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Sample records for acute myeloid leukaemia

  1. Prolonged remission maintenance in acute myeloid leukaemia.

    Science.gov (United States)

    Spiers, A S; Goldman, J M; Catovsky, D; Costello, C; Galton, D A; Pitcher, C S

    1977-08-27

    Twenty-five patients with acute myeloid leukaemia were treated with three quadruple drug combinations in predetermined rotation: TRAP (thioguanine, daunorubicin, cytarabine, prednisolone); COAP (cyclophosphamide, vincristine, cytarabine, prednisolone); and POMP (prednisolone, vincristine, methotrexate, mercaptopurine). Fifteen patients (60%) achieved complete remission and five (20%) partial remission. For maintenance, five-day courses of drugs were administered every 14 to 21 days and doses were increased to tolerance. The median length of complete remission was 66 weeks. In eight patients remission maintenance treatment was discontinued and some remained in complete remission for over two years. In this series the remission induction rate was comparable with that reported for other regimens and complete remission lasted longer with this intensive maintenance regimen than with others. Nevertheless, the TRAP programme must still be regarded as only palliative treatment for acute myeloid leukaemia.

  2. Aberrant Gene Expression in Acute Myeloid Leukaemia

    DEFF Research Database (Denmark)

    Bagger, Frederik Otzen

    model to investigate the role of telomerase in AML, we were able to translate the observed effect into human AML patients and identify specific genes involved, which also predict survival patterns in AML patients. During these studies we have applied methods for investigating differentially expressed......Summary Acute Myeloid Leukaemia (AML) is an aggressive cancer of the bone marrow, affecting formation of blood cells during haematopoiesis. This thesis presents investigation of AML using mRNA gene expression profiles (GEP) of samples extracted from the bone marrow of healthy and diseased subjects....... Here GEPs from purified healthy haematopoietic populations, with different levels of differentiation, form the basis for comparison with diseased samples. We present a mathematical transformation of mRNA microarray data to make it possible to compare AML samples, carrying expanded aberrant...

  3. Adrenal crisis in a patient with acute myeloid leukaemia

    OpenAIRE

    Li, Wang; Okwuwa, Ikemefuna; Toledo-Frazzini, Karla; Alhomosh, Alaaedin

    2013-01-01

    Adrenal crisis is a group of clinical manifestation predominantly with hypotensive shock, electrolyte imbalance in a patient with adrenal insufficiency or in a patient who was abruptly withdrawn from glucocorticoid treatment acute myeloid leukaemia (AML) is one of the most common acute leukaemia in adults. Though the above diseases are commonly seen in individual patients, the coexistence of both conditions in the same patient is rare. We reported a 64-year-old African-American man with a his...

  4. Acute myeloid leukaemia after treatment for acute lymphoblastic leukaemia in girl with Bloom syndrome.

    Science.gov (United States)

    Adams, Madeleine; Jenney, Meriel; Lazarou, Laz; White, Rhian; Birdsall, Sanda; Staab, Timo; Schindler, Detlev; Meyer, Stefan

    2013-09-18

    Bloom syndrome (BS) is an inherited genomic instability disorder caused by disruption of the BLM helicase and confers an extreme cancer predisposition. Here we report on a girl with BS who developed acute lymphoblastic leukaemia (ALL) at age nine, and treatment-related acute myeloid leukaemia (t-AML) aged 12. She was compound heterozygous for the novel BLM frameshift deletion c.1624delG and the previously described c.3415C>T nonsense mutation. Two haematological malignancies in a child with BS imply a fundamental role for BLM for normal haematopoiesis, in particular in the presence of genotoxic stress.

  5. Acute Myeloid Leukaemia of Donor Cell Origin Developing 17 Years after Allogenic Hematopoietic Cell Transplantation for Acute Promyelocytic Leukaemia

    Science.gov (United States)

    Jiménez, Pilar; Alvarez, J. Carlos; Garrido, Pilar; Lorente, J. Antonio; Palacios, Jorge; Ruiz-Cabello, Francisco

    2012-01-01

    Donor cell leukaemia (DCL) is a rare complication of allogenic hematopoietic cell transplantation (HCT). We report the case of a female patient with acute promyelocytic leukaemia (APL), FAB type M3, who developed acute myeloid leukaemia (AML) type M5 of donor origin 17 years after allogenic bone marrow transplantation (BMT) from her HLA-matched sister. Morphology and immunophenotyping showed differences with the initial leukaemia, and short tandem repeat (STR) analysis confirmed donor-type haematopoiesis. Interphase fluorescence in situ hybridisation (FISH) showed an 11q23 deletion. Given that the latency period between transplant and development of leukaemia was the longest reported to date, we discuss the mechanisms underlying delayed leukaemia onset. PMID:23675279

  6. Acute myeloid dendritic cell leukaemia with specific cutaneous involvement: a diagnostic challenge.

    Science.gov (United States)

    Ferran, M; Gallardo, F; Ferrer, A M; Salar, A; Pérez-Vila, E; Juanpere, N; Salgado, R; Espinet, B; Orfao, A; Florensa, L; Pujol, R M

    2008-05-01

    Myeloid or type 1 dendritic cell leukaemia is an exceedingly rare haematopoietic neoplasm characterized by a specific immunophenotypic profile close to plasmacytoid dendritic cell and acute myelogenous leukaemia. A 77-year-old man presenting specific cutaneous infiltration by myeloid dendritic cell leukaemia is reported. The clinical features as well as the cutaneous histopathological and immunohistochemical features led to the initial diagnosis of CD4+/CD56+ haematodermic neoplasm. However, extensive immunophenotypic studies performed from peripheral blood blasts disclosed that leukaemic cells expressed myeloid dendritic cell markers, confirming the diagnosis. The diagnostic difficulties of specific cutaneous involvement by myeloid dendritic cell leukaemia on the basis of routine histopathological and immunohistochemical features are highlighted.

  7. CBL mutations do not frequently occur in paediatric acute myeloid leukaemia

    NARCIS (Netherlands)

    Coenen, Eva A.; Driessen, Emma M. C.; Zwaan, C. Michel; Stary, Jan; Baruchel, Andre; de Haas, Valerie; de Bont, Eveline S. J. M.; Reinhardt, Dirk; Kaspers, Gertjan J. L.; Arentsen-Peters, Susan T. C. J. M.; Meyer, Claus; Marschalek, Rolf; Pieters, Rob; Stam, Ronald W.; van den Heuvel-Eibrink, Marry M.

    2012-01-01

    RAS-pathway mutations, causing a proliferative advantage, occur in acute myeloid leukaemia (AML) and MLL-rearranged leukaemia. Recently, mutations in the Casitas B lineage lymphoma (CBL) gene were reported to be involved in RAS-pathway activation in various myeloid malignancies, but their role in pa

  8. DNA sequencing of a cytogenetically normal acute myeloid leukaemia genome.

    Science.gov (United States)

    Ley, Timothy J; Mardis, Elaine R; Ding, Li; Fulton, Bob; McLellan, Michael D; Chen, Ken; Dooling, David; Dunford-Shore, Brian H; McGrath, Sean; Hickenbotham, Matthew; Cook, Lisa; Abbott, Rachel; Larson, David E; Koboldt, Dan C; Pohl, Craig; Smith, Scott; Hawkins, Amy; Abbott, Scott; Locke, Devin; Hillier, Ladeana W; Miner, Tracie; Fulton, Lucinda; Magrini, Vincent; Wylie, Todd; Glasscock, Jarret; Conyers, Joshua; Sander, Nathan; Shi, Xiaoqi; Osborne, John R; Minx, Patrick; Gordon, David; Chinwalla, Asif; Zhao, Yu; Ries, Rhonda E; Payton, Jacqueline E; Westervelt, Peter; Tomasson, Michael H; Watson, Mark; Baty, Jack; Ivanovich, Jennifer; Heath, Sharon; Shannon, William D; Nagarajan, Rakesh; Walter, Matthew J; Link, Daniel C; Graubert, Timothy A; DiPersio, John F; Wilson, Richard K

    2008-11-06

    Acute myeloid leukaemia is a highly malignant haematopoietic tumour that affects about 13,000 adults in the United States each year. The treatment of this disease has changed little in the past two decades, because most of the genetic events that initiate the disease remain undiscovered. Whole-genome sequencing is now possible at a reasonable cost and timeframe to use this approach for the unbiased discovery of tumour-specific somatic mutations that alter the protein-coding genes. Here we present the results obtained from sequencing a typical acute myeloid leukaemia genome, and its matched normal counterpart obtained from the same patient's skin. We discovered ten genes with acquired mutations; two were previously described mutations that are thought to contribute to tumour progression, and eight were new mutations present in virtually all tumour cells at presentation and relapse, the function of which is not yet known. Our study establishes whole-genome sequencing as an unbiased method for discovering cancer-initiating mutations in previously unidentified genes that may respond to targeted therapies.

  9. Clofarabine in the treatment of poor risk acute myeloid leukaemia.

    LENUS (Irish Health Repository)

    Krawczyk, Janusz

    2010-09-01

    Clofarabine is a second generation nucleoside analogue. It inhibits DNA repair and activates the mitochondrial apoptotic pathway leading to cell death. In vitro clofarabine has demonstrated synergy with daunorubicin and Ara-C and in phase II clinical trials has shown promising activity in poor risk Acute myeloid leukaemia (AML) patients. In our institution over a 24 month period 22 AML patients (11 M, 11 F) with poor risk features, deemed unsuitable for standard therapy, were treated with clofarabine, alone (eight patients) or in combination (14 patients) for up to three cycles of treatment. The median age was 67.5 years (24-76) with 16 patients > 60 years. At the time of treatment 18 patients had active AML. Four patients intolerant of standard induction received clofarabine as consolidation. The overall response rate (ORR) for the 18 patients with active AML was 61%, nine patients (50%) achieving a complete response (CR). Induction and consolidation were well tolerated with no unexpected toxicities. Predictably, all patients developed grade 4 neutropenia but the median duration was only 20 days (17-120). Induction mortality was acceptable at 17%. In conclusion, clofarabine (alone or in combination) is active in poor risk AML with an acceptable safety profile and should be considered a potential option in poor risk AML patients.

  10. Somatic PTPN11 mutations in childhood acute myeloid leukaemia.

    Science.gov (United States)

    Tartaglia, Marco; Martinelli, Simone; Iavarone, Ivano; Cazzaniga, Giovanni; Spinelli, Monica; Giarin, Emanuela; Petrangeli, Valentina; Carta, Claudio; Masetti, Riccardo; Aricò, Maurizio; Locatelli, Franco; Basso, Giuseppe; Sorcini, Mariella; Pession, Andrea; Biondi, Andrea

    2005-05-01

    Somatic mutations in PTPN11, the gene encoding the transducer SHP-2, have emerged as a novel class of lesions that upregulate RAS signalling and contribute to leukaemogenesis. In a recent study of 69 children and adolescents with de novo acute myeloid leukaemia (AML), we documented a non-random distribution of PTPN11 mutations among French-American-British (FAB) subtypes. Lesions were restricted to FAB-M5 cases, where they were relatively common (four of 12 cases). Here, we report on the results of a molecular screening performed on 181 additional unselected patients, enrolled in participating institutions of the Associazione Italiana Ematologia Oncologia Pediatrica-AML Study Group, to provide a more accurate picture of the prevalence, spectrum and distribution of PTPN11 mutations in childhood AML and to investigate their clinical relevance. We concluded that PTPN11 defects do not represent a frequent event in this heterogeneous group of malignancies (4.4%), although they recur in a considerable percentage of patients with FAB-M5 (18%). PTPN11 lesions rarely occur in other subtypes. Within the FAB-M5 group no clear association of PTPN11 mutations with any clinical variable was evident. Nearly two third of the patients with this subtype were found to harbour an activating mutation in PTPN11, NRAS, KRAS2 or FLT3.

  11. Leukaemia relapse after allogeneic transplants for acute myeloid leukaemia: predictive role of WT1 expression.

    Science.gov (United States)

    Pozzi, Sarah; Geroldi, Simona; Tedone, Elisabetta; Luchetti, Silvia; Grasso, Raffaella; Colombo, Nicoletta; Di Grazia, Carmen; Lamparelli, Teresa; Gualandi, Francesca; Ibatici, Adalberto; Bregante, Stefania; Van Lint, Maria Teresa; Raiola, Anna Maria; Dominietto, Alida; Varaldo, Riccardo; Signori, Alessio; Bacigalupo, Andrea

    2013-02-01

    We assessed WT1 expression (expressed as messenger copies/10(4) ABL1) from marrow cells of 122 patients with acute myeloid leukaemia (AML), before and after an unmanipulated allogeneic haemopoietic stem cell transplant (HSCT). The median age was 44 years (15-69), 59% were in first remission, 74% received a myeloablative conditioning regimen and the median follow up was 865 d (34-2833). Relapse was higher in 67 patients with WT1 expression, at any time post-HSCT, exceeding 100 copies (54%), as compared to 16%, for 55 patients with post-HSCT WT1 expression <100 copies (P < 0·0001). Similarly, actuarial 5-year survival (OS) was 40% vs. 63%, respectively (P = 0·03). In multivariate Cox analysis, WT1 expression post-HSCT was the strongest predictor of relapse (Hazard Ratio [HR] 4·5, P = 0·0001), independent of disease phase (HR 2·3, P = 0·002). Donor lymphocyte infusions (DLI) were given to 17 patients because of increasing WT1 levels: their OS was 44%, vs. 14% for 21 patients with increasing WT1 expression who did not receive DLI (P = 0·004). In conclusion, WT1 expression post-HSCT is a strong predictor of leukaemia relapse and survival in AML; WT1 may be used as a marker for early interventional therapy.

  12. [Necrotizing tonsillitis and renal vein thrombosis due to acute myeloid leukaemia].

    Science.gov (United States)

    Akram, Javed; Josefsson, Pernilla; Rømeling, Frans

    2012-09-01

    A 37-year-old woman was admitted to hospital with severe tonsillitis with unilateral necrotizing tonsillitis. She suddenly got fever, malaise, difficulties swallowing, pain in the throat and deterioration despite four days of penicillin treatment. During hospitalisation, she experienced abdominal pain, and blood tests showed pancytopenia. She was transferred to a haematological department, where a bone marrow biopsy showed acute myeloid leukaemia. Subsequently, an abdominal computed tomography with intravenous contrast revealed bilateral renal vein thrombosis, probably because of coagulopathy due to leukaemia.

  13. Epidural spinal cord compression as initial clinical presentation of an acute myeloid leukaemia: case report and literature review

    Institute of Scientific and Technical Information of China (English)

    Dominique N'Dri Oka; Alpha Boubacar Bah; André Valentin Tokpa; Louis Derou

    2016-01-01

    Epidural localization of myeloid leukaemia is rarely reported.Spinal cord compression as an initial presentation of acute myeloid leukaemia is extremely rare.This is a report of a 17-year-old black boy who presented to emergency department with neurological symptoms of spinal cord compression.Imaging modalities showed multiple soft tissue masses in the epidural space.After surgical treatment,histopathological examination of the epidural mass showed myeloid leukaemia cells infiltration.Literature review on Medline and "scholar Google" database was done.The characteristics and management of extra-medullary leukaemia are discussed.Granulocytic sarcoma,myeloid sarcoma or chloroma with acute myeloid leukaemia should be considered as part of epidural spinal cord compression.Therefore surgery is indicated on an emergent basis.

  14. Pharm GKB: Leukemia, Myeloid, Acute [PharmGKB

    Lifescience Database Archive (English)

    Full Text Available Amino Acid Translations are all sourced from dbSNP 144 Overview Alternate Names: Synonym AML - Acute... myeloblastic leukaemia; Acute Myeloblastic Leukemia; Acute Myeloblastic Leukemias; Acute... Myelocytic Leukemia; Acute Myelocytic Leukemias; Acute Myelogenous Leukemia; Acute Myelogenous Leukemias; Acute... granulocytic leukaemia; Acute myeloblastic leukemia; Acute myeloid leukaemia; Acute myeloid leukaemia - category; Acute... myeloid leukaemia, disease; Acute myeloid leukemia; Acute myelo

  15. Effect of glutathione S-transferases on the survival of patients with acute myeloid leukaemia

    DEFF Research Database (Denmark)

    Autrup, Judith; Hokland, Peter; Pedersen, Lars;

    2002-01-01

    The objective of the study was to investigate the effect of genetic polymorphisms in glutathione S-transferases (GST) on the survival of acute myeloid leukaemia patients receiving adriamycin induction therapy. A total of 89 patients were included in the study. Patients who carried at least one GSTM...

  16. Clinical relevance of molecular aberrations in paediatric acute myeloid leukaemia at first relapse

    NARCIS (Netherlands)

    Bachas, Costa; Schuurhuis, Gerrit Jan; Reinhardt, Dirk; Creutzig, Ursula; Kwidama, Zinia J.; Zwaan, C. Michel; van den Heuvel-Eibrink, Marry M.; De Bont, Evelina S. J. M.; Elitzur, Sarah; Rizzari, Carmelo; de Haas, Valerie; Zimmermann, Martin; Cloos, Jacqueline; Kaspers, Gertjan J. L.

    2014-01-01

    Outcome for relapsed paediatric acute myeloid leukaemia (AML) remains poor. Strong prognostic factors at first relapse are lacking, which hampers optimization of therapy. We assessed the frequency of molecular aberrations (FLT3, NRAS, KRAS, KIT, WT1 and NPM1 genes) at first relapse in a large set (n

  17. Acute myeloid leukaemia presenting as bilateral proptosis in a young child

    Directory of Open Access Journals (Sweden)

    Charudutt Kalamkar

    2016-06-01

    Full Text Available Myeloid sarcoma is an extramedullary manifestation of acute myeloid leukaemia (AML. Aims We are reporting a paediatric case presenting with bilateral proptosis, which we were able to diagnose with peripheral blood smear (PBS examination. Methods Case Report Results This case highlights the utility of simple routinely available PBS test in diagnosing this rare disease. Conclusion Our case highlights the importance of haemogram and peripheral blood smear in the initial evaluation of proptosis. Correct diagnosis of this rare entity is vital especially in cases where (myeloid sarcoma MS is the presenting feature of AML.

  18. Results of a randomized trial in children with Acute Myeloid Leukaemia : Medical Research Council AML12 trial

    NARCIS (Netherlands)

    Gibson, Brenda E. S.; Webb, David K. H.; Howman, Andrew J.; De Graaf, Siebold S. N.; Harrison, Christine J.; Wheatley, Keith

    2011-01-01

    The Medical Research Council Acute Myeloid Leukaemia 12 (MRC AML12) trial (children) addressed the optimal anthracenedione/anthracycline in induction and the optimal number of courses of consolidation chemotherapy. 504 children (

  19. Nucleophosmin mutation analysis in acute myeloid leukaemia: Immunohistochemistry as a surrogate for molecular techniques

    OpenAIRE

    Anita Chopra; Sushant Soni; Haraprasad Pati; Dev Kumar; Rahul Diwedi; Deepak Verma; Garima Vishwakama; Sameer Bakhshi; Suman Kumar; Ajay Gogia; Rajive Kumar

    2016-01-01

    Background & objectives: Mutation of nucleophosmin (NPM1) gene in the absence of FLT3-ITD (FMS related tyrosine kinase 3 - internal tandem duplications) mutation carries a good prognosis in cytogenetically normal acute myeloid leukaemia (AML). NPM1, a multifunctional nucleolar phosphoprotein that shuttles between nucleus and cytoplasm, gets trapped in the cytoplasm when mutated. Immunohistochemical (IHC) demonstration of its aberrant cytoplasmic location (NPMc+) has been suggested as a simple...

  20. Changing bone marrow micro-environment during development of acute myeloid leukaemia in rats

    DEFF Research Database (Denmark)

    Mortensen, B T; Jensen, P O; Helledie, N;

    1998-01-01

    The Brown Norwegian rat transplanted with promyelocytic leukaemic cells (BNML) has been used as a model for human acute myeloid leukaemia. We have previously shown that both the blood supply to the bone marrow and the metabolic rate decrease in relation to the leukaemic development in these rats....... Here we have investigated how the development and progression of this leukaemia affect oxygenation, pH and proliferation of normal and leukaemic cells in vivo. Bone marrow pH was measured by a needle electrode. Nitroimidazol-theophylline (NITP) was used to identify hypoxic cells, and we applied...... bromodeoxyuridine (BrdUrd) to identify DNA replicating cells. The leukaemia progressed slowly until day 27 after which a rapid deterioration could be observed leading to severe changes over the following 5 d. In whole blood there was evidence of progressing metabolic acidosis. In bone marrow the fraction...

  1. Changing bone marrow micro-environment during development of acute myeloid leukaemia in rats

    DEFF Research Database (Denmark)

    Mortensen, B T; Jensen, P O; Helledie, N;

    1998-01-01

    cells (from about 45% to 25%), evidently as a result of the severely changed microenvironment. In this study we have demonstrated in vivo the development of an acidic and hypoxic bone marrow hampering normal haemopoiesis during leukaemic growth. Our data support the notion of BNML as a valuable tool......The Brown Norwegian rat transplanted with promyelocytic leukaemic cells (BNML) has been used as a model for human acute myeloid leukaemia. We have previously shown that both the blood supply to the bone marrow and the metabolic rate decrease in relation to the leukaemic development in these rats....... Here we have investigated how the development and progression of this leukaemia affect oxygenation, pH and proliferation of normal and leukaemic cells in vivo. Bone marrow pH was measured by a needle electrode. Nitroimidazol-theophylline (NITP) was used to identify hypoxic cells, and we applied...

  2. Detailed molecular characterisation of acute myeloid leukaemia with a normal karyotype using targeted DNA capture.

    Science.gov (United States)

    Conte, N; Varela, I; Grove, C; Manes, N; Yusa, K; Moreno, T; Segonds-Pichon, A; Bench, A; Gudgin, E; Herman, B; Bolli, N; Ellis, P; Haddad, D; Costeas, P; Rad, R; Scott, M; Huntly, B; Bradley, A; Vassiliou, G S

    2013-09-01

    Advances in sequencing technologies are giving unprecedented insights into the spectrum of somatic mutations underlying acute myeloid leukaemia with a normal karyotype (AML-NK). It is clear that the prognosis of individual patients is strongly influenced by the combination of mutations in their leukaemia and that many leukaemias are composed of multiple subclones, with differential susceptibilities to treatment. Here, we describe a method, employing targeted capture coupled with next-generation sequencing and tailored bioinformatic analysis, for the simultaneous study of 24 genes recurrently mutated in AML-NK. Mutational analysis was performed using open source software and an in-house script (Mutation Identification and Analysis Software), which identified dominant clone mutations with 100% specificity. In each of seven cases of AML-NK studied, we identified and verified mutations in 2-4 genes in the main leukaemic clone. Additionally, high sequencing depth enabled us to identify putative subclonal mutations and detect leukaemia-specific mutations in DNA from remission marrow. Finally, we used normalised read depths to detect copy number changes and identified and subsequently verified a tandem duplication of exons 2-9 of MLL and at least one deletion involving PTEN. This methodology reliably detects sequence and copy number mutations, and can thus greatly facilitate the classification, clinical research, diagnosis and management of AML-NK.

  3. Label-free imaging and identification of typical cells of acute myeloid leukaemia and myelodysplastic syndrome by Raman microspectroscopy

    NARCIS (Netherlands)

    Vanna, R.; Ronchi, P.; Lenferink, A.T.M.; Terstappen, L.W.M.M.; Tresoldi, C.; Morasso, C.; Mehn, D.; Bedoni, M.; Ciceri, F.; Otto, C.; Gramatica, F.

    2015-01-01

    In clinical practice, the diagnosis and classification of acute myeloid leukaemia (AML) and myelodysplastic syndrome (MDS) start from the manual examination of stained smears of bone marrow (BM) and peripheral blood (PB) by using an optical microscope. This step is subjective and scarcely reproducib

  4. Oncogenic roles of PRL-3 in FLT3-ITD induced acute myeloid leukaemia.

    Science.gov (United States)

    Park, Jung Eun; Yuen, Hiu Fung; Zhou, Jian Biao; Al-Aidaroos, Abdul Qader O; Guo, Ke; Valk, Peter J; Zhang, Shu Dong; Chng, Wee Joo; Hong, Cheng William; Mills, Ken; Zeng, Qi

    2013-09-01

    FLT3-ITD mutations are prevalent mutations in acute myeloid leukaemia (AML). PRL-3, a metastasis-associated phosphatase, is a downstream target of FLT3-ITD. This study investigates the regulation and function of PRL-3 in leukaemia cell lines and AML patients associated with FLT3-ITD mutations. PRL-3 expression is upregulated by the FLT3-STAT5 signalling pathway in leukaemia cells, leading an activation of AP-1 transcription factors via ERK and JNK pathways. PRL-3-depleted AML cells showed a significant decrease in cell growth. Clinically, high PRL-3 mRNA expression was associated with FLT3-ITD mutations in four independent AML datasets with 1158 patients. Multivariable Cox-regression analysis on our Cohort 1 with 221 patients identified PRL-3 as a novel prognostic marker independent of other clinical parameters. Kaplan-Meier analysis showed high PRL-3 mRNA expression was significantly associated with poorer survival among 491 patients with normal karyotype. Targeting PRL-3 reversed the oncogenic effects in FLT3-ITD AML models in vitro and in vivo. Herein, we suggest that PRL-3 could serve as a prognostic marker to predict poorer survival and as a promising novel therapeutic target for AML patients.

  5. Auricular Oedema and Dyshidrotic Eczema in a Patient with Acute Myeloid Leukaemia Treated with Cytarabine

    Directory of Open Access Journals (Sweden)

    K. Brandt

    2010-10-01

    Full Text Available Cytarabine is an effective drug in the treatment of haematological malignancies. The therapy is associated with various complications. Frequencies of dermatological side-effects range from 2–72% and occur most commonly after high-dose regimens. Although most cutaneous reactions are mild and resolve spontaneously within several days, they may result in an increased risk of infection and alterations in comfort. In some cases, severe life-threatening reactions have been reported. Here we describe the case of a patient with acute myeloid leukaemia, who developed severe exceptional skin toxicity in terms of auricular oedema and palmar dyshidrotic eczema after the application of low-dose cytarabine. Re-administration of the drug resulted in reduced skin toxicity during further cycles of chemotherapy. Negative epicutaneous patch-testing supported the existence of cytarabine-provoked toxicity.

  6. Maintenance treatment with azacytidine for patients with high-risk myelodysplastic syndromes (MDS) or acute myeloid leukaemia following MDS in complete remission after induction chemotherapy

    DEFF Research Database (Denmark)

    Grövdal, Michael; Karimi, Mohsen; Khan, Rasheed

    2010-01-01

    This prospective Phase II study is the first to assess the feasibility and efficacy of maintenance 5-azacytidine for older patients with high-risk myelodysplastic syndrome (MDS), chronic myelomonocytic leukaemia and MDS-acute myeloid leukaemia syndromes in complete remission (CR) after induction...

  7. Low frequency of MLL-partial tandem duplications in paediatric acute myeloid leukaemia using MLPA as a novel DNA screenings technique.

    NARCIS (Netherlands)

    Balgobind, B.V.; Hollink, I.H.; Reinhardt, D.; Wering, E.R. van; Graaf, S.S.N. de; Baruchel, A.; Stary, J.; Beverloo, H.B.; Greef, G.E. de; Pieters, R.; Zwaan, C.M.; Heuvel-Eibrink, M.M. van den

    2010-01-01

    Mixed-lineage leukaemia (MLL)-partial tandem duplications (PTDs) are found in 3-5% of adult acute myeloid leukaemia (AML), and are associated with poor prognosis. In adult AML, MLL-PTD is only detected in patients with trisomy 11 or internal tandem duplications of FLT3 (FLT3-ITD). To date, studies i

  8. Platelet doubling after the first azacitidine cycle is a promising predictor for response in myelodysplastic syndromes (MDS), chronic myelomonocytic leukaemia (CMML) and acute myeloid leukaemia (AML) patients in the Dutch azacitidine compassionate named patient programme

    NARCIS (Netherlands)

    van der Helm, Lieke H.; Alhan, Canan; Wijermans, Pierre W.; Kooy, Marinus van Marwijk; Schaafsma, Ron; Biemond, Bart J.; Beeker, Aart; Hoogendoorn, Mels; van Rees, Bastiaan P.; de Weerdt, Okke; Wegman, Jurgen; Libourel, Ward J.; Luykx-de Bakker, Sylvia A.; Minnema, Monique C.; Brouwer, Rolf E.; Boer, Fransien Croon-de; Eefting, Matthijs; Jie, Kon-Siong G.; de Loosdrecht, Arjan A. van; Koedam, Jan; Veeger, Nic J. G. M.; Vellenga, Edo; Huls, Gerwin

    2011-01-01

    The efficacy of azacitidine in the treatment of high-risk myelodysplastic syndromes (MDS), chronic myelomonocytic leukaemia (CMML) and acute myeloid leukaemia (AML) (20-30% blasts) has been demonstrated. To investigate the efficacy of azacitidine in daily clinical practice and to identify predictors

  9. Radioimmunotherapy for treatment of acute myeloid leukaemia and myelodysplastic syndrome. Conceptual chances

    Energy Technology Data Exchange (ETDEWEB)

    Buchmann, I.; Helisch, A.; Bartenstein, P. [Klinik und Poliklinik fuer Nuklearmedizin, Universitaetsklinikum Mainz (Germany); Meyer, R.G.; Herr, W. [III. Medizinische Klinik und Poliklinik (Haematologie), Universitaetsklinikum Mainz (Germany)

    2005-07-01

    The prognosis of patients with acute myeloid leukaemia (AML) has improved considerably by introduction of aggressive consolidation chemotherapy and haematopoietic stem cell transplantation (SCT). Nevertheless, only 20-30% of patients with AML achieve long-term disease-free survival after SCT. The most common cause of treatment failure is relapse. Additionally, mortality rates are significantly increased by therapy-related causes such as toxicity of chemotherapy and complications of SCT. Including radioimmunotherapies in the treatment of AML and myelodyplastic syndrome (MDS) allows for the achievement of a pronounced antileukaemic effect for the reduction of relapse rates on the one hand. On the other hand, no increase of acute toxicity and later complications should be induced. These effects are important for the primary reduction of tumour cells as well as for the myelblative conditioning before SCT. This paper provides a systematic and critical review of the currently used radionuclides and immunoconjugates for the treatment of AML and MDS and summarizes the literature on primary tumour cell reductive radioimmunotherapies on the one hand and conditioning radioimmunotherapies before SCT on the other hand. (orig.)

  10. Symptom experience and management among people with acute myeloid leukaemia in Thailand.

    Science.gov (United States)

    Temtap, Suthisa; Nilmanat, Kittikorn

    2011-08-01

    In Thailand, haematological malignancy is one of the most common types of cancer. This cross-sectional study, conducted in Southern Thailand, aimed to describe the symptom experiences of and symptom management strategies among patients with acute myeloid leukaemia (AML). Sixty hospitalized patients with AML were recruited. The Symptom Experience Scale and two open-ended questions regarding symptom-management strategies were used to collect data via face-to-face interviews 2 weeks after the induction phase of the AML protocol. The data was analysed using descriptive statistics and content analysis. High fever, weakness, nausea, and anorexia were the four most prevalent symptoms reported. Other prevalent symptoms included weight loss, bleeding, nausea and vomiting, dysphagia, and a cluster of psycho-emotional symptoms: worrying, fear, feeling discouraged, and feeling bored. Patients used various approaches and strategies to alleviate their symptoms, which could be categorized into five groups: preventive, direct, distraction, complementary, and restorative approaches. This study has provided important information for the development of symptom-management nursing programmes for patients with AML, particularly in Thailand.

  11. Impact of NOD2 polymorphisms on infectious complications following chemotherapy in patients with acute myeloid leukaemia.

    Science.gov (United States)

    Yomade, Olaposi; Spies-Weisshart, Bärbel; Glaser, Anita; Schnetzke, Ulf; Hochhaus, Andreas; Scholl, Sebastian

    2013-08-01

    We sought to investigate the relationship between polymorphisms of the NOD2 gene and infectious complications following intensive induction chemotherapy in patients with acute myeloid leukaemia (AML). We hypothesised that single nucleotide polymorphisms (SNPs) of the NOD2 gene are associated with a higher rate of infections during the phase of severe neutropenia. In 131 AML patients receiving induction therapy, the presence of the three most frequent polymorphisms of NOD2 (Arg702Trp, Gly908Arg, Leu1007fsinsC) was analysed. SNP analyses by means of genomic PCR incorporating fluorescence-labelled probes with characteristic melting curves were performed using the LightCycler platform. Our data suggest a significantly lower probability of mucositis or enteritis in AML patients lacking any of the three evaluated NOD2 polymorphisms. Furthermore, bloodstream cultures of AML patients carrying either a missense or a frameshift mutation of NOD2 were significantly more frequently tested positive concerning Streptococcus spp. In contrast, the presence of NOD2 polymorphisms had no impact on such important infectious complications as systemic inflammatory response syndrome or sepsis, the rate of central venous catheter infections or the incidence of pneumonia including fungal infections. Our data represent one of the first reports investigating the impact of polymorphisms of the innate immune system on infectious complications in patients with neutropenia following chemotherapy. A correlation between NOD2 polymorphisms and infectious events in AML patients is demonstrated.

  12. Mitochondrial cytochrome c oxidase subunit II variations predict adverse prognosis in cytogenetically normal acute myeloid leukaemia.

    Science.gov (United States)

    Silkjaer, Trine; Nyvold, Charlotte Guldborg; Juhl-Christensen, Caroline; Hokland, Peter; Nørgaard, Jan Maxwell

    2013-10-01

    Alterations in the two catalytic genes cytochrome c oxidase subunits I and II (COI and COII) have recently been suggested to have an adverse impact on prognosis in patients with acute myeloid leukaemia (AML). In order to explore this in further detail, we sequenced these two mitochondrial genes in diagnostic bone marrow or blood samples in 235 patients with AML. In 37 (16%) patients, a non-synonymous variation in either COI or COII could be demonstrated. No patients harboured both COI and COII non-synonymous variations. Twenty-four (10%) patients had non-synonymous variations in COI, whereas 13 (6%) patients had non-synonymous variations in COII. The COI and COII are essential subunits of cytochrome c oxidase that is the terminal enzyme in the oxidative phosphorylation complexes. In terms of disease course, we observed that in patients with a normal cytogenetic analysis at disease presentation (CN-AML) treated with curative intent, the presence of a non-synonymous variation in the COII was an adverse prognostic marker for both overall survival and disease-free survival (DFS) in both univariate (DFS; hazard ratio (HR) 4.4, P = 0.006) and multivariate analyses (DFS; HR 7.2, P = 0.001). This is the first demonstration of a mitochondrial aberration playing an adverse prognostic role in adult AML, and we argue that its role as a potentially novel adverse prognostic marker in the subset of CN-AML should be explored further.

  13. New Quantitative Method to Identify NPM1 Mutations in Acute Myeloid Leukaemia

    Directory of Open Access Journals (Sweden)

    Sarah Huet

    2013-01-01

    Full Text Available Somatic mutations in the NPM1 gene, which encodes for nucleophosmin, have been reported to be the most frequent genetic abnormalities found in acute myeloid leukaemia (AML. Their identification and quantification remain crucial for the patients’ residual disease monitoring. We investigated a new method that could represent a novel reliable alternative to sequencing for its identification. This method was based on high-resolution melting analysis in order to detect mutated patients and on an allele-specific oligonucleotide real-time quantitative polymerase chain reaction (ASO-RQ-PCR for the identification and quantification of the transcripts carrying NPM1 mutations (NPM1m. Few patients carrying known NPM1m enabled us to set up a table with the different primers’ ΔCT values, identifying a profile for each mutation type. We then analysed a series of 337 AML patients' samples for NPM1 mutational status characterization and confirmed the ASO-RQ-PCR results by direct sequencing. We identified some mutations in 86 samples, and the results were fully correlated in 100% of the 36 sequenced samples. We also detected other rare NPM1m in two samples, that we confirmed by direct sequencing. This highly specific method provides a novel quick, useful, and costless tool, easy to use in routine practice.

  14. Serum posaconazole levels during acute myeloid leukaemia induction therapy: correlations with breakthrough invasive fungal infections.

    Science.gov (United States)

    Cattaneo, Chiara; Panzali, Annafranca; Passi, Angela; Borlenghi, Erika; Lamorgese, Cinzia; Petullà, Marta; Re, Alessandro; Caimi, Luigi; Rossi, Giuseppe

    2015-06-01

    The usefulness of posaconazole therapeutic drug monitoring (TDM) is still a matter of debate. A correlation between posaconazole serum levels and breakthrough invasive fungal infections (IFI) has not been clearly demonstrated so far. We analysed posaconazole serum levels in patients with acute myeloid leukaemia (AML) during induction therapy and correlated them with the incidence of breakthrough IFI and the need of systemic antifungal therapy. Overall, 77 AML patients receiving posaconazole were evaluated for serum levels; breakthrough IFI were observed in five with at least one posaconazole TDM (6.5%). Median serum level was 534 ng ml(-1) (IQ range: 298.5-750.5 ng ml(-1) ) and did not change significantly over time. Four of the 40 patients with median posaconazole levels posaconazole levels on day 7 were 384.5 ng ml(-1) (IQ range: 207-659 ng ml(-1) ) and 560.5 ng ml(-1) (IQ range: 395-756 ng ml(-1) ) in patients requiring or not systemic antifungal treatment respectively (P = 0.067). These results seem to confirm that higher median serum levels of posaconazole correlate with higher prophylactic efficacy against proven/probable IFI and with lesser need of systemic antifungal therapy.

  15. A Fatal Case of Acute Myeloid Leukaemia-Methotrexate Related or Primary Autoimmune Disease Related: A Rare Case Report.

    Science.gov (United States)

    Agarwal, Saurabh; Kaeley, Nidhi; Gupta, Priyanka; Gupta, Vibha; Bhatia, Rohan

    2016-03-01

    Methotrexate is being used for many years in the treatment of chronic medical disorders e.g. rheumatoid arthritis since 1951. It has been associated with various systemic toxicities and complications including bone marrow suppression and lymphomas. The development of leukaemia in a patient of chronic rheumatoid arthritis is either related with the primary disease or due to the drugs which are used in the treatment like cyclophosphamide. In our present case, a 70-year-old female who was a known case of Rheumatoid Arthritis (RA) and was on methotrexate once a week orally for the past 20 years presented with complaints of loss of appetite, loss of weight and anaemia since 2 months. After thorough examination and investigation, she was diagnosed with acute myeloid leukaemia (AML-M4) with bilateral chest consolidation.

  16. Principal results of the Medical Research Council's 8th acute myeloid leukaemia trial.

    Science.gov (United States)

    Rees, J K; Gray, R G; Swirsky, D; Hayhoe, F G

    1986-11-29

    Between 1978 and 1983, 1127 patients with de-novo acute myeloid leukaemia (AML) were entered into the Medical Research Council (MRC)'s 8th AML trial. All received the same induction therapy consisting of daunorubicin, cytarabine, and 6-thioguanine--DAT (1 + 5). The 67% who entered complete remission were randomised to consolidation with two or six further courses of DAT. Adults under the age of 55 were randomised for central nervous system (CNS) prophylaxis with intrathecal cytarabine and methotrexate. Finally, those still in remission after 1 year of cytarabine and 6-thioguanine (AT) maintenance were randomised to receive either late intensification with cyclophosphamide, vincristine, cytarabine, and prednisolone (COAP) or continued AT. The median survival for the whole group was 12 months; the median duration of first remission was 15 months, with relapse-free survival at 5 years estimated at 18%. The factors most strongly associated with poor survival were performance status and age at presentation, but even among those over 60 years of age, half went into remission. Six courses of DAT consolidation gave a small advantage over two courses in reducing the number of late relapses but no significant survival advantage. Late intensification showed a marginally significant advantage over continued AT maintenance. The incidence of CNS relapse was low and unaffected by prophylaxis. The second remission rate varied from 10% when the first remission was shorter than 6 months to 61% when it had continued for more than 2 years. 40 patients received histocompatible allogeneic bone-marrow transplants in first remission. There was a high procedure-related death rate, particularly among patients over 30 years of age. Thus, initially at least, the transplanted group had shorter survival than a comparable group of chemotherapy-treated patients. Treatment specifications remained unchanged throughout the trial but those enrolled in the later half of the trial had a better (p = 0

  17. Residual disease detected by flow cytometry is an independent predictor of survival in childhood acute myeloid leukaemia; results of the NOPHO-AML 2004 study

    DEFF Research Database (Denmark)

    Tierens, Anne; Bjørklund, Elizabeth; Siitonen, Sanna;

    2016-01-01

    Early response after induction is a prognostic factor for disease outcome in childhood acute myeloid leukaemia (AML). Residual disease (RD) detection by multiparameter flow cytometry (MFC) was performed at day 15 and before consolidation therapy in 101 patients enrolled in the Nordic Society...

  18. Somatic mutations of isocitrate dehydrogenases 1 and 2 are prognostic and follow-up markers in patients with acute myeloid leukaemia with normal karyotype

    Directory of Open Access Journals (Sweden)

    Virijevic Marijana

    2016-12-01

    Full Text Available Mutations in the isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2 genes are frequent molecular lesions in acute myeloid leukaemia with normal karyotype (AML-NK. The effects of IDH mutations on clinical features and treatment outcome in AML-NK have been widely investigated, but only a few studies monitored these mutations during follow-up.

  19. Post-remission treatment with allogeneic stem cell transplantation in patients aged 60 years and older with acute myeloid leukaemia : a time-dependent analysis

    NARCIS (Netherlands)

    Versluis, Jurjen; Hazenberg, Carin L. E.; Passweg, Jakob R.; van Putten, Wim L. J.; Maertens, Johan; Biemond, Bart J.; Theobald, Matthias; Graux, Carlos; Kuball, Jurgen; Schouten, Harry C.; Pabst, Thomas; Lowenberg, Bob; Ossenkoppele, Gert; Vellenga, Edo; Cornelissen, Jan J.

    2015-01-01

    Background Acute myeloid leukaemia mainly affects elderly people, with a median age at diagnosis of around 70 years. Although about 50-60% of patients enter first complete remission upon intensive induction chemotherapy, relapse remains high and overall outcomes are disappointing. Therefore, effecti

  20. Myeloid Sarcoma of the Uterine Cervix as Presentation of Acute Myeloid Leukaemia after Treatment with Low-Dose Radioiodine for Thyroid Cancer: A Case Report and Review of the Literature

    Directory of Open Access Journals (Sweden)

    Anne Sophie Weingertner

    2009-01-01

    Full Text Available The development of acute myeloid leukaemia after low-dose radioiodine therapy and its presentation as a myeloid sarcoma of the uterine cervix are both rare events. We report a case of acute myeloid leukaemia revealed by a myeloid sarcoma of the uterine cervix in a 48-year-old woman, 17 months after receiving a total dose of 100 mCi 131I for papillary thyroid cancer. A strict hematological follow-up of patients treated with any dose of 131I is recommended to accurately detect any hematological complications which might have been underestimated. Unusual presentations, such as chloroma of the uterine cervix, may reveal myeloid malignancy and should be kept in mind.

  1. Klinefelter syndrome and acute basophilic leukaemia--case report.

    Science.gov (United States)

    Ljubić, Nives; Lang, Nada; Skelin, Ika Kardum; Lasan, Ruzica; Dominis, Mara; Perković, Leila; Zupanić-Krmek, Dubraka; Grgurević-Batinica, Anita

    2010-06-01

    Patients with 47, XXY karyotype (Klinefelter syndrome) appear to have increased risk of developing cancer, especially male breast cancer, germ cell tumours and non Hodgkin lymphomas, but rarely acute myeloid leukaemia. We report a patient with acute basophilic leukaemia with 47, XXY karyotype in both the tumour and constitutional cells. Acute basophilic leukaemia is very rare disease comprising less than 1% of all acute myeloid leukaemias. Morphological characteristic of leukaemic blast cells is moderately basophilic cytoplasm containing a variable number of coarse basophilic granules. The most characteristic cytochemical reaction is metachromatic positivity with toluidine blue. Blast are myeloperoxidase negative. Also leukemic blasts express myeloid and monocyte markers. There is no consistent chromosomal abnormality identified in this leukaemia. This is the first reported case of acute basophilic leukaemia in patient with Klinefelter syndrome. In this article the medical history of the patient is given and the possible connection between Klinefelter syndrome and acute myeloid leukaemia is discussed.

  2. CD33 monoclonal antibody conjugated Au cluster nano-bioprobe for targeted flow-cytometric detection of acute myeloid leukaemia

    Energy Technology Data Exchange (ETDEWEB)

    Retnakumari, Archana; Jayasimhan, Jasusri; Chandran, Parwathy; Menon, Deepthy; Nair, Shantikumar; Mony, Ullas; Koyakutty, Manzoor, E-mail: manzoork@aims.amrita.edu, E-mail: ullasmony@aims.amrita.edu [Amrita Centre for Nanoscience and Molecular Medicine, Amrita Institute of Medical Science, Cochin 682 041 (India)

    2011-07-15

    Protein stabilized gold nanoclusters (Au-NCs) are biocompatible, near-infrared (NIR) emitting nanosystems having a wide range of biomedical applications. Here, we report the development of a Au-NC based targeted fluorescent nano-bioprobe for the flow-cytometric detection of acute myeloid leukaemia (AML) cells. Au-NCs with {approx} 25-28 atoms showing bright red-NIR fluorescence (600-750 nm) and average size of {approx} 0.8 nm were prepared by bovine serum albumin assisted reduction-cum-stabilization in aqueous phase. The protein protected clusters were conjugated with monoclonal antibody against CD33 myeloid antigen, which is overexpressed in {approx} 99.2% of the primitive population of AML cells, as confirmed by immunophenotyping using flow cytometry. Au-NC-CD33 conjugates having average size of {approx} 12 nm retained bright fluorescence over an extended duration of {approx} a year, as the albumin protein protects Au-NCs against degradation. Nanotoxicity studies revealed excellent biocompatibility of Au-NC conjugates, as they showed no adverse effect on the cell viability and inflammatory response. Target specificity of the conjugates for detecting CD33 expressing AML cells (KG1a) in flow cytometry showed specific staining of {approx} 95.4% of leukaemia cells within 1-2 h compared to a non-specific uptake of {approx} 8.2% in human peripheral blood cells (PBMCs) which are CD33{sup low}. The confocal imaging also demonstrated the targeted uptake of CD33 conjugated Au-NCs by leukaemia cells, thus confirming the flow cytometry results. This study demonstrates that novel nano-bioprobes can be developed using protein protected fluorescent nanoclusters of Au for the molecular receptor targeted flow cytometry based detection and imaging of cancer cells.

  3. Acute Myeloid Leukaemia | EU Clinical Trials Register [EU Clinical Trials Register

    Lifescience Database Archive (English)

    Full Text Available inical trial with GRASPA, Red Blood cells encapsulating L-Asparaginase, in patients affected by Acute Myeloi...ndition or disease under investigation E.1.1Medical condition(s) being investigated Acute...ion E.1.2Version 14.1 E.1.2Level LLT E.1.2Classification code 10000886 E.1.2Term Acute...old and less than 85 years old- Newly diagnosed Acute Myeloid Leukemia (AML) or post myelodysplastic syndrom

  4. Survival of Mexican Children with Acute Myeloid Leukaemia Who Received Early Intensification Chemotherapy and an Autologous Transplant

    Directory of Open Access Journals (Sweden)

    Elva Jiménez-Hernández

    2015-01-01

    Full Text Available Background. In Mexico and other developing countries, few reports of the survival of children with acute leukaemia exist. Objective. We aimed at comparing the disease-free survival of children with acute myeloid leukaemia who, in addition to being treated with the Latin American protocol of chemotherapy and an autologous transplant, either underwent early intensified chemotherapy or did not undergo such treatment. Procedure. This was a cohort study with a historical control group, forty patients, less than 16 years old. Group A (20 patients, diagnosed in the period 2005–2007, was treated with the Latin American protocol of chemotherapy with an autologous transplant plus early intensified chemotherapy: high doses of cytarabine and mitoxantrone. Group B (20 patients, diagnosed in the period 1999–2004, was treated as Group A, but without the early intensified chemotherapy. Results. Relapse-free survival for Group A was 90% whereas that for Group B it was 60% (P=0.041. Overall survival for Group A (18, 90% was higher than that for Group B (60%. Complete remission continued for two years of follow-up. Conclusions. Relapse-free survival for paediatric patients treated with the Latin American protocol of chemotherapy with an autologous transplant plus early intensified chemotherapy was higher than that for those who did not receive early intensified chemotherapy.

  5. Survival of Mexican Children with Acute Myeloid Leukaemia Who Received Early Intensification Chemotherapy and an Autologous Transplant

    Science.gov (United States)

    Jiménez-Hernández, Elva; Dueñas-González, María Teresa; Arellano-Galindo, José; Medrano-Ortíz-De-Zárate, María Elena; Bekker-Méndez, Vilma Carolina; Berges-García, Adolfina; Solís-Labastida, Karina; Sánchez-Jara, Berenice; Tiznado-García, Héctor Manuel; Jaimes-Reyes, Ethel Zulie; García-Jiménez, Xochiketzalli; Espinoza-Hernández, Laura; Núñez-Villegas, Nora Nancy; Franco-Ornelas, Sergio; Pérez-Casillas, Ruy Xavier; Martínez Villegas, Octavio; Palomares, Teresa Marin; Mejía-Aranguré, Juan Manuel

    2015-01-01

    Background. In Mexico and other developing countries, few reports of the survival of children with acute leukaemia exist. Objective. We aimed at comparing the disease-free survival of children with acute myeloid leukaemia who, in addition to being treated with the Latin American protocol of chemotherapy and an autologous transplant, either underwent early intensified chemotherapy or did not undergo such treatment. Procedure. This was a cohort study with a historical control group, forty patients, less than 16 years old. Group A (20 patients), diagnosed in the period 2005–2007, was treated with the Latin American protocol of chemotherapy with an autologous transplant plus early intensified chemotherapy: high doses of cytarabine and mitoxantrone. Group B (20 patients), diagnosed in the period 1999–2004, was treated as Group A, but without the early intensified chemotherapy. Results. Relapse-free survival for Group A was 90% whereas that for Group B it was 60% (P = 0.041). Overall survival for Group A (18, 90%) was higher than that for Group B (60%). Complete remission continued for two years of follow-up. Conclusions. Relapse-free survival for paediatric patients treated with the Latin American protocol of chemotherapy with an autologous transplant plus early intensified chemotherapy was higher than that for those who did not receive early intensified chemotherapy. PMID:25821830

  6. Treatment and long-term results in children with acute myeloid leukaemia treated according to the AIEOP AML protocols.

    Science.gov (United States)

    Pession, A; Rondelli, R; Basso, G; Rizzari, C; Testi, A M; Fagioli, F; De Stefano, P; Locatelli, F

    2005-12-01

    Since 1982, four consecutive studies on childhood acute myeloid leukaemia (AML) (namely LAM-82, -87, -87M and -92) have been conducted in Italy by the Associazione Italiana di Ematologia e Oncologia Pediatrica (AIEOP) group. The induction therapy of the first three studies consisted of daunorubicin and cytarabine structured in a 3+7 backbone. In the most recent protocol (LAM92), patients received two induction courses including idarubicin, cytarabine and etoposide. Patients with acute promyelocytic leukaemia (20% of diagnoses) were included in LAM-87 and 87M studies. Postremissional therapy significantly changed over time, with an ever-increasing role given to stem cell transplantation (SCT). The long-term outcome of patients enrolled in the LAM-82, 87 and 87M studies was comparable, whereas that of children treated according to LAM-92 study was significantly better (P<0.005). Either allogeneic or autologous SCT was employed as consolidation therapy in more than 75% of cases enrolled in this latter study. Patients enrolled in the LAM-92 study were stratified in standard and high-risk groups with different outcome (67 vs 47%, respectively, P=0.04). Altogether, the results obtained in these four studies have permitted a progressive refinement of treatment, contributing to the structure of the ongoing LAM-2002 protocol that stratifies patients according to the presence of definite genetic anomalies and response to induction therapy.

  7. Heterogeneity in the therapeutic approach to relapsed elderly patients with acute myeloid leukaemia: a survey from the Gruppo Italiano Malattie Ematologiche dell' Adulto (GIMEMA) Acute Leukaemia Working Party.

    Science.gov (United States)

    Ferrara, Felicetto; Fazi, Paola; Venditti, Adriano; Pagano, Livio; Amadori, Sergio; Mandelli, Franco

    2008-06-01

    The percentage of long-term survivors in acute myeloid leukaemia (AML) in the elderly does not exceed 10-15% of patients enrolled into clinical trials because of lower complete remission (CR) rates and higher incidence of relapse. However, few data are available as the treatment of elderly patients with relapsed disease is concerned. The aim of this study was of collecting data on criteria adopted for the treatment of these patients. A questionnaire was e-mailed to 32 haematologic institutions involved in the Gruppo Italiano per le Malattie Ematologiche dell'Adulto (GIMEMA) group. Questions to be addressed regarded: (1) per cent of relapsed elderly patients treated with aggressive salvage chemotherapy; (2) the selection criteria adopted for inclusion into intensive reinduction; (3) the specific treatment adopted; (4) the treatment given to patients not eligible for intensive salvage. Per cent of patients enrolled into aggressive salvage regimens varied from 10 to 80% (median 50%). The most frequent factor influencing the therapeutic choice was performance status (97%). Additional factors were age >70 years (44%) and duration of first CR (53%). Fludarabine including regimens were most frequently used as aggressive salvage therapy (59%), while gemtuzumab ozogamicin was adopted in various combinations at 11 out of 32 institutions (34%). For patients not eligible to aggressive therapy, the most frequent approach included hydroxyurea (59%). Low dose ARA-C (LDARA-C) was adopted at five centres: as single agent (n = 1), with 6-thioguanine (n = 1), with vitamin D3 and all-trans retinoic acid (ATRA) (n = 2), or with ATRA alone (n = 1). The FLT3 inhibitor CEP-701 was used at one centre. We conclude that the treatment of AML in elderly relapsed patients is extremely heterogeneous. A marked selection is operated as to inclusion into aggressive salvage regimens and only a small minority of patients are offered experimental approaches.

  8. Incidence and significance of FLT3-ITD and NPM1 mutations in patients with normal karyotype acute myeloid leukaemia.

    LENUS (Irish Health Repository)

    Haslam, K

    2012-02-01

    BACKGROUND: Acute myeloid leukaemia (AML) is a heterogeneous clonal disorder of haematopoietic progenitor cells. Approximately half of all adult AML patients have a normal karyotype (NK-AML) and an intermediate risk prognosis. AIMS: To determine the incidence and prognostic significance of NPM1 and FLT3-ITD mutations in a population of patients with NK-AML. METHODS: FLT3-ITD and NPM1 mutation status was retrospectively sought in presentation samples from 44 NK-AML patients. RESULTS: FLT3-ITD and NPM1 mutations were detected in 45.5 and 54.5% of patients, respectively, allowing stratification according to genotype. CONCLUSIONS: FLT3-ITD and NPM1 mutation status can be defined in NK-AML. Prospective screening for these mutations is advocated in all NK-AML patients, as the genotype is of clinical importance when considering treatment options including stem cell transplantation.

  9. Outcome of hyperleukocytic adult acute myeloid leukaemia: a single-center retrospective study and review of literature.

    Science.gov (United States)

    Marbello, Laura; Ricci, Francesca; Nosari, Anna Maria; Turrini, Mauro; Nador, Guido; Nichelatti, Michele; Tedeschi, Alessandra; Vismara, Eleonora; Morra, Enrica

    2008-08-01

    Hyperleukocytic acute myeloid leukaemia is considered to have a poor prognosis due to high early death rate secondary to leukostasis. Supportive treatments do not seem to have reduced early exitus in this subset of patients. Prognostic impact of hyperleukocytosis on outcome has been the object of few studies. Clinical characteristics and outcome of 45 consecutive adult patients with newly diagnosed acute myeloid leukaemia presenting to our institution with a white cell count (WBC) above 100 x 10(9)L(-1) were reviewed. The outcome of this subset of patients was compared with 200 patients with a leukocyte count lower than 100 x 10(9)L(-1) similarly treated in the same period. Eight hyperleukocytic patients (17%) died of intracranial haemorrhage or pulmonary failure due to leukostasis within the first 7 days of treatment. A significant association was found between complete response (CR) and absence of hyperleukocytosis, but if early deaths were removed from analysis the difference was no longer significant. Hyperleukocytosis also significantly reduces the overall survival (OS) but does not significantly influence the disease-free survival (DFS). We reviewed in literature studies in which the outcome of series of at least 10 patients with hyperleukocytosis were compared with that of patients with a leukocyte count lower than 100 x 10(9)L(-1). Our data were consistent with those of the literature regarding the rate of early mortality and causes of death. In most of the reviewed series hyperleukocytosis does not seem to influence the outcome of patients. Avoiding early death seems to be an important step in this subset of patients. New data about pathophysiology of leukostasis are needed.

  10. Genome-scale definition of the transcriptional programme associated with compromised PU.1 activity in acute myeloid leukaemia.

    Science.gov (United States)

    Sive, J I; Basilico, S; Hannah, R; Kinston, S J; Calero-Nieto, F J; Göttgens, B

    2016-01-01

    Transcriptional dysregulation is associated with haematological malignancy. Although mutations of the key haematopoietic transcription factor PU.1 are rare in human acute myeloid leukaemia (AML), they are common in murine models of radiation-induced AML, and PU.1 downregulation and/or dysfunction has been described in human AML patients carrying the fusion oncogenes RUNX1-ETO and PML-RARA. To study the transcriptional programmes associated with compromised PU.1 activity, we adapted a Pu.1-mutated murine AML cell line with an inducible wild-type PU.1. PU.1 induction caused transition from leukaemia phenotype to monocytic differentiation. Global binding maps for PU.1, CEBPA and the histone mark H3K27Ac with and without PU.1 induction showed that mutant PU.1 retains DNA-binding ability, but the induction of wild-type protein dramatically increases both the number and the height of PU.1-binding peaks. Correlating chromatin immunoprecipitation (ChIP) Seq with gene expression data, we found that PU.1 recruitment coupled with increased histone acetylation induces gene expression and activates a monocyte/macrophage transcriptional programme. PU.1 induction also caused the reorganisation of a subgroup of CEBPA binding peaks. Finally, we show that the PU.1 target gene set defined in our model allows the stratification of primary human AML samples, shedding light on both known and novel AML subtypes that may be driven by PU.1 dysfunction.

  11. Persistence of DNMT3A R882 mutations during remission does not adversely affect outcomes of patients with acute myeloid leukaemia

    Science.gov (United States)

    Bhatnagar, Bhavana; Eisfeld, Ann-Kathrin; Nicolet, Deedra; Mrózek, Krzysztof; Blachly, James S.; Orwick, Shelley; Lucas, David M.; Kohlschmidt, Jessica; Blum, William; Kolitz, Jonathan E.; Stone, Richard M.; Bloomfield, Clara D.; Byrd, John C.

    2016-01-01

    Summary Somatic mutation of the DNMT3A gene at the arginine R882 site is common in acute myeloid leukaemia (AML). The prognostic significance of DNMT3A R882 mutation clearance, using traditional diagnostic next generation sequencing (NGS) methods, during complete remission (CR) in AML patients is controversial. We examined the impact of clearing DNMT3A R882 mutations at diagnosis to the detectable threshold of NGS methods, persist in the majority of AML patients in CR. PMID:27476855

  12. Acute myeloid leukaemia as a cause of acute ischaemic heart disease

    NARCIS (Netherlands)

    van Haelst, P.L.; Schot, Bart; Hoendermis, E.S.; van den Berg, M.P.

    2006-01-01

    Ischaemic heart disease is almost invariably the result of atherosclerotic degeneration of the coronary arteries. However, other causes of ischaemic heart disease should always be considered. Here we describe two patients with a classic presentation of ischaemic heart disease resulting from acute le

  13. Case report: hydroquinone and/or glutaraldehyde induced acute myeloid leukaemia?

    Directory of Open Access Journals (Sweden)

    Alexopoulos Evangelos C

    2006-07-01

    Full Text Available Abstract Background Exposures to high doses of irradiation, to chemotherapy, benzene, petroleum products, paints, embalming fluids, ethylene oxide, herbicides, pesticides, and smoking have been associated with an increased risk of acute myelogenous leukemia (AML. Although there in no epidemiological evidence of relation between X-ray developer, fixer and replenisher liquids and AML, these included glutaraldehyde which has weakly associated with lymphocytic leukemia in rats and hydroquinone has been increasingly implicated in producing leukemia, causing DNA and chromosomal damage, inhibits topo-isomerase II, alter hematopoiesis and inhibit apoptosis of neoplastic cells. Case presentation Two white females (A and B hired in 1985 as medical radiation technologists in a primary care center, in Greece. In July 2001, woman A, 38-years-old, was diagnosed as having acute monocytic leukaemia (FAB M5. The patient did not respond to therapy and died threeweeks later. In August 2001, woman B, 35-year-old, was diagnosed with acute promyelocytic leukaemia (FAB M3. Since discharge, she is in continuous complete remission. Both women were non smokers without any medical history. Shortly after these incidents official inspectors and experts inspected workplace, examined equipment, archives of repairs, notes, interviewed and monitored employees. They concluded that shielding was inadequate for balcony's door but personal monitoring did not show any exceeding of TLV of 20 mSv yearly and cytogenetics analysis did not reveal findings considered to be characteristics of ionizing exposure. Equipment for developing photos had a long list of repairs, mainly leakages of liquids and increases of temperature. On several occasions the floor has been flooded especially during 1987–1993 and 1997–2001. Inspection confirmed a complete lack of ventilation and many spoiled medical x-ray films. Employees reported that an "osmic" level was continuously evident and frequently

  14. Acute leukaemia: making sense of a complex blood cancer.

    LENUS (Irish Health Repository)

    Meenaghan, Teresa

    2012-01-01

    Acute leukaemia represents a diverse group of blood cancers that affect both children and adults. Treatment schedules for these haematology cancers are often prolonged, with many associated side effects and complications. Nurses caring for patients with acute leukaemia require an anticipatory approach, where care is aimed at minimizing the side effects of treatment and being constantly vigilant for any impending adverse effects. Moreover, patients require support for the psychosocial issues that can arise for patients during their illness. This article provides an overview of acute lymphoblastic leukaemia and acute myeloid leukaemia. Nursing considerations in the care of patients being treated for acute leukaemia are also explored.

  15. Acute leukaemia following renal transplantation.

    Science.gov (United States)

    Subar, M; Gucalp, R; Benstein, J; Williams, G; Wiernik, P H

    1996-03-01

    Four renal transplant patients on immunosuppressive therapy who presented with acute myeloid leukaemia are described. In two cases, azathioprine may have played an important role as a cofactor in leukaemogenesis. In a third case, the alkylating agent cyclophosphamide may have contributed. All patients were treated for leukaemia with full doses of cytotoxic chemotherapy and, in each case, a functioning renal allograft was preserved throughout the treatment despite attenuation of immunosuppressive therapy. Three patients achieved complete remission. Of the three, one is surviving at 2 years and two expired during the pancytopenic phase of their treatment with no active leukaemia present, and with intact renal function. As increasing expertise in the field of organ transplantation allows patients to survive longer, such patients' exposure to immunosuppressive and potentially leukaemogenic drugs is prolonged. The risk of secondary neoplasia has been previously documented in this population. Two of the four cases reported here suffered from polycystic kidney disease as their underlying condition. While this report suggests that the leukaemias are related to renal transplantation, we cannot rule out an association with the underlying disease which led to the transplant. This report further suggests that the leukaemia that develops in such patients may respond to standard therapy, and that such treatment does not compromise the transplanted kidney.

  16. TP53 mutation in patients with high-risk acute myeloid leukaemia treated with allogeneic haematopoietic stem cell transplantation.

    Science.gov (United States)

    Middeke, Jan M; Herold, Sylvia; Rücker-Braun, Elke; Berdel, Wolfgang E; Stelljes, Matthias; Kaufmann, Martin; Schäfer-Eckart, Kerstin; Baldus, Claudia D; Stuhlmann, Reingard; Ho, Anthony D; Einsele, Hermann; Rösler, Wolf; Serve, Hubert; Hänel, Mathias; Sohlbach, Kristina; Klesse, Christian; Mohr, Brigitte; Heidenreich, Falk; Stölzel, Friedrich; Röllig, Christoph; Platzbecker, Uwe; Ehninger, Gerhard; Bornhäuser, Martin; Thiede, Christian; Schetelig, Johannes

    2016-03-01

    Treatment success in patients with acute myeloid leukaemia (AML) is heterogeneous. Cytogenetic and molecular alterations are strong prognostic factors, which have been used to individualize treatment. Here, we studied the impact of TP53 mutations on the outcome of AML patients with adverse cytogenetic risk treated with allogeneic haematopoietic stem cell transplantation (HSCT). Samples of 97 patients with AML and adverse-risk cytogenetics who had received a HSCT within three randomized trials were analysed. Complete sequencing of the TP53 coding region was performed using next generation sequencing. The median age was 51 years. Overall, TP53 mutations were found in 40 patients (41%). With a median follow up of 67 months, the three-year probabilities of overall survival (OS) and event-free survival for patients with TP53 wild type were 33% [95% confidence interval (CI), 21% to 45%] and 24% (95% CI, 13% to 35%) compared to 10% (95% CI, 0% to 19%) and 8% (95% CI, 0% to 16%) (P = 0·002 and P = 0·007) for those with mutated TP53, respectively. In multivariate analysis, the TP53-mutation status had a negative impact on OS (Hazard Ratio = 1·7; P = 0·066). Mutational analysis of TP53 might be an important additional tool to predict outcome after HSCT in patients with adverse karyotype AML.

