Acute Granulocytic Leukemia Research Articles

Real‐world effectiveness of antifungal prophylaxis with posaconazole as the primary agent in patients with haematological malignancies

Patients undergoing induction/reinduction chemotherapy for haematologic malignancies (HM) are at risk for invasive fungal infections (IFIs). In 2015, Duke University Hospital (DUH) implemented a new standardised fungal prophylaxis protocol for adult patients undergoing induction chemotherapy for acute lymphocytic leukaemia, acute myelocytic leukaemia and myelodysplastic syndrome. This study assessed the impact of protocol implementation on (1) use of antifungal prophylaxis, throughout the at-risk period and (2) patient outcomes such as IFI and mortality. Retrospective, observational study of adult HM patients admitted to DUH for induction/reinduction chemotherapy pre- (7/1/2013-12/31/2014) and post- (1/1/2015-10/31/2016) implementation of standardised antifungal prophylaxis protocol (which recommended posaconazole as the first-line agent). Patients were followed for up to 100 days after initiation of induction chemotherapy to evaluate use of antifungal prophylaxis and patient outcomes. 218 patients with haematologic malignancies were included (90 pre, 128 post). Use of antifungal prophylaxis increased from 81.1% (pre) to 97.7% (post) (p < .0001). Overall, 71% received posaconazole as initial antifungal prophylaxis (64.4% pre, 75.7% post). Approximately one-fourth of patients (25.6%, pre vs 26.6%, post) developed an IFI (proven/probable or possible using modified EORTC definitions) (p=.868); 100-day mortality remained stable (18.9% pre vs 18.8% post, respectively, p=.979). Lack of antifungal prophylaxis and older age (≥60 years) were associated with higher risk of IFI. Implementation of a standardised protocol with posaconazole as the primary agent was associated with increased use of antifungal prophylaxis among patients undergoing induction/reinduction chemotherapy for haematologic malignancies in our hospital. Lack of antifungal prophylaxis was an independent predictor of IFIs, underscoring the importance of prophylaxis in this at-risk population.

Joint impact of key air pollutants on COVID-19 severity: prediction based on toxicogenomic data analysis

Considering that some researchers point to a possible influence of air pollution on COVID-19 transmission, severity, and death rate, the aim of our in silico study was to determine the relationship between the key air pollutants [sulphur dioxide (SO), carbon monoxide (CO), 2particulate matter (PMx), nitrogen dioxide (NO2), and ozone (O3)] and COVID-19 complications using the publicly available toxicogenomic analytical and prediction tools: (i) Comparative Toxicogenomic Database (CTD) to identify genes common to air pollutants and COVID-19 complications; (ii) GeneMANIA to construct a network of these common and related genes; (iii) ToppGene Suite to extract the most important biological processes and molecular pathways; and (iv) DisGeNET to search for the top gene-disease pairs. SO2, CO, PMx, NO2, and O3 interacted with 6, 6, 18, 9, and 12 COVID-19-related genes, respectively. Four of these are common for all pollutants (IL10, IL6, IL1B, and TNF) and participate in most (77.64 %) physical interactions. Further analysis pointed to cytokine binding and cytokine-mediated signalling pathway as the most important molecular function and biological process, respectively. Other molecular functions and biological processes are mostly related to cytokine activity and inflammation, which might be connected to the cytokine storm and resulting COVID-19 complications. The final step singled out the link between the CEBPA gene and acute myelocytic leukaemia and between TNFRSF1A and TNF receptor-associated periodic fever syndrome. This indicates possible complications in COVID-19 patients suffering from these diseases, especially those living in urban areas with poor air quality.

Multiple spontaneous coronary artery dissections associated with intravenous daunorubicin treatment for acute myelocytic leukaemia: a case report.

BackgroundMultiple spontaneous coronary artery dissection (SCAD) is a rare condition which may lead to serious consequences such as sudden cardiac death, acute myocardial infarction (AMI), and acute heart failure.Case summaryIn this paper, we report the case of a 57-year-old woman with acute myelocytic leukaemia who was undergoing her second phase of chemotherapy. After the first induction cycle of intravenous infusion of daunorubicin, the patient experienced chest pain, shortness of breath, and low blood pressure. The electrocardiograms revealed significant ST-elevation in the D1, aVL, and V2–V6 leads, which indicated AMI. Coronary catheterization showed spontaneous coronary dissection in the mid-left descending coronary artery and first obtuse marginal artery of the circumflex. The patient died immediately.DiscussionThis is the first reported case of multiple SCAD associated with intravenous (IV) daunorubicin infusion. We also reviewed the literature and proposed the mechanism of this complication.

