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Refractory Cytopenia

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https://www.readbyqxmd.com/read/29427826/tocilizumab-and-refractory-takayasu-disease-four-case-reports-and-systematic-review
#1
REVIEW
P Decker, P Olivier, J Risse, S Zuily, D Wahl
BACKGROUND: Relapses upon corticosteroids tapering and immunosuppressive agents are frequent in Takayasu arteritis (TA). Interleukin-6 is highly involved in physiopathology of TA. Many reports showed efficacy of tocilizumab (TCZ) in refractory TA cases. We report four cases and an updated literature review on the TCZ efficacy and safety in patients with TA. METHODS: Patients with TA defined by ACR 1990 criteria were included. Clinical, biological and imaging data were retrospectively reported...
February 7, 2018: Autoimmunity Reviews
https://www.readbyqxmd.com/read/29415943/-relationship-between-clinical-features-and-somatic-gene-mutations-in-myelodysplastic-syndrome
#2
Nobuhiro Hirasawa, Mamiko Sakata-Yanagimoto, Yasuhito Nannya, Keiichiro Hattori, Yasuhito Suehara, Takayasu Kato, Yasuhisa Yokoyama, Naoki Kurita, Naoshi Obara, Seishi Ogawa, Yuichi Hasegawa, Shigeru Chiba
Recent progress in sequencing studies has suggested that somatic mutations can be used in clinical sequencing for predicting prognosis and selecting treatment options in myelodysplastic syndrome (MDS). A 48-year-old man was diagnosed with refractory cytopenia with multilineage dysplasia that is classified as a subtype of high-risk MDS based on both revised International Prognostic Scoring System and refined WHO classification based Prognostic Scoring System. He received a bone marrow transplant from an HLA-matched sibling donor at X+87 months because of disease progression...
2018: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
https://www.readbyqxmd.com/read/29330964/spectrum-of-bone-marrow-pathology-and-hematological-abnormalities-in-methylmalonic-acidemia
#3
Nasir A Bakshi, Talal Al-Anzi, Said Y Mohamed, Zuhair Rahbeeni, Moeen AlSayed, Mohammed Al-Owain, Raashda A Sulaiman
Patients with isolated methylmalonic acidemia (MMA) may present with a wide range of hematological complications including anemia, leukopenia, thrombocytopenia, and pancytopenia. However, there are very limited data on the development of hemophagocytosis or myelodysplasia in these patients. We report three patients with isolated MUT related MMA who presented with severe refractory pancytopenia during acute illness. Their bone marrow examination revealed a wide spectrum of pathology varying from bone marrow hypoplasia, hemophagocytosis to myelodysplasia with ring sideroblasts...
January 13, 2018: American Journal of Medical Genetics. Part A
https://www.readbyqxmd.com/read/29317997/experience-with-ibrutinib-for-first-line-use-in-patients-with-chronic-lymphocytic-leukemia
#4
REVIEW
Gilad Itchaki, Jennifer R Brown
Ibrutinib is the first in-class, orally administered, Bruton's tyrosine kinase (BTK) inhibitor that abrogates the critical signaling downstream of the B-cell receptor (BCR). This signaling is required for B-cell survival, proliferation and interaction with the microenvironment. Ibrutinib proved active in preclinical models of lymphoproliferative diseases and achieved impressive response rates in heavily pretreated relapsed and refractory (R/R) patients with chronic lymphocytic leukemia (CLL). Ibrutinib prolonged survival compared to standard therapy and mitigated the effect of most poor prognostic factors in CLL, thus becoming the main therapeutic option in high-risk populations...
