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Acute Lymphoblastic leukemia in adults

Abolghasem Allahyari, Seyed-Mehdi Hashemi, Fahimeh Nazemian, Mohammad Karimi, Mohammad-Reza Kazemi, Masoud Sadeghi
BACKGROUND: Acute lymphoblastic leukemia (ALL) is aggressive cancer, especially in adults as only 20-40% is cured with current treatment regimens. OBJECTIVES: The aim of this study is to evaluate prognostic factors and their effects on survival in ALL patients in the Northeast of Iran. METHODS: In a descriptive and retrospective study from 2009 to 2015, 48 ALL patients referred to hematology-oncology clinic. Age, sex, fever, blood group, type of ALL and consumption of amphotericin B, forms of cytogenetic, survival in the patients, WBC, hemoglobin, and platelet were checked in the first referral for every patient...
August 2016: Iranian Journal of Cancer Prevention
Wenwen Wang, Elena Foerner, Eike Buss, Anna Jauch, Volker Eckstein, Patrick Wuchter, Anthony D Ho, Christoph Lutz
In B-cell acute lymphoblastic leukemia (B-ALL) separation of normal hematopoietic stem cells (HSC) has so far been limited to a subgroup of patients. As aldehyde dehydrogenase (ALDH)-activity is enriched in various stem cells we investigated its value for HSC isolation in adult B-ALL. Based on ALDH-activity patients could be stratified in ALDH-numerous (≥1.9% ALDH(+ )cells) and ALDH-rare (<1.9% ALDH(+ )cells) cases. In ALDH-rare B-ALL clonal-marker negative HSC could be separated by the CD34(+)CD38(-)ALDH(+ ) phenotype, whereas this separation was not possible in ALDH-numerous B-ALL...
October 13, 2016: Leukemia & Lymphoma
Leylagul Kaynar, Koray Demir, Esra Ermiş Turak, Çiğdem Pala Öztürk, Gökmen Zararsız, Zeynep Burçin Gönen, Selma Gökahmetoğlu, Serdar Şıvgın, Bülent Eser, Yavuz Köker, Musa Solmaz, Ali Ünal, Mustafa Çetin
INTRODUCTION: The use of αβ+ T-cell-depleted grafts is a novel approach to prevent graft failure, graft-versus-host disease (GVHD), and non-relapse mortality (NRM) in patients undergoing haploidentical hematopoietic stem cell transplantation. PATIENT AND METHOD: Thirty-four patients with acute leukemia and lacking a match donor were treated with αβ T-cell-depleted allografts from haploidentical family donors. A total of 24 patients had acute myeloid leukemia (AML) and 10 had acute lymphoblastic leukemia...
October 10, 2016: Hematology (Amsterdam, Netherlands)
Marc Heincelman, Nithin Karakala, Don C Rockey
Acute lymphoblastic leukemia (ALL) in adults is a relatively rare malignancy. The typical presentation includes signs and symptoms associated with bone marrow failure, including fevers, infections, fatigue, and excessive bruising. In this article, we report an unusual systemic presentation of ALL in a previously healthy 18-year-old man. He initially presented with several-day history of nausea and vomiting, 10-pound weight loss, and right upper quadrant abdominal pain with evidence of acute hepatocellular liver injury (elevations in aspartate aminotransferase/alanine aminotransferase) and elevation in serum creatinine...
July 2016: Journal of Investigative Medicine High Impact Case Reports
Ashley Rosko, Hai-Lin Wang, Marcos de Lima, Brenda Sandmaier, H Jean Khoury, Andrew Artz, Johnathan Brammer, Christopher Bredeson, Sherif Farag, Mohamed Kharfan-Dabaja, Hillard M Lazarus, David I Marks, Rodrigo Martino Bufarull, Joseph McGuirk, Mohamed Mohty, Taiga Nishihori, Ian Nivison-Smith, Armin Rashidi, Olle Ringden, Matthew Seftel, Daniel Weisdorf, Veronika Bachanova, Wael Saber
: Older adults with B-cell acute lymphoblastic leukemia (B-ALL) have poor survival. We examined the effectiveness of reduced intensity conditioning (RIC) hematopoietic cell transplant (HCT) in adults with B-ALL age 55 years and older and explored prognostic factors associated with long-term outcomes. METHODS: Using CIBMTR registry data, we evaluated 273 patients (median age 61, range 55-72) with B-ALL with disease status in CR1 (71%), >CR2 (17%) and Primary Induction Failure (PIF)/Relapse (11%), who underwent RIC HCT between 2001-2012 using mostly unrelated donor (59%) or HLA-matched sibling (32%)...
