immunohistochemical profile
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Kanwardeep Singh Kwatra, Nalini Calton, James D. Cotelingam, Preethi Anni Mercy Paul, and Joseph M John
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Cancer Research ,Pathology ,medicine.medical_specialty ,CD30 ,T cell ,Primary cutaneous anaplastic large cell lymphoma ,In situ hybridization ,lcsh:RC254-282 ,ORIGINAL ARTICLE: Leukemia and Lymphoma ,030207 dermatology & venereal diseases ,03 medical and health sciences ,0302 clinical medicine ,T-cell ,Antigen ,hemic and lymphatic diseases ,medicine ,anaplastic lymphoma kinase-1 ,Anaplastic large-cell lymphoma ,Anaplastic large cell lymphoma ,epithelial membrane antigen ,business.industry ,non-Hodgkin lymphoma ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,medicine.disease ,Lymphoma ,medicine.anatomical_structure ,Oncology ,030220 oncology & carcinogenesis ,immunohistochemistry ,Immunohistochemistry ,business - Abstract
Background: T-cell lymphomas with anaplastic morphology typically comprise of anaplastic lymphoma kinase positive, anaplastic large cell lymphoma (ALK+ ALCL), ALK-negative ALCL (ALK- ALCL), and primary cutaneous ALCL (PC-ALCL). However, other entities such as diffuse large B-cell lymphoma, peripheral T-cell lymphoma, Hodgkin lymphoma, and undifferentiated carcinoma can also show similar anaplastic features. Aims: To study the clinical features and histological spectrum of ALCL and emphasize the role of immunohistochemistry (IHC) in their diagnosis and categorization. Setting and Design: Eight cases of ALCL diagnosed over a period of 4 years were selected for the study. Materials and Methods: Histopathological review and IHC was performed on all cases. Two ALK+ ALCL cases were tested by fluorescent in situ hybridization (FISH) for t(2;5)(p23;q35). Results: There were four cases of ALK+ ALCL and two each of ALK- ALCL and PC-ALCL. Histologically, all the subtypes showed pleomorphic and “hallmark” cells with strong CD30 expression and variable loss of T-cell antigens. One case of PC-ALCL was leukocyte common antigen (LCA) negative. Epithelial membrane antigen was positive in all the six systemic ALCL cases. Two cases tested for t(2;5)(p23;q35) by FISH were positive. Conclusions: Diagnosis of ALCL is based on recognizing the key morphological features, especially the presence of “hallmark” cells. IHC is essential for confirmation of diagnosis and excluding other malignancies with anaplastic morphology. The inclusion of CD30 in the initial IHC panel will help identify LCA negative cases and avoid misdiagnosis.
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- 2017
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9. No serological evidence for neuronal damage or reactive gliosis in neuro-COVID-19 patients with long-term persistent headache
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Laura de Boni, Alexandru Odainic, Natalie Gancarczyk, Luisa Kaluza, Christian P. Strassburg, Xenia A. K. Kersting, Joseph M. Johnson, Ullrich Wüllner, Susanne V. Schmidt, Jacob Nattermann, and Gabor C. Petzold
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Post-acute sequelae of SARS-CoV-2 infection ,Post-COVID-19 ,Headache ,NfL ,GFAP ,Biomarkers ,Neurosciences. Biological psychiatry. Neuropsychiatry ,RC321-571 ,Neurology. Diseases of the nervous system ,RC346-429 - Abstract
Abstract Recent studies have indicated that long-term neurological sequelae after COVID-19 are not accompanied by an increase of canonical biomarkers of central nervous system injury in blood, but subgroup stratifications are lacking. This is a particular concern in chronic headache, which can be a leading symptom of Post-COVID diseases associated with neuronal damage such as vasculitis or autoimmune encephalitis. We here compared patients with mild Post-COVID-19 syndrome and persistent headache (persistent Post-COVID-19 headache) lasting longer than 12 weeks after the initial serological diagnosis, to patients with mild and severe COVID-19 and COVID-19-negative controls. Levels of neurofilament light chain and glial fibrillary astrocytic protein, i.e. markers of neuronal damage and reactive astrogliosis, were lower in blood from patients with persistent Post-COVID-19 headache compared to patients with severe COVID-19. Hence, our pilot serological study indicates that long-term Post-COVID-19 headache may not be a sign of underlying neuronal damage or neuroinflammation.
