Search results for " Promyelocytic"
showing 10 items of 43 documents
Prognostic Factors in APL
2018
The prognosis of acute promyelocytic leukemia (APL) has significantly improved since the introduction of anthracyclines, but especially after the advent of all-trans retinoic acid (ATRA) and arsenic trioxide (ATO). The identification of prognostic factors is a key process in clinical investigation, since their recognition allows the stratification of disease risks and promotes refined therapeutic adjustments. In fact, most treatments are now designed following risk-adapted strategies in order to optimize the therapeutic efficacy and minimizing side effects. The efficacy of treatment is one major determinant in prognosis. Therefore, the impact of a number of disease and patient characteristi…
Impact Of The Pretreatment Characteristics As Well As Cyto- and Molecular-Genetic Profile On Outcome After Relapse In Acute Myeloid Leukemia
2013
Abstract Background Cyto- and molecular-genetic abnormalities evaluated at initial diagnosis are the most powerful prognostic and in part also predictive markers in acute myeloid leukemia (AML) with regard to achievement of complete remission (CR) and survival. Nonetheless, after relapse the prognostic impact of clinical characteristics and genetic abnormalities assessed at initial diagnosis with respect to achievement of subsequent CR and survival are less clear. Aims To evaluate the probability of CR achievement and survival in relapsed AML patients in correlation to clinical characteristics and genetic abnormalities assessed at initial diagnosis as well as treatment strategy. Methods The…
Myeloid sarcoma of the oral cavity : a case report and review of 89 cases from the literature
2017
Myeloid sarcoma is a tumor mass of immature myeloid or granulocytic cells that affects extramedullary anatomic sites, including uncommonly the oral cavity. A 24-year-old female was referred for evaluation of a fast growing painful gingival swelling lasting 2 weeks, associated with fever, fatigue, and cervical lymphadenopathy. Intraoral examination showed a bluish swelling on the right posterior lower gingiva exhibiting necrotic surface. Incisional biopsy of the gingival lesion displayed diffuse infiltration of undifferentiated tumor cells with granulocytic appearance, strongly immunopositive for CD99, myeloperoxidase and Ki-67 (60%), and negative for CD20, CD3, CD34 and TdT. Blood tests pre…
Improved Outcome with ATRA-Arsenic Trioxide Compared to ATRA-Chemotherapy in Non-High Risk Acute Promyelocytic Leukemia - Updated Results of the Ital…
2014
Abstract Background: We recently showed that the combination of ATRA and arsenic trioxide (ATO) is at least not inferior and possibly superior to standard ATRA and chemotherapy (CHT) in the front-line management of low/intermediate risk APL (Italian-German APL 0406 trial; Lo-Coco et al., NEJM 2013). We report herein on the extended and final series of 276 patients (162 were in the previous report) with the last case being enrolled into the study in January 2013. Methods: The APL0406 study was a prospective, open-label, randomized intergroup trial conducted by the Italian GIMEMA and the German SAL and AMLSG study groups. Eligible patients were adults aged 18-<71 years with newly diagnosed…
Predictors of Early Death in Childhood Acute Promyelocytic Leukemia: Results of an International Retrospective Study
2015
Abstract Background: Acute promyelocytic leukemia (APL) is a rare subtype of childhood acute myeloid leukemia (AML). Bleeding complications occur in 80% of patients at diagnosis and contribute to a higher incidence of early death (ED) in APL compared to other AML subtypes. However, estimates of ED in pediatric APL are imprecise and factors associated with ED in children with APL are unknown. Objectives: To determine the incidence and predictors of ED, defined as death within 60 days from presentation, in childhood APL. Methods: We conducted a retrospective international analysis of children diagnosed with APL between January 1993 and December 2013. The study included 236 patients from the I…
Slit-Robo Pathway Is Clinically Relevant and May Represent a Potential Target in Acute Promyelocytic Leukemia
2018
Abstract Background: The Slit-Robo pathway has been shown to participate in the pathogenesis of several malignant diseases in addition to its physiologic role during the development of the central nervous system (CNS). However, the relevance of the Slit-Robo pathway in acute promyelocytic leukemia (APL) is presently unknown. We investigated the status of the Slit-Robo pathway in APL following the recent demonstration by Amodeo et al (CellRep. 2017) that the PML protein induces neural stem/progenitor cells migration by inhibiting the SLIT2 gene, which was associated with an increased presence of H3K27me3 in the SLIT2 promotor region. Moreover, sensitivity towards the PML-targeting drug arsen…
Clinical and Functional Studies Reveal That TP73 Isoforms Levels Are Associated with Prognosis and RA-Resistance in Acute Promyelocytic Leukemia
2019
Background: TP73 isoforms gained particular relevance in acute promyelocytic leukemia (APL) since Bernasola et al (JEM. 2004) demonstrated that TAp73 was directly regulated by the PML protein in the nuclear body. The isoforms differ in their transcriptional activity, with those lacking domains in the N-terminal part of the protein exerting a dominant negative effect on TP73 function. In a retrospective analysis of patients with APL treated in ICAPL study, Lucena-Araujo et al (Blood 2015) demonstrated the association between higher ΔNp73/TAp73 ratio values and poor clinical outcome. However,there is a diversity of TP73 isoforms and specially those lacking N-terminal domains (e.g.ΔEx2p73, ΔEx…
Towards More Specificity and Effectivity in the Antileukemia Immune Response
2014
Experimental and clinical studies have shown that alloreactive T-cell responses derived from donor lymphocytes can effectively eliminate leukemia cells after allogeneic hematopoietic stem cell transplantation. However, there are still too many patients in whom this graft-versus-leukemia reactivity is insufficient to prevent leukemia relapse or who suffer from severe alloreactivity to nonmalignant host tissues also mediated by donor-derived T cells. Therefore, various conceptually different approaches have been developed at the level of donor T cells in order to improve the efficacy of leukemia-directed immunity while reducing the incidence of unwanted graft-versus-host disease. As outlined …
Arsenic Trioxide Abrogate MN1 Mediated RA-Resistance in Acute Promyelocytic Leukemia
2019
Introduction: Described as a well know marker of worse prognosis in acute myeloid leukemia (AML), MN1 overexpression has been associated with inv(16) or EVI1 overexpression (Heuser et al., Blood 2007). The promoter region of the MN1 gene has Retinoic Acid Response Elements (RAREs), and higher levels of MN1 expression have been associated with decreased response to retinoic acid (RA) in vitro. Nevertheless, in the context of acute promyelocytic leukemia, little is known about MN1 gene expression and functionality in vivo. Aims: Here, we investigated the effects of in vitro treatment with RA plus arsenic trioxide (ATO) in APL cell lines and primary blasts overexpressing MN1. Additionally, we …
Treatment Results In Acute Myeloid Leukemia Over a Time Period Of 20 Years: Analysis Of The German-Austrian Acute Myeloid Leukemia Study Group (AMLSG)
2013
Abstract Background Overall survival (OS) in acute myeloid leukemia (AML) treated with intensive chemotherapy has improved over the last 20 year especially in younger adults (18-60 years) but still remains poor in older patients (>60 years) (Döhner et al. Blood 2010). The German-Austrian AMLSG performed controlled prospective treatment trials since 1993 starting with a risk-adapted approach (phase I, 1993-1997), followed by randomized and risk-adapted treatment strategies based on cytogenetic risk groups (phase II, 1997-2002); since 2003 addition of differentiating agents and HiDAC inhibitors to intensive induction therapy was evaluated (phase III, 2003-2007). Of note, until 2007 younger…