October 6, 2016: American Journal of Hematology
Laurence Baranger, Wendy Cuccuini, Christine Lefebvre, Isabelle Luquet, Christine Perot, Isabelle Radford, Marina Lafage-Pochitaloff
Cytogenetic analyses (karyotype and, if necessary, appropriate complementary FISH analyses) are mandatory at diagnosis in acute lymphoblastic leukemia (ALL) as their results are taken into account in therapeutic protocols due to their diagnostic and prognostic values. In some cases, karyotype can be completed by other techniques (RT-PCR, RQ-PCR, DNA content, SNP-array, MLPA…) that can be equally or more informative than FISH. Here, we have tempted to establish guidelines concerning karyotype and FISH analyses according to the most recent data of the litterature which is reviewed here, completing the 2008 WHO classification with the recent new cytogenomic entities such as Ph-like ALL and indicating possible therapeutic implications...
October 1, 2016: Annales de Biologie Clinique
Zheng Ge, Min Li, Gang Zhao, Lichan Xiao, Yan Gu, Xilian Zhou, Michael D Yu, Jianyong Li, Sinisa Dovat, Chunhua Song
Genetic mutations on signaling pathways are found in patients with T-cell acute lymphoblastic leukemia (T-ALL) and act as markers of high-risk leukemia. Mutations in dynamin 2 (DNM2) have been reported in T-ALL, particularly in early T-cell precursor-ALL. In the present study, DNM2 mutations were screened by sequencing DNM2 exons obtained by polymerase chain reaction amplification and gel purification in adult T-ALL patients. A total of 4 novel DNM2 mutations were identified in adult T-ALL patients, with a mutation rate of 9...
October 2016: Oncology Letters
Ghayas C Issa, Hagop M Kantarjian, C Cameron Yin, Wei Qiao, Farhad Ravandi, Deborah Thomas, Nicholas J Short, Koji Sasaki, Guillermo Garcia-Manero, Tapan M Kadia, Jorge E Cortes, Naval Daver, Gautam Borthakur, Nitin Jain, Marina Konopleva, Issa Khouri, Partow Kebriaei, Richard E Champlin, Sherry Pierce, Susan M O'Brien, Elias Jabbour
BACKGROUND: The introduction of novel prognostic factors such as minimal residual disease (MRD) and genomic profiling has led to the reevaluation of the role of cytogenetics and other conventional factors in risk stratification for acute lymphoblastic leukemia (ALL). METHODS: This study assessed the impact of baseline cytogenetics on the outcomes of 428 adult patients with Philadelphia chromosome-negative ALL who were receiving frontline chemotherapy. Three hundred thirty patients (77%) were treated with hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone-based regimens, and 98 (23%) were treated with the augmented Berlin-Frankfurt-Munster regimen...
October 3, 2016: Cancer
Nikolaos Papadantonakis, Anjali S Advani
This is an exciting time in the treatment of acute lymphoblastic leukemia (ALL) given the advances in the relapsed/refractory setting. The development of antibody treatments (including antibody drug conjugates with toxins) offers a different treatment approach compared with conventional chemotherapy regimens. Moreover, the use of bispecific T-cell-engager antibodies (BiTEs) such as blinatumomab harness the cytotoxic activity of T cells against CD19-positive lymphoblasts. Another strategy involves the use of chimeric antigen receptor (CAR) T cells...
October 2016: Therapeutic Advances in Hematology
Mingming Zhang, Huarui Fu, Xiaoyu Lai, Yamin Tan, Weiyan Zheng, Jimin Shi, Yanmin Zhao, Maofang Lin, Jingsong He, Zhen Cai, Yi Luo, He Huang
We evaluated the prognostic effect of minimal residual disease at first achievement of complete remission (MRD at CR1) in adult patients with Philadelphia chromosome-negative acute lymphoblastic leukemia (ALL). A total of 97 patients received treatment in our center between 2007 and 2012 were retrospectively reviewed in this study. Patients were divided into two arms according to the post-remission therapy (chemotherapy alone or allogeneic hematopoietic stem cell transplantation (allo-HSCT)) they received. MRD was detected by four-color flow cytometry...