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- 2022
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10. Prophylactic levofloxacin in cancer chemotherapy: a randomized controlled study
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Dinesh K Badyal, Jyotika Peters, and Joseph M. John
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medicine.medical_specialty ,Cancer chemotherapy ,Randomized controlled trial ,Levofloxacin ,business.industry ,law ,Internal medicine ,medicine ,business ,medicine.drug ,law.invention - Abstract
Background: The patients on cancer chemotherapy are at substantial risk of developing febrile episodes, bacteremia and infection related mortalities, yet the prophylactic use of antimicrobials continues to be a controversial issue. Hence, this study was designed to study the effect of antimicrobial prophylaxis in cancer chemotherapy.Methods: The patients receiving the cancer chemotherapy were randomly divided into two groups. Group A patients received cancer chemotherapy and no prophylactic antimicrobials. Group B patients were given prophylactic levofloxacin with each cancer chemotherapy cycle. Patients were evaluated for febrile episodes, documented infections and hospitalizations. The Eastern Cooperative Oncology Group (ECOG) performance grade and culture sensitivity reports were also recorded.Results: Demographic profile of patients was comparable in both groups. Absolute neutrophil count at 6 weeks was significantly higher with levofloxacin prophylaxis. Levofloxacin prophylaxis led to 92% reduction in risk of having neutropenia in first cycle, 78% reduction in clinically documented febrile episodes during the first chemotherapy cycle (36 % vs 8%, 95% confidence interval 0.08 to 0.56, p
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- 2018
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11. Supportive Care and Newer Therapies in Aplastic Anaemia
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Pankaj, Malhotra and Joseph M, John
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Immunosuppression Therapy ,Hydrazines ,Hematologic Agents ,Hematopoietic Stem Cell Transplantation ,Secondary Prevention ,Anemia, Aplastic ,Humans ,Pyrazoles ,Blood Transfusion ,Hemorrhage ,Opportunistic Infections ,Prognosis ,Benzoates - Published
- 2015
12. Pre-Transplant Consolidation and Cost Effectiveness of RIC Allogeneic SCT in Patients of AML-CR1 in India
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Abhijeet Ganapule, Kavitha M Lakshmi, Reetu Jain, Amrith Mathew, Nataraj K. Srinivasarao, Alok Srivastava, Kannan Subramani, Joseph M John, Sachin Punatar, Ranjit Kumar Sahoo, Aby Abraham, Auro Viswabandya, Dinesh Bhurani, Lalit Kumar, Sharat Damodar, Tapan Saikia, Rayaz Ahmed, Navin Khattry, Biju George, Vikram Mathews, Shashikant Apte, and Alok C. Gupta
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medicine.medical_specialty ,business.operation ,Cost effectiveness ,Immunology ,Octapharma ,Biochemistry ,Gastroenterology ,Median follow-up ,Internal medicine ,medicine ,In patient ,Preparative Regimen ,Transplantation ,business.industry ,Induction chemotherapy ,Consolidation Chemotherapy ,Cell Biology ,Hematology ,Chemotherapy regimen ,Fludarabine ,Surgery ,Regimen ,Cord blood ,Gvhd prophylaxis ,business ,medicine.drug - Abstract
