Summary. We determined the hepatitis C virus (HCV) antibodies (anti-HCV) and the hepatitis B virus (HBV) surface antigen (HBsAg) in a cohort of 68 consecutive non-Hodgkin's lymphoma (NHL) patients diagnosed and treated in our institution between December 1997 and March 1999. 27 cases were diagnosed as low-grade, 33 as intermediate-grade, and eight as high-grade NHL. In 35 cases (51´4%) we found evidence of either HCV or HBV infection. Anti-HCV antibodies were found in 20 patients (29´5%) and HBsAg was found in 21 patients (30´8%). In six patients both anti-HCV and HBsAg were present. Anti-HCV were present in 12/27 low-grade NHL cases (44´4%) and in 8/41 intermediate/high-grade (aggressive) NHL cases (19´5%, P < 0´03). HBsAg was found in 10/27 low-grade NHL cases (37%) and in 11/41 aggressive NHL cases (26´8%). Evidence of liver disease, as re¯ected by elevated aminotransferases or typical alterations at liver biopsy, was present in eight patients. Cryoglobulins were present in six patients, all anti-HCV positive and with low-grade NHL. The prevalence of both HCV antibodies and HBsAg was signi®cantly higher (P < 0´0001) in our NHL cases than in a sample of the general Romanian population, where the prevalence of anti-HCV was 4´9% and that of HBsAg was 6´3%. It is dif®cult to say whether either HCV or HBV had actually been involved in lymphomagenesis or if a-interferon treatment would be effective in this subset of patients.

Polycythemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis (PMF) are classical myeloproliferative neoplasms (MPN), characterized by specific somatic mutations in JAK2, CALR or MPL genes. JAK2 46/1 and TERT rs2736100 polymorphisms are known to significantly predispose to MPN. This study aimed to establish the additional contribution of the recently described MECOM rs2201862, HBS1L-MYB rs9376092 and THRB-RARB rs4858647 polymorphisms to the occurrence of MPN. These three polymorphisms, along with JAK2 46/1 and TERT rs2736100 were genotyped in 939 MPN patients (454 with ET, 337 with PV and 148 with PMF) and 483 controls. MECOM rs2201862 associated significantly with each MPN entity, except for ET, and with all major molecular sub-types, especially those CALR-mutated (OR = 1.4; 95% CI = 1.1-1.8; P-value = .005). HBS1L-MYB rs9376092 associated only with JAK2 V617F-mutated ET (OR = 1.4; 95% CI = 1.1-1.7; P-value = .003). THRB-RARB rs4858647 had a weak association with PMF only (OR = 1.5; 95% CI = 1-2.1; P-value = .04). Surprisingly, JAK2 46/1 haplotype was associated significantly not only with JAK2 V617F-mutated MPN, but also with CALR-mutated MPN (OR = 1.4; 95% CI = 1.1-1.8; P-value = .01). TERT rs2736100 was associated equally strong with all MPN, regardless of phenotype or molecular sub-type. In conclusion, JAK2 46/1, TERT rs2736100 and MECOM rs2201862 are the chief predisposing polymorphisms to MPN.

Polycythaemia vera (PV), essential thrombocythaemia (ET) and primary myelofibrosis (PMF) represent typical myeloproliferative neoplasms (MPN), usually characterized by specific somatic driver mutations (JAK2 V617F, CALR and MPL). JAK2 46/1 haplotype and telomerase reverse transcriptase gene (TERT) rs2736100 A>C single nucleotide polymorphism (SNP) could represent a large fraction of the genetic predisposition seen in MPN. The rs10974944 C>G SNP, tagging the JAK2 46/1 haplotype, and the TERT rs2736100 A>C SNP were genotyped in 529 MPN patients with known JAK2 V617F, CALR and MPL status, and 433 controls. JAK2 46/1 haplotype strongly correlated to JAK2 V617F-positive MPN and, to a lesser extent, CALR-positive MPN. The TERT rs2736100 A>C SNP strongly correlated to all MPN, regardless of the phenotype (PV, ET or PMF) and major molecular subtype (JAK2 V617F- or CALR-positive). While both variants have a significant contribution, they have nuanced consequences, with JAK2 46/1 predisposing essentially to JAK2 V617F-positive MPN, and TERT rs2736100 A>C having a more general, non-specific effect on all MPN, regardless of phenotype or major molecular subtype.

BackgroundReleasing drug molecules at the targeted location could increase the clinical outcome of a large number of anti-tumor treatments which require low systemic damage and low side effects. Nano-carriers of drugs show great potential for such task due to their capability of accumulating and releasing their payload specifically, at the tumor site.ResultsFLT3 inhibitor - gold nanoparticle conjugates were fabricated to serve as vehicles for the delivery of anti-tumor drugs. Lestaurtinib, midostaurin, sorafenib, and quizartinib were selected among the FLT3 inhibitor drugs that are currently used in clinics for the treatment of acute myeloid leukemia. The drugs were loaded onto nanoparticle surface using a conjugation strategy based on hydrophobic-hydrophobic interactions with the Pluronic co-polymer used as nanoparticle surface coating. Optical absorption characterization of the particles in solution showed that FLT3 inhibitor-incorporated gold nanoparticles were uniformly distributed and chemically stable regardless of the drug content. Drug loading study revealed a high drug content in the case of midostaurin drug which also showed increased stability. Drug release test in simulated cancer cell conditions demonstrated more than 56 % release of the entrapped drug, a result that correlates well with the superior cytotoxicity of the nano-conjugates comparatively with the free drug.ConclusionsThis is a pioneering study regarding the efficient loading of gold nanoparticles with selected FLT3 inhibitors. In vitro cytotoxicity assessment shows that FLT3-incorporated gold nanoparticles are promising candidates as vehicles for anti-tumor drugs and demonstrate superior therapeutic effect comparatively with the bare drugs.Electronic supplementary materialThe online version of this article (doi:10.1186/s11671-015-1154-2) contains supplementary material, which is available to authorized users.

