Rusfertide, a Hepcidin Mimetic, for Control of Erythrocytosis in Polycythemia Vera.

BACKGROUND: Polycythemia vera is a chronic myeloproliferative neoplasm characterized by erythrocytosis. Rusfertide, an injectable peptide mimetic of the master iron regulatory hormone hepcidin, restricts the availability of iron for erythropoiesis. The safety and efficacy of rusfertide in patients with phlebotomy-dependent polycythemia vera are unknown. METHODS: In part 1 of the international, phase 2 REVIVE trial, we enrolled patients in a 28-week dose-finding assessment of rusfertide. Part 2 was a double-blind, randomized withdrawal period in which we assigned patients, in a 1:1 ratio, to receive rusfertide or placebo for 12 weeks. The primary efficacy end point was a response, defined by hematocrit control, absence of phlebotomy, and completion of the trial regimen during part 2. Patient-reported outcomes were assessed by means of the modified Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF) patient diary (scores range from 0 to 10, with higher scores indicating greater severity of symptoms). RESULTS: Seventy patients were enrolled in part 1 of the trial, and 59 were assigned to receive rusfertide (30 patients) or placebo (29 patients) in part 2. The estimated mean (±SD) number of phlebotomies per year was 8.7±2.9 during the 28 weeks before the first dose of rusfertide and 0.6±1.0 during part 1 (estimated difference, 8.1 phlebotomies per year). The mean maximum hematocrit was 44.5±2.2% during part 1 as compared with 50.0±5.8% during the 28 weeks before the first dose of rusfertide. During part 2, a response was observed in 60% of the patients who received rusfertide as compared with 17% of those who received placebo (P = 0.002). Between baseline and the end of part 1, rusfertide treatment was associated with a decrease in individual symptom scores on the MPN-SAF in patients with moderate or severe symptoms at baseline. During parts 1 and 2, grade 3 adverse events occurred in 13% of the patients, and none of the patients had a grade 4 or 5 event. Injection-site reactions of grade 1 or 2 in severity were common. CONCLUSIONS: In patients with polycythemia vera, rusfertide treatment was associated with a mean hematocrit of less than 45% during the 28-week dose-finding period, and the percentage of patients with a response during the 12-week randomized withdrawal period was greater with rusfertide than with placebo. (Funded by Protagonist Therapeutics; REVIVE ClinicalTrials.gov number, NCT04057040.).

Development and validation of a novel chiral chromatographic method for separation of lenalidomide enantiomers in human plasma.

Lenalidomide (LND) is an analogue of thalidomide that is second generation immunomodulatory drugs (IMiDs). LND contains asymmetric carbon atom and exist R and S enantiomer. S (-) form of enantiomer are considered to be more potent and biologically active in tumor cell. It is available in racemic form for clinical use. The study aims to develop and validate enantiomer separation of LND in human plasma. The chromatographic enantiomeric separation was achieved on a Daicel-CSP, Chiralpack IA 4.6 × 250 mm_5 µm. The mobile phase was constituted in combination of methanol:glacial acetic acid at a concentration of 499.50 ml: 50 µl. UV wavelength detection was 220 nm. The RSD% for all validation parameters was found to be within the acceptable limit. The chiral chromatographic (chiral stationary phase-high-performance liquid chromatography [CSP-HPLC]) method developed and validated for the quantitative estimation of LND enantiomers S (-) and R (+) in human plasma sample is accurate, precise, robust, stable and selective.

COVID 19 infection associated with thrombotic thrombocytopenic purpura.

Thrombotic thrombocytopenic purpura (TTP) which can cause significant mortality is a thrombotic microangiopathy due to deficiency of VWF cleaving protease ADAMTS13 and as per medical literature there are examples that TTP can be caused by COVID 19 infection. A 35 years old female after admission with right sided weakness and slurring of speech was found to be COVID positive and diagnosed as a case of TTP. Patient had absent ADAMTS13 level on day 1. Treatment was started with therapeutic plasma exchange (TPE) later injection Vincristine and Rituximab was given after 4th TPE as it was suspected as refractory case. Finally patient received 16 TPE procedures with cryo poor plasma as exchange fluid and gradually her platelet count started to maintain normal and she was discharged. Specific management and such association of this type of cases need to be studied more judiciously.

