المؤلفون: Vijaya Chaturvedi, Carl E. Allen, Hector R. Wong, Michelle L. Hermiston, Jay Greenberg, Stephan Ladisch, Jordana Goldman, Michael M. Henry, Trung C. Nguyen, Vandana Chaturvedi, Rebecca A. Marsh, Ahmed Naqvi, Erika Owsley, Michael Jeng, Michael B. Jordan, Adi Zoref-Lorenz

المصدر: Blood. 137:2337-2346

مصطلحات موضوعية: Adult, Male, endocrine system, Adolescent, T cell, Immunology, CD8-Positive T-Lymphocytes, Lymphocyte Activation, Biochemistry, Lymphohistiocytosis, Hemophagocytic, Diagnosis, Differential, Sepsis, Young Adult, Immune system, hemic and lymphatic diseases, Immunopathology, medicine, Humans, Child, Hemophagocytic lymphohistiocytosis, Membrane Glycoproteins, business.industry, Infant, HLA-DR Antigens, Cell Biology, Hematology, medicine.disease, ADP-ribosyl Cyclase 1, Phenotype, medicine.anatomical_structure, Case-Control Studies, Child, Preschool, Female, Cytokine Release Syndrome, business, Cytokine storm, CD8

الوصف: Hemophagocytic lymphohistiocytosis (HLH) is a fatal disorder of immune hyperactivation that has been described as a cytokine storm. Sepsis due to known or suspected infection has also been viewed as a cytokine storm. Although clinical similarities between these syndromes suggest similar immunopathology and may create diagnostic uncertainty, distinguishing them is critical as treatments are widely divergent. We examined T-cell profiles from children with either HLH or sepsis and found that HLH is characterized by acute T-cell activation, in clear contrast to sepsis. Activated T cells in patients with HLH were characterized as CD38high/HLA-DR+ effector cells, with activation of CD8+ T cells being most pronounced. Activated T cells were type 1 polarized, proliferative, and displayed evidence of recent and persistent activation. Circulating activated T cells appeared to be broadly characteristic of HLH, as they were seen in children with and without genetic lesions or identifiable infections and resolved with conventional treatment of HLH. Furthermore, we observed even greater activation and type 1 polarization in tissue-infiltrating T cells, described here for the first time in a series of patients with HLH. Finally, we observed that a threshold of >7% CD38high/HLA-DR+ cells among CD8+ T cells had strong positive and negative predictive value for distinguishing HLH from early sepsis or healthy controls. We conclude that the cytokine storm of HLH is marked by distinctive T-cell activation whereas early sepsis is not, and that these 2 syndromes can be readily distinguished by T-cell phenotypes.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::dde66b5af7239cec550b4ec6de47b0d3Test
https://doi.org/10.1182/blood.2020009499Test

المؤلفون: David A. Jacobsohn, Christine Duncan, Giorgos Bakoyannis, Francis Pike, Jamie L. Renbarger, Robert A. Krance, Kenneth R. Cooke, Conrad Russell Y. Cruz, Paul A. Carpenter, Courtney M. Rowan, Sherif S. Farag, Samir M. Hanash, Hao Liu, Sophie Paczesny, Catherine M. Bollard, Abhijeet Malatpure

المصدر: Blood. 135:1428-1437

مصطلحات موضوعية: Adult, Male, medicine.medical_specialty, Adolescent, Immunology, Graft vs Host Disease, Biochemistry, Adult age, Young Adult, Risk Factors, Internal medicine, Biomarkers, Tumor, medicine, Humans, Prospective Studies, Child, Prospective cohort study, Aged, business.industry, Hazard ratio, Age Factors, Hematopoietic Stem Cell Transplantation, Infant, Newborn, Infant, Cell Biology, Hematology, Middle Aged, Prognosis, medicine.disease, Interleukin-1 Receptor-Like 1 Protein, Confidence interval, Survival Rate, Transplantation, Graft-versus-host disease, Child, Preschool, Hematologic Neoplasms, Cohort, Biomarker (medicine), Female, Neoplasm Recurrence, Local, business, Follow-Up Studies

