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Hematopoietic diseases

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https://www.readbyqxmd.com/read/28229434/preclinical-pharmacokinetics-and-pharmacodynamics-of-pinometostat-epz-5676-a-first-in-class-small-molecule-s-adenosyl-methionine-competitive-inhibitor-of-dot1l
#1
Nigel J Waters
Acute leukemias bearing mixed lineage leukemia (MLL) rearrangements are aggressive diseases characterized by a poor overall prognosis despite multi-agent chemotherapy. Aberrant fusion proteins involving the MLL histone methyltransferase (HMT) lead to recruitment of DOT1L, to a multi-protein complex resulting in aberrant methylation of histone H3 lysine 79 at MLL target genes, and ultimately enhanced expression of critical genes for hematopoietic differentiation, including HOXA9 and MEIS1, and as such defines the established mechanism for leukemogenesis in MLL-rearrangement (MLL-r) leukemias...
February 22, 2017: European Journal of Drug Metabolism and Pharmacokinetics
https://www.readbyqxmd.com/read/28229405/compact-bone-derived-multipotent-mesenchymal-stromal-cells-mscs-for-the-treatment-of-sjogren-s-like-disease-in-nod-mice
#2
Ghada Abu Elghanam, Younan Liu, Saeed Khalili, Dongdong Fang, Simon D Tran
Compact bone (cortical or dense bone) is among the organs that contain multipotent mesenchymal stromal cells (MSCs). Unlike bone marrow plugs where MSCs were initially isolated, compact bone has minimal (amount of) hematopoietic cells and thus facilitates the MSCs isolation process. In vitro, MSCs from compact bone show multipotency and differentiation into mesenchymal tissues such as bone, adipose, and cartilage, under certain conditions. MSCs therapy has been promising in preclinical and clinical studies against autoimmune diseases...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28228753/reduction-of-relapse-after-unrelated-donor-stem-cell-transplantation-by-kir-based-graft-selection
#3
REVIEW
Silke Heidenreich, Nicolaus Kröger
Besides donor T cells, natural killer (NK) cells are considered to have a major role in preventing relapse after allogeneic hematopoietic stem cell transplantation (HSCT). After T-cell-depleted haploidentical HSCT, a strong NK alloreactivity has been described. These effects have been attributed to killer-cell immunoglobulin-like receptors (KIR). Abundant reports suggest a major role of KIR not only on outcome after haploidentical HSCT but also in the unrelated donor setting. In this review, we give a brief overview of the mechanism of NK cell activation, nomenclature of KIR haplotypes, human leukocyte antigen (HLA) groups, and distinct models for prediction of NK cell alloreactivity...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28223256/role-of-the-leukocyte-response-in-normal-and-immunocompromised-host-after-clostridium-difficile-infection
#4
Edwin Vargas, Senu Apewokin, Rajat Madan
Clostridium difficile is the leading cause of healthcare-associated infections in the United States. Clinically, C. difficile-associated disease can present as asymptomatic colonization, self-limited diarrheal illness or severe colitis (that may result in death). This variability in disease course and outcomes suggests that host factors play an important role as key determinants of disease severity. Currently, there are several scoring indices to estimate severity of C. difficile-associated disease. Leukocytosis and renal failure are considered to be the most important predictors of C...
February 18, 2017: Anaerobe
https://www.readbyqxmd.com/read/28222648/autologous-stem-cell-transplantation-as-frontline-strategy-for-peripheral-t-cell-lymphoma-a-single-centre-experience
#5
Xiao Han, Wei Zhang, Daobin Zhou, Jing Ruan, Minghui Duan, Tienan Zhu, Jian Li, Huacong Cai, Xinxin Cao, Mingqi Ouyang
Objective To determine the efficacy and prognosis of autologous hematopoietic stem cell transplantation (ASCT) as frontline treatment for peripheral T cell lymphoma (PTCL). Methods Clinical data from 46 PTCL patients who achieved complete (CR) or partial remission (PR) after ASCT from October 1996 to July 2014 were analysed retrospectively. Results Median patient age was 32 (range: 15-68) years. Disease types included PTCL, unspecified type, in 23 patients, anaplastic large cell lymphoma in eight, angioimmunoblastic lymphoma in eight, extranodal NK/T-cell lymphoma in five, and hepatosplenic T-cell lymphoma and enteropathy associated T-cell lymphoma in one each...
February 2017: Journal of International Medical Research
https://www.readbyqxmd.com/read/28221102/rhodococcus-infection-in-solid-organ-and-hematopoietic-stem-cell-transplant-recipients-1
#6
Pascalis Vergidis, Ella J Ariza-Heredia, Anoma Nellore, Camille N Kotton, Daniel R Kaul, Michele I Morris, Theodoros Kelesidis, Harshal Shah, Seo Young Park, M Hong Nguyen, Raymund R Razonable
We conducted a case-control study of 18 US transplant recipients with Rhodococcus infection and 36 matched controls. The predominant types of infection were pneumonia and bacteremia. Diabetes mellitus and recent opportunistic infection were independently associated with disease. Outcomes were generally favorable except for 1 relapse and 1 death.