Evaluation of Vascular Health of E-Beta Thalassemia Patients: Effect of Iron Overload.

Hb E-ß thalassemia is the most common form of hemoglobinopathy in Southeast Asia and eastern India. Iron overload resulting from blood transfusion and increased intestinal iron absorption promotes the formation of reactive oxygen species (ROS), leading to oxidative stress, organ dysfunction, and tissue damage. Of these, cardiovascular complications are the leading cause of mortality. Impaired endothelial function is a biomarker of vascular health in patients with cardiovascular risks. Therefore, assessment of endothelial function is a useful prognostic tool. In the present study, 60 E- ß thalassemia patients and 60 healthy, age, sex matched control subjects were taken. The mean hemoglobin and ferritin of thalassemic patients were 7.43gm/dl and 1032 mcg/dl respectively. The vascular health was compared by measuring flow-mediated vasodialation (FMD), arterial elastic parameters, and carotid intima-medial thickness (CIMT). There was lower FMD (7.49%) and higher CIMT (0.46mm) in thalassemic group than control (10.52 % and 0.36mm respectively) (p value< 0.05). Also arterial stiffness is elevated and arterial distensibility is lower in thalassemic patients than control. Among the thalassemic patients FMD or CIMT did not correlate with serum ferritin value. So, the E- ß thalassemia patients had poor vascular health and are at a higher risk of developing atherosclerosis and cardio-vascular complication than normal population. The vascular dysfunction does not correlate with serum ferritin value, so regular monitoring with Doppler study is required for early diagnosis of subclinical atherosclerosis in this group of patients. However the effects of chelation therapy, Hydroxyurea, or other targeted therapies needs to be validated by further study.

Optimizing the dose of hydroxyurea therapy for patients with ß-thalassemia intermedia (Hb E-ß-thalassemia): a single center study from Eastern India.

Over the past 20 years, hydroxyurea (HU) has emerged as an important therapeutic agent to augment Hb F and thus total hemoglobin (Hb) in Hb E [ß26(B8)Glu→Lys; HBB: c.79G > A]-ß-thalassemia (Hb E-ß-thal), albeit used in varying doses with little consensus on its optimal dose. We report the interim analysis findings of a broader study to assess the impact of Comprehensive Thalassemia Care, of which the present report was a part. Sixty-one Hb E-ß-thal patients who were transfusion independent or requiring occasional transfusions [ß-thal intermedia (ß-TI)] were randomized to one of two groups; A (n = 32) and B (n = 29) to receive 10 and 20 mg/kg/day HU, respectively. The primary objective of the study was to assess the differences in responses to different doses of HU. Secondary end points were to see the tolerability and safety of HU in different doses. Good response (GR) was defined as a rise of Hb by > 1.0 g/dL; intermediate response (IR) as a rise in Hb by 0.6-1.0 g/dL anytime during the study period. No response (NR): rise in Hb by < 0.5 g/dL in 12 weeks or drop in Hb level from the previous value. Over a follow-up period of 24 weeks, we had 18 (56.2%) GRs, nine (28.2%) IRs and five (15.6%) NRs, while the number of GRs, IRs and NRs in group B were five (17.2%) 12 (41.4%) and 12 (41.4%), respectively. Adverse effects were more common in group B, making this dose (20 mg/kg/day) of HU more myelo-suppressive than Hb F inducing.

A Rare Case of Familial Methemoglobinemia with Congenital Heart Disease.