January 2018: Therapeutic Advances in Hematology
https://www.readbyqxmd.com/read/29296758/inotuzumab-ozogamicin-in-adults-with-relapsed-or-refractory-cd22-positive-acute-lymphoblastic-leukemia-a-phase-1-2-study
#5
Daniel J DeAngelo, Wendy Stock, Anthony S Stein, Andrei Shustov, Michaela Liedtke, Charles A Schiffer, Erik Vandendries, Katherine Liau, Revathi Ananthakrishnan, Joseph Boni, A Douglas Laird, Luke Fostvedt, Hagop M Kantarjian, Anjali S Advani
This study evaluated the safety, antitumor activity, pharmacokinetics, and pharmacodynamics of inotuzumab ozogamicin (InO) for CD22-positive relapsed/refractory acute lymphoblastic leukemia. In phase 1, patients received InO 1.2 (n = 3), 1.6 (n = 12), or 1.8 (n = 9) mg/m2 per cycle on days 1, 8, and 15 over a 28-day cycle (≤6 cycles). The recommended phase 2 dose (RP2D) was confirmed (expansion cohort; n = 13); safety and activity of InO were assessed in patients receiving the RP2D in phase 2 (n = 35) and in all treated patients (n = 72)...
June 27, 2017: Blood Advances
https://www.readbyqxmd.com/read/29285268/reactive-oxygen-species-levels-control-nf-%C3%AE%C2%BAb-activation-by-low-dose-deferasirox-in-erythroid-progenitors-of-low-risk-myelodysplastic-syndromes
#6
Mathieu Meunier, Sarah Ancelet, Christine Lefebvre, Josiane Arnaud, Catherine Garrel, Mylène Pezet, Yan Wang, Patrice Faure, Gautier Szymanski, Nicolas Duployez, Claude Preudhomme, Denis Biard, Benoit Polack, Jean-Yves Cahn, Jean Marc Moulis, Sophie Park
Anemia is a frequent cytopenia in myelodysplastic syndromes (MDS) and most patients require red blood cell transfusion resulting in iron overload (IO). Deferasirox (DFX) has become the standard treatment of IO in MDS and it displays positive effects on erythropoiesis. In low risk MDS samples, mechanisms improving erythropoiesis after DFX treatment remain unclear. Herein, we addressed this question by using liquid cultures with iron overload of erythroid precursors treated with low dose of DFX (3μM), which corresponds to DFX 5 mg/kg/day, an unusual dose used for iron chelation...
December 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/29281873/safety-results-and-analysis-of-eribulin-efficacy-according-to-previous-microtubules-inhibitors-sensitivity-in-the-french-prospective-expanded-access-program-for-heavily-pre-treated-metastatic-breast-cancer
#7
Renaud Sabatier, Véronique Diéras, Xavier Pivot, Etienne Brain, Henri Roché, Jean-Marc Extra, Audrey Monneur, Magali Provansal, Carole Tarpin, François Bertucci, Patrice Viens, Christophe Zemmour, Anthony Gonçalves
Purpose: Eribulin is approved for advanced breast cancers refractory to anthracyclines and taxanes. Efficacy according to sensitivity to previous therapies has been poorly explored. Materials and Methods: Safety data were collected prospectively and we retrospectively collected efficacy data from the five French centres that participated in the Eribulin E7389-G000-398 expanded access program. Our main objectives were exploration of safety and analysis of eribulin efficacy (progression-free survival [PFS] and overall survival [OS]) according to sensitivity to the last microtubule-inhibiting agent administered...
December 28, 2017: Cancer Research and Treatment: Official Journal of Korean Cancer Association
https://www.readbyqxmd.com/read/29275390/hhv-8-associated-haemophagocytic-lymphohistiocytosis-in-a-patient-with-advanced-aids
#8
Saroja Bangaru, Amanda Strickland, Dominick Cavuoti, Nainesh Shah
We present a patient with advanced AIDS admitted with recurrent shock of unclear aetiology, fevers, altered mental status and refractory cytopenias. His case posed a diagnostic challenge because evaluation of septic shock in the setting of advanced AIDS requires a time-consuming work-up for broad infectious aetiologies that can delay consideration of other diagnoses, including primary or secondary haemophagocytic lymphohistiocytosis (HLH). After this patient did not improve with supportive care and empiric antimicrobials, there was concern for HLH given that he met ≥5 of the HLH consortium criteria...