March 2017: Emerging Infectious Diseases
https://www.readbyqxmd.com/read/28220349/clofarabine-based-chemotherapy-as-a-bridge-to-transplant-in-the-setting-of-refractory-or-relapsed-acute-myeloid-leukemia-after-at-least-one-previous-unsuccessful-salvage-treatment-containing-fludarabine-a-single-institution-experience
#7
Alfredo Molteni, Marta Riva, Emanuele Ravano, Laura Marbello, Valentina Mancini, Giovanni Grillo, Elisa Zucchetti, Rosa Greco, Roberto Cairoli
For refractory or relapsed acute myeloid leukemia patients, allogeneic hematopoietic stem cell transplantation is the only curative treatment option, but the disease must be in remission before this can be attempted. "Salvage" therapy regimens containing high-dose cytarabine plus fludarabine or cladribine with or without anthracyclines or plus mitoxantrone and etoposide fail in 30-50% of cases. We report the outcome of 14 patients treated with a clofarabine-based treatment administered after at least one failed fludarabine-based "salvage" attempt in a "real life" (outside a clinical trial) context...
February 20, 2017: International Journal of Hematology
https://www.readbyqxmd.com/read/28219836/donor-lymphocyte-infusion-for-relapsed-hematological-malignancies-after-unrelated-allogeneic-bone-marrow-transplantation-facilitated-by-the-japan-marrow-donor-program
#8
Toshihiro Miyamoto, Takahiro Fukuda, Marie Nakashima, Tomoko Henzan, Shinsuke Kusakabe, Naoki Kobayashi, Junichi Sugita, Takeshi Mori, Mineo Kurokawa, Shin-Ichiro Mori
To evaluate the safety and efficacy of donor lymphocyte infusion (DLI), we retrospectively analyzed 414 recipients who received unrelated DLI (UDLI) for the treatment of relapsed hematological malignancy after unrelated bone marrow transplantation (BMT). UDLI was administered for acute myelogenous leukemia (n=184), myelodysplastic syndrome (n=69), acute lymphocytic leukemia (n=57), chronic myelogenous leukemia (CML, n=36), lymphoid neoplasms (n=38), adult T-cell leukemia/lymphoma (n=18), and multiple myeloma (n=12)...
February 17, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28219835/marked-in-vivo-donor-treg-expansion-via-il-2-and-tl1a-ig-stimulation-ameliorates-gvhd-but-preserves-gvl-in-recipients-post-hsct
#9
Dietlinde Wolf, Henry Barreras, Cameron S Bader, Sabrina Copsel, Casey O Lightbourn, Brent J Pfeiffer, Norman H Altman, Eckhard R Podack, Krishna V Komanduri, Robert B Levy
Regulatory T cells (Tregs) are critical for self-tolerance. While adoptive transfer of expanded Tregs limits graft-versus-host disease (GVHD) after hematopoietic cell transplantation (HCT), ex vivo generation of large numbers of functional Tregs remains difficult. Here, we demonstrate that in vivo targeting of the TNF superfamily receptor TNFRSF25 using the TL1A-Ig fusion protein, along with IL-2, resulted in transient but massive Treg expansion in donor mice, which peaked within days and was nontoxic. Tregs increased in multiple compartments, including blood, lymph nodes, spleen and colon (a GVHD target tissue)...
February 17, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28219834/incidence-and-outcomes-of-central-nervous-system-hemophagocytic-lymphohistiocytosis-relapse-after-reduced-intensity-conditioning-hematopoietic-stem-cell-transplant
#10
Dana T Lounder, Pooja Khandelwal, Sharat Chandra, Michael B Jordan, Ashish R Kumar, Michael Grimley, Stella M Davies, Jack J Bleesing, Rebecca A Marsh
Hemophagocytic Lymphohistiocytosis (HLH) is an immune regulatory disorder that commonly presents with CNS involvement. The only cure for genetic HLH is hematopoietic stem cell transplantation (HSCT), typically treated with reduced intensity conditioning (RIC) regimens. We sought to estimate the incidence of CNS relapse after RIC HSCT, determine risk factors, and evaluate outcomes. We performed a retrospective chart review of 94 consecutive children and young adults with primary HLH who received RIC HSCT. CNS relapse within 1 year after transplant was diagnosed by review of clinical symptoms, cerebral spinal fluid (CSF), and radiologic findings...
