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Acute promyelocytic leukemia high risk

Na Gao, Wen-Zheng Yu, Nong-Jian Guo, Xue-Xia Wang, Jian-Rong Sun
Galectin-3 plays an increasingly important role in development and progression of tumor. However, little is known about the clinical impact of galectin-3 in non-acute promyelocytic leukemia (non-M3 AML). Peripheral blood of 298 patients with primary non-M3 AML and 30 normal donors was collected for measurement of galectin-3. Galectin-3 levels were significantly higher compared with the control group (p < .001). Patients with higher galectin-3 levels had lower CR rates (p = .001) and 1-year overall survival (OS) rates (p = ...
October 13, 2016: Leukemia & Lymphoma
Osamu Imataki, Makiko Uemura
BACKGROUND: The recent study described a better outcome in acute promyelocytic leukemia patients treated with all-trans retinoic acid and arsenic oxide compared to those treated with all-trans retinoic acid combined with conventional chemotherapy. The pivotal study indicated that favorable-risk acute promyelocytic leukemia patients can be cured without any cytotoxic chemotherapy. Even high-risk patients are treatable with cytotoxic agents. Acute promyelocytic leukemia does not develop only by the dedifferentiation caused by PML-RARA...
2016: BMC Clinical Pathology
Muhamed Baljevic, Bogdan Dumitriu, Ju-Whei Lee, Elisabeth M Paietta, Peter H Wiernik, Janis Racevskis, Christina Chen, Eytan M Stein, Robert E Gallagher, Jacob M Rowe, Frederick R Appelbaum, Bayard L Powell, Richard A Larson, Steven E Coutré, Jeffrey Lancet, Mark R Litzow, Selina M Luger, Neal S Young, Martin S Tallman
Telomeres are the capping ends of chromosomes that protect the loss of genetic material and prevent chromosomal instability. In human tissue-specific stem/progenitor cells, telomere length (TL) is maintained by the telomerase complex, which consists of a reverse transcriptase catalytic subunit (TERT) and an RNA template (TERC). Very short telomeres and loss-of-function mutations in the TERT and TERC genes have been reported in acute myeloid leukemia, but the role of telomeres in acute promyelocytic leukemia (APL) has not been well established...
September 16, 2016: Acta Haematologica
Tilmann Bochtler, Stefan Fröhling, Wilko Weichert, Volker Endris, Christian Thiede, Barbara Hutter, Michael Hundemer, Anthony D Ho, Alwin Krämer
Here, we report the case of an acute promyelocytic leukemia (APL) patient who-although negative for FLT3 mutations at diagnosis-developed isolated FLT3 tyrosine kinase II domain (FLT3-TKD)-positive meningeal relapse, which, in retrospect, could be traced back to a minute bone marrow subclone present at first diagnosis. Initially, the 48-yr-old female diagnosed with high-risk APL had achieved complete molecular remission after standard treatment with all-trans retinoic acid (ATRA) and chemotherapy according to the AIDA (ATRA plus idarubicin) protocol...
September 2016: Cold Spring Harbor Molecular Case Studies
S Ganesan, A A Alex, E Chendamarai, N Balasundaram, H K Palani, S David, U Kulkarni, M Aiyaz, R Mugasimangalam, A Korula, A Abraham, A Srivastava, R A Padua, C Chomienne, B George, P Balasubramanian, V Mathews
Arsenic trioxide (ATO) mediates PML-RARA oncoprotein degradation via the proteasome pathway and this degradation appears to be critical for achieving cure in acute promyeloytic leukemia (APL). We have previously demonstrated significant micro-environment mediated drug resistance (EMDR) to arsenic trioxide (ATO) in APL. Here we demonstrate that this EMDR could be effectively overcome by combining a proteasome inhibitor (bortezomib) with ATO. A synergistic effect on combining these two agents, in-vitro, was noted in both ATO sensitive and ATO resistant APL cell lines...