Management of acute myeloid leukemia (AML) in India remains a challenge. A major constraint is the cost of therapy. In a predominantly self paying system the majority of patients will not have the resources to manage a subsequent relapse. Hence, the choice of consolidation therapy has to be carefully considered to balance cost and efficacy. An allogeneic SCT (alloSCT) with a reduced intensity conditioning regimen (RIC) in first remission (CR1) is an attractive option to fulfill these requirements of relatively low cost without compromising efficacy. The need for consolidation chemotherapy prior to offering a RIC alloSCT for AML CR1 remains controversial. To evaluate these aspects we undertook a retrospective analysis of patients with AML CR1 who received a RIC alloSCT from multiple centers in India. Conventional criteria were used for definition of conditioning regimens to be considered RIC (CIBMTR). Data from 8 centers in India was collected between 2005 and 2013. A total of 138 patients fulfilled the criteria of AML CR1 having received an alloSCT with a RIC regimen. The median age was 34 years (range: 2 – 63) and 60% were males. The median time from diagnosis of AML to transplant was 99 days (range: 41 – 504). 123 (89%) were HLA matched related donors, 3 (2.1%) were MUD transplants and the rest were HLA mismatched related donors. The majority by cytogenetics (n=115) were intermediate risk (76%) followed by high risk (23%). 70 (51%) received chemotherapy consolidation prior to transplant, 61 (44%) did not and data was not available in 7 (5%). 68% of those that received consolidation received intermediate or low dose cytosine based regimens. 129 (94%) were CMV serology positive pre-transplant. Fludarabine with melphalan (140mg/m2) (128{93%}) was the most commonly used regimen and cyclosporine with short course low dose methotrexate (126{91%}) the most commonly used GVHD prophylaxis regime. All patients received a PBSC graft with a median CD34 cell dose of 9.1x106/kg (range: 1.3 – 43). With the exception of one, all patients engrafted. The median time to ANC >500/mm3 was 13 days (range: 7 – 22) and platelet count of >20,000/mm3 was 15 days (range: 0-33). Of those that engrafted, 97% achieved complete chimerism at one month post transplant (data not available in 4). Post transplant CMV reactivation was seen in 32% and a fungal infection (possible, probable or definitive) in 13%. Acute GVHD Grade 2-4 was seen in 29% and of patients evaluated 62% had chronic GVHD, the majority of these being limited (61%). The 100 day treatment related mortality (TRM) was 7.5% and the one year TRM was 25.6%. At a median follow up of 24 months the 5 year EFS and OS was 64.0±5.07 (Figure 1A) and 71.1±4.0 respectively. The 5 year cumulative incidence of relapse was 21.8% (Figure 1A). The baseline characteristics as mentioned above were not significantly different between the group that received consolidation and the group that did not. The use of consolidation therapy prior to alloSCT did not have a significant impact on EFS or OS (Figure 1B). On univariate analysis the factors that adversely impacted EFS were mismatched non sibling family donor (RR 8.1; P-value 0.001), CMV reactivation (RR 2.6; P-value 0.001), fungal infection post transplant (RR 6.8; P-value 0.000) and acute GVHD (RR 2.1; P-value 0.02). On a forward stepwise multivariate analysis adjusting for these and other conventional risk factors only CMV reactivation (RR 2.0; 95% CI 1.03-3.87; P-value 0.042) and fungal infection (RR 7.1; 95%CI 3.154-16.12; P-value 0.000) retained their adverse impact. There was no correlation between CMV reactivation and relapse of disease post transplant. The mean costs of induction chemotherapy for these patients was US$ 9239±3596 (n=74), for consolidation chemotherapy it was 5007±3490 (n=21) and for alloSCT it was 18138±13826 (n=118; costing up to 1 year post transplant). Induction chemotherapy followed by HLA matched RIC alloSCT is likely to be a cost effective and affordable treatment option for young adults with AML in CR1in an Indian context. With an average gross net income in India of US$3500/year (http://indiabudget.nic.in) the limitation still remains the cost of treatment and number of centers that can offer this therapy. Figure 1 Figure 1. Disclosures Srivastava: Octapharma: Consultancy, Other. Off Label Use: Bortezomib in the treatment of acute promyelocytic leukemia.
