Chimeric antigen receptor (CAR) T cells provide a promising approach to the treatment of hematologic malignancies and solid tumors. Flow cytometry is a powerful analytical modality, which plays an expanding role in all stages of CAR T therapy, from lymphocyte collection, to CAR T cell manufacturing, to in vivo monitoring of the infused cells and evaluation of their function in the tumor environment. Therefore, a thorough understanding of the new directions is important for designing and implementing CAR T-related flow cytometry assays in the clinical and investigational settings.
View Article and Find Full Text PDFBackground: Outcomes for patients with relapsed/refractory acute myeloid leukemia (R/R AML) remain poor. Novel therapies specifically targeting AML are of high interest. Brentuximab vedotin (BV) is an antibody-drug conjugate that is specific for human CD30.
View Article and Find Full Text PDFChimeric antigen receptor (CAR) T cells have emerged as a novel form of treatment of patients with B-cell malignancies. In particular, anti-CD19 CAR T-cell therapy has effected impressive clinical responses in B-cell acute lymphoblastic leukemia and diffuse large B-cell lymphoma. However, not all patients respond, and relapse with antigen loss has been observed in all patient subsets.
View Article and Find Full Text PDFBackground: The underlying biological mechanism in the formation of adverse local tissue reaction in taper corrosion of total hip arthroplasty (THA) remains unknown. This study evaluated whether there was a dose-dependent relationship between metal ion levels, intraoperative tissue damage and ALVAL (aseptic lymphocyte-dominated vasculitis-associated lesion) scores in dual taper THA patients who underwent revisions for taper corrosion.
Methods: We performed a retrospective review of 31 dual taper THA patients who underwent revision surgery from May 2013 to October 2013.
Although chronic inflammatory disorders of the ocular adnexa are relatively common, their pathogenesis is in many cases poorly understood. Recent investigation suggests that many cases of sclerosing orbital inflammation are a manifestation of IgG4-related disease; however, most patients reported have been Asian, and it is not clear whether the results of studies from the Far East can be reliably extrapolated to draw conclusions about Western patients. We evaluated 38 cases previously diagnosed as orbital inflammatory pseudotumor or chronic dacryoadenitis to determine whether our cases fulfill the criteria for IgG4-RD (IgG4-related dacryoadenitis when involving the lacrimal gland, and IgG4-related sclerosing orbital inflammation when involving orbital soft tissue).
View Article and Find Full Text PDFAs the technology of cytometry matures, there is mounting pressure to address two major issues with data analyses. The first issue is to develop new analysis methods for high-dimensional data that can directly reveal and quantify important characteristics associated with complex cellular biology. The other issue is to replace subjective and inaccurate gating with automated methods that objectively define subpopulations and account for population overlap due to measurement uncertainty.
View Article and Find Full Text PDFBackground: Human progenitor and B-cell development is a highly regulated process characterized by the ordered differential expression of numerous cell-surface and intracytoplasmic antigens. This study investigates the underlying coordination of these modulations by examining a series of normal bone marrow samples with the method of probability state modeling or PSM.
Results: The study is divided into two sections.
Flow cytometry (FCM) is an adjunct study to routine analysis of cerebrospinal fluid (CSF) to investigate for involvement by a hematologic malignancy. However, in our experience, FCM only infrequently detects abnormalities in CSF. To help optimize resources without forfeiting clinically important data, we sought to determine evidence-based indications and criteria for performing FCM on CSF.
View Article and Find Full Text PDFThe zinc finger transcriptional repressor Gfi-1b is essential for erythroid and megakaryocytic development in the embryo. Its roles in the maintenance of bone marrow erythropoiesis and thrombopoiesis have not been defined. We investigated Gfi-1b's adult functions using a loxP-flanked Gfi-1b allele in combination with a novel doxycycline-inducible Cre transgene that efficiently mediates recombination in the bone marrow.
