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refractory myelodysplastic syndrome

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https://www.readbyqxmd.com/read/28711727/a-chemotherapy-only-regimen-of-busulfan-melphalan-and-fludarabine-and-rabbit-atg-followed-by-allogeneic-t-cell-depleted-hematopoietic-stem-cell-transplants-for-the-treatment-of-myeloid-malignancies
#1
Barbara Spitzer, Ann A Jakubowski, Esperanza B Papadopoulos, Kirsten Fuller, Patrick D Hilden, James W Young, Juliet Barker, Guenther Koehne, Miguel-Angel Perales, Katharine C Hsu, Marcel R M van den Brink, Nancy A Kernan, Susan E Prockop, Andromachi Scaradavou, Hugo Castro-Malaspina, Richard J O'Reilly, Farid Boulad
We sought to develop a myeloablative chemotherapeutic regimen to secure consistent engraftment of T-cell depleted (TCD) hematopoietic stem cell transplants (HSCT) without the need for total body irradiation, thereby reducing toxicity, while maintaining low rates of GvHD and without increasing relapse. We investigated the myeloablative combination of busulfan and melphalan, with the immunosuppressive agents fludarabine and rabbit anti-thymocyte gloubin (r-ATG) as cytoreduction prior to a T-cell depleted HSCT...
July 12, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28705838/leukofiltration-plus-pathogen-reduction-prevents-alloimmune-platelet-refractoriness-in-a-dog-transfusion-model
#2
Sherrill J Slichter, Esther Pellham, S Lawrence Bailey, Todd Christoffel, Irena Gettinger, Lakshmi Gaur, Yvette Latchman, Karen Nelson, Doug Bolgiano
Human Lymphocyte Antigen (HLA) alloimmunization to filter leukoreduced (F-LR) platelets occurs in about 18% of immunosuppressed thrombocytopenic hematology/oncology patients and represents a significant challenge for effective chemotherapy. In a dog platelet transfusion model, we have evaluated other methods of preventing alloimmune platelet refractoriness and demonstrated that successful methods in our dog model are transferable to man. In the present study, donor/recipient pairs were dog lymphocyte antigen (DLA) DR-B incompatible (88% of the pairs), and recipient dogs received up to 8 weekly treated transfusions from a single donor (a highly immunogenic stimulus), or until platelet refractoriness...
July 13, 2017: Blood
https://www.readbyqxmd.com/read/28705782/biologics-in-myelodysplastic-syndrome-related-systemic-inflammatory-and-autoimmune-diseases-french-multicenter-retrospective-study-of-29-patients
#3
REVIEW
Arsene Mekinian, Guillaume Dervin, Nathanael Lapidus, Jean-Emmanuel Kahn, Louis Terriou, Eric Liozon, Eric Grignano, Jean-Charles Piette, Odile Beyne Rauzy, Vincent Grobost, Pascal Godmer, Jerome Gillard, Julien Rossignol, David Launay, Achille Aouba, Thierry Cardon, Laurence Bouillet, Jonathan Broner, Julien Vinit, Lionel Ades, Fabrice Carrat, Clementine Salvado, Eric Toussirot, Mathilde Versini, Nathalie Costedoat-Chalumeau, Jean Baptiste Fraison, Philippe Guilpain, Pierre Fenaux, Olivier Fain
BACKGROUND: Systemic inflammatory and autoimmune diseases (SIADs) associated with myelodysplastic syndromes are often difficult to treat. Corticosteroids are efficient but only usually at high doses. The use of biologics needs to be specified. METHODS: In a French multicenter retrospective study, we analyzed the efficacy and safety of biologics (tumor necrosis factor-α [TNF-α] antagonists, tocilizumab, rituximab and anakinra) for SIADs associated with myelodysplastic syndromes (MDSs)...
