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Leukemia stem cell

Mari Wilhelmsson, Heidi Glosli, Marianne Ifversen, Jonas Abrahamsson, Jacek Winiarski, Kirsi Jahnukainen, Henrik Hasle
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) improves event-free survival in acute myeloid leukemia (AML); however, the burden of late effects may be increased. We compared health-related outcomes in childhood AML survivors treated according to the NOPHO-AML protocols either with or without allo-HSCT at age < 21 years. Out of the 147 eligible AML survivors treated with allo-HSCT, 95 (65%) and 53 (75%) of their eligible siblings completed a questionnaire. Their data were compared to corresponding data collected previously from NOPHO-AML survivors treated with chemotherapy only (CT) (n = 101)...
September 21, 2018: Bone Marrow Transplantation
Philipp J Jost, Ulrike Höckendorf
The hematopoietic system represents an organ system with an exceptional capacity for the production of mature blood cells from a small and mostly quiescent pool of hematopoietic stem cells (HSCs). This extraordinary capacity includes self-renewal but also the propensity to rapidly respond to extrinsic needs, such as acute infections, severe inflammation, and wound healing. In recent years, it became clear that inflammatory signals such as cytokines, chemokine and danger signals from pathogens (PAMPs) or dying cells (DAMPs) impact on HSCs, shaping their proliferation status, lineage bias, and repopulating ability and subsequently increasing the output of mature effector cells...
September 21, 2018: Cell Death and Differentiation
Eytan M Stein, Min Yang, Annie Guerin, Wei Gao, Philip Galebach, Cheryl Q Xiang, Subrata Bhattacharyya, Gaetano Bonifacio, George J Joseph
BACKGROUND: Preference valuations of health status are essential in health technology and economic appraisal. This study estimated utilities for treatment-related health states of acute myeloid leukemia (AML) and disutilities of severe adverse events (SAEs) using a representative sample of adults from the general population in the United States (US). METHODS: Treatment-related AML health states, defined based on literature and interviews with clinicians, included complete remission (CR), no CR, relapse, stem cell transplant (SCT), and post SCT short-term recovery...
September 21, 2018: Health and Quality of Life Outcomes
S Warrier, J Taelman, L Tilleman, M Van der Jeught, G Duggal, S Lierman, M Popovic, A Van Soom, L Peelman, F Van Nieuwerburgh, D Deforce, S M Chuva de Sousa Lopes, P De Sutter, B Heindryckx
STUDY QUESTION: What are the transcriptional changes occurring during the human embryonic stem cell (hESC) derivation process, from the inner cell mass (ICM) to post-ICM intermediate stage (PICMI) to hESC stage, that have downstream effects on pluripotency states and differentiation? SUMMARY ANSWER: We reveal that although the PICMI is transcriptionally similar to the hESC profile and distinct from ICM, it exhibits upregulation of primordial germ cell (PGC) markers, dependence on leukemia inhibitory factor (LIF) signaling, upregulation of naïve pluripotency-specific signaling networks and appears to be an intermediate switching point from naïve to primed pluripotency...
September 17, 2018: Molecular Human Reproduction
Xingchen Pang, Hongjiao Li, Feng Guan, Xiang Li
The three types of blood cells (red blood cells for carrying oxygen, white blood cells for immune protection, and platelets for wound clotting) arise from hematopoietic stem/progenitor cells in the adult bone marrow, and function in physiological regulation and communication with local microenvironments to maintain systemic homeostasis. Hematological malignancies are relatively uncommon malignant disorders derived from the two major blood cell lineages: myeloid (leukemia) and lymphoid (lymphoma). Malignant clones lose their regulatory mechanisms, resulting in production of a large number of dysfunctional cells and destruction of normal hematopoiesis...
