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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]

Introduction: mSMART classifies high-risk Multiple Myeloma patients into Double Hit and Triple Hit Myeloma (DH/THM) on the basis of the number of high-risk cytogenetic abnormalities detected. We aimed to study the clinical profile and outcomes of patients with DH/THM detected at relapse in a real-world setting. Methods: The case records of all relapsed multiple myeloma patients with DH/THM diagnosed between January 2018 and December 2020 were identified and information regarding baseline characteristics, therapy and outcomes was noted. Results: Seventeen patients were diagnosed with DH/THM at relapse during the study period. Twelve patients (70.6%) were in first relapse, while 3 patients were diagnosed at second relapse and 1 patient each at 3rd and 5th relapse respectively. The most common cytogenetic combination was IgH-FGFR3 translocation with gain of 1q (seen in 10 patients; 58.8%). Ten patients (58.8%) died within the first 2 months of diagnosis and 16 patients (94.1%) died during follow up (range 0–16 months). The most common cause of death was progressive/active disease (9 patients, 56.3%). Discussion: The outcome of DH/THM at relapse is associated with an aggressive presentation and poor outcomes in the real-world setting. These patients are candidates for early aggressive or novel therapy or clinical trials. [ABSTRACT FROM AUTHOR]

Pediatric HIV is a significant contributor to childhood morbidity and mortality. As HIV infects bone marrow CD34-positive progenitor cells, the hematological abnormalities are well-expected. The viral load is much higher in children predisposing them to opportunistic infections and hematopoietic malignancies. The present study aimed to determine the spectrum of hematological abnormalities that may yield clinically useful information in HIV-infected children. This was a retrospective study of 19 HIV-infected children who underwent bone marrow examination. Overall, 20 peripheral blood and bone marrow samples were analyzed for morphological changes in all hematopoietic lineages. Immunohistochemistry was performed on trephine biopsy sections for evaluation of B and T cells and cytomegalovirus inclusions. Anemia was the most common cytopenia (95%), followed by thrombocytopenia (45%) and leukopenia (40%). Myelodysplasia was noted in 70% of cases. Dysmegakaryopoiesis was predominant in 65% of cases, while dyserythropoiesis was noted in 25% of cases. Hemophagocytosis and reactive cellular changes were noted in 20% of cases each. Benign lymphoid aggregates and granulomatous inflammation were observed in 15% and 10% of cases, respectively. Significant myelofibrosis was found in 35% of cases. One case showed infiltration by Burkitt lymphoma. Parvoviral inclusions were identified in 1 case. An interstitial increase and aggregates of CD8 + T cells and reduced CD4 + T cells were noted. CD20 + B cells were normal to mildly increased in the bone marrow. Bone marrow examination provides clinically significant information in pediatric HIV revealing the underlying cause of hematopoietic abnormalities and allows the exclusion of major hematological neoplasms. [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]

To report the efficacy, safety, and quality of life (QoL) on generic and innovator ibrutinib in Indian CLL patients. This was a single centre, prospective study of treatment-naive (TN), and relapsed/refractory (R/R) CLL patients receiving ibrutinib in India. The choice of innovator or generic ibrutinib was as per patient discretion. Response and adverse events were recorded as per the 2018 iwCLL guidelines and CTCAEv4.0. QoL was assessed using the EORTC QLQ-C30 and CLL17 questionnaires. A total of 32 CLL patients (TN, n = 7 and R/R, n = 25) received ibrutinib from 2016–2019. The median age was 60 years (37–84). All TN patients attained partial response without any grade 3/4 adverse events (AE). Ibrutinib was less tolerated in the R/R setting, with 52% patients developing grade 3/4 AE and required dose reduction. Eleven patients (44%) died during follow-up. Grade 3–5 infections were seen in 44% of R/R CLL patients. Generic ibrutinib (n = 8) was comparable to innovator ibrutinib (n = 17) in terms of efficacy, safety, and QoL. Ibrutinib is less well tolerated in Indian R/R CLL patients. Infections are a common cause of morbidity and mortality. This study affirms the safety and efficacy of generic ibrutinib. [ABSTRACT FROM AUTHOR]

