Idiopathic hypereosinophilic syndrome presenting with stroke.

Hypereosinophilic syndrome (HES) is characterized by eosinophilia associated with organ damage. The disorder has substantial clinical heterogeneity and a highly variable prognosis. This report describes an interesting autopsy case of a 62-year-old lady presenting with itching and stroke-like symptoms. She was diagnosed with an "idiopathic" variant of HES after a thorough exclusion of all known causes. Despite adequate measures, she deteriorated rapidly. At autopsy, acute cerebral infarcts were identified in multiple vascular territories including infarcts in watershed areas. Additionally, her heart showed classic pathological features of eosinophilic myocarditis spanning all three stages.

Screening for paroxysmal nocturnal hemoglobinuria (PNH) in patients presenting with cerebral sinovenous thrombosis (CSVT): Results of a FLAER based flowcytometry study in Indian patients.

Patients with paroxysmal nocturnal hemoglobinuria (PNH) may present with thrombosis at unusual sites, of which cerebral sinovenous thrombosis (CSVT) is one and screening for PNH is recommended in this condition. Though many patients diagnosed with PNH develop CSVT, it is unclear how many patients with PNH would present for the first time with thrombosis. We analysed the results of screening for PNH by flowcytometry in our patients with CSVT. The laboratory data of patients referred for thrombophilia and PNH testing in CSVT was examined to assess the frequency of PNH at presentation in these patients. FLAER and CD24 on granulocytes and FLAER and CD14 on monocytes respectively were used to screen the leucocytes for PNH by flowcytometry. The data for Protein C, S and Antithrombin deficiency, antiphospholipid antibodies and the Factor V Leiden mutation was examined and circumstantial risk factors were also assessed. Of the 180 cases of CSVT screened by flowcytometry for PNH, not a single case tested positive. Positivity for anti-phospholipid antibodies was the most common thrombophilic risk factor (5%). Pregnancy was the most common circumstantial risk factor. Our data on FLAER based flowcytometry in the North Indian population with CSVT suggests that PNH is not a common risk factor in our patients with thrombosis at this unusual site.

Randomized controlled trial of individualized, low dose, fixed duration lenalidomide maintenance versus observation after frontline chemo-immunotherapy in CLL.

Lenalidomide maintenance after frontline chemo-immunotherapy (CIT) in chronic lymphocytic leukemia (CLL) has not been standard due to the availability of novel therapies, though these remain out of reach for most in low-middle income countries. This single-center, open-label study randomized CLL patients (non-deletion 17p) after frontline therapy to lenalidomide maintenance (dose-escalated 2.5-10mg, 20/28 days per cycle for six months) or observation (2:1 allocation). Forty patients were included over 2018-2020. At a median follow-up of 22 months, median progression-free survival (PFS) with lenalidomide was not significantly different than observation (26 vs. 18 months, p = 0.4). Patients with minimal residual disease >10-2 had a trend toward better PFS with lenalidomide (19 vs. 7 months, p = 0.07). Grade 3 neutropenia was seen in 16.7% of patients on lenalidomide. Quality of life was comparable between the two arms. Low dose, fixed duration lenalidomide maintenance is not an effective strategy after frontline CIT in CLL.

Chronic Lymphocytic Leukemia: Real-World Data From India.

PURPOSE: Chronic lymphocytic leukemia (CLL) is uncommon in India. There are limited studies on CLL from the Indian subcontinent. METHODS: This was a prospective study (2011-2017) of consecutively diagnosed patients with CLL at a single center. The diagnosis, prognosis, treatment indication, response criteria, and adverse events were recorded as per International Workshop on Chronic Lymphocytic Leukemia guidelines. Biosimilar rituximab dosing (375 mg/m2) was fixed for all cycles. Time to next treatment (TTNT) was defined as the time from front-line treatment initiation to next treatment or death from any cause. Overall survival (OS) was defined as the time from treatment initiation until death from any cause. RESULTS: A total of 409 patients with CLL were enrolled over the study period. The median follow-up was 32 months (range, 2-135 months). The median age was 61 years, and 31.8% of patients with CLL were ≤ 55 years of age; 43.3% of patients had a cumulative illness rating scale score ≥ 3. Prognostic fluorescence in situ hybridization data were available in 53.3% of patients. Chlorambucil (94/180; 52.2%) and bendamustine + rituximab (BR; 57/180; 31.6%) were the most common regimens used up front. The overall response rates after front-line therapy were 74.4% and 91.2%, respectively. The TTNT was 33 months and not reached, respectively (P = .001). Grade 3/4 neutropenia and infections were seen in 52.6% and 38.5% of patients receiving BR. The median OS was not reached in both regimens (P = .25). CONCLUSION: Indian patients with CLL are younger in chronological age but have higher morbidity burden. Treatment outcomes with biosimilar fixed-dose BR are comparable to those reported in the literature. Chlorambucil is still a valid option, given the economic burden of the disease and treatment.

Deletion of CDKN2A/B is associated with inferior relapse free survival in pediatric B cell acute lymphoblastic leukemia.