2018: Frontiers in Oncology
Chunfa Huang, Yifan Tu, Carl E Freter
Fludarabine (flu) -containing regimens such as flu, cyclophosphamide and rituximab have been established as one of the standard first line therapy in medically-fit chronic lymphocytic leukemia (CLL) patients. Therefore, flu-refractory (primary flu-insensitivity or flu-caused relapse) remains a major problem causing treatment failure for CLL patients. We isolated the peripheral blood mononuclear cells (PBMCs) from CLL patients and treated with flu to find flu-refractory cases, and established flu-resistant clonal cells to study molecular mechanism of flu-resistance...
September 4, 2018: Oncotarget
Aicha Laghmouchi, Conny Hoogstraten, Peter Van Balen, J H Frederik Falkenburg, Inge Jedema
Stem cell grafts from 10/10 HLA-matched unrelated donors are often mismatched for HLA-DP. In some patients, donor T cell responses targeting the mismatched HLA-DP allele(s) have been found to induce a specific graft-versus-leukemia effect without coinciding graft-versus-host disease, whereas in other cases significant graft-versus-host disease occurred. Cell-lineage-specific recognition patterns within the allo-HLA-DP specific donor T cell repertoire could explain the differential clinical effects mediated by donor T cells after HLA-DP mismatched allogeneic-stem-cell-transplantation...
September 20, 2018: Haematologica
Rafael Díaz de la Guardia, Belen Lopez-Millan, Heleia Roca-Ho, Clara Bueno, Francisco Gutiérrez-Agüera, Jose Luis Fuster, Eduardo Anguita, Samanta Zanetti, Susana Vives, Josep Nomdedeu, Robert Sackstein, Jessie Lavoie, Elena Gónzalez-Rey, Mario Delgado, Michael Rosu-Myles, Pablo Menendez
Acute myeloid leukemia represents a heterogeneous group of disorders characterized by the rapid expansion of immature myeloid cells (blasts) in the bone marrow. There is wide disease heterogeneity and patient risk-stratification principally relies on cytogenetic-molecular data. Bone-marrow mesenchymal stem/stromal cells are key components of the hematopoietic niche thought to contribute to leukemia pathogenesis. We recently reported a correlation between behaviors of bone-marrow mesenchymal stem/stromal cells from acute myeloid leukemia patients in vitro and overall survival...
September 20, 2018: Haematologica
Beatrice U Mueller, Katja Seipel, Ulrike Bacher, Thomas Pabst
While the majority of patients with acute myeloid leukemia (AML) are above the age of 65 years at diagnosis, the outcome of older AML patients remains disappointing. Even if standard intensive chemotherapy induces morphologic complete remission (CR1), relapses in older AML patients are common leading to poor long-term survival outcomes. Since autologous hematopoietic stem cell transplantation (HCT) offers distinct anti-leukemic effectiveness while avoiding graft-versus-host disease associated with allogeneic transplantation, it represents an option for consolidation treatment in selected older AML patients...
September 19, 2018: Cancers
Lixia Sheng, Huarui Fu, Yamin Tan, Yongxian Hu, Qitian Mu, Yi Luo, Jianmin Shi, Zhen Cai, Guifang Ouyang, He Huang
RATIONALE: Basiliximab and etanercept have achieved promising responses in steroid-refractory graft versus host disease (SR-GVHD). However, the in vivo immune changes following the treatment have not been elucidated. PATIENT CONCERNS: A 14-year-old boy presented with skin rash and diarrhea 20 days after haploidentical hemotopoietic stem cell transplantation. DIAGNOSES: We made the diagnose of grade 3 acute GVHD with skin and gastrointestinal involvement...
September 2018: Medicine (Baltimore)
Christine M McMahon, Alexander E Perl
Primary refractory acute myeloid leukemia (AML), or primary induction failure, represents a continued challenge in clinical management. This review presents an overview of primary refractory disease and a discussion of risk factors for induction failure, including current evidence regarding the impact of karyotype and molecular mutation status on responsiveness to chemotherapy. We review the evidence for various treatment options for refractory AML including salvage chemotherapy regimens, allogeneic hematopoietic stem cell transplantation, targeted agents, and non-intensive therapies such as hypomethylating agents...
