Resolution of Anterior Uveal Infiltration of Acute Lymphoblastic Leukemia After Chimeric Antigen Receptor T-Cell Therapy.

To present a case of acute B-cell lymphoblastic leukemia (B-ALL) ocular relapse treated with chimeric antigen receptor T-cell (CAR T) therapy. A retrospective case review was evaluated. A 69-year-old woman with a history of BALL presented with bilateral hypopyons and 3+ anterior chamber cells that responded to topical prednisolone.

Clonal Dynamics and Relapse Risk Revealed by High-Sensitivity FLT3-Internal Tandem Duplication Detection in Acute Myeloid Leukemia.

The ability to detect low-level disease is key to our understanding of clonal heterogeneity in acute myeloid leukemia (AML) and residual disease that elude conventional assays and seed relapse. We developed a high-sensitivity next-generation sequencing (HS-NGS) clinical assay, able to reliably detect low levels (1 × 10) of FLT3-ITD, a frequent, therapeutically targetable and prognostically relevant mutation in AML. By applying this assay to 289 longitudinal samples from 62 patients at initial diagnosis and/or clinical follow-up (mean follow-up of 22 months), we reveal the frequent occurrence of FLT3-ITD subclones at diagnosis and demonstrate a significantly decreased relapse risk when FLT3-ITD is cleared after induction or thereafter.

Side scatter ratio of the CD105-positive and CD105-negative red blood cell fractions is useful for the detection of low-grade myelodysplastic neoplasms by flow cytometry.

Objectives: We assessed the utility of red blood cell (RBC) CD105 and side scatter (SSC) parameters by flow cytometry for the detection of low-grade myelodysplastic neoplasms (MDS) in bone marrow specimens.

Methods: Ten RBC parameters incorporating CD105 or SSC combined with the Meyerson-Alayed scoring system (MASS) metrics were retrospectively evaluated by flow cytometry for utility in detecting low-grade MDS (n = 56) compared with cytopenic controls (n = 86).

Results: Myelodysplastic neoplasms were associated with 7 of the RBC parameters in univariate analysis.

IGJ and SPATS2L immunohistochemistry sensitively and specifically identify BCR::ABL1+ and BCR::ABL1-like B-acute lymphoblastic leukaemia.

Therapeutic management and prognostication for patients with B-acute lymphoblastic leukaemia (B-ALL) require appropriate disease subclassification. BCR::ABL1-like B-ALL is unique in that it is defined by a gene expression profile similar to BCR::ABL1+ B-ALL rather than a unifying recurrent translocation. Current molecular/cytogenetic techniques to identify this subtype are expensive, not widely accessible, have long turnaround times and/or require an adequate liquid biopsy.

Aggressive Lymphoplasmacytic Neoplasm With an Unusual In-frame Deletion of Associated With and Mutations and Complex Karyotype.

Lymphoplasmacytic lymphoma often needs to be differentiated from other B-cell lymphomas with plasmacytic differentiation, especially marginal zone cell lymphoma. Molecular detection of p.L265P hotspot mutation supports the diagnosis of lymphoplasmacytic lymphoma since it is seen in about 90% of such lymphoma, which is much higher than other B-cell lymphomas.

Mucin 4 protein is expressed in B-acute lymphoblastic leukemia and is restricted to BCR::ABL1-positive and BCR::ABL-like subtypes.

Mucin 4 (MUC4) is a transmembrane mucin that, like most mucins, is not expressed in normal hematopoietic cells, but little is known about its expression in malignant hematopoiesis. B-acute lymphoblastic leukemia (B-ALL) consists of genetically distinct disease subtypes with similarities and differences in gene expression most frequently studied at the mRNA level, which is less amenable to widespread routine clinical use. Here, we demonstrate using immunohistochemistry (IHC) that MUC4 protein is expressed in less than 10% of B-ALL, with expression restricted to BCR::ABL1+ and BCR::ABL1-like (CRLF2 rearranged) subtypes of B-ALL (4/13, 31%).

Monoclonal B-cell lymphocytosis in the bone marrow: revisiting the criteria for chronic lymphocytic leukemia/small lymphocytic lymphoma.

Monoclonal B-cell lymphocytosis is a clonal B-cell population in the peripheral blood (PB) of <5x10ˆ9/L without extramedullary (EM) disease, often with a chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) phenotype. The degree of bone marrow (BM) involvement is not currently a part of the diagnostic criteria for MBL or CLL/SLL, but CLL-type MBLs in BM can be seen in patients lacking PB lymphocytosis. Data are limited on the outcome of such cases.

Identification of a Cancer-Predisposing Germline p.Ile49Metfs*7 Variant by Targeted Sequencing of a Splenic Marginal Zone Lymphoma.

Germline disruptive variants in () predispose to a wide variety of cancers, including melanoma, chronic lymphocytic leukemia (CLL), Hodgkin lymphoma, myeloproliferative neoplasms, and glioma. We report the first case of splenic marginal zone lymphoma (SMZL) arising in a patient with a germline variant: a 65-year-old male with an extensive history of cancer, including melanoma and papillary thyroid carcinoma, who presented with circulating atypical lymphocytosis. Bone marrow biopsy revealed 20% involvement by a CD5CD10 B-cell lymphoma that was difficult to classify.

Clinical Utility of Targeted Next-Generation Sequencing in the Evaluation of Low-Grade Lymphoproliferative Disorders.

Objectives: We investigated the usefulness of a custom-designed 31-gene next-generation sequencing (NGS) panel implemented on a routine basis for the evaluation of low-grade lymphoproliferative disorders (LPDs).

Methods: In total, 147 blood, bone marrow, and tissue specimens were sequenced, including 81% B-cell, 15% T-cell, and 3% natural killer (NK)-cell neoplasms.

Results: Of the cases, 92 (63%) of 147 displayed at least one pathogenic variant while 41 (28%) of 147 had two or more.

Clonal cytopenia of undetermined significance (CCUS) with dysplasia is enriched for MDS-type molecular findings compared to CCUS without dysplasia.

Objectives: Although morphologic dysplasia is not typically considered a feature of CCUS, we have consistently observed low-level bone marrow (BM) dysplasia among CCUS patients. We sought to determine whether sub-diagnostic BM dysplasia in CCUS patients is associated with other clinico-pathologic findings of myelodysplastic syndrome (MDS).

Methods: We identified 49 CCUS patients, 25 with sub-diagnostic dysplasia (CCUS-D), and 24 having no dysplasia (CCUS-ND).

Myeloid skewing in murine autoimmune arthritis occurs in hematopoietic stem and primitive progenitor cells.

Skewing toward myeloid cell production is often observed in chronic inflammation and autoimmune diseases. Herein, we determined whether persistent myeloid activation and proinflammatory output occurring in pathologic conditions is at the level of hematopoietic stem and primitive progenitor cells (HSPPCs). By using a mouse arthritis model, we found that even though HSPPCs in arthritis still retained the capacity to differentiate into different lineages, they acquired enhanced in vitro and in vivo propensity in a disease-dependent manner to generate myeloid cells, the key perpetrators of tissue damage in arthritis.

Defects in osteoblast function but no changes in long-term repopulating potential of hematopoietic stem cells in a mouse chronic inflammatory arthritis model.

Recent studies support the notion that there is an intricate relationship between hematopoiesis and bone homeostasis in normal steady states. Using mice undergoing chronic inflammatory arthritis, we investigated the relationship between hematopoiesis and bone homeostasis in pathologic conditions. We demonstrate that mice undergoing chronic inflammatory arthritis displayed osteoporosis resulting from a severe defect in osteoblast function.