Background India faces a challenge of dual burden of tuberculosis (TB) and anaemia. The later has a bidirectional relationship with TB and is associated with delayed recovery, poor treatment outcomes, and increased mortality. However, anaemia and its types are often overlooked in routine TB management, and little is known about how its pathophysiology changes during anti-tubercular treatment (ATT). Objective To observe changes in the types of anaemia in a cohort of new pulmonary TB patients in Puducherry post ATT, focussing on ACD. Methods A community based prospective longitudinal cohort study was conducted among sputum smear- positive TB patients (N=176, aged ≥18 years), newly diagnosed and enrolled between 2017-2019 and followed-up until the end of ATT in 2022. 145 participants completed the follow-up. In addition to sociodemographic characteristics haematological and biochemical parameters such as CBC, ferritin, transferrin, serum iron, sTfR, and CRP were measured at the start and end of treatment. Anaemia was classified based on WHO definition and it types were classified using sTfR/Log10 ferritin values. Data were collected using Epicollect and analysed with STATA14. Results Among 176 participants who met the inclusion criteria, majority were aged 31-60 years (71%), and were males (73.3%). At the start of ATT, 63% (111/176) had anaemia, ACD being the predominant [84.6% (94/111)] type, followed by IDA [13.5% (15/111)], other types being ACD+IDA and macrocytic anaemia (0.9% each). Anaemia prevalence declined to 44% (64/145) by the end of ATT; ACD declined by 29.9% (from 84.6% to 54.7%) whereas IDA increased by 22.4% (from 13.5% to 35.9%). Anemia prevalence among women at baseline (82 %) and endline (78 %) were substantially higher. The increase in ferritin levels among women was much lower compared to men. On categorizing the participants based on the types of anaemia at the beginning and of ATT, the levels were suboptimal even after ATT, especially in women with IDA (11 ng/mL in ACD to IDA and 13 ng/mL in IDA groups). Despite a decline in overall CRP levels post ATT, the levels were high (5.7 to 9.8 mg/L) compared to the RIR cut-off of 2 mg/L. Conclusion Anaemia, particularly ACD, is highly prevalent in newly diagnosed TB patients and does not completely resolve with ATT alone, with residual inflammatory risk. Women have iron deficiency in addition to ACD and could be treated with iron supplements at least after the intensive phase of TB treatment.

Context Chronic myeloid leukemia (CML) is a clonal myeloproliferative neoplasm. Recent studies have suggested that CD26-positive leukemic stem cells (LSCs) circulating in peripheral blood are specific for CML. Objective This study was undertaken to determine the proportion of CD26-positive LSCs at diagnosis and its change during tyrosine kinase inhibitor therapy. Design This prospective study was conducted on 43 cases of CML at diagnosis. For flow cytometry, peripheral blood cells were stained with CD45, CD34, CD38, CD3, and CD26. A sequential gating strategy with CD45/SSC (side scatter), CD34/SSC, and CD34/CD38 was applied to identify CD45+/34+/38- populations, from which CD26-positive stem cells were identified and compared with controls. Data analysis was done with Kaluza software. Results All patients diagnosed with CML were detected with CD26-positive LSCs. The median percentage of CD26-positive CML LSCs was 0.02 with a range of 0.001 to 1.77. None of the control samples showed CD26 positivity. The percentage and absolute count of CD26-positive CML LSCs were reduced after six months of tyrosine kinase therapy in patients with complete hematological remission. Conclusion Flow cytometric analysis of circulating CD26-positive CML LSCs is a non-invasive, rapid, and useful tool in the diagnosis and follow-up of CML.

Antiphospholipid syndrome (APS) is an autoimmune disease with specific clinical features and the presence of antiphospholipid antibodies (aPL) like anti-beta2 glycoprotein 1 (anti-β2gp1), anti-cardiolipin antibody (aCL), and/or lupus anticoagulant (LA). The purpose of this study was to evaluate the laboratory profile of LA-positive cases and study its association with various clinical presentations. In this ambispective analytical study over 20 months, LA-positive cases (n = 167) from among 970 cases screened were included. Tests for LA were integrated dilute Russell’s Viper venom time (dRVVT) and silica clotting time (SCT) using screen-confirm procedure with mixing whenever necessary. The clinical profile and other investigations like aCL and anti-β2gp1were noted from records. The sensitivity of dRVVT and SCT for LA positivity were 78.4