The Modulated Expression of Mo5, a Human Myelomonocytic Plasma Membrane Antigen

Mo5 is a 94-kd protein antigen expressed by human peripheral blood monocytes, neutrophils, and by all bone marrow myeloperoxidase-positive myeloid precursors (promyelocytes, myelocytes, metamyelocytes, and bands). Mo5 is borne by the malignant cells of 74% of patients (N = 27) with acute monocytic leukemia (French-American-British [FAB] group M4, M5), and 50% of patients (N = 38) with acute granulocytic leukemia (FAB M1, M2, and M3). Nonmyeloid cells in peripheral blood and bone marrow are Mo5-negative. The surface expression of Mo5 by myeloid cells is modulated by several experimental conditions: Exposure of neutrophils to calcium ionophore (1 mumol/L, 37 degrees C, ten minutes) under conditions resulting in degranulation of specific granules produces a three- to fourfold increase in the plasma membrane density of Mo5 antigen. This suggests that, in neutrophils, there is an intracellular pool of Mo5 antigen, which may be associated with specific granules, and that granule-associated Mo5 is translocated to the plasma membrane upon degranulation. Conversely, incubation of monocytes, neutrophils, U-937, and Mo5-positive leukemia cells in medium containing anti-Mo5 monoclonal antibody results in a significant decrease in surface Mo5 expression. This loss of surface Mo5 is a rapid, temperature-dependent process (occurring within 30 minutes at 37 degrees C) that is produced by divalent anti-Mo5 immunoglobulin [F(ab')2 but not F(ab)]. After down-modulation, Mo5 is reexpressed by monocytes within 48 hours. Mo5 is therefore a human myelomonocytic differentiation antigen whose expression is modulated up or down depending on the nature of extracellular stimuli.

Autologous non-human primate model for safety assessment of piggyBac transposon-mediated chimeric antigen receptor T cells on granulocyte-macrophage colony-stimulating factor receptor.

ObjectivesChimeric antigen receptor (CAR)‐T cell therapy redirected to specific antigens on tumor cells is a promising immunotherapy strategy for various cancers. Most target antigens are also expressed on normal tissues at varying levels, and therefore, a considerable challenge in the field is determining safety profiles, including life‐threatening off‐tumor and off‐target toxicities. The granulocyte–macrophage colony‐stimulating factor receptor (hGMR) is a promising target for CAR T‐cell therapy for a subset of acute myelocytic leukaemia, although it is also expressed on normal cells including monocytes, macrophages, CD34‐positive haematopoietic cells and vascular endothelial cells. hGMR and other immune‐related proteins are highly conserved between humans and cynomolgus macaques (Macaca fascicularis). Therefore, in this study, we engineered cynomolgus T cells to express CAR molecules redirected to hGMR by piggyBac (PB) transposon‐based gene transfer and adoptively transferred autologous hGMR‐CAR T cells into cynomolgus macaques.MethodsWe established PB‐mediated human GMR (hGMR)‐specific CAR T cells using cynomolgus peripheral blood mononuclear cells and transferred them into autologous individuals, and evaluated the potential toxicity related to hGMR‐CAR T cells.ResultshGMR‐CAR T cells did not exert overt organ toxicities such as bone marrow suppression, monocytopenia and vasculitis, although they recognised and killed cynomolgus monocytes and macrophages in vitro.ConclusionAlthough our model did not simulate a tumor‐bearing model, it supports the safety of hGMR‐CAR T cells and demonstrates the usefulness of a non‐human primate model to evaluate the safety of T‐cell products by assessing off‐tumor/off‐target toxicity before clinical trials.

Evaluation of diet as a risk factor in the development of childhood leukaemia: a case control study.