الوصف: Assessment of prognostic biomarkers of nonrelapse mortality (NRM) after allogeneic hematopoietic cell transplantation (HCT) in the pediatric age group is lacking. To address this need, we conducted a prospective cohort study with 415 patients at 6 centers: 170 were children age 10 years or younger and 245 were patients older than age 10 years (both children and adults were accrued from 2013 to 2018). The following 4 plasma biomarkers were assessed pre-HCT and at days +7, +14, and +21 post-HCT: stimulation-2 (ST2), tumor necrosis factor receptor 1 (TNFR1), regenerating islet–derived protein 3α (REG3α), and interleukin-6 (IL-6). We performed landmark analyses for NRM, dichotomizing the cohort at age 10 years or younger and using each biomarker median as a cutoff for high- and low-risk groups. Post-HCT biomarker analysis showed that ST2 (>26 ng/mL), TNFR1 (>3441 pg/mL), and REG3α (>25 ng/mL) are associated with NRM in children age 10 years or younger (ST2: hazard ratio [HR], 9.13; 95% confidence interval [CI], 2.74-30.38; P = .0003; TNFR1: HR, 4.29; 95% CI, 1.48-12.48; P = .0073; REG3α: HR, 7.28; 95% CI, 2.05-25.93; P = .0022); and in children and adults older than age 10 years (ST2: HR, 2.60; 95% CI, 1.15-5.86; P = .021; TNFR1: HR, 2.09; 95% CI, 0.96-4.58; P = .06; and REG3α: HR, 2.57; 95% CI, 1.19-5.55; P = .016). When pre-HCT biomarkers were included, only ST2 remained significant in both cohorts. After adjustment for significant covariates (race/ethnicity, malignant disease, graft, and graft-versus-host-disease prophylaxis), ST2 remained associated with NRM only in recipients age 10 years or younger (HR, 4.82; 95% CI, 1.89-14.66; P = .0056). Assays of ST2, TNFR1, and REG3α in the first 3 weeks after HCT have prognostic value for NRM in both children and adults. The presence of ST2 before HCT is a prognostic biomarker for NRM in children age 10 years or younger allowing for additional stratification. This trial was registered at www.clinicaltrials.gov as #NCT02194439.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::7737622ba67c6716c0751fb431b8532cTest
https://doi.org/10.1182/blood.2019002334Test

المؤلفون: Ashish Gupta, Paul J. Orchard, Troy C. Lund, Daniel L. Kenney-Jung, Weston P. Miller, David Nascene

المصدر: Blood. 133:1378-1381

مصطلحات موضوعية: Adult, Graft Rejection, Male, 0301 basic medicine, Pathology, medicine.medical_specialty, Myeloid, Adolescent, medicine.medical_treatment, Gadolinium, Immunology, Central nervous system, chemistry.chemical_element, Hematopoietic stem cell transplantation, Blood–brain barrier, ATP Binding Cassette Transporter, Subfamily D, Member 1, Biochemistry, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Humans, Medicine, Adrenoleukodystrophy, Child, business.industry, Graft Survival, Hematopoietic Stem Cell Transplantation, Biological Transport, Cell Biology, Hematology, Middle Aged, Peroxisome, Prognosis, medicine.disease, Tissue Donors, Transplantation, 030104 developmental biology, medicine.anatomical_structure, chemistry, Blood-Brain Barrier, Child, Preschool, Mutation, Disease Progression, business, 030217 neurology & neurosurgery, Follow-Up Studies