  17. Epigenetic Guardian: A Review of the DNA Methyltransferase DNMT3A in Acute Myeloid Leukaemia and Clonal Haematopoiesis

    Science.gov (United States)

    Chaudry, Sabah F.

    2017-01-01

    Acute myeloid leukaemia (AML) is a haematological malignancy characterized by clonal stem cell proliferation and aberrant block in differentiation. Dysfunction of epigenetic modifiers contributes significantly to the pathogenesis of AML. One frequently mutated gene involved in epigenetic modification is DNMT3A (DNA methyltransferase-3-alpha), a DNA methyltransferase that alters gene expression by de novo methylation of cytosine bases at CpG dinucleotides. Approximately 22% of AML and 36% of cytogenetically normal AML cases carry DNMT3A mutations and around 60% of these mutations affect the R882 codon. These mutations have been associated with poor prognosis and adverse survival outcomes for AML patients. Advances in whole-exome sequencing techniques have recently identified a large number of DNMT3A mutations present in clonal cells in normal elderly individuals with no features of haematological malignancy. Categorically distinct from other preleukaemic conditions, this disorder has been termed clonal haematopoiesis of indeterminate potential (CHIP). Further insight into the mutational landscape of CHIP may illustrate the consequence of particular mutations found in DNMT3A and identify specific “founder” mutations responsible for clonal expansion that may contribute to leukaemogenesis. This review will focus on current research and understanding of DNMT3A mutations in both AML and CHIP. PMID:28286768

  18. Minimal residual disease evaluation by flow cytometry is a complementary tool to cytogenetics for treatment decisions in acute myeloid leukaemia.

    Science.gov (United States)

    Vidriales, María-Belén; Pérez-López, Estefanía; Pegenaute, Carlota; Castellanos, Marta; Pérez, José-Juan; Chandía, Mauricio; Díaz-Mediavilla, Joaquín; Rayón, Consuelo; de Las Heras, Natalia; Fernández-Abellán, Pascual; Cabezudo, Miguel; de Coca, Alfonso García; Alonso, Jose M; Olivier, Carmen; Hernández-Rivas, Jesús M; Montesinos, Pau; Fernández, Rosa; García-Suárez, Julio; García, Magdalena; Sayas, María-José; Paiva, Bruno; González, Marcos; Orfao, Alberto; San Miguel, Jesús F

    2016-01-01

    The clinical utility of minimal residual disease (MRD) analysis in acute myeloid leukaemia (AML) is not yet defined. We analysed the prognostic impact of MRD level at complete remision after induction therapy using multiparameter flow cytometry in 306 non-APL AML patients. First, we validated the prognostic value of MRD-thresholds we have previously proposed (≥ 0.1%; ≥ 0.01-0.1%; and Cytogenetics is the most relevant prognosis factor in AML, however intermediate risk cytogenetics represent a grey zone that require other biomarkers for risk stratification, and we show that MRD evaluation discriminate three prognostic subgroups (p=0.03). Also, MRD assessments yielded relevant information on favourable and adverse cytogenetics, since patients with favourable cytogenetics and high MRD levels have poor prognosis and patients with adverse cytogenetics but undetectable MRD overcomes the adverse prognosis. Interestingly, in patients with intermediate or high MRD levels, intensification with transplant improved the outcome as compared with chemotherapy, while the type of intensification therapy did not influenced the outcome of patients with low MRD levels. Multivariate analysis revealed age, MRD and cytogenetics as independent variables. Moreover, a scoring system, easy in clinical practice, was generated based on MRD level and cytogenetics.

  19. Dose intensification in acute myeloid leukaemia: greater effectiveness at lower cost. Principal report of the Medical Research Council's AML9 study. MRC Leukaemia in Adults Working Party.

    Science.gov (United States)

    Rees, J K; Gray, R G; Wheatley, K

    1996-07-01

    Between 1984 and 1990, 972 patients aged 1-79 years with acute myeloid leukaemia (AML), from 85 British hospitals, were entered into the MRC's 9th AML trial. Patients were randomized between DAT 1 + 5 (daunorubicin for 1 d, with cytarabine and 6-thioguanine for 5 d) and DAT 3 + 10 (same dose drugs for 3 and 10 d respectively) as induction therapy. The 63% who achieved complete remission (CR) were randomized to receive two courses of DAT 2 + 7 alternating with two courses of either MAZE (m-AMSA, 5-azacytidine, etoposide) or COAP (cyclophosphamide, vincristine, cytarabine, prednisone). Finally, those still in CR were randomized to receive either 1 year of maintenance treatment with eight courses of cytarabine and thioguanine followed by four courses of COAP, or no further cytotoxic therapy. Resistance to induction therapy was less common with the DAT 3 + 10 regimen than with DAT 1 + 5 (13% v 23%; P = 0.0001) and hence, despite a 5% increase in the risk of induction death, the CR rate was higher (66% v 61%; P = 0.15). Moreover, CR was achieved more rapidly with DAT 3 + 10 (median 34 v 46 d; P COAP. 5-year survival was not significantly higher with MAZE (37% v 31%). Finally, although 1 year of outpatient maintenance treatment appeared to delay, but not prevent, recurrence it did not improve 5-year survival which was non-significantly worse for those allocated maintenance treatment (41% v 44%). We conclude that the more intensive induction regimen, DAT 3 + 10, is not only more effective than DAT 1 + 5, even for older patients, but is also less expensive; intensive post-remission therapy with MAZE achieves better leukaemic control but at the cost of substantial toxicity; whereas low-level maintenance therapy confers no apparent advantage in survival as well as being inconvenient and costly.

  20. Maintenance treatment with azacytidine for patients with high-risk myelodysplastic syndromes (MDS) or acute myeloid leukaemia following MDS in complete remission after induction chemotherapy

    DEFF Research Database (Denmark)

    Grövdal, Michael; Karimi, Mohsen; Khan, Rasheed

    2010-01-01

    This prospective Phase II study is the first to assess the feasibility and efficacy of maintenance 5-azacytidine for older patients with high-risk myelodysplastic syndrome (MDS), chronic myelomonocytic leukaemia and MDS-acute myeloid leukaemia syndromes in complete remission (CR) after induction...... and 24 months post CR. Twenty-four (40%) patients achieved CR after induction chemotherapy and 23 started maintenance treatment with azacytidine. Median CR duration was 13.5 months, >24 months in 17% of the patients, and 18-30.5 months in the four patients with trisomy 8. CR duration was not associated......-IV thrombocytopenia and neutropenia occurred after 9.5 and 30% of the cycles, respectively, while haemoglobin levels increased during treatment. 5-azacytidine treatment is safe, feasible and may be of benefit in a subset of patients....

  1. Label-free imaging and identification of typical cells of acute myeloid leukaemia and myelodysplastic syndrome by Raman microspectroscopy.

    Science.gov (United States)

    Vanna, R; Ronchi, P; Lenferink, A T M; Tresoldi, C; Morasso, C; Mehn, D; Bedoni, M; Picciolini, S; Terstappen, L W M M; Ciceri, F; Otto, C; Gramatica, F

    2015-02-21

    In clinical practice, the diagnosis and classification of acute myeloid leukaemia (AML) and myelodysplastic syndrome (MDS) start from the manual examination of stained smears of bone marrow (BM) and peripheral blood (PB) by using an optical microscope. This step is subjective and scarcely reproducible. Therefore, the development of subjective and potentially automatable methods for the recognition of typical AML/MDS cells is necessary. Here we have used Raman spectroscopy for distinguishing myeloblasts, promyelocytes, abnormal promyelocytes and erhytroblasts, which have to be counted for a correct diagnosis and morphological classification of AML and MDS. BM samples from patients affected by four different AML subtypes, mostly characterized by the presence of the four subpopulations selected for this study, were analyzed. First, each cell was scanned by acquiring 4096 spectra, thus obtaining Raman images which demonstrate an accurate description of morphological features characteristic of each subpopulation. Raman imaging coupled with hierarchical cluster analysis permitted the automatic discrimination and localization of the nucleus, the cytoplasm, myeloperoxidase containing granules and haemoglobin. Second, the averaged Raman fingerprint of each cell was analysed by multivariate analysis (principal component analysis and linear discriminant analysis) in order to study the typical vibrational features of each subpopulation and also for the automatic recognition of cells. The leave-one-out cross validation of a Raman-based classification model demonstrated the correct classification of myeloblasts, promyelocytes (normal/abnormal) and erhytroblasts with an accuracy of 100%. Normal and abnormal promyelocytes were distinguished with 95% accuracy. The overall classification accuracy considering the four subpopulations was 98%. This proof-of-concept study shows that Raman micro-spectroscopy could be a valid approach for developing label-free, objective and automatic

  2. The new low-toxic histone deacetylase inhibitor S-(2) induces apoptosis in various acute myeloid leukaemia cells.

    Science.gov (United States)

    Cellai, C; Balliu, M; Laurenzana, A; Guandalini, L; Matucci, R; Miniati, D; Torre, E; Nebbioso, A; Carafa, V; Altucci, L; Romanelli, M N; Paoletti, F

    2012-08-01

    Histone deacetylase inhibitors (HDACi) induce tumour cell cycle arrest and/or apoptosis, and some of them are currently used in cancer therapy. Recently, we described a series of powerful HDACi characterized by a 1,4-benzodiazepine (BDZ) ring hybridized with a linear alkyl chain bearing a hydroxamate function as Zn(++)--chelating group. Here, we explored the anti-leukaemic properties of three novel hybrids, namely the chiral compounds (S)-2 and (R)-2, and their non-chiral analogue 4, which were first comparatively tested in promyelocytic NB4 cells. (S)-2 and partially 4--but not (R)-2--caused G0/G1 cell-cycle arrest by up-regulating cyclin G2 and p21 expression and down-regulating cyclin D2 expression, and also apoptosis as assessed by cell morphology and cytofluorimetric assay, histone H2AX phosphorylation and PARP cleavage. Notably, these events were partly prevented by an anti-oxidant. Moreover, novel HDACi prompted p53 and α-tubulin acetylation and, consistently, inhibited HDAC1 and 6 activity. The rank order of potency was (S)-2 > 4 > (R)-2, reflecting that of other biological assays and addressing (S)-2 as the most effective compound capable of triggering apoptosis in various acute myeloid leukaemia (AML) cell lines and blasts from patients with different AML subtypes. Importantly, (S)-2 was safe in mice (up to 150 mg/kg/week) as determined by liver, spleen, kidney and bone marrow histopathology; and displayed negligible affinity for peripheral/central BDZ-receptors. Overall, the BDZ-hydroxamate (S)-2 showed to be a low-toxic HDACi with powerful anti-proliferative and pro-apototic activities towards different cultured and primary AML cells, and therefore of clinical interest to support conventional anti-leukaemic therapy.

  3. Central line-related bacteraemia due to Roseomonas mucosa in a neutropenic patient with acute myeloid leukaemia in Piraeus, Greece.

    Science.gov (United States)

    Christakis, G B; Perlorentzou, S; Alexaki, P; Megalakaki, A; Zarkadis, I K

    2006-08-01

    A case of central venous catheter-related bacteraemia due to Roseomonas mucosa in a neutropenic patient with acute myelogenous leukaemia is reported. The patient was successfully treated with amikacin and piperacillin-tazobactam. The clinical isolate was identified as R. mucosa by 16S rRNA gene sequencing.

  4. Implication of Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) and Interleukin-3 (IL-3) in Children with Acute Myeloid Leukaemia (AML).

    Science.gov (United States)

    Elbaz, O; Shaltout, A

    2000-01-01

    Granulocyte-macrophage colony stimulating factor (GM-CSF) and Interleukin-3 (IL-3) are increasingly used to stimulate granulopoiesis in neutropenic patients but these are rarely used in the lights of knowledge of the endogenous CSF-levels. In this study we measured serum levels of GM-CSF and IL-3 at diagnosis and after remission in children with acute leukaemia, using an enzyme linked immuno-sorbent assay (ELISA) techniques in 14 patients with acute myeloid leukaemia (AML) and 27 patients with acute lymphoblastic leukaemia (ALL). Twelve healthy age-matched children were used as a reference group. AML patients showed a highly significant increase in serum levels of GM-CSF and IL-3 before induction of therapy (p 0.5), with no significant difference between preinduction and postinduction serum levels of either (p > 0.5). Since these cytokines are known to be fundamental for the growth of AML cells, we postulate that the pretreatment levels of both GM-CSF and IL-3 could play a role in the pathogenesis of AML.

  5. Implication of Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) and Interleukin-3 (IL-3) in Children with Acute Myeloid Leukaemia (AML); Malignancy.

    Science.gov (United States)

    Elbaz, Osama; Shaltout, Ali

    2001-01-01

    Granulocyte-macrophage colony stimulating factor (GM-CSF) and Interleukin-3 (IL-3) are increasingly used to stimulate granulopoiesis in neutropenic patients but these are rarely used in the lights of knowledge of the endogenous CSF-levels. In this study we measured serum levels of GM-CSF and IL-3 at diagnosis and after remission in children with acute leukaemia, using an enzyme linked immuno-sorbent assay (ELISA) techniques in 14 patients with acute myeloid leukaemia (AML) and 27 patients with acute lymphoblastic leukaemia (ALL). Twelve healthy age-matched children were used as a reference group. AML patients showed a highly significant increase in serum levels of GM-CSF and IL-3 before induction of therapy (p 0.5), with no significant difference between preinduction and postinduction serum levels of either (p > 0.5). Since these cytokines are known to be fundamental for the growth of AML cells, we postulate that the pretreatment levels of both GM-CSF and IL-3 could play a role in the pathogenesis of AML.

  6. A novel RT-qPCR assay for quantification of the MLL-MLLT3 fusion transcript in acute myeloid leukaemia

    DEFF Research Database (Denmark)

    Abildgaard, Lotte; Ommen, Hans Beier; Lausen, Birgitte Frederiksen

    2013-01-01

    OBJECTIVES: Patients with acute myeloid leukaemia (AML) of the monocytic lineage often lack molecular markers for minimal residual disease (MRD) monitoring. The MLL-MLLT3 fusion transcript found in patients with AML harbouring t(9;11) is amenable to RT-qPCR quantification but because of the heter......OBJECTIVES: Patients with acute myeloid leukaemia (AML) of the monocytic lineage often lack molecular markers for minimal residual disease (MRD) monitoring. The MLL-MLLT3 fusion transcript found in patients with AML harbouring t(9;11) is amenable to RT-qPCR quantification but because...... of the heterogeneity of translocation break points, the MLL-MLLT3 fusion gene is a challenging target. We hypothesised that MRD monitoring using MLL-MLLT3 as a RT-qPCR marker is feasible in the majority of patients with t(9;11)-positive AML. METHODS: Using a locked nucleic acid probe, we developed a sensitive RT-qPCR...... follow-up. Two patients relapsed, and both were MRD positive in BM after first induction course. A total of three relapses occurred, and they were detected by RT-qPCR 3 wks before haematological relapse was diagnosed. CONCLUSION: This MLL-MLLT3 RT-qPCR assay could be useful in MRD monitoring of a group...

  7. Live cell detection of chromosome 2 deletion and Sfpi1/PU1 loss in radiation-induced mouse acute myeloid leukaemia.

    Science.gov (United States)

    Olme, C-H; Finnon, R; Brown, N; Kabacik, S; Bouffler, S D; Badie, C

    2013-10-01

    The CBA/H mouse model of radiation-induced acute myeloid leukaemia (rAML) has been studied for decades to bring to light the molecular mechanisms associated with multistage carcinogenesis. A specific interstitial deletion of chromosome 2 found in a high proportion of rAML is recognised as the initiating event. The deletion leads to the loss of Sfpi, a gene essential for haematopoietic development. Its product, the transcription factor PU.1 acts as a tumour suppressor in this model. Although the deletion can be detected early following ionising radiation exposure by cytogenetic techniques, precise characterisation of the haematopoietic cells carrying the deletion and the study of their fate in vivo cannot be achieved. Here, using a genetically engineered C57BL/6 mouse model expressing the GFP fluorescent molecule under the control of the Sfpi1 promoter, which we have bred onto the rAML-susceptible CBA/H strain, we demonstrate that GFP expression did not interfere with X-ray induced leukaemia incidence and that GFP fluorescence in live leukaemic cells is a surrogate marker of radiation-induced chromosome 2 deletions with or without point mutations on the remaining allele of the Sfpi1 gene. This study presents the first experimental evidence for the detection of this leukaemia initiating event in live leukemic cells.

  8. Acute myeloid leukaemia induced by mitoxantrone: case report Leucemia mielóide aguda induzida por mitoxantrone: relato de caso

    Directory of Open Access Journals (Sweden)

    Walter Oleschko Arruda

    2005-06-01

    Full Text Available Mitoxantrone (MX is an immunosupressant drug used in secondarily progressive multiple sclerosis (SPMS and in relapsing-remitting multiple sclerosis (RRMS. It has a leukemogenesis potential induced by cytogenetic abnormalities, though with a low incidence. Promyelocitic leukaemia (type M3 and other forms of acute myeloblastic leukaemias (M4 and M5 have been described in a few MS patients who received MX during their treatment. We describe a white female patient, 47 year-old, with SPMS (EDSS = 4 with 14 years of disease. She received MX during her disease and developed acute promyelocytic leukaemia (M3, with severe thrombocytopenia 30 months later. She ultimately died due to intracerebral hemorrhage. Other cases of treatment related to AML are reviewed and discussed.Mitoxantrone (MX é uma agente imunossupressor utilizado nas formas progressivas secundárias de esclerose múltipla (EM ou formas surto-remissão sem resposta com outras formas de tratamento (p.ex. beta-interferon, acetato de glatirâmer. Com o uso desta medicação, ocorre uma incidência maior, embora pequena, de desenvolvimento de leucemia mielóide aguda induzida por quimioterápicos. Descrevemos o caso de uma paciente com forma progressiva secundária de EM, submetida a uma dose única de MX de 15mg e que 30 meses após desenvolveu quadro fulminante de leucemia promieloblástica aguda (M3, com trombocitopenia grave. A paciente faleceu por hemorragia intracerebral maciça. É feita revisão de outros casos relatados na literatura e os possíveis mecanismos de desenvolvimento desta complicação grave secundária ao uso do MX.

  9. Massive myeloid sarcoma affecting the central nervous system, mediastinum, retroperitoneum, liver, and rectum associated with acute myeloblastic leukaemia: a case report

    Science.gov (United States)

    Best-Aguilera, C R; Vazquez-Del Mercado, M; Muñoz-Valle, J F; Herrera-Zarate, L; Navarro-Hernandez, R E; Martin-Marquez, B T; Oregon-Romero, E; Ruiz-Quezada, S; Bonilla, G M; Lomeli-Guerrero, A

    2005-01-01

    Myeloid sarcomas are extramedullary tumours with granulocytic precursors. When associated with acute myelogenous leukaemia (AML), these tumours usually affect no more than two different extramedullary regions. This report describes a myeloid sarcoma associated with AML with tumour formation at five anatomical sites. The patient was a 37 year old man admitted in September 1999 with a two month history of weight loss, symptoms of anaemia, rectal bleeding, and left facial nerve palsy. The anatomical sites affected were: the rectum, the right lobe of the liver, the mediastinum, the retroperitoneum, and the central nervous system. A bone marrow smear was compatible with AML M2. Flow cytometry showed that the peripheral blood was positive for CD4, CD11, CD13, CD14, CD33, CD45, and HLA-DR. A karyotypic study of the bone marrow revealed an 8;21 translocation. The presence of multiple solid tumours in AML is a rare event. Enhanced expression of cell adhesion molecules may be the reason why some patients develop myeloid sarcomas. PMID:15735171

  10. NPM1 mutation is a stable marker for minimal residual disease monitoring in acute myeloid leukaemia patients with increased sensitivity compared to WT1 expression*

    DEFF Research Database (Denmark)

    Kristensen, Thomas; Møller, Michael B; Friis, Lone;

    2011-01-01

    Mutation in the NPM1 gene occurs in 60% of acute myeloid leukaemia (AML) patients with normal karyotype. NPM1 mutation is potentially a superior minimal residual disease (MRD) marker compared to WT1 gene overexpression by being specific to the malignant clone, although experimental evidence...... published so far includes very limited numbers of relapsed cases. Also, the stability of the NPM1 mutation has been questioned by reports of the mutation being lost at relapse. In the present study we compared NPM1 mutation and WT1 overexpression as MRD markers in 20 cases of relapsed AML. The 20 patients...... experienced a total of 28 morphological relapses. Karyotypic evolution was detected in 56% of relapses. All relapses were accompanied by high levels of NPM1 mutation, along with high WT1 mRNA levels, thus demonstrating complete stability of both markers during relapse. Detectable NPM1 mutation following...

  11. Randomized trial of two schedules of low-dose gemtuzumab ozogamicin as induction monotherapy for newly diagnosed acute myeloid leukaemia in older patients not considered candidates for intensive chemotherapy. A phase II study of the EORTC and GIMEMA leukaemia groups (AML-19).

    NARCIS (Netherlands)

    Amadori, S.; Suciu, S.; Selleslag, D.; Stasi, R.; Alimena, G.; Baila, L.; Rizzoli, V.; Borlenghi, E.; Gaidano, G.; Magro, D.; Torelli, G.; Muus, P.; Venditti, A.; Cacciola, E.; Lauria, F.; Vignetti, M.; Witte, T.J.M. de

    2010-01-01

    This study compared two schedules of low-dose gemtuzumab ozogamicin (GO) as induction monotherapy for untreated acute myeloid leukaemia in older patients unfit for intensive chemotherapy, to identify the more promising regimen for further study. Patients were randomized to receive either best suppor

  12. [Biphenotypic acute leukaemia with Burkitt-like cytology].

    Science.gov (United States)

    Coche, D; Bergues, B; Harrivel, V; Guillaume, N

    2009-01-01

    Biphenotypic acute leukaemia (BAL) represents about 5% of adult acute leukaemia. Based on a previously described scoring system, the European Group for Immunologic Classification of Leukaemia (EGIL) proposed a set of diagnostic criteria for BAL. This scoring system is based on the number and degree of the specificity of several markers for myeloid or T/B lymphoid blasts. Here, we report the case of a BAL with Burkitt-like cytology, corresponding to "the acute lymphoblastic leukaemia, Burkitt type" L3 for the FAB classification. By flow cytometry, the blasts showed a positivity for B lymphoid cytoplasmic (CD79a and mu) and membrane (CD19, CD22, CD24, IgM) markers AND a positivity for the myeloid (CD13, CD33, CD65, CD15) markers.

  13. KEGG DISEASE / Acute myeloid leukemia (AML) [KEGG DISEASE

    Lifescience Database Archive (English)

    Full Text Available DISEASE: H00003 Entry H00003Disease Name Acute myeloid leukemia (AML) Description Acute.... Category Cancer Brite Human diseases [BR:br08402] Cancers Cancers of haematopoietic and lymphoid tissues H00003Acute...atopoietic and related tissue C92Myeloid leukaemia H00003Acute myeloid leukemia (AML) Cancer-accociated carb...ohydrates [br08441.html] H00003 Pathway hsa05221Acute myeloid leukemiahsa05202Transcriptional misregulation ... or t(16; 16)(p13, q22), (CBF-beta/MYH11) ICD-O: 9866/3, Tumor type: Acute promyelocytic leukaemia (AML with

  14. The role of hematopoietic stem cell transplantation in the elderly patient with acute myeloid leukaemia O papel do transplante de célula-tronco hematopoiética em pacientes idosos com leucemia mielóide aguda

    OpenAIRE

    2008-01-01

    Older adults with Acute Myeloid Leukaemia (AML), when compared to younger patients with the same disease, have a poor prognosis and represent a discrete population in terms of disease biology, treatment-related complications, and overall outcome. As a result, older patients require distinctive management approaches. For 85%-95% of older AML patients, any therapy ultimately will be purely palliative. No randomized trial has ever demonstrated that any amount of post-remission therapy in older A...

  15. Low frequency of MLL-partial tandem duplications in paediatric acute myeloid leukaemia using MLPA as a novel DNA screenings technique.

    Science.gov (United States)

    Balgobind, Brian V; Hollink, Iris H I M; Reinhardt, Dirk; van Wering, Elisabeth R; de Graaf, Siebold S N; Baruchel, Andre; Stary, Jan; Beverloo, H Berna; de Greef, Georgine E; Pieters, Rob; Zwaan, C Michel; van den Heuvel-Eibrink, Marry M

    2010-07-01

    Mixed-lineage leukaemia (MLL)-partial tandem duplications (PTDs) are found in 3-5% of adult acute myeloid leukaemia (AML), and are associated with poor prognosis. In adult AML, MLL-PTD is only detected in patients with trisomy 11 or internal tandem duplications of FLT3 (FLT3-ITD). To date, studies in paediatric AML are scarce, and reported large differences in the frequency of MLL-PTD, frequently utilising mRNA RT-PCR only to detect MLL-PTDs. We studied the frequency of MLL-PTD in a large cohort of paediatric AML (n=276) and the results from two different methods, i.e. mRNA RT-PCR, and multiplex ligation-dependent probe amplification (MLPA), a method designed to detect copy number differences of specific DNA sequences. In some patients with an MLL-rearrangement, MLL-PTD transcripts were detected, but were not confirmed by DNA-MLPA, indicating that DNA-MLPA can more accurately detect MLL-PTD compared to mRNA RT-PCR. In paediatric AML, MLL-PTD was detected in 7/276 patients (2.5%). One case had a trisomy 11, while the others had normal cytogenetics. Furthermore 4 of the 7 patients revealed a FLT3-ITD, which was significantly higher compared with the other AML cases (p=0.016). In conclusion, using DNA-MLPA as a novel screenings technique in combination with mRNA RT-PCR a low frequency of MLL-PTD in paediatric AML was found. Larger prospective studies are needed to further define the prognostic relevance of MLL-PTD in paediatric AML.

  16. Oral manifestations of acute leukaemia

    Directory of Open Access Journals (Sweden)

    Ivanović Mirjana

    2011-01-01

    Full Text Available Acute leukaemia is the most common form of chilhood cancer. The aim of this paper was to underline the importance of oral manifestations in children with acute leukaemia. The disease and its treatment can directly or indirectly affect oral health. Oral manifestations are gingival inflammation and enlargement. Leukaemic cells are capable of infiltrating the gingiva and the deeper periodontal tissues which leads to ulceration and infection of oral tissues. Gingival bleeding is a common sign in patients with leukaemia. Symptoms include local lymphadenopathy, mucous membrane Petechiae and ecchymoses. Cytotoxic drugs have direct effects like mucositis, involving atrophy, desquamation and ulceration of the mucosa, with increasing the risk for local and systemic infections. Leukaemia can directly influence dental care and dental treatment, while oral lesions may have life-threatening consequences. Knowledge and skills among dentists may also not be adequate to treat children with acute leukaemia. It is therefore imperative that all stomatologists be aware of dental problems that occur in leukaemia in order to be able to effectively carry out appropriate measures to mitigate these problems.

  17. Fucoidan inhibits proliferation of the SKM-1 acute myeloid leukaemia cell line via the activation of apoptotic pathways and production of reactive oxygen species.

    Science.gov (United States)

    Wei, Chunmei; Xiao, Qing; Kuang, Xingyi; Zhang, Tao; Yang, Zesong; Wang, Li

    2015-11-01

    Myelodysplastic syndromes (MDS) are a heterogeneous group of myeloid disorders characterized by peripheral blood cytopenias and a high risk of progression to acute myeloid leukaemia (AML). Fucoidan, a complex sulphated polysaccharide isolated from the cell wall of brown seaweeds, has recently attracted attention for its multiple biological activities and its potential as a novel candidate for cancer therapy. In the present study, the anti‑cancer activity of fucoidan was investigated in the MDS/AML cell line SKM‑1. Fucoidan inhibited proliferation, induced apoptosis and caused G1-phase arrest of the cell cycle in SKM‑1 cells as determined by a cell counting kit 8 assay and flow cytometry. Furthermore, reverse transcription quantitative polymerase chain reaction and western blot analyses indicated that treatment with fucoidan (100 µg/ml for 48 h) activated Fas and caspase‑8 in SKM‑1 cells, which are critical for the extrinsic apoptotic pathway; furthermore, caspase‑9 was activated via decreases in phosphoinositide-3 kinase/Akt signaling as indicated by reduced levels of phosphorylated Akt, suggesting the involvement of the intrinsic apoptotic pathway. In addition, fucoidan treatment of SKM‑1 cells resulted in the generation of reactive oxygen species (ROS) as determined by staining with dichloro-dihydro-fluorescein diacetate. These results suggested that the mechanisms of the anti‑cancer effects of fucoidan in SKM‑1 are closely associated with cell cycle arrest and apoptotic cell death, which partly attributed to the activation of apoptotic pathways and accumulation of intracellular ROS. Our results demonstrated that Fucoidan inhibits proliferation and induces the apoptosis of SKM‑1 cells, which provides substantial therapeutic potential for MDS treatment.

  18. Outpatient bendamustine and idarubicin for upfront therapy of elderly acute myeloid leukaemia/myelodysplastic syndrome: a phase I/II study using an innovative statistical design.

    Science.gov (United States)

    Lionberger, Jack M; Pagel, John M; Sandhu, Vicky K; Xie, Hu; Shadman, Mazyar; Mawad, Raya; Boehm, Alexandra; Dean, Carol; Shannon-Dorcy, Kathleen; Scott, Bart L; Deeg, Hans Joachim; Becker, Pamela S; Hendrie, Paul C; Walter, Roland B; Ostronoff, Fabiana; Appelbaum, Frederick R; Estey, Elihu H

    2014-08-01

    Combinations of agents may improve outcomes among elderly acute myeloid leukaemia (AML) and high-risk myelodysplastic syndrome (MDS) patients. We performed an adaptive phase I/II trial for newly-diagnosed AML or high-risk MDS patients aged ≥50 years using a Bayesian approach to determine whether 1 of 3 doses of bendamustine (45, 60, 75 mg/m(2) days 1-3), together with idarubicin (12 mg/m(2) days 1-2), might provide a complete response (CR) rate ≥40% with 10% marrow blasts; median age 73 years). None of the three bendamustine doses in combination with idarubicin met the required CR and toxicity rates; the 75 mg/m(2) dose because of excess toxicity (two of three patients) and the 60 mg/m(2) dose because of low efficacy (CR rate 10/33), although no grade 3-4 non-haematological toxicity was seen at this dose. Median survival was 7·2 months. All patients began treatment as outpatients but hospitalization was required in 90% (35/39). Although we did not find a dose of bendamustine combined with idarubicin that would provide a CR rate of >40% with acceptable toxicity, bendamustine may have activity in AML/MDS patients, suggesting its addition to other regimens may be warranted.

  19. Predictors of early death and survival among children, adolescents and young adults with acute myeloid leukaemia in California, 1988-2011: a population-based study.

    Science.gov (United States)

    Abrahão, Renata; Keogh, Ruth H; Lichtensztajn, Daphne Y; Marcos-Gragera, Rafael; Medeiros, Bruno C; Coleman, Michel P; Ribeiro, Raul C; Keegan, Theresa H M

    2016-04-01

    A better understanding of factors associated with early death and survival among children, adolescents and young adults with acute myeloid leukaemia (AML) may guide health policy aimed at improving outcomes in these patients. We examined trends in early death and survival among 3935 patients aged 0-39 years with de novo AML in California during 1988-2011 and investigated the associations between sociodemographic and selected clinical factors and outcomes. Early death declined from 9·7% in 1988-1995 to 7·1% in 2004-2011 (P = 0·062), and survival improved substantially over time. However, 5-year survival was still only 50% (95% confidence interval 47-53%) even in the most recent treatment period (2004-2011). Overall, the main factors associated with poor outcomes were older age at diagnosis, treatment at hospitals not affiliated with National Cancer Institute-designated cancer centres, and black race/ethnicity. For patients diagnosed during 1996-2011, survival was lower among those who lacked health insurance compared to those with public or private insurance. We conclude that mortality after AML remained strikingly high in California and increased with age. Possible strategies to improve outcomes include wider insurance coverage and treatment at specialized cancer centres.

  20. A prospective phase II randomized study of deferasirox to prevent iatrogenic iron overload in patients undertaking induction/consolidation chemotherapy for acute myeloid leukaemia.

    Science.gov (United States)

    Kennedy, Glen A; Morris, Kirk L; Subramonpillai, Elango; Curley, Cameron; Butler, Jason; Durrant, Simon

    2013-06-01

    This prospective randomized phase II study aimed to determine the safety and efficacy of deferasirox in preventing iatrogenic iron overload in patients receiving induction/consolidation chemotherapy for acute myeloid leukaemia (AML) ize. Serum ferritin, transferrin saturation and CRP were measured pre-, mid- and post- each chemotherapy cycle. Patients were randomized to receive either therapy with deferasirox vs. no deferasirox therapy once serum ferritin increased to >500 μg/l. The trial was stopped prematurely due to excess gastrointestinal (GI) and infectious toxicity demonstrable in the deferasirox arm, after 10 patients had been randomized to deferasirox and 6 patients to the control arm. Overall, deferasirox was poorly tolerated, with median maximum tolerated dose only 13·8 mg/kg/d and no patient able to tolerate doses >20 mg/kg/d. Median duration of deferasirox therapy was only 72 d (range 19-130 d), with 9/10 patients requiring unplanned dose interruptions and 4/10 patients unable to continue the drug predominantly due to GI effects. Although all 3 treatment-related deaths occurred in the deferasirox arm (P = 0·25), median overall survival was similar between treatment arms. Use of deferasirox to prevent iatrogenic iron overload in AML patients undertaking induction/consolidation is poorly tolerated and appears to be associated with excess GI and infectious toxicity.

  1. Increased cellular hypoxia and reduced proliferation of both normal and leukaemic cells during progression of acute myeloid leukaemia in rats

    DEFF Research Database (Denmark)

    Jensen, P O; Mortensen, B T; Hodgkiss, R J;

    2000-01-01

    The microenvironmental changes in the bone marrow, spleen and liver during progression of the transplantable promyelocytic leukaemia in the Brown Norwegian rat (BNML) have been studied. We used flow cytometry to estimate cellular hypoxia and proliferation based on in vivo pulse-labelling with a m......The microenvironmental changes in the bone marrow, spleen and liver during progression of the transplantable promyelocytic leukaemia in the Brown Norwegian rat (BNML) have been studied. We used flow cytometry to estimate cellular hypoxia and proliferation based on in vivo pulse...

  2. Increased cellular hypoxia and reduced proliferation of both normal and leukaemic cells during progression of acute myeloid leukaemia in rats

    DEFF Research Database (Denmark)

    Jensen, P O; Mortensen, B T; Hodgkiss, R J

    2000-01-01

    The microenvironmental changes in the bone marrow, spleen and liver during progression of the transplantable promyelocytic leukaemia in the Brown Norwegian rat (BNML) have been studied. We used flow cytometry to estimate cellular hypoxia and proliferation based on in vivo pulse-labelling with a m......The microenvironmental changes in the bone marrow, spleen and liver during progression of the transplantable promyelocytic leukaemia in the Brown Norwegian rat (BNML) have been studied. We used flow cytometry to estimate cellular hypoxia and proliferation based on in vivo pulse......-labelling with a mixture of 2-nitroimidazole linked to theophylline (NITP) and bromodeoxyuridine (BrdUrd). The leukaemic cells were identified with the RM124 antibody. In rats inoculated with leukaemic cells the fraction of RM124+ cells was significantly increased from day 20 onwards in the spleen and from day 27...

  3. Quantitative multiplex quantum dot in-situ hybridisation based gene expression profiling in tissue microarrays identifies prognostic genes in acute myeloid leukaemia

    Energy Technology Data Exchange (ETDEWEB)

    Tholouli, Eleni [Department of Haematology, Manchester Royal Infirmary, Oxford Road, Manchester, M13 9WL (United Kingdom); MacDermott, Sarah [The Medical School, The University of Manchester, Oxford Road, M13 9PT Manchester (United Kingdom); Hoyland, Judith [School of Biomedicine, Faculty of Medical and Human Sciences, The University of Manchester, Oxford Road, M13 9PT Manchester (United Kingdom); Yin, John Liu [Department of Haematology, Manchester Royal Infirmary, Oxford Road, Manchester, M13 9WL (United Kingdom); Byers, Richard, E-mail: richard.byers@cmft.nhs.uk [School of Cancer and Enabling Sciences, Faculty of Medical and Human Sciences, The University of Manchester, Stopford Building, Oxford Road, M13 9PT Manchester (United Kingdom)

    2012-08-24

    Highlights: Black-Right-Pointing-Pointer Development of a quantitative high throughput in situ expression profiling method. Black-Right-Pointing-Pointer Application to a tissue microarray of 242 AML bone marrow samples. Black-Right-Pointing-Pointer Identification of HOXA4, HOXA9, Meis1 and DNMT3A as prognostic markers in AML. -- Abstract: Measurement and validation of microarray gene signatures in routine clinical samples is problematic and a rate limiting step in translational research. In order to facilitate measurement of microarray identified gene signatures in routine clinical tissue a novel method combining quantum dot based oligonucleotide in situ hybridisation (QD-ISH) and post-hybridisation spectral image analysis was used for multiplex in-situ transcript detection in archival bone marrow trephine samples from patients with acute myeloid leukaemia (AML). Tissue-microarrays were prepared into which white cell pellets were spiked as a standard. Tissue microarrays were made using routinely processed bone marrow trephines from 242 patients with AML. QD-ISH was performed for six candidate prognostic genes using triplex QD-ISH for DNMT1, DNMT3A, DNMT3B, and for HOXA4, HOXA9, Meis1. Scrambled oligonucleotides were used to correct for background staining followed by normalisation of expression against the expression values for the white cell pellet standard. Survival analysis demonstrated that low expression of HOXA4 was associated with poorer overall survival (p = 0.009), whilst high expression of HOXA9 (p < 0.0001), Meis1 (p = 0.005) and DNMT3A (p = 0.04) were associated with early treatment failure. These results demonstrate application of a standardised, quantitative multiplex QD-ISH method for identification of prognostic markers in formalin-fixed paraffin-embedded clinical samples, facilitating measurement of gene expression signatures in routine clinical samples.

  4. Outcome of children with acute myeloid leukaemia (AML) experiencing primary induction failure in the AIEOP AML 2002/01 clinical trial.

    Science.gov (United States)

    Quarello, Paola; Fagioli, Franca; Basso, Giuseppe; Putti, Maria C; Berger, Massimo; Luciani, Matteo; Rizzari, Carmelo; Menna, Giuseppe; Masetti, Riccardo; Locatelli, Franco

    2015-11-01

    Paediatric patients with acute myeloid leukaemia (AML) who fail induction due to primary resistance to chemotherapy account for a significant proportion of cases and have a particularly dismal prognosis. We report the clinical and biological data, and final outcome of 48 paediatric patients with primary-resistant AML enrolled in the Associazione Italiana di Ematologia e Oncologia Pediatrica AML 2002/01 clinical trial. These patients had a significantly higher white blood cell count at diagnosis compared to other AML patients. Cytogenetic and molecular features did not differ between patients with primary induction failure and patients allocated to the high-risk group. For the whole patient population, the probability of overall survival, event-free survival (EFS) and disease-free survival (DFS) was 21·8% ± 6·2, 20·4% ± 5·9, and 49·5% ± 11·3, respectively. Twenty-eight (58%) patients received haematopoietic stem cell transplantation (HSCT); 3 were autologous and 25 were allogeneic. Patients who underwent HSCT had improved EFS (31·2% vs. 5%, P < 0·0001). Only one of the 20 patients who did not receive HSCT is alive and disease free. The 19 patients in complete remission at time of HSCT showed significantly better DFS than the 9 with active disease (46% vs. 0%, P = 0·02). This study represents one of the largest series with long-term follow up of paediatric AML patients with primary refractory disease. Children who underwent transplantation had an encouraging long-term outcome. Disease recurrence remains the major cause of treatment failure; a better understanding of the disease biology is desirable to develop more effective treatment strategies.

  5. Phase II study of tosedostat with cytarabine or decitabine in newly diagnosed older patients with acute myeloid leukaemia or high-risk MDS.

    Science.gov (United States)

    Mawad, Raya; Becker, Pamela S; Hendrie, Paul; Scott, Bart; Wood, Brent L; Dean, Carol; Sandhu, Vicky; Deeg, Hans Joachim; Walter, Roland; Wang, Lixia; Myint, Han; Singer, Jack W; Estey, Elihu; Pagel, John M

    2016-01-01

    Tosedostat, an oral aminopeptidase inhibitor, has synergy with cytarabine and hypomethylating agents. We performed a Phase II trial to determine rates of complete remission (CR) and survival using tosedostat with cytarabine or decitabine in older patients with untreated acute myeloid leukaemia (AML) or high-risk myelodysplastic syndrome (MDS). Thirty-four patients ≥60 years old (median age 70 years; range, 60-83) were randomized to receive tosedostat (120 mg on days 1-21 or 180 mg continuously) with 5 d of either cytarabine (1 g/m2 /d) or decitabine (20 mg/m2 /d) every 35 d. Twenty-nine patients (85%) had AML, including 15 (44%) with secondary AML/MDS, and 5 (15%) had MDS-refractory anaemia with excess blasts type 2. The CR/CR with incomplete count recovery (CRi) rate was 53% [9 in each arm; 14 CR (41%) and 4 CRi (12%)], attained in 6 of 14 patients with adverse cytogenetics and 4 of 7 with FLT3-internal tandem duplication mutations. Median follow-up was 11.2 months (range, 0.5-22.3), and median survival was 11.5 months (95% confidence interval, 5.2-16.7). Twenty-three patients (67.6%) were treated as outpatients and 10 of these patients required hospitalization for febrile neutropenia. No Grade 3-4 non-haematological toxicities required withdrawal from study. Tosedostat with cytarabine or decitabine is tolerated in older patients with untreated AML/MDS, results in a CR/CRi rate of >50%, and warrants further study in larger trials.

  6. Increased cellular hypoxia and reduced proliferation of both normal and leukaemic cells during progression of acute myeloid leukaemia in rats

    DEFF Research Database (Denmark)

    Jensen, P O; Mortensen, B T; Hodgkiss, R J;

    2000-01-01

    The microenvironmental changes in the bone marrow, spleen and liver during progression of the transplantable promyelocytic leukaemia in the Brown Norwegian rat (BNML) have been studied. We used flow cytometry to estimate cellular hypoxia and proliferation based on in vivo pulse...... in the bone marrow and liver, reaching a level of 65-87% in these organs at day 32. At day 32, the NITP+ fraction of RM124+ cells had increased significantly in the bone marrow and spleen to 88% and 90%, respectively. The corresponding fractions of NITP+ normal cells reached 63% and 65%, respectively. From......-labelling with a mixture of 2-nitroimidazole linked to theophylline (NITP) and bromodeoxyuridine (BrdUrd). The leukaemic cells were identified with the RM124 antibody. In rats inoculated with leukaemic cells the fraction of RM124+ cells was significantly increased from day 20 onwards in the spleen and from day 27...

  7. Pharm GKB: Leukemia, Promyelocytic, Acute [PharmGKB

    Lifescience Database Archive (English)

    Full Text Available Overview Alternate Names: Synonym APL - Acute promyelocytic leukaemia; APL - Acute ...promyelocytic leukemia; APML - Acute promyelocytic leukaemia; APML - Acute promyelocytic leukemia; Acute Promyelocytic Leukemia; Acut...e Promyelocytic Leukemias; Acute myeloid leukaemia, PML/RAR-alpha; Acute myeloid le...ukemia, PML/RAR-alpha; Acute myeloid leukemia, t(15;17)(q22;q11-12); Acute promye...locytic leukaemia (clinical); Acute promyelocytic leukaemia, FAB M3; Acute promyelocytic leukaemia, PML/RAR-alpha; Acute

  8. Atypical Chronic Myeloid Leukaemia with Trisomy 13: a Case Report

    Institute of Scientific and Technical Information of China (English)

    Guo-yu Hu; Chao-hui Yuan; Kui Tan; Zhen-zhen Chen

    2011-01-01

    ATYPICAL chronic myeloid leukaemia (aCML),which shows both myeloproliferative and myeIodysplastic features,is a type of myeloproliferative/myelodysplastic disease as defined by the World Health Organisation (WHO) classification of the myeloid neoplasms.1 Because of the presence of neutrophilic leukocytosis,aCML may resemble chronic myeIogenous leukemia (CML).However,in contrast with CML,aCML does not have the Philadelphia chromosome or the bcr/abl fusion gene.

  9. BMX tyrosine kinase gene is expressed in granulocytes and myeloid leukaemias.

    Science.gov (United States)

    Kaukonen, J; Lahtinen, I; Laine, S; Alitalo, K; Palotie, A

    1996-09-01

    The growth and maturation of haemopoietic cells is regulated by signal transduction through tyrosine protein kinases. Recently, a novel cytoplasmic tyrosine kinase gene in chromosome X, called Bmx, was identified in human bone marrow RNA. Bmx belongs to a subfamily of tyrosine kinases which are expressed in various haemopoietic cell lineages. We studied Bmx expression using RT-PCR of RNA from fractionated peripheral blood leucocytes, progenitor-enriched fractions of cord blood and from bone marrow or peripheral blood samples from leukaemia patients. Bmx was strongly expressed in haemopoietic tissues and enhanced in neutrophilic granulocytes. Bmx mRNA was also found in CD34-positive progenitor cells from cord blood. All samples (10/10) of patients with acute myeloid leukaemia and (4/4) with chronic myeloid leukaemia showed expression of Bmx. In contrast, none of the samples of acute lymphoid leukaemia (0/8) and only one out of six samples of chronic lymphoid leukaemia expressed Bmx. In conclusion, Bmx expression seems to be associated with myelopoiesis.

  10. Vosaroxin plus cytarabine versus placebo plus cytarabine in patients with first relapsed or refractory acute myeloid leukaemia (VALOR): a randomised, controlled, double-blind, multinational, phase 3 study

    Science.gov (United States)

    Ravandi, Farhad; Ritchie, Ellen K.; Sayar, Hamid; Lancet, Jeffrey E.; Craig, Michael D.; Vey, Norbert; Strickland, Stephen A.; Schiller, Gary J.; Jabbour, Elias; Erba, Harry P.; Pigneux, Arnaud; Horst, Heinz-August; Recher, Christian; Klimek, Virginia M.; Cortes, Jorge; Roboz, Gail J.; Odenike, Olatoyosi; Thomas, Xavier; Havelange, Violaine; Maertens, Johan; Derigs, Hans-Günter; Heuser, Michael; Damon, Lloyd; Powell, Bayard L.; Gaidano, Gianluca; Carella, Angelo-Michele; Wei, Andrew; Hogge, Donna; Craig, Adam R.; Fox, Judith A.; Ward, Renee; Smith, Jennifer A.; Acton, Gary; Mehta, Cyrus; Stuart, Robert K.; Kantarjian, Hagop M.

    2016-01-01

    Summary Background Safe and effective treatments are urgently needed for patients with relapsed/refractory acute myeloid leukaemia (AML). We investigated the efficacy and safety of vosaroxin, a first-in-class anticancer quinolone derivative, plus cytarabine in patients with relapsed/refractory AML. Methods VALOR was a phase 3, double-blind, placebo-controlled trial conducted at 101 international sites. Patients were randomised 1:1 to vosaroxin (90 mg/m2 IV days 1,4) plus cytarabine (1 g/m2 IV days 1–5) (vos/cyt) or placebo plus cytarabine (pla/cyt) using a permuted block procedure stratified by disease status, age, and geographic location. All participants were blind to treatment assignment. Primary endpoints were overall survival (OS) and 30- and 60-day mortality. Efficacy analyses were by intention-to-treat; safety analyses included all treated patients. This study is registered at clinicaltrials.gov (NCT01191801). Findings Between December 2010 and September 2013, 711 patients were randomised to vos/cyt (n=356) or pla/cyt (n=355). Median OS was 7·5 months with vos/cyt and 6·1 months with pla/cyt (hazard ratio 0·87; unstratified log-rank p=0·061; stratified p=0·0241) and was supported by a sensitivity analysis censoring for subsequent transplant (6·7 and 5·3 months; p=0·0243). Complete remission (CR) rate was higher with vos/cyt vs pla/cyt (30·1% vs 16·3%, p<0·0001). Early mortality rates were equivalent (vos/cyt vs pla/cyt: 30-day, 7·9% vs 6·6%; 60-day, 19·7% vs 19·4%). Treatment-related deaths occurred at any time in 18 patients (5·1%) with vos/cyt and 8 (2·3%) with pla/cyt. Grade ≥3 adverse events more frequent with vos/cyt included febrile neutropenia (167/355 [47%] vs 117/350 [33%]), stomatitis (54 [15%] vs 10 [3%]), hypokalaemia (52 [15%] vs 21 [6%]), sepsis (42 [12%] vs 18 [5%]), and pneumonia (39 [11%] vs 26 [7%]). Interpretation Addition of vosaroxin to cytarabine prolonged survival in patients with relapsed/refractory AML

  11. Allogeneic stem cell transplantation in adult patients with acute myeloid leukaemia and 17p abnormalities in first complete remission: a study from the Acute Leukemia Working Party (ALWP of the European Society for Blood and Marrow Transplantation (EBMT

    Directory of Open Access Journals (Sweden)

    Xavier Poiré

    2017-01-01

    Full Text Available Abstract Background Acute myeloid leukaemia (AML with 17p abnormalities (abn(17p carries a very poor prognosis due to high refractoriness to conventional chemotherapy, and allogeneic stem cell transplantation (allo-SCT appears as the only potential curative option. Methods To address outcomes after allo-SCT in patients with abn(17p, we retrospectively analysed de novo or secondary AML undergoing SCT between 2000 and 2013 from the EBMT registry. Results One hundred thirty-nine patients with confirmed abn(17p have been selected. At the time of transplant, one hundred twenty-five were in first remission (CR1. Median age was 54 years old. Abn(17p was associated with a monosomal karyotype in 83% of patients, complex karyotype in 91%, monosomy 5 or 5q deletion (-5/5q- in 55%, monosomy 7 (-7 in 39% and both -5/5q and -7 in 27%. Seventy-three patients (59% had a reduced-intensity conditioning regimen. The 2-year overall survival (OS and leukaemia-free survival (LFS were 28 and 24%, respectively. The 2-year non-relapse mortality (NRM was 15%, and 2-year relapse incidence (RI was 61%. The cumulative incidence of grade II to IV acute graft-versus-host disease (GvHD was 24% and that of chronic GvHD was 21%. In multivariate analysis, the presence of a -5/5q- in addition to abn(17p was significantly and independently associated with worse OS, LFS and higher RI. Age and donor types did not correlate with outcome. Conditioning intensity was not statistically associated with OS, LFS and NRM when adjusted for patients’ age. Conclusions In contrast to the dismal prognosis reported for AML patients harbouring abn(17p undergoing conventional chemotherapy, allogeneic SCT provides responses in about 25% of those patients transplanted in CR1.

  12. Acute myeloid leukemia (AML) - children

    Science.gov (United States)

    Acute myeloid leukemia is a cancer of the blood and bone marrow. Bone marrow is the soft tissue inside ... develops quickly. Both adults and children can get acute myeloid leukemia ( AML ). This article is about AML in children.

  13. A Novel Three-Colour Fluorescence in Situ Hybridization Approach for the Detection of t(7;12)(q36;p13) in Acute Myeloid Leukaemia Reveals New Cryptic Three Way Translocation t(7;12;16)

    Energy Technology Data Exchange (ETDEWEB)

    Naiel, Abdulbasit [Leukaemia and Chromosome Research Laboratory, Division of Biosciences, Brunel University, London, Middlesex UB8 3PH (United Kingdom); Vetter, Michael [MetaSystems, Altlussheim 68804 (Germany); Plekhanova, Olga [Regional Children’s Hospital N 1, Ekaterinburg 620149 (Russian Federation); Fleischman, Elena; Sokova, Olga [N.N. Blokhin Russian Cancer Research Center Russian Academy of Medical Science, Moscow 115478 (Russian Federation); Tsaur, Grigory [Regional Children’s Hospital N 1, Ekaterinburg 620149 (Russian Federation); Research Institute of Medical Cell Technologies, Ekaterinburg 620149 (Russian Federation); Harbott, Jochen [Oncogenetic Laboratory, Department of Paediatric Haematology and Oncology, Justus Liebig University, Giessen 35392 (Germany); Tosi, Sabrina, E-mail: sabrina.tosi@brunel.ac.uk [Leukaemia and Chromosome Research Laboratory, Division of Biosciences, Brunel University, London, Middlesex UB8 3PH (United Kingdom)

    2013-03-11

    The t(7;12)(q36;p13) translocation is a recurrent chromosome abnormality that involves the ETV6 gene on chromosome 12 and has been identified in 20–30% of infant patients with acute myeloid leukaemia (AML). The detection of t(7;12) rearrangements relies on the use of fluorescence in situ hybridization (FISH) because this translocation is hardly visible by chromosome banding methods. Furthermore, a fusion transcript HLXB9-ETV6 is found in approximately 50% of t(7;12) cases, making the reverse transcription PCR approach not an ideal screening method. Considering the report of few cases of variant translocations harbouring a cryptic t(7;12) rearrangement, we believe that the actual incidence of this abnormality is higher than reported to date. The clinical outcome of t(7;12) patients is believed to be poor, therefore an early and accurate diagnosis is important in the clinical management and treatment. In this study, we have designed and tested a novel three-colour FISH approach that enabled us not only to confirm the presence of the t(7;12) in a number of patients studied previously, but also to identify a cryptic t(7;12) as part of a complex rearrangement. This new approach has proven to be an efficient and reliable method to be used in the diagnostic setting.

  14. Phase II study of targeted therapy with temozolomide in acute myeloid leukaemia and high-risk myelodysplastic syndrome patients pre-screened for low O(6) -methylguanine DNA methyltransferase expression.

    Science.gov (United States)

    Brandwein, Joseph M; Kassis, Jeannine; Leber, Brian; Hogge, Donna; Howson-Jan, Kang; Minden, Mark D; Galarneau, André; Pouliot, Jean-François

    2014-12-01

    Resistance to temozolomide is largely mediated by the DNA repair enzyme O(6) -methylguanine DNA methyltransferase (MGMT). We conducted a prospective multicentre study of patients with previously untreated acute myeloid leukaemia (AML) or high-risk myelodysplastic syndrome (MDS) who were not candidates for intensive therapy. Patient selection was based on MGMT expression by Western blot. Patients with MGMT:ACTB (β-actin) ratio temozolomide 200 mg/m(2) /d ×7 d. Patients achieving a complete response (CR) could receive up to 12 monthly cycles of temozolomide ×5/28 d. Of 166 patients screened, 81 (49%) demonstrated low MGMT expression; 45 of these were treated with temozolomide. The overall response rate was 53%; 36% achieved complete clearance of blasts, with 27% achieving a CR/CR with incomplete platelet recovery (CRp). Factors associated with a trend toward a higher response rate included MDS, methylated MGMT promoter and standard cytogenetic risk group. Induction and post-remission cycles were well-tolerated and most patients were treated on an outpatient basis. Patient who achieved CR/CRp had a superior overall survival compared to partial or non-responders. In conclusion, targeted therapy based on pre-selection for low MGMT expression was associated with a higher response rate to temozolomide compared to previous reports of unselected patients.

  15. Posaconazole for primary antifungal prophylaxis in patients with acute myeloid leukaemia or myelodysplastic syndrome during remission induction chemotherapy: a single-centre retrospective study in Korea and clinical considerations.

    Science.gov (United States)

    Cho, Sung-Yeon; Lee, Dong-Gun; Choi, Su-Mi; Choi, Jae-Ki; Lee, Hyo-Jin; Kim, Si-Hyun; Park, Sun Hee; Choi, Jung-Hyun; Yoo, Jin-Hong; Kim, Yoo-Jin; Kim, Hee-Je; Min, Woo-Sung

    2015-09-01

    Posaconazole was introduced as the primary antifungal prophylaxis (PAP) in acute myeloid leukaemia (AML) or myelodysplastic syndrome (MDS) patients during remission induction chemotherapy. Data on breakthrough invasive fungal infections (IFIs) from various centres are essential, as there are several considerations in treating IFIs in the posaconazole era. The aim of this study was to evaluate the effectiveness of posaconazole PAP and identify characteristics of IFIs at a single centre in Korea. We retrospectively reviewed consecutive patients with AML/MDS undergoing remission induction chemotherapy between December 2010 and November 2013. Of the 424 patients, 140 received posaconazole and 284 received fluconazole prophylaxis. The incidence of breakthrough proven/probable IFIs (15.5% vs. 2.9%, P posaconazole group compared to the fluconazole group. In the posaconazole PAP group, two cases of breakthrough mucormycosis were noted among 13 proven/probable/possible IFI cases (15.4%). Overall and IFI-related mortality was 12.1% and 1.9% respectively. Fungus-free survival was significantly higher in the posaconazole group (74.7% vs. 87.1%, P = 0.028). Breakthrough IFIs and EAFT decreased significantly after posaconazole PAP. The benefit in fungus-free survival was noted with posaconazole PAP. Clinicians should be vigilant to identify non-Aspergillus IFIs with active diagnostic effort.

  16. KEGG PATHWAY / Acute myeloid leukemia [KEGG

    Lifescience Database Archive (English)

    Full Text Available PATHWAY: map05221 Entry map05221Pathway Name Acute myeloid leukemia Description Acute...Class Human Diseases; Cancers Pathwaymap map05221Acute myeloid leukemia Disease H00003Acute myeloid leukemia...inkDB DBGET integrated database retrieval system KEGG PATHWAY / Acute myeloid leukemia ...

  17. Granulocytic sarcoma of the femur in a patient with acute megakaryoblastic leukaemia

    Directory of Open Access Journals (Sweden)

    Čolović Milica

    2011-01-01

    Full Text Available Introduction. Granulocytic sarcoma, chloroma or myeloblastoma are observed in 3% to7% of acute myeloid leukaemia and represents localized tumour composed of collection of immature leukaemic cells. It appears most frequently in patients with M2, M4 and M5 subtypes of acute myeloid leukaemia Case Outline. A 58-year-old female presented with pain and oedema of the right upper limb in November 2009. After two months the patinet had fracture dislocation and numerous osteolytic lesions of the right femur. Immunohistochemistry of tumour biopsy showed megakaryoblastic granulocytic sarcoma which was CD31++, F-XIII++, CD34-, FVIII+++, S100-, aktin-, EMA++, Bcl2++, CD43++, with positive proliferative marker measured with Ki-67 positivity in more of 50% of cells. Aspirate of bone marrow and immunophenotyping with flowcytometry revealed diagnosis of acute megakaryoblastic leukaemia. The course of the disease was rapid and the patient died before commencing chemotherapy, five months after first complaints. Conclusion. Granulocytic sarcoma is extramedullary localization of collection of leukaemia cells which can proceed, to arise concomitantly with leukaemia, or may be the only manifestation of the disease. The diagnosis can be established only with immunohystochemistry.

  18. Azacitidine for Treating Acute Myeloid Leukaemia with More Than 30 % Bone Marrow Blasts: An Evidence Review Group Perspective of a National Institute for Health and Care Excellence Single Technology Appraisal.

    Science.gov (United States)

    Tikhonova, Irina A; Hoyle, Martin W; Snowsill, Tristan M; Cooper, Chris; Varley-Campbell, Joanna L; Rudin, Claudius E; Mujica Mota, Ruben E

    2017-03-01

    The National Institute for Health and Care Excellence (NICE) invited the manufacturer of azacitidine (Celgene) to submit evidence for the clinical and cost effectiveness of this drug for the treatment of acute myeloid leukaemia with more than 30 % bone marrow blasts in adults who are not eligible for haematopoietic stem cell transplantation, as part of the NICE's Single Technology Appraisal process. The Peninsula Technology Assessment Group was commissioned to act as the Evidence Review Group (ERG). The ERG produced a critical review of the evidence contained within the company's submission to NICE. The clinical effectiveness data used in the company's economic analysis were derived from a single randomised controlled trial, AZA-AML-001. It was an international, multicentre, controlled, phase III study with an open-label, parallel-group design conducted to determine the efficacy and safety of azacitidine against a conventional care regimen (CCR). The CCR was a composite comparator of acute myeloid leukaemia treatments currently available in the National Health Service: intensive chemotherapy followed by best supportive care (BSC) upon disease relapse or progression, non-intensive chemotherapy followed by BSC and BSC only. In AZA-AML-001, the primary endpoint was overall survival. Azacitidine appeared to be superior to the CCR, with median overall survival of 10.4 and 6.5 months, respectively. However, in the intention-to-treat analysis, the survival advantage associated with azacitidine was not statistically significant. The company submitted a de novo economic evaluation based on a partitioned survival model with four health states: "Remission", "Non-remission", "Relapse/Progressive disease" and "Death". The model time horizon was 10 years. The perspective was the National Health Service and Personal Social Services. Costs and health effects were discounted at the rate of 3.5 % per year. The base-case incremental cost-effectiveness ratio (ICER) of azacitidine

  19. Prognostic significance of flow-cytometry evaluation of minimal residual disease in children with acute myeloid leukaemia treated according to the AIEOP-AML 2002/01 study protocol.

    Science.gov (United States)

    Buldini, Barbara; Rizzati, Frida; Masetti, Riccardo; Fagioli, Franca; Menna, Giuseppe; Micalizzi, Concetta; Putti, Maria Caterina; Rizzari, Carmelo; Santoro, Nicola; Zecca, Marco; Disarò, Silvia; Rondelli, Roberto; Merli, Pietro; Pigazzi, Martina; Pession, Andrea; Locatelli, Franco; Basso, Giuseppe

    2017-04-01

    In children with acute myeloid leukaemia (AML), assessment of initial treatment response is an essential prognostic factor; methods more sensitive than morphology are still under evaluation. We report on the measurement of minimal residual disease (MRD), by multicolour flow-cytometry in one centralized laboratory, in 142 children with newly diagnosed AML enrolled in the Associazione Italiana di EmatoOncologia Pediatrica-AML 2002/01 trial. At the end of the first induction course, MRD was 1% in 51 patients. The 8-year disease-free survival (DFS) of 125 children in morphological complete remission and with MRD <0·1%, 0·1-1% and ≥1% was 73·1 ± 5·6%, 37·8 ± 12·1% and 34·1 ± 8·8%, respectively (P < 0·01). MRD was also available after the second induction course in 92/142 patients. MRD was ≥0·1% at the end of the first induction course in 36 patients; 13 reached an MRD <0·1% after the second one and their DFS was 45·4 ± 16·7% vs. 22·8 ± 8·9% in patients with persisting MRD ≥0·1% (P = 0·037). Multivariate analysis demonstrated that MRD ≥0·1% after first induction course was, together with a monosomal karyotype, an independent adverse prognostic factor for DFS. Our results show that MRD detected by flow-cytometry after induction therapy predicts outcome in patients with childhood AML and can help stratifying post-remission treatment.

  20. MicroRNAs as Potential Biomarkers in Acute Promyelocytic Leukaemia

    Directory of Open Access Journals (Sweden)

    Imilia Ismail

    2014-01-01

    Full Text Available Acute promyelocytic leukaemia (APL is an M3 subtype of acute myeloid leukaemia (AML. This classification is based on the morphology of promyelocytic cell. The clinical characteristics of APL can be recognized by haemorrhagic episodes, a differentiation block at the promyelocytic stage, and sensitivity to the differentiation response to all-trans-retinoic acid (ATRA. Cytogenetically, APL is characterized by a balanced reciprocal translocation between chromosomes 15 and 17, which results in the production of PML/RARα fusion protein. Recent studies reported that microRNAs (miRNAs have also been proposed to contribute to the pathogenesis of APL. miRNAs have been associated with the pathogenesis of cancer and their involvement as oncogenic and tumour suppressor activities have been identified. They are involved in various biological processes including the cell proliferation, differentiation, growth and development, metabolism, apoptosis, and haematopoiesis. The new discovery of miRNAs as possible therapeutic markers will provide new insight for the diagnosis and therapeutic entries for the treatment of APL. This review highlights the potential of miRNAs as biomarkers in APL.

  1. Randomized trial of two schedules of low-dose gemtuzumab ozogamicin as induction monotherapy for newly diagnosed acute myeloid leukaemia in older patients not considered candidates for intensive chemotherapy. A phase II study of the EORTC and GIMEMA leukaemia groups (AML-19).