To study the clinico-haematological and histopathological characteristics of FIP1L1-PDGFRA rearranged hypereosinophilia/hypereosinophilic syndrome (F/P+ve HE/HES), a retrospective analysis of patients with F/P+ve HE diagnosed over a period of 43 months was performed. Peripheral blood smears, bone marrow aspirate (BMA) and biopsies (BMB) were reviewed in each case and; reticulin stain and immunohistochemistry for mast cell tryptase (MCT) and CD117 was performed. F/P+ve HE was diagnosed in a total of ten patients during study period. All patients were males with a median age of 36 years (23–44 years). The median duration of presenting complaints was 7 months (2 months–3 years) which included specific symptoms related to various organs (80% of cases). Anaemia, thrombocytopenia and splenomegaly were seen in 60%, 50% and 90% of the cases respectively. Mastocytosis was not obvious in BMA but identified by MCT on BMB in all cases. Myelofibrosis (grade ≥ 1) was seen in 80% of the cases and includes multifocal paratrabecular fibrosis in 50% of the biopsies. Our study shows that bone marrow mastocytosis and myelofibrosis are very useful morphological indicators to suspect F/P+ve HE and suggests the routine use of reticulin staining and MCT immunohistochemistry in all BMBs performed for the evaluation of HE/HES. [ABSTRACT FROM AUTHOR]

The Antiphospholipid Syndrome (APS) is classified based on the presence of both clinical and laboratory criteria. Both sets of criteria are subject to much review and intense research as it is becoming increasingly clear that no single test is specific for defining this autoimmune disorder. A number of leading international bodies have released guidelines in an attempt to improve the laboratory testing and reporting. The current review is an appraisal of some of the literature pertaining to the laboratory testing. [ABSTRACT FROM AUTHOR]

We report a rare CD5 positive B cell acute lymphoblastic leukemia (B-ALL) with a review of the clinopathological features and prognosis of previously reported cases in the literature. The aberrant expression of CD 5 antigen is uncommon in B-ALL; the morphological differential diagnosis includes blastic mantle cell lymphoma, denovo CD5 diffuse large B cell lymphoma and secondary diffuse large cell lymphoma/Richter's transformation. CD5 B cell ALL is commonly reported in younger patients (<18 years). Though the expression of T cell antigens is reported to have poor prognosis, the experience with CD5 B-ALL is limited to draw any firm conclusion regarding its prognosis. [ABSTRACT FROM AUTHOR]

Indolent γδ T cell lymphomas/leukemias are rare and overlap with the morphological spectrum of large granular lymphocyte (LGL) leukemia. We report an extremely rare case of CD103(+) γδ T LGL leukemia in a patient with celiac disease who presented with refractory diarrhea. Whether the refractory diarrhea in our patient was a manifestation of LGL leukemia itself or whether the clonal LGL expansion is a manifestation of refractory celiac disease (RCD) remains an enigma. This report highlights the diagnostic difficulties and the need of consensus in categorizing clonal CD103(+) lymphocytosis in patients with RCD. [ABSTRACT FROM AUTHOR]

Background: Several polyposis syndromes of the gastrointestinal tract have been recognized which carry increased risk for cancer and have a genetic predisposition. There is a paucity of literature regarding the occurrence and the burden of colonic polyposis syndromes in the Indian subcontinent. This study attempts to highlight this hitherto unaddressed burden and the associated increased risk for inherited colonic cancer in this geographical location. Methods: A retrospective study of various colonic polyposis syndromes encountered at a tertiary centre in South India over a period of 8 years (2005 to 2012) was performed. The diagnosis in each case was made histologically with clinicopathological correlation. Results: Fifty cases were identified as belonging to a colonic polyposis syndrome, during the study period. There were 27 males and 23 females with a median age of 36.5 years (range 19 months to 78 years). The commonest syndrome was familial adenomatous polyposis ( n = 27; 54 %) followed by Peutz-Jeghers syndrome ( n = 11), attenuated familial adenomatous polyposis ( n = 7), juvenile polyposis syndrome ( n = 3), hyperplasic polyposis syndrome ( n = 1) and Cronkhite-Canada syndrome ( n = 1). Colonic malignancy was documented at first presentation in 22 patients (44 %). Conclusions: Our study highlights the various colonic polyposis syndromes encountered in a tertiary care institution in Southern India. [ABSTRACT FROM AUTHOR]

Myeloma cells are known to show varied morphology and various types of nuclear or cytoplasmic inclusions. There are a few reports of myeloma with presence of pseudo-Gaucher type histiocytes; however myeloma cells itself resembling storage histiocytes is distinctly uncommon. We report images of plasma cells resembling storage cells from a case of IgG/lambda plasma cell myeloma. Hematopathologist must be aware of such varied morphology of plasma cells especially while dealing with extra medullary plasmacytomas. [ABSTRACT FROM AUTHOR]

Competing Interests: Authors' Disclosures of Potential Conflicts of Interest: No potential conflicts of interest relevant to this article were reported.