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Hypereosinophilia (HE) can be caused by a wide variety of non-hematologic (secondary or reactive) and hematologic (primary, clonal) disorders. Diagnosing hypereosinophilia/hypereosinophilic syndrome (HE/HES) is challenging due to the complex nature of disease manifestations and numerous underlying etiologies. Knowing that only rare cases are clonal, it is wise to rule out reactive conditions and proceed with molecular and other advanced tools. The exclusion of secondary causes needs a detailed clinical evaluation followed by a wide range of serological and imaging investigations. Once reactive eosinophilia has been ruled out, the diagnosis of primary HE/HES is made using a combination of morphologic examination of the blood and bone marrow, conventional cytogenetics, fluorescent in situ hybridization, flow-cytometry, and T-cell clonality evaluation to look for histopathologic or clonal evidence of an underlying hematological disorder. The accurate diagnosis of clonal eosinophilia-causing myeloid and lymphoid neoplasms and the identification of numerous gene rearrangements significantly enhance patient outcomes, because a proportion of these patients (such as PDGFRA and PDGFRB rearrangements) responds well to tyrosine kinase inhibitors. Considering the complex etiopathologies, the cost of testing, and the time involved, the workup needs to be tailored according to the urgency of the situation and the resources available. In urgent situations with organ damage, it is crucial to initiate appropriate management without waiting for the results of investigations. In contrast, in a resource-limited situation, it is acceptable to employ step-by-step rather than comprehensive testing to rule out the most common causes first. Here, we discuss various laboratory investigations employed in diagnosing HE/HES, highlighting their importance in different situations. [ABSTRACT FROM AUTHOR]

Introduction: The categorization of mature B cell neoplasms (MBN) infiltrating blood and bone marrow are met with difficulties. The inclusion of CD148 and CD180 in the routine flow cytometry/FCM panels has been suggested to refine the diagnosis. We studied the discriminatory ability of CD148 and CD180 median fluorescence intensity(MFI), CD148/CD180 ratio and their expression relative to T cells (CD148ab/T, CD180ab/T), neutrophils (CD148ab/gr, CD180ab/gr) and normal B cells (CD148ab/n, CD180ab/n) in the differentiation of mature B cell neoplasms (MBN) especially non‐chronic lymphocytic leukaemia (CLL). Methodology: The flow cytometric (FCM) expression of CD148 and CD180 was studied prospectively in 102 patients (non‐CLL; n = 72); diagnosed by a comprehensive panel of immunophenotypic and cytogenetic studies. The MFI and ratios were statistically compared across MBNs by Mann‐Whitney U test. Cut‐off values, sensitivity and specificity were calculated for significant parameters by receiver operator characteristic curve. Results: CD180MFI > 4.35 showed 100% sensitivity and 90.9% specificity for a diagnosis of marginal zone lymphoma (MZL) while, CD148/180 > 5.15 was 100% specific and 81.8% sensitive for lymphoplasmacytic lymphoma. CD148ab/T(>4.3; 100% specificity, 83.4% sensitivity) and CD148ab/gr(>1.1; 100% sensitivity, 90% sensitivity) were useful for differentiating blastoid‐mantle cell lymphoma/MCL from diffuse large B cell lymphoma; while CD148MFI (≥20.25), CD148ab/T(>3.35) and CD148ab/gr(>0.95) showed >90% specificity and sensitivity for distinguishing MCL from CLL. Pairwise analysis also showed a good discriminant function of various parameters for distinguishing SMZL from other MBNs like FL, MCL as well as CLL. Conclusions: The current study shows an excellent utility of CD148MFI, CD180MFI, their ratio and relative expression levels in the subcategorization of immunophenotypically related MBNs. [ABSTRACT FROM AUTHOR]

Aim We evaluated the frequency of antiphospholipid antibody syndrome (APS) in patients presenting with thrombosis of various vascular beds from North India and report the antibody profiles encountered. Patients and methods A retrospective analysis was performed on the laboratory results of aCL (anticardiolipin), aβ2Gp1 (anti-βeta-2 glycoprotein 1) antibody and LAC (lupus anticoagulant) of 1222 consecutive patients referred to the coagulation laboratory work-up for a hypercoagulable/thrombophilic state over a period of 4 years between 2009 and 2013. LAC was screened with dRVVT (diluted Russel Viper Venom Test) and KCT (Kaolin clotting time), and aCL and aβ2Gp1 antibodies with commercial enzyme-linked immunosorbent assy kits. Results The current APS criteria was satisfied in 3.85% of all patients and 4.2% of pediatric patients with thrombosis. The venous circulation was more frequently affected (59.6%). Cerebral arterial and intra-abdominal vein involvement was common. Transient antibody positivity was seen in 44 (3.6%) cases. aβ2Gp1, aCL and LAC were positive in 95%, 54.5% and 23% of patients with APS, respectively, during the initial visit and 93.6%, 23% and 17%, respectively, during the follow-up visit. Persistent triple positivity was seen in only three cases. At initial testing, positivity for both aCL and aβ2Gp1 was the most frequent pattern (38% of cases). Conclusions aβ2Gp1 antibody was the commonest antibody that was persistently positive in patients with thrombosis. Triple positivity for all antibodies had the highest specificity and positive predictive value to diagnose APS in the first visit, whereas aβ2Gp1 antibody had the highest sensitivity and negative predictive value. [ABSTRACT FROM AUTHOR]