    Science.gov (United States)

    Amadori, Sergio; Suciu, Stefan; Selleslag, Dominik; Stasi, Roberto; Alimena, Giuliana; Baila, Liliana; Rizzoli, Vittorio; Borlenghi, Erika; Gaidano, Gianluca; Magro, Domenico; Torelli, Giuseppe; Muus, Petra; Venditti, Adriano; Cacciola, Emma; Lauria, Francesco; Vignetti, Marco; de Witte, Theo

    2010-05-01

    This study compared two schedules of low-dose gemtuzumab ozogamicin (GO) as induction monotherapy for untreated acute myeloid leukaemia in older patients unfit for intensive chemotherapy, to identify the more promising regimen for further study. Patients were randomized to receive either best supportive care or a course of GO according to one of two schedules: 3 mg/m(2) on days 1, 3 and 5 (arm A), or GO 6 mg/m(2) on day 1 and 3 mg/m(2) on day 8 (arm B). Primary endpoint was the rate of disease non-progression (DnP), defined as the proportion of patients either achieving a response or maintaining a stable disease following GO induction in each arm. Fifty-six patients were randomized in the two GO arms (A, n = 29; B, n = 27). The rate of DnP was 38% [90% confidence interval (CI), 23-55] in arm A, and 63% (90% CI, 45-78) in arm B. Peripheral cytopenias were the most common adverse events for both regimens. The all-cause early mortality rate was 14% in arm A and 11% in arm B. The day 1 + 8 schedule, which was associated with the highest rate of DnP, met the statistical criteria to be selected as the preferred regimen for phase III comparison with best supportive care.

  2. Acute leukaemia following malignant ependymoma: a case report

    Energy Technology Data Exchange (ETDEWEB)

    Pai, M.R.; Advani, S.H.; Gopal, R.; Nair, C.N.; Saikia, T.; Kamat, D.M.

    1985-05-01

    Though an increasing number of chemotherapy- and radiotherapy-related leukaemias are being reported, acute promyelocytic leukaemia developing as a therapy-related second malignancy is still uncommon. Here the authors report a case of acute promyelocytic leukemia, microgranular variant, developing in a case of intracranial malignant ependymoma, 1.5 years following treatment with craniospinal radiotherapy.

  3. Myeloid leukaemia frequency after protracted exposure to ionizing radiation: experimental confirmation of the flat dose-response found in ankylosing spondylitis after a single treatment course with x-rays

    Energy Technology Data Exchange (ETDEWEB)

    Mole, R.H.; Major, I.R. (Medical Research Council, Harwell (UK). Radiobiological Research Unit)

    1983-01-01

    The dose-response for leukaemia induction by exposure to ionizing radiation protracted over several weeks was largely independent of dose not only in X-rayed patients with ankylosing spondylitis but also in experimentally ..gamma..-rayed CBA/H mice. In the experiment the induced leukaemia frequency of acute myeloid leukaemia was independent of a several thousand-fold variation in physical dose rate. Any difference in leukaemia induction between brief and protracted exposures must therefore depend on specifically biological consequences of protracted exposures. Experimental analysis is required to provide the guides for inference about risks of low level exposure from observations on relatively heavily irradiated populations.

  4. Decitabine and Bortezomib in Treating Patients With Acute Myeloid Leukemia

    Science.gov (United States)

    2014-11-06

    Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Recurrent Adult Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

  5. Phenotypical difference in deamination of cytarabine is not evident in induction therapy for acute myeloid leukemia

    DEFF Research Database (Denmark)

    Krogh-Madsen, Mikkel; Hansen, Steen Honore'; Jensen, Morten Krogh;

    2013-01-01

    Objective To investigate the uracil arabinoside/cytarabine (Ara-U/Ara-C) ratios with the lower dose in adult acute myeloid leukaemia (AML) induction therapy (100 mg/m2 Ara-C) where no enzyme saturation is expected. Methods A precise and robust high-performance liquid chromatography (HPLC) method...... for simultaneous determination of Ara-C and its main inactive metabolite Ara-U in human plasma was developed and validated. Nineteen patients with acute myeloid leukaemia were treated with Ara-C in a dose of 100 mg/m2 together with daunorubicin and etoposide. Plasma concentrations were used to construct...

  6. A Case of Abdominal Sarcoidosis in a Patient with Acute Myeloid Leukemia

    Directory of Open Access Journals (Sweden)

    Vadsala Baskaran

    2013-01-01

    Full Text Available The allogeneic bone marrow transplantation usually preceded by induction chemotherapy, in fit patients, represents the gold standard in the acute myeloid leukaemia. In the last years, many trials have been set up with the view of improving the number of remissions during the induction by adding new drugs. Several early or late side effects have been described in the literature. We herein present a patient with acute myeloid leukaemia patient who, after chemotherapy, developed ascites that turned out to be abdominal sarcoidosis.

  7. Pharm GKB: Leukemia, Monocytic, Acute [PharmGKB

    Lifescience Database Archive (English)

    Full Text Available Overview Alternate Names: Synonym Acute Monoblastic Leukemia; Acute Monoblastic Leukemias; Acute... Monocytic Leukemia; Acute Monocytic Leukemias; Acute monoblastic leukaemia; Acute monoblastic leukemia; Acute... monocytic leukaemia; Acute monocytic leukemia, morphology; Acute monocytoid leukemia; Leukemia, Acute... Monoblastic; Leukemia, Acute Monocytic; Leukemia, Monoblastic, Acute; Leukemia, Myeloid, Acute... Schilling-Type Myeloid; Leukemias, Acute Monoblastic; Leukemias, Acute Monocytic; M5a - Acute monoblastic leukaemia; M5a - Acute

  8. Estimation of current cumulative incidence of leukaemia-free patients and current leukaemia-free survival in chronic myeloid leukaemia in the era of modern pharmacotherapy

    Directory of Open Access Journals (Sweden)

    Trněný Marek

    2011-10-01

    Full Text Available Abstract Background The current situation in the treatment of chronic myeloid leukaemia (CML presents a new challenge for attempts to measure the therapeutic results, as the CML patients can experience multiple leukaemia-free periods during the course of their treatment. Traditional measures of treatment efficacy such as leukaemia-free survival and cumulative incidence are unable to cope with multiple events in time, e.g. disease remissions or progressions, and as such are inappropriate for the efficacy assessment of the recent CML treatment. Methods Standard nonparametric statistical methods are used for estimating two principal characteristics of the current CML treatment: the probability of being alive and leukaemia-free in time after CML therapy initiation, denoted as the current cumulative incidence of leukaemia-free patients; and the probability that a patient is alive and in any leukaemia-free period in time after achieving the first leukaemia-free period on the CML treatment, denoted as the current leukaemia-free survival. The validity of the proposed methods is further documented in the data of the Czech CML patients consecutively recorded between July 2003 and July 2009 as well as in simulated data. Results The results have shown a difference between the estimates of the current cumulative incidence function and the common cumulative incidence of leukaemia-free patients, as well as between the estimates of the current leukaemia-free survival and the common leukaemia-free survival. Regarding the currently available follow-up period, both differences have reached the maximum (12.8% and 20.8%, respectively at 3 years after the start of follow-up, i.e. after the CML therapy initiation in the former case and after the first achievement of the disease remission in the latter. Conclusions Two quantities for the evaluation of the efficacy of current CML therapy that may be estimated with standard nonparametric methods have been proposed in

  9. The genetic basis of early T-cell precursor acute lymphoblastic leukaemia.

    Science.gov (United States)

    Zhang, Jinghui; Ding, Li; Holmfeldt, Linda; Wu, Gang; Heatley, Sue L; Payne-Turner, Debbie; Easton, John; Chen, Xiang; Wang, Jianmin; Rusch, Michael; Lu, Charles; Chen, Shann-Ching; Wei, Lei; Collins-Underwood, J Racquel; Ma, Jing; Roberts, Kathryn G; Pounds, Stanley B; Ulyanov, Anatoly; Becksfort, Jared; Gupta, Pankaj; Huether, Robert; Kriwacki, Richard W; Parker, Matthew; McGoldrick, Daniel J; Zhao, David; Alford, Daniel; Espy, Stephen; Bobba, Kiran Chand; Song, Guangchun; Pei, Deqing; Cheng, Cheng; Roberts, Stefan; Barbato, Michael I; Campana, Dario; Coustan-Smith, Elaine; Shurtleff, Sheila A; Raimondi, Susana C; Kleppe, Maria; Cools, Jan; Shimano, Kristin A; Hermiston, Michelle L; Doulatov, Sergei; Eppert, Kolja; Laurenti, Elisa; Notta, Faiyaz; Dick, John E; Basso, Giuseppe; Hunger, Stephen P; Loh, Mignon L; Devidas, Meenakshi; Wood, Brent; Winter, Stuart; Dunsmore, Kimberley P; Fulton, Robert S; Fulton, Lucinda L; Hong, Xin; Harris, Christopher C; Dooling, David J; Ochoa, Kerri; Johnson, Kimberly J; Obenauer, John C; Evans, William E; Pui, Ching-Hon; Naeve, Clayton W; Ley, Timothy J; Mardis, Elaine R; Wilson, Richard K; Downing, James R; Mullighan, Charles G

    2012-01-11

    Early T-cell precursor acute lymphoblastic leukaemia (ETP ALL) is an aggressive malignancy of unknown genetic basis. We performed whole-genome sequencing of 12 ETP ALL cases and assessed the frequency of the identified somatic mutations in 94 T-cell acute lymphoblastic leukaemia cases. ETP ALL was characterized by activating mutations in genes regulating cytokine receptor and RAS signalling (67% of cases; NRAS, KRAS, FLT3, IL7R, JAK3, JAK1, SH2B3 and BRAF), inactivating lesions disrupting haematopoietic development (58%; GATA3, ETV6, RUNX1, IKZF1 and EP300) and histone-modifying genes (48%; EZH2, EED, SUZ12, SETD2 and EP300). We also identified new targets of recurrent mutation including DNM2, ECT2L and RELN. The mutational spectrum is similar to myeloid tumours, and moreover, the global transcriptional profile of ETP ALL was similar to that of normal and myeloid leukaemia haematopoietic stem cells. These findings suggest that addition of myeloid-directed therapies might improve the poor outcome of ETP ALL.

  10. Gemtuzumab Ozogamicin in Treating Patients With Acute Myeloid Leukemia

    Science.gov (United States)

    2013-09-23

    Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Promyelocytic Leukemia (M3); Recurrent Adult Acute Myeloid Leukemia

  11. Thiotepa-based versus total body irradiation-based myeloablative conditioning prior to allogeneic stem cell transplantation for acute myeloid leukaemia in first complete remission: a retrospective analysis from the Acute Leukemia Working Party of the European Group for Blood and Marrow Transplantation.

    Science.gov (United States)

    Eder, Sandra; Labopin, Myriam; Arcese, William; Or, Reuven; Majolino, Ignazio; Bacigalupo, Andrea; de Rosa, Gennaro; Volin, Liisa; Beelen, Dietrich; Veelken, Hendrik; Schaap, Nicolaas P M; Kuball, Jurgen; Cornelissen, Jan; Nagler, Arnon; Mohty, Mohamad

    2016-01-01

    Thiotepa is an alkylating compound with an antineoplastic and myeloablative activity and can mimic the effect of radiation. However, it is unknown whether this new regimen could safely replace the long-established ones. This retrospective matched-pair analysis evaluated the outcome of adults with acute myeloid leukaemia in first complete remission who received myeloablative conditioning either with a thiotepa-based (n = 121) or a cyclophosphamide/total body irradiation-based (TBI; n = 358) regimen for allogeneic hematopoietic stem cell transplantation from an HLA-matched sibling or an unrelated donor. With a median follow-up of 44 months, the outcome was similar in both groups. Acute graft-versus-host disease grade II-IV was observed in 25% after thiotepa-containing regimen versus 35% after TBI (P = 0.06). The 2-yr cumulative incidence of chronic graft-versus-host disease was 40.5% for thiotepa and 41% for TBI (P = 0.98). At 2 yrs, the cumulative incidences of non-relapse mortality and relapse incidence were 23.9% (thiotepa) vs. 22.4% (TBI; P = 0.66) and 17.2% (thiotepa) vs. 23.3% (TBI; P = 0.77), respectively. The probabilities of leukaemia-free and overall survival at 2 yrs were not significantly different between the thiotepa and TBI groups, at 58.9% vs. 54.2% (P = 0.95) and 61.4% vs. 58% (P = 0.72), respectively. Myeloablative regimens using combinations including thiotepa can provide satisfactory outcomes, but the optimal conditioning remains unclear for the individual patient in this setting.

  12. Serum & cerebrospinal fluid ferritin levels in children with acute leukaemia.

    Science.gov (United States)

    Srinivasan, A; Rusia, U; Anand, N K; Sood, S K

    1989-06-01

    Serum and CSF ferritin were estimated in 35 consecutive patients of acute leukaemia at the time of admission and on induction of remission. Serum ferritin levels were significantly raised in 94 per cent patients of acute leukaemia. The mean (+/- SD) serum ferritin (314.36 +/- 158.4 micrograms/1) was significantly higher when compared with control values (P less than 0.001). Remission induction resulted in significant fall in serum ferritin values to a mean of 149 (+/- 98.7) micrograms/l (P less than 0.05). Serum ferritin is thus of value in assessing the state of remission and is a sensitive indicator of the leukaemic cell mass and the state of activity of the disease. CSF ferritin levels in acute leukaemia were comparable to normal control values. CSF ferritin did not reflect CNS involvement in acute leukaemia and therefore its value as a tumour marker of CNS infiltration is doubtful.

  13. Tailored therapy of adult acute leukaemia in Jehovah's Witnesses: unjustified reluctance to treat.

    Science.gov (United States)

    Laszlo, Daniele; Agazzi, Alberto; Goldhirsch, Aron; Cinieri, Saverio; Bertolini, Francesco; Rabascio, Cristina; Pruneri, Giancarlo; Calabrese, Liliana; Cocquio, Angela; Martinelli, Giovanni

    2004-04-01

    Treatment of acute leukaemia in adult Jehovah's Witnesses (JW) is challenging because of 'a priori' refusal of most physicians to apply diagnostic and therapeutic procedures to haematological abnormalities resembling acute leukaemia. Rejection of blood transfusions by individuals of this faith is usually blamed to justify this attitude, thus leading to severe personal, medical and psychological distress related to the lack of care. We therefore intended to verify whether a standard (tailored) chemotherapy, without the use of prophylactic blood product transfusions, could be applied during treatment of acute leukaemia under such circumstances. Eleven consecutive JW adult patients with acute leukaemia, all of whom had been denied care in other institutions, were treated at the European Institute of Oncology (EIO) in Milan, Italy. Five had acute lymphoblastic leukaemia (ALL) (one bcr/abl positive), six had acute myeloid leukaemia (AML) with immunophenotype and/or cytogenetic intermediate-high risk features, except one patient with acute promyelocytic leukaemia (APML). Standard induction chemotherapy [cytosine arabinoside (ARA-C) and daunorubicin (DNR) for AML, vincristine (VCR), DNR and prednisone (PDN) for ALL, all-trans retinoic acid (ATRA) and DNR for APML] with the antracycline dose of at least 30 mg/sqm were used. All patients experienced severe anaemia after induction chemotherapy despite erythropoietin. Median haemoglobin nadir for patients with ALL and AML was 4.5 g/dL (range 1.3-6.9) and 5.1 g/dL (range 2.6-6.8), respectively. Median platelet nadir counts for all patients was 14.5 x 10(9))/L (range 1-24). One patient died during induction probably due to haemorrhage. Four of five patients with ALL achieved a complete remission (CR) (including the bcr/abl case) while among patients with AML only the one with APML achieved CR. Three patients (APML = 1 and ALL = 2) are still alive and disease-free. This small series of adult patients with leukaemia illustrates

  14. Study of clinical, haematological and cytogenetic profile of patients with acute erythroid leukaemia

    Science.gov (United States)

    Linu, Jacob Abraham; Udupa, MS Namratha; Madhumathi, DS; Lakshmaiah, KC; Babu, K Govind; Lokanatha, D; Babu, MC Suresh; Lokesh, KN; Rajeev, LK; Rudresha, AH

    2017-01-01

    Background Acute erythroid leukaemia (AEL) is a rare subtype of acute myeloid leukaemia (AML), constituting cytogenetic profile of this disease, considering the rarity of its occurrence and poor prognosis. Materials and methods This study was done by retrospective analysis of data from 32 case files of patients diagnosed with AEL. Clinical details noted down were the demographic profile, peripheral blood smear details and bone marrow examination details: (1) blasts-erythroblasts and myeloblasts, (2) dysplasia in the cell lineages and (3) cytogenetic abnormalities. Results The most common presenting symptom was fever. Pancytopenia at presentation was seen in 81.25% of patients. Dysplasia was observed in bone marrow in 100% of erythroblasts and in 40% of myeloblasts in erythroid/myeloid subtype. In pure myeloid subtype, myeloid and megakaryocytic dysplasias were not obvious. Complex karyotype was noticed only in patients of pEL. Conclusion AEL is a rare group of heterogeneous diseases with many neoplastic and non-neoplastic conditions mimicking the diagnosis. The clinical presentation and cytogenetics are also non-specific, presenting additional challenges to the diagnosis. PMID:28144286

  15. Analysis of immunophenotyping characteristics and clinical prognosis of 108 patients with acute myeloid leukaemia%急性髓系白血病108例免疫表型特征与临床预后分析

    Institute of Scientific and Technical Information of China (English)

    马瑞霞; 乔振华; 叶芳; 李国霞; 任方刚; 王宏伟; 魏百合; 何玉梅; 甄祯; 周文峰

    2013-01-01

    目的 评价免疫分型在判断急性髓系白血病(AML)预后中的作用.方法 采用流式细胞术对108例初发AML患者骨髓进行免疫表型检测.结果 ①AML患者中髓系抗原表达率以CD33 (96.3%)、CD13(88.0%)、髓过氧化物酶(MPO)(88.0%)最常见,造血祖/干细胞抗原表达以CD38最常见,为95.4%;②有52.8%(57/108)AML患者同时伴有淋巴系抗原表达,主要为CD19、CD7、CD4,表达率分别为23.1%、21.3%、17.6%;③高、中、低危3组AML患者淋巴系抗原表达率进行比较,发现CD4、CD7低危组低于中危组和高危组(P均<0.01),而CD19的表达率则相反,低危组高于中、高危组(P均<0.05).结论 免疫分型在诊断AML及判断预后中起重要作用.%Objective To evaluate the impact of immunophenotyping on diagnosis and prognosis of acute myeloid leukaemia (AML). Methods Flow cytometry (FCM) was used to detect the immunophenotype of bone marrow in 108 patients with primary AML Results ①of AML patients, the expression rates of antigens were mainly CD33 (96.3%), CD13 (88.0%) and MPO (88.0%) in bone mallow. Notably, CD38 was most commonly seen in hematopoietic stem / progenitor of antigen, being 95.4%. ②There were 52.8% (57/108) AML patients had expressions of lymphoid-associated antigen, mainly CD19 (23.1%), CD7 (21.3%) and CD4 (17.6%). ③Among 3 groups of AML patients in high, moderate and low risk degrees, the lymphoid antigen expressions of CD4 and CD7 in low risk group were lower than those in moderate and high risk group (both P<0.01), which was on contrary to the expression of CD 19 (both P<0.05). Conclusion The immunophenotyping played an important role in diagnosis and prognosis of AML

  16. The role of hematopoietic stem cell transplantation in the elderly patient with acute myeloid leukaemia O papel do transplante de célula-tronco hematopoiética em pacientes idosos com leucemia mielóide aguda

    Directory of Open Access Journals (Sweden)

    Attilio Olivieri

    2008-06-01

    Full Text Available Older adults with Acute Myeloid Leukaemia (AML, when compared to younger patients with the same disease, have a poor prognosis and represent a discrete population in terms of disease biology, treatment-related complications, and overall outcome. As a result, older patients require distinctive management approaches. For 85%-95% of older AML patients, any therapy ultimately will be purely palliative. No randomized trial has ever demonstrated that any amount of post-remission therapy in older AML patients provides better outcomes than no post-remission therapy. The only studies demonstrating that long-term Disease Free Survival (DFS is possible in older AML patients have included remission induction and post-remission therapy. For these reasons alternative post-remission strategies, including autologous or allogeneic transplantation have been explored also in people over sixty considered fit for aggressive therapy. Up to now the data available from clinical trials suggest that the stem cell transplant procedure is promising, and can lead to long-term survival, but it is feasible only in a minority of fit elderly patients. The main limits of Autologous Stem Cell Transplantation (ASCT are represented by the low percentage of patients able to mobilize a sufficient amount of stem cells and by the still high relapse incidence after ASCT, especially in those with poor prognostic factors; for these patients the allogeneic transplant procedure, by using non myeloablative conditioning regimens, could offer a better chance of cure, thanks to the Graft versus Leukemia (GVL effect, but there are no prospective trials showing the superiority of any transplant approach over conventional treatment in this subset of patients.Pacientes idosos com leucemia mielóide aguda (LMA, quando comparados com pacientes jovens com a mesma doença, apresentam prognóstico pobre e representam uma população particular em termos biológicos, complicações relacionadas ao

  17. Decitabine in Treating Children With Relapsed or Refractory Acute Myeloid Leukemia or Acute Lymphoblastic Leukemia

    Science.gov (United States)

    2013-01-22

    Childhood Acute Myeloblastic Leukemia With Maturation (M2); Childhood Acute Promyelocytic Leukemia (M3); Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia

  18. Treatment of adult acute lymphoblastic leukaemia.

    Science.gov (United States)

    Jacobs, P; Wood, L; Novitzky, N

    1990-01-01

    Eighty-five consecutive patients with acute lymphoblastic leukaemia (ALL), having a median age of 24 years (range 10-69 years), underwent induction and consolidation chemotherapy with weekly parenteral vincristine, Adriamycin, l-asparaginase and daily oral prednisone (VAAP), followed by standard (CNS) prophylaxis. Maintenance therapy was given for 3 years and consisted of daily 6-mercaptopurine, weekly methotrexate and monthly intrathecal therapy, with drug intensification comprising either vincristine, Adriamycin and l-asparaginase (VAA) or cyclophosphamide, vincristine, cytosine arabinoside and prednisone (COAP). Complete remission (CR) was obtained in 59 patients (69%) and only the French-American-British (FAB) L1 morphology was a significant predictive factor (P = 0.048). Twenty-three patients failed to achieve CR and of these 12 had primary drug resistance. Median follow-up is currently 260 weeks, median predicted survival of all patients is 58 weeks and for those who achieved CR it is 104 weeks. Median duration of CR is 70 weeks. Of the prognostic factors for survival, only FAB L1 subtype was significant. Bone marrow relapses occurred in 29 patients, and of these 9 (31%) achieved CR. There has been CNS relapse in two patients and both have died. Eleven patients continue in CR off therapy, with a median of 152 weeks. This regimen is effective, with acceptable toxicity, and a number of patients are potentially cured. The incidence of resistant and relapsing disease is an argument for further intensifying both induction and postinduction therapy.

  19. Pharm GKB: Leukemia, Erythroblastic, Acute [PharmGKB

    Lifescience Database Archive (English)

    Full Text Available Overview Alternate Names: Synonym AML M6; Acute Erythroblastic Leukemia; Acute Erythroblastic Leukemias; Acu...te erythraemic myelosis [obs]; Acute erythremia [obs]; Acute erythremic myelosis [obs]; Acute... erythroid leukaemia; Acute erythroid leukemia; Acute myeloid leukaemia, M6 type; Acute myeloid le...Erythroblastic Leukemia, Acute; Erythroblastic Leukemias, Acute; Erythroleukaemia...; Erythroleukemia; Erythroleukemias; FAB M6; Leukemia, Acute Erythroblastic; Leukemia, Myeloid, Acute, M6; Leukemias, Acute

  20. Vorinostat in Treating Patients With Acute Myeloid Leukemia

    Science.gov (United States)

    2014-04-30

    Adult Acute Erythroid Leukemia (M6); Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Acute Promyelocytic Leukemia (M3); Recurrent Adult Acute Myeloid Leukemia; Refractory Cytopenia With Multilineage Dysplasia; Secondary Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

  1. Treatment of acute lymphoblastic leukaemia (ALL).

    Science.gov (United States)

    Jacobs, P; Wood, L

    1992-08-01

    Forty-six consecutive patients with acute lymphoblastic leukaemia (ALL), having a median age of 23 years (range 14 to 64), underwent induction and consolidation chemotherapy with weekly parenteral vincristine, adriamycin, l-asparaginase and daily oral prednisone (VAAP), followed by standard central nervous system (CNS) prophylaxis. Maintenance therapy was given for 3 years and consisted of daily 6-mercaptopurine, weekly methotrexate, and monthly intrathecal chemotherapy, with drug intensification comprising either vincristine, adriamycin and l-asparaginase (VAA) or cyclophosphamide, vincristine, cytosine arabinoside and prednisone (COAP). Complete remission (CR) was achieved in 36 patients (78%) and only the FAB L1 morphology was a significant predictive factor (Chi-squared = 3.91: p < 0.05). Eight of the 10 non-responders had significant drug resistance and 3 deaths were associated with marrow hypoplasia. Median follow-up is 52 months. Median duration of CR is 28 months, median survival of all patients is 16 months, and for those who achieved CR is 44 months. There was no difference between the two maintenance arms. Significant prognostic factors for survival are French-American-British (FAB) subtype, in which the L1 is better than L2 (p = 0.05), and age (p = 0.035). Nineteen patients have experienced medullary relapse and 7 (37%) achieved subsequent CR; this is durable in a single patient who underwent allogeneic bone marrow transplantation. Eight patients (17%) had CNS disease at diagnosis; 5 achieved CR and 1 is alive and disease-free at 65+ months. There has been 1 CNS relapse. These results demonstrate that prolonged remissions and survival can be achieved with this protocol and many patients possibly cured. The level of toxicity is acceptable and the pattern of induction failure indicates that a margin exists for intensifying chemotherapy and thereby possibly further improving results.

  2. Treatment Option Overview (Adult Acute Myeloid Leukemia)

    Science.gov (United States)

    ... Childhood AML Treatment Research Adult Acute Myeloid Leukemia Treatment (PDQ®)–Patient Version General Information About Adult Acute ... bleeding and forming blood clots. Smoking, previous chemotherapy treatment, and exposure to radiation may affect the risk ...

  3. Decitabine, Cytarabine, and Daunorubicin Hydrochloride in Treating Patients With Acute Myeloid Leukemia

    Science.gov (United States)

    2016-07-20

    Adult Acute Basophilic Leukemia; Adult Acute Eosinophilic Leukemia; Adult Acute Monoblastic Leukemia; Adult Acute Monocytic Leukemia; Adult Acute Myeloid Leukemia With Maturation; Adult Acute Myeloid Leukemia With t(9;11)(p22;q23); MLLT3-MLL; Adult Acute Myeloid Leukemia Without Maturation; Adult Acute Myelomonocytic Leukemia; Alkylating Agent-Related Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

  4. Pharm GKB: Leukemia, Myelomonocytic, Acute [PharmGKB

    Lifescience Database Archive (English)

    Full Text Available Overview Alternate Names: Synonym Acute Myelomonocytic Leukemia; Acute Myelomonocytic Leukemias; Acute... myelomonocytic leukaemia (clinical); Acute myelomonocytic leukemia (clinical); Acute mye...lomonocytic leukemia, FAB M4; Leukemia, Acute Myelomonocytic; Leukemia, Myeloid, Acute, M4; Leukemia, Myeloi...d, Naegeli-Type; Leukemia, Naegeli-Type Myeloid; Leukemias, Acute Myelomonocytic; Myeloid Leukemia, Acute..., M4; Myeloid Leukemia, Naegeli Type; Myeloid Leukemia, Naegeli-Type; Myelomonocytic Leukemia, Acute

  5. [Clinical and genetic background of familial myelodysplasia and acute myeloid leukemia].

    Science.gov (United States)

    Király, Péter Attila; Kállay, Krisztián; Marosvári, Dóra; Benyó, Gábor; Szőke, Anita; Csomor, Judit; Bödör, Csaba

    2016-02-21

    Myelodysplastic syndrome and acute myeloid leukaemia are mainly sporadic diseases, however, rare familial cases exist. These disorders are considered rare, but are likely to be more common than currently appreciated, and are characterized by the autosomal dominant mutations of hematopoietic transcription factors. These syndromes have typical phenotypic features and are associated with an increased risk for developing overt malignancy. Currently, four recognized syndromes could be separated: familial acute myeloid leukemia with mutated CEBPA, familial myelodysplastic syndrome/acute myeloid leukemia with mutated GATA2, familial platelet disorder with propensity to myeloid malignancy with RUNX1 mutations, and telomere biology disorders due to mutations of TERC or TERT. Furthermore, there are new, emerging syndromes associated with germline mutations in novel genes including ANKRD26, ETV6, SRP72 or DDX41. This review will discuss the current understanding of the genetic basis and clinical presentation of familial leukemia and myelodysplasia.

  6. IDH mutations in acute myeloid leukemia.

    Science.gov (United States)

    Rakheja, Dinesh; Konoplev, Sergej; Medeiros, L Jeffrey; Chen, Weina

    2012-10-01

    Acute myeloid leukemia is a heterogeneous group of diseases. Mutations of the isocitrate dehydrogenase (IDH) genes represent a novel class of point mutations in acute myeloid leukemia. These mutations prevent oxidative decarboxylation of isocitrate to α-ketoglutarate and confer novel enzymatic activity, facilitating the reduction of α-ketoglutarate to d-2-hydroxyglutarate, a putative oncometabolite. IDH1/IDH2 mutations are heterozygous, and their combined frequency is approximately 17% in unselected acute myeloid leukemia cases, 27% in cytogenetically normal acute myeloid leukemia cases, and up to 67% in acute myeloid leukemia cases with cuplike nuclei. These mutations are largely mutually exclusive. Despite many similarities of IDH1 and IDH2 mutations, it is possible that they represent distinct molecular or clinical subgroups of acute myeloid leukemia. All known mutations involve arginine (R), in codon 132 of IDH1 or codon 140 or 172 of IDH2. IDH1(R132) and IDH2(R140) mutations are frequently accompanied by normal cytogenetics and NPM1 mutation, whereas IDH2(R172) is frequently the only mutation detected in acute myeloid leukemia. There is increasing evidence that the prognostic impact of IDH1/2 mutations varies according to the specific mutation and also depends on the context of concurrent mutations of other genes. IDH1(R132) mutation may predict poor outcome in a subset of patients with molecular low-risk acute myeloid leukemia, whereas IDH2(R172) mutations confer a poor prognosis in patients with acute myeloid leukemia. Expression of IDH1/2 mutants induces an increase in global DNA hypermethylation and inhibits TET2-induced cytosine 5-hydroxymethylation, DNA demethylation. These data suggest that IDH1/2 mutations constitute a distinct mutational class in acute myeloid leukemia, which affects the epigenetic state, an important consideration for the development of therapeutic agents.

  7. Academic career after treatment for acute lymphoblastic leukaemia

    NARCIS (Netherlands)

    Kingma, A; Rammeloo, LAJ; van der Does-van den Berg, A; Rekers-Mombarg, L; Postma, A

    2000-01-01

    Aim-To evaluate academic career in long term survivors of childhood acute lymphoblastic leukaemia (ALL), in comparison to their healthy siblings. Patients-Ninety four children treated for ALL with cranial irradiation 18 or 25 Gy and intrathecal methotrexate as CNS prophylaxis. Median age at evaluati

  8. Acute Myeloid Leukemia - Genetics Home Reference [Genetics Home Reference (Conditions)

    Lifescience Database Archive (English)

    Full Text Available Conditions Genes Chromosomes Handbook Glossary Resources Conditions > Acute Myeloid...te myeloid leukemia with mutated CEBPA Fanconi anemia You may also search Genetics Home Reference for Acut...e Myeloid Leukemia for additional information. Published : October 27, 2014 Acute Myeloid Leukemia - Genetics Home Reference ...

  9. Ipilimumab and Decitabine in Treating Patients With Relapsed or Refractory Myelodysplastic Syndrome or Acute Myeloid Leukemia

    Science.gov (United States)

    2016-09-12

    Chimerism; Hematopoietic Cell Transplantation Recipient; Previously Treated Myelodysplastic Syndrome; RAEB-1; RAEB-2; Recurrent Adult Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

  10. Autologous Stem Cell Transplantation in Patients with Acute Myeloid Leukemia: a Single-Centre Experience

    Directory of Open Access Journals (Sweden)

    Kakucs Enikő

    2013-04-01

    Full Text Available Introduction: Autologous haemopoietic stem cell transplantation (SCT is an important treatment modality for patients with acute myeloid leukemia with low and intermediate risk disease. It has served advantages over allogenic transplantation, because it does not need a matched donor, there is no graft versus host disease, there are less complications and a faster immune reconstitution than in the allo-setting. The disadvantage is the lack of the graft versus leukaemia effect.

  11. Gemtuzumab Ozogamicin in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia or Acute Promyelocytic Leukemia

    Science.gov (United States)

    2016-07-26

    Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Promyelocytic Leukemia (M3); Childhood Acute Promyelocytic Leukemia (M3); Recurrent Adult Acute Myeloid Leukemia; Recurrent Childhood Acute Myeloid Leukemia

  12. Acute myeloid leukemia presenting as galactorrhea

    Science.gov (United States)

    Nambiar, K. Rakul; Devi, R. Nandini

    2016-01-01

    Acute myeloid leukemia (AML) presents with symptoms related to pancytopenia (weakness, infections, bleeding diathesis) and organ infiltration with leukemic cells. Galactorrhea is an uncommon manifestation of AML. We report a case of AML presenting with galactorrhea. PMID:27695173

  13. Acute myeloid leukemia presenting as galactorrhea

    OpenAIRE

    Nambiar, K. Rakul; Nair, Sreejith G.; Devi, R. Nandini

    2016-01-01

    Acute myeloid leukemia (AML) presents with symptoms related to pancytopenia (weakness, infections, bleeding diathesis) and organ infiltration with leukemic cells. Galactorrhea is an uncommon manifestation of AML. We report a case of AML presenting with galactorrhea.

  14. BCR-ABL DERIVED PEPTIDE VACCINES FOR CHRONIC MYELOID LEUKAEMIA

    Directory of Open Access Journals (Sweden)

    M. Bocchia

    2012-01-01

    Full Text Available Chronic Myeloid Leukemia (CML is a myeloproliferative pluripotent stem cell disorder characterized by the presence of a cytogenetic hallmark, the Philadelphia (Ph chromosome, and accounts for 15% of adult leukemias. The disease progresses from a chronic phase through an accelerated phase to a blast phase and its natural course accounts for a median 4 years survival1. The Ph chromosome is derived by a reciprocal translocation termed t(9;22 in which the c-abl oncogene has moved from chromosome 9 into the breakpoint cluster region (bcr, within the bcr gene on chromosome 22, resulting in a chimeric bcr-abl fusion gene that encodes a 210 KD protein (p210 with constitutive tyrosine kinase activity. Two major alternative chimeric p210 can result from this fusion gene: p210-b2a2 where the junction occurs between bcr exon 2 (b2 and abl exon 2 (a2 and p210-b3a2 where the the junction occurs between bcr exon 3 (b3 and abl exon 2 (a2. About 40% of CML patients harbor the p210-b2a2 and about 60% of them show the p210-b3a2.

  15. High-flow priapism in acute lymphatic leukaemia

    Energy Technology Data Exchange (ETDEWEB)

    Mentzel, Hans-Joachim; Vogt, Susanna; Kaiser, Werner A. [Institute of Diagnostic and Interventional Radiology, Department of Pediatric Radiology, Friedrich-Schiller-Universitaet Jena, Bachstrasse 18, 07740, Jena (Germany); Kentouche, Karim; Doerfel, Claus; Zintl, Felix [Department of Paediatrics, University of Jena (Germany)

    2004-07-01

    Priapism is defined as prolonged and persistent erection of the penis without sexual stimulation. It is associated with excessive hyperleukocytosis (e.g. in acute or chronic leukaemia); however, this complication is rarely seen in the pediatric population. We report a 12-year-old boy suffering from acute leukaemia presenting with, at first intermittent, but increasingly persistent erection. Doppler US revealed signs of high-flow priapism. MRI excluded intrapelvic tumour masses, and three-dimensional contrast-enhanced MR angiography could not demonstrate an arteriovenous fistula or thrombosis. Cavernosal blood-gas measurement was in agreement with high-flow priapism. On the basis of the imaging findings, invasive therapeutic management was avoided in our patient with a successful outcome. (orig.)

  16. SCENARIO OF ACUTE LYMPHOBLASTIC LEUKAEMIA IN GWALIOR REGION

    Directory of Open Access Journals (Sweden)

    Mangal

    2016-04-01

    Full Text Available BACKGROUND Leukaemia is the most prevalent childhood cancer and Acute Lymphoblastic Leukaemia (ALL constitutes about 75% of all cases. The most frequent presenting symptoms are fever, weight loss and pallor. Early diagnosis of this haematological malignancy can be helpful for prognosis of disease. AIMS AND OBJECTIVES The objectives of the present study were to assess frequency of presenting symptoms, laboratory data and prognostic factors in children with diagnosis of ALL. MATERIALS AND METHODS The present study (2014 was performed in the Department of Pathology of Gajra Raja Medical College, Gwalior, over a period of one year from October 2013 to September 2014. The blood samples were received from patients attending various Departments of Jayarogya Groups of Hospitals, a tertiary care hospital. RESULTS Out of the 37 cases diagnosed as Acute Lymphoblastic Leukaemia, 25 (67.57% were male and 12 (32.43% were female, (male:female ratio: 2.1:1; 43.35% of patients which comprises highest number of cases belonged to 11-20 years of age group. The most frequent presenting symptoms was fever (83.78% followed by weakness (70.27% and loss of appetite (27%, while most frequent presenting sign was pallor (86.48% followed by lymphadenopathy (67.57% and splenomegaly (48.65%. Complete blood cell count was abnormal in all of the patients and pancytopenia was detected in 10.81% of the patients. Of all the patients, 91.89% had abnormal White Blood Cell (WBC count at presentation with about 80% were presented with Leukocytosis. FAB L1 subtype was more common as compared to FAB L2 subtype. CONCLUSION In our study (2014, Acute Lymphoblastic Leukaemia was more prevalent in males than in females and more common in childhood than in adult. FAB L1 subtype was more common as compared to FAB L2 subtype.

  17. Decitabine With or Without Bortezomib in Treating Older Patients With Acute Myeloid Leukemia

    Science.gov (United States)

    2016-03-14

    Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome; Adult Acute Megakaryoblastic Leukemia; Adult Acute Monoblastic Leukemia; Adult Acute Monocytic Leukemia; Adult Acute Myeloid Leukemia With Minimal Differentiation; Adult Acute Myeloid Leukemia With t(9;11)(p22;q23); MLLT3-MLL; Adult Acute Myeloid Leukemia Without Maturation; Adult Erythroleukemia; Adult Pure Erythroid Leukemia; Alkylating Agent-Related Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

  18. Chronic Myeloid Leukaemia Presenting as Bilateral Retinal Haemorrhages with Multiple Retinal Infiltrates.

    Science.gov (United States)

    Rane, Priyanka Ramkrishna; Barot, Rakesh K; Gohel, Devadatta Jayantilal; Bhagat, Nupur

    2016-05-01

    Chronic Myeloid Leukaemia (CML) causes retinopathy manifesting as venous dilation and tortuosity, perivascular sheathing, retinal haemorrhages, microaneurysms, cotton-wool spots and optic nerve infiltration. Retina is the most commonly involved intraocular structure in CML. However, retinal involvement is a rare form of presentation of CML and few cases have been reported. We report a case of CML presenting as unilateral sudden visual loss. Fundus showed multiple white centered retinal haemorrhages in both eyes with unilateral macular oedema. Blood work-up showed raised WBC count, high platelet count and low Haemoglobin. Cytological analysis of bone marrow biopsy confirmed Philadelphia chromosome. After a course of Imatinib, visual acuity improved and haemorrhages resolved with normalization of macular thickness. In our case, patient presented early, leading to early detection producing better visual prognosis. This highlights the importance of detailed hematological work up in patients with retinal involvement to rule out leukaemic retinopathy.

  19. AR-42 and Decitabine in Treating Patients With Acute Myeloid Leukemia

    Science.gov (United States)

    2016-04-21

    Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Recurrent Adult Acute Myeloid Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

  20. Clofarabine, Cytarabine, and G-CSF in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia

    Science.gov (United States)

    2015-05-05

    Acute Myeloid Leukemia; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Promyelocytic Leukemia (M3); Recurrent Adult Acute Myeloid Leukemia

  1. Romidepsin in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia

    Science.gov (United States)

    2015-12-03

    Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Promyelocytic Leukemia (M3); Recurrent Adult Acute Myeloid Leukemia

  2. Differentiation Therapy of Acute Myeloid Leukemia

    Directory of Open Access Journals (Sweden)

    Elzbieta Gocek

    2011-05-01

    Full Text Available Acute Myeloid Leukemia (AML is a predominant acute leukemia among adults, characterized by accumulation of malignantly transformed immature myeloid precursors. A very attractive way to treat myeloid leukemia, which is now called ‘differentiation therapy’, was proposed as in vitro studies have shown that a variety of agents stimulate differentiation of the cell lines isolated from leukemic patients. One of the differentiation-inducing agents, all-trans retinoic acid (ATRA, which can induce granulocytic differentiation in myeloid leukemic cell lines, has been introduced into clinics to treat patients with acute promyelocytic leukemia (APL in which a PML-RARA fusion protein is generated by a t(15;17(q22;q12 chromosomal translocation. Because differentiation therapy using ATRA has significantly improved prognosis for patients with APL, many efforts have been made to find alternative differentiating agents. Since 1,25-dihydroxyvitamin D3 (1,25D is capable of inducing in vitro monocyte/macrophage differentiation of myeloid leukemic cells, clinical trials have been performed to estimate its potential to treat patients with AML or myelodysplastic syndrome (MDS. Unfortunately therapeutic concentrations of 1,25D can induce potentially fatal systemic hypercalcemia, thus limiting clinical utility of that compound. Attempts to overcome this problem have focused on the synthesis of 1,25D analogs (VDAs which retain differentiation inducing potential, but lack its hypercalcemic effects. This review aims to discuss current problems and potential solutions in differentiation therapy of AML.

  3. Differentiation Therapy of Acute Myeloid Leukemia

    Energy Technology Data Exchange (ETDEWEB)

    Gocek, Elzbieta; Marcinkowska, Ewa, E-mail: ema@cs.uni.wroc.pl [Department of Biotechnology, University of Wroclaw, ul Tamka 2, Wroclaw 50-137 (Poland)

    2011-05-16

    Acute Myeloid Leukemia (AML) is a predominant acute leukemia among adults, characterized by accumulation of malignantly transformed immature myeloid precursors. A very attractive way to treat myeloid leukemia, which is now called ‘differentiation therapy’, was proposed as in vitro studies have shown that a variety of agents stimulate differentiation of the cell lines isolated from leukemic patients. One of the differentiation-inducing agents, all-trans retinoic acid (ATRA), which can induce granulocytic differentiation in myeloid leukemic cell lines, has been introduced into clinics to treat patients with acute promyelocytic leukemia (APL) in which a PML-RARA fusion protein is generated by a t(15;17)(q22;q12) chromosomal translocation. Because differentiation therapy using ATRA has significantly improved prognosis for patients with APL, many efforts have been made to find alternative differentiating agents. Since 1,25-dihydroxyvitamin D{sub 3} (1,25D) is capable of inducing in vitro monocyte/macrophage differentiation of myeloid leukemic cells, clinical trials have been performed to estimate its potential to treat patients with AML or myelodysplastic syndrome (MDS). Unfortunately therapeutic concentrations of 1,25D can induce potentially fatal systemic hypercalcemia, thus limiting clinical utility of that compound. Attempts to overcome this problem have focused on the synthesis of 1,25D analogs (VDAs) which retain differentiation inducing potential, but lack its hypercalcemic effects. This review aims to discuss current problems and potential solutions in differentiation therapy of AML.

  4. The effect of dietary intake changes on nutritional status in acute leukaemia patients after first induction chemotherapy.

    Science.gov (United States)

    Malihi, Z; Kandiah, M; Chan, Y M; Esfandbod, M; Vakili, M; Hosseinzadeh, M; Zarif Yeganeh, M

    2015-07-01

    This study aimed to evaluate how changes in dietary intake among acute lymphoblastic and acute myeloid leukaemia (ALL and AML) patients affect nutritional status after the first induction chemotherapy. Dietary intake was assessed using 24-h recall and a 136-item food frequency questionnaire. Nutritional status was assessed by Patients Subjective Global Assessment questionnaire before starting induction therapy and again after 1 month. All newly diagnosed acute leukaemia patients aged 15 years old and older who attended three referral hospitals for initiation of their induction chemotherapy were included in the sample selection provided that they gave informed consent. A total of 30 AML and 33 ALL patients participated in the study. Dietary intake and nutritional status worsened after the chemotherapy treatment. Dietary intake in terms of macronutrients, micronutrients, food variety and diet diversity score changed significantly after the induction chemotherapy. No significant relationship was found between the changes in dietary indices and nutritional status. Chemotherapy-related side effects as an additional factor to cancer itself could affect dietary intake of leukaemia patients. The effectiveness of an early assessment of nutritional status and dietary intake should be further investigated in order to deter further deterioration.

  5. [Disseminated fusariosis in a patient with acute lymphoblastic leukaemia

    DEFF Research Database (Denmark)

    Hermansen, N.E.; Ralfkiaer, E.M.; Kjeldsen, L.

    2008-01-01

    Invasive mould infections are a major cause of infectious mortality in highly immunosuppressed patients. Incidence in this high risk group is 10-20% with a death rate in excess of 50%. Most invasive moulds are Aspergillus spp. We present a case of a 74-year-old woman with acute lymphoblastic...... leukaemia who developed a rare disseminated mould infection with Fusarium solani during induction chemotherapy. We present the case story and discuss the pathogenesis, clinical characteristics and treatment of invasive fusariosis Udgivelsesdato: 2008/9/8...

  6. Treatment strategies in acute myeloid leukemia

    NARCIS (Netherlands)

    Han Li-na, [No Value; Zhou Jin, [No Value; Schuringa, Jan Jacob; Vellenga, Edo

    2011-01-01

    Objective To summarize the risk stratification and current treatment strategies for acute myeloid leukemia (AML) and discuss the role of emerging novel agents that might be applied in future clinical trials. Data sources The data in this article were collected from PubMed database with relevant Engl

  7. Cytarabine dose for acute myeloid leukemia

    NARCIS (Netherlands)

    B. Löwenberg (Bob); T. Pabst (Thomas); E. Vellenga (Edo); W. van Putten; H.C. Schouten (Harry); C. Graux (Carlos); A. Ferrant (Augustin); P. Sonneveld (Pieter); B.J. Biemond (Bart); A. Gratwohl (Alois); G.E. de Greef (Georgine); L.F. Verdonck (Leo); M.R. Schaafsma (Martijn); M. Gregor (Michael); M. Theobald; U. Schanz (Urs); J. Maertens (Johan); G.J. Ossenkoppele (Gert)

    2011-01-01

    textabstractBACKGROUND: Cytarabine (ara-C) is an important drug in the treatment of acute myeloid leukemia (AML). High-dose cytarabine (2000 to 3000 mg per square meter of body-surface area) is toxic but results in higher rates of relapse-free survival than does the conventional dose of 100 to 400 m

  8. Cytarabine Dose for Acute Myeloid Leukemia

    NARCIS (Netherlands)

    Lowenberg, Bob; Pabst, Thomas; Vellenga, Edo; van Putten, Wim; Schouten, Harry C.; Graux, Carlos; Ferrant, Augustin; Sonneveld, Pieter; Biemond, Bart J.; Gratwohl, Alois; de Greef, Georgine E.; Verdonck, Leo F.; Schaafsma, Martijn R.; Gregor, Michael; Theobald, Matthias; Schanz, Urs; Maertens, Johan; Ossenkoppele, Gert J.

    2011-01-01

    BACKGROUND Cytarabine (ara-C) is an important drug in the treatment of acute myeloid leukemia (AML). High-dose cytarabine (2000 to 3000 mg per square meter of body-surface area) is toxic but results in higher rates of relapse-free survival than does the conventional dose of 100 to 400 mg per square

  9. Selumetinib in Treating Patients With Recurrent or Refractory Acute Myeloid Leukemia

    Science.gov (United States)

    2015-07-06

    Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Promyelocytic Leukemia (M3); Myelodysplastic Syndromes; Myelodysplastic/Myeloproliferative Neoplasms; Recurrent Adult Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia

  10. Probability Prediction in Multistate Survival Models for Patients with Chronic Myeloid Leukaemia

    Institute of Scientific and Technical Information of China (English)

    FANG Ya; Hein Putter

    2005-01-01

    In order to find an appropriate model suitable for a multistate survival experiment, 634 patients with chronic myeloid leukaemia (CML) were selected to illustrate the method of analysis.After transplantation, there were 4 possible situations for a patient: disease free, relapse but still alive, death before relapse, and death after relapse. The last 3 events were considered as treatment failure. The results showed that the risk of death before relapse was higher than that of the relapse,especially in the first year after transplantation with competing-risk method. The result of patients with relapse time less than 12 months was much poor by the Kaplan-Meier method. And the multistate survival models were developed, which were detailed and informative based on the analysis of competing risks and Kaplan-Meier analysis. With the multistate survival models, a further analysis on conditional probability was made for patients who were disease free and still alive at month 12 after transplantation. It was concluded that it was possible for an individual patient to predict the 4 possible probabilities at any time. Also the prognoses for relapse either death or not and death either before or afterrelapse may be given. Furthermore, the conditional probabilities for patients who were disease free and still alive in a given time after transplantation can be predicted.

  11. Decitabine in Treating Patients With Myelodysplastic Syndromes or Acute Myeloid Leukemia

    Science.gov (United States)

    2013-09-27

    Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Atypical Chronic Myeloid Leukemia, BCR-ABL1 Negative; de Novo Myelodysplastic Syndromes; Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndromes; Untreated Adult Acute Myeloid Leukemia

  12. Acute myeloid leukemia in the pregnant patient.

    Science.gov (United States)

    Thomas, Xavier

    2015-08-01

    Although acute myeloid leukemia (AML) mostly occurs in older patients, it could be seen in women of childbearing age. It is therefore not surprising that in some patients, the management of AML will be complicated by a coexistent pregnancy. However, the association of leukemia and pregnancy is uncommon. Its incidence is estimated to be 1 in 75,000-100,000 pregnancies. During pregnancy, most leukemias are acute: two-thirds are myeloid and one-third are lymphoblastic. There is no standard approach for this clinical dilemma, in part because of variables such as the type of AML, the seriousness of the symptoms, and the patient's personal beliefs. In many cases, the diagnostic workup has to be altered because of the pregnancy, and often available treatments have varying risks to the fetus. While chemotherapy is reported to have some risks during the first trimester, it is admitted that it can be administered safely during the second and the third trimesters.

  13. Bortezomib in Treating Patients With High-Risk Acute Myeloid Leukemia in Remission

    Science.gov (United States)

    2014-10-30

    Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome; Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Promyelocytic Leukemia (M3); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Secondary Acute Myeloid Leukemia

  14. Midostaurin and Decitabine in Treating Older Patients With Newly Diagnosed Acute Myeloid Leukemia and FLT3 Mutation

    Science.gov (United States)

    2016-10-10

    Acute Myeloid Leukemia With FLT3/ITD Mutation; Acute Myeloid Leukemia With Gene Mutations; FLT3 Tyrosine Kinase Domain Point Mutation; Secondary Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

  15. Decitabine, Donor Natural Killer Cells, and Aldesleukin in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia

    Science.gov (United States)

    2016-01-07

    Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Recurrent Adult Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia

  16. Management of acute myeloid leukemia during pregnancy.

    Science.gov (United States)

    Avivi, Irit; Brenner, Benjamin

    2014-06-01

    Diagnosis of acute leukemia during pregnancy presents significant medical challenges. Pancytopenia, caused by bone marrow substitution with leukemic cells, impairs maternal and fetal health. Chemotherapeutic agents required to be immediately used to save the mother's life are likely to adversely affect fetal development and outcome, especially if administered at an early gestational stage. Patients diagnosed with acute leukemia during the first trimester are, therefore, recommended to undergo pregnancy termination. At later gestational stages, antileukemic therapy can be administered, although in this case, fetal outcome is still associated with increased incidence of growth restriction and loss. Special attention to the issue of future reproduction, adopting a personalized fertility preservation approach, is required. This article addresses these subjects, presenting women diagnosed with acute myeloid and acute promyelocytic leukemia in pregnancy. The rarity of this event, resulting in insufficient data, emphasizes the need for collaborative efforts to optimize management of this complicated clinical condition.

  17. A 17-gene stemness score for rapid determination of risk in acute leukaemia.

    Science.gov (United States)

    Ng, Stanley W K; Mitchell, Amanda; Kennedy, James A; Chen, Weihsu C; McLeod, Jessica; Ibrahimova, Narmin; Arruda, Andrea; Popescu, Andreea; Gupta, Vikas; Schimmer, Aaron D; Schuh, Andre C; Yee, Karen W; Bullinger, Lars; Herold, Tobias; Görlich, Dennis; Büchner, Thomas; Hiddemann, Wolfgang; Berdel, Wolfgang E; Wörmann, Bernhard; Cheok, Meyling; Preudhomme, Claude; Dombret, Herve; Metzeler, Klaus; Buske, Christian; Löwenberg, Bob; Valk, Peter J M; Zandstra, Peter W; Minden, Mark D; Dick, John E; Wang, Jean C Y

    2016-12-15

    Refractoriness to induction chemotherapy and relapse after achievement of remission are the main obstacles to cure in acute myeloid leukaemia (AML). After standard induction chemotherapy, patients are assigned to different post-remission strategies on the basis of cytogenetic and molecular abnormalities that broadly define adverse, intermediate and favourable risk categories. However, some patients do not respond to induction therapy and another subset will eventually relapse despite the lack of adverse risk factors. There is an urgent need for better biomarkers to identify these high-risk patients before starting induction chemotherapy, to enable testing of alternative induction strategies in clinical trials. The high rate of relapse in AML has been attributed to the persistence of leukaemia stem cells (LSCs), which possess a number of stem cell properties, including quiescence, that are linked to therapy resistance. Here, to develop predictive and/or prognostic biomarkers related to stemness, we generated a list of genes that are differentially expressed between 138 LSC(+) and 89 LSC(-) cell fractions from 78 AML patients validated by xenotransplantation. To extract the core transcriptional components of stemness relevant to clinical outcomes, we performed sparse regression analysis of LSC gene expression against survival in a large training cohort, generating a 17-gene LSC score (LSC17). The LSC17 score was highly prognostic in five independent cohorts comprising patients of diverse AML subtypes (n = 908) and contributed greatly to accurate prediction of initial therapy resistance. Patients with high LSC17 scores had poor outcomes with current treatments including allogeneic stem cell transplantation. The LSC17 score provides clinicians with a rapid and powerful tool to identify AML patients who do not benefit from standard therapy and who should be enrolled in trials evaluating novel upfront or post-remission strategies.

  18. Environmental factors and leukaemia

    Energy Technology Data Exchange (ETDEWEB)

    Brandt, L.

    1985-01-01

    Investigations on the association between environmental hazards and the development of various types of leukaemia are reviewed. Regarding acute non-lymphocytic leukaemia (ANLL) exposure to ionizing radiation is a well-documented risk factor. According to several recent studies exposure to strong electromagnetic fields may be suspected to be of etiologic importance for ANLL. There is evidence that occupational handling of benzene is a risk factor and other organic solvents may also be leukaemogenic. Occupational exposure to petrol products has been proposed to be a risk factor although the hazardous substances have not yet been defined. Results of cytogenetic studies in ANLL suggest that exposure to certain environmental agents may be associated with relatively specific clonal chromosome aberrations. Exposure in utero to ionizing radiation has been proposed to be a risk factor for acute lymphocytic leukaemia (ALL) in children. Unlike ANLL there seems at present to be little evidence that ALL is related to exposure to some chemicals. Chronic myeloid leukaemia (CML) may follow exposure to high doses of ionizing radiation whereas such exposure seems to be of insignificant importance for the development of chronic lymphocytic leukaemia (CLL). According to some studies an abnormally high incidence of CLL may be found among farmers in the USA. These results have not been confirmed in Scandinavian studies. There seems to be little evidence that CML or CLL are related to occupational handling of some chemicals. 35 references.

  19. Precision Medicine for Acute Myeloid Leukemia

    Science.gov (United States)

    Lai, Catherine; Karp, Judith E.; Hourigan, Christopher S.

    2016-01-01

    The goal of precision medicine is to personalize therapy based on individual patient variation, to correctly select the right treatment, for the right patient, at the right time. Acute myeloid leukemia (AML) is a heterogeneous collection of myeloid malignancies with diverse genetic etiology and the potential for intra-patient clonal evolution over time. We discuss here how the precision medicine paradigm might be applied to the care of AML patients by focusing on the potential roles of targeting therapy by patient-specific somatic mutations and aberrant pathways, ex-vivo drug sensitivity and resistance testing, high sensitivity measurements of residual disease burden and biology along with potential clinical trial and regulatory constraints. PMID:26514194

  20. New Complex Chromosomal Translocation in Chronic Myeloid Leukaemia: t(9;18;22(q34;p11;q11

    Directory of Open Access Journals (Sweden)

    Abdeljabar El Andaloussi

    2007-01-01

    Full Text Available A Chronic myeloid leukaemia (CML case with a new complex t(9;18;22(q34;p11;q11 of a 29-year-old man is being reported. For the first time, this translocation has been characterized by karyotype complemented with fluorescence in situ hybridization (FISH. In CML, the complex and standard translocations have the same prognosis. The patient was treated with standard initial therapy based on hydroxyurea before he died due to heart failure four months later. Our finding indicates the importance of combined cytogenetic analysis for diagnosis and guidance of treatment in clinical diagnosis of CML.

  1. Proven/Probable Invasive Fungal Infection in hematologic patients with Acute Myeloid Leukaemia and/or in Allogeneic Hematopoietic Stem Cell Transplant recipients. | EU Clinical Trials Register [EU Clinical Trials Register

    Lifescience Database Archive (English)

    Full Text Available ni fungine invasive certe/probabilili in pazienti ematologici con leucemia mieloide acuta e/o in pazienti co... settimane come terapia di mantenimento per infezioni fungine invasive certe/probabilili in pazienti ematologici con leucemia...oietic Stem Cell Transplant recipients. infezioni fungine invasive certe/probabilili in pazienti ematologici con leucemia... recipients. infezioni fungine invasive certe/probabilili in pazienti ematologici con leucemia mieloide acut...ndard con L-AMB 3 mg / kg una volta al giorno nei pazienti ematologici in trattamento per leucemia

  2. Liver Involvement with Acute Myeloid Leukemia

    Directory of Open Access Journals (Sweden)

    Emily Mathews

    2008-03-01

    Full Text Available Liver involvement with acute myeloid leukemia (AML is rarely reported. The majority of published cases suggest a cholestatic picture and obstructive jaundice at presentation. On the contrary, our patient presented with transaminitis without cholestasis. Elevated liver function tests persisted in our patient despite cholecystectomy; however, they normalized with chemotherapy administration, suggesting that AML was the causative effect of the hepatitis-like picture. Our review of the literature revealed that most reported cases of AML with liver involvement had short-lived remissions and an overall ominous prognosis. In our opinion, patients who have liver involvement with AML should be offered alternative investigational therapies with a low hepatic toxicity profile.

  3. Blood group change in acute myeloid leukemia

    Science.gov (United States)

    Nambiar, Rakul K.; Prakash, N. P.; Vijayalakshmi, K.

    2017-01-01

    Blood group antigens are either sugars or proteins found attached to the red blood cell membrane. ABO blood group antigens are the most clinically important antigens because they are the most immunogenic. As red blood cell antigens are inherited traits, they are usually not altered throughout the life of an individual. There have been occasional case reports of ABO blood group antigen change in malignant conditions. We report two such cases of ABO antigen alteration associated with acute myeloid leukemia. These patients had suppression of their blood group antigens during their leukemic phase, and the antigens were reexpressed when the patients attained remission.

  4. Decitabine, Vorinostat, and Cytarabine in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia

    Science.gov (United States)

    2014-12-19

    Adult Acute Myeloid Leukemia With Inv(16)(p13.1q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With t(16;16)(p13.1;q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); RUNX1-RUNX1T1; Adult Acute Myeloid Leukemia With t(9;11)(p22;q23); MLLT3-MLL; Adult Acute Promyelocytic Leukemia With t(15;17)(q22;q12); PML-RARA; Alkylating Agent-Related Acute Myeloid Leukemia; Recurrent Adult Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia

  5. Is this acute lymphoblastic leukaemia or juvenile rheumatoid arthritis.

    Science.gov (United States)

    Kirubakaran, Chellam; Scott, Julius Xavier; Ebenezer, Sam

    2011-08-01

    Arthritis could be a presenting feature of acute lymphoblastic leukaemia (ALL) and could be wrongly diagnosed as juvenile rheumatoid arthritis (JRA). Clinical and laboratory parameters might differentiate ALL and JRA in children who present with arthritis. Out of a total of 250 children of ALL, 10 were referred to the department of child health and paediatric haemato-oncology of Christian Medical College, Vellore during 1990-2002. They were compared with 10 age-matched children who had systematic onset of JRA. The age groups in ALL and JRA were 6.05 +/- 2.45 years and 5.47 +/- 4.4 years respectively. Severe pain as evidenced by inability to walk was found in children but one child with JRA was unable to walk (p JRA group. ESR was elevated in all cases in both the groups. One case in each group had antinuclear antibody positivity. It can be concluded that ALL can masquerade as systematic onset of JRA. So paediatricians should be careful enough while diagnosing the disease process.

  6. A new Leukemia Prognostic Scoring System for refractory/relapsed adult acute myelogeneous leukaemia patients: a GOELAMS study.

    Science.gov (United States)

    Chevallier, P; Labopin, M; Turlure, P; Prebet, T; Pigneux, A; Hunault, M; Filanovsky, K; Cornillet-Lefebvre, P; Luquet, I; Lode, L; Richebourg, S; Blanchet, O; Gachard, N; Vey, N; Ifrah, N; Milpied, N; Harousseau, J-L; Bene, M-C; Mohty, M; Delaunay, J

    2011-06-01

    A simplified prognostic score is presented based on the multivariate analysis of 138 refractory/relapsed acute myeloid leukaemia (AML) patients (median age 55 years, range: 19-70) receiving a combination of intensive chemotherapy+Gemtuzumab as salvage regimen. Overall, 2-year event-free survival (EFS) and overall survival (OS) were 29±4% and 36±4%, respectively. Disease status (relapse Leukemia Prognostic Scoring System was then validated on an independent cohort of 111 refractory/relapsed AML patients. This new simplified prognostic score, using three clinical and biological parameters routinely applied, allow to discriminate around two third of the patients who should benefit from a salvage intensive regimen in the setting of refractory/relapsed AML patients. The other one third of the patients should receive investigational therapy.

  7. Consensus definitions of 14 severe acute toxic effects for childhood lymphoblastic leukaemia treatment

    DEFF Research Database (Denmark)

    Schmiegelow, Kjeld; Attarbaschi, Andishe; Barzilai, Shlomit

    2016-01-01

    Although there are high survival rates for children with acute lymphoblastic leukaemia, their outcome is often counterbalanced by the burden of toxic effects. This is because reported frequencies vary widely across studies, partly because of diverse definitions of toxic effects. Using the Delphi...... method, 15 international childhood acute lymphoblastic leukaemia study groups assessed acute lymphoblastic leukaemia protocols to address toxic effects that were to be considered by the Ponte di Legno working group. 14 acute toxic effects (hypersensitivity to asparaginase, hyperlipidaemia, osteonecrosis......, thromboembolism, and Pneumocystis jirovecii pneumonia) that are serious but too rare to be addressed comprehensively within any single group, or are deemed to need consensus definitions for reliable incidence comparisons, were selected for assessment. Our results showed that none of the protocols addressed all 14...

  8. Birth weight in offspring and leukaemia risk in parents-A nation-wide register-based cohort study from Denmark

    DEFF Research Database (Denmark)

    Marklund, Maria; Rostgaard, Klaus; Hjalgrim, Lisa

    2013-01-01

    Spurred by previous observations we assessed the relationship between offspring birth weight and parental leukaemia risk in a register-based investigation including 2.4 million parents of 2 million Danish children. Regardless of analytical approach, offspring birth weight was not associated...... with parental risk of leukaemia overall or of leukaemia subtypes except for a twofold increased acute lymphatic leukaemia risk in fathers of high birth weight offspring and an increasing paternal risk of chronic myeloid leukaemia with increasing offspring birth weight. These may both be chance findings. Our...... investigation indicates that offspring birth weight is not strongly associated with parental leukaemia risk....

  9. Proteasome subunit expression analysis and chemosensitivity in relapsed paediatric acute leukaemia patients receiving bortezomib-containing chemotherapy

    Directory of Open Access Journals (Sweden)

    Denise Niewerth

    2016-09-01

    Full Text Available Abstract Background Drug combinations of the proteasome inhibitor bortezomib with cytotoxic chemotherapy are currently evaluated in phase 2 and 3 trials for the treatment of paediatric acute myeloid leukaemia (AML and acute lymphocytic leukaemia (ALL. Methods We investigated whether expression ratios of immunoproteasome to constitutive proteasome in leukaemic cells correlated with response to bortezomib-containing re-induction chemotherapy in patients with relapsed and refractory acute leukaemia, enrolled in two Children’s Oncology Group phase 2 trials of bortezomib for ALL (COG-AALL07P1 and AML (COG-AAML07P1. Expression of proteasome subunits was examined in 72 patient samples (ALL n = 60, AML n = 12 obtained before start of therapy. Statistical significance between groups was determined by Mann-Whitney U test. Results Ratios of immunoproteasome to constitutive proteasome subunit expression were significantly higher in pre-B ALL cells than in AML cells for both β5i/β5 and β1i/β1 subunits (p = 0.004 and p < 0.001. These ratios correlated with therapy response in AML patients; β1i/β1 ratios were significantly higher (p = 0.028 between patients who did (n = 4 and did not reach complete remission (CR (n = 8, although for β5i/β5 ratios, this did not reach significance. For ALL patients, the subunit ratios were also higher for patients who showed a good early response to therapy but this relation was not statistically significant. Overall, for this study, the patients were treated with combination therapy, so response was not only attributed to proteasome inhibition. Moreover, the leukaemic blast cells were not purified for these samples. Conclusions These first ex vivo results encourage further studies into relative proteasome subunit expression to improve proteasome inhibition-containing therapy and as a potential indicator of bortezomib response in acute leukaemia.

