Planning and designing of an inpatient isolation facility for hematopoietic stem cell transplant patients.

During the last two decades the world has seen an increase in the use of Hematopoietic Stem Cell Transplant (HSCT) which has led to its worldwide expansion. Since, HSCT unit is an advanced set up, developing and maintaining a successful hematopoietic stem cell transplant program with a properly functioning unit enhances the credibility of any tertiary level medical facility especially for a country like ours which is in its early expanding phase of providing transplant services. The underlying principle for designing any HSCT facility is to maintain the highest possible level of aseptic environment for patients undergoing the transplant in order to prevent healthcare associated infections. Basic premises of designing the entire HSCT unit was to ensure restricted access to the facility and having an aseptic environment by implementing infection control parameters in design elements, which are explained subsequently in the article. The present manuscript describes the project experience of creating a positive pressure isolation facility for HSCT patients at a tertiary care hospital, India, which is a resource limited setting with an emphasis on need assessment, key elements in planning and designing along with the challenges associated with it.

Clinico-pathological profile of patients with plasma cell neoplasms with special reference to bone marrow fibrosis and amyloid deposition.

To clarify the significance of bone marrow fibrosis and amyloid deposition in plasma cell neoplasm, a retrospective cross-sectional study for a period of 3 years was conducted. Patients who underwent bone marrow aspiration and biopsy with suspicion of plasma cell neoplasms were included in the study. The bone marrow findings were correlated with clinical profile of the patient along with biochemical parameters, cytogenetics, Fluorescent in situ hybridization (FISH) wherever available. A total of 273 bone marrow aspirates and biopsies of patients with suspected plasma cell neoplasms were analyzed. There were 181 male patients and 92 female patients (Male: Female = 1.96: 1). There were 245 cases of multiple myeloma (89.7%), 8 cases of primary amyloidosis (2.9%) and 6 monoclonal gammopathy of undetermined significance (MGUS) (2.1%), 5 cases of plasmacytoma (1.8%) and 4 cases of smouldering myeloma (1.4%), 5 cases of POEMS syndrome (1.8%). Bone marrow fibrosis was noted in 12 patients at diagnosis (4.3%). Among the parameters studied, only the mean Hemoglobin was significantly low in patients with marrow fibrosis. Amyloid deposition in various organs including bone marrow, kidney, liver etc., were noted in 17 patients overall (6.2%). In conclusion, the incidence of fibrosis (4.3%) and amyloidosis (6.2%) associated with plasma cell neoplasms were much lower in our study as compared to published studies.

Second stem cell transplantation for treatment of relapsed/refractory multiple myeloma after first autologous stem cell transplant: A 15-year retrospective institutional analysis.

Background: Multiple myeloma remains an incurable disease, with the majority of patients relapsing after autologous stem cell transplant (ASCT). After relapse, second transplant remains one of the therapeutic options, along with novel agents. Methods: We reviewed the data of our patients who underwent ASCT for myeloma (N = 202) over the last two decades (2004-2019). Of these, 12 patients underwent a second transplant. Results: Out of 12 patients, nine underwent second autologous stem cell transplant, whereas three received an allogeneic stem cell transplantation (Allo-SCT). Median progression-free survival (PFS) after the first ASCT was 32 months (5-84 months). Median interval between both the transplants was 35 months (4-159 months). Median age of our cohort which underwent second transplant was 56 years. Overall response rate (ORR) post-second transplant on day +100 was 83.3%, without any transplant-related mortality (TRM). With the use of preemptive plerixafor, none of our patients required a second day for stem cell harvest. Median CD34 dose of stem cells infused was 4.11 × 106/kg. Similar to the first ASCT, the median time to neutrophil and platelet engraftment was 11 and 12 days, respectively. At a median follow-up of 41 months, estimated 3-year PFS and overall survival (OS) was 37% ± 15% and 63% ± 15%, respectively. Conclusion: ">Among all relapsed myeloma patients who were transplant eligible, 11% underwent a second transplant. Second transplant is well tolerated with similar time to engraftment after first ASCT. Hence, we believe that second transplant is a feasible, cost-effective option in a resource-limited setting, which should be more widely utilized.