Compound heterozygosity for one of the Hb Lepore mutations and β-thalassemia (β-thal) is a rare cause of non transfusion-dependent thalassemia. We report a 4-year-old boy who presented clinically as homozygous/compound heterozygous β-thal intermedia (β-TI), an impression that was corroborated by the initial hemoglobin (Hb) high performance liquid chromatography (HPLC). However, the correct diagnosis of a rare compound heterozygous Hb Lepore-Hollandia/β-thal was revealed after parental studies and molecular analyses including β-globin gene sequencing. Our patient highlights the importance of a logical stepwise multi modality approach and the vital importance of parental screening and molecular studies in accurate characterization of complex hemoglobinopathies. Correct diagnosis is especially crucial if pre natal detection is anticipated for future pregnancies. Molecular analyses alone may not compensate for the unavailability of parental testing. This is because the molecular results may be misinterpreted, especially if limited tests are conducted. The infrequent prior reports of this combination from distant parts of the Indian subcontinent suggests that the origin of Hb Lepore-Hollandia from sporadic mutations occurs in isolated families. [ABSTRACT FROM AUTHOR]

Objectives Mature lymphoid neoplasms presenting with 'prominent splenomegaly without significant lymphadenopathy' are uncommon and pose unique diagnostic challenges as compared to those associated with lymphadenopathy. Their descriptions in the literature are largely limited to a few case series. We analyzed the spectrum of these lymphomas diagnosed by peripheral blood (PB) and/or bone marrow (BM) examination. Methods Over a period of 6 years, 75 patients were diagnosed with a lymphoma from PB/BM who had presented with predominant splenomegaly. Their clinical and laboratory records including PB and BM morphology; immunophenotyping using multi-parametric flow-cytometry and immunohistochemistry were reviewed. Wherever indicated, an extended panel of immunohistochemistry (IHC) was performed on BM biopsies for accurate sub-classification. Results and Discussion The commonest lymphomas were hairy cell leukemia (HCL) (32%) and splenic marginal zone lymphoma (SMZL) (24%). Others included diffuse large B cell lymphoma (8%), chronic lymphocytic leukemia/small lymphocytic lymphoma (8%), mantle cell lymphoma (2.7%), and follicular lymphoma (1.3%), all of which usually presents with lymphadenopathy. SMZL was the commonest lymphoma among females and those with massive splenomegaly and lymphocytosis; while HCL was commonest in patients with pancytopenia. SMZL commonly presented with lymphocytosis; however, 22% of them also presented with pancytopenia. Conclusion The high diagnostic efficacy of PB and BM examination using flow-cytometry and immunohistochemistry in confirming and sub-classifying splenic lymphomas suggests that a thorough hematological evaluation should always precede a diagnostic splenectomy. Immunohistochemistry remains the best modality to identify sparse or intra-sinusoidal infiltration on BM biopsy and is particularly useful in patients with fibrotic marrows and pancytopenia. [ABSTRACT FROM AUTHOR]

Background: Early detection of BCR::ABL1-like ALL could impact treatment management and improve the overall survival/outcome. BCR::ABL1-like ALL cases are characterised by diverse genetic alterations activating cytokine receptors and kinase signalling. Its detection is still an unmet need in low–middle-income countries due to the unavailability of a patented TLDA assay. Methods: This study's rationale is to identify BCR::ABL1-like ALLs using the PHi-RACE classifier, followed by the characterisation of underlying adverse genetic alterations in recurrent gene abnormalities negative (RGAneg) B-ALLs (n = 108). Results: We identified 34.25% (37/108) BCR::ABL1-like ALLs using PHi-RACE classifier, characterised by TSLPR/CRLF2 expression (11.58%), IKZF1 (Δ4–7) deletion (18.9%) and chimeric gene fusions (34.61%). In overexpressed TSLPR/CRLF2 BCR::ABL1-like ALLs, we identified 33.33% (1/3) CRLF2::IGH and 33.33% (1/3) EPOR::IGH rearrangements with concomitant JAK2 mutation R683S (50%). We identified 18.91% CD13 (P = 0.02) and 27.02% CD33 (P = 0.05) aberrant myeloid markers positivity, which was significantly higher in BCR::ABL1-like ALLs compared to non-BCR::ABL1-like ALLs. MRD positivity was considerably higher (40% in BCR::ABL1-like vs. 19.29% in non-BCR::ABL1-like ALLs). Conclusions: With this practical approach, we reported a high incidence of BCR::ABL1-like ALLs, and a lower frequency of CRLF2 alteration & associated CGFs. Recognising this entity, early at diagnosis is crucial to optimise personalised treatment strategies. [ABSTRACT FROM AUTHOR]

Objectives Bone marrow (BM) aspiration and trephine biopsy is one of the most valuable procedures in the evaluation of hematological disorders. There is a shortage of published literature regarding the indications, procedure, and outcome of bone marrow examination (BME) in neonates and infants. The aim of the present study is to analyze the common indications of performing BME and to assess the spectrum of disorders diagnosed from BM of neonates and infants. Methods A retrospective analysis of BMEs performed in infants over a period of 5 years, between 2009 and 2013 was done. Results and discussion A total of 297 BME were performed on 285 infants, which constitutes 10.3% of pediatric BME procedures during the same period. In our institute, BME is routinely performed by trained pathologists from posterior superior iliac spine in children including infants and neonates with an overall sample adequacy of 97%. Evaluation of cytopenias and suspicion of storage disorder were the most common indications for BME procedure, while acute leukemias and storage disorders were the most common diagnoses offered in infant BM. Conclusions Posterior superior iliac spine is a good site of BME in neonates and infants. BM trephine biopsy is a difficult procedure in this age group, however remains indispensable in situations where an infiltrative pathology is suspected. BME not only helps to make specific diagnoses but should also be used as an extremely valuable, quick, and economically viable procedure to exclude major hematological disorders including certain forms of storage disorder and hematological malignancy in this age group. [ABSTRACT FROM AUTHOR]

