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lymphoblastic acute leukemia

Yu Akahoshi, Shuichi Mizuta, Hiroaki Shimizu, Naoyuki Uchida, Takahiro Fukuda, Heiwa Kanamori, Makoto Onizuka, Yukiyasu Ozawa, Kazuteru Ohashi, Shuichi Ohta, Tetsuya Eto, Junji Tanaka, Yoshiko Atsuta, Shinichi Kako
Cytogenetic abnormalities are well-known and powerful independent prognostic factor for various hematological disorders. Although the combination of chemotherapy with tyrosine kinase inhibitor (TKI) is now considered the standard of care in patients with Philadelphia chromosome-positive acute lymphoblastic leukemia, little is known about the impact of additional cytogenetic abnormalities (ACAs). Therefore, we retrospectively evaluated 1375 adult patients who underwent their first allogeneic hematopoietic stem cell transplantation in the TKI era...
June 13, 2018: Biology of Blood and Marrow Transplantation
Avichai Shimoni, Myriam Labopin, Francesca Lorentino, Maria Teresa Van Lint, Yener Koc, Zafer Gülbas, Johanna Tischer, Benedetto Bruno, Didier Blaise, Pietro Pioltelli, Boris Afanasyev, Fabio Ciceri, Mohamad Mohty, Arnon Nagler
Haploidentical stem cell transplantation with T cell-replete grafts and post-transplant cyclophosphamide (PTCy) is increasingly used with encouraging outcome. Natural killer (NK) cell alloreactivity, predicted by missing killer cell immunoglobulin-like receptor (KIR) ligands in the recipient that are present in their donor improves outcome of T cell-depleted haploidentical transplants. We explored the role of KIR ligand mismatching in 444 acute leukemia patients after T cell-replete transplants with PTCy. Thirty-seven percent of all patients had KIR ligand mismatching...
June 15, 2018: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
Sang-Kyu Kim, Deborah A Knight, Lisa R Jones, Stephin Vervoort, Ashley P Ng, John F Seymour, James E Bradner, Michaela Waibel, Lev Kats, Ricky W Johnstone
Activating JAK2 point mutations are implicated in the pathogenesis of myeloid and lymphoid malignancies, including high-risk B-cell acute lymphoblastic leukemia (B-ALL). In preclinical studies, treatment of JAK2 mutant leukemias with type I JAK2 inhibitors (e.g., Food and Drug Administration [FDA]-approved ruxolitinib) provided limited single-agent responses, possibly due to paradoxical JAK2Y1007/1008 hyperphosphorylation induced by these agents. To determine the importance of mutant JAK2 in B-ALL initiation and maintenance, we developed unique genetically engineered mouse models of B-ALL driven by overexpressed Crlf2 and mutant Jak2, recapitulating the genetic aberrations found in human B-ALL...
June 15, 2018: Genes & Development
Ibrahim Aldoss, Tracey Stiller, Ni-Chun Tsai, Joo Y Song, Thai Cao, N Achini Bandara, Amadeep Salhotra, Samer Khaled, Ahmed Aribi, Monzr M Al Malki, Matthew Mei, Haris Ali, Ricardo Spielberger, Margaret O'Donnell, David Snyder, Thomas Slavin, Ryotaro Nakamura, Anthony S Stein, Stephen J Forman, Guido Marcucci, Vinod Pullarkat
Therapy-related acute lymphoblastic leukemia remains poorly defined due to a lack of large data sets recognizing the defining characteristics of this entity. We reviewed all consecutive cases of adult acute lymphoblastic leukemia treated at our institution between 2000 and 2017 and identified therapy-related cases-defined as acute lymphoblastic leukemia preceded by prior exposure to cytotoxic chemotherapy and/or radiation. Of 1022 patients with acute lymphoblastic leukemia, 93 (9.1%) were classified as therapy-related...
June 14, 2018: Haematologica
María Lilia Adriana Juárez-López, Marlen Nicolett Solano-Silva, Rodolfo Fragoso-Ríos, Francisco Murrieta-Pruneda
Background: Pediatric patients with acute lymphoblastic leukemia (ALL) usually develop oral manifestations due to the disease itself, as well as side effects of chemotherapy that severely affect their health and quality of life. The aim of this paperis to determine the prevalence of oral diseases in pediatric all patients with and without chemotherapy and its relation to the different phases of chemotherapy. Methods: A cross-sectional observational study was conducted in 103 pediatric patients with all between 3-15 years...