Acute promyelocytic leukemia masquerading as myeloid maturation arrest- A Case report.

Acute promyelocytic leukemia (APL) is a medical emergency. The diagnosis of APL requires morphological examination, cytochemistry, immunophenotyping, and reverse transcriptase polymerase chain reaction (RT-PCR) for PML::RARA or its variants. However, due to the rapid development of complications, diagnosis often relies on morphology and cytochemistry for early treatment. Herein, we describe a 72-year-old gentleman who presented with pancytopenia diagnosed as acute promyelocytic leukemia with an unusual morphology. The bone marrow smear showed 80% myelocyte-like cells with prominent granules and maturation arrest, with an occasional neutrophil. On careful re-examination of the peripheral smear and bone marrow, an occasional poorly preserved cell with a bundle of Auer rods was identified. Cytochemistry for MPO was strongly positive in abnormal promyelocytes and flow cytometry showed positivity for MPO, CD13, CD33, and CD117 and was negative for CD34 and HLA-DR. Cytogenetics showed a complex karyotype of 45,XY, -14, t(15;17)(q24;21)t(14;21)(q11.2;p13)[10]/ 45, XY, idem, add(5)(q35)[5]/ 45,X,-Y[5]. RT-PCR for PML-RARA was positive for the bcr-3 transcript and FISH was positive for t(15;17) (q24;q21). The take home point from our case is to look for the presence of cells with bundle of Auer rods whenever there is pancytopenia with the presence of myelocyte-like cells with prominent granulations.

Splenic Lymphomas: A Tertiary Care Center Experience and Review of Literature.

Primary splenic lymphomas are rare with the majority of lymphomas in spleen being secondary to an extra-splenic lymphoma. We aimed to analyze the epidemiological profile of the splenic lymphoma and review the literature. This was a retrospective study including all splenectomies and splenic biopsies from 2015 to September 2021. All the cases were retrieved from Department of Pathology. Detailed histopathological, clinical and demographic evaluation was done. All the lymphomas were classified according to WHO 2016 classification. A total of 714 splenectomies were performed for a variety of benign causes, as part of tumor resections and for the diagnosis of lymphoma. Few core biopsies were also included. A total of 33 lymphomas diagnosed in the spleen, primary splenic lymphomas constituted 84.84% (n = 28) of the cohort with 5 (15.15%) having the primary site elsewhere. The primary splenic lymphomas constituted 0.28% of all the lymphomas arising at various sites. Adult population (19-65 years) formed the bulk (78.78%) with a slight male preponderance. Splenic marginal zone lymphomas (n = 15, 45.45%) comprised of major proportion of cases followed by primary splenic diffuse large B-cell lymphoma (n = 4, 12.12%). Splenectomy was the main course of treatment for SMZL with a good overall outcome, with chemotherapy ± radiotherapy forming the mainstay in other lymphomas. Lymphomas in spleen can be infiltrative or a primary, hence proper clinic-radiological and pathological evaluation is required. Appropriate management is guided by the precise and detailed evaluation by the pathologist, requiring understanding of the same.

Clinical lesson to not overlook venous thrombosis: a case of primary antiphospholipid syndrome.

A man in his early 30s presented to us with progressive shortness of breath limiting activities of daily living. An important clue in history was the episode of a deep vein thrombosis 5 years ago treated with short-term anticoagulation. His echocardiography revealed elevated estimated pulmonary artery systolic pressure. A CT pulmonary angiography confirmed chronic thromboembolic pulmonary hypertension. Blood investigations established primary antiphospholipid syndrome. He underwent pulmonary endarterectomy, relieving his symptoms and was started on indefinite oral anticoagulation with warfarin. He is currently under follow-up with no recurrence of thrombosis.We wish to highlight the importance of an appropriate workup of venous thrombosis in all patients. Antiphospholipid syndrome is a rare disease with important implications in the management of patients with thromboses. The delay in his diagnosis had several causes including the unclear distinction between provoked and unprovoked thrombosis and socioeconomic factors in a developing nation limiting referral and testing.