Glomerular diseases of the transplanted kidney are the most important cause of poor long- term outcome. The estimation of the magnitude of this problem and an elucidation of pathogenic mechanism is essential for improvement of graft survival. This study from the Indian subcontinent aims (i) to determine the incidence of transplant glomerulopathy ( TG) and thrombotic microangiopathy ( TMA) in a large cohort of indicated renal transplant biopsies, (ii) to evaluate the histological and ultrastructural features of TG and TMA, and (iii) to assess the relationship between the two glomerular lesions. Of a total of 1792 indication renal transplant biopsies received over 5 years (2006-2010), 266 biopsies (of 249 patients) had significant glomerular pathology and were further analyzed along with immunofluorescence, electron microscopy ( EM), and C4d immunohistochemistry. TG is the most common glomerular lesion followed by TMA seen in 5.97% and 5.08% of allograft biopsies, respectively, which constitutes 40.23% and 34.2% of biopsies with significant glomerular lesions. Pathologic antibody-mediated rejection ( AMR) is associated with both TG and TMA in 71% and 46.5%, respectively. A coexistent TG was found in 18.4% of biopsies with TMA. Endothelial swelling with subendothelial widening, a feature of TMA, is also seen in early TG by EM. Our findings support the concept that TG evolves from a smoldering TMA of various causes. [ABSTRACT FROM AUTHOR]

The article discusses the findings of a study which investigated the application of cation-exchange (CE)-high performance liquid chromatography (HPLC) in the quantification of hemoglobins and its variants. Topics covered include the unpredictable discrepancies of cellulose acetate electrophoresis (CAE) densitometric hemoglobin fraction levels and the disadvantages of using quantitative screening technique in clinical practice.

Intrathyroidal metastasis and direct extension of extrathyroidal malignancies can present with palpable thyroid nodules or may be detected as suspicious nodules in a thyroid scan. They can lead to diagnostic difficulty in fine needle aspiration cytology (FNAC) of the thyroid, especially in the absence of any previous history of such malignancies. Here we report an interesting case of intrathyroidal metastasis, which was initially suspected as a primary carcinoma of the thyroid; along with a short summary of a series of 11 cases of carcinomas of extrathyroidal origin, diagnosed in the FNACs of thyroid over the past three years in our institute. Knowledge of the potential diagnostic pitfalls in thyroid FNAC, a proper clinical evaluation, and judicious use of the ancillary techniques will help to attain a proper diagnosis. [ABSTRACT FROM AUTHOR]

This article discusses a case of VEXAS syndrome, a genetic autoinflammatory disorder that presents with various cutaneous manifestations, hematological abnormalities, and systemic inflammation. The case involves a 54-year-old Indian male who presented with red, raised, and mildly painful skin lesions, along with other symptoms such as fever, weight loss, and joint pain. The patient had a history of nodular skin lesions, scleritis, and diabetes mellitus. Laboratory evaluations revealed abnormalities in blood counts and bone marrow biopsy confirmed myelodysplasia. Genetic analysis confirmed the diagnosis of VEXAS syndrome. Treatment options for VEXAS syndrome are limited, with oral glucocorticoids being the most reliable. The article emphasizes the importance of dermatologists being aware of the cutaneous manifestations of VEXAS syndrome and collaborating with hematologists for multidisciplinary care. [Extracted from the article]

Introduction: X-linked lymphoproliferative syndrome (XLP) is a rare primary immune deficiency. Two types of XLP have been described: XLP-1 and XLP-2. Methods: We found 7 patients with XLP (3 had XLP-1 and 4 had XLP-2) after reviewing the data from Pediatric Immunodeficiency Clinic from 1997 to 2021. Results: Mean age at diagnosis was 3.8 years, and mean delay in diagnosis was 2.6 years. Five patients had recurrent episodes of infections. Four patients developed at least one episode of hemophagocytic lymphohistiocytosis (HLH) (2 with XLP-1 and 2 with XLP-2). Of these, 2 had recurrent HLH (both with XLP-2). Epstein-Barr virus (EBV) infection was detected in 2 (1 with XLP-1 and 1 with XLP-2). Both these patients had HLH. One child with XLP-2 had inflammatory bowel disease. Hypogammaglobulinemia was seen in 3 (2 with XLP-1 and 1 with XLP-2). Genetic analysis showed previously reported variants in 5, while 2 had novel variants (one in exon 7 of XIAP gene [c.1370dup p.Asn457Lysfs Ter16] and other had splice site variant in intron 1 of SH2D1A gene [c.138-2_138-1insG]). Episodes of HLH were managed with intravenous immunoglobulin (IVIg), methylprednisolone, oral prednisolone, cyclosporine, and rituximab. Inflammatory bowel disease was managed using oral prednisolone and azathioprine. One patient underwent haploidentical hematopoietic stem cell transplantation. One child with XLP-2 and WAS died because of fulminant pneumonia. Discussion/Conclusions: XLP should be considered as a strong possibility in any patient with features of HLH, repeated infections with hypogammaglobulinemia, persistent EBV infection, and early-onset IBD. [ABSTRACT FROM AUTHOR]

Introduction: T-cell acute lymphoblastic leukemia (T-ALL) is a genetically heterogeneous disease with poor prognosis and inferior outcome. Although multiple studies have been perform on genomics of T-ALL, data from Indian sub-continent is scarce. Methods: In the current study we aimed to identify the genetic variability of T-ALL in an Indian cohort of pediatric (age ≤ 12 years) T-ALL patients (n = 25) by whole transcriptome sequencing along with whole exome sequencing and correlated the findings with clinical characteristics and disease outcome. Results: The median age was 7 years (range 3 -12 years). RNA sequencing revealed a definitive fusion event in 14 cases (56%) (including a novel fusions) with STIL::TAL1 in 4 (16%), followed by NUP21::ABL1, TCF7::SPI1, ETV6::HDAC8, LMO1::RIC3, DIAPH1::JAK2, SETD2::CCDC12 and RCBTB2::LPAR6 in 1 (4%) case each. Significant aberrant expression was noted in RAG1 (64%), RAG2 (80%), MYCN (52%), NKX3-1 (52%), NKX3-2 (32%), TLX3 (28%), LMO1 (20%) and MYB (16%) genes. WES data showed frequent mutations in NOTCH1 (35%) followed by WT1 (23%), FBXW7 (12%), KRAS (12%), PHF6 (12%) and JAK3 (12%). Nearly 88.2% of cases showed a deletion of CDKN2A/CDKN2B/MTAP genes. Clinically significant association of a better EFS and OS (p=0.01) was noted with RAG2 over-expression at a median follow up of 22 months, while a poor EFS (p=0.041) and high relapse rate (p=0.045) was observed with MYB over-expression. Conclusion: Overall, the present study demonstrates the frequencies of transcriptomic and genetic alterations from Indian cohort of pediatric T-ALL and is a salient addition to current genomics data sets available in T-ALL. [ABSTRACT FROM AUTHOR]