March 2018: Revista Médica del Instituto Mexicano del Seguro Social
Dezhi Li, Qian Liu, Zhifang Feng, Qi Zhang, Saran Feng
RATIONALE: Nephrogenic diabetes insipidus (NDI) rarely presents in the initial stage of acute lymphoblastic leukemia (ALL) and relapse due to renal infiltration is also rare. PATIENT CONCERNS: A 19-year-old man presented with weakness, polydipsia, and polyuria for 1 month. DIAGNOSES: NDI was diagnosed with insignificant response to a water deprivation test after stimulation with vasopressin injection. Bone marrow examination combined with immunophenotypic analysis, cerebrospinal cytology, and abdominal ultrasonography confirmed the diagnoses of precursor B cell ALL with renal infiltration...
June 2018: Medicine (Baltimore)
Charlene Rae, William Furlong, David Feeny, Rana Couchman, Lewis Silverman, Stephen Sallan, Caroline Laverdiere, Luis Clavell, Bruno Michon, Kara Kelly, Eric Larsen, Eleanor Pullenayegum, Uma Athale, Ronald Barr
Health-related quality of life (HRQL) improved progressively during therapy and beyond in children treated for acute lymphoblastic leukemia on the Dana-Farber Cancer Institute (DFCI) 95-01 protocol. This study aimed to validate that trajectory in a successor study (DFCI 00-01) and to compare the HRQL of patients in the 2 studies. Children aged above 5 years were assessed during each phase of treatment (N=4) and 2 years after completion of therapy. Health status and HRQL were measured using Health Utilities Index (HUI) instruments, HUI2 and HUI3...
June 12, 2018: Journal of Pediatric Hematology/oncology
E Delvin, M Boisvert, M-A Lecours, Y Théorêt, M Kaufmann, G Jones, E Levy
This article describes data related to a companion research paper entitled "Vitamin D nutritional status and bone turnover biomarkers in childhood acute lymphoblastic leukemia (cALL) survivors." (Delvin et al., submitted for publication) [1]. Various methods for the measurement of serum 25OHD3 , the accepted biomarker for assessing vitamin D nutritional status, have been described (Le Goff et al., 2015; Jensen et al., 2016) [2], [3]. This article describes a novel mass spectrometry-QTOF method for the quantification of circulating 25OHD3 , 3-epi-25OHD3 and 24,25(OH)2 D3 ...
June 2018: Data in Brief
Sarah K Tasian
Chemotherapy resistance and relapse remain significant sources of mortality for children and adults with acute myeloid leukemia (AML). Further intensification of conventional cytotoxic chemotherapy is likely not feasible due to the severity of acute and long-term side effects upon normal tissues commonly induced by these drugs. Successful development and implementation of new precision medicine treatment approaches for patients with AML, which may improve leukemia remission and diminish toxicity, is thus a major priority...
June 2018: Therapeutic Advances in Hematology
Agata Pastorczak, Lukasz Sedek, Marcin Braun, Joanna Madzio, Alicja Sonsala, Magdalena Twardoch, Wojciech Fendler, Karin Nebral, Joanna Taha, Marta Bielska, Patryk Gorniak, Magdalena Romiszewska, Michal Matysiak, Katarzyna Derwich, Monika Lejman, Jerzy Kowalczyk, Wanda Badowska, Maciej Niedzwiecki, Bernarda Kazanowska, Katarzyna Muszynska-Roslan, Grazyna Sobol-Milejska, Grazyna Karolczyk, Andrzej Koltan, Tomasz Ociepa, Tomasz Szczepanski, Wojciech Młynarski
We prospectively examined whether surface expression of Cytokine Receptor-Like Factor 2 (CRLF2) on leukemic blasts is associated with survival and induction treatment response in pediatric B-cell precursor acute lymphoblastic leukemia (BCP-ALL) patients. Flow cytometric analysis of bone marrow-derived leukemia cells revealed that 7.51% (29/286) of 386 pediatric BCP-ALL patients were CRLF2-positive (CRLF2pos) at diagnosis. The median minimal residual disease (MRD) was lower in CRLF2pos than CRLF2-negative (CRLF2neg) patients on day 15 (MRD15) after induction therapy [0...
