Pediatric Non-Down Syndrome Acute Megakaryoblastic Leukemia With Unusual Immunophenotype.

Acute megakaryoblastic leukemia (AMKL) is a rare subtype of acute myeloid leukemia (AML) characterized by abnormal megakaryoblasts expressing platelet-specific surface antigens. 4%-16% of childhood AMLs are AMKL. Childhood AMKL is usually associated with Down syndrome (DS). It is 500 times more common in patients with DS when compared to the general population. In contrast, non-DS-AMKL is much rarer. We describe a case of de novo non-DS-AMKL in a teenage girl child who presented with a history of excessive tiredness, fever, abdominal pain for three months, and vomiting for four days. She had lost appetite, and weight. On examination she was pale; there was no clubbing, hepatosplenomegaly or lymphadenopathy. There were no dysmorphic features or neurocutaneous markers. Laboratory tests showed bicytopenia (Hb: 6.5g/dL, total WBC count: 700/µL, platelet count: 216,000/ µL, Reticulocyte %: 0.42) and 14% blasts on the peripheral blood smear. Platelet clumps and anisocytosis were also noted. Bone marrow aspirate showed a few hypocellular particles with dilute cell trails but showed 42% blasts. Mature megakaryocytes showed marked dyspoiesis. Flow cytometry on bone marrow aspirate showed myeloblasts and megakaryoblasts. Karyotyping showed 46 XX. Hence, a final diagnosis of non-DS-AMKL was established. She was treated symptomatically. However, she was discharged on request. Interestingly, the expression of erythroid markers such as CD36 and lymphoid markers like CD7 is usually seen in DS-AMKL and not in non-DS-AMKL. AMKL is treated with AML-directed chemotherapies. Although complete remission rates are similar to other AML subtypes, overall survival is only about 18-40 weeks.

Microparticles in diabetic kidney disease.

Diabetic kidney disease (DKD) is the most common cause of renal failure and a major contributor to the socioeconomic burden in chronic kidney disease (CKD) patients worldwide. The pathogenesis of DKD involves all the structures in the nephron, and it is indicated by proteinuria, hypertension, and progressive decline in renal function, leading to substantial morbidity and mortality. Due to the limitations of currently available standard markers (albuminuria and glomerular filtration rate) in the diagnosis and clinical grading of DKD, it's time to have novel biomarkers for early detection, targeted and effective therapy to prevent the progression. Microparticles (MPs) are extracellular vesicles measuring 0.1-1 µm derived by cytoskeletal reorganization in the form of cytoplasmic blebs which alters the phospholipid cytochemistry of the cell membrane. They are shed during cell activation and apoptosis as well as plays an important role in cell-to-cell communication. Over the last few decades, both plasma and urinary MPs have been investigated, validated and the preliminary research looks promising. With alterations in their number and composition documented in clinical situations involving both Type1 and 2 diabetes mellitus, microparticles assay appears to be promising in early diagnosis and prognostication of DKD. We cover the basics of microparticles and their involvement in DKD in this review article.

Acute Kidney Injury and Progressive Diabetic Kidney Disease: An Epidemiological Perspective.

PURPOSE: Diabetic kidney disease (DKD) represents a unique subset of patients with chronic kidney disease (CKD). Acute kidney injury (AKI) is implicated in DKD progression; however, their interplay is not studied well. We studied risk factors for AKI and the effect of AKI on disease progression in a homogeneous group of patients with DKD. PATIENTS AND METHODS: We conducted a retrospective open cohort study of patients with DKD at a single tertiary care centre between August 2016 - August 2019. Patients with a minimum follow-up of 2 years were included in the study. The incidence, etiology and risk factors for AKI were studied. The primary outcome studied was the effect of AKI on reduction in estimated glomerular filtration rate (eGFR) in DKD. Loss in eGFR by 50% and need for renal replacement therapy or reaching CKD stage V were studied as secondary outcomes. RESULTS: Two hundred and ninety-two DKD patients meeting the study criteria with a follow-up of 29.57 (±4.3) months were included. The incidence of AKI was 31.1%. Sepsis was the most common etiology (61%). Proteinuria was an independent risk factor for AKI after adjusting for covariates (adjusted OR - 1.158; 95% CI (1.018-1.316); p=0.025). In patients with AKI, median decline in eGFR was 10.29 mL/min/1.73m2/year (IQR-5.58-13.84) which was significantly higher compared to patients with no AKI [eGFR 7.25 (IQR 5.06-11.38); p-0.014]. On subgroup analysis, sepsis-induced AKI (versus non-sepsis AKI; p<0.001) and higher AKI stage (stage 2/3 versus stage 1; p=0.019) were associated with a faster decline in eGFR. CONCLUSION: AKI is common in patients with DKD with sepsis being the most common etiology. AKI in diabetic kidney disease is associated with a faster decline in eGFR. Baseline proteinuria is an independent risk factor for AKI.

Impact of World Health Organization (WHO) Revised Criteria-2016 on the Diagnosis of Polycythemia Vera.