Methemoglobinemia is a rare dyshemoglobin disorder which can either be congenital or acquired. Dyshemoglobin disorders can be asymptomatic or symptomatic. We narrate the case of a 12-year-old girl who presented with a fever, cough, and oxygen saturation of 85%. She was diagnosed with COVID-19, along with a large atrial septal defect and pulmonary arterial hypertension. Arterial blood gas analysis revealed normal partial pressure of oxygen and on 100% exposure to oxygen, blood color turned chocolate brown. After the resolution of COVID-19 in 10 days, the patient was treated with oral ascorbic acid and successful atrial septal defect repair. It is important to suspect dyshemoglobin disorder in a patient who presents with hypoxia/hypoxemia.

Prevalence, Attributes, and Risk Factors of QT-Interval-Prolonging Drugs and Potential Drug-Drug Interactions in Cancer Patients: A Prospective Study in a Tertiary Care Hospital.

Introduction Cancer chemotherapy regimens include multiple classes of adjuvant drugs as supportive therapy. Because of the concurrent intake of other drugs (like antiemetics, antidepressants, analgesics, and antimicrobials), there is a heightened risk for possible QT interval prolongation. There is a dearth of evidence in the literature regarding the usage of QT-prolonging anticancer drugs and associated risk factors that have the propensity to prolong QT interval. The purpose was to explore the extent of the use of QT-interval-prolonging drugs and potential QT-prolonging drug-drug interactions (QT-DDIs) in cancer patients attending OPD in a tertiary-care hospital. Methods This was a hospital-based, cross-sectional, observational study. Risk stratification of QT-prolonging drugs for torsades de pointes (TdP) was done by the Arizona Center for Education and Research on Therapeutics (AzCERT)/CredibleMeds-lists, and potential QT-DDIs were determined with four online DDI-checker-software. Results In 1331 cancer patients, the overall prevalence of potential QT-prolonging drug utilization was 97.3%. Ondansetron, pantoprazole, domperidone, and olanzapine were the most frequent QT-prolonging drugs in cancer patients. The top six antineoplastics with potential QT-prolonging and torsadogenic actions were capecitabine, oxaliplatin, imatinib, bortezomib, 5-fluorouracil, and bendamustine. Evidence-based pragmatic QTc interval prolongation risk assessment tools are imperative for cancer patients. Conclusion This study revealed a high prevalence of QT-prolonging drugs and QT-DDIs among cancer patients who are treated with anticancer and non-anticancer drugs. As a result, it's critical to take precautions, stay vigilant, and avoid QT-prolonging in clinical situations. Evidence-based pragmatic QTc interval prolongation risk assessment tools are needed for cancer patients.

A Validated Chiral Chromatography Method for Enantiomeric Separation of Pomalidomide in Human Plasma.

In the present work, new chiral stationary phase high-performance liquid chromatography (CSP-HPLC) method was established and validated for the quantification of pomalidomide (PMD) enantiomers in human plasma. The chromatographic enantiomeric separation was achieved on a Daicel-CSP, Chiralpack IA 4.6 × 250 mm, 5 µm; because of its advantages of high degree of retention, high resolution capacity, better reproducibility, ability to produce lower back pressure and low degree of tailing. The mobile phase was maintained as methanol: glacial acetic acid (499.50 ml:50 µL). Ultraviolet wavelength for detection was 220 nm. PMD enantiomer-I and enantiomer-II were separated at 8.83 and 15.34 min, respectively. Limit of detection and limit of quantification for each enantiomer and the calibration curve of standard PMD was linear in range between 10-5,000 ng mL-1. The method was validated according to The International Council for Harmonisation of Technical Requirements of Pharmaceuticals for Human Use (ICH(Q2R1)) specific guidelines. We found no interference peak with PMD chromatogram obtained. This is a simple, reliable and specific method for detection and quantification of enantiomer of PMD in human plasma sample.

Targeting CERS6-AS1/FGFR1 axis as synthetic vulnerability to constrain stromal cells supported proliferation in Mantle cell lymphoma.