2016: PloS One
Sebastian Giebel, Myriam Labopin, Gerard Socie', Dietrich Beelen, Paul Browne, Liisa Volin, Slawomira Kyrcz-Krzemien, Ibrahim Yakoub-Agha, Mahmoud Aljurf, Depei Wu, Mauricette Michallet, Renate Arnold, Mohamad Mohty, Arnon Nagler
Allogeneic hematopoietic cell transplantation is widely used to treat adults with high risk acute lymphoblastic leukemia. The aim of this study was to analyze whether the results changed over time and to identify prognostic factors. Adult patients treated between year 1993 and 2012 with myeloablative allogeneic hematopoietic cell transplantation from HLA matched sibling (n=2681) or unrelated donors (n=2178) in first complete remission were included. For transplantations from sibling donors performed between 2008-2012, the following two-year probabilities of the overall survival were obtained: 76% (18-25 years old group), 69% (26-35 and 36-45 years old groups) and 60% (46-55 years old group)...
September 29, 2016: Haematologica
Sandra Eder, Eric Beohou, Myriam Labopin, Jaime Sanz, Jürgen Finke, William Arcese, Reuven Or, Francesca Bonifazi, Mahmoud Aljurf, Gerard Socié, Jakob Passweg, Sebastian Giebel, Mohamad Mohty, Arnon Nagler
In this study, we analyzed a thiotepa-based conditioning regimen for allogeneic stem cell transplantation in adults with acute lymphoblastic leukemia, using the EBMT database. A total of 323 patients were identified. The median age was 43 years. Disease status at transplant was first complete remission (CR1) in 48.9%, CR2 in 21.7%, CR3 in 6.2%, while 23.2% of the patients had an active disease at the time of transplant. This was performed from a HLA-matched sibling (49.8%) or a matched-unrelated donor (51.2%)...
September 27, 2016: American Journal of Hematology
Lia Minculescu, Hanne Vibeke Marquart, Lone Smidstrups Friis, Soeren Lykke Petersen, Ida Schiødt, Lars Peter Ryder, Niels Smedegaard Andersen, Henrik Sengeloev
Early immune reconstitution plays a critical role in clinical outcome after allogeneic hematopoietic stem cell transplantation (HSCT). Natural killer (NK) cells are the first lymphocytes to recover after transplantation and are considered powerful effector cells in HSCT. We aimed to evaluate the clinical impact of early NK cell recovery in T cell-replete transplant recipients. Immune reconstitution was studied in 298 adult patients undergoing HSCT for acute myeloid leukemia, acute lymphoblastic leukemia, and myelodysplastic syndrome from 2005 to 2013...
September 21, 2016: Biology of Blood and Marrow Transplantation
N Gökbuget, M Kelsh, V Chia, A Advani, R Bassan, H Dombret, M Doubek, A K Fielding, S Giebel, V Haddad, D Hoelzer, C Holland, N Ifrah, A Katz, T Maniar, G Martinelli, M Morgades, S O'Brien, J-M Ribera, J M Rowe, A Stein, M Topp, M Wadleigh, H Kantarjian
We compared outcomes from a single-arm study of blinatumomab in adult patients with B-precursor Ph-negative relapsed/refractory acute lymphoblastic leukemia (R/R ALL) with a historical data set from Europe and the United States. Estimates of complete remission (CR) and overall survival (OS) were weighted by the frequency distribution of prognostic factors in the blinatumomab trial. Outcomes were also compared between the trial and historical data using propensity score methods. The historical cohort included 694 patients with CR data and 1112 patients with OS data compared with 189 patients with CR and survival data in the blinatumomab trial...
2016: Blood Cancer Journal
L Fransecky, M Neumann, S Heesch, C Schlee, J Ortiz-Tanchez, S Heller, M Mossner, S Schwartz, L H Mochmann, K Isaakidis, L Bastian, U R Kees, T Herold, K Spiekermann, N Gökbuget, C D Baldus
BACKGROUND: GATA3 is pivotal for the development of T lymphocytes. While its effects in later stages of T cell differentiation are well recognized, the role of GATA3 in the generation of early T cell precursors (ETP) has only recently been explored. As aberrant GATA3 mRNA expression has been linked to cancerogenesis, we investigated the role of GATA3 in early T cell precursor acute lymphoblastic leukemia (ETP-ALL). METHODS: We analyzed GATA3 mRNA expression by RT-PCR (n = 182) in adult patients with T-ALL...
