István Benedek, Erzsébet Lázár, Annamária Pakucs, Judit-Beáta Köpeczi, István Benedek, Szende Jakab and Johanna Sándor-Kéri
Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma (NHL), representing up to 30 percent of all lymphomas. DLBCL is a fast-growing, aggressive form of NHL, which can appear as a transformation from a less aggressive form of lymphoma or can be de novo pathology. The following article describes the case of a 55-year-old female patient who developed a DLBCL as a second malignancy after an R-CHOP-treated marginal zone splenic lymphoma. This was followed by the transformation of the DLBCL into an aggressive acute lymphoblastic leukemia, for which the patient needed aggressive treatment according to the international acute lymphoblastic leukemia protocol.
Barbara Faganel Kotnik, Janez Jazbec, Petra Bohanec Grabar, Cristina Rodriguez-Antona and Vita Dolzan
We investigated the clinical relevance of SLC 19A1 genetic variability for high dose methotrexate (HD-MTX) related toxicities in children and adolescents with acute lymphoblastic leukaemia (ALL) and non Hodgkin malignant lymphoma (NHML).
Patients and methods
Eighty-eight children and adolescents with ALL/NHML were investigated for the influence of SLC 19A1 single nucleotide polymorphisms (SNPs) and haplotypes on HD-MTX induced toxicities.
Patients with rs2838958 TT genotype had higher probability for mucositis development as compared to carriers of at least one rs2838958 C allele (OR 0.226 (0.071–0.725), p < 0.009). Haplotype TGTTCCG (H4) statistically significantly reduced the risk for the occurrence of adverse events during treatment with HD-MTX (OR 0.143 (0.023–0.852), p = 0.030).
SLC 19A1 SNP and haplotype analysis could provide additional information in a personalized HD-MTX therapy for children with ALL/NHML in order to achieve better treatment outcome. However further studies are needed to validate the results.
Cristina Marinescu, Ana-Maria Vladareanu and Felicia Mihai
Acute lymphoblastic leukemia (ALL) is a malignant neoplasm of the lymphocyte precursor cells. Among adults it is a relatively rare neoplasm with a curability rate around 30% at 5 years. Currently, the diagnosis and classification of ALL is a multistep procedure that relies on the simultaneous application of multiple techniques that include: cytomorphology, immunophenotype and cytogenetic assays . Some of which have important clinical implications for both diagnosis and predicting response to specific treatment regimens, while the role of others is still to be defined. Over the years, several prognostic factors have been identified and today a risk stratification at diagnosis and during the follow -up is based on the characteristics of the leukemic cells.
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.
Patients suffering from adult acute lymphoblastic leukemia (ALL) are very ill and present most commonly with shortness of breath during physical activity, a pale complexion from anemia, a very low platelet count, the appearance of pinhead-sized red spots under the skin called petechiae, or prolonged bleeding from minor cuts and discomfort in the bones and joints. Fever in the absence of an obvious cause is common. Leukemic lymphoblasts may accumulate in the lymphatic system, and lymph nodes can be enlarged. We report a young adult male with a novel translocation in ALL, who had vague (uncertain) minimal symptoms and splenomegaly. The patient had a unique cytogenetic abnormality: 45,XY,der(9)t(9;12)(p24;q12),-12, which has not been previously described in ALL. This is categorized as a poor risk due to his failure to achieve complete remission after induction chemotherapy.
Luidmyla F. Kaskova, Nataliia V. Yanko and Irena Y. Vashchenko
Acute lymphoblastic leukemia (ALL), the most common type of leukemia in children, has diverse oral cavity complications. While periodontal alterations in such patients are widely known, there were no studies evaluating gingival health from the time of diagnosis to the remission phase. In our study, we, therefore, analysed the frequency of periodontal diseases and the gingival indices in the different phases of ALL in children. Children aged 7-15 years were involved into the cross-sectional study. Therein, 160 children with ALL were divided into three groups: L1 – 50 children examined before the initiation phase, L2 – 50 children examined after 1 month of the chemotherapy, L3 – 60 children examined in permanent hematologic remission. The control (HC) included 150 healthy children. The L1, L2 and L3 groups had significantly worse gingival indices and frequency of gingivitis than the HC group (p < 0.0001). Frequency of gingivitis increased from before the initiation to the remission phase, but significantly only in 7-11 year-old children (p = 0.0004). Gingival indices increased after 1 month of chemotherapy (p < 0.0001), but decreased in the permanent remission phase (p < 0.0001).
Our study stresses the need for children with ALL to not only require prevention courses before the initiation and during the chemotherapy phases, but also in the permanent remission phase to minimize the long-term impact of leukemia treatment on gingival health.
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.
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.
Acute lymphoblastic leukemia (ALL) is a type of cancer that most frequently affects children, and its treatment involves intensive chemotherapy, which might interfere with the normal development of dental tissues. The aim of our study was to measure the incidence of dental caries and enamel hypoplasia in children diagnosed with ALL treated according to the Berlin-Frankfurt-Munster-95 (ALL-BFM-95) protocol during the complete remission phase. Two groups of children between 8-12 years of age were investigated: Group 1 consisted of 36 children with ALL, and Group 2 of 58 control age-matched children. The decay-missing-filling index for the deciduous teeth (DMFT) and the presence of hypoplasia in the first permanent molars (MH) or in both incisors and molars (MIH) were recorded. The results were statistically analyzed and showed that there were no differences between the groups regarding the DMFT values (p >0.05), but there was a statistically significant difference in the incidence of MH and MIH between groups (p <0.05). According to our results, chemotherapy was not responsible for the decay process, as there were no differences in DMFT indices between the groups, but the high incidence of MH and MIH in the ALL group indicates the need of a good dental care for these children in order to prevent future dental complications.
Patrycja Sujka-Kordowska, Agnieszka Malińska and Maciej Zabel
It is well established that angiogenesis is necessary in solid tumours development. Interesingly, the role of angiogensis in haematological malignancies has been also recognized. Recent publicationts indicate that microvessel density in bone marrow and angiogenic factors like endoglin, placental growth factor and cyclooxygenase 1 are increased in lymphoproliferative disorders and suggest that angiogensis is a part of pathomechanism of these malignancies. However, it has not been identified how angiogenesis can be involved in progression of haematological disorders. There is a strong need for further investigations in this area, since antiangiogenic therapy is a potential adjunct to conventional therapy of lymphoproliferative disorders.