To evaluate probable association of dietary risk factors with childhood leukaemia. The case-control study was conducted at the Children Hospital, Pakistan Institute of Medical Sciences, Islamabad, Pakistan, from January to December 2017, and comprised children of either gender aged 2-12 years with recently diagnosed acute lymphocytic or acute myelocytic leukaemia An age and gender matched equal group of healthy children was taken as controls. Dietary-intake data was collected for six food groups, namely raw vegetables, fresh fruits, packed fruit juices, caffeinated drinks, junk foods, and processed/precooked food items. Frequency of the selected food group consumption was summarised in six categories: rarely/never, 1-3 days/week, 4-6 days/week, once daily, twice daily and thrice daily. Data was collected through interviews with the mothers using a pre-designed questionnaire, and was analysed using SPSS 21. Of the 90 subjects, 45(50%) were in each of the two groups. There were no differences in baseline characteristics between the two groups (p>0.05). Consumption of caffeinated drinks and junk food was significantly higher in cases (p=0.001) while controls showed significantly higher consumption of fresh fruits (p=0.0012). No significant difference was noted for consumption of vegetables, packed fruit juices and processed food between the groups (p> 0. 05 ). Higher consumption of caffeinated drinks and junk food was observed in cases compared to controls.

Bradicardia inducida por quimioterapia en pacientes oncológicos

IntroductionThere are daily reports of the toxic effects of chemotherapy on the heart, among them are the arrhythmias. However, there are very few publications on bradycardia caused by anti-neoplastic treatment. ObjectiveTo describe and analyse the presence of post-chemotherapy bradycardia in the oncology patient. Materials and methodsA non-experimental, descriptive and retrospective study was conducted on patients seen during the year 2017 in a Cardiology Department due to post-chemotherapy bradycardia. ResultsA total of 59 patients were evaluated, of whom 31 (52.5%) were males and 28 (47.5%) women, and with a median age of 42 years. The median heart rate was 46 beats per minute. The bradycardia was more common in acute myelocytic leukaemia (25.42%), followed by acute lymphoblastic leukaemia (20.34%). It was asymptomatic in 88.31% of cases. The chemotherapy drugs associated with bradycardia in acute myelocytic leukaemia were cytarabine in combination with daunorubicin, whilst in acute lymphoblastic leukaemia they were vincristine in combination with daunorubicin. A prolonged QTc interval was present in 12 (20.34%) of cases. The time between the chemotherapy and the onset of bradycardia was 24 to 48hours in 35.6%, and the recovery of the heart rate was between 24 and 48hours in 61.02%. ConclusionsSinus bradycardia as an adverse effect of chemotherapy is more frequent in acute myelocytic leukaemia, whilst the most common anti-neoplastic drugs associated with bradycardia were cytarabine and daunorubicin.

My Path from Hiroshima to Houston

How did I, a Japanese woman raised in Hiroshima, come to be a professor of radiation oncology at MD Anderson Cancer Center in Houston? My decision to become a cancer investigator and physician was made very early in my life through my experiences with my family in Japan and with 1 of my best friends, Sadako Sasaki, who died of acute granulocytic leukemia at the age of 11 after exposure to atomic bomb radiation.

Matrine induces Akt/mTOR signalling inhibition-mediated autophagy and apoptosis in acute myeloid leukaemia cells.

Pharmacological modulation of autophagy has been referred to as a promising therapeutic strategy for cancer. Matrine, a main alkaloid extracted from Sophora flavescens Ait, has antitumour activity against acute myelocytic leukaemia (AML). Whether autophagy is involved in antileukaemia activity of matrine remains unobvious. In this study, we demonstrated that matrine inhibited cell viability and colony formation via inducing apoptosis and autophagy in AML cell lines HL‐60, THP‐1 and C1498 as well as primary AML cells. Matrine promoted caspase‐3 and PARP cleavage dose‐dependently. Matrine up‐regulated the level of LC3‐II and down‐regulated the level of SQSTM1/p62 in a dose‐dependent way, indicating that autophagy should be implicated in anti‐AML effect of matrine. Furthermore, the autophagy inhibitor bafilomycin A1 relieved the cytotoxicity of matrine by blocking the autophagic flux, while the autophagy promoter rapamycin enhanced the cytotoxicity of matrine. Additionally, matrine inhibited the phosphorylation of Akt, mTOR and their downstream substrates p70S6K and 4EBP1, which led to the occurrence of autophagy. In vivo study demonstrated that autophagy was involved in antileukaemia effect of matrine in C57BL/6 mice bearing murine AML cell line C1498, and the survival curves showed that mice did benefit from treatment with matrine. Collectively, our findings indicate that matrine exerts antitumour effect through apoptosis and autophagy, and the latter one might be a potential therapeutic strategy for AML.