December 22, 2017: BMJ Case Reports
https://www.readbyqxmd.com/read/29214694/myelodysplastic-syndromes-2018-update-on-diagnosis-risk-stratification-and-management
#9
Guillermo Montalban-Bravo, Guillermo Garcia-Manero
DISEASE OVERVIEW: The myelodysplastic syndromes (MDS) are a very heterogeneous group of myeloid disorders characterized by peripheral blood cytopenias and increased risk of transformation to acute myelogenous leukemia (AML). MDS occurs more frequently in older males and in individuals with prior exposure to cytotoxic therapy. DIAGNOSIS: Diagnosis of MDS is based on morphological evidence of dysplasia upon visual examination of a bone marrow aspirate and biopsy. Information obtained from additional studies such as karyotype, flow cytometry or molecular genetics is usually complementary and may help refine diagnosis...
January 2018: American Journal of Hematology
https://www.readbyqxmd.com/read/29118268/azacitidine-in-lower-risk-myelodysplastic-syndromes-a-meta-analysis-of-data-from-prospective-studies
#10
Rami Komrokji, Arlene S Swern, David Grinblatt, Roger M Lyons, Magnus Tobiasson, Lewis R Silverman, Hamid Sayar, Ravi Vij, Albert Fliss, Nora Tu, Mary M Sugrue
BACKGROUND: After erythropoiesis-stimulating agent (ESA) failure, lenalidomide and hypomethylating agents are the only remaining treatment options for most patients with lower-risk myelodysplastic syndromes (LR-MDS). Optimal choice of these agents as front-line therapy in non-del(5q) LR-MDS is unclear. Because azacitidine clinical data mainly describe experience in higher-risk MDS, we performed a meta-analysis of patient-level data to evaluate azacitidine in patients with red blood cell (RBC) transfusion-dependent LR-MDS...
November 8, 2017: Oncologist
https://www.readbyqxmd.com/read/29070129/-clinical-efficacy-of-low-dose-decitabine-combined-with-cag-regimen-in-patients-with-myelodysplastic-syndrome-refractory-anemia-with-excess-blasts-mds-raeb
#11
Meng Wang, Hao-Hao Han, Rong Guo, Yan-Fang Liu, Zhong-Xing Jiang, Hui Sun
OBJECTIVE: To investigate the clinical efficacy of low-dose decitabine combined with CAG regimen in patients with myelodysplastic syndrome-refractory anemia with excess blasts (MDS-RAEB) through retrospective analysis. METHODS: Thirty-six patients with MDS-RAEB who ever received low-dose decitabine combined with CAG regimen were enrolled into decitabine + CAG group and 40 patients with MDS-RAEB treated by decitabine alone in our center were enolled into the control group...
October 2017: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/29024842/peritoneal-carcinomatosis-like-implants-of-extramedullary-hematopoiesis-an-insolite-occurrence-during-splenectomy-for-myelofibrosis
#12
Marco Casaccia, Rosario Fornaro, Marco Frascio, Denise Palombo, Cesare Stabilini, Emma Firpo, Ezio Gianetta
INTRODUCTION: Primary myelofibrosis (MF) is a myeloproliferative neoplasm that results in debilitating constitutional symptoms, splenomegaly, and cytopenias. In patients with symptomatic splenomegaly, splenectomy remains a viable treatment option for MF patients with medically refractory symptomatic splenomegaly that precludes the use of ruxolitinib. CASE PRESENTATION: We present the clinical case of a patient who was admitted to our Department to perform a splenectomy in MF as a therapeutic step prior to an allogeneic stem cell transplantation (ASCT)...