July 10, 2017: Autoimmunity Reviews
https://www.readbyqxmd.com/read/28687223/how-to-prevent-relapse-after-allogeneic-hematopoietic-stem-cell-transplantation-in-patients-with-acute-leukemia-and-myelodysplastic-syndrome
#4
REVIEW
N Yafour, F Beckerich, C E Bulabois, P Chevallier, E Daguindau, C Dumesnil, T Guillaume, A Huynh, S Masouridi Levrat, A L Menard, C Pautas, X Poiré, A Ravinet, M Michallet, A Bazarbachi
Disease relapse remains the first cause of mortality of hematological malignancies after allogeneic hematopoietic stem cell transplantation (allo-HCT). The risk of recurrence is elevated in acute myeloid leukemia (AML) patients with high-risk cytogenetic or molecular abnormalities, as well as when allo-HCT is performed in patients with refractory hematological malignancies or with persistent molecular or radiological (PET-CT scan) residual disease. For high risk AML and myelodysplasia (MDS), a post transplant maintenance strategy is possible, using hypomethylating agents or tyrosine kinase inhibitors (TKI) anti-FLT3 when the target is present...
July 4, 2017: Current Research in Translational Medicine
https://www.readbyqxmd.com/read/28687222/tp53-and-idh2-somatic-mutations-are-associated-with-inferior-overall-survival-after-allogeneic-hematopoietic-cell-transplantation-for-myelodysplastic-syndrome
#5
Mohamed A Kharfan-Dabaja, Rami S Komrokji, Qing Zhang, Ambuj Kumar, Athanasios Tsalatsanis, Janelle Perkins, Taiga Nishihori, Teresa Field, Najla Al Ali, Asmita Mishra, David Sallman, Karma Z Salem, Ling Zhang, Lynn Moscinski, Hugo F Fernandez, Jeffrey Lancet, Alan List, Claudio Anasetti, Eric Padron
BACKGROUND: Next-generation sequencing has identified somatic mutations that are prognostic of cancer. PATIENTS AND METHODS: We evaluated the incidence and prognostic significance of somatic mutations in 89 myelodysplastic syndrome (MDS) patients who received an allogeneic hematopoietic cell transplantation. Next-generation sequencing was performed on paraffin embedded bone marrow, which was obtained at a median of 31 days before initiating the preparative regimen...
June 16, 2017: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/28680340/successful-treatment-of-pulmonary-candidiasis-and-aspergillosis-in-patient-with-refractory-hodgkin-lymphoma-using-micafungin-case-study-and-brief-literature-review
#6
Marta Barańska, Renata Kroll-Balcerzak, Lidia Gil, Joanna Rupa-Matysek, Mieczysław Komarnicki
The number of patients with hematological malignancies who develop invasive fungal disease (IFD) has increased dramatically in recent decades. This increase is attributed to impairment of the host immune system due to intensive cytotoxic chemotherapies, use of corticosteroids and profound immunosuppression after hematopoietic stem cell transplantation (HSCT). Additionally, the increasing prevalence of fungal infections caused by emerging and rare pathogens, IFD of mixed etiology or of atypical localization is observed...
2017: Central-European Journal of Immunology
https://www.readbyqxmd.com/read/28679999/bone-marrow-failure-in-childhood-central-pathology-review-of-a-nationwide-registry
#7
Masafumi Ito
Refractory cytopenia of childhood (RCC) was proposed as a provisional entity in the 2008 WHO classification of myelodysplastic syndromes (MDS). It is defined as a childhood MDS featuring persistent cytopenia without increase blasts in bone marrow (BM) or peripheral blood (PB). Because the majority of RCC cases feature hypocellularity and pancytopenia, it is quite challenging to differentiate RCC from acquired aplastic anemia (AA) and many kinds of inherited bone marrow failure syndromes (IBMFS). Diagnosis of RCC requires BM histology of characteristic features such as isolated erythroid islet with left shift, abnormal localization and micromegakaryocytes...
2017: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
https://www.readbyqxmd.com/read/28675065/hypomethylating-agents-hma-treatment-for-myelodysplastic-syndromes-alternatives-in-the-frontline-and-relapse-settings
#8
Natalie Uy, Abhay Singh, Steven D Gore, Thomas Prebet
Hypomethylating agents (HMA) have played a pivotal role for treating myelodysplastic syndromes (MDS) over the past decade, inducing sustained hematological responses and delaying progression to leukemia. However, a vast majority of patients will experience treatment failure within 2 years, with poor prognoses and limited options, and management of this growing patient population remains unclear. Areas Covered: With the introduction of new agents in the MDS field, a better understanding of the biology of MDS, and updated information on standard of care options (including allogeneic transplantation), we re-evaluate the global treatment strategy in MDS via novel agents, focusing in particular on investigational approaches for patients who fail to respond to HMA when applicable...