  10. Cutaneous myeloid sarcoma: natural history and biology of an uncommon manifestation of acute myeloid leukemia.

    Science.gov (United States)

    Hurley, M Yadira; Ghahramani, Grant K; Frisch, Stephanie; Armbrecht, Eric S; Lind, Anne C; Nguyen, Tudung T; Hassan, Anjum; Kreisel, Friederike H; Frater, John L

    2013-05-01

    We conducted a retrospective study of patients with cutaneous myeloid sarcoma, from 2 tertiary care institutions. Eighty-three patients presented, with a mean age of 52 years. Diagnosis of myeloid sarcoma in the skin was difficult due to the low frequency of myeloperoxidase and/or CD34+ cases (56% and 19% of tested cases, respectively). Seventy-one of the 83 patients (86%) had ≥ 1 bone marrow biopsy. Twenty-eight (39%) had acute myeloid leukemia with monocytic differentiation. Twenty-three had other de novo acute myeloid leukemia subtypes. Thirteen patients had other myeloid neoplasms, of which 4 ultimately progressed to an acute myeloid leukemia. Seven had no bone marrow malignancy. Ninety-eight percent of the patients received chemotherapy, and approximately 89% died of causes related to their disease. Cutaneous myeloid sarcoma in most cases represents an aggressive manifestation of acute myeloid leukemia. Diagnosis can be challenging due to lack of myeloblast-associated antigen expression in many cases, and difficulty in distinguishing monocyte-lineage blasts from neoplastic and non-neoplastic mature monocytes.

  11. Importance of genetics in acute myeloid leukemia

    Directory of Open Access Journals (Sweden)

    R. Pippa

    2014-12-01

    Full Text Available Acute myeloid leukemia (AML comprises a biologically and clinically heterogeneous group of aggressive disorders that occur as a consequence of a wide variety of genetic and epigenetic abnormalities in hematopoietic progenitors. Despite significant advances in the understanding of the biology of AML, most patients will die from relapsed disease. Whole-genome studies have identified novel recurrent gene mutations with prognostic impact in AML; furthermore, it is likely that in the near future genome-wide sequencing will become a routine for newly diagnosed patients with AML. Therefore, future clinical trials should aim to identify genetically defined high-risk patients, and further research is necessary to identify effective agents and develop new individualized therapeutic strategies for the treatment of this deadly disease.

  12. Treatment strategies in acute myeloid leukemia

    Institute of Scientific and Technical Information of China (English)

    HAN Li-na; ZHOU Jin; Jan Jacob Schuringa; Edo Vellenga

    2011-01-01

    Objective To summarize the risk stratification and current treatment strategies for acute myeloid leukemia (AML) and discuss the role of emerging novel agents that might be applied in future clinical trials.Data sources The data in this article were collected from PubMed database with relevant English articles published from 1991 to 2009.Study selection Articles regarding the risk stratification and therapeutic options of AML, as well as the characteristics of leukemic stem cells were selected.Results AML is a heterogeneous disease with variable clinical outcome dependent on several prognostic factors,including age, cytogenetics and molecular markers. The advances in the understanding of AML pathogenesis and development will generate potential novel agents that might improve the treatment results of standard chemotherapy.Conclusion Deeper insight into the multiple transforming events of AML may aid us in designing combinations of small molecule inhibitors based on the individual patient characteristics.

  13. Histamine revisited: Role in acute myeloid leukemia

    Directory of Open Access Journals (Sweden)

    Prasan R Bhandari

    2013-01-01

    Full Text Available Histamine dihydrochloride (HDC is derived from biogenic amine histamine. It suppresses the production of reactive oxygen species which inhibits the stimulation of T cells and natural killer (NK cells. Co-administration of the cytokine interleukin (IL-2 and HDC assists the activation of T cells and NK cells by IL-2, causing in the destruction of cancer cells, including those of acute myeloid leukemia (AML. A significantly longer leukemia-free survival (LFS; primary endpoint was demonstrated in a phase III trial in adult patients with AML in first or subsequent remission, in those who received subcutaneous HDC and concomitant subcutaneous IL-2 as maintenance therapy compared to that of patients receiving no treatment. However, the difference in overall survival (OS between the two groups was not significant. Patients had acceptable levels of adverse effects. Thus, HDC in addition to IL-2 appears to be a useful maintenance therapy option for adult patients with AML in remission.

  14. Aplastic anaemia preceding acute lymphoblastic leukaemia in an adult with isolated deletion of chromosome 9q.

    LENUS (Irish Health Repository)

    Kelly, Kevin

    2008-12-01

    Aplastic anaemia (AA) can precede acute lymphoblastic leukaemia (ALL) in 2% of children but this is rarely reported to occur in adults. A 21-year-old male presented with bone marrow failure and bone marrow biopsy showed a profoundly hypocellular marrow. He recovered spontaneously but represented 2 months later when he was diagnosed with pre-B acute lymphoblastic leukaemia. Chromosomal examination revealed 46,XY,del(9)(q13q34). To the best of our knowledge this is the first case to be reported of aplasia preceding ALL with 9q minus as the sole chromosomal abnormality.

  15. Symptom-Adapted Physical Activity Intervention in Minimizing Physical Function Decline in Older Patients With Acute Myeloid Leukemia Undergoing Chemotherapy

    Science.gov (United States)

    2016-07-26

    Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Recurrent Adult Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

  16. Endometrial and acute myeloid leukemia cancer genomes characterized

    Science.gov (United States)

    Two studies from The Cancer Genome Atlas (TCGA) program reveal details about the genomic landscapes of acute myeloid leukemia (AML) and endometrial cancer. Both provide new insights into the molecular underpinnings of these cancers.

  17. Genome wide molecular analysis of minimally differentiated acute myeloid leukemia

    NARCIS (Netherlands)

    Silva, Fernando P. G.; Almeida, Ines; Morolli, Bruno; Brouwer-Mandema, Geeske; Wessels, Hans; Vossen, Rolf; Vrieling, Harry; Marijt, Erik W. A.; Valk, Peter J. M.; Kluin-Nelemans, Hanneke C.; Sperr, Wolfgang R.; Ludwig, Wolf-Dieter; Giphart-Gassler, Micheline

    2009-01-01

    Background Minimally differentiated acute myeloid leukemia is heterogeneous in karyotype and is defined by immature morphological and molecular characteristics. This originally French-American-British classification is still used in the new World Health Organization classification when other criteri

  18. Lenalidomide, Cytarabine, and Idarubicin in Treating Patients With Acute Myeloid Leukemia

    Science.gov (United States)

    2014-12-22

    Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome; Adult Acute Myeloid Leukemia With Inv(16)(p13.1q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With t(16;16)(p13.1;q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); RUNX1-RUNX1T1; Adult Acute Myeloid Leukemia With t(9;11)(p22;q23); MLLT3-MLL; Adult Acute Promyelocytic Leukemia With t(15;17)(q22;q12); PML-RARA; Alkylating Agent-Related Acute Myeloid Leukemia; de Novo Myelodysplastic Syndrome; Previously Treated Myelodysplastic Syndrome; Recurrent Adult Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndrome; Untreated Adult Acute Myeloid Leukemia

  19. Molecular Genetic Markers in Acute Myeloid Leukemia

    Directory of Open Access Journals (Sweden)

    Sophia Yohe

    2015-03-01

    Full Text Available Genetics play an increasingly important role in the risk stratification and management of acute myeloid leukemia (AML patients. Traditionally, AML classification and risk stratification relied on cytogenetic studies; however, molecular detection of gene mutations is playing an increasingly important role in classification, risk stratification, and management of AML. Molecular testing does not take the place of cytogenetic testing results, but plays a complementary role to help refine prognosis, especially within specific AML subgroups. With the exception of acute promyelocytic leukemia, AML therapy is not targeted but the intensity of therapy is driven by the prognostic subgroup. Many prognostic scoring systems classify patients into favorable, poor, or intermediate prognostic subgroups based on clinical and genetic features. Current standard of care combines cytogenetic results with targeted testing for mutations in FLT3, NPM1, CEBPA, and KIT to determine the prognostic subgroup. Other gene mutations have also been demonstrated to predict prognosis and may play a role in future risk stratification, although some of these have not been confirmed in multiple studies or established as standard of care. This paper will review the contribution of cytogenetic results to prognosis in AML and then will focus on molecular mutations that have a prognostic or possible therapeutic impact.

  20. Cytogenetics of pediatric acute myeloid leukemia.

    Science.gov (United States)

    Manola, Kalliopi N

    2009-11-01

    Acute myeloid leukemia (AML) is a clinically and genetically heterogeneous disease accounting for 15-20% of all childhood acute leukemias, while it is responsible for more than half of the leukemic deaths in these patients. This article focuses on the significance of cytogenetic analysis in pediatric AML supporting the importance of cytogenetic analysis in the pathogenesis, diagnosis, prognosis, follow-up and treatment selection in childhood AML. It reviews in detail the types and frequencies of most common chromosomal aberrations, their molecular background, their correlation with French American British (FAB) subtypes and age distribution and their prognostic relevance. It also summarizes some less frequent or rare chromosome aberrations in which the prognostic classification has not been determined yet owning to the small number of patients and the variable treatment modalities used in different study groups. Furthermore, it discusses the association of specific chromosome rearrangements with prenatal exposure to carcinogenic agents or therapeutic agents and highlights the ongoing and future research on pediatric AML in the evolving field of Cytogenetics.

  1. An analysis of prognostic variables in acute lymphocytic leukaemia in a heterogenous South African population

    NARCIS (Netherlands)

    Hesseling, PB; Buurman, M; Oud, C; Nel, ED

    1997-01-01

    The records of all 96 children below the age of 15 years diagnosed with acute lymphoblastic leukaemia at Tygerberg Hospital in the Republic of South African between 1983 and 1995 were reviewed to determine risk factors which may predict poor outcome. Age <2 and > 8 years, and white cell count >20 x

  2. Gemtuzumab-induced orchitis in a patient with refractory acute promyelocytic leukaemia.

    Science.gov (United States)

    Jalil-ur-Rehman; Kelta, Muhammad; Awad, Khalid; Beirouti, Basim Al; Nasser, Shahzad; Aslam, Muhammad

    2012-09-01

    We report the case of a 22-year-old Saudi male patient who was treated extensively in the past with various regimens for acute promyelocytic leukaemia that was refractory to all standard treatments. He was ultimately administered Gemtuzumab to induce remission and subjected to an allogeneic bone marrow transplant. However, he developed orchitis, which has not been previously reported with this agent.

  3. High white blood cell count at diagnosis of childhood acute lymphoblastic leukaemia

    DEFF Research Database (Denmark)

    Vaitkeviciene, Goda; Forestier, Erik; Hellebostad, Marit;

    2011-01-01

    Prognostic impact of peripheral blood white blood cell count (WBC) at the diagnosis of childhood acute lymphoblastic leukaemia (ALL) was evaluated in a population-based consecutive series of 2666 children aged 1-15 treated for ALL between 1992 and 2008 in the five Nordic countries (Denmark, Finland...

  4. Venous thromboembolism in adults treated for acute lymphoblastic leukaemia: Effect of fresh frozen plasma supplementation

    NARCIS (Netherlands)

    I. Lauw (Ivoune); B. van der Holt (Bronno); S. Middeldorp (Saskia); J.C.M. Meijers; J.J. Cornelissen (Jan); B.J. Biemond (Bart)

    2013-01-01

    textabstractTreatment of acute lymphoblastic leukaemia (ALL) is frequently complicated by venous thromboembolism (VTE). The efficacy and optimal approach of VTE prevention are unclear, particularly in adult patients. We assessed the effect of thromboprophylaxis on symptomatic VTE incidence in cycle

  5. Prognosis in childhood and adult acute lymphoblastic leukaemia : a question of maturation?

    NARCIS (Netherlands)

    Plasschaert, SLA; Kamps, WA; Vellenga, E; de Vries, EGE; de Bont, ESJM

    2004-01-01

    Acute lymphoblastic leukaemia (ALL) is a disease diagnosed in children as well as adults. Progress in the treatment of ALL has led to better survival rates, however, children have benefited more from improved treatment modalities than adults. Recent evidence has underscored that the difference in ch

  6. Human herpes virus-6 seroprevalence and leukaemias: a case-control study. GIMEMA (Gruppo Italiano Malattie Ematologiche dell' Adulto).

    Science.gov (United States)

    Gentile, G; Mele, A; Ragona, G; Faggioni, A; Zompetta, C; Tosti, M E; Visani, G; Castelli, G; Pulsoni, A; Monarca, B; Martino, P; Mandelli, F

    1999-06-01

    The relationships between acute myeloid leukaemia (AML), acute lymphocytic leukaemia (ALL), chronic myeloid leukaemia (CML) and refractory anaemia with excess of blasts (RAEB) and human herpes virus (HHV)-6 antibody level were investigated in a multicentre case-control study. An association between increased HHV-6 seropositivity and geometric mean titre ratio with AML was shown: P for trend = 0.022, adjusted odds ratio 1.20, 95% confidence interval 1.07-1.33 respectively. No association was found between HHV-6 and ALL, CML or RAEB.

  7. Combination Chemotherapy in Treating Young Patients With Down Syndrome and Acute Myeloid Leukemia or Myelodysplastic Syndromes

    Science.gov (United States)

    2017-02-07

    Childhood Acute Basophilic Leukemia; Childhood Acute Eosinophilic Leukemia; Childhood Acute Erythroleukemia (M6); Childhood Acute Megakaryocytic Leukemia (M7); Childhood Acute Minimally Differentiated Myeloid Leukemia (M0); Childhood Acute Monoblastic Leukemia (M5a); Childhood Acute Monocytic Leukemia (M5b); Childhood Acute Myeloblastic Leukemia With Maturation (M2); Childhood Acute Myeloblastic Leukemia Without Maturation (M1); Childhood Acute Myelomonocytic Leukemia (M4); Childhood Myelodysplastic Syndromes; de Novo Myelodysplastic Syndromes; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndromes; Untreated Childhood Acute Myeloid Leukemia and Other Myeloid Malignancies

  8. Arsenic Trioxide in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia

    Science.gov (United States)

    2016-10-04

    Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Recurrent Adult Acute Myeloid Leukemia

  9. Decitabine as Maintenance Therapy After Standard Therapy in Treating Patients With Previously Untreated Acute Myeloid Leukemia

    Science.gov (United States)

    2016-07-19

    Acute Myeloid Leukemia With Myelodysplasia-Related Changes; Adult Acute Myeloid Leukemia With Inv(16)(p13.1q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With t(16;16)(p13.1;q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); RUNX1-RUNX1T1; Adult Acute Myeloid Leukemia With t(9;11)(p22;q23); MLLT3-MLL; Untreated Adult Acute Myeloid Leukemia

  10. ERYTHEMA NODOSUM REVEALING ACUTE MYELOID LEUKEMIA

    Directory of Open Access Journals (Sweden)

    Chebbi Wafa

    2013-07-01

    Full Text Available Introduction: Erythema nodosum (EN is the most common type of panniculitis. It may be idiopathic or secondary to various etiologies. However, the occurrence of erythema nodosum in malignant hemopathy had rarely been reported. Case report: A 42 year-old woman presented with a four week history of recurrent multiple painful erythematous nodules developed on the lower limbs associated with arthralgia of the ankles and fever. The clinical features of skin lesions with contusiform color evolution allowed establishing the diagnosis of EN. No underlying cause was found. The skin lesions were improved with non-steroidal anti-inflammatory drugs and colchicine. Three months later, the patient consulted for recurrence of EN associated with fever, inflammatory polyarthralgia and hepatosplenomegaly. The peripheral blood count revealed pancytopenia. A bone marrow examination confirmed the diagnosis of acute myeloid leukemia type 2. Initiation of chemotherapy was followed by the complete disappearance of skin lesions of EN. Conclusion: Paraneoplastic erythema nodosum is a rare entity. In the literature, a few cases of association with leukemia have been reported. Exploration for solid neoplasms or hemopathy in case of recurrent EN or resistance to conventional treatment should be systematic

  11. Targeting the acute myeloid leukemia stem cells.

    Science.gov (United States)

    Krause, Alexandre; Luciana, M; Krause, Fontanari; Rego, Eduardo M

    2010-02-01

    The idea that within the bulk of leukemic cells there are immature progenitors which are intrinsically resistant to chemotherapy and able to repopulate the tumor after treatment is not recent. Nevertheless, the term leukemia stem cells (LSCs) has been adopted recently to describe these immature progenitors based on the fact that they share the most relevant features of the normal hematopoetic stem cells (HSCs), i.e. the self-renewal potential and quiescent status. LSCs differ from their normal counterparts and from the more differentiated leukemic cells regarding the default status of pathways regulating apoptosis, cell cycle, telomere maintenance and transport pumps activity. In addition, unique features regarding the interaction of these cells with the microenvironment have been characterized. Therapeutic strategies targeting these unique features are at different stages of development but the reported results are promising. The aim of this review is, by taking acute myeloid leukemia (AML) as a bona fide example, to discuss some of the mechanisms used by the LSCs to survive and the strategies which could be used to eradicate these cells.

  12. Novel therapeutic options in Acute Myeloid Leukemia

    Directory of Open Access Journals (Sweden)

    Michael Medinger

    2016-01-01

    Full Text Available Acute myeloid leukemia (AML is a biologically complex and molecularly and clinically heterogeneous disease, and its incidence is increasing as the population ages. Cytogenetic anomalies and mutation testing remain important prognostic tools for tailoring treatment after induction therapy. Despite major advances in understanding the genetic landscape of AML and its impact on the pathophysiology and biology of the disease, as well as the rapid development of new drugs, standard treatment options have not experienced major changes during the past three decades. Especially for patients with intermediate or high-risk AML, which often show relapse. Allogeneic hematopoietic stem cell transplantation (HSCT remains the best chance for cure. Here we review the state of the art therapy of AML, with special focus on new developments in immunotherapies and cellular therapies including HSCT and particularly discuss the impact of new conditioning and haplo-identical donor regimens for HSCT, post-transplant strategies for preventing and treating relapse, and emerging novel therapeutic options.

  13. Caspofungin Acetate or Fluconazole in Preventing Invasive Fungal Infections in Patients With Acute Myeloid Leukemia Who Are Undergoing Chemotherapy

    Science.gov (United States)

    2017-01-31

    Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Childhood Acute Erythroleukemia (M6); Childhood Acute Megakaryocytic Leukemia (M7); Childhood Acute Minimally Differentiated Myeloid Leukemia (M0); Childhood Acute Monoblastic Leukemia (M5a); Childhood Acute Monocytic Leukemia (M5b); Childhood Acute Myeloblastic Leukemia With Maturation (M2); Childhood Acute Myeloblastic Leukemia Without Maturation (M1); Childhood Acute Myeloid Leukemia in Remission; Childhood Acute Myelomonocytic Leukemia (M4); Fungal Infection; Neutropenia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia; Untreated Childhood Acute Myeloid Leukemia and Other Myeloid Malignancies

  14. Quercus Suber L. Cork Extracts Induce Apoptosis in Human Myeloid Leukaemia HL-60 Cells.

    Science.gov (United States)

    Bejarano, Ignacio; Godoy-Cancho, Belén; Franco, Lourdes; Martínez-Cañas, Manuel A; Tormo, María A

    2015-08-01

    Quercus suber L. cork contains a diversity of phenolic compounds, mostly low molecular weight phenols. A rising number of reports support with convergent findings that polyphenols evoke pro-apoptotic events in cancerous cells. However, the literature related to the anti-cancer bioactivity of Q. suber L. cork extractives (QSE) is still limited. Herein, we aim to describe the antitumor potential displayed by cork extractives obtained by different extraction methods in the human promyelocytic leukaemia cells. In order to quantify the effects of QSE on cancer cells viability, phosphatidylserine exposure, caspase-3 activity, mitochondrial membrane potential and cell cycle were evaluated. The results indicated that the QSE present a time-dependent and dose-dependent cytotoxicity in the human promyelocytic leukaemia cells. Such a noxious effect leads these leukaemia cells to their death through apoptotic processes by altering the mitochondrial outer membrane potential, activating caspase-3 and externalizing phosphatidylserine. However, cells cycle progression was not affected by the treatments. This study contributes to open a new way to use this natural resource by exploiting its anti-cancer properties. Moreover, it opens new possibilities of application of cork by-products, being more efficient in the sector of cork-based agriculture. Copyright © 2015 John Wiley & Sons, Ltd.

  15. Role of autophagy in acute myeloid leukemia therapy

    Institute of Scientific and Technical Information of China (English)

    Su-Ping Zhang; Yu-Na Niu; Na Yuan; Ai-Hong Zhang; Dan Chao; Qiu-Ping Xu; Li-Jun Wang

    2013-01-01

    Despite its dual role in determining cell fate in a wide array of solid cancer cell lines,autophagy has been robustly shown to suppress or kill acute myeloid leukemia cells via degradation of the oncogenic fusion protein that drives leukemogenesis.However,autophagy also induces the demise of acute leukemia cells that do not express the known fusion protein,though the molecular mechanism remains elusive.Nevertheless,since it can induce cooperation with apoptosis and differentiation in response to autophagic signals,autophagy can be manipulated for a better therapy on acute myeloid leukemia.

  16. Geographical and ecological analyses of childhood acute leukaemias and lymphomas in north-west England.

    Science.gov (United States)

    McNally, Richard J Q; Alston, Robert D; Cairns, Donal P; Eden, Osborn B; Birch, Jillian M

    2003-10-01

    Childhood leukaemias and lymphomas have been associated with exposure to environmental factors, including infections, which show geographical variation. This study examined the geographical distribution of the incidence of acute leukaemia and lymphoma using Manchester Children's Tumour Registry (MCTR) data 1976-2000. A total of 910 children were included, all of whom had histologically and/or cytologically verified leukaemia or lymphoma. At the time of their diagnoses, all the children were aged 0-14 years and were resident in the counties of Greater Manchester or Lancashire. Standardized morbidity ratios were calculated. Poisson regression was used to examine the relationship between incidence rates and small-area (census ward) population density, ethnic composition and deprivation index. There was a monotonic relationship between acute lymphoblastic leukaemia (ALL) incidence and population density (P = 0.05). Higher rates were seen in more densely populated areas. There was evidence for a monotonic relationship between the incidence of the mixed cellularity subtype of Hodgkin's disease (HD) and the Townsend deprivation score (P = 0.001). Markedly higher incidence was associated with greater levels of unemployment and household overcrowding. The results for ALL and mixed cellularity HD support the involvement of environmental factors, such as infections, in disease aetiology.

  17. Treosulfan, Fludarabine Phosphate, and Total-Body Irradiation Before Donor Stem Cell Transplant in Treating Patients With High-Risk Acute Myeloid Leukemia, Myelodysplastic Syndrome, Acute Lymphoblastic Leukemia

    Science.gov (United States)

    2013-10-29

    Accelerated Phase Chronic Myelogenous Leukemia; Adult Acute Lymphoblastic Leukemia in Remission; Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Blastic Phase Chronic Myelogenous Leukemia; Childhood Acute Lymphoblastic Leukemia in Remission; Childhood Acute Myeloid Leukemia in Remission; Childhood Chronic Myelogenous Leukemia; Childhood Myelodysplastic Syndromes; Chronic Myelomonocytic Leukemia; de Novo Myelodysplastic Syndromes; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Secondary Myelodysplastic Syndromes; Untreated Adult Acute Lymphoblastic Leukemia; Untreated Childhood Acute Lymphoblastic Leukemia

  18. Diffusion tensor imaging and neurocognition in survivors of childhood acute lymphoblastic leukaemia.

    Science.gov (United States)

    Edelmann, Michelle N; Krull, Kevin R; Liu, Wei; Glass, John O; Ji, Qing; Ogg, Robert J; Sabin, Noah D; Srivastava, Deo Kumar; Robison, Leslie L; Hudson, Melissa M; Reddick, Wilburn E

    2014-11-01

    Survivors of childhood acute lymphoblastic leukaemia are at risk for neurocognitive impairment, though little information is available on its association with brain integrity, particularly for survivors treated without cranial radiation therapy. This study compares neurocognitive function and brain morphology in long-term adult survivors of childhood acute lymphoblastic leukaemia treated with chemotherapy alone (n = 36) to those treated with cranial radiation therapy (n = 39) and to healthy control subjects (n = 23). Mean (standard deviation) age at evaluation was 24.9 (3.6) years for the chemotherapy group and 26.7 (3.4) years for the cranial radiation therapy group, while time since diagnosis was 15.0 (1.7) and 23.9 (3.1) years, respectively. Brain grey and white matter volume and diffusion tensor imaging was compared between survivor groups and to 23 healthy controls with a mean (standard deviation) age of 23.1 (2.6) years. Survivors treated with chemotherapy alone had higher fractional anisotropy in fibre tracts within the left (P < 0.05), but not in the right, hemisphere when compared to controls. Survivors of acute lymphoblastic leukaemia, regardless of treatment, had a lower ratio of white matter to intracranial volume in frontal and temporal lobes (P < 0.05) compared with control subjects. Survivors of acute lymphoblastic leukaemia treated with chemotherapy alone performed worse in processing speed (P < 0.001), verbal selective reminding (P = 0.01), and academics (P < 0.05) compared to population norms and performed better than survivors treated with cranial radiation therapy on verbal selective reminding (P = 0.02), processing speed (P = 0.05) and memory span (P = 0.009). There were significant associations between neurocognitive performance and brain imaging, particularly for frontal and temporal white and grey matter volume. Survivors of acute lymphoblastic leukaemia treated with chemotherapy alone demonstrated significant long-term differences in

  19. Characterization of CEBPA mutations and promoter hypermethylation in pediatric acute myeloid leukemia

    OpenAIRE

    2011-01-01

    textabstractBackground Dysfunctioning of CCAAT/enhancer binding protein α (C/EBP α) in acute myeloid leukemia can be caused, amongst others, by mutations in the encoding gene (CEBPA) and by promoter hypermethylation. CEBPA-mutated acute myeloid leukemia is associated with a favorable outcome, but this may be restricted to the case of double mutations in CEBPA in adult acute myeloid leukemia. In pediatric acute myeloid leukemia, data on the impact of these mutations are limited to one series, ...

  20. Cholecalciferol in Treating Patients With Acute Myeloid Leukemia Undergoing Intensive Induction Chemotherapy

    Science.gov (United States)

    2015-06-18

    Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Untreated Adult Acute Myeloid Leukemia

  1. Molecular-genetic insights in paediatric T-cell acute lymphoblastic leukaemia.

    Science.gov (United States)

    Van Vlierberghe, Pieter; Pieters, Rob; Beverloo, H Berna; Meijerink, Jules P P

    2008-10-01

    Paediatric T-cell acute lymphoblastic leukaemia (T-ALL) is an aggressive malignancy of thymocytes that accounts for about 15% of ALL cases and for which treatment outcome remains inferior compared to B-lineage acute leukaemias. In T-ALL, leukemic transformation of maturating thymocytes is caused by a multistep pathogenesis involving numerous genetic abnormalities that drive normal T-cells into uncontrolled cell growth and clonal expansion. This review provides an overview of the current knowledge on onco- and tumor suppressor genes in T-ALL and suggests a classification of these genetic defects into type A and type B abnormalities. Type A abnormalities may delineate distinct molecular-cytogenetic T-ALL subgroups, whereas type B abnormalities are found in all major T-ALL subgroups and synergize with these type A mutations during T-cell pathogenesis.

  2. Decitabine and Total-Body Irradiation Followed By Donor Bone Marrow Transplant and Cyclophosphamide in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia

    Science.gov (United States)

    2017-01-09

    Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome; Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); de Novo Myelodysplastic Syndromes; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia

  3. Difficult diagnosis of invasive fungal infection predominantly involving the lower gastrointestinal tract in acute lymphoblastic leukaemia

    Directory of Open Access Journals (Sweden)

    Gulhadiye Avcu

    2016-03-01

    Full Text Available Invasive fungal infections are most commonly seen in immunocompromised patients and usually affect the respiratory system. Gastrointestinal system involvement of mucormycosis and invasive aspergillosis is rarely reported in childhood. Here we describe a 5 year old boy with acute lymphoblastic leukaemia who developed invasive fungal infection particularly affecting the lower gastrointestinal system to emphasise the difficulties in diagnosis and management of invasive fungal infections in immunocompromised patients.

  4. Outcomes of patients with acute leukaemia who relapsed after reduced-intensity stem cell transplantation from HLA-identical or one antigen-mismatched related donors.

    Science.gov (United States)

    Kobayashi, Kazuhiko; Kami, Masahiro; Murashige, Naoko; Kusumi, Eiji; Kishi, Yukiko; Hamaki, Tamae; Hori, Akiko; Matsumura, Tomoko; Yuji, Koichiro; Masuo, Shigeru; Mori, Shinichiro; Miyakoshi, Shigesaburo; Tanosaki, Ryuji; Mitamura, Tadayuki; Takaue, Yoichi; Taniguchi, Shuichi

    2005-06-01

    The characteristics of relapse following reduced-intensity stem-cell transplantation (RIST) remain to be clarified. We reviewed the medical records of 19 patients with acute leukaemia [acute myeloid leukaemia (AML), 16; acute lymphoblastic leukaemia (ALL), 3] who relapsed after RIST from related donors using purine-analogue-based regimens. Their median age was 55 years (range, 29-65 years). Median interval between RIST and relapse was 4.9 months (range, 1.8-24.9 months). Three chose not to receive interventions. The remaining 16 patients received withdrawal of immunosuppression (n = 3), chemotherapy (n = 2), donor lymphocyte infusion (n = 10) and second transplantation (n = 7), alone (n = 9) or in combination (n = 7). Four are alive with a median follow-up of 27.6 months (range, 16.0-28.9 months); three in remission and one in relapse. The 2-year overall survival after relapse was 28.9%. Causes of death in 15 patients included progressive disease (n = 7), graft-versus-host disease (n = 5) and infections (n = 3). Cumulative incidences of relapse-related and non-relapse-related deaths at 2 years after relapse were 37% and 32% respectively. Two prognostic factors were identified on univariate analysis: age [P = 0.017; hazard ratio (HR), 1.16; 95% confidence interval (CI), 1.03-1.32], and ALL as underlying disease (P = 0.011; HR, 10.4; 95% CI, 1.73-62.4). Some AML patients who relapse after RIST achieve durable remission with allogeneic immunotherapy-based interventions; however they carry a significant risk of non-relapse mortality.

  5. Azacitidine With or Without Entinostat in Treating Patients With Myelodysplastic Syndromes, Chronic Myelomonocytic Leukemia, or Acute Myeloid Leukemia

    Science.gov (United States)

    2016-03-16

    Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome; Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With Inv(16)(p13.1q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With t(16;16)(p13.1;q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); RUNX1-RUNX1T1; Adult Acute Myeloid Leukemia With t(9;11)(p22;q23); MLLT3-MLL; Adult Acute Promyelocytic Leukemia With t(15;17)(q22;q12); PML-RARA; Alkylating Agent-Related Acute Myeloid Leukemia; Chronic Myelomonocytic Leukemia; de Novo Myelodysplastic Syndrome; Previously Treated Myelodysplastic Syndrome; Recurrent Adult Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndrome; Untreated Adult Acute Myeloid Leukemia

  6. BMS-214662 in Treating Patients With Acute Leukemia, Myelodysplastic Syndrome, or Chronic Myeloid Leukemia

    Science.gov (United States)

    2013-01-22

    Adult Acute Promyelocytic Leukemia (M3); Blastic Phase Chronic Myelogenous Leukemia; Childhood Myelodysplastic Syndromes; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Refractory Anemia With Excess Blasts; Refractory Anemia With Excess Blasts in Transformation; Relapsing Chronic Myelogenous Leukemia

  7. Managing children with chronic myeloid leukaemia (CML): recommendations for the management of CML in children and young people up to the age of 18 years.

    Science.gov (United States)

    de la Fuente, Josu; Baruchel, André; Biondi, Andrea; de Bont, Eveline; Dresse, Marie-Françoise; Suttorp, Meinolf; Millot, Frédéric

    2014-10-01

    Chronic myeloid leukaemia in children and young people is a relatively rare form of leukaemia that shows increased incidence with age and some evidence suggests that the molecular basis differs from that in adults. Significant advances in targeted therapy with the development and use in children of tyrosine kinase inhibitors and the ability to monitor and understand the prognostic significance of minimal residual disease by standardized molecular techniques has shifted the management of this condition from bone marrow transplantation as the main therapeutic modality to individualized treatment for each patient based on achieving specific milestones. The physiological changes occurring during childhood, particularly those affecting growth and development and the long-term use of treatment, pose specific challenges in this age group, which we are only beginning to understand.

  8. Aberrant signal transduction and protein expression in acute myeloid leukemia

    NARCIS (Netherlands)

    Schepers, Hein

    2007-01-01

    Het proces van hematopoiese voorziet het lichaam van miljarden bloedcellen per dag. Het is een strak geregisseerd proces. Acute myeloide leukemie (AML) is een afwijking in de bloedcelontwikkeling. Behandeling van deze en andere vormen van leukemie is veelal gebaseerd op het principe van de geprogram

  9. Collaborative efforts driving progress in pediatric acute myeloid leukemia

    NARCIS (Netherlands)

    C.M. Zwaan (Michel); E.A. Kolb (Edward A.); D. Reinhardt (Dirk); J. Abrahamsson; S. Adachi (Susumu); R. Aplenc (Richard); E.S.J.M. de Bont (Eveline); B. de Moerloose (Barbara); M.N. Dworzak (Michael); B. Gibson (Brenda); H. Hasle (Henrik); G. Leverger (Guy); F. Locatelli (Franco); C. Ragu (Christine); R.C. Ribeiro (Raul C.); C. Rizzari (Carmelo); J.E. Rubnitz (Jeffrey); O.P. Smith (Owen Patrick); L. Sung (Lillian); D. Tomizawa (Daisuke); M.M. van den Heuvel-Eibrink (Marry); U. Creutzig; G.J. Kaspers (Gertjan)

    2015-01-01

    textabstractDiagnosis, treatment, response monitoring, and outcome of pediatric acute myeloid leukemia (AML) have made enormous progress during the past decades. Because AML is a rare type of childhood cancer, with an incidence of approximately seven occurrences per 1 million children annually, nati

  10. Comorbidity and performance status in acute myeloid leukemia patients

    DEFF Research Database (Denmark)

    Ostgård, L S G; Nørgaard, J M; Sengeløv, H

    2015-01-01

    As the world population ages, the comorbidity burden in acute myeloid leukemia (AML) patients increases. Evidence on how to integrate comorbidity measures into clinical decision-making is sparse. We determined the prognostic impact of comorbidity and WHO Performance Status (PS) on achievement...

  11. Collaborative Efforts Driving Progress in Pediatric Acute Myeloid Leukemia

    NARCIS (Netherlands)

    Zwaan, C. Michel; Kolb, Edward A.; Reinhardt, Dirk; Abrahamsson, Jonas; Adachi, Souichi; Aplenc, Richard; De Bont, Eveline S. J. M.; De Moerloose, Barbara; Dworzak, Michael; Gibson, Brenda E. S.; Hasle, Henrik; Leverger, Guy; Locatelli, Franco; Ragu, Christine; Ribeiro, Raul C.; Rizzari, Carmelo; Rubnitz, Jeffrey E.; Smith, Owen P.; Sung, Lillian; Tomizawa, Daisuke; van den Heuvel-Eibrink, Marry M.; Creutzig, Ursula; Kaspers, Gertjan J. L.

    2015-01-01

    Diagnosis, treatment, response monitoring, and outcome of pediatric acute myeloid leukemia (AML) have made enormous progress during the past decades. Because AML is a rare type of childhood cancer, with an incidence of approximately seven occurrences per 1 million children annually, national and int

  12. Occupational exposure to solvents and acute myeloid leukemia

    DEFF Research Database (Denmark)

    Talibov, Madar; Lehtinen-Jacks, Susanna; Martinsen, Jan Ivar;

    2014-01-01

    OBJECTIVE: The aim of the current study was to assess the relation between occupational exposure to solvents and the risk of acute myeloid leukemia (AML). METHODS: Altogether, this study comprises 15 332 incident cases of AML diagnosed in Finland, Norway, Sweden and Iceland from 1961-2005 and 76...

  13. Characterization of miRNomes in Acute and Chronic Myeloid

    Directory of Open Access Journals (Sweden)

    Qian Xiong

    2014-04-01

    Full Text Available Myeloid leukemias are highly diverse diseases and have been shown to be associated with microRNA (miRNA expression aberrations. The present study involved an in-depth miRNome analysis of two human acute myeloid leukemia (AML cell lines, HL-60 and THP-1, and one human chronic myeloid leukemia (CML cell line, K562, via massively parallel signature sequencing. mRNA expression profiles of these cell lines that were established previously in our lab facilitated an integrative analysis of miRNA and mRNA expression patterns. miRNA expression profiling followed by differential expression analysis and target prediction suggested numerous miRNA signatures in AML and CML cell lines. Some miRNAs may act as either tumor suppressors or oncomiRs in AML and CML by targeting key genes in AML and CML pathways. Expression patterns of cell type-specific miRNAs could partially reflect the characteristics of K562, HL-60 and THP-1 cell lines, such as actin filament-based processes, responsiveness to stimulus and phagocytic activity. miRNAs may also regulate myeloid differentiation, since they usually suppress differentiation regulators. Our study provides a resource to further investigate the employment of miRNAs in human leukemia subtyping, leukemogenesis and myeloid development. In addition, the distinctive miRNA signatures may be potential candidates for the clinical diagnosis, prognosis and treatment of myeloid leukemias.

  14. Traffic-related air pollution and risk for leukaemia of an adult population.

    Science.gov (United States)

    Raaschou-Nielsen, Ole; Ketzel, Matthias; Harbo Poulsen, Aslak; Sørensen, Mette

    2016-03-01

    Air pollution causes lung cancer, but associations with other cancers have not been established. We investigated whether long-term exposure to traffic-related air pollution is associated with the risk of the general population for leukaemia. We identified 1,967 people in whom leukaemia was diagnosed in 1992-2010 from a nation-wide cancer registry and selected 3,381 control people at random, matched on sex and year of birth, from the entire Danish population. Residential addresses since 1971 were traced in a population registry, and outdoor concentrations of NOx and NO2 , as indicators of traffic-related air pollution, were calculated at each address in a dispersion model. We used conditional logistic regression to estimate the risk for leukaemia after adjustment for income, educational level, cohabitation status and co-morbidity. In linear analyses, we found odds ratios for acute myeloid leukaemia of 1.20 (95% confidence interval: 1.04-1.38) per 20 µg/m(3) increase in NOx and 1.31 (1.02-1.68) per 10 µg/m(3) increase in NO2 , calculated as time-weighted average exposure at all addresses since 1971. We found no association with chronic myeloid or lymphocytic leukaemia. This study indicates an association between long-term exposure to traffic-related air pollution and acute myeloid leukaemia in the general population, but not for other subtypes of leukaemia.

  15. CD19 CAR immune pressure induces B-precursor acute lymphoblastic leukaemia lineage switch exposing inherent leukaemic plasticity.

    Science.gov (United States)

    Jacoby, Elad; Nguyen, Sang M; Fountaine, Thomas J; Welp, Kathryn; Gryder, Berkley; Qin, Haiying; Yang, Yinmeng; Chien, Christopher D; Seif, Alix E; Lei, Haiyan; Song, Young K; Khan, Javed; Lee, Daniel W; Mackall, Crystal L; Gardner, Rebecca A; Jensen, Michael C; Shern, Jack F; Fry, Terry J

    2016-07-27

    Adoptive immunotherapy using chimeric antigen receptor (CAR) expressing T cells targeting the CD19 B lineage receptor has demonstrated marked success in relapsed pre-B-cell acute lymphoblastic leukaemia (ALL). Persisting CAR-T cells generate sustained pressure against CD19 that may drive unique mechanisms of resistance. Pre-B ALL originates from a committed pre-B cell or an earlier progenitor, with potential to reprogram into other hematopoietic lineages. Here we report changes in lineage markers including myeloid conversion in patients following CD19 CAR therapy. Using murine ALL models we study the long-term effects of CD19 CAR-T cells and demonstrate partial or complete lineage switch as a consistent mechanism of CAR resistance depending on the underlying genetic oncogenic driver. Deletion of Pax5 or Ebf1 recapitulates lineage reprogramming occurring during CD19 CAR pressure. Our findings establish lineage switch as a mechanism of CAR resistance exposing inherent plasticity in genetic subtypes of pre-B-cell ALL.

  16. Acute sinusitis and blindness as the first presentation of chronic lymphocytic leukaemia.

    Science.gov (United States)

    Lim, K H; Thomas, G; van Beers, E J; Hosman, A E; Mourits, M P; van Noesel, C J M; Kater, A P; Reinartz, S M

    2014-12-01

    Chronic lymphocytic leukaemia (CLL) is the most frequent form of leukaemia among adults in the Western world, presenting at a median age of 65 years. The diagnosis is usually made incidentally during routine blood examination while the disease is still in its early phase. We report a case of blindness of 24 hours due to acute sinusitis based on CLL localisation in a patient with undiagnosed CLL. Emergency endoscopic sinus surgery and intra- and extra-ocular orbital decompression were performed. The sinusitis resolved after surgery and intravenous antibiotics. Her vision improved within 24 hours and eventually recovered completely after six months. Her CLL remained in an indolent state, needing no active treatment. This case illustrates that blindness from a lymphoproliferative disorder may be treated with emergency endoscopic sinus surgery instead of conventional chemotherapy in order to salvage the vision first, even if the vision is lost for more than 24 hours.

  17. Combination chemotherapy for marrow relapse in children and adolescents with acute lymphocytic leukaemia.

    Science.gov (United States)

    Amadori, S; Spiriti, M A; Meloni, G; Pacilli, L; Papa, G; Mandelli, F

    1981-04-01

    38 children with acute lymphocytic leukaemia (ALL) in haematologic relapse were retreated with vincristine, daunomycin and prednisone (VPD) together with intrathecal methotrexate and prednisone, followed by asparaginase in those patients not in complete remission after 4 weeks. The overall complete remission (CR) rate was 79%; asparaginase was needed to achieve CR in 7 of the 30 responding patients. The median duration of second remission was only 36 weeks, but 6 out of 15 children receiving the COAP-POMP-CART consolidation regimen remain in continuous second remission after 37-260 weeks; 3 of them are currently off all therapy. It is concluded that a prolonged second remission can be achieved in children with ALL in bone marrow relapse by combining intensive chemotherapy with the prevention of meningeal leukaemia.

  18. Acute myelomonocytic leukaemia with short-term spontaneous remission in a cat.

    Science.gov (United States)

    Mylonakis, M E; Petanides, T A; Valli, V E; Vernau, W; Koytinas, A F; Michael, R S

    2008-06-01

    A 2-year-old, spayed female domestic shorthair cat was referred with a history of anorexia and depression of 1 week duration. On physical examination, the cat was lethargic and febrile, with splenomegaly, anisocoria and ulcerative stomatitis. A complete blood count (CBC) and a biochemistry profile showed leukocytosis, numerous blast cells in the peripheral blood, thrombocytopenia, hyperglobulinaemia and a positive test for feline leukaemia virus antigen. A diagnosis of acute myelomonocytic leukaemia was made on the basis of the results of bone marrow cytology, histopathology, and immunochemistry (CD3, CD79a, lysozyme, and myeloperoxidase) tests. Following an unexpected 1-month period of clinical and clinicopathological remission without chemotherapy, the cat relapsed and died 1 week later.

  19. European LeukemiaNet recommendations for the management and avoidance of adverse events of treatment in chronic myeloid leukaemia

    Science.gov (United States)

    Steegmann, J L; Baccarani, M; Breccia, M; Casado, L F; García-Gutiérrez, V; Hochhaus, A; Kim, D-W; Kim, T D; Khoury, H J; Le Coutre, P; Mayer, J; Milojkovic, D; Porkka, K; Rea, D; Rosti, G; Saussele, S; Hehlmann, R; Clark, R E

    2016-01-01

    Most reports on chronic myeloid leukaemia (CML) treatment with tyrosine kinase inhibitors (TKIs) focus on efficacy, particularly on molecular response and outcome. In contrast, adverse events (AEs) are often reported as infrequent, minor, tolerable and manageable, but they are increasingly important as therapy is potentially lifelong and multiple TKIs are available. For this reason, the European LeukemiaNet panel for CML management recommendations presents an exhaustive and critical summary of AEs emerging during CML treatment, to assist their understanding, management and prevention. There are five major conclusions. First, the main purpose of CML treatment is the antileukemic effect. Suboptimal management of AEs must not compromise this first objective. Second, most patients will have AEs, usually early, mostly mild to moderate, and which will resolve spontaneously or are easily controlled by simple means. Third, reduction or interruption of treatment must only be done if optimal management of the AE cannot be accomplished in other ways, and frequent monitoring is needed to detect resolution of the AE as early as possible. Fourth, attention must be given to comorbidities and drug interactions, and to new events unrelated to TKIs that are inevitable during such a prolonged treatment. Fifth, some TKI-related AEs have emerged which were not predicted or detected in earlier studies, maybe because of suboptimal attention to or absence from the preclinical data. Overall, imatinib has demonstrated a good long-term safety profile, though recent findings suggest underestimation of symptom severity by physicians. Second and third generation TKIs have shown higher response rates, but have been associated with unexpected problems, some of which could be irreversible. We hope these recommendations will help to minimise adverse events, and we believe that an optimal management of them will be rewarded by better TKI compliance and thus better CML outcomes, together with better

  20. Prevention of infection in children with acute leukaemia - No major difference between total and selective bowel decontamination

    NARCIS (Netherlands)

    Muis, N; Kamps, WA

    1996-01-01

    To evaluate the effect of total bowel decontamination (TD) and selective bowel decontamination (SD) in a non-protective environment clinical and laboratory data of children treated for acute leukaemia between 1983 and 1991 were analysed retrospectively. From 1983 until 1989 34 patients [18 acute non

  1. Biological Therapy in Treating Patients With Advanced Myelodysplastic Syndrome, Acute or Chronic Myeloid Leukemia, or Acute Lymphoblastic Leukemia Who Are Undergoing Stem Cell Transplantation

    Science.gov (United States)

    2017-03-27

    Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); B-cell Adult Acute Lymphoblastic Leukemia; B-cell Childhood Acute Lymphoblastic Leukemia; Childhood Chronic Myelogenous Leukemia; Childhood Myelodysplastic Syndromes; Chronic Myelomonocytic Leukemia; Essential Thrombocythemia; Polycythemia Vera; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Refractory Anemia With Excess Blasts; Refractory Anemia With Excess Blasts in Transformation; Relapsing Chronic Myelogenous Leukemia; Secondary Acute Myeloid Leukemia; T-cell Adult Acute Lymphoblastic Leukemia; T-cell Childhood Acute Lymphoblastic Leukemia

  2. [Transformation of secondary myelodysplastic syndrome to atypical chronic myeloid leukemia in a female patient with acute myeloid leukemia].

    Science.gov (United States)

    Gritsaev, S V; Kostroma, I I; Zapreeva, I M; Shmidt, A V; Tiranova, S A; Balashova, V A; Martynkevich, I S; Chubukina, Zh V; Semenova, N Yu; Chechetkin, A V

    Secondary myeloid neoplasia may be a complication of intensive cytostatic therapy. The most common types of secondary neoplasias are acute myeloid leukemia and myelodysplastic syndrome. The development of secondary atypical chronic myeloid leukemia (aCML) is an extremely rare phenomenon. The paper describes transformation of secondary myelodysplastic syndrome to aCML 6 months after its diagnosis. The development of aCML was accompanied by additional chromosomal aberration as monosomy of chromosome 17. No mutations in the JAK2, MPL, and CalR genes were detected. It is concluded that the clinical course of secondary myeloid neoplasias is variable.

  3. Azacitidine in Combination With Mitoxantrone, Etoposide Phosphate, and Cytarabine in Treating Patients With Relapsed and Refractory Acute Myeloid Leukemia

    Science.gov (United States)

    2016-12-19

    Adult Acute Myeloid Leukemia With Inv(16)(p13.1q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With t(16;16)(p13.1;q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With t(8;21); (q22; q22.1); RUNX1-RUNX1T1; Adult Acute Myeloid Leukemia With t(9;11)(p22.3;q23.3); MLLT3-KMT2A; Adult Acute Promyelocytic Leukemia With PML-RARA; Alkylating Agent-Related Acute Myeloid Leukemia; Recurrent Adult Acute Myeloid Leukemia

  4. The Polo-Like Kinase 1 (PLK1) inhibitor NMS-P937 is effective in a new model of disseminated primary CD56+ acute monoblastic leukaemia.

    Science.gov (United States)

    Casolaro, Alessia; Golay, Josee; Albanese, Clara; Ceruti, Roberta; Patton, Veronica; Cribioli, Sabrina; Pezzoni, Alice; Losa, Marco; Texido, Gemma; Giussani, Ursula; Marchesi, Francesco; Amboldi, Nadia; Valsasina, Barbara; Bungaro, Silvia; Cazzaniga, Gianni; Rambaldi, Alessandro; Introna, Martino; Pesenti, Enrico; Alzani, Rachele

    2013-01-01

    CD56 is expressed in 15-20% of acute myeloid leukaemias (AML) and is associated with extramedullary diffusion, multidrug resistance and poor prognosis. We describe the establishment and characterisation of a novel disseminated model of AML (AML-NS8), generated by injection into mice of leukaemic blasts freshly isolated from a patient with an aggressive CD56(+) monoblastic AML (M5a). The model reproduced typical manifestations of this leukaemia, including presence of extramedullary masses and central nervous system involvement, and the original phenotype, karyotype and genotype of leukaemic cells were retained in vivo. Recently Polo-Like Kinase 1 (PLK1) has emerged as a new candidate drug target in AML. We therefore tested our PLK1 inhibitor NMS-P937 in this model either in the engraftment or in the established disease settings. Both schedules showed good efficacy compared to standard therapies, with a significant increase in median survival time (MST) expecially in the established disease setting (MST = 28, 36, 62 days for vehicle, cytarabine and NMS-P937, respectively). Importantly, we could also demonstrate that NMS-P937 induced specific biomarker modulation in extramedullary tissues. This new in vivo model of CD56(+) AML that recapitulates the human tumour lends support for the therapeutic use of PLK1 inhibitors in AML.

  5. Recurrence of acute myeloid leukemia in cryptorchid testis: case report

    Energy Technology Data Exchange (ETDEWEB)

    Góes, Luccas Santos Patto de [Hospital do Servidor Público Municipal de São Paulo, São Paulo, SP (Brazil); Lopes, Roberto Iglesias [Hospital do Servidor Público Municipal de São Paulo, São Paulo, SP (Brazil); Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP (Brazil); Campos, Octavio Henrique Arcos [Hospital do Servidor Público Municipal de São Paulo, São Paulo, SP (Brazil); Oliveira, Luiz Carlos Neves de; Sant' Anna, Alexandre Crippa; Dall' Oglio, Marcos Francisco; Srougi, Miguel [Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP (Brazil)

    2014-07-01

    A 23-year-old male with a history of bone marrow transplant for acute myeloid leukemia. He presented a large mass in the right inguinal region 5 years ago. Upon physical examination, right-sided cryptorchidism was observed. The tumor markers alpha-fetoprotein and beta-HCG were within normalcy range and lactate dehydrogenase was raised. Computed tomography of the abdomen and pelvis revealed right testicular mass in contiguity with the inguinal canal to the ipsilateral retroperitoneum, associated with right hydronephrosis. Due to the risk of germ-cell tumor in undescended testicle, the patient underwent radical right orchiectomy. The pathological examination showed recurrence of acute myeloid leukemia in the testis. He was referred to oncology for adjuvant therapy. Our literature review found no similar cases described.

  6. Competitive PCR for quantification of minimal residual disease in acute lymphoblastic leukaemia

    DEFF Research Database (Denmark)

    Nyvold, C; Madsen, H O; Ryder, L P;

    2000-01-01

    A very precise and reproducible polymerase chain reaction (PCR) method was developed in order to quantify minimal residual disease (MRD) in children with acute lymphoblastic leukaemia (ALL). A clone-specific competitor was constructed by introducing a restriction site in a PCR product identical...... under identical conditions. After restriction enzyme cleavage, the PCR products originating from the competitor and the malignant clone can be distinguished by size in a gel electrophoresis step and the amount of residual disease can be determined. The method is very sensitive with a detection limit...

  7. Allogeneic stem cell transplantation in acute myeloid leukemia

    Directory of Open Access Journals (Sweden)

    Natasha Ali

    2012-11-01

    Full Text Available We report a case series of 12 patients with acute myeloid leukemia who underwent allogeneic stem cell transplant with a matched related donor. Male to female ratio was 1:1. The main complication post-transplant was graft-versus-host disease (n=7 patients. Transplant-related mortality involved one patient; cause of death was multi-organ failure. After a median follow up of 36.0±11.3 months, overall survival was 16%.

  8. Yttrium Y 90 Anti-CD45 Monoclonal Antibody BC8 Followed by Donor Stem Cell Transplant in Treating Patients With High-Risk Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia, or Myelodysplastic Syndrome

    Science.gov (United States)

    2016-09-29

    Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome; Chronic Myelomonocytic Leukemia; Previously Treated Myelodysplastic Syndrome; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Refractory Anemia With Excess Blasts; Secondary Acute Myeloid Leukemia

  9. Ploidy and clinical characteristics of childhood acute myeloid leukemia

    DEFF Research Database (Denmark)

    Sandahl, Julie Damgaard; Kjeldsen, Eigil; Abrahamsson, Jonas;

    2014-01-01

    We report the first large series (n = 596) of pediatric acute myeloid leukemia (AML) focusing on modal numbers (MN) from the population-based NOPHO-AML trials. Abnormal karyotypes were present in 452 cases (76%) and numerical aberrations were present in 40% (n = 237) of all pediatric AML. Among...... with early onset (median age 2 years), female sex (57%), and a dominance of acute megakaryoblastic leukemia (AMKL) (29%). Hypodiploidy constituted 8% of all AML and was associated with older age (median age 9 years), male predominance (60%), FAB M2 (56%), and t(8;21)(q22;q22) (56%) with loss of sex...

  10. A rare case of acute lymphoblastic leukaemia with hemophilia A

    Directory of Open Access Journals (Sweden)

    John Biju

    2009-12-01

    Full Text Available Abstract A rare case of Acute lymphoblastic leukemia with hemophillia in a 12 year old boy is presented in the article. Patient was known case of hemophillia (factor VIII deficiency. He was diagnosed as a case of ALL based on bone marrow examination and immunophenotypic study. Patient was treated as per Children Cancer group guidelines. The main aim of reporting this rare association lies in developing treatment strategies in preventing life threatening bleeding due to this rare association which though may be accidental but need further research.

  11. Bcl-xL and Myeloid cell leukaemia-1 contribute to apoptosis resistance of colorectal cancer cells

    Institute of Scientific and Technical Information of China (English)

    Henning Schulze-Bergkamen; Steffen Heeger; Peter R Galle; Markus Moehler; Roland Ehrenberg; Lothar Hickmann; Binje Vick; Toni Urbanik; Christoph C Schimanski; Martin R Berger; Arno Schad; Achim Weber

    2008-01-01

    AIM: To explore the role of Bd-x,and Myeloid cell leukaemia (Mcl)-1 for the apoptosis resistance of colorectal carcinoma (CRC) cells towards current treatment modalities.METHODS: BCl-XL and Mcl-1 mRNA and protein expression were analyzed in CRC cell lines as well as human CRC tissue by Western blot,quantitative PCR and immunohistochemistry.Bcl-x,and Mcl-1 protein expression was knocked down or increased in CRC cell lines by applying specific siRNAs or expression plasmids,respectively.After modulation of protein expression,CRC cells were treated with chemotherapeutic agents,an antagonistic epidermal growth factor receptor (EGFR1) antibody,an EGFR1 tyrosine kinase inhibitor,or with the death receptor ligand TRAIL.Apoptosis induction and cell viability were analyzed.RESULTS: Here we show that in human CRC tissue and various CRC cell lines both Bcl-x,and Mcl-1 are expressed.Bcl-x,expression was higher in CRC tissue than in surrounding non-malignant tissue,both on protein and mRNA level.Mcl-1 mRNA expression was significantly lower in malignant tissues.However,protein expression was slightly higher.Viability rates of CRC cells were significantly decreased after knock down of Bcl-XL expression,and,to a lower extent,after knock down of Mcl-1 expression.Furthermore,cells with reduced Bcl-xL or Mcl-1 expression was more sensitive towards oxaliplatin- and irinotecan-induced apoptosis,and in the case of Bcl-xL also towards 5-FU-induced apoptosis.On the other hand,upregulation of Bcl-XL by transfection of an expression plasmid decreased chemotherapeutic drug-induced apoptosis.EGF treatment clearly induced Bcl-xL and Mcl-1 expression in CRC cells.Apoptosis induction upon EGFR1 blockage by cetuximab or PD168393 was increased by inhibiting Hcl-1 and Bcl-xL expression.More strikingly,CD95- and TRAIL-induced apoptosis was increased by Bcl-xL knock down.CONCLUSION: Our data suggest that Bcl-xL and,to a lower extent,Mcl-1,are important anti-apoptotic factors in CRC

  12. Medical neglect death due to acute lymphoblastic leukaemia: an autopsy case report.

    Science.gov (United States)

    Usumoto, Yosuke; Sameshima, Naomi; Tsuji, Akiko; Kudo, Keiko; Nishida, Naoki; Ikeda, Noriaki

    2014-12-01

    We report the case of 2-year-old girl who died of precursor B-cell acute lymphoblastic leukaemia (ALL), the most common cancer in children. She had no remarkable medical history. She was transferred to a hospital because of respiratory distress and died 4 hours after arrival. Two weeks before death, she had a fever of 39 degrees C, which subsided after the administration of a naturopathic herbal remedy. She developed jaundice 1 week before death, and her condition worsened on the day of death. Laboratory test results on admission showed a markedly elevated white blood cell count. Accordingly, the cause of death was suspected to be acute leukaemia. Forensic autopsy revealed the cause of death to be precursor B-cell ALL. With advancements in medical technology, the 5-year survival rate of children with ALL is nearly 90%. However, in this case, the deceased's parents preferred complementary and alternative medicine (i.e., naturopathy) to evidence-based medicine and had not taken her to a hospital for a medical check-up or immunisation since she was an infant. Thus, if she had received routine medical care, she would have a more than 60% chance of being alive 5 years after diagnosis. Therefore, we conclude that the parents should be accused of medical neglect regardless of their motives.

  13. 47,XYY karyotype in acute myeloid leukemia.

    Science.gov (United States)

    Palanduz, S; Aktan, M; Ozturk, S; Tutkan, G; Cefle, K; Pekcelen, Y

    1998-10-01

    A case of acute myelomonocytic leukemia (AMMoL; M4) with a 47,XYY karyotype is reported. This chromosome aneuploidy was found in both bone marrow cells and mitogen-stimulated lymphocytes. The contribution of XYY chromosomal constitution in the pathogenesis of AMMoL is controversial.

  14. Tretinoin in pregnancy complicated with acute promyelocytic leukaemia.

    Science.gov (United States)

    Leong, K W; Teh, A; Bosco, J J

    2000-06-01

    Acute promyelocytic leukemia (APL) in pregnancy poses serious danger to both the mother and fetus. Cytotoxic chemotherapy may cause teratogenicity to the fetus. APL is unique because it is usually associated with a coagulopathy that markedly increases the risk for the mother and fetus. A 21 year old lady with APL in her third trimester of pregnancy was treated with oral tretinoin. Tretinoin reversed the coagulopathy and normalised her blood counts without causing cytotoxic damage associated with cancer chemotherapy. Fetal distress occurred at 37 weeks of gestation and an emergency caesarean section was performed without complications and no blood transfusion support was needed as her coagulopathy and thrombocytopenia had resolved. A remission was achieved with only tretinoin induction. She subsequently had consolidation and maintenance chemotherapy. The mother and baby remain well at 4 years from completion of chemotherapy. A total of 10 pregnancies associated with APL have been reported in the current literature. Premature delivery and a fetal arrhythmia were the only complications. Although retinoin is considered teratogenic, its use so far in second and third trimester has been safe.

  15. Decitabine and Valproic Acid in Treating Patients With Refractory or Relapsed Acute Myeloid Leukemia or Previously Treated Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma

    Science.gov (United States)

    2013-09-27

    Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Recurrent Adult Acute Myeloid Leukemia; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Untreated Adult Acute Myeloid Leukemia

  16. Prolonged bone marrow T1-relaxation in acute leukaemia. In vivo tissue characterization by magnetic resonance imaging

    DEFF Research Database (Denmark)

    Thomsen, C; Sørensen, P G; Karle, H;

    1987-01-01

    osseous tissue. Nine patients with acute leukaemia, one patient with myelodysplastic syndrome, and ten normal volunteers were included in the study. The T1- and T2-relaxation processes were measured in the lumbar spine bone marrow using a wholebody superconductive MR-scanner operating at 1.5 Tesla...

  17. Variation in survival of European children with acute lymphoblastic leukaemia, diagnosed in 1978-1992 : the EUROCARE study

    NARCIS (Netherlands)

    Coebergh, JW; Pastore, G; Gatta, G; Corazziari, [No Value; Kamps, W

    2001-01-01

    The aim of this study was to provide a comparative description of geographical variations and time trends in the population-based survival of European children with acute lymphoblastic leukaemia (ALL). Data on 13 344 newly diagnosed children (0-14 years) with ALL were included in the EUROCARE study

  18. Genome‐wide analysis of cytogenetic aberrations in ETV6/RUNX1‐positive childhood acute lymphoblastic leukaemia

    DEFF Research Database (Denmark)

    Borst, Louise; Wesolowska, Agata; Joshi, Tejal;

    2012-01-01

    The chromosomal translocation t(12;21) resulting in the ETV6/RUNX1 fusion gene is the most frequent structural cytogenetic abnormality among patients with childhood acute lymphoblastic leukaemia (ALL). We investigated 62 ETV6/RUNX1‐positive childhood ALL patients by single nucleotide polymorphism...

  19. Splenic artery pseudoaneurysm due to acute pancreatitis in a 6-year-old boy with acute lymphoblastic leukaemia treated with L-aspariginase

    DEFF Research Database (Denmark)

    Larsen, Cæcilie Crawley; Laursen, Christian B; Dalby, Kasper;

    2014-01-01

    Acute pancreatitis is a rare phenomenon in children but its incidence seems to be increasing. In children, it is generally caused due to systemic illness, biliary disease, trauma, idiopathy and side effects of medicines like L-aspariginase. Acute pancreatitis is difficult to diagnose in children...... pseudoaneurysm due to acute pancreatitis in a 6-year-old boy with acute lymphoblastic leukaemia treated with L-aspariginase. He presented with fever, irritability and pain in his left groin region....

  20. Acquired mutations in ASXL1 in acute myeloid leukemia: prevalence and prognostic value

    OpenAIRE

    2012-01-01

    Somatic mutations in the additional sex comb-like 1 (ASXL1) gene have been described in various types of myeloid malignancies, including acute myeloid leukemia. Analysis of novel markers, such as ASXL1 mutations, in independent clinical trials is indispensable before considering them for clinical decision-making. We analyzed 882 well-characterized acute myeloid leukemia cases to determine the prevalence and prognostic impact of ASXL1 exon12 mutations. Truncating ASXL1 mutations were present i...

  1. Genomic analyses identify recurrent MEF2D fusions in acute lymphoblastic leukaemia

    Science.gov (United States)

    Gu, Zhaohui; Churchman, Michelle; Roberts, Kathryn; Li, Yongjin; Liu, Yu; Harvey, Richard C.; McCastlain, Kelly; Reshmi, Shalini C.; Payne-Turner, Debbie; Iacobucci, Ilaria; Shao, Ying; Chen, I-Ming; Valentine, Marcus; Pei, Deqing; Mungall, Karen L.; Mungall, Andrew J.; Ma, Yussanne; Moore, Richard; Marra, Marco; Stonerock, Eileen; Gastier-Foster, Julie M.; Devidas, Meenakshi; Dai, Yunfeng; Wood, Brent; Borowitz, Michael; Larsen, Eric E.; Maloney, Kelly; Mattano Jr, Leonard A.; Angiolillo, Anne; Salzer, Wanda L.; Burke, Michael J.; Gianni, Francesca; Spinelli, Orietta; Radich, Jerald P.; Minden, Mark D.; Moorman, Anthony V.; Patel, Bella; Fielding, Adele K.; Rowe, Jacob M.; Luger, Selina M.; Bhatia, Ravi; Aldoss, Ibrahim; Forman, Stephen J.; Kohlschmidt, Jessica; Mrózek, Krzysztof; Marcucci, Guido; Bloomfield, Clara D.; Stock, Wendy; Kornblau, Steven; Kantarjian, Hagop M.; Konopleva, Marina; Paietta, Elisabeth; Willman, Cheryl L.; L. Loh, Mignon; P. Hunger, Stephen; Mullighan, Charles G.