الوصف: Adrenoleukodystrophy (ALD) is caused by mutations within the X-linked ABCD1 gene, resulting in the inability to transport acylated very long chain fatty acids (VLCFAs) into the peroxisome for degradation. VLCFAs subsequently accumulate in tissues, including the central nervous system. Up to 40% of boys develop a severe progressive demyelinating form of ALD, cerebral ALD, resulting in regions of demyelination observed on brain magnetic resonance imaging that are associated with a “garland ring” of gadolinium contrast enhancement. Gadolinium enhancement indicates blood-brain barrier (BBB) disruption and an active inflammatory disease process. Only hematopoietic cell transplant (HCT) has been shown to halt neurologic progression, although the mechanism of disease arrest is unknown. We evaluated imaging- and transplant-related biomarkers in 66 males who underwent HCT. In 77% of patients, gadolinium contrast resolved by 60 days post-HCT. We determined that time to neutrophil recovery and extent of donor chimerism correlated significantly with time to contrast resolution post-HCT. Graft failure was associated with a significantly slower rate of contrast resolution (P < .0001). Time to neutrophil recovery remained significant in multivariate analysis with other biomarkers (P = .03). Our data suggest that robust donor myeloid recovery is necessary for timely repair of the BBB.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::92d100c06f6ac59fd39ac4194fe0eb15Test
https://doi.org/10.1182/blood-2018-11-887240Test

المؤلفون: Hong Liu, Wei Gao, Hong Tian, Biqi Zhou, Suning Chen, Shaoyan Hu, Tianhui Liu, Depei Wu, Yang Xu, Xinran Chu

المصدر: Blood. 138:212-212

مصطلحات موضوعية: Adult, Male, Oncology, medicine.medical_specialty, Neoplasm, Residual, Adolescent, Oncogene Proteins, Fusion, medicine.medical_treatment, Immunology, Hematopoietic stem cell transplantation, Immunotherapy, Adoptive, Biochemistry, Clonal Evolution, Young Adult, CDKN2A, hemic and lymphatic diseases, Internal medicine, Basic Helix-Loop-Helix Transcription Factors, medicine, Humans, Cumulative incidence, Retrospective Studies, Homeodomain Proteins, business.industry, Pre-B-Cell Leukemia Transcription Factor 1, Hematopoietic Stem Cell Transplantation, Induction chemotherapy, Retrospective cohort study, Cell Biology, Hematology, Precursor Cell Lymphoblastic Leukemia-Lymphoma, medicine.disease, Survival Analysis, Minimal residual disease, Leukemia, Cohort, Female, Transcriptome, business