July 4, 2017: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/28652792/severe-atypical-herpes-zoster-as-an-initial-symptom-of-fatal-myelodysplastic-syndrome-with-refractory-anemia-and-blast-excess-raeb-ii
#9
Uwe Wollina, Gesina Hansel, Anja Baunacke, Georgi Tchernev
Herpes zoster is a common disease caused due to varicella zoster virus (VZV) infection with increasing incidence by age. If the patient has a severe, extended, or treatment-recalcitrant course of herpes zoster, this must be a red flag to search for underlying pathologies. Here, we report about a 64-year-old male patient with diabetes, who came to our emergency department because of general malaise, fever, chills, and a pronounced nuchal and facial swelling on the left side. Based on herpetiform-grouped vesicles and yellowish crusts, an impetiginized facial herpes zoster was diagnosed, and combined antiviral and antibiotic treatment was initiated...
2017: Clinical, Cosmetic and Investigational Dermatology
https://www.readbyqxmd.com/read/28643044/pd-1-signaling-and-inhibition-in-aml-and-mds
#10
REVIEW
Faysal Haroun, Sade A Solola, Samah Nassereddine, Imad Tabbara
Acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) are clinically and molecularly heterogeneous clonal myeloid disorders with a poor prognosis especially in the relapsed refractory setting and in patients above the age of 60. While allogeneic hematopoietic stem cell transplantation (ASCT) is a potentially curative approach, high relapse, morbidity, and mortality rates necessitate the development of alternative therapies. Immune checkpoint inhibitors unmask tumoral immune tolerance and have demonstrated efficacy in the treatment of chemotherapy-resistant hematologic and solid malignancies...
June 22, 2017: Annals of Hematology
https://www.readbyqxmd.com/read/28588781/p53-protein-expression-in-patients-with-myelodysplasia-treated-with-allogeneic-bone-marrow-transplantation
#11
Achille Pich, Laura Godio, Laura Davico Bonino
Tumor protein 53 mutations adversely affect the prognosis of myelodysplastic syndromes (MDS); however, few studies have reported on the prognostic significance of the expression of p53 protein in MDS. The current study investigated p53 immunoreactivity (p53-IR) in bone marrow biopsies (BMBs) obtained at diagnosis from 18 patients (6 females and 12 males; mean age, 50.5 years) with MDS that underwent bone marrow transplantation (BMT) to determine the associations between clinical and histopathological data and outcome...
June 2017: Molecular and Clinical Oncology
https://www.readbyqxmd.com/read/28554891/dna-repair-gene-expressions-are-related-to-bone-marrow-cellularity-in-myelodysplastic-syndrome
#12
Howard L Ribeiro, Allan Rodrigo S Maia, Roberta Taiane G de Oliveira, Marília Braga Costa, Izabelle Rocha Farias, Daniela de Paula Borges, Juliana Cordeiro de Sousa, Silvia Maria M Magalhães, Ronald F Pinheiro
OBJECTIVE: To evaluate the expression of genes related to nuclear excision (ERCC8, XPA and XPC), homologous recombination and non-homologous end-joining (ATM, BRCA1, BRCA2 and LIG4) repair mechanisms, using quantitative PCR methodologies, and it relation with bone marrow cellularity in myelodysplastic syndrome (MDS). METHODS AND RESULTS: A total of 51 adult de novo patients with MDS (3 refractory anaemia (RA), 11 refractory anaemia with ringed sideroblasts (RARS), 28 refractory cytopenia with multilineage dysplasia (RCMD), 3 refractory anaemia with excess blasts type I (RAEB-I), 5 refractory anaemia with excess blasts type II (RAEB-II), and 1 chronic myelomonocytic leukaemia (CMML) were evaluated...