Clinical Study of Allo-HSCT with Conditioning Regimen Containing Decitabine in the Treatment of advanced Acute Myloid Leukemia and Myelodysplastic Syndrom

▪Background: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the only curative treatment options to hematologic malignancies. However, majority of patients with refractory or resistant hematologic malignancies can not achieve remission before transplantation. And the relapse rate of these patients after transplantation remains high obviously. Therefore, it is necessary to design a safe and effective conditioning regimen to improve the remission rate of these patients and disease-free survival (DFS), but to reduce transplantation related mortality (TRM). The optimal conditioning regimen not only can reduce tumor burden and eradicate minimal residual disease but also can make immunosuppressive state to ensure engraftment. As well as, it does not increase the TRM. One of the promising drugs of epigenetics is decitabine (DAC), which has a significant effect on a variety of hematologic malignancies. It is widely used in myelodysplastic syndromes(MDS) even for relapsed and refractory acute myelocytic leukaemia (AML). Because decitabine can not only up-modulate the tumor-associated antigen express on surface of leukemia cells to increase graft-versus-leukemia (GVL) effect but also can reduce the incidence of graft-versus-host disease (GVHD) by increase the number of regulatory T Cells（Tregs）.Aims: This clinical study will investigate the security and efficacy of conditioning regimen containing decitabine. Further to explore the role in advanced malignant hematologic disease.Methods: We retrospectively studied 20 cases of patients with hematologic malignancies, who underwent allo-HSCT with decitabine combined with conditioning regimens in the Department of Hematology, the First Affiliated Hospital of Soochow University during May 1, 2012 to April 30, 2014.Results: 19 patients achieved complete remission and hematopoietic reconstitution after transplantation. Only 1 NR case died on day +27 post transplant. The median time of neutrophil and platelet reconstitution were 12 (10-22) and 14.5 (12-35) days respectively. The median time of archiving full donor chimerism [short tandem repeat (STR)STR>95%] was 18(13-62) days. The median follow-up post transplant was 246 (19-582) days. 3 cases relapsed. 2 cases were dead due to relapse.1 case achieved complete remission again after donor lymphocyte infusion (DLI). 1 CR case was dead due to hemorrhage of digestive tract. The other 15 CR cases were survival with continued remission. The estimated 2-year overall survival (2yr-OS) rate was 78%.The 2 year disease-free survival (2yr-DFS) rate was 62.6%. The cumulative relapse rate was 26.7%. The transplantation-related mortality (TRM) rate was 0. Furthermore, the estimated 2-yr OS and DFS of patients with DNMT3A mutations or abnormalities of chromosome 7 and complex chromosomal karyotype were 72.9% and 60.6% respectively. Concerning about transplant related toxicity, except one case has grade III gastrointestinal toxicity, all the other toxicities were mild (grade I-II). The cumulative rate of aGVHD and cGVHD were 20.5% and 48.3%.And the cumulative rate of aGVHD for grade I-II and grade II-IV were 15% and 10.5%.Conclusions1.Allo-HSCT is an effective treatment for refractory and relapsed AML and high- risk MDS. It is feasible to use conditioning regimen containing decitabine before allo-HSCT. The treatment were well tolerated.2.92.3% of the patiants achieved CR, and were well engraftment. Because of decitabine can promote megakaryocytic maturation and accelerate the release of platelet, so hematopoietic was reconstructed rapidly, especially for the megakaryocyte. The 2yr-DFS rate was 62.6%, the cumulative relapse rate was 26.7%. The conditioning regimen containing decitabine before allo-HSCT seems to reduce the incidence of aGVHD.The prognosis and survival of the patients with complex chromosomal karyotype or chromosome 7 abnormalities or DNMT3A mutation may be improved by treating with decitabine containing conditioning regimen. DisclosuresNo relevant conflicts of interest to declare.