Background: Philadelphia chromosome (Ph)–like B‐acute lymphoblastic leukemia (B‐ALL) is a clinically significant, high‐risk genetic subtype of B‐ALL cases. There are few data on the incidence, characterization, and treatment outcomes of Ph‐like ALL cases from low‐ and middle‐income countries. There is a pressing need to establish a well‐organized/cost‐effective approach for identifying Ph‐like ALL instances. Methods: Multiplex reverse transcriptase polymerase chain reaction, nCounter NanoString, and fluorescence in situ hybridization were used to detect and characterize Ph‐like ALL cases among recurrent genetic abnormalities (RGA)neg B‐ALL cases. At the end of induction therapy, flow cytometry‐minimal residual disease (MRD) assay was used to quantify MRD positivity in Ph‐like ALL cases. Results: Of 130 newly diagnosed B‐ALL cases, 25% (BCR::ABL1), 4% (ETV6::RUNX1), 5% (TCF3::PBX1), 2% (KM2TA::AFF1), and 65% RGAneg B‐ALL cases were revealed by multiplex reverse transcriptase polymerase chain reaction. Among RGAneg B‐ALL cases, 24% Ph‐like ALL cases using nCounter NanoString were identified, with 48% CRLF2high cases with 45% CRLF2::P2RY8 and 18% CRLF2::IGH rearrangements(∼r) revealed by fluorescence in situ hybridization. In 52% of CRLF2low cases, 17% ABL1 and JAK2∼r 8% EPOR::IGH & PDGRFB∼r were identified. Ph‐like ALL cases had higher total leukocyte count (p <.05), male preponderance (p <.05), and high MRD‐positivity/induction failure compared with RGAneg B‐ALL cases. Furthermore, in Ph‐like ALL cases, 11 significant genes using quantitative polymerase chain reaction were identified and validated. CRLF2, IGJ, CEACAM6, MUC4, SPATS2L and NRXN3 genes were overexpressed and show statistical significance (p <.05) in Ph‐like ALL cases. Conclusions: This study showed the high incidence of Ph‐like ALL cases with kinase activating alterations and treatment outcomes from low‐ and middle‐income region. Furthermore, a surrogate cost‐effective multiplex panel of 11 overexpressed genes for the prompt detection of Ph‐like ALL cases is proposed. Plain Language Summary: Identification of recurrent gene abnormalities (RGA)neg B‐acute lymphoblastic leukemia (B‐ALL) cases using multiplex‐reverse transcriptase polymerase chain reaction.Identification and characterization of Philadelphia (Ph)–like ALL cases using nCounter NanoString gene expression profiling and fluorescence in situ hybridization.Furthermore, Ph‐like ALL cases were characterized according to CRLF2 expression and kinase‐activating genomic alterations. Minimal residual disease of Ph‐like ALL cases were quantified using flow cytometry‐minimal residual disease assay.A surrogate molecular approach was established to detect Ph‐like ALL cases from low‐ and middle‐income countries. A surrogate approach for the rapid baseline detection of Philadelphia chromosome (Ph)–like acute lymphoblastic leukemia cases, followed by its kinase gene alterations. Early detection of Ph–like acute lymphoblastic leukemia cases is extremely important to start personalized treatments to improve the overall survival/outcomes of these cases. [ABSTRACT FROM AUTHOR]

Introduction: Pediatric T-cell acute lymphoblastic leukemia (T-ALL) poses significant challenges due to its aggressive nature and resistance to standard treatments. Long non-coding RNAs (lncRNAs) have emerged as potential biomarkers and therapeutic targets in leukemia. This study aims to characterize the lncRNA landscape in pediatric T-ALL, identify specific lncRNAs signatures, and assess their clinical relevance. Methods: RNA sequencing was performed on T-ALL patient and control samples. Differential expression analysis identified dysregulated lncRNAs and mRNAs. Functional enrichment analysis revealed potential roles of these lncRNAs in cancer pathogenesis. Validation of candidate lncRNAs was conducted using real-time PCR. Clinical correlations were assessed, including associations with patients' clinical characteristics and survival outcomes. Results: Analysis identified 674 dysregulated lncRNAs in pediatric T-ALL, with LINC01221 and CRNDE showing the most interactions in cancer progression pathways. Functional enrichment indicated involvement in apoptosis, survival, proliferation, and metastasis. Top 10 lncRNAs based on adjusted p value < 0.05 and Fold Change > 2 were selected for validation. Seven lncRNAs LINC01221, PCAT18, LINC00977, RP11-620J15.3, RP11-472G21.2, CTD-2291D10.4, and CRNDE showed correlation with RNA sequencing data. RP11-472G21.2 and CTD-2291D10.4 were highly expressed in T-ALL patients, with RP11-620J15.3 correlating significantly with better overall survival (p = 0.0007) at a median follow up of 32 months. The identified lncRNAs were further analysed in B-ALL patients. Distinct lncRNAs signatures were noted, distinguishing T-ALL from B-ALL and healthy controls, with lineage-specific overexpression of LINC01221 (p < 0.0001), RP11-472G21.2 (p < 0.001) and CRNDE (p = 0.04) in T-ALL. Conclusion: This study provides insights into the lncRNA landscape of pediatric T-ALL, offering potential diagnostic and prognostic markers. RP11-620J15.3 emerges as a promising prognostic marker, and distinct lncRNAs signatures may aid in the differentiation of T-ALL subtypes. Further research with larger cohorts is warranted to validate these findings and advance personalized treatment strategies for pediatric T-ALL patients. [ABSTRACT FROM AUTHOR]