September 20, 2018: Leukemia & Lymphoma
Suresh Babu Mc, Abhishek Anand, Kuntegowdanahalli C Lakshmaiah, Govind Babu K, Dasappa Lokanatha, Linu Abraham Jacob, D S Madhumathi, Kadabur N Lokesh, A H Rudresha, L K Rajeev, Rajesh Patidar
Background: T-cell prolymphocytic leukemia (T-PLL) is a rare lymphoid malignancy with dismal prognosis. Most patients have increased lymphocyte count (>1,00,000/dL) and widespread disease at presentation. Despite high response rate seen with alemtuzumab, the disease relapse is inevitable. Materials and Methods : This was a retrospective observational study done at a tertiary cancer center in South India. All patients diagnosed with T-PLL from August 2010 to July 2015 were studied for the clinical characteristics, pathological findings and treatment outcomes...
April 1, 2018: International Journal of Hematology-oncology and Stem Cell Research
Maryam Barkhordar, Mehdi Mohammadi, Molouk Hadjibabaie, Ardeshir Ghavamzadeh
Background: Allogeneic hematopoietic stem cell transplantation has been used widely to treat various types of malignant and non-malignant disorders. Graft-versus-host disease is one of the main complications of this procedure which is associated with considerable mortality and affects quality of life. Despite careful selection of HLA-matched donors and implementing immunosuppressive therapy, the incidence rate of graft-versus-host disease remains high. Macrolide antibiotics are well-known immunomodulatory agents and have been effective as prophylaxis for graft-versus-host disease in preclinical studies...
April 1, 2018: International Journal of Hematology-oncology and Stem Cell Research
Emanuela Zappulo, Laura Ambra Nicolini, Carmen Di Grazia, Alida Dominietto, Teresa Lamparelli, Francesca Gualandi, Patrizia Caligiuri, Bianca Bruzzone, Emanuele Angelucci, Claudio Viscoli, Malgorzata Mikulska
PURPOSE: Hepatitis B virus (HBV) reactivation during immunosuppressive therapy is common in patients with hematological malignancies, even in case of resolved infection. Prophylaxis of HBV reactivation is universally recommended in stem cell transplant (SCT) recipients and patients treated with anti-CD20 agents (i.e., rituximab). Despite its well-established favorable safety profile, lamivudine (LAM) use in prophylaxis has been debated because of the possible emergence of resistant viral strains...
September 19, 2018: Infection
Philipp Koehler, Norma Jung, Matthias Kochanek, Philipp Lohneis, Alexander Shimabukuro-Vornhagen, Boris Böll
INTRODUCTION: Staphylococcus aureus frequently causes infections in outpatient and hospital settings and can present as a highly variable entity. Typical manifestations are endocarditis, osteoarticular infections or infection of implanted prostheses, intravascular devices or foreign bodies. A thorough diagnostic evaluation with early focus identification is mandatory to improve patient outcome. CASE REPORT: We report a case of a 68-year old patient with a history of double allogeneic stem cell transplant for acute myeloid leukemia who developed a S...
September 18, 2018: Infection
Todd A Braciak, Claudia C Roskopf, Sarah Wildenhain, Nadja C Fenn, Christian B Schiller, Ingo A Schubert, Uwe Jacob, Annemarie Honegger, Christina Krupka, Marion Subklewe, Karsten Spiekermann, Karl-Peter Hopfner, Georg H Fey, Michael Aigner, Stefan Krause, Andreas Mackensen, Fuat S Oduncu
A number of agents designed for immunotherapy of Acute Myeloid Leukemia (AML) are in preclinical and early clinical development. Most of them target a single antigen on the surface of AML cells. Here we describe the development and key biological properties of a tri-specific agent, the dual-targeting triplebody SPM-2, with binding sites for target antigens CD33 and CD123, and for CD16 to engage NK cells as cytolytic effectors. Primary blasts of nearly all AML patients carry at least one of these target antigens and the pair is particularly promising for the elimination of blasts and leukemia stem cells (LSCs) from a majority of AML patients by dual-targeting agents...