May 25, 2018: Oncotarget
Maria Gabelli, Marco Zecca, Chiara Messina, Elisa Carraro, Barbara Buldini, Attilio Maria Rovelli, Franca Fagioli, Alice Bertaina, Edoardo Lanino, Claudio Favre, Marco Rabusin, Arcangelo Prete, Mimmo Ripaldi, Walter Barberi, Fulvio Porta, Maurizio Caniglia, Stella Santarone, Paolo D'Angelo, Giuseppe Basso, Franco Locatelli
Relapse of acute lymphoblastic leukemia (ALL) may occur in extramedullary sites, mainly central nervous system (CNS) and testis. Optimal post-remissional treatment for isolated extramedullary relapse (IEMR) is still controversial. We collected data of children treated with hematopoietic stem cell transplantation (HSCT) for ALL IEMR from 1990 to 2015 in Italy. Among 281 patients, 167 had a relapse confined to CNS, 73 to testis, 14 to mediastinum, and 27 to other organs. Ninety-seven patients underwent autologous HSCT, 79 received allogeneic HSCT from a matched family donor, 75 from a matched unrelated donor, and 30 from an HLA-haploidentical donor...
June 13, 2018: Bone Marrow Transplantation
Mohammad Reza Sam, Somayyeh Ghoreishi
AIMS: Matrix metalloproteinase-9 (MMP-9) and survivin are involved in several steps of carcinogenesis in acute lymphoblastic leukemia (ALL). Yet, no MMP-9 and survivin-modulating drugs with low toxicity on normal cells but high efficacy against high MMP-9- and survivin- expressing leukemia cells have been approved for clinical application in ALL. Prodigiosin a secondary metabolite of Serratia marcescens induces apoptosis in different kinds of cancer cells with low toxicity on normal cells...
June 13, 2018: Journal of Applied Microbiology
Nicolas Boissel, André Baruchel
Adolescent and young adult (AYA) patients with acute lymphoblastic leukemia (ALL) are recognized as a unique population with specific characteristics and needs. In adolescents aged 15-20 years old, the use of full pediatric protocols is supported by many comparative studies of pediatric and adult cooperative groups. In young adults, growing evidence suggests that pediatric-inspired or even fully pediatric approaches may also dramatically improve outcomes, leading to long-term survival rates of almost 70%, despite diminishing indications of hematopoietic stem cell transplantation...
June 12, 2018: Blood
Christos Demosthenous, Chrysavgi Lalayanni, Michalis Iskas, Vassiliki Douka, Nikoleta Pastelli, Achilles Anagnostopoulos
Blinatumomab, a bispecific T-cell engager antibody construct targeting CD19, has been shown to improve the outcome in patients with relapsed and/or refractory B-cell acute lymphoblastic leukemia. Treatment with blinatumomab demonstrated significant survival benefit over chemotherapy, supporting its use as a bridge therapy to allogeneic hematopoietic stem cell transplantation. Unfortunately, following initial response, approximately 50% of responding patients eventually relapse. At the time of failure, the majority of patients have CD19-positive blasts, yet a concerning number of CD19-negative relapses has been reported...
May 7, 2018: Current Problems in Cancer
Amitabh Singh, Lesa Dawman, Rachna Seth
Aim of Study: Hemophagocytic lymphohistiocytosis (HLH) is a rare disorder of immune dysregulation resulting in abnormal T-cell activation and inflammatory cytokine production which produces a constellation of clinical features unique to HLH. Pediatric secondary HLH is usually triggered by infection, malignancy, or rheumatological disorders. The diagnosis of malignancy-associated HLH (MA-HLH) poses a difficult challenge as clinical features may be attributed to the underlying disease or chemotherapy...