The interaction between stromal and tumor cells in tumor microenvironment is a crucial factor in Mantle cell lymphoma (MCL) progression and therapy resistance. We have identified a long non-coding RNA, CERS6-AS1, upregulated in MCL and associated with poor overall survival. CERS6-AS1 expression was elevated in primary MCL within stromal microenvironment and in a subset of MCL cells adhered to stromal layer. These stromal-adhered MCL-subsets exhibited cancer stem cell signatures than suspension counterparts. Mechanistically, we found that downregulating CERS6-AS1 in MCL reduced Fibroblast Growth Factor Receptor-1 (FGFR1), expression attributed to loss of its interaction with RNA-binding protein nucleolin. In addition, using in-silico approach, we have discovered a direct interaction between nucleolin and 5'UTR of FGFR1, thereby regulating FGFR1 transcript stability. We discovered a positive association of CERS6-AS1 with cancer stem cell signatures, and Wnt signaling. Building on these, we explored potential therapeutic strategies where combining nucleolin-targeting agent with FGFR1 inhibition significantly contributed to reversing cancer stem cell signatures and abrogated primary MCL cell growth on stromal layer. These findings provide mechanistic insights into regulatory network involving CERS6-AS1, nucleolin, and FGFR1 axis-associated crosstalk between tumor cells and stromal cell interaction and highlights therapeutic potential of targeting a non-coding RNA in MCL.

Mucocutaneous Findings in Hematolymphoid Neoplasms: An Observational Study.

Background: Cutaneous manifestations of hematological neoplasms can be divided into three broad categories - direct infiltration, paraneoplastic conditions, and those due to the treatment of hematological cancers. Objectives: To study the frequency and patterns of mucocutaneous manifestations in patients with hematolymphoid neoplasms and those due to chemotherapy. Materials and Methods: This was an observational study done with 172 patients. Categorization of mucocutaneous manifestations was done into malignancy-associated and chemotherapeutic drugs-associated and data was analyzed. Results: Out of a total of 172 patients, 15.6% (27/172) had malignancy-related mucocutaneous manifestations. Among these, 4.6% (8/172) had direct infiltration of malignant cells into the skin and 11% (19/172) had paraneoplastic manifestations. The most common chemotherapy-related mucocutaneous manifestations were nail changes - 47.1% (81/172), of which transverse melanonychia was the most common (20.9%). About 44.2% (76/172) had a cutaneous infection, the commonest of which was a fungal infection (15.1%). Chemotherapy-induced alopecia was noted in 46.5% (80/172) and found to be significantly associated with cytarabine, daunorubicin, doxorubicin, methotrexate, and vincristine. Cutaneous hyperpigmentation was found to be significantly associated with cytarabine, doxorubicin, and vincristine. Conclusion: Mucocutaneous manifestations cause additional discomfort to a patient undergoing chemotherapy. Early recognition and timely and appropriate management facilitate symptom control and prevent treatment-related morbidity. A multidisciplinary approach involving hemato-oncologists and dermatologists can help achieve this target.

Identification and in-vitro analysis of potential proteasome inhibitors targeting PSMß5 for multiple myeloma.

The proteasome subunit ß5 (PSMß5) is a chief target of proteasome inhibitors (PIs) for treatment of multiple myeloma (MM). The relevance of PSMß5 mutations and their functional impact on the development of resistance to PIs have been demonstrated recently. Therefore, this present study deals with an in-depth E-pharmacophore based screening and repurposing of FDA-approved drugs that could target PSMß5 for MM. Our molecular docking-based investigation revealed risedronate and zoledronate as potential alternative therapeutic molecules for targeting the PSMß5 gene. Risedronate and zoledronate displayed high binding affinity (-9.51 and -8.56 kcal/mol respectively) to PSMß5. Moreover, 100 ns molecular dynamics simulation analysis of docking complexes revealed risedronate and zoledronate with a superior binding free energies and stable interactions with PSMß5. The RMSD plot shows that the risedronate-PSMß5 (mean: 0.24 nm) and zoledronate-PSMß5 (mean: 0.25 nm) complexes are identical and stays stable until 100 ns. We further validated the activity of zoledronate in MM cell lines RPMI8226 and U266 where zoledronate showed significant anti-proliferative and apoptotic activity. Importantly, zoledronate showed an enhanced anti-proliferative activity when combined with bortezomib in MM cell lines. Thus, this study demonstrates that combining bortezomib with zoledronate could have a significant impact on reducing MM cell growth and can be an alternative strategy for treating MM.