Acquired dyschromatopsia in acute myelocytic leukaemia

Patients with haematological malignancy are referred to the ophthalmologist either with visual symptoms or to exclude orbital or intraocular involvement after the diagnosis has been established. This report describes a patient with acute myelocytic leukaemia (AML) whose presenting symptom was dyschromatopsia. A 52-year-old female, previously in good health, presented with a disturbance of colour vision. On examination, there was bilateral reduction in visual acuity, impaired colour vision and severely constricted visual fields. Electrophysiological testing and colour contrast sensitivity (CCS) assessment were performed. CCS showed bilateral threshold elevation in the tritan axis of both eyes, right worse than left. Pattern ERG showed marked macular dysfunction in the right eye, but was normal in the left eye. Full-field ERGs fell within the normal range. Pattern VEPs were reduced in the right eye, without peak time shift; flash VEPs showed bilateral delay. Investigation showed severe anaemia, and a bone marrow biopsy confirmed a diagnosis of acute AML. There was symptomatic improvement in visual acuity and colour vision following blood transfusion and initiation of chemotherapy. This appears to be the first case report of dyschromatopsia in AML with symptomatic improvement following treatment. The case lends support to previously suggested hypotheses of chromatic visual disturbance in association with presumed hypoxia.

Acute myeloid leukaemia with abnormal eosinophil precursors without inversion 16

A 46-year-old previously healthy man presented with a 2week history of fever and diarrhoea. A full blood count showed: white blood cells 49·5 9 10/l (blast cells 42 9 10/l, eosinophils 1·5 9 10/l), haemoglobin concentration 166 g/l and platelets 52 9 10/l. There was no basophilia and Auer rods were not seen. A coagulation screen was normal. The bone marrow was markedly hypercellular with over 80% cellularity, including 80% myeloblasts, which were positive for CD13, CD33, CD43, CD64 (dim), CD117 and myeloperoxidase, and negative for CD14, CD15, CD34, CD45, CD64, terminal deoxynucleotidyl transferase, human leucocyte antigen (HLA)-DR and lysozyme. Notably, there were 12% eosinophil precursors, many of which displayed large basophilic granules admixed with eosinophilic granules (image), morphologically strongly reminiscent of acute myelocytic leukaemia with inv (16)(p13·1q22) or t(16;16)(p13·1;q22). Fluorescence in situ hybridization was negative for an inversion 16, as well as for PDGFRA and PDGFRB rearrangement. Karyotypic analysis demonstrated a normal male karyotype. Molecular analysis showed a FLT3 internal tandem duplication and an NPM1 exon 12 mutation. This analysis was negative for the FLT3D835 variant. The patient underwent induction chemotherapy (cytarabine and idarubicin; 7 + 3) with a diagnosis of acute myeloid leukaemia. He achieved complete remission, and was referred for evaluation for bone marrow transplantation. The absence of inversion 16 and other recurrent abnormalities associated with eosinophilia was a surprise in this case given the striking morphological features.

Amphotericin Bin vitroresistance is associated with fatalAspergillus flavusinfection

Whether in vitro antifungal susceptibility findings correlate with the outcome of patients with invasive aspergillosis (IA) remains debated. This study aimed to test whether IA patients' outcomes were associated with in vitro susceptibility results. To do so, we determined the in vitro susceptibility to amphotericin B (AMB) of 37 Aspergillus flavus isolates from 14 patients with haematological malignancies diagnosed with proven or probable IA, of which 13 were treated with AMB deoxycholate. Minimal inhibitory concentrations (MICs) were determined by Etest with the isolates classified as in vitro sensitive (AMB-S) or resistant (AMB-R) if their MICs were < 2 or ≥ 2 mg/l, respectively. The association of the patients' death with primary disease, administered antifungal treatment, and infection with AMB-R A. flavus was tested using generalized estimating equations logistic regression. We assessed AMB-R in 31/37 (84%) isolates. In the patients treated with AMB, the survival rate was 2/3 (67%) and 2/9 (22%) for those infected with AMB-S or AMB-R A. flavus, respectively. Both infection with AMB-R A. flavus (P = 0.014) strain and acute myelocytic leukaemia as the underlying primary disease (P = 0.036) were independent predictors of death. Our findings indicate that in vitro resistance predicts a poor outcome in patients with A. flavus invasive disease treated with AMB. Recent advances in non-culture-based microbiological methods should not discourage efforts to obtain in vitro antifungal susceptibility results, which are critical for the choice of antifungal therapy in patients with IA.