The article describes the case of a previously one-year, three-month-old child with a history of intermittent low-grade fever relieved by antipyretics for one month. Topics discussed include findings on clinical examination, factor which raised the possibility of acute monocytic leukemia (AMoL), and laboratory results which led to the diagnosis of histiocytic sarcoma (HS).

The article presents a case study of 33-year-old man presented with pain abdomen, loss of appetite, weight loss, and generalized lymphadenopathy for three months. It mentions deviation from well-established investigative algorithms may lead to unnecessary diagnostic confusion with potentially serious consequences; and also mentions high-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements (HGBL-DH/TH) showing discordant PB morphology.

Background: Infections are a significant cause of morbidity and mortality after autologous hematopoietic cell transplantation (AHCT) in multiple myeloma (MM) patients. There has been a rapid advancement and evolution in MM treatment landscape in the last decade. There is limited information on post‐AHCT infectious complications among MM patients with or without levofloxacin prophylaxis from developing countries. Materials and methods: We performed a retrospective study to explore the incidence, pattern, and clinical outcome of infections following AHCT in MM patients from 2010 to 2019 at our center. Patient‐specific, disease‐specific, and transplant‐specific details were retrieved from the case files. The characteristics of infectious complications (site, intensity, organism, treatment, and outcomes) were analyzed. All patients who underwent transplantation from 2010 to 2016 received levofloxacin antibiotic prophylaxis. Common terminology criteria for adverse events (CTCAE) criteria (v5.0) were used for the grading of infections and regimen‐related toxicity. International Myeloma Working Group updated criteria were used for the assessment of disease response before transplant and at day +100. Results: Ninety‐five consecutive patients with newly diagnosed multiple myeloma (NDMM) (n = 85), RRMM (n = 7), plasma cell leukemia (n = 2), and Polyneuropathy, Orgaomegaly, Endocrinopathy, Monoclonal gammopathy, skin abnormalities (POEMS) syndrome (n = 1) underwent AHCT during the study period. Their median age was 55 years (range 33–68); 55.8% were males. Immunoglobulin IgG kappa was the most common monoclonal protein (32.6%), International Staging System stage III disease was present in 45.3%, and 84.2% of patients achieved more than very good partial response before AHCT. The median time from diagnosis to AHCT was 10 months (range 4–144). Eighty‐nine patients (93.7%) developed fever after AHCT. Fever of unknown focus, microbiologically confirmed infections, and clinically suspected infections were found in 50.5%, 37.9%, and 5.3% of patients, respectively. Clostridiodes difficile‐associated diarrhea was observed in eight patients (8.4%). Neutrophil and platelet engraftment occurred after a median of 11 days (range 9–14) and 12 days (range 9–23), respectively. The median duration of hospital stay was 16 days (range 9–29). Only two patients (2.1%) required readmission for infections within 100 days of AHCT. Transplant‐related mortality (TRM) in the study population was 4.2% (n = 4). The levofloxacin prophylaxis group (n = 32, 33.7%) had earlier neutrophil engraftment (day +10 vs. day +11) and platelet engraftment (day +11 vs. day +12), but time to fever onset, duration of fever, hospital stay, TRM, and day +100 readmission rates were not significantly different from those of patients without levofloxacin prophylaxis. There was no significant difference in the spectrum of infections between patients with and without levofloxacin prophylaxis. The overall survival and progression‐free survival of the study population at 5 years were 72.7% and 64.8%, respectively. Conclusion: This study shows that the incidence of infections and TRM are higher in MM patients from lower‐middle income countries after AHCT than in those from developed countries. The majority of such patients lack clinical localization and microbiological proof of infection. There was no significant difference in the spectrum of infections and their outcomes in patients with and without levofloxacin prophylaxis. [ABSTRACT FROM AUTHOR]

Magnetic resonance imaging revealed an epidural soft tissue mass lesion involving the dorsolumbar and sacral region with extension into the neural foramina [Figure 1]a and [Figure 1]b. A 28-year-old female presented with conus-cauda syndrome. [Extracted from the article]