Adipose Tissue in Peripheral Obesity as an Assessment Factor for Pressure Ulcers.

Scope and Significance: Pressure ulcers are very difficult to treat and pose an economic burden, just below cancer and cardiovascular illness, at 4.82 billion U.S. dollars. It is important to understand the pathophysiology of the condition, risk stratification, and ways of preventing it. Prevention forms the most important aspect of their management. The authors systematically evaluated the existing risk prediction scales and explored the evidence from literature regarding the role of additional factors including body mass index, obesity, subcutaneous tissue thickness, and skin integrity in pressure ulcers. With this review it is hoped that the future management of pressure ulcers will concentrate on the preventable and alterable factors in its pathophysiology. Translational Relevance: The review focuses on how adipose tissue thickness can predict the occurrence of pressure ulcer. If adequately proved that a definite thickness of peripheral adipose tissue is efficient in prevention of pressure ulcers, then methods of maintaining the thickness of this tissue will be the next effective strategy in the management of this chronic issue. Clinical Relevance: The review addresses the management of pressure ulcers to wound care providers and emphasize on confounding parameters of obesity, subcutaneous tissue thickness, and skin integrity during the treatment regimen of pressure ulcers. Objectives: The main objective of this review is to draw a consensus concerning the role of adipose tissue in pressure ulcers, based on the published research. A review of the various preexisting predictive scales for pressure ulcers is a secondary objective to highlight the shortcomings in ulcer management. This review finally aims in the future at paving a way to refine our prognosticating scales for pressure sores based on these results. Accurate preventative injury risk scales are needed so that preventative resources can be directed to the patients for whom they are the most appropriate.

Leukemia-associated aberrant immunophenotype: A flow cytometry-based experience of 110 cases from a tertiary care center in Northern India.

Background: Leukemic cells express a characteristic set of "cluster of differentiation" (CD) markers, which forms the basis of the current WHO classification. Leukemia-associated aberrant immunophenotype (LAIP) refers to expression of unusual CD markers by leukemic cells, which are not normally expressed by their respective lineage. The incidence of LAIP varies considerably, and its clinical implications, prognostic relevance, and sensitivity to therapy are still debatable. This study was conducted to identify the immunophenotypic aberrancies in newly diagnosed leukemias in our Institute. Method: This was an observational study, which included newly diagnosed leukemias on flow cytometry. Aberrant immunophenotypic expressions were recorded whenever present and were correlated with prognostic factors like age, gender, and total leucocyte count (TLC). Results: The study included 110 newly diagnosed cases of leukemias (85 acute and 25 chronic) over 1.5 years. Immunophenotypic aberrancies were detected in 40.4% of the cases. The highest incidence of aberrations was detected in acute myeloid leukemia (60.7%). LAIPs were detected in 50% of T-acute lymphoblastic leukemia and 25% cases of in B-cell acute lymphoblastic leukemia (B-ALL). Aberrant CD33 and CD56 expression in B-ALL correlated with poor prognostic factors like higher age and higher TLC, respectively. Immunophenotypic aberrancies were present in 28% cases of chronic lymphocytic leukemia. Conclusion: The results of this study have generated valuable baseline data on the incidence of LAIPs in this region. This information is vital because establishing LAIPs at the time of diagnosis is crucial for disease monitoring. Some LAIPs are associated with underlying cytogenetic abnormalities and hence impact the management and prognosis.

Safety and efficacy of Vitamin D3 supplementation with Imatinib in Chronic Phase- Chronic Myeloid Leukaemia: an Exploratory Randomized Controlled Trial.