BACKGROUND:Myeloid sarcoma (MS) is a tumor mass comprising myeloid blasts with or without maturation occurring in any site other than bone marrow. It is a rare and distinct clinical presentation of myeloid neoplasm. MATERIALS AND METHODS:This is a retrospective study over 7 years (2015-2022) comprising a series of eight cases, which includes clinical details, morphology, immunohistochemistry (IHC) markers, cytogenetics, and molecular details. RESULTS:These cases showed up as an isolated MS (3/8), as an initial clinical presentation in acute myeloid leukemia (1/8), as acute myeloid leukemia (1/8), as a disease progression in primary myelofibrosis (1/8), as chronic myeloid leukemia (1/8), and as BCR-ABL-negative myelodysplastic syndrome/myeloproliferative neoplasm (1/8). One of the three isolated MS was incorrectly identified as having Ewing's sarcoma. One case each presented at the cervical lymph node, mediastinum, skin, sacral soft tissue, maxillary sinus, and perinephric fat, and two cases presented at the hard palate. CONCLUSION:Four of the cases in our study were clinically thought of as lymphoma/sarcoma, which was a major diagnostic challenge. All but one case succumbed to their disease. Without adequate clinical history and appropriate use of ancillary techniques such as IHC in tissue biopsies, flow cytometry, cytogenetics, and molecular studies, these cases have a high chance of being misdiagnosed as non-Hodgkin lymphoma, small round blue cell tumor, or undifferentiated carcinomas, which can complicate patient management and prognosis.

Background:Tuberculosis (TB) disrupts iron balance through systemic inflammation. Pulmonary tuberculosis (PTB) is linked to diverse anaemia types, necessitating intricate haematological and biochemical assessments for diagnosis. This study aims to describe the prevalence of anaemia of chronic disease (ACD), iron deficiency anaemia (IDA) among PTB patients and factors associated with these types of anaemia. Methods:A cross-sectional analysis was conducted from community-based cohort study involving sputum-positive PTB patients from 2018 to 2020 in urban Puducherry. Participants were enrolled from 10 primary health centres within 2 weeks of initiating anti-tubercular treatment (ATT). Blood samples were collected for assessing haematological and biochemical parameters. The sTfR/log ferritin ratio was used to distinguish between ACD and IDA. Data were captured using Epicollect5 and analysed using STATA V14. Result:Of the 176 PTB patients included, 63.07% (111/176) had anaemia, with ACD being the predominant type (84.6%, 94/111). The C-reactive protein (CRP) levels were higher among the anaemic group [40.77 (16.66-58.51) mg/dl vs 24.65 (14.23-47.26) mg/dl] and higher among the ACD as compared to IDA [46.9 (22.3-61.2) vs 20.8 (13.0-39.1) mg/dl]. Undernourished [adjusted prevalence ratio (APR) =3.43; confidence interval (CI): 1.21-9.69] and patients having low risk of dependence on tobacco [APR = 1.52; CI: 1.10-2.11] had higher risk of ACD. Female patients had higher risk of IDA [APR = 4.95, P < 0.01]. Conclusion:The largest proportion of the PTB participants with anaemia had ACD. Acute-phase reactant and inflammatory marker are increased among newly diagnosed new sputum smear-positive (NSP) PTB participants at the start of ATT. Addressing inflammation is needed for combating anaemia in PTB patients.

Objective: Significant involvement of the cardiovascular system is known in multisystem inflammatory syndrome in children (MIS-C).This study aimed to examine the recovery of affected cardiovascular parameters over a medium-term follow-up.Methods: A cohort of 69 children was studied prospectively.Assessments of left ventricular (LV) function and coronary artery abnormalities (CAA) were conducted at admission, 1.5 months, and 3 months.Coronavirus Disease 2019 (COVID-19) antibody titers were assessed at these three time points.Echocardiographic and antibody parameters (rising/decreasing) were analyzed for correlation.Outcomes were assessed using logistic regression.Results: At admission, among the 78.2% of patients who were tested, 88.9% tested positive for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2).A quarter of the patients had pericardial effusion, and half had valvulitis.Decreased ejection fraction, global circumferential strain (GCS), and global longitudinal strain (GLS) were seen in 54.4%, 68.6%, and 35.8% of patients, respectively.CAAs were observed in 27.78% of patients.Systolic dysfunction was significantly associated with older age.During follow-up, severe LV dysfunction normalized within 6-7 weeks, while mild to moderate dysfunction reached normalcy by two weeks.Both GCS and GLS reached normalcy within a median of two weeks.Diastolic parameters recovered by six weeks.Most small and moderate coronary aneurysms resolved, but a giant aneurysm in an infant remained large even after 15 months.Trends in antibodies and ejection fraction (EF) at three months were significantly correlated.Admission EF, GLS (at 6 weeks) and deceleration time (at 3 months) were significantly associated with intensive care unit (ICU) admission.The median segmental strain of the cohort remained low in certain segments at three months.Conclusion: Smaller CAAs resolve, whereas giant CAAs persist.EF and GLS are important predictors of Pediatric Intensive Care Unit (PICU) stay.The residual impairment of median segmental strain and persistent diastolic dysfunction at three months indicate the need for long-term follow-up.