August 18, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
David P Steensma, Medrdad Abedi, Rafael Bejar, Christopher R Cogle, Kathryn Foucar, Guillermo Garcia-Manero, Tracy I George, David Grinblatt, Rami Komrokji, Xiaomei Ma, Jaroslaw Maciejewski, Daniel A Pollyea, Michael R Savona, Bart Scott, Mikkael A Sekeres, Michael A Thompson, Arlene S Swern, Melissa Nifenecker, Mary M Sugrue, Harry Erba
BACKGROUND: Myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) are myeloid neoplasms in which outgrowth of neoplastic clones disrupts normal hematopoiesis. Some patients with unexplained persistent cytopenias may not meet minimal diagnostic criteria for MDS but an alternate diagnosis is not apparent; the term idiopathic cytopenia of undetermined significance (ICUS) has been used to describe this state. MDS and AML occur primarily in older patients who are often treated outside the clinical trial setting...
2016: BMC Cancer
Patricia Rubio, B Campos, J A Digiorge, M S Gallego, A Medina, J G Rossi, M S Felice, C N Alonso
Mutations in NPM1, FLT3 and CEBPA genes are found in 25-35 % of adult acute myeloblastic leukemia (AML) cases and correlate with prognosis. To date, there have been no reports about these mutations in pediatric AML from Argentina. The aims of the present study were to describe the incidence of NPM1, FLT3 and CEBPA mutations and to analyze their prognostic impact in this population. The incidences of these mutations within a population of 216 pediatric AML cases were: NPM1-mutated 4.2 %, CEBPA-mutated 1.9 %, FLT3-ITD 10...
July 19, 2016: International Journal of Hematology
Ji Hyun Kwon, Young-Il Koh, Sung-Soo Yoon, Seonyang Park, Inho Kim
We investigated risk factors and outcome in acute myeloid leukemia (AML) patients with leptomeningeal involvement. Medical records of patients with non-promyelocytic AML at Seoul National University Hospital from January of 2000 to November of 2013 were reviewed. Leptomeningeal involvement was defined as the presence of atypical or malignant hematopoietic cells in the cerebrospinal fluid. Among 775 patients with AML, 141 patients (18.2 %) underwent cerebrospinal fluid examination. Leptomeningeal involvement of AML, confirmed in 38 patients (4...
July 18, 2016: International Journal of Hematology
Fang Huang, Jun Chang, Chao Du, Rong Tao
Acute promyelocytic leukemia (APL) has been regarded as a highly curable disease. Therapy-related leukemia is one of the important late complications that affect long-term survival rates in APL patients. Therapy-related acute myeloid leukemia and myelodysplastic syndrome are the major forms of therapy-related leukemias. We report a rare event of chronic myeloid leukemia (CML) that developed after successful treatment of APL with all-trans-retinoic acid in combination with chemotherapy. Rather unexpectedly, CML developed 7 years after APL...
June 2016: Indian Journal of Hematology & Blood Transfusion
Uwe Platzbecker, Giuseppe Avvisati, Laura Cicconi, Christian Thiede, Francesca Paoloni, Marco Vignetti, Felicetto Ferrara, Mariadomenica Divona, Francesco Albano, Fabio Efficace, Paola Fazi, Marco Sborgia, Eros Di Bona, Massimo Breccia, Erika Borlenghi, Roberto Cairoli, Alessandro Rambaldi, Lorella Melillo, Giorgio La Nasa, Walter Fiedler, Peter Brossart, Bernd Hertenstein, Helmut R Salih, Mohammed Wattad, Michael Lübbert, Christian H Brandts, Mathias Hänel, Christoph Röllig, Norbert Schmitz, Hartmut Link, Chiara Frairia, Enrico Maria Pogliani, Claudio Fozza, Alfonso Maria D'Arco, Nicola Di Renzo, Agostino Cortelezzi, Francesco Fabbiano, Konstanze Döhner, Arnold Ganser, Hartmut Döhner, Sergio Amadori, Franco Mandelli, Gerhard Ehninger, Richard F Schlenk, Francesco Lo-Coco
PURPOSE: The initial results of the APL0406 trial showed that the combination of all-trans-retinoic acid (ATRA) and arsenic trioxide (ATO) is at least not inferior to standard ATRA and chemotherapy (CHT) in first-line therapy of low- or intermediate-risk acute promyelocytic leukemia (APL). We herein report the final analysis on the complete series of patients enrolled onto this trial. PATIENTS AND METHODS: The APL0406 study was a prospective, randomized, multicenter, open-label, phase III noninferiority trial...