Role of Demodex folliculorum in the pathogenesis of blepharitis

Editor, T he ectoparasite Demodex folliculorum (Simon 1843) is most common parasite of humans. In the eye, D. folliculorum is found in the eyelash follicle. The aim of this study was to examine the prevalence of D. folliculorum in the eyelashes in patients with haematologic disorders. Eyelashes were collected from 95 patients of the Clinic of Haematology Pomeranian Medical University, Szczecin, Poland, and from 1091 healthy controls. There were 47 (49%) women and 48 (51%) men in the patients group (age range: 58.6 ± 13.1) and 759 (69.6%) women and 332 (30.4%) men in the control group (age range: 58.6 ± 13.0). From each patient, we aseptically collected two lashes from the upper right eyelid and two lashes from the upper left eyelid. The collected material was used in preparations examined using light microscopy (magnified 100 times). Infection of the examined subjects was confirmed by the detection of adult and larval forms of D. folliculorum. Demodex folliculorum is found in 21.8% of healthy controls and 18.9% of haematologic patients (Fig. 1; Table 1). In the control group, D. folliculorum occurred in 22.3% of women and in 20.8% of men. In patients with haematologic disorders, D. folliculorum occurred in 17.5% of women and in 25% of men. A much lower rate of infestation of D. folliculorum (12%) was found in immunosuppressed patients with rheumatoid arthritis (Ciftci et al. 2006). On the other hand, in patients with final-stage renal failure (ESRF) on dialysis treatment, D. folliculorum found in 44.4% of patients (Karincaoglu et al. 2005). In our study, the percentage of D. folliculorum infestation in haematologic patients ranged from 16% of patients with acute leukaemia, MPS and other haematologic diseases, and 21.7% with multiple myeloma, to about 24.1% in patients with nonHodgkin’s lymphoma and CLL. Seyhan et al. (2004) found D. folliculorum in the skin of patients with acute lymphocytic leukaemia (12%), acute myelocytic leukaemia (32%), chronic lymphocytic leukaemia (4%), chronic myelocytic leukaemia (10%), Hodgkin’s lymphoma (4%) and nonHodgkin’s lymphoma (38%). Demodex folliculorum seem to be a mediator of chronic blepharitis; some recommend that mites be sought in cilia of chronic blepharitis patients (Czepita et al. 2007). Elevated subjective symptoms of the ocular surface were caused by increased levels of D. folliculorum. Itching, burning, foreign body sensation, crusting and redness of the lid margin, and blurry vision are the main symptoms. Signs include disorders of eyelashes, lid margin inflammation, meibomian gland dysfunction, blepharoconjunctivitis and blepharokeratitis (Czepita et al. 2007). In the control group, the most common symptoms related to D. folliculorum infestation included sensitivity to light, dacryorrhea and itching of the eyelids; loss of eyelashes was the least common. In the group of haematology patients, dacryorrhea was most frequent, without any reports of sensitivity to smoke, light, foreign body sensation under the eyelids or loss of eyelashes. A 61.7% of D. folliculorum-infected patients in the ophthalmology clinic reported itching, and 59.1% reported red eyes (Inceboz et al. 2009). In our study, we found that D. folliculorum infestation was correlated with cylindrical dandruff in the lash roots, both in the control group and in haematologic patients. In patients with D. folliculorum infestation in eyelashes, we found trichiasis, meibomian gland dysfunction with lipid tear deficiency and conjunctival inflammation (Czepita et al. 2007). The prevalence of D. folliculorum in patients with haematologic diseases was similar to that of the control group. Demodicosis may cause itchiness in the eyelids and cylindrical dandruff in the lash roots.

Plasma Ghrelin Levels For The Patients With Acute Myelocytic Leukaemia (AML)

Plasma Ghrelin Levels For The Patients With Acute Myelocytic Leukaemia (AML)

MicroRNA expression in childhood acute granulocytic leukemia and its subtypes

Recent studies have suggested that there is a close relation between microRNA and acute leukemia (AL). The aim of this study was to investigate and better understand the classification and diagnosis of AL as well as pathogenesis and prognosis of this disease. A total of 93 children with AL and and 12 cases of idiopathic thrombocytopenic purpura (as control group) were enrolled in this study. Microarray chip analysis of their bone marrow samples was conducted to evaluate the microRNA profiles. Quantitative real-time PCR was performed for validating the abnormal expression of microRNA. The microRNA expression profiles were different between acute granulocytic leukemia and acute lymphoblastic leukemia and also between the three subtypes (M1, M2 and M3) of acute granulocytic leukemia according to FAB classification based on leukemic cell differentiation. These three subtypes of leukemia could be identified by unsupervised hierarchical cluster analysis of microRNA expression and had specific up-regulation of miR-335, miR-126 and miR-125b, respectively. However, in the M2 and M3 subtypes with positive AML1-ETO and PML-RARα, respectively, which have a better prognosis, the expressions of miR-126 and miR-125b were significantly higher than those with negative AML1-ETO and PML-RARα. Further more, miR-335 and miR-146 were up-regulated in acute granulocytic leukemia observed in this study, which are different from those reported for adult patients. microRNA cascade may serve as new biomarkers for the classification and diagnosis of pediatric AL. It is also suggested that there might be different pathogenesis and prognosis between AL types related to specific expression and regulation of microRNA.