Considering conflicting data on CDKN2A/B deletion in ALL, this study to assess its prognostic significance as an independent marker in a total of 96 pediatric B and T-ALL cases was planned. The overall frequency of CDKN2A/B deletion was 44% (n = 43) with 36% (30/83) in B-ALL and 100% (13/13) in T-ALL. CDKN2A/B deletion was significantly associated with high WBC count (p = .002) and National Cancer Institute risk (p = .01) in B-ALL. Importantly, CDKN2A/B deletion cases had poor EFS of 42% at 28 months compared to EFS of 90% in rest (p = .0004). Further, relapse free survival was only 56% for cases with CDKN2A/B deletions (n = 25), compared to 100% in control group (p = .001). Moreover, CDKN2A/B deletion was the only risk factor associated with early relapse (p = .01) compared to IKZF1 deletion (p = .73) or occurrence of BCR-ABL1 fusion transcript (p = .26). Thus our study data highlights potential prognostic role of CDKN2A/B deletions in early disease stratification in pediatric B-ALL.

High frequency of intermediate and poor risk copy number abnormalities in pediatric cohort of B-ALL correlate with high MRD post induction.

Copy number abnormalities (CNAs) and recurrent fusion transcripts are important genetic events which define and prognosticate B-Cell Acute Lymphoblastic Leukemia (B-ALL). We evaluated CNAs and fusion transcripts in 67 pediatric B-ALL cases and correlated the data with standard risk factors and early treatment outcome parameters. Common fusion transcripts ETV6-RUNX1, E2A-PBX, BCR-ABL1 and MLL-AF4 were examined by RT-PCR and noted in 15%, 15%, 13% and 1.4% of all cases respectively. CNAs in IKZF1, PAX5, EBF1, BTG1, RB1, CDKN2A/B and genes from PAR1 region viz., CSF2RA, IL3RA,P2RY8, SHOX region and CRLF2 were analyzed by multiplex ligation dependent probe amplification assay and were detected in 70% (47/67) of cases, with predominantly deletions in CDKN2A/B (36%), PAX5 (18%) and IKZF1 (16%). A statistically significant association of intermediate/poor risk CNAs was noted with high WBC count (p = 0.001), NCI group (p = 0.02) and minimal residual disease at Day35 (p < 0.0001). IKZF1 and CDKN2A/B deletion revealed poor EFS of 56% at 24 months as compared to EFS of 80% in rest of the cases (p = 0.05) suggesting their potential role in early risk stratification.

Low Expression of Leucocyte Associated Immunoglobulin Like Receptor-1 (LAIR-1/CD305) in a Cohort of Pediatric Acute Lymphoblastic Leukemia Cases

Background: Immunophenotypic markers can play significant role in prognostic assessment for different cancers and leukocyte-associated Ig-like receptor (LAIR-1) is a recently identified inhibitory immuno-receptor. Methods: We measured LAIR-1 expression in paediatric ALL patients (n-42) and appropriate controls by flow cytometry. Median fluorescence intensities (MFIs) were calculated and correlated with demographic and clinical variables and early treatment outcome parameters. Results: The ALL cohort had an age range of 1 - 11 y and a M:F ratio of 2.5:1. 64% had WBC counts <50 x 109/L and 15 (36%) >50 x 109/L, 52% being standard risk and 48% high risk. There were 6 cases of T-ALL and 36 of B-ALL. AML1-TEL, E2A-PBX, BCR-ABL and MLL-AF4 transcripts were noted in 3, 6, 2 and 1 patient, respectively. Day 8 ABC was <1,000 in 31 and >1,000 in 8 cases, while 30 had low and 7 high MRD (both >0.01) at day 35 of treatment. The median MFI for LAIR-1 expression in control cases was 8.2 (range 7.76-11.69) and in ALL cases 4.02 (range 0.56 to 11.87), with 74% (n-31) of ALL cases showing reduced LAIR-1 expression. However, no significant correlations were found between standard ALL risk factors and LAIR-1 expression. Out of 42 patients, 4 died during induction treatment and one exited therapy, 60% (n-3/5) of these featuring low expression of LAIR-1. Also ALL patients with low LAIR-1 expression had t (12;21), t (1;19) and t (4;11) translocations in 2, 4 and 1 samples, respectively, but none had t (9;22). Of those with high LAIR-1 expression, 2 had t (9;22) (MFIs-14.43 and 11.87). Conclusions: This pilot study of LAIR-1expression in ALL suggests low expression of the inhibitory molecule in leukemic cells. However, the findings need to be confirmed with larger cohort, along with studies focusing on pathophysiological roles in leukemic clone survival and escape from the immune system.

T-cell/Natural killer-cell neoplasms presenting as leukemia- Case series from single tertiary care center.