July 11, 2016: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
Marta Chisini, Caterina Stefanizzi, Teresa Ceglie, Sara Raponi, Federico Vozella, Gioia Colafigli, Adriano Salaroli, Mariella D'Angiò, Marco Mancini, Daniela Diverio, Massimo Breccia, Francesca Mancini, Clara Minotti, Silvia Trisolini, Saveria Capria, Anna Maria Testi, Anna Guarini, Roberto Latagliata, Maria Stefania De Propris, Robin Foà
The prognostic role of CD15 in acute myeloid leukemia (AML) has been tested in different studies with conflicting results. To address this issue, we retrospectively evaluated a cohort of 460 AML patients of all ages with the exclusion of acute promyelocytic leukemia (M/F 243/217, median age 50.6 years [range 0.9-81.2]) intensively treated at our institute between January 1999 and December 2010. CD15 positivity was found in 171 of 406 evaluable patients (42.1%). Complete remission (CR) was achieved by 334 patients (72...
July 12, 2016: Hematological Oncology
Yafang Ma, Lu Liu, Jie Jin, Yinjun Lou
BACKGROUND: Recently, the all-trans retinoic acid (ATRA) plus arsenic trioxide (ATO) protocol has become a promising first-line therapeutic approach in patients with newly diagnosed acute promyelocytic leukemia (APL), but its benefits compared with standard ATRA plus chemotherapy regimen needs to be proven. Herein, we conducted a meta-analysis comparing the efficacy of ATRA plus ATO with ATRA plus chemotherapy for adult patients with newly diagnosed APL. METHODS: We systematically searched biomedical electronic databases and conference proceedings through February 2016...
2016: PloS One
John Savooji, Fouzia Shakil, Humayun Islam, Delong Liu, Karen Seiter
Therapy-related acute myeloid leukemia (AML) is a long term complication of chemotherapy for a variety of cancers. In most cases, the marrow demonstrates high risk cytogenetics and the prognosis is poor. In a minority of patients "good risk" cytogenetics, including t(15;17)(q22;q12), are seen and the patient's prognosis is similar to those who have de novo disease. Currently we present a patient who developed therapy-related acute promyelocytic leukemia (APL) after chemoradiotherapy for breast cancer. This case was especially atypical because the leukemic cells were CD34(+), which is an unusual immunophenotype for APL...
2016: Stem Cell Investigation
Kristen Pettit, Wendy Stock, Roland B Walter
Curative-intent therapy leads to complete remissions in many adults with acute myeloid leukemia (AML), but relapse remains common. Numerous studies have unequivocally demonstrated that the persistence of measurable ('minimal') residual disease (MRD) at the submicroscopic level during morphologic remission identifies patients at high risk of disease recurrence and short survival. This association has provided the impetus to customize anti-leukemia therapy based on MRD data, a strategy that is now routinely pursued in acute promyelocytic leukemia (APL)...
July 2016: Leukemia & Lymphoma
R Z Pei, T Si, Y Lu, P S Zhang, X H Liu, P P Ye, D Chen, X H Du, J X Ma, J Jin
OBJECTIVE: To investigate the clinical features and outcomes of high-risk acute promyelocytic leukemia (APL) patients. METHODS: A retrospective analysis was conducted to compare the clinical characteristics and prognosis of 118 high-risk APL patients (WBC≥10 × 10(9)/L) and 234 low and intermedia-risk patients (WBC <10×10(9)/L) from January 2003 to April 2015, who were treated in the First Affiliated Hospital of Zhejiang University and Yinzhou People's Hospital affiliated to Medical College of Ningbo University...