الوصف: Introduction Patients with E2A-PBX1 fusion are expected to have an aggressive disease course. Because of the rarity of this genotype (nearly 5% of pediatric and 3% of adult B-cell acute lymphoblastic leukemia (B-ALL) cases), a consensus on the clinical and prognostic characteristics of adult E2A-PBX1-positive B-ALL patients, especially in adult patients, has not yet been reached. Patients and Methods We retrospectively summarized our clinical findings from 137 B-ALL patients diagnosed with E2A-PBX at our centers from 2009 to 2019, including 56 adolescents/adults (≥15 years old) and 81 children ( Results The proportions of E2A-PBX1-positive B-ALL in our centers were 5.3% (81/1526) in children, 4.6% (43/925) in AYA and 2.1% (15/713) in older adults. The complete remission rate among all E2A-PBX1-positive B-ALL patients in this study was 94.9% (129/136) after one course of induction chemotherapy. The 5-year overall survival (OS) and disease-free survival (DFS) rates of the whole cohort were 68.6% and 61.0%, respectively. Allo-HSCT at CR1 in adolescents/adults could dramatically improve the 5-year prognoses (OS: 80.8% vs. 25.7%, P A total of 12 patients received CD19-targeted CAR-T cell therapy for disease progression (Figure 1C), and 91.7% (11/12) of patients achieved remission. Two patients died of relapse, and 3 patients died of complications (One died of grade 4 CRS, one died of cerebral hemorrhage after transfusion, and the other one died of infection after 14 months). Three patients received CAR-T bridging to allo-HSCT, and all of them remained in remission within the follow-up period. Univariate and multivariate analysis showed that t(1;19)(q23;p13) only (OS: P=0.020, HR=0.387, 95% CI: 0.174-0.862; DFS: P=0.004, HR= 0.375, 95% CI: 0.193-0.729; CIR: P=0.009, HR= 0.400, 95% CI: 0.200-0.799), Age (DFS: P=0.037, HR=1.009, 95% CI: 1.001-1.018; CIR: P=0.005, HR=1.025, 95% CI: 1.008-1.044) and the level of minimal residual disease (MRD) after induction chemotherapy (OS: P=0.020, HR=2.971, 95% CI: 1.185-7.452; DFS: P=0.002, HR= 3.218, 95% CI: 1.510-6.861; CIR: P=0.006, HR= 3.190, 95% CI: 1.406-7.246) were independent risk factors in E2A-PBX1-positive B-ALL (Figure 1D). In the diagnosis samples, mutations in PBX1, PAX5, CTCF and SETD2, amplification of AKT3, and deletion of CDKN2A/B were common in the total cohort, while transcriptome differences were found in the cell cycle, NGF signaling pathway and transcriptional regulation by TP53 between adolescents/adults and children (Figure 2A,B). More DNA repair gene mutations were detected in the relapse samples (7.9% vs. 57.1%, P Conclusions Our study indicated that age, the level of MRD and DNA repair gene mutations were associated with E2A-PBX1-positive B-ALL outcomes. Allo-HSCT, especially haploidentical-HSCT, could improve the prognosis of adolescent/adult patients. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::a9f45449aca3f802e5eaa5889bb7cad8Test
https://doi.org/10.1182/blood-2021-146889Test

المؤلفون: Richard F. Schlenk, Richard Greil, Hartmut Döhner, Arnold Ganser, Lars Bullinger, Verena I. Gaidzik, Felicitas Thol, Michael Lübbert, Mark Ringhoffer, Mridul Agrawal, Konstanze Döhner, Nikolaus Jahn, Jürgen Krauter, Thomas Heinicke, Peter Paschka, Karin Mayer, Roland Schroers, Elisabeth Koller, Andrea Corbacioglu, Thomas Schroeder, Walter Fiedler, Silke Kapp-Schwoerer, Michael Heuser, Daniela Weber, Jörg Westermann, Heinz A. Horst, Thomas Kindler, Katharina Götze, Mohammed Wattad, Frank G. Rücker

المصدر: Blood

مصطلحات موضوعية: Adult, Male, medicine.medical_specialty, Myeloid, Neoplasm, Residual, Adolescent, Oncogene Proteins, Fusion, Immunology, Real-Time Polymerase Chain Reaction, Biochemistry, Gastroenterology, Translocation, Genetic, Young Adult, RUNX1 Translocation Partner 1 Protein, hemic and lymphatic diseases, Internal medicine, medicine, Humans, Cumulative incidence, Young adult, Aged, Myeloid Neoplasia, business.industry, Myeloid leukemia, Cancer, Cell Biology, Hematology, Middle Aged, medicine.disease, Prognosis, Leukemia, Leukemia, Myeloid, Acute, medicine.anatomical_structure, Core Binding Factor Alpha 2 Subunit, Female, Bone marrow, T(8, 21)(q22, q22), business