An early detection and segmentation of Brain Tumor using Deep Neural Network.

BACKGROUND: Magnetic resonance image (MRI) brain tumor segmentation is crucial and important in the medical field, which can help in diagnosis and prognosis, overall growth predictions, Tumor density measures, and care plans needed for patients. The difficulty in segmenting brain Tumors is primarily because of the wide range of structures, shapes, frequency, position, and visual appeal of Tumors, like intensity, contrast, and visual variation. With recent advancements in Deep Neural Networks (DNN) for image classification tasks, intelligent medical image segmentation is an exciting direction for Brain Tumor research. DNN requires a lot of time & processing capabilities to train because of only some gradient diffusion difficulty and its complication. METHODS: To overcome the gradient issue of DNN, this research work provides an efficient method for brain Tumor segmentation based on the Improved Residual Network (ResNet). Existing ResNet can be improved by maintaining the details of all the available connection links or by improving projection shortcuts. These details are fed to later phases, due to which improved ResNet achieves higher precision and can speed up the learning process. RESULTS: The proposed improved Resnet address all three main components of existing ResNet: the flow of information through the network layers, the residual building block, and the projection shortcut. This approach minimizes computational costs and speeds up the process. CONCLUSION: An experimental analysis of the BRATS 2020 MRI sample data reveals that the proposed methodology achieves competitive performance over the traditional methods like CNN and Fully Convolution Neural Network (FCN) in more than 10% improved accuracy, recall, and f-measure.

Type 2 hyper-IgM syndrome with a rare variant of AICDA gene mutation in a young woman.

We report the case of a woman in her early 20s with a history of recurrent infection, atopic dermatitis, filariasis and bilateral purulent ear discharge since childhood with tonsillar enlargement on examination. She was started on supportive care and evaluated for primary immunodeficiency disease. Blood investigations revealed increased IgM levels with reduced IgG, IgA and IgE levels. Radiological imaging of the chest revealed bilateral bronchiectasis. Otoscopic examination showed features suggestive of chronic suppurative otitis media. Next-generation sequencing identified homozygous single base pair deletion in exon 2 of the activation-induced cytidine deaminase gene. Thus, a diagnosis of hyper-IgM syndrome type 2 was confirmed. The patient was started on monthly intravenous immunoglobulin replacement therapy and is currently symptomatically better, and she remains under regular follow-up.

Current state of non-hematologic cancer-associated thrombosis at a tertiary care hospital in India

Abstract Introduction Cancer-associated thrombosis is a leading cause of morbidity and mortality in malignancy patients. Prophylactic anticoagulation is under-utilized and the cost of low-molecular-weight heparin (LMWH) and direct oral anticoagulants is a major barrier in developing countries. Material and methods A retrospective analysis was performed of all cancer-associated thrombosis patients attending the thrombosis clinic at a tertiary-level referral hospital based in North India between 2011 and 2015. Patient demographics and disease-related parameters were collected and analyzed. Results A total of 771 patients attended the thrombosis clinic during study period, of which 64 cases were malignancy-associated. Of these, 56% of the patients were female and 20% were bedridden. The median age was 48.5 years, adenocarcinoma (48%) being the most common histological subtype. Gynecological malignancies (30%) were the most common malignancies, followed by genitourinary (11%) malignancies. Most of the cases occurred during first year of diagnosis (51%), and only 14% occurred after 3 years. Most of the patients were on combined treatment. Almost 40% of the patients developed thrombosis within 30 days of surgical treatment. Lower limb thrombosis was the most commonly seen type (56%), while abdominal and pulmonary thrombosis were both seen in 5%. Patients were managed with LMWH and vitamin K antagonists (84.3%) and only 6.25% with LMWH alone. Direct oral anticoagulants were not commonly used during the study period. Discussion At the hospital studied, most of the cases occurred early in the disease course. Postoperative prophylaxis could have contributed towards reducing thrombosis in the peri-operative period. Early suspicion and prompt treatment can improve quality of life in such patients.