OBJECTIVES: The study aimed to compare early molecular response (EMR) rates at 3 months of imatinib therapy with and without vitamin D3 supplementation in patients newly diagnosed with chronic-phase chronic myeloid leukaemia (CML-CP). The secondary objective was to assess the effects of vitamin D3 on complete haematological response (CHR) and its safety. DESIGN: Double-blind, placebo-controlled, exploratory randomised trial. SETTING: Tertiary care hospital in northern India. PARTICIPANTS: Treatment-naive patients with chronic phase chronic myeloid leukaemia (n=62) aged >12 years were recruited from January 2020 to January 2021. Patients with progressive disease, pregnancy and hypercalcaemia were excluded. INTERVENTION: Oral vitamin D3 supplementation (60 000 IU) or matched placebo was given once weekly for an initial 8 weeks along with imatinib after randomisation with 1:1 allocation ratio. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome was to compare EMR (defined as BCR-ABL1 transcript level ≤10%, international scale) at 3 months. The secondary outcomes were to compare effect of the intervention on CHR, correlation of 25(OH)2D3 levels with treatment response and safety according to Common Terminology Criteria for Adverse Events (CTCAE) version 5. RESULTS: At baseline, 14.5% of the patients had normal vitamin D3 levels. EMR at 3 months was attained in 24 patients (82.7%) of the vitamin D3 group and 21 (75%) of the placebo group (OR 1.6, 95% CI 0.37 to 7.37, p=0.4). A significant difference in vitamin D3 levels from baseline to the end of study was observed. Patients with vitamin D3 supplementation did not achieve higher CHR in comparison with placebo (OR 1.3, 95% CI 0.25 to 7.23, p=1.0). Vitamin D3 levels were not significantly correlated with BCR-ABL1 levels. No dose-limiting toxicities were observed. CONCLUSION: Vitamin D3 levels were low among patients with CML-CP in this study. Vitamin D3 supplementation with imatinib therapy did not have significant effect on EMR or CHR. Further clinical trials could be undertaken to assess the effective dosage and duration of vitamin D3 supplementation in these patients. TRIAL REGISTRATION NUMBER: CTRI/2019/09/021164.

A sequential exploratory study to develop and validate neutropenic nursing care bundle for neutropenic patients admitted in a tertiary care hospital, Uttarakhand.

BACKGROUND: Patients diagnosed with cancer and who undergo cancer treatment are at potential risk of bone marrow suppression leading to prolonged hospitalization, delay in treatment, and chemotherapy dose reductions, which ultimately results in significant morbidity and mortality. This sequential exploratory study using a mixed-method approach was aimed to develop and validate a neutropenic nursing care (NNC) bundle for neutropenic patients admitted in a tertiary care hospital, Uttarakhand. MATERIAL AND METHODS: This sequential exploratory study design with an instrument developmental model was used to develop the NNC bundle. It consisted of two phases: Qualitative phase and quantitative phase. In the qualitative phase, focused group discussion with eight oncology nurses was performed to derive themes related to neutropenic nursing care using conventional content analysis. An extensive literature review was also performed on these themes to explore the current pieces of evidence for item pool generation. In the quantitative phase, a preliminary draft bundle was developed, and two Delphi rounds (I and II) were carried out among the five experts for the content validation of the NNC bundle and a final bundle was developed. RESULTS: Major domains identified for the bundle were hand hygiene, care of central and peripheral lines, routine oral care, antiseptic bath, peri-anal care, diet, and environmental hygiene. The content validity index (CVI) of the bundle was found to be >80% for all the items with I-CVI >0.8 and S-CVI = 0.99 after conducting two rounds of Delphi. CONCLUSION: The present study has provided a set of valid written neutropenic nursing interventions to prevent complications in neutropenic patients. The NNC bundle should be subjected to other levels of evaluation that measure the bundle's practicability and suitability for the intended field.

Hepatic Plasmacytoma With DEL13q14 Positive on Fluorescent In Situ Hybridization (FISH) on Tissue Biopsy.