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- 2015
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13. Local democracy in India: Interpreting decentralization Girish Kumar
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Joseph, M. John
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- 2007
14. Health by the people: Sociology of medical lore V. Sujatha
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Joseph, M. John
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- 2004
15. Methylene blue provides behavioral and metabolic neuroprotection against optic neuropathy
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Joseph M. John, Francisco Gonzalez-Lima, Jung Lee, and Julio C. Rojas
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Retinal degeneration ,Male ,Insecticides ,Nerve fiber layer ,Biology ,Pharmacology ,Toxicology ,Neuroprotection ,Choice Behavior ,Retina ,chemistry.chemical_compound ,Discrimination, Psychological ,Rotenone ,Optic Nerve Diseases ,medicine ,Reaction Time ,Animals ,Drug Interactions ,Rats, Long-Evans ,Visual Pathways ,Ganglion cell layer ,Neurons ,Analysis of Variance ,Electron Transport Complex I ,Dose-Response Relationship, Drug ,Adaptation, Ocular ,General Neuroscience ,Neurotoxicity ,Brain ,Retinal ,NADH Dehydrogenase ,medicine.disease ,Mitochondria ,Rats ,Methylene Blue ,Disease Models, Animal ,medicine.anatomical_structure ,Neuroprotective Agents ,chemistry ,sense organs ,Neuroscience ,Photic Stimulation - Abstract
Methylene blue (MB) is a diaminophenothiazine with potent antioxidant and unique redox properties that prevent morphologic degenerative changes in the mouse retina induced by rotenone, a specific mitochondrial complex I inhibitor. This study evaluated pigmented rats to determine whether MB's neuroprotective effects against rotenone-mediated retinal neurotoxicity have functional relevance and whether these effects are mediated by an improvement in neuronal energy metabolism in vivo. Visual function was behaviorally assessed by determining differences in the illuminance sensitivity threshold pre- and post-bilateral intravitreal injection of rotenone (200 microg/kg) or rotenone plus MB (70 microg/kg). Retinal degeneration was morphologically studied using unbiased stereological tools. Changes in histochemically determined cytochrome oxidase activity in the visual pathway were used to evaluate the impact of treatments on neuronal energy metabolism. Rotenone induced a 1.4 log unit increase in the illumination threshold compared to baseline, as well as a 32% decrease in ganglion cell layer cell (GCL) density, and a 56% decrease in GCL layer + nerve fiber layer thickness. Co-administration of MB prevented the changes in visual function and the retinal histopathology. Furthermore, rotenone induced a functional deafferentation of the visual system, as revealed by decreases in the metabolic activity of the retina, superior colliculus, and visual cortex. These metabolic changes were also prevented by MB. The results provided the first demonstration of MB's behavioral and metabolic neuroprotection against optic neuropathy, and implicate MB as a candidate neuroprotective agent with metabolic-enhancing properties that may be used in the treatment of neurodegenerative diseases associated with mitochondrial dysfunction.
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- 2008
16. Improved Outcomes with Allogeneic Stem Cell Transplantation for Aplastic Anaemia Using HLA Identical Sibling Donors: The Indian Stem Cell Transplant Registry (ISCTR) Experience
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Pankaj Malhotra, A. K. Dixit, Revathi Raj, Gaurav Prakash, Abhijeet Ganapule, Aby Abraham, Sanjeev Kumar Sharma, Alok Srivastava, Jose Easow, Kavitha M Lakshmi, Shashikant Apte, Kannan Subramaniam, Navin Khattry, Neeraj Sidharthan, Sunil Bhat, Fouzia N. Abubacker, Manoranjan Mahapatra, Biju George, Amit Rauthan, Narendra Agarwal, Soniya Nityanand, Joseph M John, Vikram Mathews, Sharat Damodar, Sanjeevan Sharma, Anupam Chakrapani, Dharma Choudhary, Alka Khadwal, Chirag Shah, Ajay K. Sharma, Sameer Ramesh Melinkeri, Rayaz Ahmed, Uday R Deotare, V. Lakshmanan, Pravas Mishra, Mammen Chandy, T. V. Raja, Ramesh Nimmagadda, Tulika Seth, Velu Nair, Dinesh Bhurani, Bhausaheb Bagal, Satyaranjan Das, Seema S. Bhatwadekar, Chandran K Nair, and Anu Korula
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medicine.medical_specialty ,Pediatrics ,Neutrophil Engraftment ,Platelet Engraftment ,business.industry ,medicine.medical_treatment ,Immunology ,Cell Biology ,Hematology ,Hematopoietic stem cell transplantation ,medicine.disease ,Biochemistry ,Fludarabine ,Transplantation ,Graft-versus-host disease ,Median follow-up ,Internal medicine ,medicine ,Aplastic anemia ,business ,medicine.drug - Abstract