October 5, 2017: International Journal of Surgery Case Reports
https://www.readbyqxmd.com/read/29018077/efficacy-of-venetoclax-as-targeted-therapy-for-relapsed-refractory-t-11-14-multiple-myeloma
#13
Shaji Kumar, Jonathan L Kaufman, Cristina Gasparetto, Joseph Mikhael, Ravi Vij, Brigitte Pegourie, Lofti Benboubker, Thierry Facon, Martine Amiot, Philippe Moreau, Elizabeth A Punnoose, Stefanie Alzate, Martin Dunbar, Tu Xu, Suresh K Agarwal, Sari Heitner Enschede, Joel D Leverson, Jeremy A Ross, Paulo C Maciag, Maria Verdugo, Cyrille Touzeau
Venetoclax is a selective, orally bioavailable BCL-2 inhibitor that induces cell death in MM cells, particularly in those harboring t(11;14), which express high levels of BCL-2 relative to BCL-XL and MCL-1. In this phase I study, patients with relapsed/refractory MM received venetoclax monotherapy. After a 2-week lead-in with weekly dose escalation, daily venetoclax was given at 300, 600, 900, or 1200 mg in dose-escalation cohorts and 1200 mg in the safety expansion. Dexamethasone could be added upon progression during treatment...
October 10, 2017: Blood
https://www.readbyqxmd.com/read/28942350/refractory-macrocytic-anemias-in-patients-with-clonal-hematopoietic-disorders-and-isolated-mutations-of-the-spliceosome-gene-zrsr2
#14
Roger A Fleischman, Shannon S Stockton, Christopher R Cogle
Although mutations in RNA splicing genes occur frequently in patients with clonal cytopenias of unknown significance (CCUS) and myelodysplastic syndromes (MDS), very often additional common myeloid gene driver mutations are present at diagnosis. Thus, the clinical significance of isolated mutations in the most commonly mutated RNA splicing genes remains unknown. Here we report five unusual patients with an isolated mutation causing a loss of function of ZRSR2, a protein required for recognition of a functional 3' splice site...
October 2017: Leukemia Research
https://www.readbyqxmd.com/read/28927162/myelodysplastic-syndrome-unclassifiable-mds-u-with-1-blasts-is-a-distinct-subgroup-of-mds-u-with-a-poor-prognosis
#15
Elizabeth Margolskee, Robert P Hasserjian, Duane Hassane, Wayne Tam, Susan Mathew, Chi Young Ok, Sa A Wang, Jean Oak, Daniel A Arber, Attilio Orazi
Objectives: Three situations qualify as myelodysplastic syndrome, unclassifiable (MDS-U): (1) refractory cytopenia with dysplasia and 1% blasts in peripheral blood (BL), (2) pancytopenia with unilineage dysplasia (Pan), and (3) persistent cytopenia, less than 5% bone marrow blasts, and less than 10% dysplastic cells and presence of MDS-defining cytogenetic abnormalities (CG). We compared the clinicopathologic features and mutational profiles for these three groups. Methods: MDS-U cases were reviewed at four major academic institutions...
July 1, 2017: American Journal of Clinical Pathology
https://www.readbyqxmd.com/read/28921816/comprehensive-genetic-analysis-of-donor-cell-derived-leukemia-with-kmt2a-rearrangement
#16
Rieko Taniguchi, Hideki Muramatsu, Yusuke Okuno, Kyogo Suzuki, Satoshi Obu, Masahiro Nakatochi, Teppei Shimamura, Yoshiyuki Takahashi, Yasuo Horikoshi, Kenichiro Watanabe, Seiji Kojima
BACKGROUND: Donor cell leukemia (DCL) occurs after allogeneic hematopoietic stem cell transplantation. Several mechanisms, including occult leukemic/preleukemic subclones in the donor graft and germline predisposition to leukemia, are proposed to be associated with DCL's molecular pathogenesis. We report a comprehensive genetic analysis of a patient with KMT2A-rearranged DCL after allogeneic bone marrow transplantation for refractory cytopenia of childhood. PROCEDURE: We performed a whole-exome sequencing of the recipient's peripheral blood before transplant and the donor's peripheral blood and the recipient's bone marrow at the time of DCL diagnosis...