May 29, 2017: Journal of Clinical Pathology
https://www.readbyqxmd.com/read/28525589/bone-marrow-involvement-in-systemic-lupus-erythematosus
#13
Emilie Chalayer, Nathalie Costedoat-Chalumeau, Odile Beyne-Rauzy, Jacques Ninet, Stephane Durupt, Jacques Tebib, Bouchra Asli, Olivier Lambotte, Martine Ffrench, Christian Vasselon, Pascal Cathébras
BACKGROUND: Besides peripheral cytopenias, bone marrow abnormalities, such as fibrosis, pure red cell aplasia, and aplastic anemia have been reported in patients with systemic lupus erythematosus (SLE), suggesting that bone marrow may be a target organ in SLE. Our objective was to describe this bone marrow involvement. METHODS: This registry is a nationwide retrospective study. Centers provided data concerning medical history, SLE manifestations, type of hematologic disorder, treatments and outcome...
May 19, 2017: QJM: Monthly Journal of the Association of Physicians
https://www.readbyqxmd.com/read/28502939/myelodysplastic-syndrome-developing-presacral-extramedullary-hematopoiesis-with-atypical-mri-findings
#14
Haruki Sawada, Takakazu Higuchi, Ryosuke Koyamada, Sadamu Okada
A 64-year-old woman was diagnosed to have refractory cytopenia with multilineage dysplasia (RCMD) including an increased number of sideroblasts in the bone marrow (BM). Computed tomography (CT) revealed a presacral mass which showed iso- or high-intensity signals according to T1-weighted and hypo-intensity signals on T2-weighted magnetic resonance imaging (MRI). CT-guided biopsy revealed the presence of hematopoietic tissue with features that correlated with the BM findings. While the formation of extramedullary hematopoiesis in the presacral area is rare, it is important to differentiate it from other parasacral tumors even though such differentiation is often difficult...
2017: Internal Medicine
https://www.readbyqxmd.com/read/28491138/clinicohematological-and-cytogenetic-profile-of-myelodysplastic-syndromes-in-pakistan-compare-and-contrast
#15
Nida Anwar, Aisha Arshad, Muhammad Nadeem, Sana Khurram, Naveena Fatima, Sumaira Sharif, Saira Shan, Tahir Shamsi
BACKGROUND: Myelodysplastic syndromes (MDS) are clonal stem cell disorders exhibiting cytopenias, ineffective hematopoiesis and morphological dysplasia. Bone marrow cytogenetics, inspite of being incorporated as mandatory tool in diagnosis are done less frequently due to limited availability of this technique in Pakistan. The aim of the study was to study baseline clinicohematological and cytogenetic characteristics of patients presenting with de novo MDS. RESULTS: A retrospective cross sectional study was done at National Institute of Blood Diseases and Bone Marrow Transplantation, Karachi, Pakistan from 2010 to 2016...
2017: Molecular Cytogenetics
https://www.readbyqxmd.com/read/28451433/lenalidomide-induced-eosinophilic-pneumonia
#16
Andrew Toma, Aaron P Rapoport, Allen Burke, Ashutosh Sachdeva
Multiple myeloma is a plasma cell dyscrasia accounting for 10% of haematologic malignancies. Lenalidomide is an immunomodulatory drug analogous to thalidomide that is approved for use in patients with myelodysplastic syndrome, and in combination with dexamethasone for refractory or relapsed multiple myeloma. Lenalidomide is preferred to thalidomide because of reduced toxicity, and pulmonary side effects are considered rare. We present, to our knowledge, an unusual and first reported case of a patient with relapsed multiple myeloma who received lenalidomide after autologous stem cell transplant, then developed eosinophilic pneumonia presenting as dyspnoea, peripheral eosinophilia, and bilateral pulmonary opacities...