May 14, 2016: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
E J Libourel, C Klerk, Y van Norden, M P M de Maat, M J Kruip, P Sonneveld, B Löwenberg, F W G Leebeek
INTRODUCTION: Acute myeloid leukemia (AML) is associated with a slightly increased risk of VTE with an incidence of 1.7-8.9%, but only limited data are available. The mechanism of the occurrence of thrombosis in hematological disorders is still unresolved. Disseminated intravascular coagulation (DIC) is associated with VTE and bleeding in acute promyelocytic leukemia and acute lymphoblastic leukemia. Although DIC has also been reported in AML, no data exist on the relationship between DIC and VTE in AML patients...
April 2016: Thrombosis Research
Aki Saito, Yasuhiro Okamoto, Yuko Seki, Manaka Matsunaga, Shunsuke Nakagawa, Yuichi Kodama, Takuro Nishikawa, Takayuki Tanabe, Yoshifumi Kawano
An 8-year-old boy developed anorexia, fatigue, and fever. Laboratory examination revealed a high white blood cell (WBC) count of 145×10/μL with 97.5% abnormal promyelocytic cells that contained Auer bodies. Faggot cells were seen. He was diagnosed with acute promyelocytic leukemia. Later, a chromosome analysis showed 46,XY,t(15;17)(q22;q12). Promyelocytic Leukemia-retinoic acid receptor α-fused gene and chimeric mRNA were confirmed by fluorescence in situ hybridization and reverse transcriptase polymerase chain reaction, respectively...
August 2016: Journal of Pediatric Hematology/oncology
L Cicconi, F Lo-Coco
The management of acute promyelocytic leukemia (APL) has considerably evolved during the past two decades. The advent of all-trans retinoic acid (ATRA) and its inclusion in combinatorial regimens with anthracycline chemotherapy has provided cure rates exceeding 80%; however, this widely adopted approach also conveys significant toxicity including severe myelosuppression and rare occurrence of secondary leukemias. More recently, the advent of arsenic trioxide (ATO) and its use in association with ATRA with or without chemotherapy has further improved patient outcome by allowing to minimize the intensity of chemotherapy, thus reducing serious toxicity while maintaining high anti-leukemic efficacy...
August 2016: Annals of Oncology: Official Journal of the European Society for Medical Oncology
Nirav N Shah, Mark Stonecypher, Pallavi Gopal, Selina Luger, Adam Bagg, Alexander Perl
Acute promyelocytic leukemia (APL) is a distinct subtype of acute myeloid leukemia (AML) that is characterized by a balanced translocation between chromosomes 15 and 17 [t(15;17)], which results in the fusion of the promyelocytic leukemia (PML) and retinoic acid receptor α (RARA) genes. Historically, APL was a fatal disease because of the high relapse rates with cytotoxic chemotherapy alone and a significant bleeding risk secondary to disseminated intravascular coagulation (DIC). However, APL is now one of the most curable hematological malignancies because of molecularly targeted therapies...
March 2016: Journal of Community and Supportive Oncology
Y Wang, B C Liu, H Wei, D Lin, C L Zhou, K Q Liu, W Li, S N Wei, J Y Wang, B F Gong, G J Zhang, X L Zhao, Y T Liu, X Y Gong, Y Li, R X Gu, Y C Mi, J X Wang
OBJECTIVE: To compare the efficacy and toxicities of combining homoharringtonine (HHT)±daunorubicin (DNR) with all-trans-retinoic acid (ATRA) based therapy and DNR plus ATRA based therapy in newly diagnosed low/intermediate risk acute promyelocytic leukemia (APL). METHODS: A total of 96 newly diagnosed patients with APL were randomized to HHT group, DNR group and HHT+ DNR group prospectively. The complete remission (CR) rate, the overall survival (OS) and event-free survival (EFS) of three groups were analyzed...
March 2016: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
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