September 17, 2017: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/28822917/coexistence-of-aberrant-hematopoietic-and-stromal-elements-in-myelodysplastic-syndromes
#17
Salar Abbas, Archana Kini, Vivi M Srivastava, Marie Therese M, Sukesh C Nair, Aby Abraham, Vikram Mathews, Biju George, Sanjay Kumar, Aparna Venkatraman, Alok Srivastava
Myelodysplastic syndromes (MDS) are a group of clonal hematopoietic disorders related to hematopoietic stem and progenitor cell dysfunction. Several studies have shown the role of the bone marrow microenvironment in regulating hematopoietic stem, and progenitor function and their individual abnormalities have been associated with disease pathogenesis. In this study, we simultaneously evaluated hematopoietic stem cells (HSC), hematopoietic stem progenitor cells (HSPCs) and different stromal elements in a cohort of patients with MDS-refractory cytopenia with multilineage dysplasia (RCMD)...
August 9, 2017: Blood Cells, Molecules & Diseases
https://www.readbyqxmd.com/read/28818807/early-treatment-initiation-in-lower-risk-myelodysplastic-syndromes-produces-an-earlier-and-higher-rate-of-transfusion-independence
#18
Christopher R Cogle, Sheila R Reddy, Eunice Chang, Elya Papoyan, Michael S Broder, Michael McGuire, Gary Binder
Myelodysplastic syndromes (MDS) are characterized by ineffective hematopoiesis resulting in refractory cytopenias. Red blood cell (RBC) transfusions can improve anemia; however, prolonged transfusion dependence (TD) is associated with increased morbidity and mortality. Disease-modifying therapy (DMT) for MDS can reduce transfusion requirements, although the optimum timing of DMT initiation is unclear. This retrospective study analyzed linked SEER registry and Medicare claims (2006-2012) to estimate the impact of DMT-initiation (azacitidine, decitabine, or lenalidomide) timing (≤ 3 vs...
September 2017: Leukemia Research
https://www.readbyqxmd.com/read/28817190/a-phase-1-and-2-study-of-filanesib-alone-and-in-combination-with-low-dose-dexamethasone-in-relapsed-refractory-multiple-myeloma
#19
Jatin J Shah, Jonathan L Kaufman, Jeffrey A Zonder, Adam D Cohen, William I Bensinger, Brandi W Hilder, Selena A Rush, Duncan H Walker, Brian J Tunquist, Kevin S Litwiler, Mieke Ptaszynski, Robert Z Orlowski, Sagar Lonial
BACKGROUND: Filanesib (ARRY-520) is a highly selective inhibitor of kinesin spindle protein, which has demonstrated preclinical antimyeloma activity. METHODS: This open-label Phase 1/2 study determined the maximum tolerated dose of Filanesib administered on Days 1 and 2 of 14-Day Cycles in patients with multiple myeloma (MM) and included expansion cohorts with and without dexamethasone (40 mg/week). Patients in the dose-escalation (N = 31) and Phase 2 single-agent (N = 32) cohorts had received prior bortezomib as well as prior thalidomide and/or lenalidomide...
December 1, 2017: Cancer
https://www.readbyqxmd.com/read/28810323/-the-efficacy-and-safety-of-the-patients-of-myelodysplastic-syndromes-refractory-anemia-with-excess-blasts-treated-with-decitabine-alone-or-cag-hag-regimen
#20
Z F Xu, T J Qin, H L Zhang, L W Fang, Y Zhang, L J Pan, N B Hu, S Q Qu, B Li, Z J Xiao
Objective: To observe the clinical efficacy and safety of the patients of myelodysplastic syndromes-refractory anemia with excess blasts (MDS-REAB) treated with decitabine alone or based on low dose cytarabine (Ara-C) regimen CAG/HAG [aclarubrci (ACR) /homoharring-tonine (HHT) +cytarabine+granulocyte colony stimulating factor (G-CSF) ]. Methods: Totally 121 patients with MDS-REAB were retrospectively analyzed, including 59 patients treated with decitabine alone (20 mg·m(-2)·d(-1) for 5 days) , the rest 62 ones treated with low-dose Ara-C-based regimen CAG/HAG...
July 14, 2017: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
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