February 17, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28219225/-effect-of-nccn-2015-risk-stratification-on-prognosis-of-patients-with-acute-myeloid-leukemia-after-allogeneic-hematopoietic-stem-cell-transplantation
#11
Y Lu, T Wu, Y L Zhao, X Y Cao, D Y Liu, J P Zhang, M Xiong, J R Zhou, R J Sun, Z J Wei, H Wang, H X Liu, T Wang, C R Tong, S Q Ji, D P Lu
Objective: To analyze the effect of NCCN (2015) risk stratification on prognosis of patients with acute myeloid leukemia (AML) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) . Methods: Retrospective analysis of 258 patients with AML in CR (186 cases in CR(1), 72 cases in CR(2)) who underwent allogeneic HSCT in our hospital between April 2012 and March 2015 according to NCCN (2015) risk stratification. Of them, 63 cases were classified as low risk, 112 cases intermediate risk and 83 cases high risk...
January 14, 2017: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
https://www.readbyqxmd.com/read/28219218/-prognostic-significance-of-early-assessment-of-minimal-residual-disease-in-acute-myeloid-leukemia-with-mutated-npm1-patients
#12
T Zhao, H H Zhu, J Wang, J S Jia, S M Yang, H Jiang, J Lu, H Chen, L P Xu, X H Zhang, B Jiang, G R Ruan, D B Wang, X J Huang, Q Jiang
Objective: To explore prognostic significance of early assessment of minimal residual leukemia (MRD) in adult patients with de novo acute myeloid leukemia (AML) with mutated NPM1. Methods: The response, NPM1 mutated transcript level after induction chemotherapy and the first 2 cycles of consolidation chemotherapy, disease-free survival (DFS) and overall survival (OS) in 137 patients with AML with NPM1 mutations of A, B and D were retrospectively analyzed. Results: Data of 137 patients were collected, 67 were male, the median age was 49 years (16-67 years) , 107 (78...
January 14, 2017: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
https://www.readbyqxmd.com/read/28218755/changes-in-the-incidence-patterns-and-outcomes-of-graft-failure-following-hematopoietic-stem-cell-transplantation-for-hurler-syndrome
#13
S H Lum, W P Miller, S Jones, K Poulton, W Ogden, H Lee, A Logan, D Bonney, T C Lund, P J Orchard, R F Wynn
Hematopoietic stem cell transplantation (HSCT) is the standard of care in children with Hurler syndrome (HS) as it is the only therapy that can arrest disease progression. We examined the incidence, patterns and outcomes of graft failure in all HS children undergoing first HSCT at the Royal Manchester Children's Hospital or the University of Minnesota Children's Hospital from 1983 to 2016. Implementation of busulfan pharmacokinetic monitoring started in 2004 in both institutions. Two hundred and forty HS children were included in this analysis (historical era (pre-2004), n=131; current era (post 2004), n=109)...
February 20, 2017: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/28218754/cmv-viral-load-in-bronchoalveolar-lavage-for-diagnosis-of-pneumonia-in-allogeneic-hematopoietic-stem-cell-transplantation
#14
L Iglesias, M M Perera, L Torres-Miñana, M J Pena-López
The objective of this report is to analyze the value of CMV viral load (VL) in bronchoalveolar lavage (BAL) in recipients of allogeneic hematopoietic stem cell transplantation (AHSCT) and to analyze the concordance between CMV quantification in plasma and BAL samples. Fifty-six patients were included; in 16 (28.6%) patients with symptoms of lung disease a BAL sample was collected, 7 (43.7%) patients had a VL >150 copies/mL (six had probable CMV pneumonia). Patients with CMV pneumonia were female (100%), of median age 53...
February 20, 2017: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/28218751/scleral-lenses-for-severe-chronic-gvhd-related-keratoconjunctivitis-sicca-a-retrospective-study-by-the-sfgm-tc
#15
L Magro, J Gauthier, M Richet, M Robin, S Nguyen, F Suarez, J-H Dalle, T Fagot, A Huynh, M-T Rubio, R Oumadely, S Vigouroux, N Milpied, A Delcampe, I Yakoub-Agha
Chronic GvHD-related keratoconjunctivitis sicca (cGvHD-related KCS) can significantly alter the quality of life of patients after allogeneic hematopoietic stem cell transplantation. The aim of this work was to assess the efficacy and tolerability of scleral lenses to treat severe cGvHD-related KCS. In this retrospective, multicenter study, we included 60 consecutive patients diagnosed with cGvHD-related KCS and fitted with scleral lenses. Patients were evaluated at baseline and at 2 months with the following tests: the Ocular Surface Disease Index (OSDI) to assess quality of life, the Oxford score to grade corneal damage and the logarithm of minimal angle of resolution (Log MAR) scale to determine visual acuity...