الوصف: We performed serial measurable residual disease (MRD) monitoring in bone marrow (BM) and peripheral blood (PB) samples of 155 intensively treated patients with RUNX1-RUNX1T1(+) AML, using a qRT-PC–based assay with a sensitivity of up to 10(−6). We assessed both reduction of RUNX1-RUNX1T1 transcript levels (TLs) and achievement of MRD negativity (MRD(−)) for impact on prognosis. Achievement of MR(2.5) (>2.5 log reduction) after treatment cycle 1 and achievement of MR(3.0) after treatment cycle 2 were significantly associated with a reduced risk of relapse (P = .034 and P = .028, respectively). After completion of therapy, achievement of MRD(−) in both BM and PB was an independent, favorable prognostic factor in cumulative incidence of relapse (4-year cumulative incidence relapse: BM, 17% vs 36%, P = .021; PB, 23% vs 55%, P = .001) and overall survival (4-year overall survival rate BM, 93% vs 70%, P = .007; PB, 87% vs 47%, P < .0001). Finally, during follow-up, serial qRT-PCR analyses allowed prediction of relapse in 77% of patients exceeding a cutoff value of 150 RUNX1-RUNX1T1 TLs in BM, and in 84% of patients exceeding a value of 50 RUNX1-RUNX1T1 TLs in PB. The KIT mutation was a significant factor predicting a lower CR rate and inferior outcome, but its prognostic impact was outweighed by RUNX1-RUNX1T1 TLs during treatment. Virtually all relapses occurred within 1 year after the end of treatment, with a very short latency from molecular to morphologic relapse, necessitating MRD assessment at short intervals during this time period. Based on our data, we propose a refined practical guideline for MRD assessment in RUNX1-RUNX1T1(+) AML.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::817b74c07bd7d7b653f7d43a8cc47144Test
https://europepmc.org/articles/PMC9635584Test/

المؤلفون: Anne S. Renteria, Michael A. Pulsipher, James L.M. Ferrara, Ivan J. Torres, Aaron Etra, Andrew C. Harris, Ernst Holler, Nicolaus Kröger, Mohammed S. Chaudhry, Wolf Rösler, George Morales, Rainer Ordemann, Yvonne A. Efebera, Muna Qayed, John E. Levine, Elizabeth O. Hexner, Yi-Bin Chen, Hannah Major-Monfried, Umut Ozbek, Pavan Reddy, William J. Hogan, Steven Kowalyk, Attaphol Pawarode, Kitsada Wudhikarn, Francis Ayuk, Mina Aziz, Ryotaro Nakamura, Carrie L. Kitko, Rachel Young, Matthias Wölfl, Jay Shah, Ran Reshef, Gregory A. Yanik, Daniela Weber, Matthew J. Hartwell

المصدر: Blood. 131:2846-2855

مصطلحات موضوعية: Adult, Oncology, medicine.medical_specialty, Multivariate analysis, Adolescent, medicine.medical_treatment, Immunology, Drug Resistance, Graft vs Host Disease, Pancreatitis-Associated Proteins, Biochemistry, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Adrenal Cortex Hormones, Internal medicine, medicine, Humans, Transplantation, Homologous, Child, Aged, Transplantation, Receiver operating characteristic, business.industry, Hematopoietic Stem Cell Transplantation, Area under the curve, Infant, Immunosuppression, Cell Biology, Hematology, Middle Aged, Prognosis, medicine.disease, Interleukin-1 Receptor-Like 1 Protein, Treatment Outcome, Graft-versus-host disease, Child, Preschool, 030220 oncology & carcinogenesis, Cohort, Biomarker (medicine), business, Biomarkers, 030215 immunology

الوصف: Acute graft-versus-host disease (GVHD) is treated with systemic corticosteroid immunosuppression. Clinical response after 1 week of therapy often guides further treatment decisions, but long-term outcomes vary widely among centers, and more accurate predictive tests are urgently needed. We analyzed clinical data and blood samples taken 1 week after systemic treatment of GVHD from 507 patients from 17 centers of the Mount Sinai Acute GVHD International Consortium (MAGIC), dividing them into a test cohort (n = 236) and 2 validation cohorts separated in time (n = 142 and n = 129). Initial response to systemic steroids correlated with response at 4 weeks, 1-year nonrelapse mortality (NRM), and overall survival (OS). A previously validated algorithm of 2 MAGIC biomarkers (ST2 and REG3α) consistently separated steroid-resistant patients into 2 groups with dramatically different NRM and OS (P < .001 for all 3 cohorts). High biomarker probability, resistance to steroids, and GVHD severity (Minnesota risk) were all significant predictors of NRM in multivariate analysis. A direct comparison of receiver operating characteristic curves showed that the area under the curve for biomarker probability (0.82) was significantly greater than that for steroid response (0.68, P = .004) and for Minnesota risk (0.72, P = .005). In conclusion, MAGIC biomarker probabilities generated after 1 week of systemic treatment of GVHD predict long-term outcomes in steroid-resistant GVHD better than clinical criteria and should prove useful in developing better treatment strategies.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::6a1e0e71c0b509f432cdd5374eab6952Test
https://doi.org/10.1182/blood-2018-01-822957Test