Background: The gold standard for the identification of Philadelphia (Ph)‐like acute lymphoblastic leukemia (ALL) patients is gene expression profiling. Because of its diverse nature, its identification is extremely difficult and expensive. On the genomic and proteomic landscape of Ph‐like ALL patients, there is a paucity of published literature from developing countries. Methods: The authors used digital barcoded nCounter NanoString gene expression profiling for its detection, followed by molecular and proteomic characterization using fluorescence in situ hybridization and liquid chromatography–tandem mass spectrometry (LC–MS/MS). Results: The authors found 32.05% Ph‐like ALL patients and their median age at presentation was considerably higher than Ph‐negative ALL cases (p =.0306). Furthermore, we identified 20% CRLF2 overexpressed cases having 8.33% CRLF2‐IGH translocation with concomitant R683S mutation and 8.33% CRLF2‐P2RY8 translocation. In 80% of CRLF2 downregulated cases, we identified 10% as having JAK2 rearrangement. Minimal residual disease‐positivity was more common in Ph‐like ALL cases (55.55% vs. 25% in Ph‐negative ALL cases). Immunoglobulin J chain (Jchain), small nuclear ribonucleoprotein SmD1 (SNRPD1), immunoglobulin κ constant (IGKC), NADH dehydrogenase (ubiquinone) 1 α subcomplex subunit 2 (NDUFA2), histone H2AX (H2AFX), charged multivesicular body protein 4b (CHMP4B), and carbonyl reductase (NADPH) (CBR1) proteins were identified to be substantially expressed in Ph‐like ALL patients, using LC–MS/MS. Gene enrichment analysis indicated that involvement of spliceosomal mediated messenger RNA splicing pathway and four microRNAs was statistically significant in Ph‐like ALL patients. Conclusions: For the first time, we have described incidence, molecular, and proteomic characterization of Ph‐like ALL, in developing nations. Plain language summary: In developing countries, detecting Philadelphia (Ph)‐like B‐lineage acute lymphoblastic leukemia is complicated and challenging due to its diverse genetic landscape.There is no well‐defined and cost‐effective methodology for its detection.The incidence of this high‐risk subtype is very high in adult cases, and there is an urgent need for its accurate detection.We have developed an online PHi‐RACE classifier for its rapid detection, followed by delineating the genomic and proteomic landscape of Ph‐like acute lymphoblastic leukemias for the first time in Indian patients. The identification of Philadelphia chromosome (Ph)–like acute lymphoblastic leukemia (ALL) cases with NanoString nCounter digital‐barcoded gene expression profiling was examined in Indian patients. A higher incidence of Ph‐like ALL cases (32.05%) was identified. Furthermore, genomic and proteomic characterization of Ph‐like ALL cases was performed in Indian patients. This is the first report on the incidence and characterization of Ph‐like ALL cases from developing nations. [ABSTRACT FROM AUTHOR]

Methods: Forty pediatric (0–12 years) B-ALL DNA samples (20 paired Diagnosis-Relapse) and an additional six B-ALL DNA samples (without relapse at 3 years post treatment), as the non-relapse arm, were retrieved from the biobank for advanced genomic analysis. Deep sequencing (1050–5000X; mean 1600X) was performed using a custom NGS panel of 74 genes incorporating unique molecular barcodes. Results: A total 47 major clones (>25% VAF) and 188 minor clones were noted in 40 cases after bioinformatic data filtering. Of the forty-seven major clones, eight (17%) were diagnosis-specific, seventeen (36%) were relapse-specific and 11 (23%) were shared. In the control arm, no pathogenic major clone was noted in any of the six samples. The most common clonal evolution pattern observed was therapy-acquired (TA), with 9/20 (45%), followed by M-M, with 5/20 (25%), m-M, with 4/20 (20%) and unclassified (UNC) 2/20 (10%). The TA clonal pattern was predominant in early relapses 7/12 (58%), with 71% (5/7) having major clonal mutations in the NT5C2 or PMS2 gene related to thiopurine-dose response. In addition, 60% (3/5) of these cases were preceded by an initial hit in the epigenetic regulator, KMT2D. Mutations in common relapse-enriched genes comprised 33% of the very early relapses, 50% of the early and 40% of the late relapses. Overall, 14/46 (30%) of the samples showed the hypermutation phenotype, of which the majority (50%) had a TA pattern of relapse. Conclusions: Our study highlights the high frequency of early relapses driven by TA clones, demonstrating the need to identify their early rise during chemotherapy by digital PCR. [ABSTRACT FROM AUTHOR]

The patient was diagnosed as a case of FIP1L1-PDGFRA-positive myeloid neoplasm with T-LBL (stage IV disease) and was started on modified Berlin-Frankfurt-Münster 2000 protocol; and imatinib 100 mg was added from second week. A neoplasm with FIP1L1-PDGFRA fusion presenting as pediatric T-cell lymphoblastic leukemia/lymphoma without eosinophilia. "Likely to be missed if unsuspected": FIP1L1-PDGFRA positive myeloid neoplasm in a patient with nodal T-lineage lymphoblastic lymphoma. [Extracted from the article]

60% (6/10) with I BCR-ABL i SP like sp CGFs showed MRD positivity compared to 41.1% (23/56) of I BCR-ABL1 i SP pos sp B-ALLs. Summary of the diagnostic approach used to detect BCR-ABL1-like B-acute lymphoblastic leukemia associated chimeric gene fusions (BCR-ABL-like CGFs). I BCR-ABL1 i -like or Philadelphia chromosome-like B-acute lymphoblastic leukemia/lymphoma ( I BCR-ABL1 i SP like sp B-ALL) initially described based on gene expression profiles (GEP) is characterized by the presence of tyrosine-kinase inhibitor (TKI) targetable chimeric gene fusions (CGF), the spectrum of which is yet to be fully elucidated. The higher frequency of MRD positivity compared to I BCR-ABL1 i SP pos sp group (60% vs. 41%) can be explained by the inclusion of TKIs in treatment of I BCR-ABL1 i SP pos sp cases. [Extracted from the article]

Background: Chronic myeloid leukemia (CML) is a hematopoietic stem cell (SC) neoplasm diagnosed by the demonstration of t(9;22)(BCR‐ABL1) fusion gene. We performed a flow cytometric assay to identify CD26+ CML leukemic stem cells (LSCs) for its value as a standalone diagnostic investigation for CML and its utility for detection of residual disease in CML patients on therapy. Methods: Patients with clinical suspicion of CML/CML on follow‐up were included, and peripheral (PB) and/or bone marrow (BM) samples were utilized for flow cytometric analysis. PB and/or BM of patients with diseases other than CML were used as controls. A pre‐titrated antibody cocktail containing CD45, CD34, CD38, and CD26 MoABs was used. Results: A total of 104 samples (63 PB and 41 BM) from 64 patients [suspected CML (n = 30), CML on follow‐up (n = 15), and non‐CML (n = 19)] were tested. CD26+ LSCs were identified in all patients with a confirmed diagnosis of CML (median = 0.07 (range 0.002%–26.79%)). None of the patients in the control group (non‐CML) and follow‐up patients with negative reverse transcriptase‐polymerase chain reaction (RT‐PCR) results showed the presence of CD26+ LSCs. Also, there was a strong correlation between CD26+ CML LSCs in the PB and BM (r =.917). Conclusion: Flow cytometric identification of CD26+ LSCs in the peripheral blood can be a cheap, rapid, robust, and potential diagnostic tool for the diagnosis of CML compared to available testing methods. It is irrespective of BCR‐ABL1 transcript type, and its role in residual disease monitoring needs thorough investigation. [ABSTRACT FROM AUTHOR]