Introduction: Allogeneic stem cell transplantation (SCT) is the best form of therapy for a young patient (< 50 years) with severe aplastic anaemia. In developing countries, there is a big time interval between diagnosis and SCT leading to increased transfusions and increased risk of infections, both of which adversely affects transplant outcome. This retrospective analysis is aimed at studying the outcomes of SCT among Indian patients with aplastic anaemia. Methodology: The Indian Stem cell transplant registry (ISCTR) is a group of transplant physicians representing about 30 active transplant centres in India. This retrospective analysis was done on data reported on 634 patients by 20 centres who reported outcomes of SCT for aplastic anaemia. Data was collected from individual medical records and databases. Analysis was done using SPSS software version 16.0 Results: Six hundred and thirty four patients [445 males and 189 females] with a median age of 21 years (range: 2 - 65) underwent allogeneic SCT between 1990 and March 2015. There were 209 children (age < 15 years). The median time from diagnosis to SCT was 5 months (range: 1 - 120) while the median number of transfusions was 20 (range: 1 - 150). All donors were HLA identical sibling or family donors; matched unrelated and haplo-identical donor transplants were excluded from this analysis. Conditioning regimen was Cyclophosphamide based (Cy/ Cy+ ATG/ Cy+ TBI/TLI) in 78 patients (12.3%) while majority received Fludarabine with Cyclophosphamide (n = 481; 75.8%) and 75 received other conditioning regimens (Flu/TBI, Flu/Bu, Bu/Cy etc). Graft source was bone marrow [BM] in 124 (19.5%) and peripheral blood stem cells in 510 patients (80.5%). Graft versus host disease (GVHD) prophylaxis predominantly consisted of Cyclosporine and methotrexate in 543 patients (85.6%). Engraftment was seen in 572 patients (90.4%) while 19 (2.9%) had primary graft failure and 43 (6.7%) expired prior to engraftment due to infection or bleeding. The median time to neutrophil engraftment was 13 days (range: 8 - 21) while platelet engraftment occurred at 13 days (range: 5 - 37). Grade II - IV acute GVHD occurred in 29.3% while grade III-IV was seen in 14.1%. Chronic GVHD was seen in 41% of evaluable patients which was limited in most patients. At a median follow up of 43 months (range: 1 - 264), 431 patients are alive. The 5 yr OS for the entire group is 66.3 + 2.0%. The OS was higher in children compared to adults (73.4 + 3.3% vs 62.8 + 2.5%; p = 0.006), better for Flu/Cy compared to Cy based conditioning (69.8 + 2.2% vs 57.8 + 5.6%; p = 0.002) and better for PBSC compared to BM (68.9 + 2.2% vs 56.1 + 4.8%; p = 0.020). There has been significant improvement in outcomes over the past 15 years [3 yr OS of 41.9 + 1.3% for 1984-1995, 40.9 + 1.2% for 1996-2000, 70.6 + 5.0% for 2001 -2005, 70.3 + 3.1% for 2006-2010 and 68.8 + 3.0% from 2011 onwards]. Conclusion: Outcomes of patients with aplastic anaemia are improving and patients have a 70% chance of getting cured with a HLA identical sibling donor transplant. The use of PBSC as graft source is not associated with inferior outcomes. Disclosures No relevant conflicts of interest to declare.
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- 2015
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17. N-protein presents early in blood, dried blood and saliva during asymptomatic and symptomatic SARS-CoV-2 infection
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Dandan Shan, Joseph M. Johnson, Syrena C. Fernandes, Hannah Suib, Soyoon Hwang, Danica Wuelfing, Muriel Mendes, Marcella Holdridge, Elaine M. Burke, Katie Beauregard, Ying Zhang, Megan Cleary, Samantha Xu, Xiao Yao, Purvish P. Patel, Tatiana Plavina, David H. Wilson, Lei Chang, Kim M. Kaiser, Jacob Nattermann, Susanne V. Schmidt, Eicke Latz, Kevin Hrusovsky, Dawn Mattoon, and Andrew J. Ball
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Science - Abstract
Here the authors develop a single molecule array (Simoa) immunoassay for detection of SARS-CoV-2 nucleocapsid protein in venous and dried capillary blood as well as saliva. The assay shows good performance in symptomatic, asymptomatic, and pre-symptomatic PCR+ individuals.
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- 2021
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18. Imatinib in India: Is the efficacy universal?