المؤلفون: Ezgi Karaesmen, David Van Den Berg, Tao Wang, Philip L. McCarthy, Alexander James Dile, Abbas Rizvi, Qianqian Zhu, Daniel O. Stram, Stephen R. Spellman, Stephanie J. Lee, Lara E. Sucheston-Campbell, Amy Webb, Leah Preus, Song Liu, Li Yan, Junke Wang, Xin Sheng, Sophie Paczesny, Marcelo C. Pasquini, Qian Liu, Christopher A. Haiman, Guy Brock, Theresa Hahn, Loreall Pooler, Michael Haagenson

مصطلحات موضوعية: 0301 basic medicine, Adult, Male, Genotype, IL1RL1, Graft vs Host Disease, Single-nucleotide polymorphism, Disease, Polymorphism, Single Nucleotide, Linkage Disequilibrium, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Medicine, Humans, Transplantation, Homologous, Cumulative incidence, Genetic Predisposition to Disease, Transplantation, business.industry, Donor selection, Hematopoietic Stem Cell Transplantation, Computational Biology, Genetic Variation, Molecular Sequence Annotation, Hematology, Middle Aged, medicine.disease, Prognosis, Interleukin-1 Receptor-Like 1 Protein, Tissue Donors, 030104 developmental biology, Graft-versus-host disease, surgical procedures, operative, 030220 oncology & carcinogenesis, Immunology, Biomarker (medicine), Female, business, Biomarkers

الوصف: Graft-versus-host disease (GVHD) and infections are the 2 main causes of death without relapse after allogeneic hematopoietic cell transplantation (HCT). Elevated soluble serum simulation-2 (sST2), the product of IL1RL1 in plasma/serum post-HCT, is a validated GVHD biomarker. Hundreds of SNPs at 2q12.1 have been shown to be strongly associated with sST2 concentrations in healthy populations. We therefore hypothesized that the donor genetic variants in IL1RL1 correlate with sST2 protein levels associated with patient survival outcomes after HCT. We used DISCOVeRY-BMT (Determining the Influence of Susceptibility Conveying Variants Related to 1-Year Mortality after Blood and Marrow Transplantation), a genomic study of >3000 donor–recipient pairs, to inform our hypothesis. We first measured pre-HCT plasma/serum sST2 levels in a subset of DISCOVeRY-BMT donors (n = 757) and tested the association of donor sST2 levels with donor single nucleotide polymorphisms (SNPs) in the 2q12.1 region. Donor SNPs associated with sST2 levels were then tested for association with recipient death caused by acute GVHD (aGVHD)–, infection-, and transplant-related mortality in cohorts 1 and 2. Meta-analyses of cohorts 1 and 2 were performed using fixed-effects inverse variance weighting, and P values were corrected for multiple comparisons. Donor risk alleles in rs22441131 (Pmeta = .00026) and rs2310241 (Pmeta = .00033) increased the cumulative incidence of aGVHD death up to fourfold and were associated with high sST2 levels. Donor risk alleles at rs4851601 (Pmeta = 9.7 × 10−7), rs13019803 (Pmeta = 8.9 × 10−6), and rs13015714 (Pmeta = 5.3 × 10−4) increased cumulative incidence of infection death to almost sevenfold and were associated with low sST2 levels. These functional variants are biomarkers of infection or aGVHD death and could facilitate donor selection, prophylaxis, and a conditioning regimen to reduce post-HCT mortality.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::67f671ca83c8429ed922dea33d217548Test
https://europepmc.org/articles/PMC6712530Test/