    2016-01-01

    Chromosomal rearrangements are initiating events in acute lymphoblastic leukaemia (ALL). Here using RNA sequencing of 560 ALL cases, we identify rearrangements between MEF2D (myocyte enhancer factor 2D) and five genes (BCL9, CSF1R, DAZAP1, HNRNPUL1 and SS18) in 22 B progenitor ALL (B-ALL) cases with a distinct gene expression profile, the most common of which is MEF2D-BCL9. Examination of an extended cohort of 1,164 B-ALL cases identified 30 cases with MEF2D rearrangements, which include an additional fusion partner, FOXJ2; thus, MEF2D-rearranged cases comprise 5.3% of cases lacking recurring alterations. MEF2D-rearranged ALL is characterized by a distinct immunophenotype, DNA copy number alterations at the rearrangement sites, older diagnosis age and poor outcome. The rearrangements result in enhanced MEF2D transcriptional activity, lymphoid transformation, activation of HDAC9 expression and sensitive to histone deacetylase inhibitor treatment. Thus, MEF2D-rearranged ALL represents a distinct form of high-risk leukaemia, for which new therapeutic approaches should be considered. PMID:27824051

  2. Adult acute lymphoblastic leukaemia in Denmark. A national population-based retrospective study on acute lymphoblastic leukaemia in Denmark 1998-2008

    DEFF Research Database (Denmark)

    Toft, Nina; Schmiegelow, Kjeld; Klausen, Tobias W

    2012-01-01

    with historical controls, we performed a retrospective national population-based study of adult ALL between 1998 and 2008. Patients were identified through the Danish Patobank and the Danish Cancer Registry; data was collected from patient files, and included 277 patients (median age, 47 years, range 15-91 years......Since July 2008, children and adults 1-45 years, diagnosed with acute lymphoblastic leukaemia (ALL) in Denmark have been treated according to the common Nordic Society for Paediatric Haematology and Oncology ALL2008 protocol. To explore whether this strategy will improve survival compared......). The 5-year projected event-free survival (pEFS(5y) ) and overall survival (pOS(5y) ) for the whole cohort was 27·5% [95% confidence interval (CI) 22·4-33·6] and 34·1% (95% CI 28·7-40·4), respectively. No patient above 65 years survived beyond 5 years from diagnosis. For patients receiving curatively...

  3. Response-guided induction therapy in pediatric acute myeloid leukemia with excellent remission rate

    DEFF Research Database (Denmark)

    Abrahamsson, Jonas; Forestier, Erik; Heldrup, Jesper;

    2011-01-01

    To evaluate the early treatment response in children with acute myeloid leukemia (AML) using a response-guided induction strategy that includes idarubicin in the first course.......To evaluate the early treatment response in children with acute myeloid leukemia (AML) using a response-guided induction strategy that includes idarubicin in the first course....

  4. Characterization of CEBPA mutations and promoter hypermethylation in pediatric acute myeloid leukemia

    NARCIS (Netherlands)

    Hollink, Iris H. I. M.; van den Heuvel-Eibrink, Marry M.; Arentsen-Peters, Susan T. C. J. M.; Zimmermann, Martin; Peeters, Justine K.; Valk, Peter J. M.; Balgobind, Brian V.; Sonneveld, Edwin; Kaspers, Gertjan J. L.; de Bont, Eveline S. J. M.; Trka, Jan; Baruchel, Andre; Creutzig, Ursula; Pieters, Rob; Reinhardt, Dirk; Zwaan, C. Michel

    2011-01-01

    Background Dysfunctioning of CCAAT/enhancer binding protein alpha (C/EBP alpha) in acute myeloid leukemia can be caused, amongst others, by mutations in the encoding gene (CEBPA) and by promoter hypermethylation. CEBPA-mutated acute myeloid leukemia is associated with a favorable outcome, but this m

  5. Prediction of molecular subtypes in acute myeloid leukemia based on gene expression profiling

    NARCIS (Netherlands)

    R.G.W. Verhaak (Roel); B.J. Wouters (Bas); C.A.J. Erpelinck (Claudia); S. Abbas (Saman); H.B. Beverloo (Berna); S. Lugthart (Sanne); B. Löwenberg (Bob); H.R. Delwel (Ruud); P.J.M. Valk (Peter)

    2009-01-01

    textabstractWe examined the gene expression profiles of two independent cohorts of patients with acute myeloid leukemia [n=247 and n=214 (younger than or equal to 60 years)] to study the applicability of gene expression profiling as a single assay in prediction of acute myeloid leukemia-specific mol

  6. Characterization of CEBPA mutations and promoter hypermethylation in pediatric acute myeloid leukemia

    NARCIS (Netherlands)

    I.H.I.M. Hollink (Iris); M.M. van den Heuvel-Eibrink (Marry); S.T.C.J.M. Arentsen-Peters (Susan); M. Zimmermann (Martin); J. Peeters (Justine); P.J.M. Valk (Peter); B.V. Balgobind (Brian); E. Sonneveld (Edwin); G.J. Kaspers (Gertjan); E.S.J.M. de Bont (Eveline); J. Trka (Jan); A. Baruchel (André); U. Creutzig (Ursula); R. Pieters (Rob); D. Reinhardt (Dirk); C.M. Zwaan (Michel)

    2011-01-01

    textabstractBackground Dysfunctioning of CCAAT/enhancer binding protein α (C/EBP α) in acute myeloid leukemia can be caused, amongst others, by mutations in the encoding gene (CEBPA) and by promoter hypermethylation. CEBPA-mutated acute myeloid leukemia is associated with a favorable outcome, but th

  7. Effect of age and body weight on toxicity and survival in pediatric acute myeloid leukemia

    DEFF Research Database (Denmark)

    Løhmann, Ditte J A; Abrahamsson, Jonas; Ha, Shau-Yin

    2016-01-01

    Treatment for pediatric acute myeloid leukemia is very toxic and the association between outcome and age and Body Mass Index is unclear. We investigated effect of age and Body Mass Index on toxicity and survival in pediatric acute myeloid leukemia. We studied all patients who completed first indu...

  8. Clofarabine, Cytarabine, and Filgrastim Followed by Infusion of Non-HLA Matched Ex Vivo Expanded Cord Blood Progenitors in Treating Patients With Acute Myeloid Leukemia

    Science.gov (United States)

    2014-08-13

    Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Acute Promyelocytic Leukemia (M3); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Recurrent Adult Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

  9. Genital Infection as a First Sign of Acute Myeloid Leukemia

    Directory of Open Access Journals (Sweden)

    Naoki Oiso

    2010-02-01

    Full Text Available Fournier’s gangrene is a life-threatening disorder caused by aerobic and anaerobic bacterial infection. We report a case of genital infection as the initial warning sign of acute myeloid leukemia. We were able to prevent progression to Fournier’s gangrene in our patient by immediate intensive therapy with incision, blood transfusions and intravenous administration of antibiotics. This case suggests that hematologists and dermatologists should keep in mind that genital infection can be a first sign of hematologic malignancy.

  10. Esophageal Candidiasis as the Initial Manifestation of Acute Myeloid Leukemia.

    Science.gov (United States)

    Komeno, Yukiko; Uryu, Hideki; Iwata, Yuko; Hatada, Yasumasa; Sakamoto, Jumpei; Iihara, Kuniko; Ryu, Tomiko

    2015-01-01

    A 47-year-old woman presented with persistent dysphagia. A gastroendoscopy revealed massive esophageal candidiasis, and oral miconazole was prescribed. Three weeks later, she returned to our hospital without symptomatic improvement. She was febrile, and blood tests showed leukocytosis (137,150 /μL, blast 85%), anemia and thrombocytopenia. She was diagnosed with acute myeloid leukemia (AML). She received chemotherapy and antimicrobial agents. During the recovery from the nadir, bilateral ocular candidiasis was detected, suggesting the presence of preceding candidemia. Thus, esophageal candidiasis can be an initial manifestation of AML. Thorough examination to detect systemic candidiasis is strongly recommended when neutropenic patients exhibit local candidiasis prior to chemotherapy.

  11. Acute myeloid leukemia: conventional cytogenetics, FISH, and moleculocentric methodologies.

    Science.gov (United States)

    Morrissette, Jennifer J D; Bagg, Adam

    2011-12-01

    Acute myeloid leukemia (AML) is a complex group of hematologic neoplasms characterized by distinctive morphologic, immunophenotypic, and genetic abnormalities. However, it has become evident that genetic aberrations are central to the genesis of AML and have assumed an increasingly relevant role in the classification of AML. Here we discuss hallmark recurrent translocations that define specific World Health Organization (WHO) entities and other frequently encountered genetic aberrations that do not (yet) define specific entities. Additionally, we discuss emerging technologies and their application to the discovery of new abnormalities and to their potential role in the future diagnosis and classification of AML.

  12. [Nursing diagnosis in adult patients with acute myeloid leukemia].

    Science.gov (United States)

    de Souza, Luccas Melo; Gorini, Maria Isabel Pinto Coelho

    2006-09-01

    This case study aimed at identifying Nursing Diagnosis (ND) in adult patients with Acute Myeloid Leukemia, with the purpose of contributing to the Systematization of Nurse Care. Interviews and observation were used for data collection, in addition to Nursing Process application. During the three months of data collection, other NDs were obtained by searching the files of the 6 patients. The 32 ND found in this study were grouped according to Maslow's hierarchy of needs. Out of these 32 ND, 15 corresponded to changes in Physiological Needs, and 10 to changes in Protection and Safety Needs.

  13. Complexity on Acute Myeloid Leukemia mRNA Transcript Variant

    Directory of Open Access Journals (Sweden)

    Carlo Cattani

    2011-01-01

    Full Text Available This paper deals with the sequence analysis of acute myeloid leukemia mRNA. Six transcript variants of mlf1 mRNA, with more than 2000 bps, are analyzed by focusing on the autocorrelation of each distribution. Through the correlation matrix, some patches and similarities are singled out and commented, with respect to similar distributions. The comparison of Kolmogorov fractal dimension will be also given in order to classify the six variants. The existence of a fractal shape, patterns, and symmetries are discussed as well.

  14. Decitabine Followed by Idarubicin and Cytarabine in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia or Myelodysplastic Syndromes

    Science.gov (United States)

    2013-10-09

    Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Myeloid Leukemia; Refractory Anemia With Excess Blasts

  15. PS-341 in Treating Patients With Refractory or Relapsed Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia, Chronic Myeloid Leukemia in Blast Phase, or Myelodysplastic Syndrome

    Science.gov (United States)

    2013-01-22

    Adult Acute Promyelocytic Leukemia (M3); Blastic Phase Chronic Myelogenous Leukemia; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Refractory Anemia With Excess Blasts; Refractory Anemia With Excess Blasts in Transformation; Relapsing Chronic Myelogenous Leukemia

  16. Arthroplasties of hips and knees ankylosis in an adolescent with acute lymphoblastic leukaemia.

    Directory of Open Access Journals (Sweden)

    Dipo Samuel OLABUMUYI

    2011-10-01

    Full Text Available Acute lymphoblastic leukaemia (ALL is the most common malignancy in children, representing one third of all paediatric malignancies. Patients are often at high risk for complications due aggressive chemotherapy regimes required for treatment. Musculoskeletal complications include septic arthritis, osteonecrosis, osteoporosis, avascular necrosis and bony ankylosis. We report the case of a 16-year-old boy with ALL who developed osteonecrosis of multiple bones on a background of septicaemia, resulting in bony ankylosis of both hips and knees. He was treated with bilateral conversion of ankylosed hips (one hip to total hip replacement, the second hip to Girdlestone arthroplasty and bilateral ankylosed knees to total knee replacements. He remained well in remission five years after the last surgery. Our case highlights he possible musculoskeletal complications of ALL. 

  17. Fetal liver transplantation in 2 patients with acute leukaemia after total body irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Lucarelli, G.; Izzi, T.; Porcellini, A.; Delfini, C.; Galimberti, M.; Moretti, L.; Polchi, P.; Agostinelli, F.; Andreani, M.; Manna, M. (Haematological Department, Pesaro Hospital, Pesaro, Italy)

    1982-01-01

    2 patients with acute leukaemia in relapse were transplanted with fetal liver cells following a conditioning regimen of cyclophosphamide (120 mg/kg) and total body irradiation (1000 r). Each patient achieved a remission with haematopoietic recovery that was rapid in one case and delayed in the other. In one case there was evidence of chimerism as demonstrated by the presence of the XYY karyotype of the donor fetus in 20 % of marrow metaphases, by the presence of double Y bodies in the peripheral blood, by the appearance of new HLA-antigens, and by red cell isoenzyme phenotypes of donor origin. In the second case there was prompt haemotopoietic recovery and the appearance of red cell isoenzyme phenotypes of donor origin. Survival was 153 and 30 d, respectively, and both patients died of interstitial pneumonia without evidence of graft versus host disease.

  18. Laboratory-Treated Donor Cord Blood Cell Infusion Following Combination Chemotherapy in Treating Younger Patients With Relapsed or Refractory Acute Myeloid Leukemia

    Science.gov (United States)

    2016-10-31

    Acute Leukemia of Ambiguous Lineage; Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With Inv(16)(p13.1q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With t(16;16)(p13.1;q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); RUNX1-RUNX1T1; Adult Acute Myeloid Leukemia With t(9;11)(p22;q23); MLLT3-MLL; Adult Acute Promyelocytic Leukemia With t(15;17)(q22;q12); PML-RARA; Alkylating Agent-Related Acute Myeloid Leukemia; Childhood Acute Myeloid Leukemia in Remission; Recurrent Adult Acute Myeloid Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

  19. Organ irradiation and combination chemotherapy in treatment of acute lymphocytic leukaemia in children.

    Science.gov (United States)

    Lanzkowsky, P; Shende, A; Aral, I; Saluja, G

    1975-01-01

    Lanzkowsky, P., Shende, A., Aral, I., Saluja, G. (1975). Archives of Disease in Childhood, 50, 685. Organ irradiation and combination chemotherapy in treatment of acute lymphocytic leukaemia in children. A total of 30 consecutive children with acute lymphocytic leukaemia (ALL) were treated from June 1971 until December 1974. Remission was induced with the use of vincristine and prednisone. After induction of remission, cranial irradiation and intrathecal methotrexate were given. Then the liver, spleen, and kidney were irradiated and 6-mercaptopurine, cyclophosphamide, and methotrexate were administered during the maintenance phase. Pulsed doses of vincristine and prednisone were administered at 10- to 12-week intervals. The patients were subdivided into two groups based on their initial white blood cell (WBC) counts: a standard risk group with an initial WBC count of less than 25 000/mm3 (25 X 10(9)/1) and a high risk group with an initial WBC count greater than 25 000/mm3 (25 X 10(9)/1). Of the 30 children entered in this study one standard risk patient died in the induction phase before attaining remission. Analysis of the results is therefore based on the remaining 29 patients, 22 standard risk and 7 high risk patients, who attained complete remission. Survival rates in continuous remission were found to be 43% of the high risk group, 88% for the standard risk group, and 77% for the combined group. Analysis of the data indicates that this therapy is unsatisfactory in high risk ALL. The results to date of this therapy for standard risk are sufficiently encouraging to continue its use in this subgroup of patients. PMID:1059384

  20. Alantolactone selectively ablates acute myeloid leukemia stem and progenitor cells

    Directory of Open Access Journals (Sweden)

    Yahui Ding

    2016-09-01

    Full Text Available Abstract Background The poor outcomes for patients diagnosed with acute myeloid leukemia (AML are largely attributed to leukemia stem cells (LSCs which are difficult to eliminate with conventional therapy and responsible for relapse. Thus, new therapeutic strategies which could selectively target LSCs in clinical leukemia treatment and avoid drug resistance are urgently needed. However, only a few small molecules have been reported to show anti-LSCs activity. Methods The aim of the present study was to identify alantolactone as novel agent that can ablate acute myeloid leukemia stem and progenitor cells from AML patient specimens and evaluate the anticancer activity of alantolactone in vitro and in vivo. Results The present study is the first to demonstrate that alantolactone, a prominent eudesmane-type sesquiterpene lactone, could specifically ablate LSCs from AML patient specimens. Furthermore, in comparison to the conventional chemotherapy drug, cytosine arabinoside (Ara-C, alantolactone showed superior effects of leukemia cytotoxicity while sparing normal hematopoietic cells. Alantolactone induced apoptosis with a dose-dependent manner by suppression of NF-kB and its downstream target proteins. DMA-alantolactone, a water-soluble prodrug of alantolactone, could suppress tumor growth in vivo. Conclusions Based on these results, we propose that alantolactone may represent a novel LSCs-targeted therapy and eudesmane-type sesquiterpene lactones offer a new scaffold for drug discovery towards anti-LSCs agents.

  1. Rapid Evolution to Blast Crisis Associated with a Q252H ABL1 Kinase Domain Mutation in e19a2 BCR-ABL1 Chronic Myeloid Leukaemia

    Directory of Open Access Journals (Sweden)

    Sarah L. McCarron

    2013-01-01

    Full Text Available A minority of chronic myeloid leukaemia (CML patients express variant transcripts of which the e19a2 BCR-ABL1 fusion is the most common. Instances of tyrosine kinase inhibitor (TKI resistance in e19a2 BCR-ABL1 CML patients have rarely been reported. A case of e19a2 BCR-ABL1 CML is described in whom imatinib resistance, associated with a Q252H ABL1 kinase domain mutation, became apparent soon after initiation of TKI therapy. The patient rapidly transformed to myeloid blast crisis (BC with considerable bone marrow fibrosis and no significant molecular response to a second generation TKI. The clinical course was complicated by comorbidities with the patient rapidly succumbing to advanced disease. This scenario of Q252H-associated TKI resistance with rapid BC transformation has not been previously documented in e19a2 BCR-ABL1 CML. This case highlights the considerable challenges remaining in the management of TKI-resistant BC CML, particularly in the elderly patient.

  2. ST-Elevation Myocardial Infarction and Myelodysplastic Syndrome with Acute Myeloid Leukemia Transformation

    OpenAIRE

    2014-01-01

    Acute myocardial infarction and acute myeloid leukemia are rarely reported as concomitant conditions. The management of ST-elevation myocardial infarction (STEMI) in patients who have acute myeloid leukemia is challenging: the leukemia-related thrombocytopenia, platelet dysfunction, and systemic coagulopathy increase the risk of bleeding, and the administration of thrombolytic agents can be fatal. We report the case of a 76-year-old man who presented emergently with STEMI, myelodysplastic syn...

  3. Conventional chemotherapy for acute myeloid leukemia: a Brazilian experience

    Directory of Open Access Journals (Sweden)

    Kátia Borgia Barbosa Pagnano

    2000-11-01

    Full Text Available CONTEXT: Young patients affected by acute myeloid leukemia (AML achieve complete remission (CR using conventional chemotherapy in about 55-85%. However, 30% of patients fail to achieve CR and the remission duration is often only about 12 months. More intensive treatment after CR seems to be necessary in order to maintain CR and obtain a definitive cure. In Brazil, few reports have been published on this important subject. OBJECTIVE: The aim of this study was to describe a Brazilian experience in the treatment of "de novo" acute myeloid leukemia (AML in younger adult patients (age < 60 years. DESIGN: Retrospective analysis. SETTING: University Hospital, Hematology and Hemotherapy Center, State University of Campinas, Brazil. PARTICIPANTS: Newly diagnosed cases of "de novo" AML in the period from January 1994 to December 1998 were evaluated retrospectively, in relation to response to treatment, overall survival (OS and disease free survival (DFS. Cases with acute promyelocytic leukemia (APL were also included in this analysis. RESULTS: On the basis of an intention to treat, 78 cases of AML, including 17 cases of APL, were evaluated. The overall median follow-up was 272 days. The complete remission (CR rate was 63.6% in the AML group (excluding APL and 78% in the APL group. The 5-year estimated disease-free survival (DFS was 80% for the APL group and 34% for the AML group (P = 0.02. The 5-year estimated overall survival (OS was 52% for the APL group and 20.5% for the AML group, respectively (P = NS. Relapse was observed in 12/39 (30.7% patients with AML and 1/11 (9% with APL. CONCLUSIONS: These results are similar to those reported in the literature. However, relapse and mortality rates remain high, and a search for more aggressive strategies in order to prevent relapse is recommended.

  4. TESTIN Induces Rapid Death and Suppresses Proliferation in Childhood B Acute Lymphoblastic Leukaemia Cells.

    Directory of Open Access Journals (Sweden)

    Robert J Weeks

    Full Text Available Childhood acute lymphoblastic leukaemia (ALL is the most common malignancy in children. Despite high cure rates, side effects and late consequences of the intensive treatments are common. Unquestionably, the identification of new therapeutic targets will lead to safer, more effective treatments. We identified TES promoter methylation and transcriptional silencing as a very common molecular abnormality in childhood ALL, irrespective of molecular subtype. The aims of the present study were to demonstrate that TES promoter methylation is aberrant, to determine the effects of TES re-expression in ALL, and to determine if those effects are mediated via TP53 activity.Normal fetal and adult tissue DNA was isolated and TES promoter methylation determined by Sequenom MassARRAY. Quantitative RT-PCR and immunoblot were used to confirm re-expression of TES in ALL cell lines after 5'-aza-2'-deoxycytidine (decitabine exposure or transfection with TES expression plasmids. The effects of TES re-expression on ALL cells were investigated using standard cell proliferation, cell death and cell cycle assays.In this study, we confirm that the TES promoter is unmethylated in normal adult and fetal tissues. We report that decitabine treatment of ALL cell lines results in demethylation of the TES promoter and attendant expression of TES mRNA. Re-expression of TESTIN protein in ALL cells using expression plasmid transfection results in rapid cell death or cell cycle arrest independent of TP53 activity.These results suggest that TES is aberrantly methylated in ALL and that re-expression of TESTIN has anti-leukaemia effects which point to novel therapeutic opportunities for childhood ALL.

  5. A Ten Year Descriptive Study of Adult Leukaemia at Al-Jomhori Teaching Hospital in Sana'a, Yemen

    Directory of Open Access Journals (Sweden)

    Jameel Al-Ghazaly

    2014-12-01

    Full Text Available Background: There is scarcity of data of the epidemiology of leukaemia in Arab countries including Yemen. Understanding patterns of leukaemia underpins epidemiology and can provide insight into disease etiology. The aim of this research is to determine the epidemiologic pattern of adult leukaemia in Yemen. Methods: The research is a descriptive cross-sectional study. We analyzed the data of 702 adult patients with leukaemia, who were newly diagnosed over a ten-year period between October 1999 and October 2009 at the referral haematology centre in Sana’a at Al-Jomhori Teaching Hospital, according to type of leukaemia, age, sex, geographic distribution and time of diagnosis. Results: Acute Myeloid Leukaemia (AML was found to be the most common (45.1% followed by Chronic Myeloid Leukaemia (CML (26.5%, Acute Lymphoid Leukaemia (ALL (17.7% and Chronic Lymphoid Leukaemia (CLL (10.7%, respectively. There was an almost equal prevalence of AML and CML for males and females but males had significantly more cases of ALL and CLL (p =0.008. A significant variation in geographic pattern showed that the highest number of cases is seen the Central mountainous region and the least number of cases in the South-eastern region which is coastal and lowland (p<0.001. The seasonal variation showed that higher number of ALL cases was seen in the summer months (33% compared with other seasons (21% in the spring, 24.2% in autumn and 21.8% in winter. Conclusions: The pattern of adult leukaemia in Yemen is different from that seen in western countries which could be attributed to different environmental exposure. The geographic pattern indicates a possible role of certain environmental factors which warrant further investigations. The pattern of seasonal variation needs further studies for evaluating the seasonality.

  6. Treatment and prognostic assessment of acute myeloid leukemia

    Directory of Open Access Journals (Sweden)

    Bannur Ramanna Nandeesh

    2016-06-01

    Full Text Available Acute myeloid leukemia (AML is a heterogeneous group of clonal malignant myeloid neoplasms. Malignant transformation of hematopoietic progenitor cell leads to clonal expansion and replacement of normal bone marrow cells with malignant cells leading to suppression of normal haematopoiesis. Advancements in our understanding of disease biology have allowed AML to be classified based on its gene expression profile, which includes previously identified cytogenetic subgroups, and distinct novel subgroups which have prognostic significance. Identification of mutations in DNMT3A and IDH 1 genes in cytogenetically normal AML (by gene sequencing helps to identify patients with poor prognosis. Redesigning the treatment regimen consisting of cytarabine and daunorubicin has improved the treatment outcomes without increase in the treatment-related mortality. Increasing the dose of daunorubicin to 90 mg/m2 improves complete remission rates without increasing treatment-related complications both in young and elderly patients. Cytarabine (200 mg/m2 in cycle I and 2 g/m2 in cycle 2 is shown to be as effective as high dose cytarabine (1000 mg/m2 twice daily in cycle 1and 2 g/m2 twice daily in cycle 2 and is associated with less treatment-related toxicities. [Int J Basic Clin Pharmacol 2016; 5(3.000: 579-586

  7. Combination Chemotherapy With or Without PSC 833, Peripheral Stem Cell Transplantation, and/or Interleukin-2 in Treating Patients With Acute Myeloid Leukemia

    Science.gov (United States)

    2013-06-03

    Adult Acute Basophilic Leukemia; Adult Acute Eosinophilic Leukemia; Adult Acute Erythroid Leukemia (M6); Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monoblastic Leukemia and Acute Monocytic Leukemia (M5); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Childhood Acute Basophilic Leukemia; Childhood Acute Eosinophilic Leukemia; Childhood Acute Erythroleukemia (M6); Childhood Acute Megakaryocytic Leukemia (M7); Childhood Acute Minimally Differentiated Myeloid Leukemia (M0); Childhood Acute Monoblastic Leukemia (M5a); Childhood Acute Monoblastic Leukemia and Acute Monocytic Leukemia (M5); Childhood Acute Monocytic Leukemia (M5b); Childhood Acute Myeloblastic Leukemia With Maturation (M2); Childhood Acute Myeloblastic Leukemia Without Maturation (M1); Childhood Acute Myelomonocytic Leukemia (M4); Childhood Myelodysplastic Syndromes; de Novo Myelodysplastic Syndromes; Untreated Adult Acute Myeloid Leukemia; Untreated Childhood Acute Myeloid Leukemia and Other Myeloid Malignancies

  8. Transformation of myelodysplastic syndromes into acute myeloid leukemias

    Institute of Scientific and Technical Information of China (English)

    施均; 邵宗鸿; 刘鸿; 白洁; 曹燕然; 何广胜; 凃梅峰; 王秀丽; 郝玉书; 杨天楹; 杨崇礼

    2004-01-01

    Background Myelodysplastic syndromes (MDSs), also called preleukemias, are a group of myeloid hematopoietic malignant disorders. We studied the transformation of MDS into acute myeloid leukemia (AML).Methods Leukemic transformation in 151 patients with MDS was dynamically followed up. The clinical manifestation, peripheral blood and bone marrow condition, karyotypes, immunophenotypes, response to treatment, and prognosis of AML evolution from MDS (MDS-AML) were also observed.Results During the course of this study, over the past eight years and seven months, 21 (13.91%) of 151 MDS patients progressed to overt leukemia, with a median interval of 5 (1-23) months. There were no significant differences between rates of leukemic transformation in comparison with the refractory anemia (RA), RA with excess of blasts (RAEB), and RAEB in transformation (RAEB-t) patient groups. Transformation occurred either gradually or rapidly. There were five parameters positively correlated to leukemic transformation: under 40 years of age, pancytopenia of 3 lineages, more than 15% blasts in the bone marrow, at least two abnormal karyotypes, and treatment with combined chemotherapy. All of the 21 patients with leukemia suffered from MDS-AML, and most of them were M2, M4, or M5. Two (9.52%) MDS-AML patients developed extramedullary infiltration. Leukopenia was found in 47.62% of these patients. Two thirds of these patients, whose bone marrows were generally hypercellular, suffered from neutropenia. After developing AML, 8 (47.06%) patients developed abnormal karyotypes. High expression of immature myeloid antigens, including CD33 [(49.83±24.50)%], CD13 [(36.38±33.84)%], monocytic antigen CD14 [(38.50±24.60)%], and stem cell marker CD34 [(34.67±30.59)%], were found on bone marrow mononuclear cells from MDS-AML patients after leukemic transformation. In some cases, lymphoid antigens, such as CD5, CD7, CD9, and CD19, coexisted with myeloid antigens. A low complete remission rate (31

  9. Angiogenesis in Acute Myeloid Leukemia and Opportunities for Novel Therapies

    Directory of Open Access Journals (Sweden)

    Angelica Trujillo

    2012-01-01

    Full Text Available Acute myeloid leukemia (AML arises from neoplastic transformation of hematopoietic stem and progenitor cells, and relapsed disease remains one of the greater challenges in treating this hematologic malignancy. This paper focuses on angiogenic aspects of AML including the significance and prognostic value of bone marrow microvessel density and circulating cytokine levels. We show three general mechanisms whereby AML exploits angiogenic pathways, including direct induction of angiogenesis, paracrine regulation, and autocrine stimulation. We also present early evidence that leukemia cells contribute directly to vascular endothelia. Novel treatment strategies are proposed, and a review of relevant antiangiogenic clinical trials is presented. By understanding how blood vessels can serve as a reservoir for refractory and relapsed AML, new diagnostics and promising treatment strategies can be developed.

  10. Analogue peptides for the immunotherapy of human acute myeloid leukemia.

    Science.gov (United States)

    Hofmann, Susanne; Mead, Andrew; Malinovskis, Aleksandrs; Hardwick, Nicola R; Guinn, Barbara-Ann

    2015-11-01

    The use of peptide vaccines, enhanced by adjuvants, has shown some efficacy in clinical trials. However, responses are often short-lived and rarely induce notable memory responses. The reason is that self-antigens have already been presented to the immune system as the tumor develops, leading to tolerance or some degree of host tumor cell destruction. To try to break tolerance against self-antigens, one of the methods employed has been to modify peptides at the anchor residues to enhance their ability to bind major histocompatibility complex molecules, extending their exposure to the T-cell receptor. These modified or analogue peptides have been investigated as stimulators of the immune system in patients with different cancers with variable but sometimes notable success. In this review we describe the background and recent developments in the use of analogue peptides for the immunotherapy of acute myeloid leukemia describing knowledge useful for the application of analogue peptide treatments for other malignancies.

  11. Sapacitabine in the treatment of acute myeloid leukemia.

    Science.gov (United States)

    Norkin, Maxim; Richards, Ashley I

    2015-01-01

    Prognosis of elderly patients with acute myeloid leukemia (AML) remains poor and new treatment approaches are urgently needed. A novel nucleoside analog sapacitabine has recently emerged as a feasible agent because of its oral administration and acceptable toxicity profile. Clinical efficacy of sapacitabine, both as a single agent and in combination, has been evaluated in elderly AML patients or AML patients unfit for standard intensive chemotherapy. Response rates varied from 15 to 45% in phase II studies. Sapacitabine was overall well-tolerated with gastrointestinal and myelosuppression-related complications were the most common side effects. Unfortunately, in a phase III study sapacitabine showed no clinical superiority as compared to low-dose cytarabine (LDAC) in patients with AML. Another large phase III study comparing the combination of sapacitabine with decitabine to decitabine alone is currently ongoing and is expected to be completed by the end of 2015 or by the first half of 2016.

  12. Clinical activity of alvocidib (flavopiridol) in acute myeloid leukemia.

    Science.gov (United States)

    Zeidner, Joshua F; Karp, Judith E

    2015-12-01

    There have been minimal therapeutic advancements in acute myeloid leukemia (AML) over the past 4 decades and outcomes remain unsatisfactory. Alvocidib (formerly flavopiridol) is a multi-serine threonine cyclin-dependent kinase inhibitor with demonstrable in vitro and clinical activity in AML when combined in a timed sequential chemotherapy regimen, FLAM (alvocidib followed by cytarabine continuous infusion and mitoxantrone). FLAM has been evaluated in sequential phase 1 and phase 2 studies in 149 and 256 relapsed/refractory and newly diagnosed non-favorable risk AML patients, respectively, with encouraging findings in both patient populations warranting further investigation. This review highlights the mechanism of action of alvocidib, pre-clinical studies of alvocidib in AML, and the clinical trials evaluating alvocidib alone and in combination with cytotoxic agents (FLAM) in AML.

  13. Current findings for recurring mutations in acute myeloid leukemia

    Directory of Open Access Journals (Sweden)

    Takahashi Shinichiro

    2011-09-01

    Full Text Available Abstract The development of acute myeloid leukemia (AML is a multistep process that requires at least two genetic abnormalities for the development of the disease. The identification of genetic mutations in AML has greatly advanced our understanding of leukemogenesis. Recently, the use of novel technologies, such as massively parallel DNA sequencing or high-resolution single-nucleotide polymorphism arrays, has allowed the identification of several novel recurrent gene mutations in AML. The aim of this review is to summarize the current findings for the identification of these gene mutations (Dnmt, TET2, IDH1/2, NPM1, ASXL1, etc., most of which are frequently found in cytogenetically normal AML. The cooperative interactions of these molecular aberrations and their interactions with class I/II mutations are presented. The prognostic and predictive significances of these aberrations are also reviewed.

  14. Relapsing acute myeloid leukemia presenting as hypopyon uveitis

    Directory of Open Access Journals (Sweden)

    Sapna P Hegde

    2011-01-01

    Full Text Available Anterior segment infiltration in acute myeloid leukemia (AML presenting as hypopyon uveitis is very rare. We report this case as an uncommon presentation in a patient on remission after bone marrow transplant for AML. In addition to the hypopyon, the patient presented with "red eye" caused by ocular surface disease due to concurrent graft-versus-host disease and glaucoma. The classical manifestations of masquerade syndrome due to AML were altered by concurrent pathologies. Media opacities further confounded the differential diagnosis. We highlight the investigations used to arrive at a definitive diagnosis. In uveitis, there is a need to maintain a high index of clinical suspicion, as early diagnosis in ocular malignancy can save sight and life.

  15. MicroRNA expression profiling in relation to the genetic heterogeneity of acute myeloid leukemia

    NARCIS (Netherlands)

    M. Jongen-Lavrencic (Mojca); S.M. Sun; M.K. Dijkstra; P.J.M. Valk (Peter); B. Löwenberg (Bob)

    2008-01-01

    textabstractAcute myeloid leukemia (AML) is a highly diverse disease characterized by various cytogenetic and molecular abnormalities. MicroRNAs are small noncoding RNAs that show variable expression during myeloid differentiation. MicroRNA expression in marrow blasts in 215 cases of newly diagnosed

  16. Absence of mutations in the RET gene in acute myeloid leukemia

    NARCIS (Netherlands)

    Visser, M; Hofstra, RMW; Stulp, RP; Wu, Y; Buys, CHCM; Willemze, R; Landegent, JE

    1997-01-01

    Expression of the tyrosine kinase receptor RET has previously been detected in normal hematopoietic cells, and especially in cells of the myeloid lineage. Furthermore, RET was shown to be differentially expressed in acute myeloid leukemia (AML), a disease characterized by excessive cell growth and a

  17. Acquired mutations in ASXL1 in acute myeloid leukemia: Prevalence and prognostic value

    NARCIS (Netherlands)

    M. Pratcorona (Marta); S. Abbas (Saman); M.A. Sanders (Mathijs); J.E. Koenders (Jasper); F.G. Kavelaars (Francois); C.A.J. Erpelinck-Verschueren (C. A J); A. Zeilemakers (Annelieke); B. Löwenberg (Bob); P.J.M. Valk (Peter)

    2012-01-01

    textabstractSomatic mutations in the additional sex comb-like 1 (ASXL1) gene have been described in various types of myeloid malignancies, including acute myeloid leukemia. Analysis of novel markers, such as ASXL1 mutations, in independent clinical trials is indispensable before considering them for

  18. Acute lymphoblastic leukaemia after treatment of nephrotic syndrome with immunosuppressive drugs.

    Science.gov (United States)

    Kuis, W; de Kraker, J; Kuijten, R H; Donckerwolcke, R A; Voûte, P A

    1976-06-01

    The authors present a 4-year-old girl with nephrotic syndrome who developed actue lymphoblastic leukaemia 5 months after the start of a combined treatment of alternate day prednisone and daily cyclophosphamide during 3 months. The nephrotic syndrome was due to focal segmental glomerulosclerosis. The occurrence of leukaemia might be related to the preceeding treatment with cyclophosphamide.

  19. Elevated frequencies of leukemic myeloid and plasmacytoid dendritic cells in acute myeloid leukemia with the FLT3 internal tandem duplication

    OpenAIRE

    Rickmann, Mareike; Krauter, Juergen; Stamer, Kathrin; Heuser, Michael; Salguero, Gustavo; Mischak-Weissinger, Eva; Ganser, Arnold; Stripecke, Renata

    2011-01-01

    Abstract Some 30% of acute myeloid leukemia (AML) patients display an internal tandem duplication (ITD) mutation in the FMS-like tyrosine kinase 3 (FLT3) gene. FLT3-ITDs are known to drive hematopoietic stem cells towards FLT3 ligand independent growth, but the effects on dendritic cell (DC) differentiation during leukemogenesis are not clear. We compared the frequency of cells with immunophenotype of myeloid DC (mDC: Lin?, HLA-DR+, CD11c+, CD86+) and plasmacytoid DC (pDC: Lin?, HL...

  20. ST-elevation myocardial infarction and myelodysplastic syndrome with acute myeloid leukemia transformation.

    Science.gov (United States)

    Jao, Geoffrey T; Knovich, Mary Ann; Savage, Rodney W; Sane, David C

    2014-04-01

    Acute myocardial infarction and acute myeloid leukemia are rarely reported as concomitant conditions. The management of ST-elevation myocardial infarction (STEMI) in patients who have acute myeloid leukemia is challenging: the leukemia-related thrombocytopenia, platelet dysfunction, and systemic coagulopathy increase the risk of bleeding, and the administration of thrombolytic agents can be fatal. We report the case of a 76-year-old man who presented emergently with STEMI, myelodysplastic syndrome, and newly recognized acute myeloid leukemia transformation. Standard antiplatelet and anticoagulation therapy were contraindicated by the patient's thrombocytopenia and by his reported ecchymosis and gingival bleeding upon admission. He declined cardiac catheterization, was provided palliative care, and died 2 hours after hospital admission. We searched the English-language medical literature, found 8 relevant reports, and determined that the prognosis for patients with concomitant STEMI and acute myeloid leukemia is clearly worse than that for either individual condition. No guidelines exist to direct the management of STEMI and concomitant acute myeloid leukemia. In 2 reports, dual antiplatelet therapy, anticoagulation, and drug-eluting stent implantation were used without an increased risk of bleeding in the short term, even in the presence of thrombocytopenia. However, we think that a more conservative approach--balloon angioplasty with the provisional use of bare-metal stents--might be safer. Simultaneous chemotherapy for the acute myeloid leukemia is crucial. Older age seems to be a major risk factor: patients too frail for emergent treatment can die within hours or days.

  1. Acute Myeloid Leukemia NOS | EU Clinical Trials Register [EU Clinical Trials Register

    Lifescience Database Archive (English)

    Full Text Available abel Study of Sargramostim Among Patients Receiving Myelosuppressive Induction Chemotherapy for Acute Myelog...g Myelosuppressive Induction Chemotherapy for Acute Myelogenous Leukemia A.4.1Sponsor's protocol code number...r disease under investigation E.1.1Medical condition(s) being investigated Acute ...Myeloid Leukemia NOS E.1.1.1Medical condition in easily understood language Acute Myeloid Leukemia NOS E.1.1...r investigation E.1.2Version 18.0 E.1.2Level PT E.1.2Classification code 10000880 E.1.2Term Acute

  2. Cardiac function in survivors of childhood acute myeloid leukemia treated with chemotherapy only

    DEFF Research Database (Denmark)

    Jarfelt, Marianne; Andersen, Niels Holmark; Glosli, Heidi

    2015-01-01

    OBJECTIVES: We report cardiac function of patients treated for Childhood acute myeloid leukemia with chemotherapy only according to three consecutive Nordic protocols. METHODS: Ninety-eight of 138 eligible patients accepted examination with standardized echocardiography. Results were compared...

  3. Management of adult and paediatric acute lymphoblastic leukaemia in Asia: resource-stratified guidelines from the Asian Oncology Summit 2013.

    Science.gov (United States)

    Yeoh, Allen E J; Tan, Daryl; Li, Chi-Kong; Hori, Hiroki; Tse, Eric; Pui, Ching-Hon

    2013-11-01

    Survival for adults and children with acute lymphoblastic leukaemia has risen substantially in recent years because use of improved risk-directed treatments and supportive care has widened. In nearly all developed countries, multidisciplinary panels of leukaemia experts have formulated clinical practice guidelines in which standard treatment approaches are recommended on the basis of current evidence. However, those guidelines do not take into account resource limitations in low-income countries, including financial and technical challenges. In Asia, huge disparities in economy and infrastructure exist between countries, and even among different regions in some large countries. At a consensus session held as part of the 2013 Asian Oncology Summit in Bangkok, Thailand, a panel of experts summarised recommendations for management of adult and paediatric acute lymphoblastic leukaemia. Strategies were developed for Asian countries on the basis of available financial, skill, and logistical resources and were stratified in a four-tier system according to the resources available in a particular country or region (basic, limited, enhanced, and maximum).

  4. Clinical impact of leukemic blast heterogeneity at diagnosis in cytogenetic intermediate-risk acute myeloid leukemia

    DEFF Research Database (Denmark)

    Hoffmann, Marianne Hutchings; Klausen, Tobias Wirenfeldt; Boegsted, Martin;

    2012-01-01

    Individual cellular heterogeneity within the acute myeloid leukemia (AML) bone marrow samples can be observed by multi parametric flow cytometry analysis (MFC) indicating that immunophenotypic screening for leukemic blast subsets may have prognostic impact.......Individual cellular heterogeneity within the acute myeloid leukemia (AML) bone marrow samples can be observed by multi parametric flow cytometry analysis (MFC) indicating that immunophenotypic screening for leukemic blast subsets may have prognostic impact....

  5. Relapsed/Refractory acute myeloid leukemia patients | EU Clinical Trials Register [EU Clinical Trials Register

    Lifescience Database Archive (English)

    Full Text Available Treatment of relapsed/refractory leukemia with intravenous administration of Dacarbazine Trattamento della leucemia...tment of relapsed/refractory leukemia with intravenous administration of Dacarbazine Trattamento della leucemia...on(s) being investigated Relapsed/Refractory acute myeloid leukemia patients Pazienti affetti da leucemia... language Relapsed/Refractory acute myeloid leukemia patients Pazienti affetti da leucemia acuta mieloide re...arbazina nei pazienti affetti da leucemia acuta mieloide recidivata/refrattaria i cui blasti esprimono bassi

  6. Detection of FLT3 Oncogene Mutations in Acute Myeloid Leukemia Using Conformation Sensitive Gel Electrophoresis

    OpenAIRE

    2008-01-01

    FLT3 (fms-related tyrosine kinase 3) is a receptor tyrosine kinase class III that is expressed on by early hematopoietic progenitor cells and plays an important role in hematopoietic stem cell proliferation, differentiation and survival. FLT3 is also expressed on leukemia blasts in most cases of acute myeloid leukemia (AML). In order to determine the frequency of FLT3 oncogene mutations, we analyzed genomic DNA of adult de novo acute myeloid leukemia (AML). Polymerase chain reaction (PCR) and...

  7. Prediction of molecular subtypes in acute myeloid leukemia based on gene expression profiling.

    Science.gov (United States)

    Verhaak, Roel G W; Wouters, Bas J; Erpelinck, Claudia A J; Abbas, Saman; Beverloo, H Berna; Lugthart, Sanne; Löwenberg, Bob; Delwel, Ruud; Valk, Peter J M

    2009-01-01

    We examined the gene expression profiles of two independent cohorts of patients with acute myeloid leukemia [n=247 and n=214 (younger than or equal to 60 years)] to study the applicability of gene expression profiling as a single assay in prediction of acute myeloid leukemia-specific molecular subtypes. The favorable cytogenetic acute myeloid leukemia subtypes, i.e., acute myeloid leukemia with t(8;21), t(15;17) or inv(16), were predicted with maximum accuracy (positive and negative predictive value: 100%). Mutations in NPM1 and CEBPA were predicted less accurately (positive predictive value: 66% and 100%, and negative predictive value: 99% and 97% respectively). Various other characteristic molecular acute myeloid leukemia subtypes, i.e., mutant FLT3 and RAS, abnormalities involving 11q23, -5/5q-, -7/7q-, abnormalities involving 3q (abn3q) and t(9;22), could not be correctly predicted using gene expression profiling. In conclusion, gene expression profiling allows accurate prediction of certain acute myeloid leukemia subtypes, e.g. those characterized by expression of chimeric transcription factors. However, detection of mutations affecting signaling molecules and numerical abnormalities still requires alternative molecular methods.

  8. Oncogenic NRAS Primes Primary Acute Myeloid Leukemia Cells for Differentiation.

    Directory of Open Access Journals (Sweden)

    Cornelia Brendel

    Full Text Available RAS mutations are frequently found among acute myeloid leukemia patients (AML, generating a constitutively active signaling protein changing cellular proliferation, differentiation and apoptosis. We have previously shown that treatment of AML patients with high-dose cytarabine is preferentially beneficial for those harboring oncogenic RAS. On the basis of a murine AML cell culture model, we ascribed this effect to a RAS-driven, p53-dependent induction of differentiation. Hence, in this study we sought to confirm the correlation between RAS status and differentiation of primary blasts obtained from AML patients. The gene expression signature of AML blasts with oncogenic NRAS indeed corresponded to a more mature profile compared to blasts with wildtype RAS, as demonstrated by gene set enrichment analysis (GSEA and real-time PCR analysis of myeloid ecotropic viral integration site 1 homolog (MEIS1 in a unique cohort of AML patients. In addition, in vitro cell culture experiments with established cell lines and a second set of primary AML cells showed that oncogenic NRAS mutations predisposed cells to cytarabine (AraC driven differentiation. Taken together, our findings show that AML with inv(16 and NRAS mutation have a differentiation gene signature, supporting the notion that NRAS mutation may predispose leukemic cells to AraC induced differentiation. We therefore suggest that promotion of differentiation pathways by specific genetic alterations could explain the superior treatment outcome after therapy in some AML patient subgroups. Whether a differentiation gene expression status may generally predict for a superior treatment outcome in AML needs to be addressed in future studies.

  9. Longitudinal assessment of nutritional status in children treated for acute lymphoblastic leukaemia in Cuba.

    Science.gov (United States)

    González, A; Cortina, L; González, P; González, C; García, T; de Svarch, E G

    2004-05-01

    Malnutrition has a deleterious effect on the results of therapy for malignant diseases in childhood. The impact of radiotherapy on growth is well known but the impact of cytotoxic drugs on nutritional status is more controversial. The purpose of this study was to determine the nutritional status of a cohort of children treated for acute lymphoblastic leukaemia (ALL) in Cuba. The study involved 49 children admitted to a single center and treated with a Berlin-Frankfurt-Munster-based protocol. Nutritional assessment included measurements of height, weight, body mass index and skin-fold thickness, made at diagnosis, after the intensive phase of treatment and at the end of therapy. Z-scores were used for height and comparison of percentiles for the rest of the variables. All the patients were above the third percentile in all the measurements. There were no statistically significant differences between the results at diagnosis, after intensive therapy and at the end of treatment. Although the sample was small, there was no demonstrable effect of chemotherapy on nutritional status in this Cuban paediatric population, in contrast to that reported in children with ALL in other developing countries.

  10. Clinical characteristics and outcomes in patients with acute promyelocytic leukaemia and hyperleucocytosis.

    Science.gov (United States)

    Daver, Naval; Kantarjian, Hagop; Marcucci, Guido; Pierce, Sherry; Brandt, Mark; Dinardo, Courtney; Pemmaraju, Naveen; Garcia-Manero, Guillermo; O'Brien, Susan; Ferrajoli, Alessandra; Verstovsek, Srdan; Popat, Uday; Hosing, Chitra; Anderlini, Paolo; Borthakur, Gautam; Kadia, Tapan; Cortes, Jorge; Ravandi, Farhad

    2015-03-01

    The clinical characteristics, treatment options and outcomes in patients with acute promyelocytic leukaemia (APL) and hyperleucocytosis remain poorly defined. This study reviewed 242 consecutive patients with APL; 29 patients (12%) had a white blood cell count (WBC) ≥ 50 × 10(9) /l at presentation (median WBC 85·5 × 10(9) /l). Patients with hyperleucocytosis had inferior complete remission (CR) rates (69% vs. 88%; P = 0·004) and higher 4-week mortality (24% vs. 9%; P = 0·018) compared to patients without hyperleucocytosis. We noted a trend towards inferior 3-year disease-free survival (DFS) (69% vs. 80%; P = 0·057) and inferior 3-year overall survival (OS) (74% vs. 92%; P = 0·2) for patients with hyperleucocytosis. Leukapheresis was performed in 11 (38%) of the 29 patients with hyperleucocytosis. CR rate and 3-year OS were not significantly improved in patients who received leukapheresis. CR rate and 3-year OS for the 15 patients with hyperleucocytosis treated with all-trans retinoic acid (ATRA) plus arsenic trioxide (ATO) plus cytotoxic therapy (idarubicin or gemtuzumab ozogamicin) combinations were 100% and 100% vs. 57% and 35% for the 14 patients treated with non-ATRA/ATO combinations (P = 0·004 and P = 0·002). Leukapheresis does not improve the outcomes in patients with APL presenting with hyperleucocytosis. ATRA/ATO-based combinations are superior to other regimens in these patients.

  11. Developing "Care Assistant": A smartphone application to support caregivers of children with acute lymphoblastic leukaemia.

    Science.gov (United States)

    Wang, Jingting; Yao, Nengliang; Wang, Yuanyuan; Zhou, Fen; Liu, Yanyan; Geng, Zhaohui; Yuan, Changrong

    2016-04-01

    Acute lymphoblastic leukaemia (ALL) is the most common childhood malignancy. Caring for children with ALL is an uncommon experience for parents without medical training. They urgently need professional assistance when their children are recovering at home. This paper documents the process of developing an Android application (app) "Care Assistant" for family caregivers of children with ALL. Key informant interviews and focus group studies were used before programming the app. The key informants and focus group members included: caregivers of children with ALL, cancer care physicians and nurses, and software engineers. We found several major challenges faced by caregivers: limited access to evidence-based clinic information, lack of financial and social assistance, deficient communications with doctors or nurses, lack of disease-related knowledge, and inconvenience of tracking treatments and testing results. This feedback was used to develop "Care Assistant". This app has eight modules: personal information, treatment tracking, family care, financial and social assistance, knowledge centre, self-assessment questionnaires, interactive platform, and reminders. We have also developed a web-based administration portal to manage the app. The usability and effectiveness of "Care Assistant" will be evaluated in future studies.

  12. Immunoglobulin genes and T-cell receptors as molecular markers in children with acute lymphoblastic leukaemia

    Directory of Open Access Journals (Sweden)

    Lazić Jelena

    2009-01-01

    Full Text Available Introduction. Acute lymphoblastic leukaemia (ALL is a malignant clonal disease, one of the most common malignancies in childhood. Contemporary protocols ensure high remission rate and long term free survival. The ability of molecular genetic methods help to establish submicroscopic classification and minimal residual disease (MRD follow up, in major percent responsible for relapse. Objective. The aim of the study was to detect the frequency of IgH and TCR gene rearrangements and their correlation with clinical parameters. Methods. Forty-one children with ALL were enrolled in the study group, with initial diagnosis of IgH and TCR gene rearrangements by polimerase chain reaction ( PCR. MRD follow-up was performed in induction phase when morphological remission was expected, and after intensive chemiotherapy. Results. In the study group IgH rearrangement was detected in 82.9% of children at the diagnosis, while TCR rearrangement was seen in 56.1%. On induction day 33, clonal IgH rearrangements persisted in 39% and TCR rearrangements in 36.5% of children. Conclusion. Molecular analysis of genetic alterations and their correlation with standard prognostic parameters show the importance of risk stratification revision which leads to new therapy intensification approach. MRD stands out as a precise predictive factor for the relapse of disease.

  13. Acute lymphoblastic leukaemia: cyclical chemotherapy with three combinations of four drugs (COAP-POMP-CART regimen).

    Science.gov (United States)

    Spiers, A S; Roberts, P D; Marsh, G W; Parekh, S J; Franklin, A J; Galton, D A; Szur, Z L; Paul, E A; Husband, P; Wiltshaw, E

    1975-12-13

    Forty-two adults and children with previously untreated acute lymphoblastic leukaemia (ALL) were entered into a programme of chemotherapy in which three combinations, each of four drugs were administered in a predetermined cyclical rotation together with cranial irradiation and intrathecal injections of methotrexate. Forty-one patients (98%) entered remission and no patient developed neuroleukaemia. Relapse of ALL occurred in 10 patients, and three patients died during remission, while eight patients stopped treatment after two and a half years and have remained in remission for two to 26 months. Comparison of remission and survival experience in this mixed group of children and adults with the experience of children treated at Memphis and in the Medical Research Council's UKALL-I trial showed no significant differences. On the other hand, analysis by prognostic factors showed that neither age nor blast cell count at presentation had any adverse effect in patients treated in this study. No relapses occurred in nine patients with blast cell counts greater than 20 x 109/1 at presentation. This regimen is effective treatment for ALL and may be of special value in patients with poor prognoses. The regiment has not as yet proved superior for the treatment of children with ALL who do not have adverse prognostic features.

  14. Identification of Arsenic Direct-Binding Proteins in Acute Promyelocytic Leukaemia Cells

    Directory of Open Access Journals (Sweden)

    Tao Zhang

    2015-11-01

    Full Text Available The identification of arsenic direct-binding proteins is essential for determining the mechanism by which arsenic trioxide achieves its chemotherapeutic effects. At least two cysteines close together in the amino acid sequence are crucial to the binding of arsenic and essential to the identification of arsenic-binding proteins. In the present study, arsenic binding proteins were pulled down with streptavidin and identified using a liquid chromatograph-mass spectrometer (LC-MS/MS. More than 40 arsenic-binding proteins were separated, and redox-related proteins, glutathione S-transferase P1 (GSTP1, heat shock 70 kDa protein 9 (HSPA9 and pyruvate kinase M2 (PKM2, were further studied using binding assays in vitro. Notably, PKM2 has a high affinity for arsenic. In contrast to PKM2, GSTP1and HSPA9 did not combine with arsenic directly in vitro. These observations suggest that arsenic-mediated acute promyelocytic leukaemia (APL suppressive effects involve PKM2. In summary, we identified several arsenic binding proteins in APL cells and investigated the therapeutic mechanisms of arsenic trioxide for APL. Further investigation into specific signal pathways by which PKM2 mediates APL developments may lead to a better understanding of arsenic effects on APL.

  15. Constitutional abnormalities of chromosome 21 predispose to iAMP21-acute lymphoblastic leukaemia.

    Science.gov (United States)

    Harrison, Christine J; Schwab, Claire

    2016-03-01

    In addition to Down syndrome, individuals with other constitutional abnormalities of chromosome 21 have an increased risk of developing childhood acute lymphoblastic leukaemia (ALL). Specifically, carriers of the Robertsonian translocation between chromosomes 15 and 21, rob(15;21) (q10; q10)c, have ∼2,700 increased risk of developing ALL with iAMP21 (intrachromosomal amplification of chromosome 21). In these patients, chromosome 15 as well as chromosome 21 is involved in the formation of iAMP21, referred to here as der(21)(15;21). Individuals with constitutional ring chromosomes involving chromosome 21, r(21)c, are also predisposed to iAMP21-ALL, involving the same series of mutational processes as seen in sporadic- and der(21)(15;21)-iAMP21 ALL. Evidence is accumulating that the dicentric nature of the Robertsonian and ring chromosome is the initiating factor in the formation of the complex iAMP21 structure. Unravelling these intriguing predispositions to iAMP21-ALL may provide insight into how other complex rearrangements arise in cancer.

  16. Modelling the mechanism of GR/c-Jun/Erg crosstalk in apoptosis of acute lymphoblastic leukaemia

    Directory of Open Access Journals (Sweden)

    Daphne eChen

    2012-11-01

    Full Text Available Acute lymphoblastic leukaemia (ALL is one of the most common forms of malignancy that occurs in lymphoid progenitor cells, particularly in children. Synthetic steroid hormones glucocorticoids (GCs are widely used as part of the ALL treatment regimens due to their apoptotic function, but their use also brings about various side effects and drug resistance. The identification of the molecular differences between the GCs responsive and resistant cells therefore are essential to decipher such complexity and can be used to improve therapy. However, the emerging picture is complicated as the activities of genes and proteins involved are controlled by multiple factors. By adapting the systems biology framework to address this issue, we here integrated the available knowledge together with experimental data via the building of a series of mathematical models. This rationale enabled us to unravel molecular interactions involving c-Jun in GC induced apoptosis and identify Erg as determinant for GC resistance. The results revealed an alternative potential mechanism where c-Jun may be an indirect GR target that is controlled via an upstream repressor protein. The models also highlight the importance of Erg for GR function, particularly in GC sensitive C7 cells where Erg directly regulates GR in agreement with our previous experimental results. Our models describe potential GR-controlled molecular mechanisms of c-Jun/Bim and Erg regulation. We also demonstrate the importance of using a systematic approach to translate human disease processes into computational models in order to derive information-driven new hypotheses.

  17. Childhood T-cell acute lymphoblastic leukaemia expressing "Ia-like" antigen:" a case report.

    Science.gov (United States)

    Kupa, A; Beckman, I G; Bradley, J; Moore, H; Thomas, M; Zola, H; Cheney, K; Rice, M; Toogood, I

    1982-01-01

    A 4-year-old girl presenting with vomiting, abdominal pain, and renal failure was found to have gross hepatosplenomegaly, a renal mass, and bilateral pleural effusions. A diagnosis of acute lymphoblastic leukaemia (ALL) was suggested by a peripheral white cell count (WCC) of 119,000 x 10(6)mm3, 57% blasts, 22% lymphocytes, and confirmed by bone marrow examination. Lymphocyte surface marker studies at diagnosis enabled classification as a T-ALL, with a significant proportion of the T cells also bearing receptors for the third component of complement (C3). Seventy-two percent of the peripheral blood mononuclear cells reacted with anti-Ia monoclonal antibody (FMC44), and a smaller proportion (25%) carried receptors for the Fc portion of IgG. The T-classification of this ALL was verified at central nervous system (CNS) relapse and at a subsequent nodal relapse. Double-marker studies on cells from the infiltrated lymph node prepared in suspension confirmed the presence of Ia-positive T cells. The Ia marker is usually a useful discriminant between T and non-T cells in normal and ALL cell populations. The case described here highlights the need for a panel of markers to be used in classification of childhood ALL and supports the suggestion that there is a distinct subtype of Ia-positive T-ALL.

  18. Noma in a child with acute leukaemia: when the 'face of poverty' finds an ally.

    Science.gov (United States)

    Singh, Amitabh; Mandal, Anirban; Seth, Rachna; Kabra, Sushil Kumar

    2016-01-06

    A 2-year-6-month old, appropriately immunised, well-thriving boy, symptomatic for the past 6 months, presented with recurrent fever, progressive pallor, lymphadenopathy and a raw area on the right cheek, with discharging sinus. The necrotising infection of the face developed after one and half months of febrile illness. This febrile illness with bicytopaenia was diagnosed as enteric fever and treated with antibiotics. Skin grafting was performed for the full-thickness defect of the face. The patient continued to have a non-healing oral ulcer with progressive pallor and was finally diagnosed as having acute lymphoblastic leukaemia. Immunodeficiency was ruled out by appropriate investigations. Noma is an indirect measure of extreme poverty, but malignancy is known to predispose to this debilitating condition. The worldwide incidence of Noma is reported to be 30,000-140,000, with a preponderance in sub-Saharan Africa. This case emphasises the need for a thorough search for the underlying illness predisposing to a rare opportunistic infection such as Noma in a well-thriving child.

  19. Therapeutic Effects of Myeloid Cell Leukemia-1 siRNA on Human Acute Myeloid Leukemia Cells

    Directory of Open Access Journals (Sweden)

    Hadi Karami

    2014-05-01

    Full Text Available Purpose: Up-regulation of Mcl-1, a known anti-apoptotic protein, is associated with the survival and progression of various malignancies including leukemia. The aim of this study was to explore the effect of Mcl-1 small interference RNA (siRNA on the proliferation and apoptosis of HL-60 acute myeloid leukemia (AML cells. Methods: siRNA transfection was performed using Lipofectamine™2000 reagent. Relative mRNA and protein expressions were quantified by quantitative real-time PCR and Western blotting, respectively. Trypan blue assay was performed to assess tumor cell proliferation after siRNA transfection. The cytotoxic effect of Mcl-1 siRNA on leukemic cells was measured using MTT assay. Apoptosis was detected using ELISA cell death assay. Results: Mcl-1 siRNA clearly lowered both Mcl-1 mRNA and protein levels in a time-dependent manner, leading to marked inhibition of cell survival and proliferation. Furthermore, Mcl-1 down-regulation significantly enhanced the extent of HL-60 apoptotic cells. Conclusion: Our results suggest that the down-regulation of Mcl-1 by siRNA can effectively trigger apoptosis and inhibit the proliferation of leukemic cells. Therefore, Mcl-1 siRNA may be a potent adjuvant in AML therapy.

  20. A single nucleotide polymorphism in cBIM is associated with a slower achievement of major molecular response in chronic myeloid leukaemia treated with imatinib.

    Directory of Open Access Journals (Sweden)

    Vanessa Augis

    Full Text Available PURPOSE: BIM is essential for the response to tyrosine-kinase inhibitors (TKI in chronic myeloid leukaemia (CML patients. Recently, a deletion polymorphism in intron 2 of the BIM gene was demonstrated to confer an intrinsic TKI resistance in Asian patients. The present study aimed at identifying mutations in the BIM sequence that could lead to imatinib resistance independently of BCR-ABL mutations. EXPERIMENTAL DESIGN: BIM coding sequence analysis was performed in 72 imatinib-treated CML patients from a French population of our centre and in 29 healthy controls (reference population as a case-control study. Real-time quantitative PCR (RT qPCR was performed to assess Bim expression in our reference population. RESULTS: No mutation with amino-acid change was found in the BIM coding sequence. However, we observed a silent single nucleotide polymorphism (SNP c465C>T (rs724710. A strong statistical link was found between the presence of the T allele and the high Sokal risk group (p = 0.0065. T allele frequency was higher in non responsive patients than in the reference population (p = 0.0049. Similarly, this T allele was associated with the mutation frequency on the tyrosine kinase domain of BCR-ABL (pT SNP of BIM could be useful for predicting the outcome of imatinib-treated CML patients.