July 2017: Respirology Case Reports
https://www.readbyqxmd.com/read/28419413/long-term-outcomes-secondary-malignancies-and-stem-cell-collection-following-bendamustine-in-patients-with-previously-treated-non-hodgkin-lymphoma
#17
Peter Martin, Zhengming Chen, Bruce D Cheson, Katherine S Robinson, Michael Williams, Saurabh A Rajguru, Jonathan W Friedberg, Richard H van der Jagt, Ann S LaCasce, Robin Joyce, Kristen N Ganjoo, Nancy L Bartlett, Bernard Lemieux, Ari VanderWalde, Jordan Herst, Jeffrey Szer, Michael H Bar, Fernando Cabanillas, Anthony J Dodds, Paul G Montgomery, Bryn Pressnail, Tricia Ellis, Mitchell R Smith, John P Leonard
Despite the long history of bendamustine as treatment for indolent non-Hodgkin lymphoma, long-term efficacy and toxicity data are minimal. We reviewed long-term data from three clinical trials to characterize the toxicity and efficacy of patients receiving bendamustine. Data were available for 149 subjects at 21 sites. The median age was 60 years at the start of bendamustine (range 39-84), and patients had received a median of 3 prior therapies. The histologies included grades 1-2 follicular lymphoma (FL; n = 73), grade 3 FL (n = 23), small lymphocytic lymphoma (n = 20), marginal zone lymphoma (n = 15), mantle cell lymphoma (n = 9), transformed lymphomas (n = 5), lymphoplasmacytic lymphoma (n = 2) and not reported (n = 2)...
April 17, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28409853/a-phase-1-study-of-the-cxcr4-antagonist-plerixafor-in-combination-with-high-dose-cytarabine-and-etoposide-in-children-with-relapsed-or-refractory-acute-leukemias-or-myelodysplastic-syndrome-a-pediatric-oncology-experimental-therapeutics-investigators-consortium
#18
Todd M Cooper, Edward Allan Racela Sison, Sharyn D Baker, Lie Li, Amina Ahmed, Tanya Trippett, Lia Gore, Margaret E Macy, Aru Narendran, Keith August, Michael J Absalon, Jessica Boklan, Jessica Pollard, Daniel Magoon, Patrick A Brown
BACKGROUND: Plerixafor, a reversible CXCR4 antagonist, inhibits interactions between leukemic blasts and the bone marrow stromal microenvironment and may enhance chemosensitivity. A phase 1 trial of plerixafor in combination with intensive chemotherapy in children and young adults with relapsed or refractory acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), and myelodysplastic syndrome (MDS) was performed to determine a tolerable and biologically active dose. PROCEDURE: Plerixafor was administered daily for 5 days at four dose levels (6, 9, 12, and 15 mg/m(2) /dose) followed 4 hr later by high-dose cytarabine (every 12 hr) and etoposide (daily)...
April 14, 2017: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/28395942/ex-vivo-t-cell-depleted-allogeneic-stem-cell-transplantation-for-hematologic-malignancies-the-search-for-an-optimum-transplant-t-cell-dose-and-t-cell-add-back-strategy
#19
Prathima Anandi, Xin Tian, Sawa Ito, Pawel Muranski, Puja D Chokshi, Noelle Watters, Upneet Chawla, Nancy Hensel, David F Stroncek, Minoo Battiwalla, A John Barrett
BACKGROUND: T-cell depletion (TCD) of allogeneic stem cell transplants (SCT) can reduce graft-versus-host disease but may negatively affect transplant outcome by delaying immune recovery. To optimize TCD in HLA-matched siblings with hematologic malignancies, we explored varying the transplant CD3+ T-cell dose between 2 and 50 × 10(4)/kg (corresponding to 3-4 log depletion) and studied the impact of 0-6 × 10(7)/kg CD3+ donor lymphocyte infusion (DLI) "add-back" on immune recovery post-SCT...
April 7, 2017: Cytotherapy
https://www.readbyqxmd.com/read/28388253/lenalidomide-in-the-treatment-of-chronic-lymphocytic-leukemia
#20
REVIEW
Gilad Itchaki, Jennifer R Brown
Lenalidomide is an immunomodulatory drug (IMiD) with a unique mode of action (MOA) that may vary across disease-type. It is currently approved in multiple myeloma (MM), myelodysplastic syndrome (MDS) and mantle cell lymphoma (MCL), yet is also clinically active in a host of lymphoproliferative diseases, including chronic lymphocytic leukemia (CLL). Due to its protean effects on the immune system, lenalidomide may be particularly appealing in CLL, which is distinct in its ability to evade immune recognition and cause immunosuppression...
May 2017: Expert Opinion on Investigational Drugs
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