Background: Immunomagnetic cell sorting (IMCS) is a preferred technique for the enrichment of plasma cells (PC) before fluorescence in situ hybridization (FISH). Here, we share our real‐world experience regarding the success rate of IMCS, its limitations, and the utility of alternate sources to obtain a successful FISH in various PC disorders. Materials and Methods: A retrospective analysis was performed in patients with a PC neoplasm, who underwent bone marrow (BM) examination, and FISH testing over 30 months. In all cases with an unsuccessful IMCS, an attempt was made to identify the cause of failure. Results: Immunomagnetic cell sorting of PCs was successful in 395/450 cases (87.8%; 77/98 cases (78.6%) with <10% PCs and 318/352 (90.3%) with ≥10% PCs in BM aspirate; P =.003). Among cases with unsuccessful IMCS (<10% PCs; n = 21 and ≥10% PCs; n = 34), an alternate source could be used successfully in 34 (62%) patients and includes air‐dried trephine biopsy imprint smears (n = 28) with aggregates or sheets of PCs, fine‐needle aspiration smears/biopsy from plasmacytoma (n = 5), and ascitic fluid (n = 1). 284/395 (71.9%) patients with successful IMCS and all 34 cases with an alternate source of PCs showed at least one cytogenetic abnormality on four‐probe FISH. Conclusion: Variations in the sample quality together with significant variation in the number of PCs between BM aspirate and the trephine biopsy imprint smears/biopsy reduce the success rate of IMCS in a real‐world scenario and necessitate utilization of patient‐specific alternate sources of PCs like a trephine biopsy imprint or cytology smears from extramedullary sources for successful FISH testing in PC neoplasms. [ABSTRACT FROM AUTHOR]

Evaluation of pediatric hypereosinophilia (HE) is challenging, especially in the tropical developing countries, as appropriate diagnostic facilities may be lacking, parasitic/helminthic infections are common, and existing data on the etiology of severe eosinophilia are sparse. Second, data on long-term follow-up of these children including the temporal course of eosinophilia are also scarce. Besides, questions regarding the coexistence of multiple etiologies and their association with the severity of HE are largely unexplored. These challenges and questions often lead to diagnostic and therapeutic dilemmas. We highlight these difficulties utilizing a real-life clinical description. We emphasize the need for long-term follow-up of such children as HE may be the combinatorial effect of multiple etiologies, rather than a single cause. We also describe an unusual association of severe eosinophilia in a child with toxoplasmosis that was treated successfully with 8-week combination therapy with azithromycin and cotrimoxazole (sulfadiazine and pyrimethamine were not available). [ABSTRACT FROM AUTHOR]

The overexpression of cytokine receptor-like factor-2 (CRLF2) identified by anti-thymic stromal lymphopoietin receptor/TSLPR flow cytometry (FCM) has been reported as a screening tool for the identification of BCR-ABL1-like B-cell acute lymphoblastic leukemia/B-ALL with CRLF2 re-arrangement. TSLPR expression was studied prospectively in consecutive 478 B-ALLs (≤ 12 years (n = 244); 13–25 years (n = 129); > 25 years (n = 105)) and correlated with various hematological parameters and end-of-induction measurable residual disease (day 29; MRD ≥ 0.01% by 10-color FCM). TSLPR positivity in ≥ 10% leukemic cells was detected in 14.6% (n = 70) of B-ALLs. CRLF2 re-arrangement was detected in eight cases (11.4%) including P2RY8-CRLF2 (n = 6), and IgH-CRLF2 (n = 2) with a median TSLPR positivity of 48.8% and 99% leukemic cells, respectively. Recurrent gene fusions/RGF (BCR-ABL1 (17.1%); ETV6-RUNX1 (4.2%), TCF3-PBX1 (1.4%)), other BCR-ABL1-like chimeric gene fusions/CGFs (PDGFRB-rearrangement (2.9%), IgH-EPOR (1.4%)), CRLF2 extra-copies/hyperdiploidy (17.1%), and IgH translocation without a known partner (10%) were also detected in TSLPR-positive patients. CD20 positivity (52.9% vs 38.5%; p = 0.02) as well as iAMP21 (4.3% vs 0.5%; p = 0.004) was significantly more frequent in TSLPR-positive cases. TSLPR-positive patients did not show a significantly higher MRD, compared to TSLPR-negative cases (37% vs 33%). Increasing the threshold cut-off (from ≥ 10 to > 50% or > 74%) increased the specificity to 88% and 100% respectively in identifying CRLF2 translocation. TSLPR expression is not exclusive for CRLF2 translocations and can be seen with various other RGFs, necessitating their testing before its application in diagnostic algorithms. In patients with high TSLPR positivity (> 50%), the testing may be restricted to CRLF2 aberrancies, while patients with 10–50% TSLPR positivity need to be tested for both CRLF2- and non-CRLF2 BCR-ABL1-like CGFs. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Hyperferritinemia is increasingly associated with mortality in sepsis. Studies estimating the prevalence of hyperferritinemia in pediatric scrub typhus are limited. Methods: This was a secondary analysis of a prospective observational study (FERRIS) from a tertiary care teaching hospital in North India where 72 children with confirmed scrub typhus, 4 (5.5%) PCR positive, 55 (76.4%)-IgM ELISA positive, and 13 (18.1%)-both PCR and ELISA positive, were analyzed. Serum ferritin was measured in 62 children to identify the prevalence of hyperferritinemia and determine its association with mortality. Results: Hyperferritinemia (> 500 μg/L) was seen in 72.6% [n = 45] children; 26 (41.9%) were mild (500–2000 μg/L), 13 (21%) were moderate (2000–10,000 μg/L), and 6 (9.7%) were severe (> 10,000 μg/L). Early presentation to hospital (≤ 7 days of febrile illness) had more survivors than late presentation (> 7 days). Non-survivors had significantly higher PRISM III, PELOD-2, hyperlactatemia, hypoalbuminemia, organ dysfunction, need for mechanical ventilation, and need of RRT. Ferritin had poor sensitivity and specificity in predicting survival with AUC of 0.56. Organ dysfunction and risk scores as PRISM III, PELOD 2, and VIS at admission were better predictors with AUC (95% CI) of 0.72 (0.56, 0.89), 0.77 (0.63, 0.92), and 0.90 (0.78, 1.0) respectively. Conclusions: Hyperferritinemia is common in scrub typhus but it did not predict survival. Organ dysfunction and risk scores were better predictors of mortality than ferritin. [ABSTRACT FROM AUTHOR]