February 20, 2017: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/28217887/gastric-antral-vascular-ectasia-in-systemic-sclerosis-where-do-we-stand
#16
REVIEW
Hala El-Gendy, Kyrillus S Shohdy, Gehad G Maghraby, Kerolos Abadeer, Moustafa Mahmoud
Gastric antral vascular ectasia (GAVE) continues to be a challenge in both diagnosis and treatment. GAVE has a diverse group of associations and presumed causes, including cirrhosis, chronic renal failure and autoimmune connective tissue diseases. However, in most occasions, the management plan of GAVE itself is the same whatever the underlying disease by using Argon plasma coagulation (APC). Herein, we will discuss three cases of systemic sclerosis-associated GAVE presenting with either acute or chronic gastrointestinal bleeding showing variable responses to APC...
February 20, 2017: International Journal of Rheumatic Diseases
https://www.readbyqxmd.com/read/28215825/stage-specific-human-induced-pluripotent-stem-cells-map-the-progression-of-myeloid-transformation-to-transplantable-leukemia
#17
Andriana G Kotini, Chan-Jung Chang, Arthur Chow, Han Yuan, Tzu-Chieh Ho, Tiansu Wang, Shailee Vora, Alexander Solovyov, Chrystel Husser, Malgorzata Olszewska, Julie Teruya-Feldstein, Deepak Perumal, Virginia M Klimek, Alexandros Spyridonidis, Raajit K Rampal, Lewis Silverman, E Premkumar Reddy, Elli Papaemmanuil, Samir Parekh, Benjamin D Greenbaum, Christina S Leslie, Michael G Kharas, Eirini P Papapetrou
Myeloid malignancy is increasingly viewed as a disease spectrum, comprising hematopoietic disorders that extend across a phenotypic continuum ranging from clonal hematopoiesis to myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). In this study, we derived a collection of induced pluripotent stem cell (iPSC) lines capturing a range of disease stages encompassing preleukemia, low-risk MDS, high-risk MDS, and secondary AML. Upon their differentiation, we found hematopoietic phenotypes of graded severity and/or stage specificity that together delineate a phenotypic roadmap of disease progression culminating in serially transplantable leukemia...
February 13, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/28213976/enhancement-of-%C3%AE-globin-gene-expression-in-thalassemic-ivs2-654-induced-pluripotent-stem-cell-derived-erythroid-cells-by-modified-u7-snrna
#18
Phetcharat Phanthong, Suparerk Borwornpinyo, Narisorn Kitiyanant, Natee Jearawiriyapaisarn, Lalana Nuntakarn, Jirawat Saetan, Tiwaporn Nualkaew, Khanit Sa-Ngiamsuntorn, Usanarat Anurathapan, Andras Dinnyes, Yindee Kitiyanant, Suradej Hongeng
The therapeutic use of patient-specific induced pluripotent stem cells (iPSCs) is emerging as a potential treatment of β-thalassemia. Ideally, patient-specific iPSCs would be genetically corrected by various approaches to treat β-thalassemia including lentiviral gene transfer, lentivirus-delivered shRNA, and gene editing. These corrected iPSCs would be subsequently differentiated into hematopoietic stem cells and transplanted back into the same patient. In this article, we present a proof of principle study for disease modeling and screening using iPSCs to test the potential use of the modified U7 small nuclear (sn) RNA to correct a splice defect in IVS2-654 β-thalassemia...
February 18, 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28212922/organ-specific-biomarkers-in-lupus
#19
REVIEW
Haijing Wu, Jinrong Zeng, Ming Zhao, Qianjin Lu
Systemic lupus erythematosus (SLE) is a complex and highly heterogeneous disease, which affects multiple organs, including joints, skin, kidneys, heart, hematopoietic system, and nerve system. While the etiopathogenesis of SLE still remains unclear, genetic susceptibilities and aberrant epigenetic modifications are believed to be involved. For precision therapy, it is necessary to assess accurately and objectively organ involvements and disease activity, which is difficult by current clinical laboratory tests...
February 14, 2017: Autoimmunity Reviews
https://www.readbyqxmd.com/read/28212370/the-evolution-of-allogeneic-stem-cell-transplant-for-children-and-adolescents-with-acute-myeloid-leukemia
#20
Allyson Flower, Mitchell S Cairo
Survival rates in subsets of pediatric patients who have acute myeloid leukemia (AML) with favorable risk features are now greater than 90%. However, outcomes for patients with high-risk (HR) features remain unacceptably poor. As novel technologies for the identification of HR biomarkers and the detection of residual disease are developed, risk stratification and the application of allogeneic hematopoietic stem cell transplant (HSCT) are evolving. HSCT has been shown to benefit subpopulations of pediatric patients with AML, including those with HR cytogenetic translocations, genetic mutations, and/or residual disease after induction...
January 2017: Clinical Advances in Hematology & Oncology: H&O
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