April 2018: Journal of Cancer Research and Therapeutics
Maximilian Pistor, Lisa Schrewe, Steffen Haupeltshofer, Andrei Miclea, Simon Faissner, Andrew Chan, Robert Hoepner
In acute lymphoblastic leukemia (ALL), steroid resistance and hypovitaminosis D are both associated with a poor prognosis. We show that methylprednisolone, calcitriol and the AKT-inhibitor MK-2206 have a synergistic effect on the apoptosis of steroid resistant T-ALL cells. Compared to methylprednisolone monotherapy, calcitriol increases methylprednisolone induced apoptosis dose-dependently (1.37-1.92-fold; p < 0.05). Pre-incubation with calcitriol increases the apoptotic effect of MK-2206 even further (3...
2018: Leukemia Research Reports
Jason R Schwartz, Michael P Walsh, Jing Ma, Tamara Lamprecht, Shuoguo Wang, Gang Wu, Susana Raimondi, Brandon Triplett, Jeffery Klco
Donor-derived hematologic malignancies are rare complications of hematopoietic cell transplantation (HCT). Although these are commonly either a myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML), in general, they are a heterogeneous group of diseases and a unified mechanism for their development has remained elusive. Here we report next generation sequencing, including whole exome sequencing (WES), whole genome sequencing (WGS), and targeted sequencing, of a case of donor-derived MDS (dMDS) following HCT for high-risk B-lymphoblastic leukemia (B-ALL) in an adolescent...
June 11, 2018: Cold Spring Harbor Molecular Case Studies
David Boutboul, Hye Sun Kuehn, Zoé Van de Wyngaert, Julie E Niemela, Isabelle Callebaut, Jennifer Stoddard, Christelle Lenoir, Vincent Barlogis, Catherine Farnarier, Frédéric Vely, Nao Yoshida, Seiji Kojima, Hirokazu Kanegane, Akihiro Hoshino, Fabian Hauck, Ludovic Lhermitte, Vahid Asnafi, Philip Roehrs, Shaoying Chen, James W Verbsky, Katherine R Calvo, Ammar Husami, Kejian Zhang, Joseph Roberts, David Amrol, John Sleaseman, Amy P Hsu, Steven M Holland, Rebecca Marsh, Alain Fischer, Thomas A Fleisher, Capucine Picard, Sylvain Latour, Sergio D Rosenzweig
Ikaros/IKZF1 is an essential transcription factor expressed throughout hematopoiesis. IKZF1 is implicated in lymphocyte and myeloid differentiation and negative regulation of cell proliferation. In humans, somatic mutations in IKZF1 have been linked to the development of B cell acute lymphoblastic leukemia (ALL) in children and adults. Recently, heterozygous germline IKZF1 mutations have been identified in patients with a B cell immune deficiency mimicking common variable immunodeficiency. These mutations demonstrated incomplete penetrance and led to haploinsufficiency...
June 11, 2018: Journal of Clinical Investigation
Siliang Duan, Yating Yu, Chunhui Lai, Dujin Wang, Yiwei Wang, Dabing Xue, Zixi Hu, Xiaoling Lu
Cytotoxic compounds vincristine sulphate (VCR) is widely used to against hemato-oncology, and especially the acute lymphoblastic leukemia (ALL). However, VCR's full therapeutic potential has been limited by its dose-limiting neurotoxicity, classically resulting in autonomic and peripheral sensory-motor neuropathy. Therefore, we developed a targeted liposomal drug delivery system (sgc8/VCR-Lipo) for improving the therapeutic effects of VCR against leukemia and reducing its systematic adverse effects. sgc8/VCR-Lipo could specifically bind to CCRF-CEM cells and significantly inhibit proliferation of cancer cells in vitro and tumor growth in vivo...
May 1, 2018: Journal of Biomedical Nanotechnology
Fabian Müller, Tyler Cunningham, Richard Beers, Tapan K Bera, Alan S Wayne, Ira Pastan
Moxetumomab pasudotox is a fusion protein of a CD22-targeting antibody and Pseudomonas exotoxin. Minutes of exposure to Moxetumomab achieves similar cell killing than hours of exposure to a novel deimmunized variant against some acute lymphoblastic leukemia (ALL). Because blood levels fall quickly, Moxetumomab is more than 1000-fold more active than the deimmunized variant in vivo. We aimed to identify which part of Moxetumomab increases in vivo efficacy and generated five immunotoxins, tested time-dependent activity, and determined the efficacy in a KOPN-8 xenograft model...
May 21, 2018: Toxins
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