2016: Journal of Hematology & Oncology
Y Arai, T Kondo, A Shigematsu, J Tanaka, S Takahashi, T Kobayashi, N Uchida, Y Onishi, J Ishikawa, H Kanamori, M Sawa, A Yokota, Y Kouzai, M Takanashi, T Ichinohe, Y Atsuta, S Mizuta
No abstract text is available yet for this article.
September 19, 2016: Bone Marrow Transplantation
Kenjiro Mitsuhashi, Shinichi Kako, Akio Shigematsu, Yoshiko Atsuta, Noriko Doki, Takahiro Fukuda, Heiwa Kanamori, Makoto Onizuka, Satoshi Takahashi, Yukiyasu Ozawa, Mineo Kurokawa, Yoshiko Inoue, Tokiko Nagamura-Inoue, Yasuo Morishima, Shuichi Mizuta, Junji Tanaka
We conducted a retrospective analysis to compare outcomes in adult patients with acute lymphoblastic leukemia (ALL) who underwent allogeneic hematopoietic cell transplantation (allo-HCT) with conditioning regimens containing cyclophosphamide (CY) in combination with total body irradiation (TBI), oral busulfan (p.o. BU), or intravenous busulfan (i.v. BU). We used data for January 2000 to December 2012 from the Transplant Registry Unified Management Program of the Japan Society of Hematopoietic Cell Transplantation...
September 13, 2016: Biology of Blood and Marrow Transplantation
Troy Z Horvat, Joshua J Pecoraro, Ryan J Daley, Larry W Buie, Amber C King, Raajit K Rampal, Martin S Tallman, Jae H Park, Dan Douer
Asparaginase administration has become a crucial component of front-line pediatric and pediatric-insipired multi-agent regimens for the treatment of acute lymphoblastic leukemia (ALL). The aim of this retrospective study was to assess the safety and feasibility of switching to Erwinia asparaginase after pegaspargase intolerance in adult ALL patients treated at Memorial Sloan Kettering Cancer Center. Our analysis included 10 patients, with a median age of 39 years (range 20-72), male predominance (90%), and a typical B-cell to T-cell ratio (70:30%) for ALL...
August 26, 2016: Leukemia Research
Sébastien Maury, Sylvie Chevret, Xavier Thomas, Dominik Heim, Thibaut Leguay, Françoise Huguet, Patrice Chevallier, Mathilde Hunault, Nicolas Boissel, Martine Escoffre-Barbe, Urs Hess, Norbert Vey, Jean-Michel Pignon, Thorsten Braun, Jean-Pierre Marolleau, Jean-Yves Cahn, Yves Chalandon, Véronique Lhéritier, Kheira Beldjord, Marie C Béné, Norbert Ifrah, Hervé Dombret
Background Treatment with rituximab has improved the outcome for patients with non-Hodgkin's lymphoma. Patients with B-lineage acute lymphoblastic leukemia (ALL) may also have the CD20 antigen, which is targeted by rituximab. Although single-group studies suggest that adding rituximab to chemotherapy could improve the outcome in such patients, this hypothesis has not been tested in a randomized trial. Methods We randomly assigned adults (18 to 59 years of age) with CD20-positive, Philadelphia chromosome (Ph)-negative ALL to receive chemotherapy with or without rituximab, with event-free survival as the primary end point...
September 15, 2016: New England Journal of Medicine
Gilles M Leclerc, Shuhua Zheng, Guy J Leclerc, Joanna DeSalvo, Ronan T Swords, Julio C Barredo
Acute lymphoblastic leukemia (ALL) is the leading cause of cancer-related death in children, and cure rates for adults remain dismal. Further, effective treatment strategies for relapsed/refractory ALL remain elusive. We previously uncovered that ALL cells are prone to apoptosis via endoplasmic reticulum (ER) stress/unfolded protein response (UPR)-mediated mechanisms. We investigated the antineoplastic activity of pevonedistat(®), a novel NEDD8-activating enzyme inhibitor that targets E3 cullin-RING ligases (CRLs) dependent proteasomal protein degradation, in ALL...
September 5, 2016: Leukemia Research
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