Cases Of Acute Myeloblastic Leukemia Research Articles

Optical Genome Mapping Combined with High-Throughput Sequencing Is Effective for the Diagnostic and Prognostic Genomic Classification of Acute Myeloid Leukemia and Myelodysplastic Neoplasms

Cytogenetic and molecular analyses are crucial for the diagnosis, choice of treatment and prognostic evaluation of acute myeloblastic leukemia (AML) and myelodysplastic neoplasms (MDS). Optical genome mapping (OGM) is a recent technology enabling a genome-wide high-resolution detection of structural abnormalities (SVs) and copy number variations (CNV) developed by the Bionano® company. The clinical value of OGM in AML and MDS and its positioning in relation to conventional karyotype and FISH (K&F) and targeted high throughput panel sequencing (HTS) has been little evaluated. Here, the primary objective was to evaluate prospectively the ability of OGM to apply the diagnosis (WHO 2022) and prognostic cytogenetic classification of AML (ELN 2022) and MDS (IPSSm) in comparison with K&F and HTS. The secondary objectives were to evaluate the proportion of informative cases in intention-of-analysis and among them the level of concordance of OGM versus K&F, the amount of additional information (OGM vs KF), and the potential reclassification (OMS 2022, ELN 2022, IPSSm) in addition to K&F and a targeted HTS panel (i.e. including ASXL1, CEBPA, DNMT3A, IDH1, IDH2, FLT3, KRAS, NPM1, NRAS, RUNX1, SRSF2, TP53, WT1) used in real-life. A two-stage prospective selection of bone marrow or blood samples was carried out at Nantes University Hospital between May 2022 and June 2023. A 1st collection of samples from 67 patients (pts) with AML (n=58) or MDS (n=9) was selected and cryopreserved according to pre-analytical criteria (cell count, time after collection). A 2nd final selection of 39 pts including 34 AML and 5 MDS was carried out according to their cytogenetic and/or molecular data, in order to evaluate the performance of OGM in different profiles of clinical interest (Table 1). Of these 39 intention-to-analyze patients, 35 were informative for OGM comparison with K&F (3 OGM failures, 1 K not realized). Interpretation criteria with Bionano access software considered SVs and CNVs >200 and >500 kbp respectively, or smaller if a gene of interest was found. Further details will be presented at the conference. OGM showed concordance with K&F in 30/35 (86%) of informative pts, but 5 had subclonal (<20%) gains undetected i.e. +8, +21, +6p or poorly detected i.e. t(1;15) with centromeric break. None of these OGM false negatives modify the diagnosis or prognosis. Additional information was found with OGM in 19/35 pts, with a median of 1 cryptic anomaly/patient (range = 1-13). Cryptic abnormalities were identified in 9/18 pts with normal K (7 AML, 2 MDS), including 5 pts with pathogenic SV, notably KMT2A with partial tandem duplication (PTD) and TET2 deletion, and 4 pts with SV of unknown significance (-6p, +4q, +15q, +19p, +20q). Finally, the WHO diagnosis was confirmed with OGM in all informative pts but not modified in any of them. OGM confirmed ELN prognostic classification of all the AML cases without modification. Two AML cases had >3 anomalies with OGM (range = 5-6) of which >2 were cryptic without complex karyotype (CK) (size = 226-1221 kbp, VAF% = 3-100) including gains (3q, 11q, Xp) or losses (3p, 4p, 21q) of undetermined or pathogenic ( RUNX1 deletion) significance. In this context of multiple cryptic anomalies, there is no precise definition of abnormal or CK with OGM. One is a MDS-related AML cases that also had MDS-associated somatic mutations (i.e. ASXL1, SRSF2 ELNadverse) and the other was an AML with NUP98 rearrangement and FLT3-ITD mutation (i.e ELN intermediate). OGM confirmed the IPSSm prognostic cytogenetic category in 3 pts and modified it in 2/5 MDS pts (40%). Among the two latter, K was normal (e.g. favorable) but OGM identified cryptic KMT2A- PTD of poor prognosis. These two SMD-IB2 changes the IPSSm risk category from Moderate-High or High to Very-High risk group. The combination of OGM and HTS techniques provided a more accurate prognostic classification of MDS cases. Confirmations of cryptic pathogenic anomalies detected by OGM using a 2nd technique will be presented at the congress. OGM technology is powerful for identifying pathogenic anomalies, but the criteria for abnormal K and CK need to be clarified in order to apply international diagnosis and prognosis classifications. To this end, the OGM+HTS combination is highly effective. The positioning of OGM as a complement and/or replacement for conventional cytogenetic and molecular tools, and its impact on therapeutic choice, still needs to be evaluated in AML and MDS.

