Blood
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Adoptive T-cell therapy with anti-CD19 chimeric antigen receptor (CAR)-expressing T cells is a new approach for treating advanced B-cell malignancies. To evaluate anti-CD19-CAR-transduced T cells in a murine model of adoptive T-cell therapy, we developed a CAR that specifically recognized murine CD19. We used T cells that were retrovirally transduced with this CAR to treat mice bearing a syngeneic lymphoma that naturally expressed the self-antigen murine CD19. ⋯ The antilymphoma efficacy of anti-CD19-CAR-transduced T cells was critically dependent on irradiation of mice before anti-CD19-CAR-transduced T-cell infusion. Anti-CD19-CAR-transduced T cells had superior antilymphoma efficacy compared with the anti-CD19 monoclonal antibody from which the anti-CD19 CAR was derived. Our results demonstrated impressive antilymphoma activity and profound destruction of normal B cells caused by anti-CD19-CAR-transduced T cells in a clinically relevant murine model.
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Systematic reviews and meta-analyses are being increasingly used to summarize medical literature and identify areas in which research is needed. Systematic reviews limit bias with the use of a reproducible scientific process to search the literature and evaluate the quality of the individual studies. If possible the results are statistically combined into a meta-analysis in which the data are weighted and pooled to produce an estimate of effect. This article aims to provide the reader with a practical overview of systematic review and meta-analysis methodology, with a focus on the process of performing a review and the related issues at each step.
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Long-term survival is now an expected outcome after hematopoietic cell transplantation (HCT). However, the burden of morbidity long-term after HCT remains unknown. We examined the magnitude of risk of chronic health conditions reported by 1022 HCT survivors and their siblings (n = 309). ⋯ HCT survivors were twice as likely as siblings to develop a chronic condition (95% CI, 1.6-2.1), and 3.5 times to develop severe/life-threatening conditions (95% CI, 2.3-5.4). HCT survivors with chronic graft-versus-host disease were 4.7 times as likely to develop severe/life-threatening conditions (95% CI, 3.0-7.2). The burden of long-term morbidity borne by HCT survivors is substantial, and long-term follow-up of patients who received transplantation is recommended.
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Here we report the first application of a fractal analysis of the viscoelastic properties of incipient blood clots. We sought to ascertain whether the incipient clot's fractal dimension, D(f,) could be used as a functional biomarker of hemostasis. The incipient clot is formed at the gel point (GP) of coagulating blood, the GP demarcating a functional change from viscoelastic liquid to a viscoelastic solid. ⋯ Our study reveals that unfractionated heparin not only prolongs the onset of clot formation but has a significant effect on its fractal microstructure. A progressive increase in unfractionated heparin concentration results in a linear decrease in D(f) and a corresponding prolongation in T(GP). The results represent a new, quantitative measure of clot quality derived from measurements on whole blood samples.
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The World Health Organization classification of acute myeloid leukemia (AML) is hierarchically structured and integrates genetics, data on patients' history, and multilineage dysplasia (MLD). The category "AML with myelodysplastic syndrome (MDS)-related changes" (AML-MRC) is separated from "AML not otherwise specified" (AML-NOS) by presence of MLD, MDS-related cytogenetics, or history of MDS or MDS/myeloproliferative neoplasm (MPN). We analyzed 408 adult patients categorized as AML-MRC or AML-NOS. ⋯ Contrarily, patients with AML-NOS combined with AML-MLD-sole (n = 323) had better 3-year EFS (16.9 vs 10.7 months; P = .005) and 3-year OS (55.8% vs 32.5%; P = .001) than patients with history of MDS or MDS/MPN or MDS-related cytogenetics (n = 85). Gene expression analysis showed distinct clusters for AML-MLD-sole combined with AML-NOS versus AML with MDS-related cytogenetics or MDS history. Thus, MLD alone showed no independent clinical effect, whereas cytogenetics and MDS history were prognostically relevant.