  1. Acute Myeloid Leukemia (AML) | EU Clinical Trials Register [EU Clinical Trials Register

    Lifescience Database Archive (English)

    Full Text Available cian’s Choice in Patients ≥ 60 Years Old with Relapsed/Refractory Acute Myeloid L....1 Medical condition or disease under investigation E.1.1Medical condition(s) being investigated Acute... Myeloid Leukemia (AML) E.1.1.1Medical condition in easily understood language Acute My... condition or disease under investigation E.1.2Version 18.0 E.1.2Level LLT E.1.2Classification code 10000886 E.1.2Term Acute

  2. Human leucocytic antigen-DR negative acute myeloid leukemia: A diagnostic dilemma for hematopathologist

    Directory of Open Access Journals (Sweden)

    Ashish Gupta

    2014-01-01

    Full Text Available Background: Acute myeloid leukemia (AML blast variably express Human leucocytic antigen (HLA.We retrospectively analyzed immunophenotypic and clinical profile of 12 cases of HLA -DR negative AML and correlated with their morphological, cytogenetics and Molecular findings.There is a paucity of literature mentioning morphological, immunophenotypic and cytogenetics characteristics of HLA DR negative AML. Aim: This study was designed to study the morphological, flow cytometric, and cytogenetics characteristics of HLA DR negative AML/non acute Promyelocytic Leukaemia (APML cases. Materials and Methods: Seventeen such cases were diagnosed over a period of 1 year and 8 months. Peripheral blood and bone marrow aspiration smears were stained by Wright giemsa and examined by three hematopathologist independently. Immunophenotyping was done using multicolour flow cytometry on BD FACS CANTO II using FACS DIVA software.Conventional Karyotyping was done using Wright giemsa staining (using IKAROS software and florescent in situ hybridization (FISH was done using dual color dual fusion probe from Vysis promyelocytic leukemia-retinoic acid receptor alpha (PML-RARA fusion gene probe. Molecular analysis using reverse transcriptase-polymerase chain reaction (RT-PCR was done using Thermal Cycler of Applied Biosystem and Gel-Doc by Biorad. Results : Of the 12 cases studied ten were classified as French-American-British (FAB AML-M1. Two case as FAB AML-M2. Morphologically the cells resemble abnormal promyelocytes with bilobation, convoluted and folded nucleus, inconspicuous nucleoli and open chromatin (n = 11 and with blastic morphology, open chromatin, and inconspicuous nucleoli (n = 1.Karyotyping analysis shows normal karyotype (n = 10, del 9q-(n = 1, and t (5:9 (n = 1 respectively.FISH done using dual color dual fusion probe (n = 12 do not show PML-RARA fusion signal.RT-PCR (n = 12 revealed a negative result for PML - RARA fusion transcripts. Conclusion: HLA

  3. Management of adult and paediatric acute lymphoblastic leukaemia in Asia: resource-stratified guidelines from the Asian Oncology Summit 2013

    Science.gov (United States)

    Yeoh, Allen EJ; Tan, Daryl; Li, Chi-Kong; Hori, Hiroki; Tse, Eric; Pui, Ching-Hon

    2014-01-01

    The survival rates for both adult and children with acute lymphoblastic leukaemia have improved substantially in recent years with wider use of improved risk-directed therapy and supportive care. In nearly all developed countries, clinical practice guidelines have been formulated by multidisciplinary panels of leukaemia experts, with the goal of providing recommendations on standard treatment approaches based on current evidence. However, those guidelines do not take into account resource limitations in low-income countries, including financial and technical challenges. In Asia, there are huge disparities in economy and infrastructure among the countries, and even among different regions in some large countries. This review summarizes the recommendations developed for Asian countries by a panel of adult and paediatric leukaemia therapists, based on the availability of financial, skill and logistical resources, at a consensus session held as part of the 2013 Asian Oncology Summit in Bangkok, Thailand. The management strategies described here are stratified by a four-tier system (basic, limited, enhanced and maximum) based on the resources available to a particular country or region. PMID:24176570

  4. Molecular Therapeutic Approaches for Pediatric Acute Myeloid Leukemia

    Directory of Open Access Journals (Sweden)

    Sarah K Tasian

    2014-03-01

    Full Text Available Approximately two thirds of children with acute myeloid leukemia (AML are cured with intensive multi-agent chemotherapy. However, primary chemorefractory and relapsed AML remains a significant source of childhood cancer mortality, highlighting the need for new therapies. Further therapy intensification with traditional cytotoxic agents is not feasible given the potential for significant toxicity to normal tissues with conventional chemotherapy and the risk for long-term end-organ dysfunction. Significant emphasis has been placed upon the development of molecularly targeted therapeutic approaches for adults and children with high-risk subtypes of AML with the goal of improving remission induction and minimizing relapse. Several promising agents are currently in clinical testing or late preclinical development for AML, including monoclonal antibodies against leukemia cell surface proteins, kinase inhibitors, proteasome inhibitors, epigenetic agents, and chimeric antigen receptor engineered T cell immunotherapies. Many of these therapies have been specifically tested in children with relapsed/refractory AML via phase 1 and 2 trials with a smaller number of new agents under phase 3 evaluation for children with de novo AML. Although successful identification and implementation of new drugs for children with AML remains a formidable challenge, enthusiasm for novel molecular therapeutic approaches is great given the potential for significant clinical benefit for children who will otherwise fail standard therapy.

  5. FLT3 inhibitors: clinical potential in acute myeloid leukemia

    Science.gov (United States)

    Hospital, Marie-Anne; Green, Alexa S; Maciel, Thiago T; Moura, Ivan C; Leung, Anskar Y; Bouscary, Didier; Tamburini, Jerome

    2017-01-01

    Acute myeloid leukemia (AML) is an aggressive hematopoietic malignancy that is cured in as few as 15%–40% of cases. Tremendous improvements in AML prognostication arose from a comprehensive analysis of leukemia cell genomes. Among normal karyotype AML cases, mutations in the FLT3 gene are the ones most commonly detected as having a deleterious prognostic impact. FLT3 is a transmembrane tyrosine kinase receptor, and alterations of the FLT3 gene such as internal tandem duplications (FLT3-ITD) deregulate FLT3 downstream signaling pathways in favor of increased cell proliferation and survival. FLT3 tyrosine kinase inhibitors (TKI) emerged as a new therapeutic option in FLT3-ITD AML, and clinical trials are ongoing with a variety of TKI either alone, combined with chemotherapy, or even as maintenance after allogenic stem cell transplantation. However, a wide range of molecular resistance mechanisms are activated upon TKI therapy, thus limiting their clinical impact. Massive research efforts are now ongoing to develop more efficient FLT3 TKI and/or new therapies targeting these resistance mechanisms to improve the prognosis of FLT3-ITD AML patients in the future. PMID:28223820

  6. Definition of Cure in Childhood Acute Myeloid Leukemia

    Science.gov (United States)

    Rubnitz, Jeffrey E.; Inaba, Hiroto; Leung, Wing; Pounds, Stanley; Cao, Xueyuan; Campana, Dario; Ribeiro, Raul C.; Pui, Ching-Hon

    2014-01-01

    Background A better understanding of when cure can be declared in childhood acute myeloid leukemia (AML) would reduce anxiety and improve quality of life of AML survivors. We determined the likelihood of patients with AML to maintain long-term remission after completion of therapy. Patients and Methods The cumulative risk of relapse, time to relapse, event-free survival and overall survival were analyzed for 604 patients with AML enrolled in seven successive clinical trials, divided into 3 treatment eras (1976–1991, 1991–1997, 2002–2008). Results The median time to relapse did not change over time (0.93 years vs. 0.76 vs. 0.8 years for each consecutive era, P = .22) but the risk of relapse decreased significantly (5-year cumulative incidence of relapse 52.6% ± 3.1% vs. 31.5% ± 3.9% vs. 22.0% ± 3.0%, P < .001). Among patients who were in remission 4 years from diagnosis, the probabilities of relapse were 1.7%, 2.9%, and 0.9%, respectively. In the most recent era, all 44 relapses except one occurred within four years of diagnosis. Conclusion Children with AML who are treated with contemporary therapy and remain in remission four years from diagnosis are likely cured. Although late relapses and late deaths from other causes are rare, long-term follow up of survivors is necessary for timely management of late adverse effects. PMID:24798038

  7. TP53 mutations in older adults with acute myeloid leukemia.

    Science.gov (United States)

    Yanada, Masamitsu; Yamamoto, Yukiya; Iba, Sachiko; Okamoto, Akinao; Inaguma, Yoko; Tokuda, Masutaka; Morishima, Satoko; Kanie, Tadaharu; Mizuta, Shuichi; Akatsuka, Yoshiki; Okamoto, Masataka; Emi, Nobuhiko

    2016-04-01

    The net benefits of induction therapy for older adults with acute myeloid leukemia (AML) remain controversial. Because AML in older adults is a heterogeneous disease, it is important to identify those who are unlikely to benefit from induction therapy based on information available at the initial assessment. We used next-generation sequencing to analyze TP53 mutation status in AML patients aged 60 years or older, and evaluated its effects on outcomes. TP53 mutations were detected in 12 of 77 patients (16 %), and there was a significant association between TP53 mutations and monosomal karyotype. Patients with TP53 mutations had significantly worse survival than those without (P = 0.009), and multivariate analysis identified TP53 mutation status as the most significant prognostic factor for survival. Neverthelsess, TP53-mutated patients had a 42 % chance of complete remission and a median survival of 8.0 months, which compares favorably with those who did not undergo induction therapy, even in the short term. These results suggest that screening for TP53 mutations at diagnosis is useful for identifying older adults with AML who are least likely to respond to chemotherapy, although the presence of this mutation alone does not seem to justify rejecting induction therapy.

  8. Immunohistochemistry predicts nucleophosmin (NPM) mutations in acute myeloid leukemia.

    Science.gov (United States)

    Falini, Brunangelo; Martelli, Maria Paola; Bolli, Niccolò; Bonasso, Rossella; Ghia, Emanuela; Pallotta, Maria Teresa; Diverio, Daniela; Nicoletti, Ildo; Pacini, Roberta; Tabarrini, Alessia; Galletti, Barbara Verducci; Mannucci, Roberta; Roti, Giovanni; Rosati, Roberto; Specchia, Giorgina; Liso, Arcangelo; Tiacci, Enrico; Alcalay, Myriam; Luzi, Lucilla; Volorio, Sara; Bernard, Loris; Guarini, Anna; Amadori, Sergio; Mandelli, Franco; Pane, Fabrizio; Lo-Coco, Francesco; Saglio, Giuseppe; Pelicci, Pier-Giuseppe; Martelli, Massimo F; Mecucci, Cristina

    2006-09-15

    Nucleophosmin (NPM) exon-12 mutations occur in 50% to 60% of adult acute myeloid leukemia (AML) with normal karyotype and are predictors of favorable prognosis. We evaluated bone marrow or peripheral blood samples from 450 adult patients with AML of the GIMEMA (Gruppo Italiano Malattie Ematologiche Maligne dell'Adulto)/AML12 EORTC (European Organization for Research and Treatment of Cancer) trial to (1) search for new exon-12 NPM mutations; (2) determine whether NPM immunostaining on paraffin-embedded biopsies predicts NPM mutations; and (3) investigate altered nucleocytoplasmic NPM traffic in primary AML cells. Fourteen NPM mutations, including 8 new variants, were identified. All 200 AML cases expressing cytoplasmic NPM (NPMc(+) AML) carried NPM mutations. None of the 250 cases with nucleus-restricted NPM (NPMc(-) AML) was mutated. At the C-terminus, NPM leukemic mutants carried mutations of only tryptophan 290 or of both tryptophans 288 and 290 and a new nuclear export signal (NES) motif, which appear to underlie their nuclear export. The specific Crm1/exportin-1 inhibitor leptomycin-B relocated NPM mutants from cytoplasm to nucleus of primary NPMc(+) AML cells, demonstrating that nuclear export is NES dependent. NPM mutants bound and recruited wild-type NPM into leukemic cell cytoplasm. Because alterations at C-terminus of leukemic NPM mutants are similar, immunohistochemistry detects all exon-12 NPM mutations and is a valuable, inexpensive tool in the diagnostic-prognostic work-up of patients with AML with normal karyotype.

  9. Acute myeloid leukemia with DNMT3A mutations.

    Science.gov (United States)

    Li, Yunlong; Zhu, Baosheng

    2014-09-01

    Acute myeloid leukemia (AML), a type of blood cancer, is characterized by an increase in the number of abnormal white blood cells in the bone marrow, frequently causing hematopoietic insufficiency. It is a heterogeneous disease featuring cytogenetic aberrations, recurrent somatic mutations and alterations in gene expression. DNA (cytosine-5-)-methyltransferase 3 alpha (DNMT3A) is closely associated with epigenetic modifications in mammalian development and disease. More recent studies have identified recurrent somatic mutations in DNMT3A in AML, most of which are heterozygous. The DNMT3A R882 codon is a mutational hotspot. The frequency of DNMT3A mutations varies among different countries, but mutations have been found to be associated with cytogenetics, age, white blood cell (WBC) count, prognosis and response of patients to chemotherapy. The normal function of DNMT3A can be disrupted by these mutations, which subsequently results in an abnormality of epigenetic modification. These data suggest that mutations in the DNMT3A gene represent a novel class of mutations in AML with distinct biological and clinical features. Further studies are needed to elucidate the exact molecular mechanism and function of DNMT3A mutations in leukemogenesis.

  10. Gene mutations of acute myeloid leukemia in the genome era.

    Science.gov (United States)

    Naoe, Tomoki; Kiyoi, Hitoshi

    2013-02-01

    Ten years ago, gene mutations found in acute myeloid leukemia (AML) were conceptually grouped into class I mutation, which causes constitutive activation of intracellular signals that contribute to the growth and survival, and class II mutation, which blocks differentiation and/or enhance self-renewal by altered transcription factors. A cooperative model between two classes of mutations has been suggested by murine experiments and partly supported by epidemiological findings. In the last 5 years, comprehensive genomic analysis proceeded to find new gene mutations, which are found in the epigenome-associated enzymes and the molecules never noticed so far. These new mutations apparently increase the complexity and heterogeneity of AML. Although a long list of gene mutations might have been compiled, the entire picture of molecular pathogenesis in AML remains to be elucidated because gene rearrangement, gene copy number, DNA methylation and expression profiles are not fully studied in conjunction with gene mutations. Comprehensive genome research will deepen the understanding of AML to promote the development of new classification and treatment. This review focuses on gene mutations that were recently discovered by genome sequencing.

  11. Molecular cytogenetic analysis of dicentric chromosomes in acute myeloid leukemia.

    Science.gov (United States)

    Sarova, Iveta; Brezinova, Jana; Zemanova, Zuzana; Ransdorfova, Sarka; Izakova, Silvia; Svobodova, Karla; Pavlistova, Lenka; Berkova, Adela; Cermak, Jaroslav; Jonasova, Anna; Siskova, Magda; Michalova, Kyra

    2016-04-01

    Dicentric chromosomes (DCs) have been described in many hematological diseases, including acute myeloid leukemia (AML). They are markers of cancer and induce chromosomal instability, leading to the formation of other chromosomal aberrations and the clonal evolution of pathological cells. Our knowledge of the roles and behavior of human DCs is often derived from studies of induced DCs and cell lines. It is difficult to identify all the DCs in the karyotypes of patients because of the limitations of metaphase cytogenetic methods. The aim of this study was to revise the karyotypes of 20 AML patients in whom DCs were found with conventional G-banding or multicolor fluorescence in situ hybridization (mFISH) with (multi)centromeric probes and to characterize the DCs at the molecular cytogenetic level. FISH analyses confirmed 23 of the 29 expected DCs in 18 of 20 patients and identified 13 others that had not been detected cytogenetically. Fourteen DCs were altered by other chromosomal changes. In conclusion, karyotypes with DCs are usually very complex, and we have shown that they often contain more than one DC, which can be missed with conventional or mFISH methods. Our study indicates an association between number of DCs in karyotype and very short survival of patients.

  12. Lysosomal disruption preferentially targets acute myeloid leukemia cells and progenitors

    Science.gov (United States)

    Sukhai, Mahadeo A.; Prabha, Swayam; Hurren, Rose; Rutledge, Angela C.; Lee, Anna Y.; Sriskanthadevan, Shrivani; Sun, Hong; Wang, Xiaoming; Skrtic, Marko; Seneviratne, Ayesh; Cusimano, Maria; Jhas, Bozhena; Gronda, Marcela; MacLean, Neil; Cho, Eunice E.; Spagnuolo, Paul A.; Sharmeen, Sumaiya; Gebbia, Marinella; Urbanus, Malene; Eppert, Kolja; Dissanayake, Dilan; Jonet, Alexia; Dassonville-Klimpt, Alexandra; Li, Xiaoming; Datti, Alessandro; Ohashi, Pamela S.; Wrana, Jeff; Rogers, Ian; Sonnet, Pascal; Ellis, William Y.; Corey, Seth J.; Eaves, Connie; Minden, Mark D.; Wang, Jean C.Y.; Dick, John E.; Nislow, Corey; Giaever, Guri; Schimmer, Aaron D.

    2012-01-01

    Despite efforts to understand and treat acute myeloid leukemia (AML), there remains a need for more comprehensive therapies to prevent AML-associated relapses. To identify new therapeutic strategies for AML, we screened a library of on- and off-patent drugs and identified the antimalarial agent mefloquine as a compound that selectively kills AML cells and AML stem cells in a panel of leukemia cell lines and in mice. Using a yeast genome-wide functional screen for mefloquine sensitizers, we identified genes associated with the yeast vacuole, the homolog of the mammalian lysosome. Consistent with this, we determined that mefloquine disrupts lysosomes, directly permeabilizes the lysosome membrane, and releases cathepsins into the cytosol. Knockdown of the lysosomal membrane proteins LAMP1 and LAMP2 resulted in decreased cell viability, as did treatment of AML cells with known lysosome disrupters. Highlighting a potential therapeutic rationale for this strategy, leukemic cells had significantly larger lysosomes compared with normal cells, and leukemia-initiating cells overexpressed lysosomal biogenesis genes. These results demonstrate that lysosomal disruption preferentially targets AML cells and AML progenitor cells, providing a rationale for testing lysosomal disruption as a novel therapeutic strategy for AML. PMID:23202731

  13. Pharmacokinetics of posaconazole prophylaxis of patients with acute myeloid leukemia.

    Science.gov (United States)

    Mattiuzzi, Gloria; Yilmaz, Musa; Kantarjian, Hagop; Borthakur, Gautam; Konopleva, Marina; Jabbour, Elias; Brown, Yolanda; Pierce, Sherry; Cortes, Jorge

    2015-09-01

    Antifungal prophylaxis is routinely given to patients with hematologic malignancies at high risk for invasive fungal infections (IFI), yet breakthrough IFI may still occur. Posaconazole emerged as an excellent alternative for fungal prophylaxis in high-risk patients. There is limited data about pharmacokinetics and plasma concentrations of posaconazole when given as prophylaxis in patients with hematologic malignancies. We recruited 20 adult patients for prospective, open label trial of posaconazole given as a prophylaxis in patients with newly diagnosed acute myeloid leukemia (AML) undergoing induction chemotherapy or first salvage therapy. The median age of all patients was 65 years and received prophylaxis for a median of 38 days (range: 5-42 days).Ten patients (50%) completed 42 days on posaconazole prophylaxis. Median plasma posaconazole levels showed no statistical difference across gender, body surface area, patients developing IFI, and patients acquiring grade 3 or 4 elevation of liver enzymes. However, there was an overall trend for higher trough concentrations among patients with no IFI than those with IFI. Pharmacokinetics of posaconazole varies from patient to patient, and AML patients receiving induction chemotherapy who never develop IFI tend to have higher plasma concentrations after oral administration of posaconazole.

  14. Multiplex high-throughput gene mutation analysis in acute myeloid leukemia.

    Science.gov (United States)

    Dunlap, Jennifer; Beadling, Carol; Warrick, Andrea; Neff, Tanaya; Fleming, William H; Loriaux, Marc; Heinrich, Michael C; Kovacsovics, Tibor; Kelemen, Katalin; Leeborg, Nicky; Gatter, Ken; Braziel, Rita M; Press, Richard; Corless, Christopher L; Fan, Guang

    2012-12-01

    Classification of acute myeloid leukemia increasingly depends on genetic analysis. However, the number of known mutations in acute myeloid leukemia is expanding rapidly. Therefore, we tested a high-throughput screening method for acute myeloid leukemia mutation analysis using a multiplex mass spectrometry-based approach. To our knowledge, this is the first reported application of this approach to genotype leukemias in a clinical setting. One hundred seven acute myeloid leukemia cases were screened for mutations using a panel that covers 344 point mutations across 31 genes known to be associated with leukemia. The analysis was performed by multiplex polymerase chain reaction for mutations in genes of interest followed by primer extension reactions. Products were analyzed on a Sequenom MassARRAY system (San Diego, CA). The multiplex panel yielded mutations in 58% of acute myeloid leukemia cases with normal cytogenetics and 21% of cases with abnormal cytogenetics. Cytogenetics and routine polymerase chain reaction-based screening of NPM1, CEBPA, FLT3-ITD, and KIT was also performed on a subset of cases. When combined with the results of these standard polymerase chain reaction-based tests, the mutation frequency reached 78% in cases with normal cytogenetics. Of these, 42% harbored multiple mutations primarily involving NPM1 with NRAS, KRAS, CEBPA, PTPN11, IDH1, or FLT3. In contrast, cases with abnormal cytogenetics rarely harbored more than 1 mutation (1.5%), suggesting different underlying biology. This study demonstrates the feasibility and utility of broad-based mutation profiling of acute myeloid leukemia in a clinical setting. This approach will be helpful in defining prognostic subgroups of acute myeloid leukemia and contribute to the selection of patients for enrollment into trials with novel inhibitors.

  15. Bayesian network meta-analysis comparing five contemporary treatment strategies for newly diagnosed acute promyelocytic leukaemia.

    Science.gov (United States)

    Wu, Fenfang; Wu, Di; Ren, Yong; Duan, Chongyang; Chen, Shangwu; Xu, Anlong

    2016-07-26

    Acute promyelocytic leukemia (APL) is a curable subtype of acute myeloid leukemia. The optimum regimen for newly diagnosed APL remains inconclusive. In this Bayesian network meta-analysis, we compared the effectiveness of five regimens-arsenic trioxide (ATO) + all-trans retinoic acid (ATRA), realgar-indigo naturalis formula (RIF) which contains arsenic tetrasulfide + ATRA, ATRA + anthracycline-based chemotherapy (CT), ATO alone and ATRA alone, based on fourteen randomized controlled trials (RCTs), which included 1407 newly diagnosed APL patients. According to the results, the ranking efficacy of the treatment, including early death and complete remission in the induction stage, was the following: 1. ATO/RIF + ATRA; 2. ATRA + CT; 3. ATO, and 4. ATRA. For long-term benefit, ATO/RIF + ATRA significantly improved overall survival (OS) (hazard ratio = 0.35, 95%CI 0.15-0.82, p = 0.02) and event-free survival (EFS) (hazard ratio = 0.32, 95%CI 0.16-0.61, p = 0.001) over ATRA + CT regimen for the low-to-intermediate-risk patients. Thus, ATO + ATRA and RIF + ATRA might be considered the optimum treatments for the newly diagnosed APL and should be recommended as the standard care for frontline therapy.

  16. Targeting etoposide to acute myelogenous leukaemia cells using nanostructured lipid carriers coated with transferrin

    Science.gov (United States)

    Khajavinia, Amir; Varshosaz, Jaleh; Jafarian Dehkordi, Abbas

    2012-10-01

    The aim of the present study was to evaluate the diverse properties of transferrin (Tf)-conjugated nanostructured lipid carriers (NLCs) prepared using three different fatty amines, including stearylamine (SA), dodecylamine (DA) and spermine (SP), and two different methods for Tf coupling. Etoposide-loaded NLCs were prepared by an emulsion-solvent evaporation method followed by probe sonication. Chemical coupling of NLCs with Tf was mediated by an amide linkage between the surface-exposed amino group of the fatty amine and the carboxyl group of the protein. The physical coating was performed in a Ringer-Hepes buffer medium. NLCs were characterized by their particle size, zeta potential, polydispersity index, drug entrapment percentage, drug release profiles and Tf-coupling efficiency. The cytotoxicity of NLCs on K562 acute myelogenous leukaemia cells was studied by MTT assay, and their cellular uptake was studied by a flow cytometry method. SA-containing NLCs showed the lowest particle size, the highest zeta potential and the largest coupling efficiency values. The drug entrapment percentage and the zeta potential decreased after Tf coupling, but the average particle size increased. SP-containing formulations released their drug contents comparatively slower than SA- or DA-containing NLCs. Unconjugated NLCs released moderately more drug than Tf-NLCs. Flow cytometry studies revealed enhanced cellular uptake of Tf-NLCs compared to unconjugated ones. Blocking Tf receptors resulted in a significantly higher cell survival rate for Tf-NLCs. The highest cytotoxic activity was observed in the chemically coupled SA-containing nanoparticles, with an IC50 value of 15-fold lower than free etoposide.

  17. Validation of a mouse xenograft model system for gene expression analysis of human acute lymphoblastic leukaemia

    Directory of Open Access Journals (Sweden)

    Francis Richard W

    2010-04-01

    Full Text Available Abstract Background Pre-clinical models that effectively recapitulate human disease are critical for expanding our knowledge of cancer biology and drug resistance mechanisms. For haematological malignancies, the non-obese diabetic/severe combined immunodeficient (NOD/SCID mouse is one of the most successful models to study paediatric acute lymphoblastic leukaemia (ALL. However, for this model to be effective for studying engraftment and therapy responses at the whole genome level, careful molecular characterisation is essential. Results Here, we sought to validate species-specific gene expression profiling in the high engraftment continuous ALL NOD/SCID xenograft. Using the human Affymetrix whole transcript platform we analysed transcriptional profiles from engrafted tissues without prior cell separation of mouse cells and found it to return highly reproducible profiles in xenografts from individual mice. The model was further tested with experimental mixtures of human and mouse cells, demonstrating that the presence of mouse cells does not significantly skew expression profiles when xenografts contain 90% or more human cells. In addition, we present a novel in silico and experimental masking approach to identify probes and transcript clusters susceptible to cross-species hybridisation. Conclusions We demonstrate species-specific transcriptional profiles can be obtained from xenografts when high levels of engraftment are achieved or with the application of transcript cluster masks. Importantly, this masking approach can be applied and adapted to other xenograft models where human tissue infiltration is lower. This model provides a powerful platform for identifying genes and pathways associated with ALL disease progression and response to therapy in vivo.

  18. Constitutional and somatic rearrangement of chromosome 21 in acute lymphoblastic leukaemia.

    Science.gov (United States)

    Li, Yilong; Schwab, Claire; Ryan, Sarra L; Papaemmanuil, Elli; Robinson, Hazel M; Jacobs, Patricia; Moorman, Anthony V; Dyer, Sara; Borrow, Julian; Griffiths, Mike; Heerema, Nyla A; Carroll, Andrew J; Talley, Polly; Bown, Nick; Telford, Nick; Ross, Fiona M; Gaunt, Lorraine; McNally, Richard J Q; Young, Bryan D; Sinclair, Paul; Rand, Vikki; Teixeira, Manuel R; Joseph, Olivia; Robinson, Ben; Maddison, Mark; Dastugue, Nicole; Vandenberghe, Peter; Haferlach, Claudia; Stephens, Philip J; Cheng, Jiqiu; Van Loo, Peter; Stratton, Michael R; Campbell, Peter J; Harrison, Christine J

    2014-04-03

    Changes in gene dosage are a major driver of cancer, known to be caused by a finite, but increasingly well annotated, repertoire of mutational mechanisms. This can potentially generate correlated copy-number alterations across hundreds of linked genes, as exemplified by the 2% of childhood acute lymphoblastic leukaemia (ALL) with recurrent amplification of megabase regions of chromosome 21 (iAMP21). We used genomic, cytogenetic and transcriptional analysis, coupled with novel bioinformatic approaches, to reconstruct the evolution of iAMP21 ALL. Here we show that individuals born with the rare constitutional Robertsonian translocation between chromosomes 15 and 21, rob(15;21)(q10;q10)c, have approximately 2,700-fold increased risk of developing iAMP21 ALL compared to the general population. In such cases, amplification is initiated by a chromothripsis event involving both sister chromatids of the Robertsonian chromosome, a novel mechanism for cancer predisposition. In sporadic iAMP21, breakage-fusion-bridge cycles are typically the initiating event, often followed by chromothripsis. In both sporadic and rob(15;21)c-associated iAMP21, the final stages frequently involve duplications of the entire abnormal chromosome. The end-product is a derivative of chromosome 21 or the rob(15;21)c chromosome with gene dosage optimized for leukaemic potential, showing constrained copy-number levels over multiple linked genes. Thus, dicentric chromosomes may be an important precipitant of chromothripsis, as we show rob(15;21)c to be constitutionally dicentric and breakage-fusion-bridge cycles generate dicentric chromosomes somatically. Furthermore, our data illustrate that several cancer-specific mutational processes, applied sequentially, can coordinate to fashion copy-number profiles over large genomic scales, incrementally refining the fitness benefits of aggregated gene dosage changes.

  19. A role for paclitaxel in the combination chemotherapy of acute myeloblastic leukaemia: preclinical cell culture studies.

    Science.gov (United States)

    Curtis, J E; Minkin, S; Minden, M D; McCulloch, E A

    1996-11-01

    Paclitaxel dose responses in culture have been investigated alone and in association with cytosine arabinoside (ARA-C) and all-trans retinoic acid (ATRA), with the objective of identifying a role for paclitaxel in the treatment of acute myeloblastic leukaemia (AML). Initial studies were done to determine if paclitaxel dose responses of AML blast cell precursors were altered by regulatory compounds known to modify the dose responses of ARA-C. In contrast to ARA-C, paclitaxel dose responses were independent of cell culture method, the growth factors G-CSF and GM-CSF, and the ligands all-trans retinoic acid (ATRA) and hydrocortisone. Most blast cell populations were sensitive to paclitaxel; compared with normal marrow progenitors the dose responses were markedly heterogenous with some more, and others less, sensitive. Remission marrow progenitor paclitaxel responses resembled those of AML blasts in heterogeneity. The cell culture model tested the effect of pacliataxel and ATRA on the ARA-C dose responses of OCI/ AML-5; paclitaxel exposure was either before or after ARA-C to test for an effect of schedule; ATRA was added to the MEC cultures after paclitaxel and ARA-C. Repeat experiments were done to test three dose levels each of paclitaxel and ATRA. When paclitaxel was given after ARA-C, synergism was found for all but one of the dose combinations tested; only three examples of synergy were seen when paclitaxel preceded ARA-C. The studies justify trials combining ARA-C, paclitaxel and ATRA using a schedule suggested by the cell culture findings.

  20. Alternating hemiparesis and orolingual apraxia as manifestations of methotrexate neurotoxicity in a paediatric case of acute lymphoblastic leukaemia.

    Science.gov (United States)

    Yap, Siew Mei; MacEneaney, Peter; Ryan, Clodagh; O'Toole, Orna

    2016-04-25

    A 15-year-old girl with a recent diagnosis of acute lymphoblastic leukaemia was admitted to hospital with pancytopaenia after having received high-dose intrathecal methotrexate 1 day prior. During the next week she had intermittent episodes of alternating hemiparesis associated with speech arrest lasting minutes to hours at a time. The episodes were not associated with altered level of consciousness or headache. MRI of the brain showed features consistent with methotrexate encephalopathy. This report discusses the typical clinical and radiological features of methotrexate neurotoxicity in addition to differential diagnoses and the proposed pathophysiological mechanisms.

  1. Inherited coding variants at the CDKN2A locus influence susceptibility to acute lymphoblastic leukaemia in children

    DEFF Research Database (Denmark)

    Xu, Heng; Zhang, Hui; Yang, Wenjian;

    2015-01-01

    There is increasing evidence from genome-wide association studies for a strong inherited genetic basis of susceptibility to acute lymphoblastic leukaemia (ALL) in children, yet the effects of protein-coding variants on ALL risk have not been systematically evaluated. Here we show a missense variant...... of haematopoietic progenitor cells, and is preferentially retained in ALL tumour cells. Resequencing the CDKN2A-CDKN2B locus in 2,407 childhood ALL cases reveals 19 additional putative functional germline variants. These results provide direct functional evidence for the influence of inherited genetic variation...

  2. pediatric patient with acute myeloid leukemia | EU Clinical Trials Register [EU Clinical Trials Register

    Lifescience Database Archive (English)

    Full Text Available emia in children and adolescent protocollo per la leucemia acuta mieloide in età pediatrica A.3.2Name or abb...pediatric patient with acute myeloid leukemia pazienti in età pediatrica affetti da leucemia acuta mieloide ...te myeloid leukemia pazienti in età pediatrica affetti da leucemia acuta mieloide E.1.1.2Therapeutic area Di

  3. Clinical characteristics and prognosis of acute myeloid leukemia associated with DNA-methylation regulatory gene mutations.

    Science.gov (United States)

    Ryotokuji, Takeshi; Yamaguchi, Hiroki; Ueki, Toshimitsu; Usuki, Kensuke; Kurosawa, Saiko; Kobayashi, Yutaka; Kawata, Eri; Tajika, Kenji; Gomi, Seiji; Kanda, Junya; Kobayashi, Anna; Omori, Ikuko; Marumo, Atsushi; Fujiwara, Yusuke; Yui, Shunsuke; Terada, Kazuki; Fukunaga, Keiko; Hirakawa, Tsuneaki; Arai, Kunihito; Kitano, Tomoaki; Kosaka, Fumiko; Tamai, Hayato; Nakayama, Kazutaka; Wakita, Satoshi; Fukuda, Takahiro; Inokuchi, Koiti

    2016-09-01

    In recent years, it has been reported that the frequency of DNA-methylation regulatory gene mutations - mutations of the genes that regulate gene expression through DNA methylation - is high in acute myeloid leukemia. The objective of the present study was to elucidate the clinical characteristics and prognosis of acute myeloid leukemia with associated DNA-methylation regulatory gene mutation. We studied 308 patients with acute myeloid leukemia. DNA-methylation regulatory gene mutations were observed in 135 of the 308 cases (43.8%). Acute myeloid leukemia associated with a DNA-methylation regulatory gene mutation was more frequent in older patients (Pgene mutation was an unfavorable prognostic factor for overall survival in the whole cohort (P=0.0018), in patients aged ≤70 years, in patients with intermediate cytogenetic risk, and in FLT3-ITD-negative patients (P=0.0409). Among the patients with DNA-methylation regulatory gene mutations, 26.7% were found to have two or more such mutations and prognosis worsened with increasing number of mutations. In multivariate analysis DNA-methylation regulatory gene mutation was an independent unfavorable prognostic factor for overall survival (P=0.0424). However, patients with a DNA-methylation regulatory gene mutation who underwent allogeneic stem cell transplantation in first remission had a significantly better prognosis than those who did not undergo such transplantation (P=0.0254). Our study establishes that DNA-methylation regulatory gene mutation is an important unfavorable prognostic factor in acute myeloid leukemia.

  4. Targeted positron emission tomography imaging of CXCR4 expression in patients with acute myeloid leukemia.

    Science.gov (United States)

    Herhaus, Peter; Habringer, Stefan; Philipp-Abbrederis, Kathrin; Vag, Tibor; Gerngross, Carlos; Schottelius, Margret; Slotta-Huspenina, Julia; Steiger, Katja; Altmann, Torben; Weißer, Tanja; Steidle, Sabine; Schick, Markus; Jacobs, Laura; Slawska, Jolanta; Müller-Thomas, Catharina; Verbeek, Mareike; Subklewe, Marion; Peschel, Christian; Wester, Hans-Jürgen; Schwaiger, Markus; Götze, Katharina; Keller, Ulrich

    2016-08-01

    Acute myeloid leukemia originates from leukemia-initiating cells that reside in the protective bone marrow niche. CXCR4/CXCL12 interaction is crucially involved in recruitment and retention of leukemia-initiating cells within this niche. Various drugs targeting this pathway have entered clinical trials. To evaluate CXCR4 imaging in acute myeloid leukemia, we first tested CXCR4 expression in patient-derived primary blasts. Flow cytometry revealed that high blast counts in patients with acute myeloid leukemia correlate with high CXCR4 expression. The wide range of CXCR4 surface expression in patients was reflected in cell lines of acute myeloid leukemia. Next, we evaluated the CXCR4-specific peptide Pentixafor by positron emission tomography imaging in mice harboring CXCR4 positive and CXCR4 negative leukemia xenografts, and in 10 patients with active disease. [(68)Ga]Pentixafor-positron emission tomography showed specific measurable disease in murine CXCR4 positive xenografts, but not when CXCR4 was knocked out with CRISPR/Cas9 gene editing. Five of 10 patients showed tracer uptake correlating well with leukemia infiltration assessed by magnetic resonance imaging. The mean maximal standard uptake value was significantly higher in visually CXCR4 positive patients compared to CXCR4 negative patients. In summary, in vivo molecular CXCR4 imaging by means of positron emission tomography is feasible in acute myeloid leukemia. These data provide a framework for future diagnostic and theranostic approaches targeting the CXCR4/CXCL12-defined leukemia-initiating cell niche.

  5. Allergy and acute leukaemia in children with Down syndrome: a population study. Report from the Mexican inter-institutional group for the identification of the causes of childhood leukaemia

    Science.gov (United States)

    Núñez-Enríquez, J C; Fajardo-Gutiérrez, A; Buchán-Durán, E P; Bernáldez-Ríos, R; Medina-Sansón, A; Jiménez-Hernández, E; Amador-Sanchez, R; Peñaloza-Gonzalez, J G; Paredes-Aguilera, R; Alvarez-Rodriguez, F J; Bolea-Murga, V; de Diego Flores-Chapa, J; Flores-Lujano, J; Bekker-Mendez, V C; Rivera-Luna, R; del Carmen Rodriguez-Zepeda, M; Rangel-López, A; Dorantes-Acosta, E M; Núñez-Villegas, N; Velazquez-Aviña, M M; Torres-Nava, J R; Reyes-Zepeda, N C; Cárdenas-Cardos, R; Flores-Villegas, L V; Martinez-Avalos, A; Salamanca-Gómez, F; Gorodezky, C; Arellano-Galindo, J; Mejía-Aranguré, J M

    2013-01-01

    Background: Allergies have been described as protective factors against the development of childhood acute leukaemia (AL). Our objective was to investigate the associations between allergy history and the development of AL and acute lymphoblastic leukaemia (ALL) in children with Down syndrome (DS). Methods: A case–control study was performed in Mexico City. The cases (n=97) were diagnosed at nine public hospitals, and the controls (n=222) were recruited at institutions for children with DS. Odds ratios (OR) were calculated. Results: Asthma was positively associated with AL development (OR=4.18; 95% confidence interval (CI): 1.47–11.87), whereas skin allergies were negatively associated (OR=0.42; 95% CI: 0.20–0.91). Conclusion: Our findings suggest that allergies and AL in children with DS share biological and immune mechanisms. To our knowledge, this is the first study reporting associations between allergies and AL in children with DS. PMID:23695017

  6. Cell sorting enables interphase fluorescence in situ hybridization detection of low BCR-ABL1 producing stem cells in chronic myeloid leukaemia patients beyond deep molecular remission.

    Science.gov (United States)

    van Kooten Niekerk, Peter B; Petersen, Charlotte C; Nyvold, Charlotte G; Ommen, Hans B; Roug, Anne S; Nederby, Line; Hokland, Peter; Kjeldsen, Eigil

    2014-01-01

    The exact disease state of chronic myeloid leukaemia (CML) patients in deep molecular remission is unknown, because even the most sensitive quantitative reverse transcription polymerase chain reaction (qPCR) methods cannot identify patients prone to relapse after treatment withdrawal. To elucidate this, CD34(+) stem cell and progenitor cell subpopulations were isolated by fluorescence-activated cell sorting (FACS), and their content of residual Philadelphia positive (Ph(+) ) cells was evaluated in 17 CML patients (major molecular response, n = 6; 4-log reduction in BCR-ABL1 expression (MR(4) ), n = 11) using both sensitive qPCR and interphase fluorescence in situ hybridization (iFISH). Despite evaluating fewer cells, iFISH proved superior to mRNA-based qPCR in detecting residual Ph(+) stem cells (P = 0·005), and detected Ph(+) stem- and progenitor cells in 9/10 patients at frequencies of 2-14%. Moreover, while all qPCR(+) samples also were iFISH(+) , 9/33 samples were qPCR-/iFISH(+) , including all positive samples from MR(4) patients. Our findings show that residual Ph(+) cells are low BCR-ABL1 producers, and that DNA-based methods are required to assess the content of persisting Ph(+) stem cells in these patients. This approach demonstrates a clinically applicable manner of assessing residual disease at the stem cell level in CML patients in MR(4) , and may enable early and safe identification of candidates for tyrosine kinase inhibitor withdrawal.

  7. Peripartum cardiomyopathy in a patient treated for acute myeloid leukemia

    Directory of Open Access Journals (Sweden)

    Čolović Nataša

    2016-01-01

    Full Text Available Introduction. Peripartum cardiomyopathy usually presents with systolic heart failure during the last months of pregnancy and up to five months postpartum. The disease is rare and can be fatal. Case Outline. We report a 30-year-old female who was diagnosed with acute myeloid leukemia, with maturation and cytogenetic finding of t(8;21(q22;q22,del(9(q22 in January 2004. She was treated with chemotherapy and achieved complete remission that lasts to date. She became pregnant and delivered a healthy newborn with caesarean section in 2009. Seven months later, she again became pregnant and delivered the second child with caesarean section in January 2011. Seven days after delivery she developed symptoms and signs of heart failure. Electrocardiogram showed sinus rhythm, low voltage and negative T-waves in inferior and lateral leads. Echocardiography revealed global left ventricular dysfunction with ejection fraction of 15%, with mobile thrombotic mass of 12 mm attached to the left ventricle wall. She was treated with both unfractionated and low-molecular heparin, diuretics, cardiotonics, and beta-blockers. Within six following weeks left ventricle systolic function improved up to 25-30%. The full clinical recovery was achieved in September 2013, resulting in absence of heart failure and left ventricular ejection fraction of 54%. Conclusion. Peripartum cardiomyopathy is a rare condition. The cause of cardiomyopathy is unknown, but it is believed that it could be triggered by various conditions and risk factors. Although the patient was treated with cardiotoxic drugs (doxorubicin and mitoxantrone in permitted doses, they could have been contributory factors of myocardial damage. Close monitoring of cardiac function in the peripartal period might be beneficial in patients treated with cardiotoxic drugs. [Projekat Ministarstva nauke Republike Srbije, br. 175080 I br. OI 175034

  8. Treatment Outcome in Older Patients with Childhood Acute Myeloid Leukemia

    Science.gov (United States)

    Rubnitz, Jeffrey E.; Pounds, Stanley; Cao, Xueyuan; Jenkins, Laura; Dahl, Gary; Bowman, W. Paul; Taub, Jeffrey W; Pui, Ching-Hon; Ribeiro, Raul C.; Campana, Dario; Inaba, Hiroto

    2013-01-01

    Background Older age has historically been an adverse prognostic factor in pediatric acute myeloid leukemia (AML). The impact of age relative to that of other prognostic factors on the outcome of patients treated in recent trials is unknown. Methods Clinical outcome and causes of treatment failure of 351 patients enrolled on three consecutive protocols for childhood AML between 1991 and 2008 were analyzed according to age and protocol. Results The more recent protocol (AML02) produced improved outcomes for 10- to 21-year-old patients compared to 2 earlier studies (AML91 and 97), with 3-year rates of event-free survival (EFS), overall survival (OS) and cumulative incidence of refractory leukemia or relapse (CIR) for this group similar to those of 0- to 9-year old patients: EFS, 58.3% ± 5.4% vs. 66.6% ± 4.9%, P=.20; OS, 68.9% ± 5.1% vs. 75.1% ± 4.5%, P=.36; cumulative incidence of refractory leukemia or relapse, 21.9% ± 4.4%; vs. 25.3% ± 4.1%, P=.59. EFS and OS estimates for 10–15-year-old patients overlapped those for 16–21-year-old patients. However, the cumulative incidence of toxic death was significantly higher for 10- to 21-year-old patients compared to younger patients (13.2% ± 3.6 vs. 4.5% ± 2.0%, P=.028). Conclusion The survival rate for older children with AML has improved on our recent trial and is now similar to that of younger patients. However, deaths from toxicity remain a significant problem in the older age group. Future trials should focus on improving supportive care while striving to develop more effective antileukemic therapy. PMID:22674050

  9. Rare myeloid sarcoma/acute myeloid leukemia with adrenal mass after allogeneic mobilization peripheral blood stem cell transplantation

    Institute of Scientific and Technical Information of China (English)

    Ya-Fei Wang; Qian Li; Wen-Gui Xu; Jian-Yu Xiao; Qing-Song Pang; Qing Yang; Yi-Zuo Zhang

    2013-01-01

    Myeloid sarcoma (MS) is a rare hematological neoplasm that develops either de novo or concurrently with acute myeloid leukemia (AML). This neoplasm can also be an initial manifestation of relapse in a previously treated AML that is in remission. A 44-year-old male patient was diagnosed with testis MS in a local hospital in August 2010. Atfer one month, bone marrow biopsy and aspiration conifrmed the diagnosis of AML. Allogeneic mobilization peripheral blood stem cell transplantation was performed, with the sister of the patient as donor, after complete remission (CR) was achieved by chemotherapy. Five months after treatment, an adrenal mass was detected by positron emission tomography-computed tomography (PET-CT). Radiotherapy was performed for the localized mass after a multidisciplinary team (MDT) discussion. hTe patient is still alive as of May 2013, with no evidence of recurrent MS or leukemia.

  10. Complex Variant of Philadelphia Translocation Involving Chromosomes 9, 12, and 22 in a Case with Chronic Myeloid Leukaemia

    Science.gov (United States)

    Malvestiti, F.; Agrati, C.; Chinetti, S.; Di Meco, A.; Cirrincione, S.; Oggionni, M.; Grimi, B.; Maggi, F.; Simoni, G.; Grati, F. R.

    2014-01-01

    Chronic myeloid leukemia (CML) is a hematopoietic stem cell disorder included in the broader diagnostic category of myeloproliferative neoplasms, associated with fusion by BCR gene at chromosome 22q11 to ABL1 gene at chromosome 9q34 with the formation of the Philadelphia (Ph) chromosome. In 2–10% of CML cases, the fusion gene arises in connection with a variant translocation, involving chromosomes 9, 22, and one or more different chromosomes; consequently, the Ph chromosome could be masked within a complex chromosome rearrangement. In cases with variant Ph translocation a deletion on der(9) may be more frequently observed than in cases with the classical one. Herein we describe a novel case of CML with complex variant Ph translocation involving chromosomes 9, 12, and 22. We present the hematologic response and cytogenetic response after Imatinib treatment. We also speculated the mechanism which had originated the chromosome rearrangement. PMID:25045550

  11. Complex Variant of Philadelphia Translocation Involving Chromosomes 9, 12, and 22 in a Case with Chronic Myeloid Leukaemia

    Directory of Open Access Journals (Sweden)

    F. Malvestiti

    2014-01-01

    Full Text Available Chronic myeloid leukemia (CML is a hematopoietic stem cell disorder included in the broader diagnostic category of myeloproliferative neoplasms, associated with fusion by BCR gene at chromosome 22q11 to ABL1 gene at chromosome 9q34 with the formation of the Philadelphia (Ph chromosome. In 2–10% of CML cases, the fusion gene arises in connection with a variant translocation, involving chromosomes 9, 22, and one or more different chromosomes; consequently, the Ph chromosome could be masked within a complex chromosome rearrangement. In cases with variant Ph translocation a deletion on der(9 may be more frequently observed than in cases with the classical one. Herein we describe a novel case of CML with complex variant Ph translocation involving chromosomes 9, 12, and 22. We present the hematologic response and cytogenetic response after Imatinib treatment. We also speculated the mechanism which had originated the chromosome rearrangement.

  12. A one-mutation mathematical model can explain the age incidence of acute myeloid leukemia with mutated nucleophosmin (NPM1)

    NARCIS (Netherlands)

    A. Liso (Arcangelo); F. Castiglione (Filippo); A. Cappuccio (Antonio); F. Stracci (Fabrizio); R.F. Schlenk (Richard); S. Amadori (Sergio); C. Thiede (Christian); S. Schnittger (Susanne); P.J.M. Valk (Peter); K. Döhner (Konstanze); M.F. Martelli (Massimo F.); M. Schaich (Markus); J. Krauter; A. Ganser (Arnold); N. Bolli (Niccolò); B. Löwenberg (Bob); T. Haferlach (Torsten); G. Ehninger (Gerhard); F. Mandelli (Franco); F. Michor (Franziska); B. Falini

    2008-01-01

    textabstractAcute myeloid leukemia with mutated NPM1 gene and aberrant cytoplasmic expression of nucleophosmin (NPMc+acute myeloid leukemia) shows distinctive biological and clinical features. Experimental evidence of the oncogenic potential of the nucleophosmin mutant is, however, still lacking, an

  13. [Research Advances of IDH2 Gene Mutation in Acute Myeloid Leukemia].

    Science.gov (United States)

    Zhao, Yan-Xia; Shen, Xu-Liang

    2016-04-01

    Acute myeloid leukemia (AML) is a malignant clonal hematologic disease from hematopoietic stem and progenitor cells. The isocitrate dehychogenase 2 (IDH2) gene mutation has been recently found, which may be associated with the course of AML. The incidence of IDH2 gene mutation in the patients with acute myeloid leukemia is high, especially in the AML patients with normal karyotype. Different subtypes of IDH2 mutation, or companing other molecular biology, will make different influence on clinical features and progress of patients with AML. IDH2 mutation is stable, which can be used as the test sign of AML and minimal residual disease (MRD), and for guiding the clinical treatment and predicting the progress. In this article, the research progress of IDH2 mutation in acute myeloid leukemia is reviewed.

  14. Behandling af akut myeloid leukæmi uden transfusion af blodprodukter hos et medlem af Jehovas Vidner

    DEFF Research Database (Denmark)

    Larsen, Christian; Jensen, Morten Krogh

    2011-01-01

    We present a case in which a young woman was diagnosed with acute myeloid leukaemia, FAB-classification type M2. As a member of Jehovah's Witnesses she refused to accept any treatment involving blood transfusions. A modified induction and consolidation chemotherapy regimen was applied, tailored...

  15. Population pharmacokinetics of cytarabine, etoposide and daunorubicin in the treatment of acute myeloid leukaemia

    DEFF Research Database (Denmark)

    Krogh-Madsen, Mikkel; Bender, B.; Jensen, M. K.;

    2012-01-01

    PURPOSE: Interpatient variability in the pharmacokinetics (PK) of cytarabine, etoposide, and daunorubicin following body surface area-adjusted doses calls for studies that point to other covariates to explain this variability. The purpose of this study was to investigate such relationships and give......(®); for daunorubicin, PK information from a prior study was utilized. RESULTS: Baseline white blood cell count (bWBC) influenced the PK for all drugs. A small, statistically insignificant improvement in model fit was achieved when a relationship between bWBC and daunorubicin central volume of distribution was included...... in creatinine clearance of 60 mL/min resulted in a decrease in etoposide clearance of 32%. CONCLUSIONS: Population-based models characterized the PK for all three drugs. bWBC was a significant covariate for etoposide and cytarabine and showed a trend for daunorubicin. Linking the significant bWBC relationships...

  16. Acute myeloid leukaemia | EU Clinical Trials Register [EU Clinical Trials Register

    Lifescience Database Archive (English)

    Full Text Available esidual disease and other risk factors for relapse. Terapia per pazienti giovani e adulti affetti da leucemia...- Pazienti di età compresa tra i 18 ed i 60 anni; - Pazienti affetti da leucemia ... agenti chemioterapici (con l’eccezione di non più di sette giorni di idrossiurea); - Diagnosi inequivocabile di leucemia...ici WHO (almeno il 20% di blasti nel midollo osseo), con classificazione FAB oltre M3 (leucemia acuta promie...dovute al coinvolgimento della leucemia; - Frazione di eiezione ventricolare sinistra (LVEF) >50%, determ

  17. Pubertal development and fertility in survivors of childhood acute myeloid leukemia treated with chemotherapy only

    DEFF Research Database (Denmark)

    Molgaard-Hansen, Lene; Skou, Anne-Sofie; Juul, Anders

    2013-01-01

    More than 60% of children with acute myeloid leukemia (AML) become long-term survivors. Most are cured using chemotherapy without hematopoietic stem cell transplantation (HSCT). We report on pubertal development and compare self-reported parenthood among AML survivors and their siblings.......More than 60% of children with acute myeloid leukemia (AML) become long-term survivors. Most are cured using chemotherapy without hematopoietic stem cell transplantation (HSCT). We report on pubertal development and compare self-reported parenthood among AML survivors and their siblings....

  18. Cerebral sinus venous thromboses in children with acute lymphoblastic leukaemia - a multicentre study from the Nordic Society of Paediatric Haematology and Oncology

    DEFF Research Database (Denmark)

    Ranta, Susanna; Tuckuviene, Ruta; Mäkipernaa, Anne

    2014-01-01

    We present a prospective multicentre cohort of 20 children with acute lymphoblastic leukaemia (ALL) and cerebral sinus venous thrombosis (CSVT). The study covers a period of 5 years and comprises 1038 children treated according to the Nordic Society of Paediatric Haematology and Oncology (NOPHO...

  19. Myocardial 2D strain echocardiography and cardiac biomarkers in children during and shortly after anthracycline therapy for acute lymphoblastic leukaemia (ALL): a prospective study

    NARCIS (Netherlands)

    Mavinkurve-Groothuis, A.M.C.; Marcus, K.A.; Pourier, M.; Loonen, J.; Feuth, T.; Hoogerbrugge, P.M.; Korte, C.L. de; Kapusta, L.

    2013-01-01

    AIMS: The aim of this study was to investigate myocardial 2D strain echocardiography and cardiac biomarkers in the assessment of cardiac function in children with acute lymphoblastic leukaemia (ALL) during and shortly after treatment with anthracyclines. METHODS AND RESULTS: Cardiac function of 60 c

  20. High white blood cell count at diagnosis of childhood acute lymphoblastic leukaemia: biological background and prognostic impact. Results from the NOPHO ALL-92 and ALL-2000 studies

    DEFF Research Database (Denmark)

    Vaitkeviciene, G; Forestier, E; Hellebostad, M;

    2011-01-01

    Prognostic impact of peripheral blood white blood cell count (WBC) at the diagnosis of childhood acute lymphoblastic leukaemia (ALL) was evaluated in a population-based consecutive series of 2666 children aged 1–15 treated for ALL between 1992 and 2008 in the five Nordic countries (Denmark, Finland...

  1. In vitro drug resistance and prognostic impact of p16(INK4A)/p15(INK4B) deletions in childhood T-cell acute lymphoblastic leukaemia

    NARCIS (Netherlands)

    Ramakers-van Woerden, NL; Pieters, R; Slater, RM; Loonen, A.H.; Beverloo, HB; van Drunen, E; Heyman, M; Moreno, TC; Rots, MG; van Wering, ER; Kamps, WA; Janka-Schaub, GE; Veerman, AJP

    2001-01-01

    p16 gene deletions are present in about 70% of primary paediatric T-cell acute lymphoblastic leukaemia (T-ALL) and 20% of common/precursor B-cell ALL cases. It is not clear what the impact of the frequent p16 deletions is within the subgroup of T-lineage ALL. We studied the relationship between p16/

  2. Isocitrate dehydrogenase 1 mutations prime the all-trans retinoic acid myeloid differentiation pathway in acute myeloid leukemia.

    Science.gov (United States)

    Boutzen, Héléna; Saland, Estelle; Larrue, Clément; de Toni, Fabienne; Gales, Lara; Castelli, Florence A; Cathebas, Mathilde; Zaghdoudi, Sonia; Stuani, Lucille; Kaoma, Tony; Riscal, Romain; Yang, Guangli; Hirsch, Pierre; David, Marion; De Mas-Mansat, Véronique; Delabesse, Eric; Vallar, Laurent; Delhommeau, François; Jouanin, Isabelle; Ouerfelli, Ouathek; Le Cam, Laurent; Linares, Laetitia K; Junot, Christophe; Portais, Jean-Charles; Vergez, François; Récher, Christian; Sarry, Jean-Emmanuel

    2016-04-04

    Acute myeloid leukemia (AML) is characterized by the accumulation of malignant blasts with impaired differentiation programs caused by recurrent mutations, such as the isocitrate dehydrogenase (IDH) mutations found in 15% of AML patients. These mutations result in the production of the oncometabolite (R)-2-hydroxyglutarate (2-HG), leading to a hypermethylation phenotype that dysregulates hematopoietic differentiation. In this study, we identified mutant R132H IDH1-specific gene signatures regulated by key transcription factors, particularly CEBPα, involved in myeloid differentiation and retinoid responsiveness. We show that treatment with all-trans retinoic acid (ATRA) at clinically achievable doses markedly enhanced terminal granulocytic differentiation in AML cell lines, primary patient samples, and a xenograft mouse model carrying mutant IDH1. Moreover, treatment with a cell-permeable form of 2-HG sensitized wild-type IDH1 AML cells to ATRA-induced myeloid differentiation, whereas inhibition of 2-HG production significantly reduced ATRA effects in mutant IDH1 cells. ATRA treatment specifically decreased cell viability and induced apoptosis of mutant IDH1 blasts in vitro. ATRA also reduced tumor burden of mutant IDH1 AML cells xenografted in NOD-Scid-IL2rγ(null)mice and markedly increased overall survival, revealing a potent antileukemic effect of ATRA in the presence of IDH1 mutation. This therapeutic strategy holds promise for this AML patient subgroup in future clinical studies.

  3. SIRT2 activates G6PD to enhance NADPH production and promote leukaemia cell proliferation

    Science.gov (United States)

    Xu, Shuang-Nian; Wang, Tian-Shi; Li, Xi; Wang, Yi-Ping

    2016-01-01

    Like most other types of cancer cells, leukaemia cells undergo metabolic reprogramming to support rapid proliferation through enhancing biosynthetic processes. Pentose phosphate pathway (PPP) plays a pivotal role in meeting the anabolic demands for cancer cells. However, the molecular mechanism by which PPP contributes to leukaemia remains elusive. Here, we report that leukaemia cell proliferation is dependent on the oxidative branch of PPP, in particular the first and rate-limiting enzyme glucose-6-phosphate dehydrogenase (G6PD). Knockdown of G6PD reduces NADPH level in acute myeloid leukaemia (AML) cell lines. Exogenous lipid supplements partially restore the proliferation of G6PD-depleted cells. Deacetylase SIRT2 promotes NADPH production through deacetylating G6PD at lysine 403 (K403). Activation of G6PD by SIRT2 supports the proliferation and clonogenic activity of leukaemia cells. Chemical inhibitors against SIRT2 suppress G6PD activity, leading to reduced cell proliferation of leukaemia cells, but not normal hematopoietic stem and progenitor cells. Importantly, SIRT2 is overexpressed in clinical AML samples, while K403 acetylation is downregulated and G6PD catalytic activity is increased comparing to that of normal control. Together, our study reveals that acetylation regulation of G6PD is involved in the metabolic reprogramming of AML, and SIRT2 serves as a promising target for further therapeutic investigations. PMID:27586085

  4. Sinonasal Lymphoma Presenting as a Probable Sanctuary Site for Relapsed B Acute Lymphoblastic Leukaemia: A Case Report and Review of the Literature

    Directory of Open Access Journals (Sweden)

    W. Y. Lim

    2015-01-01

    Full Text Available Sinonasal lymphoma is a non-Hodgkin lymphoma (NHL representing 1.5% of all lymphomas. It presents as an unremitting ulceration with progressive destruction of midline sinonasal and surrounding structures. Poor prognosis warrants early treatment although diagnosis is challenging and frequently delayed. It is usually primary in origin and to our knowledge the sinonasal region has never been reported as a sanctuary site in leukaemia/lymphoma relapse. We present a unique case of B-cell ALL (acute lymphoblastic leukaemia with late relapse to the nasal septum as a sinonasal lymphoblastic lymphoma and with genetic support for this as a sanctuary site.

  5. Fatal cardiac tamponade as the first manifestation of acute myeloid leukemia.

    Science.gov (United States)

    Leptidis, John; Aloizos, Stavros; Chlorokostas, Panagiotis; Gourgiotis, Stavros

    2014-10-01

    Acute myeloid leukemia is a hemopoietic myeloid stem cell neoplasm. It is the most common acute leukemia affecting adults,and its incidence increases with age. Acute myeloid leukemia is characterized by the rapid growth of abnormal white blood cells that accumulate in the bone marrow and interfere with the production of normal blood cells. As the leukemic cells keep filling the bone marrow, symptoms of the disease started to appear: fatigue, bleeding, increased frequency of infections, and shortness of breath. Cardiac tamponade or pericardial tamponade is an acute medical condition in which the accumulation of pericardial fluid prevents the function of the heart. Signs and symptoms include Beck triad (hypotension, distended neck veins, and muffled heart sounds), paradoxus pulses, tachycardia, tachypnea, and breathlessness. Pericardial effusion and cardiac tamponade are rare and severe complications of leukemia; they often develop during the radiation therapy, chemotherapy, or infections in the course of leukemia. This study sought to assess the fatal cardiac tamponade as the first manifestation of acute myeloid leukemia (AML). We found no reports in the literature linking these 2 clinical entities. Although the patient had no signs or diagnosis of AML previously, this case was remarkable for the rapidly progressive symptoms and the fatal outcome. The pericardial effusion reaccumulated rapidly after its initial drainage; it is a possible explanation that the leukemic cells interfered with cardiac activity or that they decreased their contractility myocytes secreting a toxic essence.

  6. Assessment of oxidative stress in acute myeloid leukemia

    Directory of Open Access Journals (Sweden)

    Esfahani A

    2011-02-01

    Full Text Available "nBackground: Many chemotherapeutic regimens used in the treatment of cancer generate free radicals that may be a part of their beneficial effects. The aim of this study was to assess the oxidative status in patients undergoing chemotherapy for acute myeloid leukemia (AML."n "nMethods: Thirty-eight patients with AML (17 female and 21 male patients with a mean age 34.05±12.49 years were included in the study. All the patients received cytarabine and daunorubicin as their standard induction therapy. Serum levels of malondialdehyde (MDA, total antioxidant capacity (TAC, and also the erythrocyte superoxide dismutase and glutathione peroxidase activities were measured before and 14 days after chemotherapy."n "nResults: Plasma malondialdehyde concentrations increased significantly (from a former 2.68±0.89 nmol/ml to 3.14±1.29 nmol/ml 14 days post chemotherapy (p=0.04. Moreover, the total plasma antioxidant capacity changed from 1.09±0.15 mmol/L to 1.02±0.14 mmol/L (p=0.005. Erythrocyte superoxide dismutase and glutathione peroxidase activity decreased over time from 1157.24±543.61 U/gHb to 984.01±419.09 U/gHb (p=0.04 and 46.96±13.70 U/gHb to 41.40±6.44 U/gHb (p=0.02, respectively."n "nConclusion: In this study, an increase in malondialdehyde levels and a decrease in the levels of antioxidant enzymes and total antioxidant capacity were observed. It seems that chemotherapy by cytarabine and daunorubicin generates enormous amounts of free radicals in patients undergoing the treatment for AML. Use of antioxidant supplementation during chemotherapy i is discouraged as it may interfere with the generation of free radicals that may be a part of the therapeutic efficacy of these drugs.

  7. Epigenetic regulators and their impact on therapy in acute myeloid leukemia.

    Science.gov (United States)

    Pastore, Friederike; Levine, Ross L

    2016-03-01

    Genomic studies of hematologic malignancies have identified a spectrum of recurrent somatic alterations that contribute to acute myeloid leukemia initiation and maintenance, and which confer sensitivities to molecularly targeted therapies. The majority of these genetic events are small, site-specific alterations in DNA sequence. In more than two thirds of patients with de novo acute myeloid leukemia mutations epigenetic modifiers are detected. Epigenetic modifiers encompass a large group of proteins that modify DNA at cytosine residues or cause post-translational histone modifications such as methylations or acetylations. Altered functions of these epigenetic modifiers disturb the physiological balance between gene activation and gene repression and contribute to aberrant gene expression regulation found in acute myeloid leukemia. This review provides an overview of the epigenetic modifiers mutated in acute myeloid leukemia, their clinical relevance and how a deeper understanding of their biological function has led to the discovery of new specific targets, some of which are currently tested in mechanism-based clinical trials.

  8. Breast cancer as second malignant neoplasm after acute myeloid leukemia: A rare occurrence

    Directory of Open Access Journals (Sweden)

    Govind Babu

    2016-01-01

    Full Text Available Cancer survivors after successful treatment of hematological and lymphoid malignancies are at an increased risk for second malignant neoplasms. As the overall survival has increased in these cancers, solid tumors are emerging as a serious long-term complication. In this article, we describe such a rare occurrence, in literature, of breast cancer after the treatment of acute myeloid leukemia.

  9. Expression level of CDX2 gene in acute myeloid leukemia and its clinical significance

    Institute of Scientific and Technical Information of China (English)

    陆瀆

    2012-01-01

    Objective To explore the expression and clinical significance of Caudal-type homeobox transcription factor 2(CDX2) gene in acute myeloid leukemia (AML) patients. Methods Real time quantitative PCR(RQ-PCR) was used to test the expression level of CDX2 gene in 108 de novo AML patients and the clinical features

  10. Downregulation of the Wnt inhibitor CXXC5 predicts a better prognosis in acute myeloid leukemia

    NARCIS (Netherlands)

    A. Kühnl (Andrea); P.J.M. Valk (Peter); M.A. Sanders (Mathijs); A. Ivey (Adam); R.K. Hills (Robert); K. Mills (Ken); R.E. Gale (Rosemary); M.F. Kaiser (Martin F.); R. Dillon (Richard); M. Joannides (Melanie); A. Gilkes (Amanda); T. Haferlach (Torsten); S. Schnittger (Susanne); E. Duprez (Estelle); D.C. Linch (David); H.R. Delwel (Ruud); B. Löwenberg (Bob); C.D. Baldus (Claudia D.); E. Solomon (Ellen); A.K. Burnett (Alan); D. Grimwade (David)

    2015-01-01

    textabstractThe gene CXXC5 on 5q31 is frequently deleted in acute myeloid leukemia (AML) with del(5q), suggesting that inactivation of CXXC5 might play a role in leukemogenesis. Here, we investigated the functional and prognostic implications of CXXC5 expression in AML.CXXC5 mRNA was downregulated i

  11. Addition of gemtuzumab ozogamicin to induction chemotherapy improves survival in older patients with acute myeloid leukemia

    DEFF Research Database (Denmark)

    Burnett, Alan K; Russell, Nigel H; Hills, Robert K

    2012-01-01

    PURPOSE There has been little survival improvement in older patients with acute myeloid leukemia (AML) in the last two decades. Improving induction treatment may improve the rate and quality of remission and consequently survival. In our previous trial, in younger patients, we showed improved sur...

  12. Defining the dose of gemtuzumab ozogamicin in combination with induction chemotherapy in acute myeloid leukemia

    DEFF Research Database (Denmark)

    Burnett, Alan; Cavenagh, Jamie; Russell, Nigel

    2016-01-01

    Arecent source data meta-analysis of randomized trials in adults assessing the immunoconjugate gemtuzumab ozogamicin combined with standard chemotherapy in acute myeloid leukemia showed a significant survival benefit in patients without an adverse karyotype. It is not clear whether the optimal do...