A 40-year-old male presented with abdominal distension and dyspnea. On evaluation found to have hepatic plasmacytoma without marrow clonal plasma cells. Fluorescent in situ hybridization (FISH) on tissue biopsy revealed myeloma-defining cytogenetics. After treating with novel agents, the patient had a complete response to therapy.

Derivative 6 as an additional chromosomal abnormality along with t(15;17): A case report.

Acute promyelocytic leukemia (APL) is a type of acute myeloid leukemia (AML) characterized by the presence of t(15;17)(q22;q21) translocation leading to fusion between PML and RARa gene. Treatment combining all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) has dramatically improved the prognosis of APL. We report a rare finding of primary clone of t(15;17) followed by a sequential clonal evolution of additional derivative chromosome 6 formation by a two hit mechanism. Our case showed a good clinical response with a four years and nine months event free survival after ATRA and ATO combination therapy in spite of existence of three chromosomal abnormalities stating that targeted therapy overcomes the adverse effects of additional genetic markers. However, close monitoring with assessment for long term prognostic behavior is required.

Flow Cytometric Expression of CD49d in Newly Diagnosed Chronic Lymphocytic Leukemia and Its Correlation with Established Prognostic Markers.

Introduction Chronic lymphocytic leukemia (CLL) is the commonest hematological malignancy in the West but is relatively uncommon in India. The prognosis of CLL is determined by well-established prognostic markers. CD49d has been emerging as a promising prognostic marker in CLL. CD49d expression in CLL has been found to have an aggressive clinical course, shorter time to first treatment, and poorer prognosis. The aim of this study was to analyze the flow cytometric expression of CD49d in newly diagnosed CLL and to correlate its expression with clinico-hematological parameters. Materials and Methods Twenty-five consecutive patients of CLL, diagnosed on flow cytometry, were included in the study. Patients on treatment or those with relapse were excluded. The panel for flow cytometry included the routine markers used for CLL diagnosis along with CD49d. The expression of CD49d was correlated with clinico-hematological parameters in all patients. "R" software was used for the statistical analysis. Fisher's exact test and Wilcox test were used to assess the correlation of CD49d to categorical and continuous data, respectively. Results The mean age of the patients was 62.6 ± 12.5 years, and 80% were symptomatic at diagnosis. CD49d expression was found in 44% cases, with a higher proportion being male patients. CD49d and prolymphocyte percentage showed a statistically significant correlation ( p = 0.0007). We found a statistically significant correlation between CD49d expression and lymphadenopathy and splenomegaly with p -values of 0.033 and 0.0472, respectively. CD49d positivity correlated significantly with a higher Rai stage ( p = 0.0196) and intermediate and high-risk cases according to Binet staging ( p = 0.033). Conclusion CD49d expression in the present study correlated with a higher prolymphocyte percentage, lymphadenopathy, splenomegaly, and higher Rai and Binet stages. CD49d expression on flow cytometry was reproducible and easy to interpret.

Diffuse large B-cell lymphoma and new insights into its pathobiology and implication in treatment.

The most common non-Hodgkin lymphoma (NHL) subtype is diffuse large B-cell lymphoma (DLBCL). It accounts for roughly 30% of all cases of NHL affecting both nodal and extra nodal sites. There are molecular subtypes of DLBCL, germinal centre subtype (GCB), and activated B-cell (ABC), based on gene expression profiling (GEP), in accumulation to distinct morphological and clinicopathological subtypes. To prognosticate patients, the International Prognostication Index (IPI) and its variants are used. In ABC type DLBCL, limited stage disease is treated with a combination of abbreviated systemic chemotherapy (three cycles) and field radiation therapy. Although advanced stage disease is treated with a full course of chemotherapy as well as novel agents (Bortezomib, Ibrutinib, Lenalidomide). In this review study, we looked at the role of multiple aspects of genetic and microenvironment changes which have effects in DLBCL tumours.