Background Tyrosine kinase inhibitors have revolutionized the treatment of chronic myeloid leukemia (CML) since the beginning of the century. However, resistance to therapy and the progression of disease tend to occur in certain patients. The bone marrow microenvironment may play a role in the disease outcome. Megakaryocytes have multiple roles in the regulation and maintenance of the hematopoietic stem cell microenvironment. In the current study, we evaluated the association of megakaryocyte morphology, morphometry, and microenvironment with disease progression and therapy resistance in CML. Methodology Megakaryocyte morphology and morphometry were analyzed and compared between the different phases (chronic and advanced) at diagnosis in 150 cases of BCR-ABL-positive CML. All CML-CP patients (n = 119) were followed up on tyrosine kinase inhibitor therapy for a minimum of 15 months and classified based on their treatment outcome as a response, resistance to therapy, or progression of disease based on standard criteria. Immunohistochemistry on a bone marrow trephine biopsy was done for vascular endothelial growth factor (VEGF), FOXP3, CD150, CD48, CD44, osteopontin, CXCL12, N-cadherin, PDL-1, and IL-7, and their expression on megakaryocytes and their association with treatment outcome was evaluated. Results The morphology and morphometry of megakaryocytes showed a heterogeneous population in CML. Morphology and morphometric parameters, when compared between the chronic and advanced phases of disease at diagnosis, did not show any statistical difference. Megakaryocytes were variably positive for VEGF, FOXP3, CD150, CD48, osteopontin, N-cadherin, CXCL12, CD44, PDL-1, and IL-7. However, only CD44positive megakaryocytes were statistically associated with the treatment outcome. The patients with a higher expression of CD44 megakaryocytes progressed to the advanced phase of the disease during therapy compared to those who responded. Conclusion Megakaryocyte morphology and morphometry were heterogeneous in CML; however, they did not show any significant difference with either the phase of the disease or with treatment outcomes. Among the various immunohistochemical markers of the microenvironment, only CD44-positivity on megakaryocytes was associated with poor treatment outcomes.

Revised International Prognostic (R-IPI) score is used widely for risk stratification of DLBCL cases, yet some patients belonging to same risk category tend to exhibit different outcomes. The role of T-cells and macrophages in prognostication of lymphomas has been a point of interest of late. We aimed to study the association of FOXP3 positive T-regulatory cells, cytotoxic T-cells and macrophages with the immunophenotypic subtypes, clinicopathological characteristics, treatment response and survival in nodal diffuse large B-cell lymphoma (DLBCL) patients. The clinicopathological and treatment data of 83 DLBCL patients diagnosed and treated at our institute from January 2015 to December 2018 were collected and followed up till June 2020. CD8, FOXP3 and CD68 immunostains were performed to highlight the cytotoxic T-cells, T-regulatory cells and macrophages respectively on the lymph node biopsies and the distribution of these cells and their association with clinico-pathological factors, treatment response and survival was analyzed. DLBCL cases with higher percentage of CD3 positive T-cells and CD8 positive cytotoxic T-cells had significant association with attainment of complete response to treatment. In addition, CD8 positive T-cells of more than 6.5

Cancer related microangiopathic hemolytic anemia is a rare entity and shares clinical and hematological features with other causes of thrombotic microangiopathy and leads to diagnostic dilemma and treatment delays. This record-based descriptive study, spanning five years, details the clinicopathological features with special emphasis on the peripheral blood findings in unsuspected cases of bone marrow metastasis of unknown primary in young adults. Seven relatively young patients, with an average age of 27 years, presented with unexplained anemia with peripheral blood showing features of microangiopathic hemolytic anemia, thrombocytopenia, and leukoerythroblastic picture. Subsequent bone marrow examination revealed presence of metastatic adenocarcinoma with the primary site being detected in five of the seven patients. This case series highlights these uncommon, but significant, hematological manifestations of metastatic adenocarcinoma in bone marrow in young adults, and the importance of astute observations of peripheral blood smear in detection of an underlying malignancy.

