Barbara Faganel Kotnik, Janez Jazbec, Petra Bohanec Grabar, Cristina Rodriguez-Antona and Vita Dolzan
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Mina Ebrahimi-Rad, Shohreh Khatami, Shahla Ansari, Shohreh Jalylfar, Shirin Valadbeigi and Reza Saghiri
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Goran Milosevic, Nikola Kotur, Nada Krstovski, Jelena Lazic, Branka Zukic, Biljana Stankovic, Dragana Janic, Theodora Katsila, George P. Patrinos, Sonja Pavlovic and Lidija Dokmanovic
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Luidmyla F. Kaskova, Nataliia V. Yanko and Irena Y. Vashchenko
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7. Lauritano D, Petruzzi M, Fumagalli T, Giacomello MS
Elena Andrus, Anca Nicolescu, H. Bumbea and Ana-Maria Vlădăreanu
We present the case of a 71-year-old woman diagnosed with chronic lymphocytic leukemia who received multiple chemotherapeutic lines and evolved to acute lymphoblastic leukemia. The patient was Rai stage 0 at the time of the diagnosis and was monitored for almost 9 years. After that, the disease progressed and the patient began chemotherapy (fludarabine/cyclophosphamide combination), obtained complete remission and relapsed one year later after finishing treatment. She received multiple therapeutic regimens, accompanied by multiple infectious complications. After 8 years of evolution since she started chemotherapy, bone marrow aspirate and immunophenotyping revealed acute lymphoblastic leukemia. The occurrence of acute leukemia in CLL is rare and may arise from the same clone; however, most cases appear after patients have received chemotherapy, suggesting that they are therapy-related.
Letiția Elena Radu, Andra Beldiman, Ioana Ghiorghiu, Alina Oprescu, Constantin Arion and Anca Coliță
The international standard protocol for acute lymphoblastic leukaemia (ALL), the most common haemato-oncological pathology at paediatric age, uses anthracyclines as antitumor agents, potentially associated with early or late onset cardiac damage. Currently, echocardiography is the gold standard in the diagnosis of cardiotoxicity, but several biomarkers are evaluated as a possible replacement, pending more extensive clinical studies. We started a prospective study in order to determine the role of two biomarkers, troponin and heart-type fatty acid binding protein, in the evaluation of cardiotoxicity in children over one year of age, diagnosed with ALL. Between February 2015 and April 2016, 20 patients were enrolled and monitored at diagnosis, during chemotherapy and four months after the end of reinduction, through cardiac evaluation and dosing of those two markers in five different points of the treatment protocol. During the first year of follow-up, the patients did not develop clinical signs of cardiac damage, but the study showed a slight increase in troponin levels during chemotherapy, with the return to baseline value after treatment cessation, and also a correlation with the total dose of anthracyclines given to the patient. On the other hand, the second biomarker, heart-type fatty acid binding protein, did not seem to be useful in detecting subclinical cardiac damage in these patients.
Ruxandra Irimia, Ioana Teodora Tofolean, Roxana Gabriela Sandu, Oana Elena Băran, Maria Cătălina Ceauşescu, Vlad Coşoreanu, Maria Teodora Ilie, Ramona Babeş, Constanţa Ganea and Irina Băran
Doxorubicin is a widely used chemotherapeutic drug, effective on patients with acute lymphoblastic leukemia but associated with significant long term cardio-toxicity. Menadione (vitamine K3) and the flavonoid quercetin are known as strong apoptogens in human leukemia Jurkat T cells.
We explored the potential synergic cytotoxic effects of doxorubicin in association with quercetin and Menadione in this cellular model for acute lymphoblastic leukemia.
Cellular viability, apoptosis, necrosis oxidative stress and cellular cycle were determined by flow cytometry utilizing Jurkat lymphoblasts labeled with Annexin V-FITC/7-AAD, CM-H2DCFDA/7-AAD and propidium iodide respectively.
Results indicate a dose-dependent oxidative-stress generation, cell cycle arrest and apoptosis induction by doxorubicin alone, correlated with a decrease of the required doses when the anticancer drug was associated with quercetin and menadione, hence supporting the theory of an additive cytotoxic effect on leukemia cells.
Introducing QC-MD combinations in leukemia doxorubicin-based treatment could significantly increase the treatment’s efficacy. The main mechanism responsible for this effect appears to be the increase in DOX affinity for DNA, which enables lowering of the therapeutic dose.