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Joseph M John and Vikram Mathews
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Oncology ,Pediatrics, Perinatology and Child Health - Published
- 2005
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19. ICT and Life Long Learning Pedagogy for Development and Empowerment: An Illustration from Farmers in India
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Amirtham, Thomas, primary and Joseph, M. John, additional
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- 2011
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20. IB1001, an Investigational Recombinant Factor IX, Pharmacokinetics in Pediatric Patients with Hemophilia B
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Amy D. Shapiro, Bonnie J. Mills, Martin Lee, Vijay Ramanan, Joseph M John, Edward D. Gomperts, Shashikant Apte, Ri Liesner, and Utpal Chaudhuri
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medicine.medical_specialty ,business.industry ,Immunology ,Cmax ,Cell Biology ,Hematology ,PK Parameters ,Haemophilia ,medicine.disease ,Biochemistry ,Washout period ,Hemophilias ,Pharmacokinetics ,Internal medicine ,medicine ,business ,Factor IX ,medicine.drug ,Recombinant factor IX - Abstract
Abstract 2225 Introduction IB1001 is a recombinant factor IX product being investigated for the treatment and prevention of bleeding in individuals with hemophilia B. Pharmacokinetics (PK) in adults (>12 years) demonstrated that IB1001 had results similar to the currently available recombinant FIX with respect to parameters such as terminal phase half-life and incremental recovery. We report the interim findings from a PK assessment in children 50 prior exposure days to FIX, and no history of or currently detectable inhibitor to FIX. Methods Non-randomized, open-label PK study with patients receiving 75±5 IU/kg of IB1001 following a washout period of ≥4 days from a previous FIX infusion. Factor IX levels were determined pre-infusion and at 15–30 minutes, 4–6, 24–26, and 68–72 hours post-infusion. Additional samples could be drawn at 1–3 and 10–14 hours. Calculated PK parameters were: half-life (β-phase t1/2, determined using a robust regression approach [Lee ML et al. XVIth ISTH Congress, Florence, Italy, 1997]) but generally assuming a single compartmental model because of the small number of points, maximum plasma concentration (Cmax), in vivo recovery (IVR) and AUC(0-∞) (determined by the trapezoidal rule). In addition, the AUC(0-t) and mean residence time (MRT) were calculated. Results When compared to the findings previously reported with IB1001 in adult (≥12 years of age) subjects (Martinowitz U et al. Haemophilia, 18, 2012), the results in pediatric patients demonstrate a more rapid metabolism of factor IX as is indicated by the shorter terminal half-life (mean±SD of 19.3±7.8 h versus 29.6±18.2 h in adults) and the smaller AUC0-∞ (mean±SD of 1059±264 versus 1668±598 in adults). In addition, the in vivo recovery was lower (mean±SD of 0.69±0.21) versus that seen in adults (mean±SD of 0.98±0.22). These results are similar to those reported by Berntorp et al (Haemophilia, 7, 2001) with nonacog alfa. Conclusions The pharmacokinetics of IB1001 has previously been shown to be non-inferior to nonacog alfa, another recombinant factor IX, in hemophilia B individuals >12 years of age. The current study is intended to provide information on children 12 years of age. Although the study is ongoing, these may represent important implications for the potential use of IB1001 in pediatric patients. Disclosures: Gomperts: Inspiration Biopharmaceuticals Inc: Consultancy. Apte:Inspiration Biopharmacauticals Inc: Research Funding. Chaudhuri:Inspiration Biopharmaceuticals Inc: Research Funding. John:Inspiration Biopharmaceuticals Inc: Research Funding. Ramanan:Inspiration Biopharmaceuticals Inc: Research Funding. Liesner:Inspiration Biopharmaceuticals Inc: Research Funding. Shapiro:Inspiration Biopharmaceuticals Inc: Honoraria, Research Funding. Mills:Inspiration Biopharmaceuticals Inc: Employment. Lee:Inspiration Biopharmaceuticals Inc: Employment.