EVALUATION OF KIDNEY FUNCTION IN AN ELDERLY PATIENT WITH ACUTE MYELOBLASTIC LEUKEMIA AFTER HEMATOPOIETIC STEM CELL TRANSPLANTATION: A CASE REPORT

Relevance: Kidney functions in treating acute myeloblastic leukemia (AML) undergo serious effects, especially in elderly patients. Chemotherapeutic drugs used to prepare for hematopoietic stem cell transplantation (HSCT) inevitably affect elderly patients’ kidney function. Moreover, involutive changes in the kidneys can physiologically decrease kidney function.
 The study aimed to evaluate kidney function in an elderly patient with AML after HSCT.
 Methods: The article describes a clinical case of AML in an elderly patient who underwent allogeneic HSCT.
 Results: We analyzed the dynamics of the functional state from the moment of registration of AML to +100 days after HSCT. During the entire follow-up period, we did not detect any renal dysfunction in the elderly patient. Despite the HSCT and the effects of nephrotoxic drugs in an elderly patient + 100 days after HSCT, kidney function was preserved.
 Conclusion: The described case highlights the importance of maintaining renal function in elderly patients after HSCT and long-term renal monitoring.

EVALUATION OF KIDNEY FUNCTION IN AN ELDERLY PATIENT WITH ACUTE MYELOBLASTIC LEUKEMIA AFTER HEMATOPOIETIC STEM CELL TRANSPLANTATION: A CASE REPORT

Relevance: Kidney functions in treating acute myeloblastic leukemia (AML) undergo serious effects, especially in elderly patients. Chemotherapeutic drugs used to prepare for hematopoietic stem cell transplantation (HSCT) inevitably affect elderly patients’ kidney function. Moreover, involutive changes in the kidneys can physiologically decrease kidney function.
 The study aimed to evaluate kidney function in an elderly patient with AML after HSCT.
 Methods: The article describes a clinical case of AML in an elderly patient who underwent allogeneic HSCT.
 Results: We analyzed the dynamics of the functional state from the moment of registration of AML to +100 days after HSCT. During the entire follow-up period, we did not detect any renal dysfunction in the elderly patient. Despite the HSCT and the effects of nephrotoxic drugs in an elderly patient + 100 days after HSCT, kidney function was preserved.
 Conclusion: The described case highlights the importance of maintaining renal function in elderly patients after HSCT and long-term renal monitoring.

Doxorubicin-Loaded Polymeric Micelles Conjugated with CKR- and EVQ-FLT3 Peptides for Cytotoxicity in Leukemic Stem Cells.

Doxorubicin (Dox) is the standard chemotherapeutic agent for acute myeloblastic leukemia (AML) treatment. However, 40% of Dox-treated AML cases relapsed due to the presence of leukemic stem cells (LSCs). Thus, poloxamer 407 and CKR- and EVQ-FLT3 peptides were used to formulate Dox-micelles (DMs) and DM conjugated with peptides (CKR and EVQ) for improving AML-LSC treatment. Results indicated that DMs with a weight ratio of Dox to P407 of 1:200 had a particle size of 23.3 ± 1.3 nm with a high percentage of Dox entrapment. They were able to prolong drug release and maintain physicochemical stability. Following effective DM preparation, P407 was modified and conjugated with FLT3 peptides, CKR and EVQ to formulate DM-CKR, DM-EVQ, and DM-CKR+DM-EVQ. Freshly synthesized DMs displaying FLT3 peptides showed particle sizes smaller than 50 nm and a high drug entrapment level, comparable with DMs. DM-CKR+DM-EVQ was considerably more toxic to KG-1a (AML LSC-like cell model) than Dox-HCl. These FLT3-targeted DMs could increase drug uptake and induce apoptosis induction. Due to an increase in micelle-LSC binding and uptake, DMs displaying both peptides tended to improve the potency of Dox compared to a single peptide-coupled micelle.