The article focuses on utility of fluorescence in situ hybridization testing in patients has suspected of myelodysplastic syndrome (MDS) or myelodysplastic syndrome/myeloproliferative neoplasm overlap (MDS/MPN) is limited in the absence of significant morphological dysplasia. Topics include the MDS/MPN are clonal disorders of hematopoietic stem cells has characterized by progression to acute myeloid leukemia, and the cytogenetic information is essential for their prognostic assessment.

The need for prognostication in chronic lymphocytic leukemia (CLL) is felt due to the heterogeneous clinical course of CLL, to counsel the patients, tailor follow-up, and to guide treatment decisions. There were predominantly CLL patients on wait and watch in our cohort compared to patients in the CLL-IPI cohort (48% I vs. i 19%, I p i <.0001). The CLL-IPI incorporating comprehensive patient data from prospective clinical trials were proposed in 2016 by a group of international CLL experts to be the standard of care in reporting of clinical trials and clinical practice. [Extracted from the article]

The article discusses that genetic abnormalities have significantly contributed to disease stratification in B‐ALL. It mentions the detection of iAMP21 can easily be achieved by multiplex ligation‐dependent probe amplification (MLPA); and also mentions that iAMP21 is reported to be a primary genetic event in B‐ALL subgroup arising due to complex structural rearrangements and is associated with a dismal outcome.

Objective: To evaluate the spectrum of genetic defects in Indian patients with unexplained erythrocytosis. Methods: Fifteen families (18 patients) with unexplained erythrocytosis were enrolled after excluding polycythemia vera and secondary erythrocytosis. Focused Sanger sequencing from genomic DNA was performed for EPOR (exon 8), VHL (exons 2‐3), EGLN1 (exons 2‐5), EPAS1 (exon 12), and all exons of HBB, HBA1, and HBA2 genes. Results: Eleven of the 18 patients (including two pairs of brothers) had Chuvash polycythemia, that is, homozygosity for VHL:c.598C > T (p.Arg200Trp). Three patients (two of whom were brothers) had HBB mutations associated with increased oxygen‐affinity hemoglobin—one had a heterozygous Hb McKees Rocks HBB:c.438T > A (p.Tyr146*), and two brothers showed heterozygous Hb Rainier HBB:c.437A > G (p.Tyr146Cys). No pathogenic variants were found in the remaining four cases. Conclusion: A gene‐by‐gene Sanger sequencing approach could determine a genetic basis for erythrocytosis in 11 of the 15 (73%) Indian families, with homozygous VHL:c.598C > T (p.Arg200Trp) being the commonest pathogenic variant. This first study from the Indian subcontinent provides a rationale for analyzing this variant in patients with suspected congenital erythrocytosis from this region. Rare first occurrences of Hb McKees Rocks and Hb Rainier in Indians are also being reported. [ABSTRACT FROM AUTHOR]

Drug rash, eosinophilia, and systemic symptoms ( DRESS) syndrome is a severe systemic hypersensitivity reaction that usually occurs within 6 weeks of exposure to the offending drug. Diagnosis is usually straightforward in patients with pyrexia, skin rash, hepatitis, and eosinophilia with a preceding history of exposure to agents often associated with DRESS syndrome, such as aromatic anticonvulsants and sulfa drugs, but diagnosis of DRESS may still be a challenge. We report a 4-year-old child with probable DRESS syndrome complicated by multiple hematologic complications that developed 1 month after exposure to fluoxetine, a drug not known to be associated with such severe reactions. [ABSTRACT FROM AUTHOR]

Primitive neuroectodermal tumors of the cervix are very rare. A 28-year-old pregnant woman presented with a cervical mass. The tumor was staged as IB2. The biopsy from tumor was suggestive of malignant small round cell tumor. She then underwent termination of pregnancy followed by radical hysterectomy. Based on morphologic and immunohistochemical profile, a diagnosis of peripheral primitive neuroectodermal tumor of the cervix was made. The patient received adjuvant chemotherapy and radiotherapy. The patient is alive and disease-free 33 months post-surgery. The present case highlights the importance of keeping primitive neuroectodermal tumors in the differential diagnosis of small cell neoplasms of the uterine cervix. Pregnancy should not be a barrier to early detection and treatment of this potentially aggressive tumor. The optimal treatment methods have not yet been established because of the rarity of the tumor. [ABSTRACT FROM AUTHOR]