The diagnosis of polycythemia vera (PV) requires the integration of clinical and laboratory findings, bone marrow morphologic features, and JAK2 analysis. JAK2V617F (exon 14) mutation is found in 95% of PV cases. In PV, addition of characteristic bone marrow morphology as one of three major diagnostic criteria allowed reduced hemoglobin/hematocrit threshold for diagnosis to 16.5 g/dL/49% in men and 16 g/dL/48% in women. JAK2 mutation is still the third major diagnostic criterion in PV. Low serum erythropoietin level is now considered as minor criterion in PV and is used to detect cases, which are negative for JAK2 mutation. In this retrospective study, cases diagnosed as PV from January 2013 to December 2015 were reclassified using WHO 2016 criteria. Their clinical and laboratory parameters along with treatment and outcome were studied. Out of 26 patients of previously diagnosed PV, either definitively or provisionally, twenty-one were found to comply with the new 2016 revision of the WHO Criteria. Median age was 55.5 years, with a male preponderance. The median values of hemoglobin, hematocrit and platelets were 17.5 gm/dL, 56.7% and 493 × 109/L, respectively. JAK2V617F was mutated in 17 cases. Bone marrow showed hypercellularity, panmyelosis and marked megakaryocyte dyspoiesis in all patients. All patients had normal oxygen saturation, confirming the primary nature of the disease. Our study, first of its kind in India, underscores the importance of the 2016 revision of the WHO document in detecting cases of masked PV.

Multiparametric Flow Cytometry in Mixed Phenotype Acute Leukemia.

Mixed phenotype acute leukaemia (MPAL) is a diverse group of leukemia of ambiguous lineage diagnosed when blasts in peripheral blood and/or bone marrow have antigens of more than one lineage or a mosaic of blasts belonging to more than one lineage. Retrospective analysis of 218 consecutive cases of acute leukaemia diagnosed by multiparametric flow cytometry (FCM) was done. MPAL cases were identified in accordance with European Group for the Immunological Classification of Leukaemias Criteria and World Health Organization 2008/2016 guidelines for lineage assignment. Nine out of 218 (4.1%) cases were classified as MPAL. Eight out of nine patients (88.8%) were male and 4/9 (44.4%) were < 20 years of age. There were three cases of B/T and T/myeloid MPAL each. Two cases were B/myeloid MPAL and one case was chronic myeloid leukaemia (CML) in B/myeloid blast crisis. B/myeloid MPAL and CML in B/myeloid blast crisis cases were Philadelphia chromosome positive. The latter case had a complex karyotype as well. Seven cases were treated with acute lymphoblastic leukaemia treatment regimen; two of them achieved complete remission (CR). The patient with CML in B/myeloid blast crisis was treated with imatinib based regimen, attained CR, underwent allogenic bone marrow stem cell transplantation, but developed graft versus host disease. Five patients died due to complications of febrile neutropenia early in the course of treatment (62.5%). The last patient (B/T MPAL) refused therapy and was lost to follow-up. Early accurate diagnosis of MPAL requires FCM. It may be misdiagnosed if a limited panel of antibodies is used.

Impact of body mass index on progression of primary immunoglobulin a nephropathy.

The role of obesity in the progression of primary glomerular diseases is controversial. A few studies report overweight/obesity as a risk factor for disease progression in immunoglobulin A nephropathy (IgAN), and the real impact of it still remains unclear. The aim of this study was to elucidate the effect of body mass index (BMI) on disease progression and proteinuria in patients with IgAN in Indian population. A cohort of biopsy-proven primary IgAN patients diagnosed between March 2010 and February 2015 who had a follow-up for a minimum of 12 months were included in the study. We defined two groups of patients according to the BMI value at diagnosis: non-obese group (Group N) with BMI <23 Kg/m2 and the overweight/obese group (Group O) with BMI >23 Kg/m2 as per Asia-Pacific task force criteria. Baseline characteristics were compared between the groups. The estimated glomerular filtration rate (eGFR) and urine protein-creatinine ratio (UPCR) were followed up at entry time, 6 months, 12 months, and at the end of follow-up. Outcomes studied were change in eGFR, proteinuria, and progression to end-stage renal disease. Statistical analysis was done using the Statistical Package for the Social Sciences version 15.0. Of 51 patients, 25 (49%) had BMI <23 kg/m2 (Group N) and 26 (51%) had BMI >23 kg/m2 (Group O) (P = 0.01). The baseline clinical, histopathological, and treatment characteristics of both the groups were comparable. The BMI at the time of diagnosis did not have any significant effect on eGFR (P = 0.41) or proteinuria (P = 0.99) at presentation. At the end of follow-up, both the groups had a similar reduction of proteinuria (UPCR) (P = 0.46) and eGFR (P = 0.20). Two patients in each group have reached chronic kidney disease Stage 5. In the present study, BMI at presentation did not have any impact on eGFR or proteinuria, either at diagnosis or at follow-up. It needs further large multicenter randomized control studies to see the effect of BMI on progression of IgAN.