المؤلفون: Karin Hartmann, Ji-Hyun Lee, Mary Beth Geeze, Gregor Eisenwort, Diane S. Lidke, Ellen W. Hatch, Peter Valent, Cheyenne Martin, Katharina Blatt, Mohamed E. Salama, Heather H. Ward, Lu Chen, Tracy I. George, Jason Gotlib

المصدر: Blood Advances. 2:189-199

مصطلحات موضوعية: Adult, Male, 0301 basic medicine, Pathology, medicine.medical_specialty, Mastocytosis, Cutaneous, Programmed Cell Death 1 Receptor, B7-H1 Antigen, Diagnosis, Differential, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Mastocytosis, Systemic, Bone Marrow, Neoplasms, medicine, Humans, Neoplasm, Systemic mastocytosis, Aged, Myeloid Neoplasia, business.industry, Cutaneous Mastocytosis, Myelodysplastic syndromes, Hematology, Middle Aged, medicine.disease, Leukemia, 030104 developmental biology, 030220 oncology & carcinogenesis, Monoclonal, Mast cell sarcoma, Immunohistochemistry, Female, business, Mastocytosis

الوصف: Mastocytosis is a rare disease with heterogeneous clinical manifestations and few effective therapies. Programmed death-1 (PD-1) and its ligands (PD-L1 and PD-L2) protect tissues from immune-mediated damage and permit tumors to evade immune destruction. Therapeutic antibodies against PD-1 and PD-L1 are effective in the treatment of a variety of neoplasms. In the present study, we sought to systematically analyze expression of PD-1 and PD-L1 in a large number of patients with mastocytosis using immunohistochemistry and multiplex fluorescence staining. PD-L1 showed membrane staining of neoplastic mast cells (MCs) in 77% of systemic mastocytosis (SM) cases including 3 of 3 patients with MC leukemia, 2 of 2 with aggressive SM, 1 of 2 with smoldering SM, 3 of 4 with indolent SM, and 9 of 12 with SM with an associated hematologic neoplasm (SM component only). Ninety-two percent (23 of 25) of cutaneous mastocytosis (CM) cases and 1 of 2 with myelomastocytic leukemia expressed PD-L1, with no expression found in 15 healthy/reactive marrows, 18 myelodysplastic syndromes (MDSs), 16 myeloproliferative neoplasms (MPNs), 5 MDS/MPNs, and 3 monoclonal MC activation syndromes. Variable PD-L1 expression was observed between and within samples, with PD-L1 staining of MCs ranging from 10% to 100% (mean, 50%). PD-1 dimly stained 4 of 27 CM cases (15%), with no expression in SM or other neoplasms tested; PD-1 staining of MCs ranged from 20% to 50% (mean, 27%). These results provide support for the expression of PD-L1 in SM and CM, and PD-1 expression in CM. These data support the exploration of agents with anti-PD-L1 activity in patients with advanced mastocytosis.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::7f0212ff6202c0db35d30110ed0b6b9aTest
https://doi.org/10.1182/bloodadvances.2017011551Test

المؤلفون: Steven C. Ziesmer, Brian K. Link, William R. Macon, Oliver W. Press, Michael LeBlanc, Sergei Syrbu, Thomas E. Witzig, Susan L. Slager, Stephen M. Ansell, Muhammad A. Mir, Jonathan W. Friedberg, Anne J. Novak, James R. Cerhan, Thomas M. Habermann, Matthew J. Maurer