Diagnostic Utility of Immunophenotyping by Flow Cytometry for Diagnosis and Classification of Acute Leukemias in Tikur Anbessa Specialized Hospital, Addis Ababa, Ethiopia

Background: Immunophenotypic characterization of acute leukemia is an important clinical application of flow cytometry and has become a powerful tool contributing to proper diagnosis and classification. The aim of this study is to phenotype and classify acute leukemias by flow cytometry using commonly used markers for leukemia diagnosis.Methods: A total of 40 pediatric and adult patients diagnosed with acute leukemia were evaluated by flow cytometry with 17 surface and cytoplasmic markers known to be useful in discriminating different types of acute leukemia. These results were compared with classification results using standard morphological criteria.Results: 21 of 40 patients (52.5%) were classified as acute myeloblastic leukemia (AML) while 19 (47.5%) were identified as acute lymphoblastic leukemia (ALL). Of all the ALL cases, 10 of the 19 (52.6%) were B-ALL and 47.4% (9/19) were T-ALL based on flow cytometry. Markers of immaturity HLA-DR and CD34 antigens were co-expressed in 61% of AML cases and 33% of T-ALL cases, whereas CD34 was expressed in 50% of the B-ALL cases. cMPO and CD13 were the most expressed markers of AML, CD19 and cCD79a were present in all cases of B-ALL, and cytoplasmic CD3 and CD7 were positive on most all T-ALL cases. Discrimination of AML from ALL patients by flow cytometry was 80% concordant with traditional morphology. Notable discrepancies occurred in cases where leukemia cells expressed markers for more than one lineage.Conclusions: In the Ethiopia setting, flow cytometry represents a feasible and promising adjunctive diagnostic approach for acute leukemia.

Leukemia cutis and other dermatological findings in pediatric patients with acute myeloid leukemia.

Leukemia cutis (LC) is the infiltration of neoplastic leukocytes into the skin, causing skin lesions. In children, it appears more frequently in patients with acute myeloblastic leukemia (AML), particularly in subtypes with a monocytic component. We studied a retrospective cohort including all AML cases from the Hospital Infantil de México Federico Gómez between January 2009 to December 2019 and described the clinical characteristics of those who presented LC and other mucocutaneous manifestations. The information was collected from clinical records and analyzed using SPSS software (version 17). We identified 54 AML cases: 53.7% were males, and 75.9% of the patients presented at least one dermatosis in the course of the disease. LC was clinically present in 14.8% of patients and was histologically confirmed in 9.2% of them; two congenital leukemia cases were identified. Among these patients, LC was more frequent in males. LC patients were younger than those without LC, the most frequent AML subtype was M2 (37.5%), and the most frequent clinical manifestations were plaques, chloromas, and gingival hyperplasia. None of the patients presented LC before AML diagnosis. Currently, only a few studies about LC on pediatric populations have been reported, and the existing ones have small sample sizes. We found clinical and epidemiological similarities with other populations in the studied sample.

Primary Tumor Infiltration and Severe Acute Kidney Injury in Patients with Acute Myeloblastic Leukemia

In patients with hematologic malignancies, acute kidney injury (AKI) is the most common kidney complication requiring nephrologist consultation. Although the causes of AKI are multifactorial, primary tumor infiltration is rare in patients with acute myeloblastic leukemia (AML). This makes it challenging to determine the cause of AKI and the optimal chemotherapy regimen for AML. We describe two cases of AML (French-American-British classification: M2, M4) in patients with AKI requiring hemodialysis. We successfully identified the cause of AKI as primary leukemic infiltration and started induction chemotherapy in the setting of hemodialysis. This treatment significantly improved renal function and resulted in AML remission. In this report, we describe several clinical characteristics of AKI due to primary tumor infiltration. In addition, we emphasize the importance of onconephrology, a new subspecialty concerned with the complex relationship between the kidneys and cancer.