OBJECTIVE:To study the kinetics of blood count nadir and time to recovery and find its association with clinical outcomes in a cohort of Acute Lymphoblastic Leukemia (ALL). METHODS:Data from 243 cases treated between January 2018 to December 2020 was retrospectively analysed. Along with baseline data, serial measures of peripheral blood counts, nadir, and time to partial and complete recovery of counts during course of induction chemotherapy were recorded. Post-induction Complete Remission (CR) status, Event-Free Survival (EFS) , and Overall Survival (OS) were recorded as clinical outcomes for analysis. RESULTS:Median age was 15 (range,1-62) years. Immunophenotype was B-ALL in 71% (n=172), and T-ALL in 27% (n=66). Good steroid response (D8) was seen in 89%(n=216), CR in 79% (n=192), and induction mortality in 12% (n=29). Median neutrophil nadir was 0.06(0-0.49) *10⁹/L and median day to nadir was D17. Median time to partial and complete platelet recovery was D18 and D25. Late neutrophil nadir (>D15) was independent predictor of refractory disease post-induction [OR=5.43 (95%CI 1.06-27.75)]. Late partial platelet recovery (>D22) was independent predictor of poorer EFS and OS [HR = 1.63 (95%CI 1.07-2.47)] and [HR = 1.5 (95% CI 1-2.4)] respectively. CONCLUSION:We found that a longer time to neutrophil nadir independently predicts refractory disease post-induction and late partial platelet recovery is an independent factor for poorer EFS and OS. Thus, Blood count kinetics as independent predictors of induction outcomes can provide a simple, easy-to-use tool for balancing toxicity-efficacy during induction therapy for ALL.

Background: Nodular Lymphocyte Predominant Hodgkin Lymphoma (NLPHL) is an uncommon subtype of Hodgkin Lymphoma associated with an indolent course. NLPHL has distinct clinical features, histological, immunohistochemical and gene expression profile when compared to Classic Hodgkin Lymphoma, and the recent World Health Organization - Hematolymphoid tumors V edition, suggests a nomenclature change to Nodular Lymphocyte Predominant B Cell Lymphoma as it appears more related to the mature B cell Non-Hodgkin Lymphoma. Various Immunoarchitectural patterns (A to F) have been described of which patterns C to F are called as variant patterns and these patterns are associated with disease recurrence and progression. This study is a retrospective and descriptive analysis of Materials And Methods: 16 lymph node biopsies from 14 patients of NLPHL diagnosed over a period of five years. Haematoxylin and Eosin-stained sections, along with CD3 and CD20 immunohistochemistry, amongst others, were used to assess the immuno-architectural patterns. Pattern Results: A was seen in five, followed by pattern C and E in four patients each. The remaining patient had pattern B. During the period of study, two patients had recurrence. The recurrent cases had pattern C and pattern E respectively at diagnosis and during recurrence both showed pattern E. This study reaf Conclusion: firms the importance of recognizing the immuno-architectural patterns in NLPHL, with variant patterns being associated with disease recurrence. Hence, it is necessary that the hematopathologist reporting on a case of NLPHL should be aware of the patterns and report on the immuno-architectural pattern accordingly.

Bone marrow biopsy (BMB) examination is the gold standard for staging of lymphoma which is interpreted along with other clinical, laboratory and radiological investigations. This study aimed to evaluate the various patterns of BMB infiltration by lymphomas which include Hodgkin and Non Hodgkin lymphoma and the usefulness of BMB compared to bone marrow aspiration (BMA). : In a period of three years, there were 212 cases which showed lymphoma infiltration in bone marrow. We assessed the peripheral blood smear (PBS), BMA and BMB slides and concordance between each was evaluated. BMB slides were assessed for the pattern of involvement. The most frequent subtype was chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) (21.70%) followed by Hodgkin lymphoma (HL)(12.73%)and follicular lymphoma (FL)(11.32%). Predominant pattern of infiltration showed by CLL/SLL cases was mixed pattern, by FL was paratrabecular pattern, mantle cell lymphoma(MCL) showed either diffuse or nodular, diffuse large B cell lymphoma (DLBCL) and Burkitt lymphoma(BL) showed predominantly diffuse pattern. Hairy cell leukemia (HCL) and peripheral T cell lymphoma (PTCL) showed an interstitial pattern. In HL, the pattern was usually focal nodular however diffuse involvement was seen in a few. Of the 212 cases, 50.94% cases had atypical lymphocytes or lymphocytosis in PBS and 81.14% cases showed infiltration in BMA. Atypical lymphoid cells may not be present at times in peripheral blood or bone marrow aspirate in spite of infiltration in the bone marrow. Different lymphomas show characteristic patterns of marrow involvement.