المصدر: Blood. 125:992-998

مصطلحات موضوعية: Adult, Male, medicine.medical_specialty, medicine.medical_treatment, Immunology, Follicular lymphoma, Chemokine CXCL9, Biochemistry, Gastroenterology, Disease-Free Survival, Cohort Studies, Antibodies, Monoclonal, Murine-Derived, Young Adult, International Prognostic Index, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, Humans, Immunologic Factors, Medicine, Lymphoma, Follicular, Aged, Aged, 80 and over, Chemotherapy, business.industry, Receptors, Interleukin-2, Cell Biology, Hematology, Middle Aged, Prognosis, medicine.disease, Lymphoma, Interleukin 1 Receptor Antagonist Protein, Cytokine, Interleukin 1 receptor antagonist, Monoclonal, Female, Rituximab, business, medicine.drug

الوصف: Serum cytokines and chemokines may reflect tumor biology and host response in follicular lymphoma (FL). To determine whether the addition of these biological factors may further refine prognostication, 30 cytokines and chemokines were measured in pretreatment serum specimens from newly diagnosed FL patients (n = 209) and from 400 matched controls. Cytokine levels were correlated with clinical outcome in patients who were observed or received single agent rituximab, or those who received chemotherapy. Correlations with outcome in chemotherapy treated patients were further examined in a separate cohort of 183 South West Oncology Group (SWOG) patients and all patients were then included in a meta-analysis. Six cytokines were associated with outcome in the Molecular Epidemiology Resource (MER) after adjusting for the FL international prognostic index. In patients who were observed or treated with rituximab alone, increased serum IL-12 and interleukin 1 receptor antagonist (IL-1RA) (P = .005 and .02) were associated with a shorter event-free survival. In patients receiving chemotherapy, hepatocyte growth factor, IL-8, IL-1RA, and CXCL9 (P = .015, .048, .004, and .0005) predicted a shorter EFS. When the MER chemotherapy treated patients and SWOG patients were combined in a meta-analysis, IL-2R, IL-1RA, and CXCL9 (P = .013, .042, and .0012) were associated with a poor EFS.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::7cd97717d19e1e6d2849fb6c2b2c69d7Test
https://doi.org/10.1182/blood-2014-06-583369Test

المؤلفون: Maria E. Arcila, Christian A. Bowers, Eli L. Diamond, Benjamin H. Durham, Lynn A. Brody, Omar Abdel-Wahab, Ahmet Dogan, Neval Ozkaya, Mark Fluchel

المصدر: Blood. 128:1896-1898

مصطلحات موضوعية: Central Nervous System, Male, 0301 basic medicine, Pathology, genetic structures, Drug Resistance, Letters to Blood, medicine.disease_cause, Biochemistry, 0302 clinical medicine, hemic and lymphatic diseases, MAP2K1, Medicine, Fatigue, Aged, 80 and over, Heart, Hematology, Middle Aged, C-Reactive Protein, Treatment Outcome, Organ Specificity, 030220 oncology & carcinogenesis, Disease Progression, Female, KRAS, medicine.drug, Adult, Erdheim-Chester Disease, medicine.medical_specialty, Immunology, Pain, Bone and Bones, Myeloid Neoplasm, Young Adult, 03 medical and health sciences, Humans, neoplasms, Aged, Anakinra, business.industry, Extramural, Myocardium, Interferon-alpha, Cell Biology, medicine.disease, Interleukin 1 Receptor Antagonist Protein, 030104 developmental biology, Positron-Emission Tomography, Erdheim–Chester disease, Cancer research, ARAF, business

الوصف: To the editor: Erdheim-Chester disease (ECD) is a myeloid neoplasm characterized by recurrent mutations in mitogen-activated protein kinase pathway genes, including BRAF , ARAF , N/KRAS , MAP2K1 , and PIK3CA mutations and fusions in ALK and NTRK1 .[1][1][⇓][2][⇓][3]-[4][4] Lesional ECD cells

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::26ca297d778ea70d8041c508849db153Test
https://doi.org/10.1182/blood-2016-06-725143Test