Clinical Manifestations and Hematological Profiles of Pediatric Acute Myeloblastic Leukemia Patients: 3 Years Observational Study in A West Java Tertiary Hospital, Indonesia

Objective: To determine and describe the clinical manifestations and hematological profiles of pediatric Acute Myeloblastic Leukemia (AML) in Dr. Hasan Sadikin General Hospital (RSHS), Bandung as a tertiary hospital in West Java, Indonesia. Methods: A retrospective cross-sectional study using the total sampling method was performed on the medical records of pediatric patients (0-18 years old)who were diagnosed as AML for the first time through bone marrow examination during the period of January 1, 2015 – December 31, 2017. Results: Of the 54 subjects who met the inclusion criteria, 42.6% were AML patients in the age group 6-12 years with male patients comprised 59.3% of the total number of subjects. Patients generally experienced pallor (83.3%), fever (75.9%), and decreased appetite (70.4%). The hematological profiles showed that 35.2% of patients had Hb <6.5 g/dL and 44.4% had a leukocyte count of of >50,000 cells/mm3. The majority of the subjects had a platelet count of <50,000 cells/mm3 (83.3%) and almost half of them had a peripheral blasts count of >50% (46.3%). Conclusion: Clinical manifestations and hematological profiles are important to diagnose AML, especially in pediatric patients. By assessing the manifestations and profiles, it is feasible to access and detect suspected cases of AML.

A Rare Case of Acute Myeloblastic Leukemia With Blast Count Less Than 20% in Bone Marrow

One of the diagnostic criteria for Acute Myeloblastic Leukemia (AML) is the presence of 20% myeloid blasts in peripheral blood or bone marrow. Some cases with recurrent cytogenetic abnormalities also fall in this category with blast cell count less than 20%. Thus, in the presence of these genetic abnormalities, the patients are classified as AML regardless of blast cell count. One of these genetic heterogeneities is t(8; 21) (q22, q22.1) which is more commonly seen in children and young adults. In this study, a 14-year-old boy is reported with a final diagnosis of AML, which was presented with fever and bicytopenia, clinically suspicious for acute leukemia. Laboratory results reported less than 20% blasts in bone marrow aspiration smears but genetic alteration t(8; 21) (q22, q22.1) was detected by molecular exams.

Unusual association of two cases of acute myeloblastic leukaemia and possible Sjogren’s syndrome and review of literature

Abstract Sjogren’s syndrome (SS) is frequently accompanied by hematologic complications, such as Hodgkin lymphoma. Here, we report on two unusual cases in which acute myeloid leukaemia (AML) and suspected SS occurred

Alpha-Synuclein Expression in Acute Erythroleukaemia, Acute Megakaryoblastic Leukemia, and Normal Counterparts in Bone Marrow

Alpha-synuclein is a member of synuclein family of proteins with unidentified function localized in the cytoplasm, mitochondria of neurons, and presynaptic nerve endings. Although it is found in the Lewy bodies in synucleinopathies and in Alzheimer's disease, the protein could also be considered as a novel marker in diagnosis of diseases related to the hematopoietic system. The current study evaluated alpha-synuclein expression in bone marrow sections obtained from 9 patients with acute myeloblastic leukemia (AML)-M6, 2 patients with AML-M7, and 56 patients with other forms of AML by immunohistochemical (IHC) analysis. Seven out of 9 cases with erythroleukemia (66.7%) and 1 of the 2 cases with M7 (50%) were positive. In contrast; the blasts in 2 out of 56 AML cases with non-M6/M7 (3.6%) showed positive staining. Accordingly, alpha-synuclein was positive in normal erythroid precursors and megakaryocytes (if existing) in these cases; while, it was negative in lymphoid and myeloid precursors. Alpha-synuclein expression in non-neoplastic and neoplastic erythroid cells and megakaryocytes could be used as a complementary and useful marker for distinction between AML-M6/M7 and other types of AML.

Biological microchip for establishing the structure of fusion transcripts involving MLL in children with acute leukemia