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- 2012
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21. Book Reviews
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Addlakha, Renu, primary, Joseph, M. John, additional, Venkataratnam, R., additional, Thakur, Manish Kumar, additional, Sengupta, Anirban, additional, Sahay, Gaurang R., additional, Mathur, Nita, additional, Kumar, Nikhlesh, additional, Panda, Biswambhar, additional, Saberwal, Satish, additional, Kadekar, Laxmi Narayan, additional, Shyam, Rama, additional, and Chauhan, Abha, additional
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- 2007
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22. Fludarabine and Melphalan Conditioning Regimen in Young Patients with Acute Myeloid Leukemia in CR1 Undergoing a Matched Related Allogeneic Stem Cell Transplant: A Single Center Experience
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Biju George, Vikram Mathews, Alok Srivastava, Auro Viswabandya, Joseph M John, Mammen Chandy, T. Rajasekar, and Kavitha M Lakshmi
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Melphalan ,medicine.medical_specialty ,Chemotherapy ,business.industry ,medicine.medical_treatment ,Immunology ,Induction chemotherapy ,Cell Biology ,Hematology ,Single Center ,Biochemistry ,Gastroenterology ,Donor lymphocyte infusion ,Fludarabine ,Surgery ,Regimen ,hemic and lymphatic diseases ,Internal medicine ,medicine ,Methotrexate ,business ,medicine.drug - Abstract
Allogeneic SCT remains the most effective anti-leukemic therapy. However, due to the associated TRM with conventional myeloablative regimens, this has often not translated to a significant improvement in EFS or OS. Since October 2005, at our center, we offered a RIC regimen consisting of fludarabine 30mg/m2 x 5days followed by one dose of melphalan 140mg/m2 for young adults with AML in CR1 after induction chemotherapy. GVHD prophylaxis consisted of cyclosporine with a low dose short course methotrexate. The graft source was a PBSC harvest. The clinical outcomes were compared with a historical control who received a conventional Bu/Cy regimen. Since October 1992, 55 of patients with AML in CR1 (constituted 47% of all AML transplants done at our center) underwent a matched related allogeneic SCT. Among these 11 received a Flu/Mel conditioning regimen while 41 received a conventional Bu/Cy conditioning regimen (3 patients excluded from analysis since they received other conditioning regimens), the clinical outcomes of these two groups were compared. All, except for one donor (one antigen mismatch) in the Bu/Cy group, were complete 6/6 HLA identical related donors. The age (mean±SD) of patients in the Flu/Mel and the Bu/Cy group was 39±14 and 27±11 respectively. The baseline characteristics of these two groups were comparable for sex, donor age, female to male transplants, AML subtypes and requirement of two course of chemotherapy to achieve CR1. Four (36.4%) of patients among the Flu/Mel group and 28 (68.3%) in the Bu/Cy group received one or two cycles of consolidation chemotherapy prior to SCT. All patients in the Flu/Mel group received a PBSC graft while only 26 (41%) among the Bu/Cy group received a PBSC graft (P=0.05). One patient in the Bu/Cy group failed to engraft. All other cases engrafted. All 11 (100%) cases in the Flu/Mel group had a complete donor chimerism documented on day 30. Prophylactic donor lymphocyte infusion was not administered for any patient. There were no treatment related deaths in the Flu/Mel group up to day 100. One patient died on day 299 following pulmonary GVHD and septicemia. In comparison, the day 100 TRM was 8 (19.5%), going up to a one year all cause mortality of 21 (51%) in the Bu/Cy group. Acute GVHD grade 2–4 occurred in 5 (45.5%) and in 14 (34.1%) among patients conditioned with Flu/Mel and Bu/Cy, respectively. Chronic GVHD occurred in 4 (36.4%) of patients conditioned with Flu/Mel and was similar to the incidence seen in the Bu/Cy group. During the period of follow up none of the patients in the Flu/Mel group have relapsed while 11 (26.8%) patients had relapsed in the Bu/Cy group. The 2 year Kaplan-Meier estimate of EFS and OS for the Flu/Mel and Bu/Cy group (mean follow up 19 and 71 months, respectively) was 85.71±13.23 vs. 43.19±7.82 (P=0.0176) and 85.71±13.23 vs. 45.59±7.86 (P=0.027) respectively. A conditioning regimen of fludarabine and melphalan in young adults with AML in CR1 is associated with a low TRM with a potential to translate into improved EFS and OS. Figure 1: Kaplan-Meier estimate of Event Free Survival among patients who received Flu/Mel conditioning (n=11) versus those that received a Bu/Cy conditioning regimen (n=41) Figure 1:. Kaplan-Meier estimate of Event Free Survival among patients who received Flu/Mel conditioning (n=11) versus those that received a Bu/Cy conditioning regimen (n=41)
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- 2007