With the increasing overall survival of cancer patients due to recent discoveries in oncology, the incidence of side effects is also rising, and along with secondary malignancies, cardiotoxicity is one of the most concerning side effects, affecting the quality of life of cancer survivors. There are two types of cardiotoxicity associated with chemotherapy; the first one is acute, life-threatening but, fortunately, in most of the cases, reversible; and the second one is with late onset and mostly irreversible. The most studied drugs associated with cardiotoxicity are anthracyclines, but many new agents have demonstrated unexpected cardiotoxic effect, including those currently used in multiple myeloma treatment (proteasome inhibitors and immunomodulatory agents), tyrosine kinase inhibitors used in the treatment of chronic myeloid leukemia and some forms of acute leukemia, and immune checkpoint inhibitors recently introduced in treatment of refractory lymphoma patients. To prevent irreversible myocardial damage, early recognition of cardiac toxicity is mandatory. Traditional methods like echocardiography and magnetic resonance imaging are capable of detecting structural and functional changings, but unable to detect early myocardial damage; therefore, more sensible biomarkers like troponins and natriuretic peptides have to be introduced into the current practice. Baseline assessment of patients allows the identification of those with high risk for cardiotoxicity, while monitoring during and after treatment is important for early detection of cardiotoxicity and prompt intervention.

Iron is an important element in living systems as it participates in a series of metabolic processes including DNA synthesis and oxygen and electron transport. Iron deficiency is the most common cause of anemia globally being an important healthcare problem. If left untreated, iron-deficiency anemia (IDA) can cause significant morbidity and often is the result of a more serious underlying condition. Correcting iron deficiency and replenishing iron reserves are important objectives of a well-conducted treatment, but diagnosis should prompt further investigation to establish the cause for potential reversal. Age, tolerance, preferred route of administration, and severity of anemia are some of the patient's characteristics which require an individualized approach.

Background:The objective of the present study was to determine the association between chemotherapy and infectious complications in patients diagnosed with Hematologic malignancies (HMs).Materials and Methods:The study included 463 patients diagnosed with HMs multiple myeloma (MM), Hodgkin's lymphoma (HL), non-HL (NHL), acute myeloid leukemia (AML), acute lymphocytic leukemia, chronic lymphocytic leukemia, and chronic myeloid leukemia, between January 2014 and June 2015. The patients were followed for 1 year after inclusion, to record the infectious complications. The collected data included age, sex, type of chemotherapy regimen, and several blood tests at admission. All patients received prophylactic treatment with antibiotics and antifungal agents. For each infection, we recorded the microbiological diagnosis and the day of occurrence since HMs diagnosis.Results:In patients with MM, we found that the treatment with growth factors (hazard ratio [HR] 2.2; confidence interval [CI] 95%: 1–4.6; P = 0.03) was associated with a higher chance of infectious complications. In patients with non-Hodgkin lymhoma (LNH), the following drugs were associated with a higher infectious incidence: cytarabine (HR: 2.3; CI 95%: 1–5; P = 0.03), methotrexate (HR: 2.1; CI 95%: 1.8–4; P = 0.01), dexamethasone (HR: 1.7; CI 95%: 0.9–3; P = 0.06), growth factors (HR: 1.7; CI 95%: 0.9–3.2; P = 0.001), and etoposide (HR: 2.5; CI 95%: 1.5–4.2; P = 0.002). Cytarabine (induction) (HR: 2; CI 95%: 1.1–3.7; P = 0.01), cytarabine (consolidation) (HR: 2.1; CI 95%: 1.3–3.5; P = 0.01), and growth factors (HR: 2.1; CI 95%: 1.3–3.5; P = 0.002) were often on the therapeutic plan of patients with AML, which developed infections.Conclusion:Regarding the chemotherapy regimen, the highest incidences of infectious complications were observed for growth factors and cytarabine.

Although the cause for bone marrow fibrosis in patients with myelofibrosis remains controversial, it has been hypothesized that it is caused by extensive fibroblast proliferation under the influence of cytokines generated by the malignant megakaryocytes. Moreover, there is no known drug therapy which could reverse the process. We studied the fibroblasts in a novel system using the hanging drop method, evaluated whether the fibroblasts obtain from patients are part of the malignant clone of not and, using this system, we screen a large library of FDA‐approved drugs to identify potential drugs candidates that might be useful in the treatment of this disease, specifically which would inhibit fibroblast proliferation and the development of bone marrow fibrosis. We have found that the BM fibroblasts are not part of the malignant clone, as previously suspected and two immunosuppressive medications—cyclosporine and mycophenolate mophetil, as most potent suppressors of the fibroblast collagen production thus potentially inhibitors of bone marrow fibrosis production in myelofibrosis.