MLL is involved in fusion genes with more than 100 partner genes, approximately 80 of which have been characterized at the molecular level. MLL fusion genes are often found in infants (60-80% of acute lymphoblastic leukemia (ALL) cases and 40-50% of acute myeloblastic leukemia (AML) cases) and are appreciably rarer (8-10%) in children older than 1 year of age. MLL rearrangements are important markers in diagnosis and treatment choice. To identify the partner gene is of primary importance for prognosis and minimal residual disease monitoring. The structure of the fusion gene, including localization of the MLL breakpoints, is also informative. A method was developed to examine the fusion transcripts in order to identify the partner gene among the six most common ones and to establish the exon structure of the rearranged MLL. The method includes a multiplex reverse transcriptase-polymerase chain reaction (RT-PCR) to amplify and to fluorescently label a fusion transcript fragment and subsequent hybridization of the product on a biological microchip with immobilized oligonucleotides complementary to exons of MLL and its partner genes AFF1, MLLT1, MLLT3, MLLT4, MLLT10, and ELL. Hybridization results were verified by sequencing the RT-PCR products and, in some cases, performing long-distance inverse PCR (LDI-PCR). The study involved 38 bone marrow samples from ALL patients (including 33 children younger than 1 year of age) and 15 samples from AML patients (including 10 from children younger than 1 year of age). The main partner genes were AFF1 (49%), MLLT1 (27%), MLLT3 (12%), and MLLT10 (12%) in ALL and MLLT3 (80%), MLLT10 (10%), and MLLT4 (10%) in AML. Fusion gene transcripts most commonly included MLL exon 11 (58% of ALL cases and 50% of AML cases), suggesting a breakpoint in MLL intron 11.

Molecular Monitoring of RUNX1-RUNX1T1 Transcript Level in Acute Myeloblastic Leukemias on Treatment

Background. The current approach to treatment of acute myeloblastic leukemia (AML) includes the achievement of maximum tumor reduction and, therefore, eradication of a leukemic clone. The goal of the therapy is to achieve undetectable levels of the target gene, except an isolated molecular rearrangement of RUNX1-RUNX1T1. Aim. To estimate the dynamics of the RUNX1-RUNX1T1 level and relevant clinical manifestations during the monitoring of various stages of the program therapy and after its completion. Methods. The article presents a description of 10 cases of AML with isolated RUNX1-RUNX1T1 expression (n = 4) and the expression in combination with different molecular and cytogenetic abnormalities (n = 6). In addition, a long-term monitoring of the gene expression by quantitative determination of RUNX1-RUNX1T1 using a real-time PCR was presented. Results. The incidence of relapses in a group with a decreased RUNX1-RUNX1T1 expression level of >2 log is 75 % as compared to patients with a less significant reduction of the transcript level (with the relapse incidence equal to 0 %) (p = 0.05). The increase of the RUNX1-RUNX1T1 level against the background of bone marrow remission by more than 1 log coincided with a bone marrow relapse within 5-18 weeks. In addition, long-term persistence of a certain transcript level after the completion of a program therapy without relapse is possible. Conclusion. The study analyzed possible molecular background of different clinical outcomes of long-term persistence of the RUNX1-RUNX1T1 transcript that might lead to an individualized approach to AML patients.

Residential Proximity to Heavy-Traffic Roads, Benzene Exposure, and Childhood Leukemia-The GEOCAP Study, 2002-2007.

Childhood leukemia may be associated with traffic-related environmental exposure to benzene, and additional data are needed. The Géolocalisation des Cancers Pédiatriques (GEOCAP) Study, a nationwide French case-control study, was designed to avoid selection bias due to differential participation and misclassification. The study compared the 2,760 childhood leukemia cases diagnosed in France between 2002 and 2007 (including 2,275 cases of acute lymphoblastic leukemia (ALL) and 418 cases of acute myeloblastic leukemia (AML)) with 30,000 contemporaneous child population controls. The residence addresses were precisely geocoded, and 3 indicators of residential proximity to traffic were considered. Estimates of benzene concentrations were also available for the Île-de-France region (including Paris). A 300-m increase in major road length within 150 m of the geocoded address was significantly associated with AML (odds ratio = 1.2, 95% confidence interval: 1.0, 1.4) but not with ALL (odds ratio = 1.0, 95% confidence interval: 0.9, 1.1), and the association was reinforced in the Île-de-France region when this indicator was combined with benzene estimates. These results, which were free from any participation bias and based on objectively determined indices of exposure, showed an increased incidence of AML associated with heavy-traffic road density near a child's home. The results support a role for traffic-related benzene exposure in the etiology of childhood AML.

Parental smoking, maternal alcohol, coffee and tea consumption during pregnancy, and childhood acute leukemia: the ESTELLE study.