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23. Treatment of Relapsed and Refractory Acute Myeloid Leukemia with a Salvage FLAG-IDA Chemotherapy Regimen Followed by a HLA Matched Related Allogeneic PBSC Infusion without Additional Conditioning
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Auro Viswabandya, Kavitha M Lakshmi, Joseph M John, T. Rajasekar, Mammen Chandy, Biju George, Vikram Mathews, and Alok Srivastava
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Chemotherapy ,medicine.medical_specialty ,business.industry ,medicine.medical_treatment ,Immunology ,Cell Biology ,Hematology ,Biochemistry ,Chemotherapy regimen ,Surgery ,Fludarabine ,Regimen ,medicine.anatomical_structure ,Refractory ,medicine ,FLAG (chemotherapy) ,Idarubicin ,Bone marrow ,business ,medicine.drug - Abstract
The clinical outcome of relapsed and refractory AML is dismal. Attempts in this setting to induce a remission, prior to an allogeneic SCT, are frequently frustrated by either failure to respond to chemotherapy or deterioration in the clinical status post chemotherapy. Since December 2005, patients with relapsed and refractory AML were offered salvage chemotherapy with a FLAG-IDA regimen (consisted of G-CSF 10mcg/kg/day starting day −1, Fludarabine 30 mg/m2 x 5 days, Cytosine 2gm/m2 x 5 days and Idarubicin 10mg/m2 x 3 days). On day 10 of chemotherapy a G-CSF mobilized PBSC harvest from a complete HLA matched related donor was infused, targeting a cell dose of 5 x 108 MNC/kg. GVHD prophylaxis consisted of low dose cyclosporine (1.5 mg/kg/day) ± short course low dose methotrexate. Eleven patients were treated with this regimen. The median age was 40 years (range: 2 – 51). There were 7 (64%) males. There were 6 relapsed cases (5 relapse-1 and one relapse-2) and 5 primary refractory cases. Of the relapsed cases, two had relapsed following a prior allogeneic SCT. Among the patients with relapsed AML, the median number of chemotherapy cycles prior to transplant was 3 (range: 2 – 5) and the median time to transplant from relapse was 5 months (range: 5 – 10). Among the 5 refractory patients, the median number of chemotherapy regimens received prior to transplant was 2 (range: 1 – 3) and the median time from diagnosis to transplant was 3 months (range: 1 – 6 months). The median number of bone marrow blasts pre-transplant was 38% (range: 5 – 70). Five cases had an ECOG performance score of 0–1 while 4 had an ECOG score of 2 and 2 had an ECOG score of 3. Salvage FLAG-IDA chemotherapy regimen was well tolerated in all cases. The median cell dose infused on day 10 was 6.59 x 108 MNC/kg (range: 3.5 – 12.73). All but one patient engrafted with a median time to ANC > 500/mm3 of 13 days (range: 9 – 21) post stem cell infusion and Platelet count > 20,000/mm3 of 12 days (range: 9 – 17). One patient failed to engraft and died on day 9 secondary to a fungal pneumonia. Nine patients achieved a complete donor chimerism on day +30 post stem cell infusion. Six (55%) developed grade 2–4 acute GVHD while 2 (18%) developed grade 3–4 acute GVHD. Six of eight who could be evaluated developed chronic GVHD, all had extensive chronic GVHD. Four patients relapsed following transplant at a median of 118 days post transplant (range: 26 – 140). At the time of this analysis 5 (45%) patients are alive and in remission at a mean follow up of 278 days (range: 119 – 551). Of the remaining 6 patients, 4 relapsed and died, 1 died prior to engraftment from a fungal pneumonia and one patient died in remission from an acute cardiac event. FLAG-IDA salvage chemotherapy followed by an allogeneic PBSC graft infusion on day 10 is a reasonable option to consider for patients in this clinical situation.
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- 2007
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24. Book Reviews
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Kaur, Kulbir, primary, Sabbarwal, Sherry, additional, Kaul, Ashok Kumar, additional, Jayalakshmi, D., additional, Sarkar, Sumita, additional, Bhattacharjee, Nabanipa, additional, Gill, Rajesh, additional, Mathew, Miriam, additional, Chatterji, Roma, additional, Kumar, Pushpesh, additional, Jain, Sheena, additional, Ranjan, Akhilesh, additional, Sekher, T.V., additional, Ganguly, Ramanuj, additional, Kadekar, Laxmi Narayan, additional, Kaur, Ravinder, additional, Abidi, Nigar F., additional, Gomes, Bernadette Maria, additional, Saha, Suhrita, additional, Joseph, M. John, additional, Arora, Meghna, additional, and Julka, Abnash C., additional
- Published
- 2004
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25. Bone marrow involvement in systemic oxalosis: A rare cause of leukoerythroblastic anemia
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Naveen Kakkar, Divya Mittal, Sheila Das, Joseph M John, and Timothy Rajamanickam
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Pathology ,RB1-214 ,Microbiology ,QR1-502 - Published
- 2011
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