Follicular Helper T-Cell-derived Nodal Lymphomas: Study of Histomorphologic, Immunophenotypic, Clinical, and RHOA G17V Mutational Profile.

The study was designed to review the demographic, clinical, and pathologic characteristics of follicular helper T cells (TFH)-derived nodal PTCL in India including angioimmunoblastic T-cell lymphoma (AITL), peripheral T-cell lymphoma (PTCL) with follicular helper T cell phenotype (P-TFH), and follicular T-cell lymphoma with additional immunohistochemistry (IHC) and RHOAG17V mutational analysis, as well as their impact on survival. This retrospective study included 88 cases of PTCL that were reclassified using IHC for TFH markers (PD1, ICOS, BCL6, and CD10) and dendritic-meshwork markers (CD21, CD23). Cases of TFH cell origin were evaluated for RHOAG17V mutation using Sanger sequencing and amplification-refractory mutation system-polymerase chain reaction (PCR) (validated using cloning and quantitative PCR) with detailed clinicopathologic correlation. Extensive re-evaluation with added IHC panel resulted in a total of 19 cases being reclassified, and the final subtypes were AITL (37 cases, 42%), PTCL-not otherwise specified (44, 50%), P-TFH (6, 7%), and follicular T-cell lymphoma (1, 1%). The presence of at least 2 TFH markers (>20% immunopositivity) determined the TFH origin. AITL patients tended to be male and showed increased presence of B-symptoms and hepatosplenomegaly. Histomorphology revealed that 92% of AITL cases had pattern 3 involvement. Sanger sequencing with conventional PCR did not yield any mutation, while RHOAG17V was detected by amplification-refractory mutation system-PCR in AITL (51%, P =0.027) and P-TFH (17%), which was validated with cloning followed by sequencing. Cases of RHOAG17V-mutant AITL had a worse Eastern Cooperative Oncology Group performance status initially but fared better in terms of overall outcome ( P =0.029). Although not specific for AITL, RHOAG17V mutation shows an association with diagnosis and requires sensitive methods for detection due to low-tumor burden. The mutant status of AITL could have prognostic implications and translational relevance.

Current state of non-hematologic cancer-associated thrombosis at a tertiary care hospital in India.

INTRODUCTION: Cancer-associated thrombosis is a leading cause of morbidity and mortality in malignancy patients. Prophylactic anticoagulation is under-utilized and the cost of low-molecular-weight heparin (LMWH) and direct oral anticoagulants is a major barrier in developing countries. MATERIAL AND METHODS: A retrospective analysis was performed of all cancer-associated thrombosis patients attending the thrombosis clinic at a tertiary-level referral hospital based in North India between 2011 and 2015. Patient demographics and disease-related parameters were collected and analyzed. RESULTS: A total of 771 patients attended the thrombosis clinic during study period, of which 64 cases were malignancy-associated. Of these, 56% of the patients were female and 20% were bedridden. The median age was 48.5 years, adenocarcinoma (48%) being the most common histological subtype. Gynecological malignancies (30%) were the most common malignancies, followed by genitourinary (11%) malignancies. Most of the cases occurred during first year of diagnosis (51%), and only 14% occurred after 3 years. Most of the patients were on combined treatment. Almost 40% of the patients developed thrombosis within 30 days of surgical treatment. Lower limb thrombosis was the most commonly seen type (56%), while abdominal and pulmonary thrombosis were both seen in 5%. Patients were managed with LMWH and vitamin K antagonists (84.3%) and only 6.25% with LMWH alone. Direct oral anticoagulants were not commonly used during the study period. DISCUSSION: At the hospital studied, most of the cases occurred early in the disease course. Postoperative prophylaxis could have contributed towards reducing thrombosis in the peri-operative period. Early suspicion and prompt treatment can improve quality of life in such patients.