To investigate the role of parental smoking during pre-conception and pregnancy, maternal beverage consumption (alcohol, coffee and tea) during pregnancy and their possible interactions, in the etiology of childhood acute leukemia (CL). The ESTELLE study included 747 cases of CL [636 cases of acute lymphoblastic leukemia (ALL) and 100 cases of acute myeloblastic leukemia (AML)] diagnosed in France in 2010-2011 and 1,421 population controls frequency-matched with the cases on age and gender. Data were obtained from structured telephone questionnaires administered to the mothers. The odds ratios (OR) and their 95 % confidence intervals were estimated using unconditional logistic regression models adjusted for potential confounders. AML, but not ALL, was non-significantly associated with alcohol drinking during pregnancy [OR = 1.3 (0.8-2.0)] with a significant positive dose-response trend (p-trend = 0.02). Pre-conception paternal smoking was significantly associated with ALL [OR = 1.2 (1.1-1.5)] and AML [OR = 1.5 (1.0-2.3)]. CL was not associated with maternal smoking [OR = 1.0 (0.8-1.2)], or maternal coffee [OR = 0.9 (0.8-1.1)] or tea drinking [OR = 0.9 (0.8-1.1)] during pregnancy. However, a high consumption of coffee (>2 cups/day) was significantly associated with ALL [OR = 1.3 (1.0-1.8)]. The findings constitute additional evidence that maternal alcohol drinking during pregnancy may be involved in AML, and that paternal smoking before pregnancy may be a risk factor for CL. The role of maternal coffee drinking in CL remains unclear and should be investigated further in consortium analyses and in large birth cohort studies with exposure assessment more contemporaneous with the exposure, before the occurrence of the disease.

Identification of Leukemic Stem Cells in Acute Myeloid Leukemia Patients

Background: Acute myeloblastic leukemia (AML) can be viewed as newly formed, abnormal hemopoeitic tissue initiated by few leukemic stem cells (LSCs). Recognizing the LSC and identifying their behavior, plays a pivotal role in the approach of a targeted therapy.Colony-stimulating factor 1 (CSF-1), also known as M-CSF, is a protein ligand that acts on the CSF1R promotes mononuclear phagocytes survival, proliferation and differentiation.Aim of the work: Defining the self-renewing [Thy1-, CD34+, CD38-] LICs in AML cases before and after induction chemotherapy as a predictor for relapse and to determine how CSF1R (Fms) and CD34 markers affect the growth and survival of human leukemic cells in the CD38- Thy1- population.Patients and methods: This study was carried out on 30 samples from the peripheral blood of adult patients with de-novo acute myeloid leukemia. The majority of the patients were monocytic AMLSamples were sorted into four populations (Fms+CD34-, Fms+CD34+, Fms-CD34+ and Fms-CD34-) according to the surface markers of the cells. Cells were cultured on mouse stromal cells transfected with a plasmid containing human CSF-1. Samples were cultured using Iscove’s modified Dulbecc’s medium (IMDM).The cultures were assessed for survival of leukemic cells in days.Results: The mean survival in days of the cells was 13.9 before chemotherapy and 14.1 after chemotherapy. The difference in growth was insignificant (p>0.05). The Fms-CD34+ population in all but two samples tested had the longest survival time in culture.Conclusion: Our results suggest that leukemic stem cells may survive chemotherapy mainly due to their quiescence.Human CSF-1 was shown to increase the number of leukemic cells in co-culture with mouse stroma after 5 weeks. A novel leukemic stem cell (Fms-CD34+) has been identified and is the cell responsible for the growth and maintenance of the leukemic bulk. DisclosuresNo relevant conflicts of interest to declare.

Novel antifungal drugs against fungal pathogens: do they provide promising results for treatment?