  13. Common and Overlapping Oncogenic Pathways Contribute to the Evolution of Acute Myeloid Leukemias

    NARCIS (Netherlands)

    Kvinlaug, Brynn T.; Chan, Wai-In; Bullinger, Lars; Ramaswami, Mukundhan; Sears, Christopher; Foster, Donna; Lazic, Stanley E.; Okabe, Rachel; Benner, Axel; Lee, Benjamin H.; De Silva, Inusha; Valk, Peter J. M.; Delwel, Ruud; Armstrong, Scott A.; Doehner, Hartmut; Gilliland, D. Gary; Huntly, Brian J. P.

    2011-01-01

    Fusion oncogenes in acute myeloid leukemia (AML) promote self-renewal from committed progenitors, thereby linking transformation and self-renewal pathways. Like most cancers, AML is a genetically and biologically heterogeneous disease, but it is unclear whether transformation results from common or

  14. CONTINUOUS-INFUSION OF CEFTAZIDIME IN FEBRILE NEUTROPENIC PATIENTS WITH ACUTE MYELOID-LEUKEMIA

    NARCIS (Netherlands)

    DAENEN, S; ERJAVEC, Z; UGES, DRA; DEVRIESHOSPERS, HG; DEJONGE, P; HALIE, MR

    1995-01-01

    Twelve febrile patients with severe neutropenia, who had undergone aggressive chemotherapy for acute myeloid leukemia, were treated empirically with a continuous infusion of ceftazidime 100 mg/kg/day after a 500 mg loading dose, in order to study the pharmacokinetics of ceftazidime after continuous

  15. Pretransplant HLA mistyping in diagnostic samples of acute myeloid leukemia patients due to acquired uniparental disomy

    NARCIS (Netherlands)

    Dubois, V.; Sloan-Bena, F.; Cesbron, A.; Hepkema, B. G.; Gagne, K.; Gimelli, S.; Heim, D.; Tichelli, A.; Delaunay, J.; Drouet, M.; Jendly, S.; Villard, J.; Tiercy, J-M

    2012-01-01

    Although acquired uniparental disomy (aUPD) has been reported in relapse acute myeloid leukemia (AML), pretransplant aUPD involving chromosome 6 is poorly documented. Such events could be of interest because loss of heterozygosity (LOH) resulting from aUPD in leukemic cells may lead to erroneous res

  16. Raman spectroscopy for the assessment of acute myeloid leukemia: a proof of concept study

    NARCIS (Netherlands)

    Vanna, R.; Tresoldi, C.; Lenferink, A.T.M.; Ronchi, P.; Morasso, C.; Mehn, D.; Bedoni, M.; Pignatari, C.; Terstappen, L.W.M.M.; Ciceri, F.; Otto, C.; Gramatica, F.

    2014-01-01

    Acute myeloid leukemia (AML) is a proliferative neoplasm, that if not properly treated can rapidly cause a fatal outcome. The diagnosis of AML is challenging and the first diagnostic step is the count of the percentage of blasts (immature cells) in bone marrow and blood sample, and their morphologic

  17. Study of nucleophosmin (NPM) gene mutation in patients with acute myeloid leukemia and myelodysplastic syndromes

    Institute of Scientific and Technical Information of China (English)

    张悦

    2006-01-01

    Objective To investigate nucleophosmin (NPM) gene mutations in patients with de novo acute myeloid leukemia (AML) with normal cytogenetics and primary myelodysplastic syndromes (MDS). Methods Genomic DNA corresponding to exon 12 of NPM gene was amplified by polymerase chain reaction (PCR) in 40 AML patients (28 case untreated and 12 in first remission) and

  18. Evaluation of gene expression signatures predictive of cytogenetic and molecular subtypes of pediatric acute myeloid leukemia

    NARCIS (Netherlands)

    Balgobind, Brian V.; Van den Heuvel-Eibrink, Marry M.; De Menezes, Renee X.; Reinhardt, Dirk; Hollink, Iris H. I. M.; Arentsen-Peters, Susan T. J. C. M.; van Wering, Elisabeth R.; Kaspers, Gertjan J. L.; Cloos, Jacqueline; de Bont, Evelien S. J. M.; Cayuela, Jean-Michel; Baruchel, Andre; Meyer, Claus; Marschalek, Rolf; Trka, Jan; Stary, Jan; Beverloo, H. Berna; Pieters, Rob; Zwaan, C. Michel; den Boer, Monique L.

    2011-01-01

    Background Pediatric acute myeloid leukemia is a heterogeneous disease characterized by non-random genetic aberrations related to outcome. The genetic subtype is currently detected by different diagnostic procedures which differ in success rate and/or specificity. Design and Methods We examined the

  19. Loss of the histone methyltransferase EZH2 induces resistance to multiple drugs in acute myeloid leukemia

    DEFF Research Database (Denmark)

    Göllner, Stefanie; Oellerich, Thomas; Agrawal-Singh, Shuchi

    2017-01-01

    In acute myeloid leukemia (AML), therapy resistance frequently occurs, leading to high mortality among patients. However, the mechanisms that render leukemic cells drug resistant remain largely undefined. Here, we identified loss of the histone methyltransferase EZH2 and subsequent reduction of h...

  20. [Abnormal reaction for anaesthetics in a critically ill child with acute myeloid leukemia--case report].

    Science.gov (United States)

    Bujok, Grzegorz; Knapik, Piotr; Macioł, Zbigniew

    2004-01-01

    The authors present a case report of an abnormal reaction for anaesthetics correlated with cytostatic therapy in the course of preparation time for bone marrow transplantation due to acute myeloid leukemia. Problems of pharmacological interaction of ketamine and benzodiazepines are emphasized. Special attention was paid to the risk of abnormal drug reactions during general anaesthesia in children with leukemia.

  1. Integrative prognostic risk score in acute myeloid leukemia with normal karyotype

    NARCIS (Netherlands)

    F. Damm (Frederik); M. Heuser (Michael); H.M. Morgan (Helen); K. Wagner (Katharina); K. Görlich (Kerstin); A. Großhennig (Anika); I. Hamwi (Iyas); F. Thol (Felicitas); E. Surdziel (Ewa); W. Fiedler (Walter); M. Lübbert (Michael); L. Kanz (Lothar); C. Reuter (Christoph); G. Heil (Gerhard); H.R. Delwel (Ruud); B. Löwenberg (Bob); P.J.M. Valk (Peter); J. Krauter; A. Ganser (Arnold)

    2011-01-01

    textabstractTo integrate available clinical and molecular information for cytogenetically normal acute myeloid leukemia (CN-AML) patients into one risk score, 275 CN-AML patients from multicenter treatment trials AML SHG Hannover 0199 and 0295 and 131 patients from HOVON/SAKK protocols as external c

  2. High-Dose Daunorubicin in Older Patients with Acute Myeloid Leukemia

    NARCIS (Netherlands)

    Lowenberg, Bob; Ossenkoppele, Gert J.; van Putten, Wim; Schouten, Harry C.; Graux, Carlos; Ferrant, Augustin; Sonneveld, Pieter; Maertens, Johan; Jongen-Lavrencic, Mojca; von Lilienfeld-Toal, Marie; Biemond, Bart J.; Vellenga, Edo; Kooy, Marinus van Marwijk; Verdonck, Leo F.; Beck, Joachim; Doehner, Hartmut; Gratwohl, Alois; Pabst, Thomas; Verhoef, Gregor

    2009-01-01

    Background A complete remission is essential for prolonging survival in patients with acute myeloid leukemia (AML). Daunorubicin is a cornerstone of the induction regimen, but the optimal dose is unknown. In older patients, it is usual to give daunorubicin at a dose of 45 to 50 mg per square meter o

  3. Infectious events prior to chemotherapy initiation in children with acute myeloid leukemia.

    Directory of Open Access Journals (Sweden)

    Carol Portwine

    Full Text Available BACKGROUND: The primary objective was to describe infectious complications in children with acute myeloid leukemia from presentation to the healthcare system to initiation of chemotherapy and to describe how these infections differ depending on neutropenia. METHODS: We conducted a retrospective, population-based cohort study that included children and adolescents with acute myeloid leukemia diagnosed and treated at 15 Canadian centers. We evaluated infections that occurred between presentation to the healthcare system (for symptoms that led to the diagnosis of acute myeloid leukemia until initiation of chemotherapy. RESULTS: Among 328 children, 92 (28.0% were neutropenic at presentation. Eleven (3.4% had sterile-site microbiologically documented infection and four had bacteremia (only one Gram negative. Infection rate was not influenced by neutropenia. No child died from an infectious cause prior to chemotherapy initiation. CONCLUSION: It may be reasonable to withhold empiric antibiotics in febrile non-neutropenic children with newly diagnosed acute myeloid leukemia until initiation of chemotherapy as long as they appear well without a clinical focus of infection. Future work could examine biomarkers or a clinical score to identify children presenting with leukemia and fever who are more likely to have an invasive infection.

  4. Central diabetes insipidus preceding acute myeloid leukemia with t(3;12)(q26;p12)

    NARCIS (Netherlands)

    Nieboer, P; Vellenga, E; Adriaanse, R; van de Loosdrecht, AA

    2000-01-01

    A 52-year-old woman presented with polyuria and polydipsia. ii diagnosis of central diabetes insipidus (DI) was made, which turned out to be the first sign of acute myeloid leukemia (AML). Cytogenetic analysis revealed a balanced translocation between chromosome 3 and 12 t(3;12)(q26;p12). The patien

  5. New treatment strategies in myelodysplastic syndromes and acute myeloid leukemia : Hypomethylating agents and proteasome inhibitors

    NARCIS (Netherlands)

    van der Helm, Lidia Henrieke

    2016-01-01

    New treatment strategies in leukemia and myelodysplastic syndromes Treatment of acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) is challenging, especially in the large group of patients older than 60 years. In these patients, results of standard chemotherapy are often disappointing

  6. Decitabine and Midostaurin in Treating Older Patients With Newly Diagnosed Acute Myeloid Leukemia

    Science.gov (United States)

    2016-04-25

    Acute Myeloid Leukemia (AML) With Multilineage Dysplasia Following Myelodysplastic Syndrome, in Adults; AML (Adult) With 11q23 (MLL) Abnormalities; AML (Adult) With Del(5q); AML (Adult) With Inv(16)(p13;q22); AML (Adult) With t(16;16)(p13;q22); AML (Adult) With t(8;21)(q22;q22); Secondary AML (Adult); Untreated AML (Adult)

  7. Treatment of Acute Myeloid Leukemia in Adolescent and Young Adult Patients

    Directory of Open Access Journals (Sweden)

    Guldane Cengiz Seval

    2015-03-01

    Full Text Available The objectives of this review were to discuss standard and investigational treatment strategies for adolescent and young adult with acute myeloid leukemia, excluding acute promyelocytic leukemia. Acute myeloid leukemia (AML in adolescent and young adult patients (AYAs may need a different type of therapy than those currently used in children and older patients. As soon as AML is diagnosed, AYA patient should be offered to participate in well-designed clinical trials. The standard treatment approach for AYAs with AML is remission induction chemotherapy with an anthracycline/cytarabine combination, followed by either consolidation chemotherapy or stem cell transplantation, depending on the ability of the patient to tolerate intensive treatment and cytogenetic features. Presently, continuing progress of novel drugs targeting specific pathways in acute leukemia may bring AML treatment into a new era.

  8. Characterization of miRNomes in Acute and Chronic Myeloid Leukemia Cell Lines

    Institute of Scientific and Technical Information of China (English)

    Qian Xiong; Jiangwei Yan; Songnian Hu; Xiangdong Fang; Yadong Yang; Hai Wang; Jie Li; Shaobin Wang; Yanming Li; Yaran Yang; Kan Cai; Xiuyan Ruan

    2014-01-01

    Myeloid leukemias are highly diverse diseases and have been shown to be associated with microRNA (miRNA) expression aberrations. The present study involved an in-depth miRNome analysis of two human acute myeloid leukemia (AML) cell lines, HL-60 and THP-1, and one human chronic myeloid leukemia (CML) cell line, K562, via massively parallel signature sequenc-ing. mRNA expression profiles of these cell lines that were established previously in our lab facil-itated an integrative analysis of miRNA and mRNA expression patterns. miRNA expression profiling followed by differential expression analysis and target prediction suggested numerous miRNA signatures in AML and CML cell lines. Some miRNAs may act as either tumor suppres-sors or oncomiRs in AML and CML by targeting key genes in AML and CML pathways. Expres-sion patterns of cell type-specific miRNAs could partially reflect the characteristics of K562, HL-60 and THP-1 cell lines, such as actin filament-based processes, responsiveness to stimulus and phag-ocytic activity. miRNAs may also regulate myeloid differentiation, since they usually suppress dif-ferentiation regulators. Our study provides a resource to further investigate the employment of miRNAs in human leukemia subtyping, leukemogenesis and myeloid development. In addition, the distinctive miRNA signatures may be potential candidates for the clinical diagnosis, prognosis and treatment of myeloid leukemias.

  9. Acute isolated appendicitis due to Aspergillus carneus in a neutropenic child with acute myeloid leukemia.

    Science.gov (United States)

    Decembrino, Nunzia; Zecca, Marco; Tortorano, Anna Maria; Mangione, Francesca; Lallitto, Fabiola; Introzzi, Francesca; Bergami, Elena; Marone, Piero; Tamarozzi, Francesca; Cavanna, Caterina

    2016-01-01

    We describe a case of isolated acute appendicitis due to Aspergillus carneus in a neutropenic child with acute myeloid leukemia (AML) treated according to the AIEOP AML 2002/01 protocol. Despite prophylaxis with acyclovir, ciprofloxacin and fluconazole administered during the neutropenic phase, 16 days after the end of chemotherapy the child developed fever without identified infective foci, which prompted a therapy shift to meropenem and liposomial amphotericin B. After five days of persisting fever he developed ingravescent abdominal lower right quadrant pain. Abdominal ultrasound was consistent with acute appendicitis and he underwent appendectomy with prompt defervescence. PAS+ fungal elements were found at histopathology examination of the resected vermiform appendix, and galactomannan was low positive. A. carneus, a rare species of Aspergillus formerly placed in section Flavipedes and recently considered a member of section Terrei, was identified in the specimen. Treatment with voriconazole was promptly started with success. No other site of Aspergillus localization was detected. Appendicitis is rarely caused by fungal organisms and isolated intestinal aspergillosis without pulmonary infection is unusual. To our knowledge, this is the first report of infection due to A. carneus in a child and in a primary gastrointestinal infection.

  10. Rhabdomyolysis Following Initiation of Posaconazole Use for Antifungal Prophylaxis in a Patient With Relapsed Acute Myeloid Leukemia

    Science.gov (United States)

    Mody, Mayur D.; Ravindranathan, Deepak; Gill, Harpaul S.; Kota, Vamsi K.

    2017-01-01

    Posaconazole is a commonly used medication for antifungal prophylaxis in patients with high-risk acute leukemia, such as acute myeloid leukemia. Despite clinical data that show that posaconazole is superior to other antifungal prophylaxis medications, posaconazole is known to have many side effects and drug-drug interactions. We present a patient who developed rhabdomyolysis after being started on posaconazole for prophylaxis in the setting of relapsed acute myeloid leukemia. PMID:28203579

  11. Rhabdomyolysis Following Initiation of Posaconazole Use for Antifungal Prophylaxis in a Patient With Relapsed Acute Myeloid Leukemia: A Case Report.

    Science.gov (United States)

    Mody, Mayur D; Ravindranathan, Deepak; Gill, Harpaul S; Kota, Vamsi K

    2017-01-01

    Posaconazole is a commonly used medication for antifungal prophylaxis in patients with high-risk acute leukemia, such as acute myeloid leukemia. Despite clinical data that show that posaconazole is superior to other antifungal prophylaxis medications, posaconazole is known to have many side effects and drug-drug interactions. We present a patient who developed rhabdomyolysis after being started on posaconazole for prophylaxis in the setting of relapsed acute myeloid leukemia.

  12. Acute myeloid leukemia in a patient with constitutional 47,XXY karyotype

    Directory of Open Access Journals (Sweden)

    Marla M. Jalbut

    2015-01-01

    Full Text Available Klinefelter syndrome (KS, a 47,XXY chromosomal abnormality, has been shown to be associated with a number of malignancies, but has not been linked to acute leukemias to date. We present a case of a 54-year-old male diagnosed with acute myeloid leukemia (AML with monocytic differentiation, whose cytogenetic and subsequent FISH analyses revealed a constitutional 47,XXY karyotype. We also review and discuss relevant prior literature.

  13. Outcome after cessation of therapy in childhood acute lymphoblastic leukaemia. The Associazione Italiana Ematologia ed Oncologia Pediatrica (AIEOP).

    Science.gov (United States)

    Jankovic, M; Fraschini, D; Amici, A; Aricò, M; Arrighini, A; Basso, G; Colella, R; DiTullio, M T; Haupt, R; Macchia, P

    1993-01-01

    A total of 2192 children with acute lymphoblastic leukaemia who had reached cessation of therapy in complete remission were followed for a median time of 52 months after treatment suspension. Of the 485 relapses observed, 62.3% occurred in the first year off therapy and 68.9% involved the bone marrow. Eight relapses were reported more than 5 years (62-143 months) after treatment withdrawal. Males fared worse than females consistently, experiencing 1.5 times more relapses (P 20 years) were married and 16 have had 21 healthy children. Twenty-four per cent of patients experienced an unfavourable event. Relapses accounted for 93% of failures. Central nervous system late effects and second malignancies were the major causes of non-leukaemic morbidity and mortality.

  14. Successful management of hepatic mucormycosis in an acute lymphoblastic leukaemia patient: a case report and review of the literature.

    Science.gov (United States)

    Tuysuz, Gulen; Ozdemir, Nihal; Senyuz, Osman Faruk; Emre, Senol; Kantarcioglu, Serda; Adaletli, Ibrahim; Kepil, Nuray; Tutuncu, Cigdem; Celkan, Tiraje

    2014-08-01

    We present a case of hepatic mucormycosis in a 9-year-old boy with acute lymphoblastic leukaemia. Despite long-term use of combined liposomal amphotericin B and posaconazole therapy, the lesion persisted and could only be treated by surgical excision. After surgery, antifungal treatment was continued with posaconazole. On follow-up, the patient had two episodes of ascending cholangitis which were responsive to intravenous antibiotics. He is doing well at the moment in remission for 2.5 years. Mucormycosis was long regarded as a fatal infection with poor prognosis. With early medical and surgical management, survival rates increase. Isolated hepatic mucormycosis is rare and only seven cases were reported in the literature up to now. We wanted to emphasise the role of early surgery in patients with hepatic mucormycosis in view of the literature.

  15. Detection of FLT3 Oncogene Mutations in Acute Myeloid Leukemia Using Conformation Sensitive Gel Electrophoresis

    Directory of Open Access Journals (Sweden)

    Mamdooh Gari

    2008-11-01

    Full Text Available FLT3 (fms-related tyrosine kinase 3 is a receptor tyrosine kinase class III that is expressed on by early hematopoietic progenitor cells and plays an important role in hematopoietic stem cell proliferation, differentiation and survival. FLT3 is also expressed on leukemia blasts in most cases of acute myeloid leukemia (AML. In order to determine the frequency of FLT3 oncogene mutations, we analyzed genomic DNA of adult de novo acute myeloid leukemia (AML. Polymerase chain reaction (PCR and conformation-sensitive gel electrophoresis (CSGE were used for FLT3 exons 11, 14, and 15, followed by direct DNA sequencing. Two different types of functionally important FLT 3 mutations have been identified. Those mutations were unique to patients with inv(16, t(15:17 or t(8;21 and comprised fifteen cases with internal tandem duplication (ITD mutation in the juxtamembrane domain and eleven cases with point mutation (exon 20, Asp835Tyr. The high frequency of the flt3 proto-oncogene mutations in acute myeloid leukemia AML suggests a key role for the receptor function. The association of FLT3 mutations with chromosomal abnormalities invites speculation as to the link between these two changes in the pathogenesis of acute myeloid leukemiaAML. Furthermore, CSGE method has shown to be a rapid and sensitive screening method for detection of nucleotide alteration in FLT3 gene. Finally, this study reports, for the first time in Saudi Arabia, mutations in the human FLT3 gene in acute myeloid leukemia AML patients.

  16. Pseudo-Guillain–Barré syndrome masking acute myeloid leukemia relapse: Brief report and review

    Directory of Open Access Journals (Sweden)

    Fadi El Karak

    2015-01-01

    Full Text Available Central nervous system (CNS relapse is not a rare presentation in acute myeloid leukemia (AML as its incidence ranges between 2% and 9%. It manifests with meningeal leukemia, cranial nerve palsies or cerebral mesenchymal myeloid sarcoma. We herein report the case of a 69 year-old female that presented a pseudo-Guillain–Barré syndrome masking an AML CNS relapse. Her symptoms completely resolved upon administration of a tailored treatment. This case suggests that puzzling neurological manifestations in patients with a history of AML should be considered as a CNS recurrence and investigated accordingly even in the context of normal imaging findings.

  17. IGK with conserved IGΚV/IGΚJ repertoire is expressed in acute myeloid leukemia and promotes leukemic cell migration.

    Science.gov (United States)

    Wang, Chong; Xia, Miaoran; Sun, Xiaoping; He, Zhiqiao; Hu, Fanlei; Chen, Lei; Bueso-Ramos, Carlos E; Qiu, Xiaoyan; Yin, C Cameron

    2015-11-17

    We have previously reported that immunoglobulin heavy chain genes were expressed in myeloblasts and mature myeloid cells. In this study, we further demonstrated that rearranged Ig κ light chain was also frequently expressed in acute myeloid leukemia cell lines (6/6), primary myeloblasts from patients with acute myeloid leukemia (17/18), and mature monocytes (11/12) and neutrophils (3/12) from patients with non-hematopoietic neoplasms, but not or only rarely expressed in mature neutrophils (0/8) or monocytes (1/8) from healthy individuals. Interestingly, myeloblasts and mature monocytes/neutrophils shared several restricted IGKV and IGKJ gene usages but with different expression frequency. Surprisingly, almost all of the acute myeloid leukemia-derived IGKV showed somatic hypermutation; in contrast, mature myeloid cells-derived IGKV rarely had somatic hypermutation. More importantly, although IGK expression appeared not to affect cell proliferation, reduced IGK expression led to a decrease in cell migration in acute myeloid leukemia cell lines HL-60 and NB4, whereas increased IGK expression promoted their motility. In summary, IGK is expressed in myeloblasts and mature myeloid cells from patients with non-hematopoietic neoplasms, and is involved in cell migration. These results suggest that myeloid cells-derived IgK may have a role in leukemogenesis and may serve as a novel tumor marker for monitoring minimal residual disease and developing target therapy.

  18. Mutations in the gene for the granulocyte colony-stimulating-factor receptor in patients with acute myeloid leukemia preceded by severe congenital neutropenia

    NARCIS (Netherlands)

    F. Dong (Fan); R.K. Brynes; N. Tidow; K. Welte (Karl); B. Löwenberg (Bob); I.P. Touw (Ivo)

    1995-01-01

    textabstractBACKGROUND. In severe congenital neutropenia the maturation of myeloid progenitor cells is arrested. The myelodysplastic syndrome and acute myeloid leukemia develop in some patients with severe congenital neutropenia. Abnormalities in the signal-transduction

  19. Extracorporeal membrane oxygenation as a rescue therapy for acute respiratory failure during chemotherapy in a patient with acute myeloid leukemia

    Science.gov (United States)

    Lee, Sang Won; Kim, Youn Seup

    2017-01-01

    Acute respiratory distress syndrome (ARDS) caused by pneumonia in patients with hematologic malignancies can be life-threatening. Extracorporeal membrane oxygenation (ECMO) is the only temporary treatment for patients with ARDS who are refractory to conventional treatment. However, the immunosuppression and coagulopathies in hematological malignancies such as lymphoma and acute leukemia are relative contraindications for ECMO, due to high risks of infection and bleeding. Here, we report a 22-year-old man with acute myeloid leukemia (AML) who developed pneumonia and ARDS during induction chemotherapy; he was treated with ECMO. PMID:28275497

  20. High syndecan-1 levels in acute myeloid leukemia are associated with bleeding, thrombocytopathy, endothelial cell damage, and leukocytosis

    DEFF Research Database (Denmark)

    Larsen, Anne Mette Vestskov; Leinøe, Eva Birgitte; Johansson, Pär I;

    2013-01-01

    The risk of hemorrhage is influenced by multiple factors in acute myeloid leukemia (AML). We investigated whether hemorrhage in AML patients was associated with endothelial perturbation, potentially caused by thrombocytopenia, platelet dysfunction and leukocytosis. Biomarkers of endothelial...

  1. The study on relationship between age and cytogenetic subgroups in 640 patients with de novo acute myeloid leukemia

    Institute of Scientific and Technical Information of China (English)

    苏龙

    2013-01-01

    Objective To analyze the cytogenetic characteristicsof different age subgroups in patients with acute myeloid leukemia(AML),and to explore the relationship between age and cytogenetics.Methods Between

  2. Clinical activity of azacitidine in patients who relapse after allogeneic stem cell transplantation for acute myeloid leukemia

    DEFF Research Database (Denmark)

    Craddock, Charles; Labopin, Myriam; Robin, Marie

    2016-01-01

    Disease relapse is the most common cause of treatment failure after allogeneic stem cell transplantation for acute myeloid leukemia and myelodysplastic syndromes, yet treatment options for such patients remain extremely limited. Azacitidine is an important new therapy in high-risk myelodysplastic...... syndromes and acute myeloid leukemia but its role in patients who relapse post allograft has not been defined. We studied the tolerability and activity of azacitidine in 181 patients who relapsed after an allograft for acute myeloid leukemia (n=116) or myelodysplastic syndromes (n=65). Sixty-nine patients...... conclude that azacitidine represents an important new therapy in selected patients with acute myeloid leukemia/myelodysplastic syndromes who relapse after allogeneic stem cell transplantation. Prospective studies to confirm optimal treatment options in this challenging patient population are required....

  3. Vorinostat and Decitabine in Treating Patients With Advanced Solid Tumors or Relapsed or Refractory Non-Hodgkin's Lymphoma, Acute Myeloid Leukemia, Acute Lymphocytic Leukemia, or Chronic Myelogenous Leukemia

    Science.gov (United States)

    2014-08-26

    Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Blastic Phase Chronic Myelogenous Leukemia; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Nodal Marginal Zone B-cell Lymphoma; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Small Lymphocytic Lymphoma; Secondary Acute Myeloid Leukemia; Splenic Marginal Zone Lymphoma; Stage III Adult Burkitt Lymphoma; Stage III Adult Diffuse Large Cell Lymphoma; Stage III Adult Diffuse Mixed Cell Lymphoma; Stage III Adult Diffuse Small Cleaved Cell Lymphoma; Stage III Adult Immunoblastic Large Cell Lymphoma; Stage III Adult Lymphoblastic Lymphoma; Stage III Grade 1 Follicular Lymphoma; Stage III Grade 2 Follicular Lymphoma; Stage III Grade 3 Follicular Lymphoma; Stage III Mantle Cell Lymphoma; Stage III Marginal Zone Lymphoma; Stage III Small Lymphocytic Lymphoma; Stage IV Adult Burkitt Lymphoma; Stage IV Adult Diffuse Large Cell Lymphoma; Stage IV Adult Diffuse Mixed Cell Lymphoma; Stage IV Adult Diffuse Small Cleaved Cell Lymphoma; Stage IV Adult Immunoblastic Large Cell Lymphoma; Stage IV Adult Lymphoblastic Lymphoma; Stage IV Grade 1 Follicular Lymphoma; Stage IV Grade 2 Follicular Lymphoma; Stage IV Grade 3 Follicular Lymphoma; Stage IV Mantle Cell Lymphoma; Stage IV Marginal Zone Lymphoma

  4. Histone deacetylases: a common molecular target for differentiation treatment of acute myeloid leukemias?

    Science.gov (United States)

    Minucci, S; Nervi, C; Lo Coco, F; Pelicci, P G

    2001-05-28

    Recent discoveries have identified key molecular events in the pathogenesis of acute promyelocytic leukemia (APL), caused by chromosomal rearrangements of the transcription factor RAR (resulting in a fusion protein with the product of other cellular genes, such as PML). Oligomerization of RAR, through a self-association domain present in PML, imposes an altered interaction with transcriptional co-regulators (NCoR/SMRT). NCoR/SMRT are responsible for recruitment of histone deacetylases (HDACs), which is required for transcriptional repression of PML-RAR target genes, and for the transforming potential of the fusion protein. Oligomerization and altered recruitment of HDACs are also responsible for transformation by the fusion protein AML1-ETO, extending these mechanisms to other forms of acute myeloid leukemias (AMLs) and suggesting that HDAC is a common target for myeloid leukemias. Strikingly, AML1-ETO expression blocks retinoic acid (RA) signaling in hematopoietic cells, suggesting that interference with the RA pathway (genetically altered in APL) by HDAC recruitment may be a common theme in AMLs. Treatment of APLs with RA, and of other AMLs with RA plus HDAC inhibitors (HDACi), results in myeloid differentiation. Thus, activation of the RA signaling pathway and inhibition of HDAC activity might represent a general strategy for the differentiation treatment of myeloid leukemias.

  5. A novel application of furazolidone: anti-leukemic activity in acute myeloid leukemia.

    Directory of Open Access Journals (Sweden)

    Xueqing Jiang

    Full Text Available Acute myeloid leukemia (AML is the most common malignant myeloid disorder of progenitor cells in myeloid hematopoiesis and exemplifies a genetically heterogeneous disease. The patients with AML also show a heterogeneous response to therapy. Although all-trans retinoic acid (ATRA has been successfully introduced to treat acute promyelocytic leukemia (APL, it is rather ineffective in non-APL AML. In our present study, 1200 off-patent marketed drugs and natural compounds that have been approved by the Food and Drug Administration (FDA were screened for anti-leukemia activity using the retrovirus transduction/transformation assay (RTTA. Furazolidone (FZD was shown to inhibit bone marrow transformation mediated by several leukemia fusion proteins, including AML1-ETO. Furazolidone has been used in the treatment of certain bacterial and protozoan infections in human and animals for more than sixty years. We investigated the anti-leukemic activity of FZD in a series of AML cells. FZD displayed potent antiproliferative properties at submicromolar concentrations and induced apoptosis in AML cell lines. Importantly, FZD treatment of certain AML cells induced myeloid cell differentiation by morphology and flow cytometry for CD11b expression. Furthermore, FZD treatment resulted in increased stability of tumor suppressor p53 protein in AML cells. Our in vitro results suggest furazolidone as a novel therapeutic strategy in AML patients.

  6. Risk factors for therapy-related myelodysplastic syndrome and acute myeloid leukemia treated with allogeneic stem cell transplantation.

    OpenAIRE

    2009-01-01

    International audience; BACKGROUND: After successful treatment of malignant diseases, therapy-related myelodysplastic syndrome and acute myeloid leukemia have emerged as significant problems. DESIGN AND METHODS: The aim of this study was to investigate outcome and risk factors in patients with therapy-related myelodysplastic syndrome or acute myeloid leukemia who underwent allogeneic stem cell transplantation. Between 1981 and 2006, 461 patients with therapy-related myelodysplastic syndrome o...

  7. Characteristics and Prognosis of Adult Acute Myeloid Leukemia with Internal Tandem Duplication in the FLT3 Gene

    OpenAIRE

    2013-01-01

    Objectives: Constitutive activation of the fms-like tyrosine kinase 3 (FLT3) receptor by internal tandem duplication (ITD) of the juxtamembrane region has been described in patients with acute myeloid leukemia. FLT3/ITDs are present in about 20-30% of all acute myeloid leukemia cases. It has been shown that the mutation is correlated with worse prognosis. However, none of the previous studies investigated which FAB subtype is associated with higher percentage of FLT3/ITD, thus the reason for ...

  8. Cyanobacteria from terrestrial and marine sources contain apoptogens able to overcome chemoresistance in acute myeloid leukemia cells

    OpenAIRE

    2014-01-01

    In this study, we investigated forty cyanobacterial isolates from biofilms, gastropods, brackish water and symbiotic lichen habitats. Their aqueous and organic extracts were used to screen for apoptosis-inducing activity against acute myeloid leukemia cells. A total of 28 extracts showed cytotoxicity against rat acute myeloid leukemia (IPC-81) cells. The design of the screen made it possible to eliminate known toxins, such as microcystins and nodularin, or known metabolites with anti-leukemi...

  9. Radiolabeled Monoclonal Antibody Therapy, Fludarabine Phosphate, and Low-Dose Total-Body Irradiation Followed by Donor Stem Cell Transplant and Immunosuppression Therapy in Treating Older Patients With Advanced Acute Myeloid Leukemia or High-Risk Myelodysplastic Syndromes

    Science.gov (United States)

    2015-11-16

    Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Chronic Myelomonocytic Leukemia; de Novo Myelodysplastic Syndromes; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Myeloid Leukemia; Refractory Anemia With Excess Blasts; Refractory Anemia With Excess Blasts in Transformation; Refractory Anemia With Ringed Sideroblasts; Refractory Cytopenia With Multilineage Dysplasia; Secondary Myelodysplastic Syndromes; Untreated Adult Acute Myeloid Leukemia

  10. Iodine I 131 Monoclonal Antibody BC8, Fludarabine Phosphate, Total Body Irradiation, and Donor Stem Cell Transplant Followed by Cyclosporine and Mycophenolate Mofetil in Treating Patients With Advanced Acute Myeloid Leukemia or Myelodysplastic Syndrome

    Science.gov (United States)

    2016-11-14

    Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Childhood Myelodysplastic Syndromes; Chronic Myelomonocytic Leukemia; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Myeloid Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Refractory Anemia With Excess Blasts; Refractory Anemia With Excess Blasts in Transformation; Refractory Anemia With Ringed Sideroblasts; Refractory Cytopenia With Multilineage Dysplasia; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndromes

  11. Acute Panmyelosis with Myelofibrosis - A Rare Subtype of Acute Myeloid Leukemia

    Directory of Open Access Journals (Sweden)

    Tathagata Chatterjee

    2013-06-01

    Full Text Available One case of acute panmyelosis with myelofibrosis (APMF is being reported. A 45 year old male presented with abrupt onset of rapidly progressing low backache, weakness and pancytopenia. On examination there was no organomegaly. Peripheral blood examination revealed normocytic normochromic red blood cells with 10% circulating blasts. Flowcytometric examination of peripheral blood revealed blasts which were positive for CD 34 ,HLA- DR and myeloid associated antigens (i.e. CD13 and CD33.Blasts were negative for anti MPO. Bone marrow aspirate resulted in a dry tap. Bone marrow biopsy revealed panmyeloid proliferation with scattered blasts which were CD 34 positive on imunohistochemistry and negative for anti MPO. Reticulin stain showed grade III myelofibrosis (WHO. Differential diagnosis considered included AML-M7, MDS-RAEB II and AML with myelodysplasia . He was started on chemotherapy [idarubicin and cytarabine; 3+7 induction regimen followed by three cycles of HIDAC (High dose cytosine arabinoside] after which patient was in complete morphological remission with markedly reduced bone marrow fibrosis. He is now being worked up for allogeneic stem cell transplantation. Patient is asymptomatic at eight months of diagnosis. In conclusion these patients should be managed aggressively with AML therapy and this case report reaffirms the fact that APMF is subtype of AML.

  12. Effect and Prognostic Analysis of Treatment for Acute Myeloid Leukemia Using Chinese Drugs Combined with Chemotherapy

    Institute of Scientific and Technical Information of China (English)

    胡晓梅; 刘锋; 郑春梅; 李柳; 刘池; 张姗姗; 肖海燕; 杨晓红; 王洪志; 许勇钢; 胡乃平; 麻柔

    2009-01-01

    Objective:To observe the clinical efficacy of Chinese drugs combined with chemotherapy in the treatment of acute myeloid leukemia(AML) and to investigate the prognostic relevance of the main parameters in AML treated with integrative medicine.Methods:Forty AML patients hospitalized at the authors' hospital were treated with Chinese drugs and chemotherapy.The routine examination,immunophenotype and karyotype analyses were carried out.The clinical efficacy was observed and the prognostic factors were analy...

  13. SAMHD1 is a biomarker for cytarabine response and a therapeutic target in acute myeloid leukemia.

    OpenAIRE

    Schneider, Constanze; Oellerich, Thomas; Baldauf, Hanna-Mari; Schwarz, Sarah-Marie; Thomas, Dominique; Flick, Robert; Bohnenberger, Hanibal; Kaderali, Lars; Stegmann, Lena; Cremer, Anjali; Martin, Margarethe; Lohmeyer, Julian; Michaelis, Martin; Hornung, Veit; Schliemann, Christoph

    2016-01-01

    The nucleoside analog cytarabine (Ara-C) is an essential component of primary and salvage chemotherapy regimens for acute myeloid leukemia (AML). After cellular uptake, Ara-C is converted into its therapeutically active triphosphate metabolite, Ara-CTP, which exerts antileukemic effects, primarily by inhibiting DNA synthesis in proliferating cells. Currently, a substantial fraction of patients with AML fail to respond effectively to Ara-C therapy, and reliable biomarkers for predicting the th...

  14. Successful hematopoietic cell transplantation in a patient with X-linked agammaglobulinemia and acute myeloid leukemia.

    Science.gov (United States)

    Abu-Arja, Rolla F; Chernin, Leah R; Abusin, Ghada; Auletta, Jeffery; Cabral, Linda; Egler, Rachel; Ochs, Hans D; Torgerson, Troy R; Lopez-Guisa, Jesus; Hostoffer, Robert W; Tcheurekdjian, Haig; Cooke, Kenneth R

    2015-09-01

    X-linked agammaglobulinemia (XLA) is a primary immunodeficiency characterized by marked reduction in all classes of serum immunoglobulins and the near absence of mature CD19(+) B-cells. Although malignancy has been observed in patients with XLA, we present the first reported case of acute myeloid leukemia (AML) in a patient with XLA. We also demonstrate the complete correction of the XLA phenotype following allogeneic hematopoietic cell transplantation for treatment of the patient's leukemia.

  15. Shortcomings in the clinical evaluation of new drugs: acute myeloid leukemia as paradigm

    OpenAIRE

    Walter, Roland B.; Appelbaum, Frederick R.; Tallman, Martin S.; Weiss, Noel S.; Larson, Richard A.; Estey, Elihu H.

    2010-01-01

    Drugs introduced over the past 25 years have benefitted many patients with acute myeloid leukemia (AML) and provided cure for some. Still, AML remains difficult to treat, and most patients will eventually die from their disease. Therefore, novel drugs and drug combinations are under intense investigation, and promising results eagerly awaited and embraced. However, drug development is lengthy and costs are staggering. While the phase 1–phase 2–phase 3 sequence of clinical drug testing has rem...

  16. Monosomal karyotype among adult acute myeloid leukemia: clinical characteristic and prognostic analysis

    Institute of Scientific and Technical Information of China (English)

    冯茹

    2014-01-01

    Objective To explore the clinical characteristics and prognostic value of monosomal karyotype(MK)patients in adult acute myeloid leukemia(AML).Methods We retrospectively studied 45 patients of MK+in newly-diagnosed adult AML in our center from Oct 2000 to Dec2012.Clinical characteristics,cytogenetic data and prognostic features were analyzed in the cohort of MK+patients.Results MK was found in 45 patients(19.0%)

  17. Acute myeloid leukemia with basophilic differentiation in a 3-year-old Standardbred gelding

    Science.gov (United States)

    Furness, Mary Catherine; Setlakwe, Emile; Sallaway, John; Wood, Darren; Fromstein, Jordan; Arroyo, Luis G.

    2016-01-01

    A 3-year-old Standardbred gelding with a history of pyrexia, persistent hemorrhage from the oral cavity, and a large, soft swelling at the junction of the caudal aspect of the mandibular rami and proximal neck was evaluated. The horse had neutropenia and anemia, with atypical granulated cells in a blood smear. Additional tests confirmed acute myeloid leukemia with basophilic differentiation, which has been reported in humans, cats, dogs, and cattle but not horses. PMID:27708445

  18. Wnt/ß-Catenin: A New Therapeutic Approach to Acute Myeloid Leukemia

    Directory of Open Access Journals (Sweden)

    Y. Kim

    2011-01-01

    Full Text Available Recent studies have shown genetic and epigenetic aberrations resulting in aberrant activation of the Wingless-Int (Wnt pathway, thus influencing the initiation and progression of acute myeloid leukemia (AML. Of major importance, these findings may lead to novel treatment strategies exploiting targeted modulation of Wnt signaling. This paper comprises the latest status of knowledge concerning the role of Wnt pathway alteration in AML and outlines future lines of research and their clinical perspectives.

  19. Acute myeloid leukemia in adults: a case-control study in Yorkshire.

    Science.gov (United States)

    Cartwright, R A; Darwin, C; McKinney, P A; Roberts, B; Richards, I D; Bird, C C

    1988-10-01

    This paper reports the results of a case-control analysis of 161 cases of acute myeloid leukemia and 310 matched hospital controls. The patients were interviewed between 1982 and 1986. The study shows a weak association for cases with previous malignant disease. Furnace workers show excess risks. Urticaria and vertigo are in excess, as well as some aspects of family medical histories, including multiple sclerosis and cases of leukemia/lymphoma in blood relations.

  20. Drug screen in patient cells suggests quinacrine to be repositioned for treatment of acute myeloid leukemia

    OpenAIRE

    Eriksson, Anna; Österroos, Albin; Hassan, Sadia Bashir; Gullbo, Joachim; Rickardson, Linda; Jarvius, Malin; Nygren, Peter; Fryknäs, Mårten; Höglund, Martin; Larsson, Rolf

    2015-01-01

    To find drugs suitable for repositioning for use against leukemia, samples from patients with chronic lymphocytic, acute myeloid and lymphocytic leukemias as well as peripheral blood mononuclear cells (PBMC) were tested in response to 1266 compounds from the LOPAC1280 library (Sigma). Twenty-five compounds were defined as hits with activity in all leukemia subgroups (<50% cell survival compared with control) at 10 mu M drug concentration. Only one of these compounds, quinacrine, showed low...

  1. [Key molecular mechanisms associated with cell malignant transformation in acute myeloid leukemia].

    Science.gov (United States)

    Orlova, N N; Lebedev, T D; Spirin, P V; Prassolov, V S

    2016-01-01

    Cancer, along with cardiovascular disorders, is one of the most important problems of healthcare. Pathologies of the hematopoietic system are the most prevalent in patients under 30 years of age, including acute myeloid leukemia (AML), which is widespread and difficult to treat. The review considers the mechanisms that play a significant role in AML cell malignant transformation and shows the contributions of certain genes to both remission and resistance of AML cells to various treatments.

  2. [Molecular biology in myelodysplastic syndromes and acute myeloid leukemias "smoldering"].

    Science.gov (United States)

    Martinelli, Giovanni; Sartor, Chiara; Papayannidis, Cristina; Iacobucci, Ilaria; Paolini, Stefania; Clissa, Cristina; Ottaviani, Emanuela; Finelli, Carlo

    2014-03-01

    Myelodysplastic syndromes (MDS) are a heterogeneous group of clonal hematopoietic disorders of the myeloid lineage characterized by peripheral cytopenias and frequent leukemic evolution. MDS differ for clinical presentation, disease behavior and progression and this is the reflection of remarkable variability at molecular level. To this moment disease diagnosis is still dependent on bone marrow morphology that, although high concordance rates among experts are reported, remains subjective. Karyotype analysis is mandatory but diagnosis may be difficult in presence of normal karyotype or non-informative cytogenetics. Standardized molecular markers are needed to better define diagnosis, prediction of disease progression and prognosis. Furthermore, a molecular biology analysis could provide an important therapeutic tool towards tailored therapy and new insights in the disease's biology.

  3. INCIDENCE OF ACUTE MYELOID LEUKEMIA AFTER BREAST CANCER

    Directory of Open Access Journals (Sweden)

    Caterina Giovanna Valentini

    2011-12-01

    Full Text Available Breast cancer is the most frequent cancer among women and the leading cause of death among middle-aged women. Early detection by mammography screening and improvement of therapeutic options have increased breast cancer survival rates, with the consequence that late side effects of cancer treatment become increasingly important. In particular, patients treated with adjuvant chemotherapy regimens, commonly including alkylating agents and anthracyclines, are at increased risk of developing leukemia, further enhanced by the use of radiotherapy. In the last few years also the use of growth factors seems to increase the risk of secondary leukemia. The purpose of this review is to update epidemiology of therapy-related myeloid neoplasms occurring in breast cancer patients

  4. Modeling of C/EBPalpha mutant acute myeloid leukemia reveals a common expression signature of committed myeloid leukemia-initiating cells

    DEFF Research Database (Denmark)

    Kirstetter, Peggy; Schuster, Mikkel B; Bereshchenko, Oksana;

    2008-01-01

    Mutations in the CEBPA gene are present in 7%-10% of human patients with acute myeloid leukemia (AML). However, no genetic models exist that demonstrate their etiological relevance. To mimic the most common mutations affecting CEBPA-that is, those leading to loss of the 42 kDa C/EBPalpha isoform ...

  5. [Advances of study on prognostic factors of molecular biology in acute myeloid leukemia with normal cytogenetics].

    Science.gov (United States)

    Han, Tian-Jie; Xu, Xiao-Ping

    2010-08-01

    Acute myeloid leukemia (AML) is a group of diseases with a conspicuous heterogeneity. Following the development of cytogenetics, multiple reproducible chromosome aberrations have been discovered in AML, many of which not only are diagnostic markers for specific AML subtypes but also significant prognostic factors for determining complete remission (CR), relapse risk, and overall survival (OS). However, with the foundation of available chromosome analysis, a large group of acute myeloid leukemia (AML) patients, 40% to 49% of adults and 25% of children had not been found abnormality of chromosome karyotype under microscope. These so-called cytogenetically normal acute myeloid leukemia (CN-AML) patients have usually been classified in an intermediate-risk prognostic category. Nevertheless, the outcome of the CN-AML patients are varied in clinical studies, likely because there exist diverse gene mutations in these patients according to recent researches. Those mutations at the molecular level, on basis of which AML could be further classified, are significantly associated with CN-AML patients and offer potential targets for specific therapeutic studies. The review focuses on research advances abroad in this field including gene mutations suggesting bad prognosis such as FMS-related tyrosine kinase 3 gene mutation, Baalc gene and ETS-related gene hyperexpression, Wilms' tumor gene mutation and other gene mutations as well as gene mutations suggesting good prognosis such as nucleophosmin gene mutation, mixed lineage leukemia-partial tandem duplication, CCAAT/enhancer-binding protein α gene mutation.

  6. Rare cytogenetic abnormalities and alteration of microRNAs in acute myeloid leukemia and response to therapy

    Directory of Open Access Journals (Sweden)

    Mohammad Shahjahani

    2015-03-01

    Full Text Available Acute myeloid leukemia (AML is the most common acute leukemia in adults, which is heterogeneous in terms of morphological, cytogenetic and clinical features. Cytogenetic abnormalities, including karyotype aberrations, gene mutations and gene expression abnormalities are the most important diagnostic tools in diagnosis, classification and prognosis in acute myeloid leukemias. Based on World Health Organization (WHO classification, acute myeloid leukemias can be divided to four groups. Due to the heterogeneous nature of AML and since most therapeutic protocols in AML are based on genetic alterations, gathering further information in the field of rare disorders as well as common cytogenetic abnormalities would be helpful in determining the prognosis and treatment in this group of diseases. Recently, the role of microRNAs (miRNAs in both normal hematopoiesis and myeloid leukemic cell differentiation in myeloid lineage has been specified. miRNAs can be used instead of genes for AML diagnosis and classification in the future, and can also play a decisive role in the evaluation of relapse as well as response to treatment in the patients. Therefore, their use in clinical trials can affect treatment protocols and play a role in therapeutic strategies for these patients. In this review, we have examined rare cytogenetic abnormalities in different groups of acute myeloid leukemias according to WHO classification, and the role of miRNA expression in classification, diagnosis and response to treatment of these disorders has also been dealt with.

  7. Mutations in the gene for the granulocyte colony-stimulating-factor receptor in patients with acute myeloid leukemia preceded by severe congenital neutropenia

    OpenAIRE

    1995-01-01

    textabstractBACKGROUND. In severe congenital neutropenia the maturation of myeloid progenitor cells is arrested. The myelodysplastic syndrome and acute myeloid leukemia develop in some patients with severe congenital neutropenia. Abnormalities in the signal-transduction pathways for granulocyte colony-stimulating factor (G-CSF) may play a part in the progression to acute myeloid leukemia. METHODS. We isolated genomic DNA and RNA from hematopoietic cells obtained from two patients with acute m...

  8. [Problems in maintenance therapy in acute myeloid leukemias in adults].

    Science.gov (United States)

    Gürtler, R; Raderecht, C

    1975-01-01

    Problems of maintaining therapy for acute myelocytic leukemias in adults are discussed. The analysis of the maintaining therapy in 22 patients affected with an acute myelocytic leukemia and living for more than 6 months revealed that the interval therapy with a high dosage of cytostatic combinations in the sense of the COAP scheme is preferable compared with the daily administration of 6-mercaptopurin, in addition methotrexate twice a week. Reasons for this are discussed.

  9. Acquired hemoglobin H disease in a patient with aplastic anemia evolving into acute myeloid leukemia

    Directory of Open Access Journals (Sweden)

    Maria Stella Figueiredo

    Full Text Available CONTEXT: The prognosis of severe aplastic anemia has improved since the introduction of bone marrow transplantation and treatment with antithymocyte globulin. In contrast to the success of these protocols, studies with long term follow-up have shown the occurrence of clonal diseases such as paroxysmal nocturnal hemoglobinuria, myelodysplastic syndrome and acute leukemia in aplastic anemia. CASE REPORT: We report the first case of a Brazilian patient with aplastic anemia who developed myelodysplastic syndrome and acute myeloid leukemia showing acquired hemoglobin H and increased fetal hemoglobin.

  10. Novel targeted therapy for acute myeloid leukemia with a dual FLT3 and JAK2 inhibitor

    Institute of Scientific and Technical Information of China (English)

    Yin-jun LOU

    2012-01-01

    Acute myeloid leukemia (AML) is a highly malignant hematopoietic tumor.The use of all-trans retinoic acid (ATRA) and arsenic trioxide,which began from China,has resulted in revolution of the acute promyelocytic leukemia (APL) that appears curable in more than 70% of patients[1].However,the treatment regimen for nonAPL AML particularly in older patients has progressed little in the past two decades.Intensive efforts have been made toward the development of novel target agents,which are based on newfound pathophysiological events crucial for cancers.

  11. Treosulfan, Fludarabine Phosphate, and Total Body Irradiation Before Donor Stem Cell Transplant in Treating Patients With Myelodysplastic Syndrome or Acute Myeloid Leukemia

    Science.gov (United States)

    2016-08-30

    Acute Myeloid Leukemia in Remission; Chronic Myelomonocytic Leukemia; Minimal Residual Disease; Myelodysplastic Syndrome; Myelodysplastic/Myeloproliferative Neoplasm; Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable

  12. Acute Myeloid Leukemia with Isolated Trisomy 19 Associated with Diffuse Myelofibrosis and Osteosclerosis

    Directory of Open Access Journals (Sweden)

    Adam Stelling

    2015-12-01

    Full Text Available Primary myelofibrosis (PMF, per WHO criteria, is a clonal myeloproliferative neoplasm that usually presents with a proliferation of granulocytic and megakaryocytic lineages with an associated fibrous deposition and extramedullary hematopoiesis. The bone marrow histologic findings of this disorder are typically characterized by the presence of myeloid metaplasia with an associated reactive fibrosis, angiogenesis, and osteosclerosis. However, marked myelofibrosis is not solely confined to PMF and may also be associated with other conditions including but not limited to acute megakaryoblastic leukemias (FAB AML-M7. Here, we describe a rare case of a non-megakaryoblastic acute myeloid leukemia with marked myelofibrosis with osteosclerosis and an isolated trisomy 19. A 19-year-old male presented with severe bone pain of one week duration with a complete blood cell count and peripheral smear showing a mild anemia and occasional circulating blasts. A follow up computed tomography (CT scan showed diffuse osteosclerosis with no evidence of hepatosplenomegaly or lymphadenopathy. Subsequently, the bone marrow biopsy showed markedly sclerotic bony trabeculae and a hypercellular marrow with marked fibrosis and intervening sheets of immature myeloid cells consistent with myeloblasts with monocytic differentiation. Importantly, these myeloblasts were negative for megakaryocytic markers (CD61 and vWF, erythroid markers (hemoglobin and E-cadherin, and lymphoid markers (CD3, CD19, and TdT. Metaphase cytogenetics showed an isolated triosomy 19 with no JAK2 V617F mutation. The patient was treated with induction chemotherapy followed by allogenic hematopoietic stem cell transplantation which subsequently resulted in a rapid resolution of bone marrow fibrosis, suggesting graft-anti-fibrosis effect. This is a rare case of a non-megakaryoblastic acute myeloid leukemia with myelofibrosis and osteosclerosis with trisomy 19 that may provide insights into the prognosis and

  13. Clinical effectiveness of palifermin in prevention and treatment of oral mucositis in children with acute lymphoblastic leukaemia:a case-control study

    Institute of Scientific and Technical Information of China (English)

    Dorina Lauritano; Massimo Petruzzi; Dario Di Stasio; Alberta Lucchese

    2014-01-01

    The aim of this study was to evaluate the efficacy of palifermin, an N-terminal truncated version of endogenous keratinocyte growth factor, in the control of oral mucositis during antiblastic therapy. Twenty patients undergoing allogeneic stem-cell transplantation for acute lymphoblastic leukaemia were treated with palifermin, and compared to a control group with the same number of subjects and similar inclusion criteria. Statistical analysis were performed to compare the outcomes in the treatment vs. control groups. In the treatment group, we found a statistically significant reduction in the duration of parenteral nutrition (P50.002), duration of mucositis (P50.003) and the average grade of mucositis (P50.03). The statistical analysis showed that the drug was able to decrease the severity of mucositis. These data, although preliminary, suggest that palifermin could be a valid therapeutic adjuvant to improve the quality of life of patients suffering from leukaemia.

  14. Therapy-induced secondary acute myeloid leukemia with t(11;19)(q23;p13.1) in a pediatric patient with relapsed acute promyelocytic leukemia.

    Science.gov (United States)

    Dang, Daniel N; Morris, Heather D; Feusner, James H; Koduru, Prasad; Wilson, Kathleen; Timmons, Charles F; Cavalier, MaryEllen; Luu, Hung S

    2014-11-01

    Acute myeloid leukemia is classified based upon recurrent cytogenetic abnormalities. The t(15;17)(q24.1;q21.1) abnormality is found in 5% to 8% of de novo acute myeloid leukemia and is diagnostic of acute promyelocytic leukemia (APL). The translocation results in fusion of the retinoic acid receptor-α (RARA) gene at 17q21.1 and the promyelocytic leukemia (PML) gene at 15q24.1. Standard APL therapy is a combination of all-trans retinoic acid and anthracycline-based chemotherapy. Anthracycline treatment is associated with secondary clonal chromosomal aberrations that can lead to therapy-related secondary myeloid neoplasms. We present a pediatric case of relapsed APL coexistent with treatment-associated secondary myeloid neoplasm with t(11;19)(q23;p13.1).

  15. Vitamin and mineral supplements in pregnancy and the risk of childhood acute lymphoblastic leukaemia: a case-control study

    Directory of Open Access Journals (Sweden)

    Skegg David CG

    2007-07-01

    Full Text Available Abstract Background An earlier case-control study from Western Australia reported a protective effect of maternal folic acid supplementation during pregnancy on the risk of childhood acute lymphoblastic leukaemia (ALL. The present study tested that association. Methods A national case-control study was conducted in New Zealand. The mothers of 97 children with ALL and of 303 controls were asked about vitamin and mineral supplements taken during pregnancy. Results There was no association between reported folate intake during pregnancy and childhood ALL (adjusted odds ratio (OR 1.1, 95% confidence interval (CI 0.5–2.7. Combining our results with the study from Western Australia and another study from Québec in a meta-analysis gave a summary OR of 0.9 (95% CI 0.8–1.1. Conclusion Our own study, of similar size to the Australian study, does not support the hypothesis of a protective effect of folate on childhood ALL. Neither do the findings of the meta-analysis.

  16. JNK and NFκB dependence of apoptosis induced by vinblastine in human acute promyelocytic leukaemia cells.

    Science.gov (United States)

    Calviño, Eva; Tejedor, M Cristina; Sancho, Pilar; Herráez, Angel; Diez, José C

    2015-06-01

    The relationship between the mitogen-activated protein kinase response, nuclear factor-κB (NFκB) expression and the apoptosis in human acute promyelocytic leukaemia NB4 cells treated with vinblastine was investigated in this work. Cell viability, subdiploid DNA and cell cycle were analysed by propidium iodide permeability and flow cytometry analyses. Apoptosis was determined by annexin V-Fluorescein isothiocyanate assays. Western-blot analysis was used for determination of expression levels of apoptotic factors (p53, Bax and Bcl2), intracellular kinases [serine/threonine-specific protein kinase, extracellular signal-regulated kinase and c-Jun N-terminal kinase (JNK)], NFκB factor and caspases. Electrophoretic mobility shift assay was usefully applied to study DNA-NFκB interaction. In NB4 cells, vinblastine produces alteration of p53 and DNA fragmentation. Vinblastine treatment had an antiproliferative effect via the induction of apoptosis producing Bax/Bcl-2 imbalance. Vinblastine treatment suppressed NFκB expression and depressed NFκB-DNA binding activity while maintaining JNK activation that subsequently resulted in apoptotic response through caspase-dependent pathway. Our study provides a possible anti-cancer mechanism of vinblastine action on NB4 cells by deregulation of the intracellular signalling cascade affecting to JNK activation and NFκB expression. Moreover, JNK activation and NFκB depression can be very significant factors in apoptosis induction by vinblastine.

  17. Anti-leukaemic activity of the TYK2 selective inhibitor NDI-031301 in T-cell acute lymphoblastic leukaemia.

    Science.gov (United States)

    Akahane, Koshi; Li, Zhaodong; Etchin, Julia; Berezovskaya, Alla; Gjini, Evisa; Masse, Craig E; Miao, Wenyan; Rocnik, Jennifer; Kapeller, Rosana; Greenwood, Jeremy R; Tiv, Hong; Sanda, Takaomi; Weinstock, David M; Look, A Thomas

    2017-04-01

    Activation of tyrosine kinase 2 (TYK2) contributes to the aberrant survival of T-cell acute lymphoblastic leukaemia (T-ALL) cells. Here we demonstrate the anti-leukaemic activity of a novel TYK2 inhibitor, NDI-031301. NDI-031301 is a potent and selective inhibitor of TYK2 that induced robust growth inhibition of human T-ALL cell lines. NDI-031301 treatment of human T-ALL cell lines resulted in induction of apoptosis that was not observed with the JAK inhibitors tofacitinib and baricitinib. Further investigation revealed that NDI-031301 treatment uniquely leads to activation of three mitogen-activated protein kinases (MAPKs), resulting in phosphorylation of ERK, SAPK/JNK and p38 MAPK coincident with PARP cleavage. Activation of p38 MAPK occurred within 1 h of NDI-031301 treatment and was responsible for NDI-031301-induced T-ALL cell death, as pharmacological inhibition of p38 MAPK partially rescued apoptosis induced by TYK2 inhibitor. Finally, daily oral administration of NDI-031301 at 100 mg/kg bid to immunodeficient mice engrafted with KOPT-K1 T-ALL cells was well tolerated, and led to decreased tumour burden and a significant survival benefit. These results support selective inhibition of TYK2 as a promising potential therapeutic strategy for T-ALL.

  18. Empirical caspofungin therapy in clinical practice for suspected invasive fungal disease in adults with acute lymphoblastic leukaemia.

    Science.gov (United States)

    Kiehl, Michael G; Egerer, Gerlinde; Engelhardt, Monika; Gross, Barbara

    2015-02-01

    Patients with acute lymphoblastic leukaemia (ALL) after cytotoxic chemotherapy or haematopoietic stem cell transplantation (HSCT) are at risk for life-threatening invasive fungal disease (IFD). The aim was to evaluate the characteristics, antifungal therapy and outcome of adult patients with ALL after chemotherapy or HSCT receiving caspofungin empirically in a clinical setting. Retrospective chart reviews were conducted at nine large tertiary care centres in Germany. Adult patients with ALL treated empirically with caspofungin according to the product label between 2006 and 2012 were eligible. Data were extracted as case reports. In total, 25 patients (12 males, 13 females; median age 37 years; 19 with B-ALL, 6 with T-ALL) with 28 treatment episodes because of suspected IFD (18 episodes after chemotherapy, 10 episodes after allogeneic HSCT) were included in the analysis. Empirical caspofungin therapy (median duration: 19 days, range 1-105 days) was given as first-line monotherapy in 20 (71.4%), second-line monotherapy in five (17.9%) and combination therapy in three (10.7%) episodes respectively. Therapy rated successful according to the physician's overall assessment (inflammatory parameters, clinical symptoms): 20 (95%) of 21 evaluable episodes with therapy duration of at least 8 days. Empirical caspofungin appears to be an effective therapeutic option in critically ill adult ALL patients with suspected IFD in clinical practice.

  19. Small Intestinal Obstruction with Intussusception due to Acute Myeloid Leukemia: A Case Report

    Directory of Open Access Journals (Sweden)

    Sangeeta Kini

    2012-01-01

    Full Text Available Myeloid sarcoma is known to precede the development of acute myeloid leukemia (AML and can be the only clinical manifestation. Gastrointestinal involvement by AML is rare with the commonest site being small intestine. Patients present with vague abdominal pain and/or obstruction. Prognosis is usually poor as most of them rapidly progress to AML. We report a case of 25-year-old man with complaints of abdominal pain and vomiting of one-year duration. OGD scopy revealed infiltration of lesser curvature of stomach. Subsequently patient came back within a week with signs and symptoms of acute intestinal obstruction for which an ileal resection was done. Although the histology of stomach biopsy and ileal segments showing similar features were thought to be non-Hodgkin's lymphoma, immunohistochemistry confirmed the diagnosis of myeloid sarcoma. Bone marrow investigations confirmed involvement by AML. Patient succumbed to the disease due to extensive involvement of AML. This case highlights the primary gastrointestinal manifestation of AML which can often prove to be a diagnostic difficulty clinically and histologically. Prompt diagnosis is essential to hasten the management.

  20. Hematopoietic stem cells express multiple myeloid markers: implications for the origin and targeted therapy of acute myeloid leukemia

    OpenAIRE

    Taussig, David C.; Pearce, Daniel J; Simpson, Catherine; Rohatiner, Ama Z; Lister, T. Andrew; Kelly, Gavin; Luongo, Jennifer L.; Danet-Desnoyers, Gwenn-aël H.; Bonnet, Dominique

    2005-01-01

    Human hematopoietic stem cells (HSCs) are generally regarded as being devoid of the markers expressed by differentiated blood cells, the lineage-specific antigens. However, recent work suggests that genes associated with the myeloid lineage are transcribed in mouse HSCs. Here, we explore whether myeloid genes are actually translated in human HSCs. We show that CD33, CD13, and CD123, well-established myeloid markers, are expressed on human long-term repopulating cells from cord blood and bone ...

  1. Childhood leukaemia in North West England 1954-1977: epidemiology, incidence and survival.

    Science.gov (United States)

    Birch, J M; Swindell, R; Marsden, H B; Morris Jones, P H

    1981-03-01

    The annual incidence of leukaemia among children aged up to 14 years as estimated by the Manchester Children's Tumour Registry has been analysed for the 24 years 1954-1977. A significant increase in acute lymphoid leukaemia (ALL) was found, while the incidence of acute myeloid leukaemia (AML) remained constant. Other types of leukaemia were too rare to be analysed separately. The increase in ALL was concentrated among boys in the 1--5-year age group. Analysis with respect to initial white-cell count showed the increase to be more pronounced in children with initial white cell counts of 1-5 x 10(4)/microliters. The proportion of cases presenting in Lancashire compared with Greater Manchester did not change during the study period. The distribution of cases with respect to social class and socio-economic group of the parents also remained constant. Due to advances in the treatment of childhood ALL survival improved considerably during the study period and no increase in mortality was seen.

  2. EFFECTS OF CURCUMIN ON PROLIFERATION AND APOPTOSIS IN ACUTE MYELOID LEUKEMIA CELLS HL-60

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    To investigate the curcumin killing leukemia cells in vitro,. Methods: The myeloid leukemic cell line HL-60 was studied by using cell culture, flow cytometrydetermining DNA content and TUNEL method measuring apoptotic cell percentage. Results: The data showed that curcumin selectively inhibited proliferation of acute myeloid leukemia (AML) HL-60 cell lines in a dose- and time-dependent manner. The growth inhibition rate was gradually increased and reached the peak at concentration of 25 m mol/L curcumin at 24h. The sub-G1 peak appeared after 12h treatment and was increased to 34.4% at 24h. The TUNEL method further certified that apoptotic cells reached 41% at the same phase. Conclusion: curcumin possesses obvious potent of anti-leukemia cell proliferation, which is contributed to the induction of HL-60 cells apoptosis. The concentration and action time of curcumin in vitro provide some reference for clinical use.

