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Fms-like tyrosine kinase 3 (FLT3) expression and mutation have been considered a poor prognostic factor in acute myeloid leukemia (AML). FLT3-ITD mutation is present in 30% of adult patients with AML and 2–5% in childhood acute lymphoblastic leukemia (ALL). The impact of these mutations on the prognosis of ALL patients, has not yet been established. Moreover, a limited number of publications regarding the level of expression of the FLT3 receptor (CD135) in both leukemias exist. This study aimed to analyze the clinical outcomes associated to the presence of FLT3-ITD mutation and the expression of CD135. 82 adult patients with newly diagnosed acute leukemia (39 with AML and 43 with ALL) were included. Flow cytometry and RT-PCR were done to analyze the expression of CD135 and the presence of FLT3 ITD mutation, respectively. FLT3-ITD was present in 14 (36%) of AML and 15 (35%) of ALL patients. Disease free survival (DFS) and overall survival (OS) were lower in ALL patients having a CD135 expression >3000 cells/μL. There was a trend for poor OS in AML patients expressing FLT3 ITD. OS was worse in AML patients with high expression of CD135. A higher (35%) frequency of FLT3-ITD was found in adult ALL patients. The presence of FLT3-ITD was associated with a trend of poor OS in AML cases, and overexpression of CD135 was correlated with poor DFS in ALL cases and poor OS in both acute leukemias. [ABSTRACT FROM AUTHOR]

Primary refractory or relapsed pediatric leukemia yield significant morbidity and mortality, with long-term survival rates <40%. Here we present a post-hoc analysis assessing safety and efficacy of infusing activated and expanded Natural Killer cells (NKAE) from haploidentical donors in patients from 2 clinical trials. In total, 18 children, adolescents and young adults with relapse or refractory acute leukemia were treated with two cycles of rescue chemotherapy followed by fresh NKAE cells infusions and low doses of IL-2. The overall response rate, complete remission achievement at the end of the study, was 72% (13 of 18). We infused 52 NKAE cell products containing a median of 6.76 × 106 NK cells/kg (0.7-34.16) and 0.49 × 106 T cells/kg (0-11). All infusions were well tolerated with no graft versus host disease nor other serious adverse events. Among the 14 patients who completed treatment, 4 of them are alive and leukemia-free more than 750 days post-transplant. We conclude that infusion of fresh NKAE cell therapy is feasible and safe in heavily pretreated pediatric population, and should be further investigated in advanced-phase clinical trials as well as a consolidation therapy to decrease relapse in patients with high-risk leukemia.Trials Registration: Registered at www.clinicaltrials.gov as NCT01944982 and NCT02074657. [ABSTRACT FROM AUTHOR]

Objective: Leukemia is the most prevalent type of cancer in children. The aim of this study was to estimate the5-year survival rates of Acute Lymphoblastic Leukemia (ALL) and Acute Myeloblastic Leukemia (AML) as well as factors influencing them.Methods: This is a non-randomized retrospective study conducted on 280 patients with ALL and AML. They were all below 15 years old children admitted to Shahid Faghihi hospital, Shiraz, Iran from 2004 to 2008.The survival rates were estimated by applying the Kaplan-Meier method. In addition, the log rank test was used to estimate the statistical significance of differences in the survival probability. Cox regression model was applied to conduct multivariate analysis for adjusting confounding variable. All analyses were performed in SPSS statistical software (version 16). P-values less than 0.05 were considered as statistically significant.Findings: The mean (± standard deviation) of the observation period was 28.2±16.1 months. In this period,60 (24.7%) patients (47 ALL and 15 AML) passed away. The cumulative rate of survival in this study was53.3±0.1 percent. This probability was 56.6±0.1% and 44.2±0.1% for ALL and AML patients, respectively,which indicates no statistically significant difference between them (P=0.8). According to Cox model, there was a significant relationship among the variables of platelet count and relapse with the survival rate.Conclusion: Platelet count was identified as a positive prognostic factor of the survival rate in ALL patients.However, on the base of our results and other studies, incidence of relapse and the number of relapses are significant factors of survival rates of leukemia. [ABSTRACT FROM AUTHOR]