View Article and Find Full Text PDFGraft-versus-host disease (GVHD) is a donor T cell driven response against host tissue that can complicate allogeneic hematopoietic stem cell transplantation (HSCT). During acute GVHD, endogenous adjuvants such as uric acid are released by damaged host tissue, activating alloreactive donor T cells. A phase I study was conducted at the Massachusetts General Hospital between 2007 and 2010 to test the hypothesis that reduction of uric acid levels during allogeneic HSCT can modulate the development of acute GVHD.
View Article and Find Full Text PDFWithin the last 25 years, flow cytometry and fluorescence-activated cell sorting have emerged as both routine diagnostic tools in clinical medicine and as advanced analytic tools critical in performing scientific research. This chapter aims at summarizing the use of flow cytometry in benign and malignant hematology and the monitoring of inherited and acquired immunodeficiency states. Numerous figures are provided from our laboratories at Massachusetts General Hospital that illustrate examples of these conditions.
View Article and Find Full Text PDFCells of the osteoblast lineage play an important role in regulating the hematopoietic stem cell (HSC) niche and early B-cell development in animal models, perhaps via parathyroid hormone (PTH)-dependent mechanisms. There are few human clinical studies investigating this phenomenon. We studied the impact of long-term daily teriparatide (PTH 1-34) treatment on cells of the hematopoietic lineage in postmenopausal women.
View Article and Find Full Text PDFBackground: B-cell lymphomas with concurrent translocations of MYC and BCL2 or BCL6, also known as "double-hit" lymphomas (DHL), are rare malignancies characterized by aggressive clinical behavior and poor prognosis. Previous reports suggest that decreased CD20 and/or CD19 expression by flow cytometry is relatively common in DHL and may help to identify cases requiring additional cytogenetic analysis.
Methods: We conducted a retrospective analysis of 26 cases of DHL, and compared their flow cytometric characteristics to cases of Burkitt lymphoma (BL) and diffuse large B-cell lymphoma (DLBCL).
The hematopoietic stem cell (HSC) niche is involved in the maintainance and regulation of quiescence, self-renewal and differentiation of hematopoietic stem cells and the fate of their progeny in mammals dealing with the daily stresses to the hematopoietic system. From the discovery that perturbations of the HSC niche can lead to hematopoietic disorders, we have now arrived at the prospect that the HSC niche may play a role in hematological malignancies and that this HSC niche may be a target for therapy. This review attempts to capture the discoveries of the last few years regarding the normal and malignant hematopoietic stem cell niche and possible ways to target this niche.
View Article and Find Full Text PDFImmune responses are modified by a diverse and abundant repertoire of carbohydrate structures on the cell surface, which is known as the glycome. In this study, we propose that a unique glycome that can be identified through the binding of galectin-4 is created on local, but not systemic, memory CD4+ T cells under diverse intestinal inflammatory conditions, but not in the healthy state. The colitis-associated glycome (CAG) represents an immature core 1-expressing O-glycan.
View Article and Find Full Text PDFBackground: Although platelets (PLTs) are known to express ABH antigens, the extent of expression is different on PLTs compared with red blood cells and the relationship between PLT ABH expression and genotype has not been thoroughly investigated.
Study Design And Methods: We measured blood group H and A antigens on PLTs from 100 normal volunteers using fluorescent-conjugated reagents and flow cytometry. Individuals were also genotyped at the ABO locus using a commercially available genotyping system.
Women with late-stage ovarian cancer usually develop chemotherapeutic-resistant recurrence. It has been theorized that a rare cancer stem cell, which is responsible for the growth and maintenance of the tumor, is also resistant to conventional chemotherapeutics. We have isolated from multiple ovarian cancer cell lines an ovarian cancer stem cell-enriched population marked by CD44, CD24, and Epcam (3+) and by negative selection for Ecadherin (Ecad-) that comprises less than 1% of cancer cells and has increased colony formation and shorter tumor-free intervals in vivo after limiting dilution.
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