2018: Oncoimmunology
Peng Zhang, Fuhong He, Jie Bai, Shohei Yamamoto, Shi Chen, Lin Zhang, Mengyao Sheng, Lei Zhang, Ying Guo, Na Man, Hui Yang, Suyun Wang, Tao Cheng, Stephen D Nimer, Yuan Zhou, Mingjiang Xu, Qian-Fei Wang, Feng-Chun Yang
ASXL1 is frequently mutated in myeloid malignancies and is known to co-occur with other gene mutations. However, the molecular mechanisms underlying the leukemogenesis associated with ASXL1 and cooperating mutations remain to be elucidated. Here we report that Asxl1 loss cooperated with haploinsufficiency of Nf1, a negative regulator of the RAS signaling pathway, to accelerate the development of myeloid leukemia in mice. Loss of Asxl1 and Nf1 in hematopoietic stem and progenitor cells resulted in a gain-of-function transcriptional activation of multiple pathways critical for leukemogenesis, such as MYC, NRAS, and BRD4...
September 18, 2018: Journal of Clinical Investigation
Leena T Rahmat, Anna Nguyen, Haifaa Abdulhaq, Sonam Prakash, Aaron C Logan, Gabriel N Mannis
Long-term disease-free survival in adults with T-cell acute lymphoblastic leukemia (T-ALL) remains poor, particularly after relapse, with few available salvage options. Preclinical data suggest that inhibition of the antiapoptotic protein BCL-2 (B-cell lymphoma 2) either alone or in combination with other agents, may be a unique therapeutic approach for the treatment of T-ALL. We present a case of a young male with T-ALL, relapsed after allogeneic hematopoietic stem cell transplant, who achieved a second complete remission following salvage therapy with combined venetoclax and decitabine...
2018: Case Reports in Hematology
Antònia Banús-Mulet, Amaia Etxabe, Josep Maria Cornet-Masana, Miguel Ángel Torrente, María Carmen Lara-Castillo, Laura Palomo, Meritxell Nomdedeu, Marina Díaz-Beyá, Francesc Solé, Benet Nomdedeu, Jordi Esteve, Ruth M Risueño
Myelodysplastic syndromes (MDS) and chronic myelomonocytic leukemia (CMML) are chronic myeloid clonal neoplasms. To date, the only potentially curative therapy for these disorders remains allogeneic hematopoietic progenitor cell transplantation (HCT), although patient eligibility is limited due to high morbimortality associated with this procedure coupled with advanced age of most patients. Dopamine receptors (DRs) and serotonin receptors type 1 (HTR1s) were identified as cancer stem cell therapeutic targets in acute myeloid leukemia...
September 17, 2018: Scientific Reports
Nikhil A Huprikar, Matthew R Peterson, Jeffrey D DellaVolpe, Valerie G Sams, James H Lantry, Robert J Walter, Michael B Osswald, Kevin K Chung, Phillip E Mason
BACKGROUND: The prognosis of hematologic malignancies has improved over the past three decades. However, the prognosis in hematologic malignancies with severe acute respiratory distress syndrome has remained poor. Initial reports regarding the utility of extracorporeal membrane oxygenation in hematologic malignancies have been controversial, with limited evaluations of acute leukemia patients supported by extracorporeal membrane oxygenation. METHODS: We conducted a retrospective review of patients with acute leukemia who developed acute respiratory distress syndrome requiring veno-venous extracorporeal membrane oxygenation support at our facility from July 2015 through August 2017...
September 17, 2018: International Journal of Artificial Organs
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