The aim of this work was to evaluate whether there is an association between genetically determined individual difference in the polymorphism of isoenzyme CYP2D6 cytochrome P450 and the risk of developing acute myeloblastic leukaemia (AML). Material and methods: The investigations involved 98 subjects, including 34 patients suffering from acute myeloblastic laukaemia and 64 healthy individuals, who constituted a control group. Oxidation phenotype and genotype, and isoenzyme CYP2D6 gene amplification were determined in 30. 34 and 34 patients with AML and in 60, 64 and 47 healthy subjects respectively. The oxidation phenotype was determined in the urine by gas chromatographic method of Eiehelbaum and Gross. CYP2D6 gene polymorphism was determined by means of PCR-RFLP method (polymerase chain reaction amplification and restriction fragment length polymorphism), investigation of CYP2D6 isoenzyme gene amplification was performed by means of PCR method. Results: Poor oxidation phenotype has not been observed in AML patients, all the patients were extensive metabolizers of spartein, lnaddiction, the study found that the prevalence of extremely extensive oxidation phenotype in the group of AML patients was statistically significant higher then in control group. Moreover, the studies revealed a statistically significantly increased prevalence of a multiplied wild-type allele of the CYP2D6 gene in comparison to healthy individuals. Conclusion: These results may suggest that the extremely extensive oxidation phenotype and multiplied wild-type allele of the CYP2D6 gene may be associated with increased risk of the development of acute myeloblastic leukemia. [ABSTRACT FROM AUTHOR]

Bilateral facial paralysis is a rare condition. We present a case of acute myeloblastic leukemia manifesting itself in bilateral hearing loss and bilateral facial paralysis. We suspected systemic disease because of the abnormal blood cell count of the case. The diagnosis of leukemia was made with histological examination of a bone marrow aspirate. Computed tomography and gadolinium-enhanced magnetic resonance imaging scans revealed bilateral infiltration of the mastoid bones, middle ears and facial nerves. One should always remember that bilateral facial paralysis may be the first sign of a life-threatening illness. If infiltration is observed in the air-filled cells of the mastoid bone, before emergency surgery is planned, the possibility of leukemic infiltration should be considered. [ABSTRACT FROM AUTHOR]

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The existence of leukemic-associated phenotypes has been suggested to be a valuable tool for the detection of minimal residual disease (MRD) in AML patients, as they would allow to distinguish leukemic blast cells from normal hematopoietic progenitors. The present study was designed to analyze in which proportion of AML patients the immunological detection of MRD is feasible, based on the presence of aberrant phenotypes that allow the distinction of leukemic from normal cells. For this purpose we have prospectively investigated the blast cells from 40 AML patients at diagnosis with a large panel of MoAb in double and triple staining combinations analyzed at flow cytometry, in order to detect aberrant phenotypes on blast cells (lineage infidelity, antigenic overexpression, and asynchronous antigenic expression, as well as aberrant light-scatter pattern). In the analysis of the 40 AML cases more than one blast cell subset, distinguished by its different antigenic expression, was detected in 85% of the patients: five different phenotypic blast cell subsets were observed in six cases, four in 13 patients, three subsets in three cases, and two in 12 patients; only six cases showed a homogeneous phenotypical blast cell population. Twenty-nine of the 40 AML cases analyzed (73%) showed the existence of at least one aberrant phenotype: in 15 cases the myeloid blast cells co-expressed lymphoid-associated antigens (CD2, CD5, CD7, and/or CD19)--lineage infidelity--; asynchronous antigen expression was detected in 25 patients (CD34+CD56+, CD34+CD11b+, CD34+CD14+, CD117+CD15+, CD33-CD13+, CD13-CD15+, HLADR + CD15 , HLADR-CD14+CD11b+ CD4+); seven cases displayed antigen overexpression (CD13, CD33, CD15, or CD14); and in 13 patients leukemic cells had an abnormal FSC/SSC distribution according to their phenotype. These results suggest that immunological methods for the detection of MRD based on the existence of aberrant phenotypes could be used in the majority of AML patients. [ABSTRACT FROM AUTHOR]

Brucellosis is a zoonotic disease and endemically seen in the Middle East, Eastern Europe and continental America. Febrile neutropenia related to Brucellosis has been reported only in a few cases. Brucella was cultured from the bone morrow of a 42-year-old woman who was admitted to hospital with symptoms of fever and fatigue and later diagnosed as acute myeloblastic leukemia (AML). The patient was treated for both AML and Brucellosis without any problems and discharged from the hospital after scheduling her follow-up visits. Brucellosis might be considered in the etiology of febrile neutropenia in endemic regions and must be treated effectively to prevent possible morbidity and mortality during or after chemotherapy. [ABSTRACT FROM AUTHOR]