Bilateral sudden onset proptosis in child: AML

Abstract Orbital infiltration with bilateral proptosis has been observed in 2% cases of acute or chronic lymphatic leukaemia [1] , [2] . In contrast myelogenous leukaemia only very rarely gives rise to extra ocular muscle infiltration [2] . We report an unusual case of acute myelocytic leukaemia in 10-year-old male child presenting with acute bilateral proptosis as its sole manifestation to an ENT surgeon and also describe characteristic radiological features.

Primary Granulocytic Sarcoma:A Allo-Transplantation Case Report and Literature Review.

Abstract 4368 ObjectiveTo investigate the effect of allogeneic transplantation in treating primary granulocytic sarcoma. MethodsWe report the diagnosis and treatment of one patient with primary granulocytic sarcoma and review the related articles. ResultsFirstly appeared as one isolated tumor in breast, the disease was diagnosed by pathological methods with immunochemistry positive stain in MPO, CD68(KP-1) and bacteriolysis enzyme. After radical operation on sick breast, the patient was treated with four courses chemotherapy according to that of acute granulocytic leukemia,then followed by matched sibling transplantation. After 6 months follow-up, the patients is still in complete remission. ConclusionIf having suitable donor, patient with primary granulocytic sarcoma shoud be treated with allogeneic transplantation. Disclosures:No relevant conflicts of interest to declare.

Risks Associated with Low Doses and Low Dose Rates of Ionizing Radiation: Why Linearity May Be (Almost) the Best We Can Do

Deterministic and stochastic effects associated with high-dose ionizing radiation (x-ray) exposure have been known for almost as long as ionizing radiation itself (1–3). At lower doses, radiation risks are primarily stochastic effects, in particular, somatic effects (cancer) rather than the deterministic effects characteristic of higher-dose exposure (4–6). In contrast to deterministic effects, for stochastic effects, scientific committees generally assume that at sufficiently low doses there is a positive linear component to the dose response—that is, that there is no threshold (4–6). This does not preclude there being higher-order (eg, quadratic) powers of dose in the dose response that may be of importance at higher doses. It is on this basis that models linear (or linear-quadratic) in dose are often used to extrapolate the experience of the Japanese atomic bomb survivors (who were typically exposed at a high dose rate to moderate doses [average, 0.1 Sv]) to estimate risks from low doses and low dose rates (4–6). Most population-based cancer risk estimates are based primarily on the Japanese atomic bomb survivor Life Span Study (LSS) cohort data (4–6). However, evidence of excess risks comes from a large number of other studies as well. In the parallel editorial (7), evidence is presented for possible real (or at least “practical”) thresholds or “hormetic” (beneficial) effects of low doses of ionizing radiation. As we summarize here, and in contrast to the arguments of Tubiana et al (7), we judge that there is little epidemiologic or biologic evidence for these for cancer. The arguments are of three forms: (a) assessment of the degree of curvature in the cancer dose response within the Japanese atomic bomb survivors and other exposed groups (in particular, departure from linear or linear-quadratic curvature), (b) consistency of risks between the Japanese and other moderate- and low-dose cohorts, and (c) assessment of biologic data on mechanisms. Most of the information on radiation-induced cancer risk comes from (a) the Japanese atomic bomb survivors, (b) medically exposed populations, (c) occupationally exposed groups, and (d) environmentally exposed groups (6). In the higher-dose radiation therapy studies, where doses received are very much higher than in the LSS, sometimes in the range at which cell sterilization occurs, excess cancer risks per unit dose tend to be less than in comparable subsets of the LSS (8,9). However, as we show, risks in moderate- and low-dose medically and occupationally exposed groups are generally consistent with those in the LSS.

C/G転座，好中球アルカリフォスファターゼ低値を示す急性骨髄性白血病病型:—15例の臨床的観察—

C/G転座，好中球アルカリフォスファターゼ低値を示す急性骨髄性白血病病型:—15例の臨床的観察—