The febrile neutropenia episodes of hematological patients and their outcomes were evaluated with respect to fungal pathogens and antifungal therapy in this retrospective study. All patients, who were older than 14years of age and developed at least one neutropenic episode after chemotherapy due to hematological cancer from November 2010 to November 2012, were included into the study. We retrospectively collected demographic, treatment, and survival data of 126 patients with neutropenia and their 282 febrile episodes. The mean Multinational Association for Supportive Care in Cancer score was 17.18±8.27. Systemic antifungal drugs were initiated in 22 patients with 30 culture-proven invasive fungal infections (IFIs), 25 attacks of 19 patients with probable invasive pulmonary aspergillosis (IPA), 42 attacks of 38 patients with possible IPA, and 31 attacks of 30 patients with suspected IFI. Voriconazole (VOR), caspofungin and liposomal amphotericin B were used to treat 72 episodes of 65 patients, 45 episodes of 37 patients and 34 episodes of 32 patients as a first-line therapy, respectively. Unfavorable conditions of our hematology ward are thought to increase the number of cases with invasive pulmonary aspergillosis and VOR use. It should be taken into consideration that increased systemic and per oral VOR usage predisposes patients to colonization and infection with azole-resistant fungal strains. Catheters should be removed in cases where patients' conditions are convenient to remove it. Acute myeloblastic leukemia cases that are more likely to develop invasive fungal infections should be monitored closely for early diagnosis and timely initiation of antifungal drugs which directly correlates with survival rates.

Leucémie aiguë néonatale révélée par Blueberry Muffin syndrome (à propos d’un cas)

Summary Acute leukemia is uncommon in neonates and has a much poorer prognosis than in older children. We report a case of acute myeloblastic leukemia observed in a neonate who had skin lesions (Blueberry Muffin syndrome), bleeding and hepatosplenomegaly at birth, which justified intensive care since the first postnatal week. The patient died 13 days after. We present here physical and laboratory findings, which indicate a grim prognosis. These criteria should be considered carefully in order to ensure realistic information for the parents and appropriate decision.

P-250 Nucleophosmin cytoplasmic and nucleus immunohistochemical cell positivity of bone marrow biopsy sections in AML and MDS patients

Background Nucleophosmin (NPM) is phosphoprotein in nucleolus and shuttles continuously between nucleus and cytoplasm. Major role of NPM is to mediate nuclear export of ribosome components to the cytoplasm and to control centrosome duplication and it also interacts with oncosupressors p53 and p19Arf thus controlling cell proliferation and apoptosis. NPM mutations are involved in pathogenesis of some AML cases. Introduction The abnormal mutated NPM1 protein shows an aberrant cytoplasmic localization in leukemic cells (NPMc), whereas the wild-type protein is mainly located in the nucleolus and on the nuclear membrane. Approximately one-third of cases of denovo acute myeloblastic leukemia (AML) carry mutations in the c-terminal region of NPM (NPM1) gene. NPM1 mutations are rare in myelodisplasia (MDS) but in some reports NPM mutations and NPMc cell bone marrow cell positivity were also found in MDS. Purpose Aim of the study were to analyze cell NPM immunohistochemical expression in nuclei (NPMn) and cytoplasm (NPMc) in bone marrow (BM) sections of 7 patients with de novo AML and 9 MDS patients. Materials and Methods Immunohistochemical procedures were performed on paraffin sections cut from B5-fixed/EDTA-decalcified BM biopsies. Sections were subjected to micro waving/antigen retrieval, pH9 and immunostained with anti-NPM monoclonal antibody (clone 376) using immuno alkaline phosphatase technique. NPMc and NPMn cell positivity between AML and MDS patients were statistically compared with Mann-Whitney and Chi-square tests. From patients informed consent was obtained. Results NPMn cell positivity was seen in 6/7 AML and in 8/9 MDS patients. NPMc was detected in 5/7 AML and in 8 out of 9 MDS patients. Percentages of NPMn of BM cells were higher in MDS than in AML patients with borderline statistical significance. NPMn immunoexpression above 30% of BM positive cells was more frequently (with statistical significance) observed in MDS than in AML patients (p< 0.05). Conclusions Higher NPMn cell positivity (above 30% of nucleated BM cells) in MDS is probably linked to higher number of normal BM cells in MDS. Lower NPMn cell positivity in AML is maybe associated to higher number of leukemic cells and also to NPM functional loss in progression and transformation of MDS to AML. NPMc was also observed in most of our AML and MDS patients. This finding is in a concordance with some recent reports also implicating that that NPM1 mutations may be also seen in MDS, but further studies are needed to analyze correlation of NPMc cell positivity and NPM1 mutations in MDS patients

Cardiac Tamponade may be the First Symptom of Leukemia

Acute myeloblastic leukemia (AML) is originating from hematopoietic precursor cells. CD7 is expressed in 30% of AML cases and is associated with poor prognosis in myeloid malignancies [1,2]. Perica...