Background Pulmonary tuberculosis (PTB) is commonly associated with reversible peripheral blood abnormalities. The evolution of tuberculosis (TB)-associated anemia with anti-tuberculosis treatment (ATT) has not been well elucidated. This study aimed to compare the hematological profiles at the start and end of the ATT among new sputum smear-positive (NSP) PTB patients in Puducherry, India. Methods A prospective cohort study was conducted in the 10 urban primary health centers of Puducherry from 2017 to 2020. All the NSP PTB participants aged ≥18 years registered under the National Tuberculosis Elimination Program (NTEP) were contacted within two weeks of the start of the ATT. All eligible participants were enrolled, and they were followed up till the end of ATT (180 days). Hematological profiles and anthropometric measurements were compared at the start and end of the ATT. Binomial logistic regression analysis was used to assess the predictors of changes in the anemia status at the start and end of the ATT. Results Out of 176 NSP PTB participants, 145 were followed up after treatment. Initially, 63% (111/176) patients had anemia, which decreased to 44% (64/145) by the end of treatment. The risk factors for a negative change in hemoglobin levels were female gender, below poverty level, underweight, and reduced iron intake. The adjusted risk ratios (ARRs) were 1.53 (1.24-1.88), 1.18 (1.01-1.38), 1.29 (1.02-1.64), and 1.26 (1.05-1.51),respectively. Conclusion ATT may lead to the resolution of TB-associated anemia. Moreover, female gender, possession of a red ration card, being underweight, and reduced iron intake were identified as risk factors for negative changes in hemoglobin levels during treatment.

Aims Of the Study: To study the type of light chain restriction and correlate it with the morphological parameters, proliferation index, angiogenesis and clinical parameters. Materials And Methods: The study includes 46 cases of myeloma diagnosed over the period of five years. The histomorphological features like plasma cell morphology, percentage of plasma cells and pattern of infiltration were studied. Immunohistochemistry for kappa and lambda light chains was done. Angiogenesis was assessed by calculating the microvessel density (MVD) using anti CD34 immunohistochemistry. Proliferation was assessed immunohistochemically using Ki67 by comparing with anti CD38 which was used to highlight the plasma cells. Results: The cases with kappa light chain restriction had significantly less of poorly differentiated morphology (7.4% vs 36.8%; p=0.02) and diffuse pattern of infiltration (22% vs 63%; p=0.01) compared to lambda. The kappa group also had lower MVD (9.9 vs 16.5; p=0.02) and proliferation index (4.7 vs 94; p=0.04) compared to the lambda. Conclusion: Therefore, the type of light chain restriction is also a prognostic factor in plasma cell myeloma.

The incidence of acute myeloid leukemia (AML) is age dependent and increasing among the patient groups aged above 60 years. The overall presentations in a case of AML is due to marrow infiltration of leukemic cells which results in fever and chills due to neutropenia, bleeding due to thrombocytopenia, fatigue and weakness due to anemia. Incidence of venous thromboembolism is very rare in hematological malignancies. We describe a case of adolescent male presented with features of lung consolidation later found to be a pulmonary infarct and finally diagnosed to have acute leukemia (AL).

Objectives: The diagnosis and classification of von Willebrand disease (VWD) is an intricate process requiring multiple hemostatic tests. Cutoff values of the tests vary with the subtype. Sometimes, all the tests are not available. This study was done to analyze the clinical and coagulation profile of VWD diagnosed and broadly classified based on a simplified algorithm. Material and Methods: This was a cross-sectional study done over 6 years. After screening tests, a simplified algorithm taking cutoff for various tests based on updated guidelines using the primary panel of von Willebrand factor antigen assay (VWF:Ag), VWF ristocetin cofactor activity (VWF:RCo), and Factor VIII:C was used. Multimer assay was done in a few cases. Data were compiled using summary statistics. Results: Forty patients fitted the diagnosis of VWD: Type 3 in 13 (32.5%), Type 2N (likely) in 8 (20%), Type 2 (not further categorized) in 9 (22.5%), and VWD, not further categorized in 10 (25%). The mean age was in the second or third decade with female predominance. Diagnosis of Type 3 was relatively straightforward due to markedly deranged parameters. Type 2N was provisionally diagnosed based on bleeding pattern and markedly reduced Factor VIII:C; further, subtyping of Type 2 and categorization of some cases was not possible due to non-availability of some tests. Conclusion: VWF:Ag assay, VWF:RCo, and Factor VIII:C form the cornerstone for diagnosing major VWD types. The under-representation of milder phenotypes and a greater proportion of severe VWD subtypes observed is likely due to hospital referral bias and may not represent population prevalence.