BACKGROUND: Mature T/ NK-cell neoplasms are a rare group of disorders and their presentation as leukemia is even rarer. Most of the previous studies have focused on mature B-cell lineage leukemias and there is a paucity of data on mature T/NK-cell lineage leukemias. We, therefore, planned this study to analyze their spectrum, frequency, morphology and immunophenotypic features. SUBJECTS AND METHODS: All cases of lymphomas presenting as leukemia over a period of two and a half years were evaluated. Detailed analysis of cases with T/NK-cell lineage was done for their clinical, hematological and immunophenotypic features. RESULTS: A total of 262 cases of mature lymphoid neoplasms presented as leukemia during the study period. Of whom, only 8 (3.1%) cases were of T /NK-cell lineage and the remaining (96.9%) were of B-cell lineage. Of 8 cases, 4 (50%) had T-prolymphocytic leukemia, 2 (25%) had chronic lymphoproliferative disorder- natural killer cell and 1 (12.5%) case of each T-large granular lymphocytic leukemia and hepatosplenic γ/δ T-NHL. CONCLUSION: T/NK-cell leukemias are rare. Along with clinical and morphological features, pattern of immunophenotypic markers is vital for their diagnosis and subcategorization.

CLL: Common Leukemia; Uncommon Presentations.

We report here a series of ten patients with uncommon presentations and associations of chronic lymphocytic leukemia (CLL) not reported hitherto or occasionally reported in literature. The first two cases describe unusual causes of abdominal distension in CLL and unusual sites infiltration by CLL. The next two cases illustrate occurrence of CLL in association with other hematological malignancies. Cases five and six describe unusual infections and their impact on CLL. Cases seven and eight depict associations of rare non-hematological autoimmune conditions with CLL. The last two cases describe transformation at unusual sites. This series of ten cases illustrates how a common leukemia like CLL can present in different forms and how despite so much progress in understanding of this leukemia so little is known of such presentations.

Hypereosinophilia in Acute Lymphoblastic Leukemia: Two Cases with Review of Literature.

Eosinophilia is rare in acute leukemia at presentation. Discrete reports and case studies in recent years have created significant interest in the field of "Acute leukemia with eosinophilia". We herein present two cases of eosinophilia in association with acute lymphoblastic leukemia with brief review of literature in this field. First case is about 21-year-old female who presented with mediastinal mass along with leukocytosis and hypereosinophilia. On evaluation, she was found to have T cell acute lymphoblastic leukemia. After ruling out benign causes of eosinophilia, she was treated with modified BFM-90 protocol. Her eosinophilia resolved after 4 weeks of induction therapy. Second case is about 32-year-old male who was diagnosed as a case of mixed phenotype leukemia (B cell/myeloid type) along with severe eosinophilia. His hypereosinophilia finally resolved by week 16 of modified BFM-90 protocol. Diagnosing ALL is challenging when eosinophilia is the initial presentation. These two cases emphasize on the importance of considering ALL amongst one of the etiological causes of eosinophilia as delay in diagnosis endangers patient's life at risk. Also eosinophilia per se is an independent poor risk factor, hence prompt diagnosis and early treatment is the key in all such cases.

The high incidence of BK polyoma virus infection among renal transplant recipients in India.

BK polyoma virus causes allograft dysfunction as a result of tubulo-interstitial nephritis in 2% to 5% of renal transplant recipients. The incidence of BK virus infection among renal transplant recipients in India is unknown. We used routine histologic examination, immunohistochemistry, and electron microscopy to retrospectively screen for BK polyoma virus in 414 renal allograft biopsy specimens from 321 transplant recipients presenting with allograft dysfunction. All patients had received a combination of cyclosporine, azathioprine, and prednisolone. A total of 30 biopsy specimens (9.3%) were positive for BK polyoma virus, suggesting a high incidence of this infection in Indian transplant recipients. BK virus infection coexisted with acute rejection in a majority of patients. This is the first report of this infection among Indian renal transplant recipients.

Epstein-barr virus infection masquerading as acute leukemia: a report of two cases and review of literature.

Epstein-Barr virus (EBV) is the first herpes virus to be completely sequenced. It is implicated in diseases from the benign infectious mononucleosis to malignant nasopharyngeal carcinoma, Burkitt's lymphoma and primary CNS lymphoma in AIDS patients. It has also been found to be associated with some miscellaneous diseases like chronic fatigue syndrome, multiple sclerosis etc. however causality still remains an issue of debate. As the virus mainly targets the lymphomonuclear cells and the reticuloendothelial system of the body, it's various manifestations are often mistaken as leukemic malignancies. We report two such cases of young adults who had been diagnosed as having acute leukemia on the basis of atypical cells in the peripheral blood. One patient later turned out to be a classical infectious mononucleosis and second patient had EBV associated hemophagocytic lymphohistiocytosis syndrome.

Hepatosplenic T-cell lymphoma is a distinct rare entity: diagnosis by fine-needle aspiration cytology.

In this brief report, we have described the fine-needle aspiration cytology (FNAC) of a hepatosplenic T-cell lymphoma (HSTCL) in a 60-year-old female patient. The patient complained of fever and heaviness of left upper abdomen. Ultrasound-guided FNAC of the spleen showed immature lymphoid cells, and a diagnosis of primary non-Hodgkin lymphoma of spleen was offered. Subsequently, the patient underwent splenectomy and wedge biopsy of liver that confirmed the cytological diagnosis. The lymphoma cells were positive for CD3 immunostain. Primary hepatosplenic T-cell lymphoma is a rare entity and may often pose diagnostic problems on FNAC.