  3. In vivo RNAi screening for the identification of oncogenes and tumor suppressors in acute myeloid leukemia

    DEFF Research Database (Denmark)

    Ge, Ying

    Acute myeloid leukemia (AML) is an aggressive malignancy characterized by uncontrolled expansion of immature myeloid cells in the hematopoietic tissues. Alternative splicing and epigenetic regulation are two mechanisms implicated in the pathogenesis of AML. In order to identify the essential...... splicing factors or epigenetic regulators for AML maintenance, we used a pool-based shRNA in vivo screens in a mouse model of human CEBPA mutated AML. Through these approaches, we found the splicing factor RBM25, and the histone methyltransferase SUV39H1 are of functional importance in AML progression....... Characterization of RBM25 indicates that low expression of RBM25 promotes expansion of both murine and human leukemic cells. Mechanistic studies show that RBM25 regulate splicing dysregulation of several crucial genes in AML. In particular, we demonstrate that RBM25 knockdown leads to the accumulation of the anti...

  4. Recurrent DNMT3A R882 Mutations in Chinese Patients with Acute Myeloid Leukemia and Myelodysplastic Syndrome

    OpenAIRE

    2011-01-01

    Somatic mutations of DNMT3A gene have recently been reported in acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). We examined the entire coding sequences of DNMT3A gene by high-resolution melting analysis and sequencing in Chinese patients with myeloid malignancies. R882 mutations were found in 12/182 AML and in 4/51 MDS, but not in either 79 chronic myeloid leukemia (CML), or 57 myeloproliferative neoplasms (MPNs), or 4 chronic monomyelocytic leukemia. No other DNMT3A mutation...

  5. Association of acute myeloid leukemia’s most immature phenotype with risk groups and outcomes

    Science.gov (United States)

    Gerber, Jonathan M.; Zeidner, Joshua F.; Morse, Sarah; Blackford, Amanda L.; Perkins, Brandy; Yanagisawa, Breann; Zhang, Hao; Morsberger, Laura; Karp, Judith; Ning, Yi; Gocke, Christopher D.; Rosner, Gary L.; Smith, B. Douglas; Jones, Richard J.

    2016-01-01

    The precise phenotype and biology of acute myeloid leukemia stem cells remain controversial, in part because the “gold standard” immunodeficient mouse engraftment assay fails in a significant fraction of patients and identifies multiple cell-types in others. We sought to analyze the clinical utility of a novel assay for putative leukemia stem cells in a large prospective cohort. The leukemic clone’s most primitive hematopoietic cellular phenotype was prospectively identified in 109 newly-diagnosed acute myeloid leukemia patients, and analyzed against clinical risk groups and outcomes. Most (80/109) patients harbored CD34+CD38− leukemia cells. The CD34+CD38− leukemia cells in 47 of the 80 patients displayed intermediate aldehyde dehydrogenase expression, while normal CD34+CD38− hematopoietic stem cells expressed high levels of aldehyde dehydrogenase. In the other 33/80 patients, the CD34+CD38− leukemia cells exhibited high aldehyde dehydrogenase activity, and most (28/33, 85%) harbored poor-risk cytogenetics or FMS-like tyrosine kinase 3 internal tandem translocations. No CD34+ leukemia cells could be detected in 28/109 patients, including 14/21 patients with nucleophosmin-1 mutations and 6/7 acute promyelocytic leukemia patients. The patients with CD34+CD38− leukemia cells with high aldehyde dehydrogenase activity manifested a significantly lower complete remission rate, as well as poorer event-free and overall survivals. The leukemic clone’s most immature phenotype was heterogeneous with respect to CD34, CD38, and ALDH expression, but correlated with acute myeloid leukemia risk groups and outcomes. The strong clinical correlations suggest that the most immature phenotype detectable in the leukemia might serve as a biomarker for “clinically-relevant” leukemia stem cells. ClinicalTrials.gov: NCT01349972. PMID:26819054

  6. Expression profile and specific network features of the apoptotic machinery explain relapse of acute myeloid leukemia after chemotherapy

    Directory of Open Access Journals (Sweden)

    Di Pietro Cinzia

    2010-07-01

    Full Text Available Abstract Background According to the different sensitivity of their bone marrow CD34+ cells to in vitro treatment with Etoposide or Mafosfamide, Acute Myeloid Leukaemia (AML patients in apparent complete remission (CR after chemotherapy induction may be classified into three groups: (i normally responsive; (ii chemoresistant; (iii highly chemosensitive. This inversely correlates with in vivo CD34+ mobilization and, interestingly, also with the prognosis of the disease: patients showing a good mobilizing activity are resistant to chemotherapy and subject to significantly higher rates of Minimal Residual Disease (MRD and relapse than the others. Based on its known role in patients' response to chemotherapy, we hypothesized an involvement of the Apoptotic Machinery (AM in these phenotypic features. Methods To investigate the molecular bases of the differential chemosensitivity of bone marrow hematopoietic stem cells (HSC in CR AML patients, and the relationship between chemosensitivity, mobilizing activity and relapse rates, we analyzed their AM expression profile by performing Real Time RT-PCR of 84 AM genes in CD34+ pools from the two extreme classes of patients (i.e., chemoresistant and highly chemosensitive, and compared them with normal controls. Results The AM expression profiles of patients highlighted features that could satisfactorily explain their in vitro chemoresponsive phenotype: specifically, in chemoresistant patients we detected up regulation of antiapoptotic BIRC genes and down regulation of proapoptotic APAF1, FAS, FASL, TNFRSF25. Interestingly, our analysis of the AM network showed that the dysregulated genes in these patients are characterized by high network centrality (i.e., high values of betweenness, closeness, radiality, stress and high involvement in drug response. Conclusions AM genes represent critical nodes for the proper execution of cell death following pharmacological induction in patients. We propose that their

  7. Iodine I 131 Monoclonal Antibody BC8, Fludarabine Phosphate, Cyclophosphamide, Total-Body Irradiation and Donor Bone Marrow Transplant in Treating Patients With Advanced Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia, or High-Risk Myelodysplastic Syndrome

    Science.gov (United States)

    2016-07-18

    Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome; Adult Acute Lymphoblastic Leukemia in Remission; Adult Acute Myeloid Leukemia in Remission; Chronic Myelomonocytic Leukemia; Previously Treated Myelodysplastic Syndrome; Refractory Anemia With Excess Blasts; Refractory Anemia With Ring Sideroblasts; Refractory Cytopenia With Multilineage Dysplasia; Refractory Cytopenia With Multilineage Dysplasia and Ring Sideroblasts

  8. Prognostic implication of N-RAS gene mutations in Egyptian adult acute myeloid leukemia.

    Science.gov (United States)

    Elghannam, Doaa M; Abousamra, Nashwa Khayrat; Shahin, Doaa A; Goda, Enas F; Azzam, Hanan; Azmy, Emad; El-Din, Manal Salah; El-Refaei, Mohamed F

    2009-01-01

    The pathogenesis of acute myeloid leukemia (AML) involves the cooperation of mutations promoting proliferation/survival and those impairing differentiation. Point mutations of the N-RAS gene are the most frequent somatic mutations causing aberrant signal-transduction in acute myeloid leukemia (AML). The aim of the present work is to study the frequency and prognostic significance of N-RAS gene mutations (N-RASmut) in de novo Egyptian adult AML. Bone marrow specimens from 150 patients with de novo acute myeloid leukemia and controls were analyzed by genomic PCR-SSCP at codons 12, 13 (exon 1), and 61 (exon 2) for N-RAS mutations. In 12.7% (19/150) AML cases, N-RAS gene mutations were found and were observed more frequently in the FAB subtype M4eo (P = 0.028) and with codon 12, 13 (14 of 19; 73.7%). Patients with N-RAS mutation had a significant lower peripheral and marrow blasts (P = 0.004, P = 0.03) and clinical outcome did not improve more than in patients without mutation. In patients with N-RAS gene mutation vs. those without, complete remission rate was (63.2% vs. 56.5%; P = 0.46), resistant disease (15.8% vs. 23.6%; P = 0.51), three years overall survival (44% vs 42%; P= 0.85) and disease free survival (42.1% vs. 38.9%, P = 0.74). Multivariate analysis showed that age was the strongest unfavorable factor for overall survival (relative risk [RR], 1.9; P = 0.002), followed by cytogenetics (P = 0.004). FAB types, N-RAS mutation and leukocytosis were the least important. In conclusion, the frequency and spectrum of N-RAS gene mutation differ between biologically distinct subtypes of AML but do not significantly influence prognosis and clinical outcome in patients with AML.

  9. Expression of ETV6 rearrangement in a subject with acute myeloid leukemia-M4Eo

    Institute of Scientific and Technical Information of China (English)

    GAO Na; LI Zhi-hong; DING Bu-tong; CHEN Yun; WANG Yun-shan; QIAO Ying; GUO Nong-jian

    2008-01-01

    @@ Acute myeloid leukemia (AML) M4Eo type is a hematological malignancy with abnormal eosinophilia,which is often accompanied by inv(16).The Ets variant gene 6 (ETV6),mapped to 12p13,is an ETS family transcription factor that is essential for hematopoietic processes,1 The ETV6 gene-involved chromosomal translocations have been found in many hematological malignancies characterized by fusing to a number of different partner genes;mainly coding for tyrosine kinases or transcription factors which are important for the initiation,progress and prognosis of disease.2 In particular,the ETV6 gene has been reported to be fused to ABL in acute lymphocytic leukemias (ALL),3 and chronic myeloid leukemia (CML).4 However,there have been few domestic reports of ETV6 fusion genes,especially in cases of acute leukemia.We investigated 3 cases of AML-M4Eo patients using Split-signal Fluorescence in situ hybridization (FISH) and found one case with a translocation between 12p13 and 1q25 co-occurring with an inv(16).The ETV6/ARG (ABL-related gene) fusion transcript was confirmed by reverse transcriptase-polymerase chain reaction (RT-PCR).This is the report of ARG involvement in a translocation in a human malignancy.

  10. ZFX Controls Propagation and Prevents Differentiation of Acute T-Lymphoblastic and Myeloid Leukemia

    Directory of Open Access Journals (Sweden)

    Stuart P. Weisberg

    2014-02-01

    Full Text Available Tumor-propagating cells in acute leukemia maintain a stem/progenitor-like immature phenotype and proliferative capacity. Acute myeloid leukemia (AML and acute T-lymphoblastic leukemia (T-ALL originate from different lineages through distinct oncogenic events such as MLL fusions and Notch signaling, respectively. We found that Zfx, a transcription factor that controls hematopoietic stem cell self-renewal, controls the initiation and maintenance of AML caused by MLL-AF9 fusion and of T-ALL caused by Notch1 activation. In both leukemia types, Zfx prevents differentiation and activates gene sets characteristic of immature cells of the respective lineages. In addition, endogenous Zfx contributes to gene induction and transformation by Myc overexpression in myeloid progenitors. Key Zfx target genes include the mitochondrial enzymes Ptpmt1 and Idh2, whose overexpression partially rescues the propagation of Zfx-deficient AML. These results show that distinct leukemia types maintain their undifferentiated phenotype and self-renewal by exploiting a common stem-cell-related genetic regulator.

  11. CMV reactivation after allogeneic HCT and relapse risk: evidence for early protection in acute myeloid leukemia.

    Science.gov (United States)

    Green, Margaret L; Leisenring, Wendy M; Xie, Hu; Walter, Roland B; Mielcarek, Marco; Sandmaier, Brenda M; Riddell, Stanley R; Boeckh, Michael

    2013-08-15

    The association between cytomegalovirus (CMV) reactivation and relapse was evaluated in a large cohort of patients with acute myeloid leukemia (AML) (n = 761), acute lymphoblastic leukemia (ALL) (n = 322), chronic myeloid leukemia (CML) (n = 646), lymphoma (n = 254), and myelodysplastic syndrome (MDS) (n = 371) who underwent allogeneic hematopoietic cell transplantation (HCT) between 1995 and 2005. In multivariable models, CMV pp65 antigenemia was associated with a decreased risk of relapse by day 100 among patients with AML (hazard ratio [HR] = 0.56; 95% confidence interval [CI], 0.3-0.9) but not in patients with ALL, lymphoma, CML, or MDS. The effect appeared to be independent of CMV viral load, acute graft-versus-host disease, or ganciclovir-associated neutropenia. At 1 year after HCT, early CMV reactivation was associated with reduced risk of relapse in all patients, but this did not reach significance for any disease subgroup. Furthermore, CMV reactivation was associated with increased nonrelapse mortality (HR = 1.31; 95% CI, 1.1-1.6) and no difference in overall mortality (HR = 1.05; 95% CI, 0.9-1.3). This report demonstrates a modest reduction in early relapse risk after HCT associated with CMV reactivation in a large cohort of patients without a benefit in overall survival.

  12. Chronic meningitis by histoplasmosis: report of a child with acute myeloid leukemia

    Directory of Open Access Journals (Sweden)

    G.H. Pereira

    2008-12-01

    Full Text Available Meningitis is a common evolution in progressive disseminated histoplasmosis in children, and is asymptomatic in many cases. In leukemia, the impaired of the T cells function can predispose to the disseminated form. The attributed mortality rate in this case is 20%-40% and the relapse rate is as high as 50%; therefore, prolonged treatment may be emphasized. We have described a child with acute myeloid leukemia (AML, that developed skin lesions and asymptomatic chronic meningitis, with a good evolution after prolonged treatment with amphotericin B deoxycholate followed by fluconazole.

  13. MicroRNAs in Acute Myeloid Leukemia and Other Blood Disorders

    Directory of Open Access Journals (Sweden)

    Yao Yuan

    2012-01-01

    Full Text Available Common blood disorders include hematopoietic cell malignancies or leukemias and plasma cell dyscrasia, all of which have associated microRNA abnormalities. In this paper, we discuss several leukemias including acute myeloid leukemia (AML and chronic lymphocytic leukemia (CLL and identify altered microRNAs and their targets. Immune disorders with altered blood levels of antibodies include autoimmune disorders, such as systemic lupus erythematosus (SLE with associated anti-self-autoantibodies and immunoglobulin A nephropathy (IgAN also have related microRNA abnormalities. The alterations in microRNAs may serve as therapeutic targets in these blood disorders.

  14. BAG1: The Guardian of Anti-Apoptotic Proteins in Acute Myeloid Leukemia

    OpenAIRE

    Sanja Aveic; Martina Pigazzi; Giuseppe Basso

    2011-01-01

    BCL2 associated Athano-Gene 1 (BAG1) is a multifunctional protein that has been described to be involved in different cell processes linked to cell survival. It has been reported as deregulated in diverse cancer types. Here, BAG1 protein was found highly expressed in children with acute myeloid leukemia at diagnosis, and in a cohort of leukemic cell lines. A silencing approach was used for determining BAG1's role in AML, finding that its down-regulation decreased expression of BCL2, BCL-XL, M...

  15. Impaired nutritional status during intensive chemotherapy in Russian and Norwegian cohorts with acute myeloid leukemia.

    Science.gov (United States)

    Iversen, Per Ole; Ukrainchenko, Ekaterina; Afanasyev, Boris; Hulbekkmo, Kristin; Choukah, Amal; Gulbrandsen, Nina; Wisløff, Finn; Tangen, Jon-Magnus

    2008-10-01

    Intensive chemotherapy is mandatory in curative treatment of acute myeloid leukemia (AML), but whether the nutritional status deteriorates during treatment, is unknown. We therefore prospectively examined anthropometric and biochemical nutritional markers during intensive chemotherapy in 26 Russian and 19 Norwegian AML patients during 9 months from diagnosis. Although the body mass index remained unchanged in both cohorts, hand grip strength and triceps skinfold thickness declined (Pchemotherapy for AML, leading to impaired nutritional status, hypofunction of the pituitary-gonadal axis and decreased health-related quality of life.

  16. [Prognostic significance of cytogenetics in aged patients with acute myeloid leukemia].

    Science.gov (United States)

    Lin, Jie; Zhu, Hong-Li

    2015-04-01

    Aged patients with acute myeloid leukemia accounted for more than half of the adult AML patients, which has characteristics of low complete remission rate, short overall survival and poor prognosis. Recently, the importance of cytogenetics in AML was gradually realized. The diagnosis and typing, prognosis stratification and guide for treatment are performed on the basis of cytogenetics, but the research on influence of cytogenetics on adged patients with AML are relatively few. This review briefly summarizes the prognostic significance of cytogenetics in aged patients with AML.

  17. Minimal residual disease assessed by multi-parameter flow cytometry is highly prognostic in adult patients with acute lymphoblastic leukaemia.

    Science.gov (United States)

    Ravandi, Farhad; Jorgensen, Jeffrey L; O'Brien, Susan M; Jabbour, Elias; Thomas, Deborah A; Borthakur, Gautam; Garris, Rebecca; Huang, Xuelin; Garcia-Manero, Guillermo; Burger, Jan A; Ferrajoli, Alessandra; Wierda, William; Kadia, Tapan; Jain, Nitin; Wang, Sa A; Konoplev, Sergei; Kebriaei, Partow; Champlin, Richard E; McCue, Deborah; Estrov, Zeev; Cortes, Jorge E; Kantarjian, Hagop M

    2016-02-01

    The prognostic value of minimal residual disease (MRD) assessed by multi-parameter flow cytometry (MFC) was investigated among 340 adult patients with B-cell acute lymphoblastic leukaemia (B-ALL) treated between 2004 and 2014 using regimens including the hyperCVAD (hyperfractionated cyclophosphamide, vincristine, doxorubicin, dexamethasone, methotrexate, cytarabine) backbone. Among them, 323 (95%) achieved complete remission (CR) and were included in this study. Median age was 52 years (range, 15-84). Median white blood cell count (WBC) was 9·35 × 10(9) /l (range, 0·4-658·1 ×1 0(9) /l). MRD by MFC was initially assessed with a sensitivity of 0·01%, using a 15-marker, 4-colour panel and subsequently a 6-colour panel on bone marrow specimens obtained at CR achievement and at approximately 3 month intervals thereafter. MRD negative status at CR was associated with improved disease-free survival (DFS) and overall survival (OS) (P = 0·004 and P = 0·03, respectively). Similarly, achieving MRD negative status at approximately 3 and 6 months was associated with improved DFS (P = 0·004 and P < 0·0001, respectively) and OS (P = 0·004 and P < 0·0001, respectively). Multivariate analysis including age, WBC at presentation, cytogenetics (standard versus high risk) and MRD status at CR, 3 and 6 months, indicated that MRD negative status at CR was an independent predictor of DFS (P < 0·05). Achievement of an MRD negative state assessed by MFC is an important predictor of DFS and OS in adult patients with ALL.

  18. Outcome of Childhood Acute Lymphoblastic Leukaemia after Induction Therapy --- Three-Year Experience in a Tertiary Care Hospital in Bangladesh

    Directory of Open Access Journals (Sweden)

    M Belayet Hossain

    2017-01-01

    Full Text Available Background: The incidence of different malignancies is increasing among the world populations. Acute lymphoblastic leukaemia (ALL is the most common of all the paediatric malignancies. Response to induction therapy is one of the most important predictors of long term outcome of ALL. Objective: To see the immediate outcome of paediatric ALL patients following induction therapy. Materials and Methods: This retrospective study was conducted from January 2013 to December 2015. Total 221 paediatric ALL patients were included in this study. Diagnosis was based on history, examination, blast cells count on peripheral blood film and bone marrow study, CSF study and immunophenotyping of peripheral blood/bone marrow aspirate in patients who were financially capable. Among them, parents of 40 (18% patients did not agree to start chemotherapy. According to Modified UK ALL 2003 protocol (Regimen A & B 181 patients were given induction therapy (vincristine, prednisolone, L-asparaginase, and daunomycin in high risk patients. Among them 14 patients discontinued, 10 patients died during chemotherapy and rest 157 patients completed induction phase. Bone marrow study was repeated after completion of induction therapy and remission pattern was seen. Results: Out of 157 chemotherapy completed patients, 137 (87% went into complete remission (25% blast cells in the bone marrow. Ten (5.5% patients died due to bleeding, febrile neutropenia and sepsis during the course of induction therapy. Conclusion: ALL in children is curable with effective chemotherapy. Poverty, ignorance and misconception regarding outcome are responsible for refusal and discontinuation of chemotherapy in third world countries like Bangladesh. Mortality and treatment cost can be reduced with the improvement of the facilities for isolation, barrier nursing and supportive treatment, and by creating awareness.

  19. Detection of dicentric chromosome (9;20) in paediatric B-cell acute lymphoblastic leukaemia: prognostic significance.

    Science.gov (United States)

    Letouzey, Mathilde; Penther, Dominique; Roche-Lestienne, Catherine; Nelken, Brigitte; Devoldère, Catherine; Vannier, Jean-Pierre; Schneider, Pascale

    2015-02-01

    The dicentric chromosome (9;20) (dic(9;20)) is described in 2 % of childhood B-acute lymphoblastic leukaemia. Fluorescence in situ hybridization (FISH) is the most reliable method to identify dic(9;20) when compared with conventional cytogenetics. To define the prognostic importance of dic(9;20), we evaluated treatment response and patient survival. This was a retrospective study in three French university centres. Patients' clinical and laboratory characteristics and treatment response are described. Nine children with dic(9;20) have been identified since 1995. All patients had at least one poor prognostic feature either among the clinical features, the initial laboratory results or in the initial treatment response: central nervous system involvement (2/9), high median leucocyte count (≥50 G/L) (8/9) and poor response to prednisone (2/9). All patients were in complete cytological remission after induction therapy but only three had a good molecular response with minimal residual disease (MRD) <10(-3). Five out of nine patients relapsed and two died, 4 and 12 months after diagnosis, respectively. The event-free survival rate in this population was 44 % (95 % confidence interval (CI) = 0.09-0.79) and overall survival 78 % (95 % CI = 0.51-1.05). In this population, dic(9;20) is associated with a relatively poor prognosis. Patients showing dic(9;20), whether this cytogenetic abnormality is associated with other poor prognostic factors or not, should be identified at the outset in order to be offered a more intensive treatment protocol.

  20. Prospective molecular monitoring of BCR/ABL transcript in children with Ph+ acute lymphoblastic leukaemia unravels differences in treatment response.

    Science.gov (United States)

    Cazzaniga, Giovanni; Lanciotti, Marina; Rossi, Vincenzo; Di Martino, Daniela; Aricò, Maurizio; Valsecchi, Maria Grazia; Basso, Giuseppe; Masera, Giuseppe; Micalizzi, Concetta; Biondi, Andrea

    2002-11-01

    Children with Philadelphia-chromosome-positive (Ph+) acute lymphoblastic leukaemia (ALL) represent a subgroup at very high risk for treatment failure, despite intensive chemotherapy. However, recent retrospective studies showed that Ph+ childhood ALL is a heterogeneous disease with regard to treatment response. We have prospectively monitored, by reverse transcription polymerase chain reaction (RT-PCR) during follow-up, the presence of the BCR/ABL fusion transcript in Ph+ ALL children diagnosed in the Italian multicentre Associazione Italiana Ematologia Oncologia Pediatrica ALL-AIEOP-95 therapy protocol. To our knowledge, this is the first report on the evaluation of minimal residual disease (MRD) in childhood Ph+ ALL prospectively enrolled in an intensive, Berlin-Frankfurt-Munster (BFM)-type treatment protocol. Twenty-seven of 36 (75.0%) Ph+ patients consecutively enrolled into the high-risk group of the AIEOP-ALL protocol between May 1995 and October 1999 were successfully analysed. Twenty were good responders to the pre-phase of prednisone/intrathecal methotrexate treatment (PGR) and seven were poor responders (PPR). Within the PPR group, the RT-PCR monitoring constantly showed positivity for the BCR/ABL fusion transcript and all the patients died of disease progression. In contrast, highly sensitive qualitative RT-PCR monitoring revealed heterogeneity within the PGR group of Ph+ childhood ALL patients. Three different subgroups could be defined, according to the clearance of Ph+ cells within the first 5 months of treatment. This provides useful information on the capability of chemotherapy to reduce the leukaemic clone, with prognostic implications.

  1. A mathematical model of phosphorylation AKT in Acute Myeloid Leukemia

    Science.gov (United States)

    Adi, Y. A.; Kusumo, F. A.; Aryati, L.; Hardianti, M. S.

    2016-04-01

    In this paper we consider a mathematical model of PI3K/AKT signaling pathways in phosphorylation AKT. PI3K/AKT pathway is an important mediator of cytokine signaling implicated in regulation of hematopoiesis. Constitutive activation of PI3K/AKT signaling pathway has been observed in Acute Meyloid Leukemia (AML) it caused by the mutation of Fms-like Tyrosine Kinase 3 in internal tandem duplication (FLT3-ITD), the most common molecular abnormality associated with AML. Depending upon its phosphorylation status, protein interaction, substrate availability, and localization, AKT can phosphorylate or inhibite numerous substrates in its downstream pathways that promote protein synthesis, survival, proliferation, and metabolism. Firstly, we present a mass action ordinary differential equation model describing AKT double phosphorylation (AKTpp) in a system with 11 equations. Finally, under the asumtion enzyme catalyst constant and steady state equilibrium, we reduce the system in 4 equation included Michaelis Menten constant. Simulation result suggested that a high concentration of PI3K and/or a low concentration of phospatase increased AKTpp activation. This result also indicates that PI3K is a potential target theraphy in AML.

  2. Adult patients with relapsed and/or refractory B-precursor Acute lymphoblastic leukaemia | EU Clinical Trials Register [EU Clinical Trials Register

    Lifescience Database Archive (English)

    Full Text Available alutare l’efficacia dell’anticorpo BiTE® blinatumomab rispetto alla chemioterapia standard in soggetti adulti affetti da leucemia...rispetto alla chemioterapia standard, in soggetti adulti con leucemia linfoblastica acuta che non hanno risp... with relapsed and/or refractory B-precursor Acute lymphoblastic leukaemia Soggetti adulti affetti da leucemia...esponding to therapy Pazienti adulti con leucemia linfoblastica acuta - un tumore del sangue e midollo - che...alattia- Neoplasia prostatica intraepiteliale senza evidenza di tumore alla prostata .2 . diagnosi di leucemia

  3. Survival of Mexican Children with Acute Lymphoblastic Leukaemia under Treatment with the Protocol from the Dana-Farber Cancer Institute 00-01

    Science.gov (United States)

    Jiménez-Hernández, Elva; Jaimes-Reyes, Ethel Zulie; Arellano-Galindo, José; García-Jiménez, Xochiketzalli; Tiznado-García, Héctor Manuel; Sánchez-Jara, Berenice; Bekker-Méndez, Vilma Carolina; Ortíz-Torres, María Guadalupe; Ortíz-Fernández, Antonio; Marín-Palomares, Teresa; Mejía-Aranguré, Juan Manuel

    2015-01-01

    Our aim in this paper is to describe the results of treatment of acute lymphoblastic leukaemia (ALL) in Mexican children treated from 2006 to 2010 under the protocol from the Dana-Farber Cancer Institute (DFCI) 00-01. The children were younger than 16 years of age and had a diagnosis of ALL de novo. The patients were classified as standard risk if they were 1–9.9 years old and had a leucocyte count 100 × 109/L. The poor outcomes were associated with toxic death during induction, complete remission, and relapse. These factors remain the main obstacles to the success of this treatment in our population. PMID:25922837

  4. Haematologic and immunophenotypic profile of acute myeloid leukemia : an experience of Tata Memorial Hospital

    Directory of Open Access Journals (Sweden)

    Ghosh S

    2003-01-01

    Full Text Available OBJECTIVES : To study the hematologic and immunophenotypic profile of 260 cases of acute myeloid leukemia at diagnosis. MATERIAL AND METHODS : This is a retrospective analysis of 260 cases of AML diagnosed at our institution between 1998 and 2000. Diagnosis was based on peripheral blood and bone marrow examination for morphology cytochemistry and immunophenotypic studies. SPSS software package, version 10, was used for statistical analysis. RESULTS : Seventy-six percent of our cases were adults. The age of the patients ranged from one year to 78 years with a median age of 27.2 years. There were 187 males and 73 females. The commonest FAB subtype, in both children and adults, was AML-M2. The highest WBC counts were seen in AML-M1 and the lowest in AML-M3 (10-97 x 10(9/L, mean 53.8 x 10(9/L. The mean values and range for hemoglobin was 6.8 gm/l (1.8 gm/l to 9.2 gm/l, platelet count 63.3 x 10(9/L (32-83 x 10(9/L, peripheral blood blasts 41.4% (5 to 77% and bone marrow blasts 57.6% (34-96%. Myeloperoxidase positivity was highest in the M1, M2 and M3 subtypes. CD13 and CD33 were the most useful markers in the diagnosis of AML. CD14 and CD36 were most often seen in monocytic (38% and myelomonocytic (44% leukemias. Lymphoid antigen expression was seen in 15% of cases. CD7 expression was the commonest (11%. CONCLUSION : AML accounted for 39.8% of all acute leukemias at this institution. The most common subtype was AML-M2. Myeloperoxidase stain was a useful tool in the diagnosis of myeloid leukemias. CD13 and CD33 were the most diagnostic myeloid markers.

  5. The role of TLR8 signaling in acute myeloid leukemia differentiation.

    Science.gov (United States)

    Ignatz-Hoover, J J; Wang, H; Moreton, S A; Chakrabarti, A; Agarwal, M K; Sun, K; Gupta, K; Wald, D N

    2015-04-01

    Acute myeloid leukemia (AML) is an aggressive disease with a poor 5-year survival of 21% that is characterized by the differentiation arrest of immature myeloid cells. For a rare subtype of AML (acute promyeloctyic leukemia, 5-10% of cases), all-trans retinoic acid therapy removes the differentiation block, yielding over a 90% cure rate. However, this treatment is not effective for the other 90-95% of AML patients, suggesting that new differentiation strategies are needed. Interestingly, differentiation is induced in normal hematopoietic cells through Toll-like receptor (TLR) stimulation and TLRs are expressed on AML cells. We present evidence that the TLR8 activation promotes AML differentiation and growth inhibition in a TLR8/MyD88/p38-dependent manner. We also show that that TLR7/TLR8 agonist, R848, considerably impairs the growth of human AML cells in immunodeficient mice. Our data suggests TLR8 activation has direct anti-leukemic effects independent of its immunomodulating properties that are currently under investigation for cancer therapy. Taken together, our results suggest that treatment with TLR8 agonists may be a promising new therapeutic strategy for AML.

  6. Association between MTHFR polymorphisms and acute myeloid leukemia risk: a meta-analysis.

    Directory of Open Access Journals (Sweden)

    Yu-Tao Qin

    Full Text Available Previous observational studies investigating the association between methylenetetrahydrofolate reductase (MTHFR polymorphisms and acute myeloid leukemia risk (AML have yielded inconsistent results. The aim of this study is to derive a more precise estimation of the association between MTHFR (C677T and A1298C polymorphisms and acute myeloid leukemia risk. PubMed and Embase databases were systematically searched to identify relevant studies from their inception to August 2013. Odds ratios (ORs with 95% confidence intervals (CIs were the metric of choice. Thirteen studies were selected for C677T polymorphism (1838 cases and 5318 controls and 9 studies (1335 patients and 4295 controls for A1298C polymorphism. Overall, pooled results showed that C677T polymorphism was not significant associated with AML risk(OR, 0.98-1.04; 95% CI, 0.86-0.92 to 1.09-1.25. Similar results were observed for the A1298C polymorphism and in subgroup analysis. All comparisons revealed no substantial heterogeneity nor did we detect evidence of publication bias. In summary, this meta-analysis provides evidence that MTHFR polymorphisms were not associated with AML risk. Further investigations are needed to offer better insight into the role of these polymorphisms in AML carcinogenesis.

  7. Prognostic significance of DNMT3A mutations in patients with acute myeloid leukemia.

    Science.gov (United States)

    Ibrahem, Lamia; Mahfouz, Rabab; Elhelw, Loie; Abdsalam, Eman M; Soliman, Rehan

    2015-01-01

    Acute myeloid leukemia (AML) represents a heterogeneous group of malignancies with great variability in clinical course and response to therapy. Several molecular markers have been described that help to classify AML patients into risk groups. Mutations in DNA methyltransferase 3A (DNMT3A) gene were recently demonstrated in AML. Approximately 20% patients with AML carry DNMT3A gene mutations and were associated with a poor clinical outcome but its clinical implications in Egyptian AML patients are largely unknown. The aim of the study was to study the incidence and prognostic impact of DNMT3A mutations in patients with de novo acute myeloid leukemia. A total of 120 patients with de novo AML were examined for mutations in DNMT3A by sequencing. DNMT3A mutations were identified in 34/120 (28%) of AML patients. 15 patients with M4, 14 patients with M5, 3 patient with M2 and 2 patient with M6. DNMT3A mutations were more frequently associated with older age, higher platelet counts and intermediate risk. DNMT3A-mutated patients did not differ regarding complete remission (CR) and disease-free survival (DFS), but had shorter overall survival (OS; P=0.048) than DNMT3A-wild-type patients. Mutations in DNMT3A independently predicted a shorter OS (P=0.049) by multivariate analysis. We concluded that DNMT3A mutations are highly frequent in Egyptian patients with AML and are associated with an unfavorable prognosis.

  8. Extramedullary Acute Myeloid Leukemia (AML: Leukemic Pleural Effusion, Case Report and Review of the Literature

    Directory of Open Access Journals (Sweden)

    Naveen ePemmaraju

    2014-06-01

    Full Text Available Objective and Importance: Malignant pleural effusions occur in the setting of both solid and hematologic malignancies. Pleural effusion caused by leukemic infiltration is an unusual extramedullary manifestation of acute myeloid leukemia (AML with fewer than 20 cases reported.1-11 We report a case of pericardial and pleural effusions in a patient with AML and review the literature. Clinical presentation: In this case, a 55 year old man with previous history of myeloproliferative neoplasm (MPN experienced transformation AML, heralded by appearance of leukemic pleural effusions. The patient was identified to have leukemic pleural effusion based upon extended cytogenetic analysis of the pleural fluid, as morphologic analysis alone was insufficient. Intervention: The patient was treated with hypomethylator-based and intensive chemotherapy strategies, both of which maintained resolution of the effusions in the remission setting. Conclusion: Due to the rarity of diagnosis of leukemic pleural effusions, both cytogenetic and fluorescence in situ hybridization (FISH testing are recommended. Futhermore, systemic chemotherapy directed at the AML can lead to complete resolution of leukemic pleural effusions. Objective and ImportancePleural effusion caused by leukemic infiltration is an unusual extramedullary manifestation of acute myeloid leukemia (AML, but may be more common than previously thought. Fewer than 20 cases have been reported.1-11 We report a case of pericardial and pleural effusions in a patient with AML and review the literature.

  9. Secondary Philadelphia chromosome and erythrophagocytosis in a relapsed acute myeloid leukemia after hematopoietic cell transplantation.

    Science.gov (United States)

    Kelemen, Katalin; Galani, Komal; Conley, Christopher R; Greipp, Patricia T

    2014-06-01

    The acquisition of the Philadelphia chromosome (Ph) as a secondary change during the course of hematopoietic malignancies is rare and is associated with poor prognosis. Few cases of secondary Ph have been reported after hematopoietic cell transplantation (HCT). A secondary Ph at relapse is of clinical importance because it provides a therapeutic target for tyrosine kinase inhibitors along with or in replacement of chemotherapy. We describe a case of relapsed acute myeloid leukemia (AML) after HCT that developed a BCR-ABL1 translocation along with erythrophagocytosis by blasts as a secondary change at the time of relapse. The progression of this patient's myeloid neoplasm from myelodysplastic syndrome to AML to relapsed AML after HCT was accompanied by a stepwise cytogenetic evolution: A deletion 20q abnormality subsequently acquired a deletion 7q and, finally, at relapse after HCT, a secondary Ph was gained. The relationship between the secondary Ph and the erythrophagocytosis by blasts is not clear. We review the possible pathogenesis and cytogenetic associations of erythrophagocytosis by blasts, a rare feature in acute leukemias.

  10. Over-Expression of Catalase in Myeloid Cells Confers Acute Protection Following Myocardial Infarction

    Directory of Open Access Journals (Sweden)

    E. Bernadette Cabigas

    2014-05-01

    Full Text Available Cardiovascular disease is the leading cause of death in the United States and new treatment options are greatly needed. Oxidative stress is increased following myocardial infarction and levels of antioxidants decrease, causing imbalance that leads to dysfunction. Therapy involving catalase, the endogenous scavenger of hydrogen peroxide (H2O2, has been met with mixed results. When over-expressed in cardiomyocytes from birth, catalase improves function following injury. When expressed in the same cells in an inducible manner, catalase showed a time-dependent response with no acute benefit, but a chronic benefit due to altered remodeling. In myeloid cells, catalase over-expression reduced angiogenesis during hindlimb ischemia and prevented monocyte migration. In the present study, due to the large inflammatory response following infarction, we examined myeloid-specific catalase over-expression on post-infarct healing. We found a significant increase in catalase levels following infarction that led to a decrease in H2O2 levels, leading to improved acute function. This increase in function could be attributed to reduced infarct size and improved angiogenesis. Despite these initial improvements, there was no improvement in chronic function, likely due to increased fibrosis. These data combined with what has been previously shown underscore the need for temporal, cell-specific catalase delivery as a potential therapeutic option.

  11. Impact of MLL5 expression on decitabine efficacy and DNA methylation in acute myeloid leukemia.

    Science.gov (United States)

    Yun, Haiyang; Damm, Frederik; Yap, Damian; Schwarzer, Adrian; Chaturvedi, Anuhar; Jyotsana, Nidhi; Lübbert, Michael; Bullinger, Lars; Döhner, Konstanze; Geffers, Robert; Aparicio, Samuel; Humphries, R Keith; Ganser, Arnold; Heuser, Michael

    2014-09-01

    Hypomethylating agents are widely used in patients with myelodysplastic syndromes and unfit patients with acute myeloid leukemia. However, it is not well understood why only some patients respond to hypomethylating agents. We found previously that the effect of decitabine on hematopoietic stem cell viability differed between Mll5 wild-type and null cells. We, therefore, investigated the role of MLL5 expression levels on outcome of acute myeloid leukemia patients who were treated with decitabine. MLL5 above the median expression level predicted longer overall survival independent of DNMT3A mutation status in bivariate analysis (median overall survival for high vs. low MLL5 expression 292 vs. 167 days; P=0.026). In patients who received three or more courses decitabine, high MLL5 expression and wild-type DNMT3A independently predicted improved overall survival (median overall survival for high vs. low MLL5 expression 468 vs. 243 days; P=0.012). In transformed murine cells, loss of Mll5 was associated with resistance to low-dose decitabine, less global DNA methylation in promoter regions, and reduced DNA demethylation upon decitabine treatment. Together, these data support our clinical observation of improved outcome in decitabine-treated patients who express MLL5 at high levels, and suggest a mechanistic role of MLL5 in the regulation of DNA methylation.

  12. The clinical significance of γ-catenin in acute myeloid leukemia

    Directory of Open Access Journals (Sweden)

    Xu J

    2016-06-01

    Full Text Available Jiadai Xu,1 Wei Wu,1 Wenyi Shen,1 Peng Liu2 1Department of Hematology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 2Department of Hematology, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China Abstract: Dysregulation of γ-catenin may function as an oncogenic factor in various malignancies. We investigated γ-catenin expression in acute myeloid leukemia (AML and explored its role in the pathogenesis of AML. γ-Catenin was significantly overexpressed in AML patients compared to healthy donors. The γ-catenin expression in AML patients with lower white blood cells (<30×109/L was significantly higher than those with higher white blood cells (≥30×109/L. The expression levels of γ-catenin in AML patients with mutated CEBPα were significantly higher than those with unmutated CEBPα. AML patients with lower γ-catenin levels were more likely to achieve complete remission compared with patients who have higher γ-catenin levels. In K562 cells, γ-catenin knockdown suppressed cellular proliferation, while the cellular migration was greatly enhanced. Moreover, knocking down of γ-catenin enhanced the cytotoxicity of decitabine in K562 cells. Our investigation has indicated a potential role of γ-catenin in the pathogenesis of AML. Keywords: γ-catenin, acute myeloid leukemia, AML, decitabine, prognosis, bone marrow, shRNA

  13. Cardiac Relapse of Acute Myeloid Leukemia after Allogeneic Hematopoietic Stem Cell Transplantation

    Science.gov (United States)

    Sánchez-Quintana, Ana; Quijada-Fumero, Alejandro; Laynez-Carnicero, Ana; Breña-Atienza, Joaquín; Poncela-Mireles, Francisco J.; Llanos-Gómez, Juan M.; Cabello-Rodríguez, Ana I.; Ramos-López, María

    2016-01-01

    Secondary or metastatic cardiac tumors are much more common than primary benign or malignant cardiac tumors. Any tumor can cause myocardial or pericardial metastasis, although isolated or combined tumor invasion of the pericardium is more common. Types of neoplasia with the highest rates of cardiac or pericardial involvement are melanoma, lung cancer, and breast and mediastinal carcinomas. Acute myeloid leukemia (AML) is the most common type of acute leukemia in adults. Initial treatment involves chemotherapy followed by consolidation treatment to reduce the risk of relapse. In high-risk patients, the treatment of choice for consolidation is hematopoietic stem cell transplantation (HSCT). Relapse of AML is the most common cause of HSCT failure. Extramedullary relapse is rare. The organs most frequently affected, called “sanctuaries,” are the testes, ovaries, and central nervous system. We present a case with extramedullary relapse in the form of a solid cardiac mass. PMID:27642531

  14. KIAA1524: A novel MLL translocation partner in acute myeloid leukemia.

    Science.gov (United States)

    Coenen, Eva A; Zwaan, C Michel; Meyer, Claus; Marschalek, Rolf; Pieters, Rob; van der Veken, Lars T; Beverloo, H Berna; van den Heuvel-Eibrink, Marry M

    2011-01-01

    The Mixed Lineage Leukemia gene on chromosome 11q23 is a frequent site of recurrent translocations in acute leukemias. Its promiscuous character is reflected by the more than 60 different translocation partners described in literature. Prompted by karyotype and atypical FISH results, we identified a new translocation partner in infant acute myeloid leukemia, KIAA1524 on 3q13.13, also known as 'Cancerous Inhibitor of Protein phosphatase 2A (CIP2A)'. This gene was recently identified as a proto-oncogene stabilizing MYC protein in gastric carcinoma. KIAA1524 has never been related to hematologic malignancies before, and the current AML case is the first case in which an MLL-KIAA1524 fusion was described.

  15. Integrated genome-wide genotyping and gene expression profiling reveals BCL11B as a putative oncogene in acute myeloid leukemia with 14q32 aberrations.

    Science.gov (United States)

    Abbas, Saman; Sanders, Mathijs A; Zeilemaker, Annelieke; Geertsma-Kleinekoort, Wendy M C; Koenders, Jasper E; Kavelaars, Francois G; Abbas, Zabiollah G; Mahamoud, Souad; Chu, Isabel W T; Hoogenboezem, Remco; Peeters, Justine K; van Drunen, Ellen; van Galen, Janneke; Beverloo, H Berna; Löwenberg, Bob; Valk, Peter J M

    2014-05-01

    Acute myeloid leukemia is a neoplasm characterized by recurrent molecular aberrations traditionally demonstrated by cytogenetic analyses. We used high density genome-wide genotyping and gene expression profiling to reveal acquired cryptic abnormalities in acute myeloid leukemia. By genome-wide genotyping of 137 cases of primary acute myeloid leukemia, we disclosed a recurrent focal amplification on chromosome 14q32, which included the genes BCL11B, CCNK, C14orf177 and SETD3, in two cases. In the affected cases, the BCL11B gene showed consistently high mRNA expression, whereas the expression of the other genes was unperturbed. Fluorescence in situ hybridization on 40 cases of acute myeloid leukemia with high BCL11B mRNA expression [2.5-fold above median; 40 out of 530 cases (7.5%)] revealed 14q32 abnormalities in two additional cases. In the four BCL11B-rearranged cases the 14q32 locus was fused to different partner chromosomes. In fact, in two cases, we demonstrated that the focal 14q32 amplifications were integrated into transcriptionally active loci. The translocations involving BCL11B result in increased expression of full-length BCL11B protein. The BCL11B-rearranged acute myeloid leukemias expressed both myeloid and T-cell markers. These biphenotypic acute leukemias all carried FLT3 internal tandem duplications, a characteristic marker of acute myeloid leukemia. BCL11B mRNA expression in acute myeloid leukemia appeared to be strongly associated with expression of other T-cell-specific genes. Myeloid 32D(GCSF-R) cells ectopically expressing Bcl11b showed decreased proliferation rate and less maturation. In conclusion, by an integrated approach involving high-throughput genome-wide genotyping and gene expression profiling we identified BCL11B as a candidate oncogene in acute myeloid leukemia.

  16. Suppressed spontaneous secretion of growth hormone in girls after treatment for acute lymphoblastic leukaemia.

    OpenAIRE

    Moëll, C; Garwicz, S; Westgren, U; Wiebe, T; Albertsson-Wikland, K.

    1989-01-01

    The spontaneous secretion of growth hormone during a 24 hour period and the response of growth hormone to growth hormone releasing hormone was studied in 13 girls who had received treatment for acute lymphoblastic leukemia that included cranial irradiation with 20-24 Gy in 12-14 fractions. At the time of investigation the girls were at varying stages of puberty and had normal concentrations of thyroid hormones. The mean interval between the end of treatment and investigation was 4.6 years. Th...

  17. Oxindole alkaloids from Uncaria tomentosa induce apoptosis in proliferating, G0/G1-arrested and bcl-2-expressing acute lymphoblastic leukaemia cells.

    Science.gov (United States)

    Bacher, Nicole; Tiefenthaler, Martin; Sturm, Sonja; Stuppner, Hermann; Ausserlechner, Michael J; Kofler, Reinhard; Konwalinka, Günther

    2006-03-01

    Natural products are still an untapped source of promising lead compounds for the generation of antineoplastic drugs. Here, we investigated for the first time the antiproliferative and apoptotic effects of highly purified oxindole alkaloids, namely isopteropodine (A1), pteropodine (A2), isomitraphylline (A3), uncarine F (A4) and mitraphylline (A5) obtained from Uncaria tomentosa, a South American Rubiaceae, on human lymphoblastic leukaemia T cells (CCRF-CEM-C7H2). Four of the five tested alkaloids inhibited proliferation of acute lymphoblastic leukaemia cells. Furthermore, the antiproliferative effect of the most potent alkaloids pteropodine (A2) and uncarine F (A4) correlated with induction of apoptosis. After 48 h, 100 micromol/l A2 or A4 increased apoptotic cells by 57%. CEM-C7H2 sublines with tetracycline-regulated expression of bcl-2, p16ink4A or constitutively expressing the cowpox virus protein crm-A were used for further studies of the apoptosis-inducing properties of these alkaloids. Neither overexpression of bcl-2 or crm-A nor cell-cycle arrest in G0/G1 phase by tetracycline-regulated expression of p16INK4A could prevent alkaloid-induced apoptosis. Our results show the strong apoptotic effects of pteropodine and uncarine F on acute leukaemic lymphoblasts and recommend the alkaloids for further studies in xenograft models.

  18. Detection of residual bcr/abl translocation by polymerase chain reaction in chronic myeloid leukaemia patients after bone-marrow transplantation.

    Science.gov (United States)

    Gabert, J; Thuret, I; Lafage, M; Carcassonne, Y; Maraninchi, D; Mannoni, P

    1989-11-11

    The polymerase chain reaction was used to evaluate minimum residual disease in chronic myelogenous leukaemia (CML) patients after bone-marrow transplantation, by amplification of the transcript of the specific bcr/abl hybrid gene. Strict precautions were taken to avoid contamination. Peripheral blood cells from 22 patients transplanted for haematological malignant disorders were analysed. The results were clearcut for positive controls (patients with CML in relapse) and negative controls (patients with malignant disorders other than CML). In 11 of 12 CML patients in clinical and cytogenetic remission the bcr/abl transcript was detected 3 months to 6 years after transplantation. Thus, it appears that cells expressing the bcr/abl mRNA are not eradicated from the blood of CML patients in complete clinical remission even years after bone-marrow transplantation.

  19. Quality of health in survivors of childhood acute myeloid leukemia treated with chemotherapy only: A NOPHO-AML study

    DEFF Research Database (Denmark)

    Molgaard-Hansen, Lene; Glosli, Heidi; Jahnukainen, Kirsi;

    2011-01-01

    More than 60% of children with acute myeloid leukemia (AML) become long-term survivors, and approximately 50% are cured with chemotherapy only. Limited data exist about their long-term morbidity and social outcomes. The aim of the study was to compare the self-reported use of health care services...

  20. Azathioprine-associated acute myeloid leukemia in a patient with Crohn's disease and thiopurine S-methyltransferase deficiency

    DEFF Research Database (Denmark)

    Yenson, P.R.; Forrest, D.; Schmiegelow, K.;

    2008-01-01

    risk of hematologic toxicity and leukemogenesis. We present such a patient who was a slow metabolizer for azathioprine, and developed a rapidly lethal form acute myeloid leukemia after relatively low dose exposure to the drug. There was prominent hemophagocytic activity in the bone marrow...

  1. Quality of health in survivors of childhood acute myeloid leukemia treated with chemotherapy only: A NOPHO-AML study

    DEFF Research Database (Denmark)

    Molgaard-Hansen, Lene; Glosli, Heidi; Jahnukainen, Kirsi;

    2010-01-01

    BACKGROUND: More than 60% of children with acute myeloid leukemia (AML) become long-term survivors, and approximately 50% are cured with chemotherapy only. Limited data exist about their long-term morbidity and social outcomes. The aim of the study was to compare the self-reported use of health...

  2. miR-125b promotes proliferation of human acute myeloid leukemia cells by targeting Bak1

    Institute of Scientific and Technical Information of China (English)

    曾巧慧

    2014-01-01

    Objective To investigate miR-125b regulation mechanism by identifying miR-125b target genes and itsfunction in acute myeloid leukemia(AML).Methods The bioinformatics software and database were applied to predict and analyze target genes of miR-125b.The vector contained the target gene 3’-UTR portion cloned into a luciferase reporter

  3. Acute myeloid leukemia with t( 11; 22 )( q23; q11.2) : two cases report and literature review

    Institute of Scientific and Technical Information of China (English)

    王彤

    2014-01-01

    Objective To report two de novo acute myeloid leukemia(AML)patients with t(11;22)(q23;q11.2)and summarize the clinical and biological characteristics.Methods Bone marrow cells morphology,immunophenotype,chromosome karyotype,fluorescence in situ hybridization(FISH),PCR and gene sequencing were performed.Clinical manifestation and routine laboratory tests

  4. Dysregulation of survival and apoptosis pathways in acute myeloid leukemia : Targeting of NF-κB in AML

    NARCIS (Netherlands)

    Bosman, Matthieu Cornelis Johannes

    2015-01-01

    Acute myeloide leukemie is een vorm van kanker van een bepaalde type witte bloedcel. Hierdoor functioneren wiite bloedcellen niet goed, terwijl de productie van rode bloedcellen en bloedplaatjes onderdrukt kan zijn. De oorzaak ligt bij het ontstaan van leukemische stamcellen uit normale bloedstamcel

  5. Monosomy 7 and deletion 7q in children and adolescents with acute myeloid leukemia: an international retrospective study

    DEFF Research Database (Denmark)

    Hasle, Henrik; Alonzo, Todd A; Auvrignon, A

    2007-01-01

    Monosomy 7 (-7) and deletion 7q \\del(7q)] are rare in childhood acute myeloid leukemia (AML). We retrospectively collected data on 258 children with AML or refractory anemia with excess blasts in transformation (RAEB-T) and -7 or del(7q) with or without other cytogenetic aberrations \\+/- other...

  6. Genome-wide epigenetic analysis delineates a biologically distinct immature acute leukemia with myeloid/T-lymphoid features

    NARCIS (Netherlands)

    M.E. Figueroa (Maria Eugenia); B.J. Wouters (Bas); L. Skrabanek (Lucy); J. Glass (Jacob); Y. Li (Yushan); C.A.J. Erpelinck (Claudia); A.W. Langerak (Anton); B. Löwenberg (Bob); M. Fazzari (Melissa); J.M. Greally (John); P.J.M. Valk (Peter); A. Melnick (Ari); H.R. Delwel (Ruud)

    2009-01-01

    textabstractAcute myeloid leukemia is a heterogeneous disease from the molecular and biologic standpoints, and even patients with a specific gene expression profile may present clinical and molecular heterogeneity. We studied the epigenetic profiles of a cohort of patients who shared a common gene e

  7. Alloreactive natural killer cells for the treatment of acute myeloid leukemia: from stem cell transplantation to adoptive immunotherapy

    Directory of Open Access Journals (Sweden)

    Loredana eRuggeri

    2015-10-01

    Full Text Available Natural killer cells express activating and inhibitory receptors which recognize MHC class I alleles, termed Killer cell Immunoglobulin-like Receptors (KIRs. Preclinical and clinical data from haploidentical T-cell depleted stem cell transplantation have demonstrated that alloreactive KIR-L mismatched natural killer cells play a major role as effectors against acute myeloid leukemia. Outside the transplantation setting, several reports have proven the safety and feasibility of natural killer cell infusion in acute myeloid leukemia patients and, in some cases, provided evidence that transferred NK cells are functionally alloreactive and may have a role in disease control. Aim of the present work is to briefly summarize the most recent advances in the field by moving from the first preclinical and clinical demonstration of donor NK alloreactivity in the transplantation setting to the most recent attempts of exploiting the use of alloreactive NK cell infusion as a means of adoptive immunotherapy against acute myeloid leukemia. Altogether, these data highlight the pivotal role of NK cells for the development of novel immunological approaches in the clinical management of acute myeloid leukemia.

  8. Two novel methods for rapid detection and quantification of DNMT3A R882 mutations in acute myeloid leukemia.

    Science.gov (United States)

    Mancini, Melissa; Hasan, Syed Khizer; Ottone, Tiziana; Lavorgna, Serena; Ciardi, Claudia; Angelini, Daniela F; Agostini, Francesca; Venditti, Adriano; Lo-Coco, Francesco

    2015-03-01

    DNMT3A mutations represent one of the most frequent gene alterations detectable in acute myeloid leukemia with normal karyotype. Although various recurrent somatic mutations of DNMT3A have been described, the most common mutation is located at amino acid R882 in the methyltransferase domain of the gene. DNMT3A mutations have been reported to be stable during disease progression and are associated with unfavorable outcome in acute myeloid leukemia patients with normal karyotype. Because of their prognostic significance and high stability during disease evolution, DNMT3A mutations might represent highly informative biomarkers for minimal residual disease monitoring. We describe a new rapid diagnostic RT-PCR assay based on TauI restriction enzyme reaction to identify DNMT3A R882 mutations at diagnosis. In addition, we developed a sensitive and specific test based on peptide nucleic acid real-time PCR technology to monitor DNMT3A R882H mutation. We identified 24 DNMT3A R882H mutated patients out of 134 acute myeloid leukemia screened samples and we analyzed in these patients the kinetics of minimal residual disease after induction and consolidation therapy. This assay may be useful to better assess response to therapy in patients with acute myeloid leukemia bearing the DNMT3A R882H mutation.

  9. G-CSF receptor (CSF3R) mutations in X-linked neutropenia evolving to acute myeloid leukemia or myelodysplasia

    OpenAIRE

    2009-01-01

    This paper shows for the first time that patients with X-linked neutropenia, caused by mutations in the Wiskott Aldrich syndrome gene, developed myelodysplasia/acute myeloid leukemia with acquisition of mutations in the CSF3R gene and loss of chromosome 7. See related perspective article on page 1333.

  10. Favorable prognostic impact of NPM1 gene mutations in childhood acute myeloid leukemia, with emphasis on cytogenetically normal AML.

    NARCIS (Netherlands)

    Hollink, I.H.; Zwaan, C.M.; Zimmermann, M.; Arentsen-Peters, T.C.; Pieters, R.; Cloos, J.; Kaspers, G.J.L.; Graaf, S.S.N. de; Harbott, J.; Creutzig, U.; Reinhardt, D.; Heuvel-Eibrink, M.M. van den; Thiede, C.

    2009-01-01

    Nucleophosmin (NPM1) mutations occur frequently in adult cytogenetically normal acute myeloid leukemia (CN-AML) and confer favorable outcome. We investigated the frequency and prognostic significance of NPM1 mutations in childhood AML (n=298), specifically focusing on the CN-AML subgroup (n=100). Mu

  11. Characterization of gene mutations and copy number changes in acute myeloid leukemia using a rapid target enrichment protocol.

    Science.gov (United States)

    Bolli, Niccolò; Manes, Nicla; McKerrell, Thomas; Chi, Jianxiang; Park, Naomi; Gundem, Gunes; Quail, Michael A; Sathiaseelan, Vijitha; Herman, Bram; Crawley, Charles; Craig, Jenny I O; Conte, Natalie; Grove, Carolyn; Papaemmanuil, Elli; Campbell, Peter J; Varela, Ignacio; Costeas, Paul; Vassiliou, George S

    2015-02-01

    Prognostic stratification is critical for making therapeutic decisions and maximizing survival of patients with acute myeloid leukemia. Advances in the genomics of acute myeloid leukemia have identified several recurrent gene mutations whose prognostic impact is being deciphered. We used HaloPlex target enrichment and Illumina-based next generation sequencing to study 24 recurrently mutated genes in 42 samples of acute myeloid leukemia with a normal karyotype. Read depth varied between and within genes for the same sample, but was predictable and highly consistent across samples. Consequently, we were able to detect copy number changes, such as an interstitial deletion of BCOR, three MLL partial tandem duplications, and a novel KRAS amplification. With regards to coding mutations, we identified likely oncogenic variants in 41 of 42 samples. NPM1 mutations were the most frequent, followed by FLT3, DNMT3A and TET2. NPM1 and FLT3 indels were reported with good efficiency. We also showed that DNMT3A mutations can persist post-chemotherapy and in 2 cases studied at diagnosis and relapse, we were able to delineate the dynamics of tumor evolution and give insights into order of acquisition of variants. HaloPlex is a quick and reliable target enrichment method that can aid diagnosis and prognostic stratification of acute myeloid leukemia patients.

  12. Diagnosis and management of acute myeloid leukemia in children and adolescents : recommendations from an international expert panel

    NARCIS (Netherlands)

    Creutzig, Ursula; van den Heuvel-Eibrink, Marry M.; Gibson, Brenda; Dworzak, Michael N.; Adachi, Souichi; de Bont, Eveline; Harbott, Jochen; Hasle, Henrik; Johnston, Donna; Kinoshita, Akitoshi; Lehrnbecher, Thomas; Leverger, Guy; Mejstrikova, Ester; Meshinchi, Soheil; Pession, Andrea; Raimondi, Susana C.; Sung, Lillian; Stary, Jan; Zwaan, Christian M.; Kaspers, Gertjan J. L.; Reinhardt, Dirk

    2012-01-01

    Despite major improvements in outcome over the past decades, acute myeloid leukemia (AML)remains a life-threatening malignancy in children, with current survival rates of similar to 70%. State-of-the-art recommendations in adult AML have recently been published in this journal by Dohner et al. The p

  13. Risk factors for therapy-related myelodysplastic syndrome and acute myeloid leukemia treated with allogeneic stem cell transplantation.

    NARCIS (Netherlands)

    Kroger, N.; Brand, R.; Biezen, A. van; Zander, A.; Dierlamm, J.; Niederwieser, D.; Devergie, A.; Ruutu, T.; Cornish, J.; Ljungman, P.; Gratwohl, A.; Cordonnier, C.; Beelen, D.; Deconinck, E.; Symeonidis, A.; Witte, T.J.M. de

    2009-01-01

    BACKGROUND: After successful treatment of malignant diseases, therapy-related myelodysplastic syndrome and acute myeloid leukemia have emerged as significant problems. DESIGN AND METHODS: The aim of this study was to investigate outcome and risk factors in patients with therapy-related myelodysplast

  14. Effect of priming with granulocyte colony-stimulating factor on the outcome of chemotherapy for acute myeloid leukemia

    NARCIS (Netherlands)

    Lowenberg, B; van Putten, W; Theobald, M; Gmur, J; Verdonck, L; Sonneveld, P; Fey, M; de Greef, G; Ferrant, A; Kovacsovics, T; Gratwohl, A; Daenen, S; Huijgens, P; Boogaerts, M

    2003-01-01

    BACKGROUND Sensitization of leukemic cells with hematopoietic growth factors may enhance the cytotoxicity of chemotherapy in acute myeloid leukemia (AML). METHODS In a multicenter randomized trial, we assigned patients (age range, 18 to 60 years) with newly diagnosed AML to receive cytarabine plus i

  15. Class II-associated invariant chain peptide as predictive immune marker in minimal residual disease in acute myeloid leukemia

    NARCIS (Netherlands)

    M.M. van Luijn (Marvin M.); W. van den Ancker (Willemijn); S.M. van Ham (Marieke); A.A. van de Loosdrecht (Arjan)

    2014-01-01

    textabstractThe majority of patients with acute myeloid leukemia (AML) reach complete remission after high-dose chemotherapy. Still, half of these patients experience a relapse due to presence of minimal residual disease (MRD). Here we discuss the poor prognostic role of class II-associated invarian

  16. Class II-associated invariant chain peptide as predictive immune marker in minimal residual disease in acute myeloid leukemia

    OpenAIRE

    van Luijn, Marvin M.; van den Ancker, Willemijn; van Ham, S Marieke; Arjan A. van de Loosdrecht

    2014-01-01

    The majority of patients with acute myeloid leukemia (AML) reach complete remission after high-dose chemotherapy. Still, half of these patients experience a relapse due to presence of minimal residual disease (MRD). Here we discuss the poor prognostic role of class II-associated invariant chain peptide (CLIP) expression on residual leukemic cells.

  17. Bloodstream infection caused by Acinetobacter junii in a patient with acute lymphoblastic leukaemia after allogenic haematopoietic cell transplantation.

    Science.gov (United States)

    Cayô, Rodrigo; Yañez San Segundo, Lucrecia; Pérez del Molino Bernal, Inmaculada Concepción; García de la Fuente, Celia; Bermúdez Rodríguez, Maria Aranzazu; Calvo, Jorge; Martínez-Martínez, Luis

    2011-03-01

    Acinetobacter junii is a rare human pathogen associated with bacteraemia in neonates and paediatric oncology patients. We present a case of A. junii causing bacteraemia in an adult transplant patient with leukaemia. The correct identification of Acinetobacter species can highlight the clinical significance of the different species of this genus.

  18. Leukemia Associated Antigens: Their Dual Role as Biomarkers and Immunotherapeutic Targets for Acute Myeloid Leukemia

    Directory of Open Access Journals (Sweden)

    Michael Schmitt

    2007-01-01

    Full Text Available Leukemia associated antigens (LAAs are being increasingly identified by methods such as cytotoxic T-lymphocyte (CTL cloning, serological analysis of recombinant cDNA expression libraries (SEREX and mass spectrometry (MS. In additional, large scale screening techniques such as microarray, single nucleotide polymorphisms (SNPs, serial analysis of gene expression (SAGE and 2-dimensional gel electrophoresis (2-DE have expanded our understanding of the role that tumor antigens play in the biological processes which are perturbed in acute myeloid leukemia (AML. It has become increasingly apparent that these antigens play a dual role, not only as targets for immunotherapy, but also as biomarkers of disease state, stage, response to treatment and survival. We need biomarkers to enable the identification of the patients who are most likely to benefit from specific treatments (conventional and/or novel and to help clinicians and scientists improve clinical end points and treatment design. Here we describe the LAAs identified in AML, to date, which have already been shown to play a dual role as biomarkers of AML disease.Abbreviations: AML: acute myeloid leukemia; APL: acute promyelocytic leukemia; ATRA: all-trans-retinoic acid; B-CLL: B-cell chronic lymphocytic leukemia; CT: cancer-testis; CTL: cytotoxic T-lymphocyte; FAB: French-American-British; HI: hypusination inhibitors; HSP: heat shock protein; ITD: internal tandem duplication; LAA: leukemia associated antigen; MDS: myelodysplastic syndrome; MGEA6: meningioma antigen 6; MPD: myeloproliferative disease; MS: mass spectrometry; NK: natural killer; PRAME: preferentially expressed antigen of melanoma; PRTN3: proteinase 3; RAGE-1: renal antigen 1; RHAMM: receptor for hyaluronic acid-mediated motility; RQ-PCR: real-time PCR; SAGE: serial analysis of gene expression; SCT: stem cell transplant; SEREX: serological analysis of recombinant cDNA expression libraries; SNPs: single nucleotide polymorphisms; UPD

  19. Characteristics and Prognosis of Adult Acute Myeloid Leukemia with Internal Tandem Duplication in the FLT3 Gene

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    Adhra Al-Mawali

    2013-11-01

    Full Text Available Objectives: Constitutive activation of the fms-like tyrosine kinase 3 (FLT3 receptor by internal tandem duplication (ITD of the juxtamembrane region has been described in patients with acute myeloid leukemia. FLT3/ITDs are present in about 20-30% of all acute myeloid leukemia cases. It has been shown that the mutation is correlated with worse prognosis. However, none of the previous studies investigated which FAB subtype is associated with higher percentage of FLT3/ITD, thus the reason for undertaking the current study.Methods: The prevalence and the potential prognostic impact of FLT3 mutations in 39 acute myeloid leukemia patients were analyzed by genomic polymerase chain reaction. Twelve samples with FLT3/ITDs and 27 acute myeloid leukemia samples without the mutations were compared with respect to clinical prognosis and FAB subtype. Results were correlated with cytogenetic data and the clinical response.Results: FLT3/ITD mutations were found in 31% of patients. FLT3/ITD was associated with similar clinical characteristics and was more prevalent in patients with normal karyotype (83%. Interestingly, half of the FLT3/ITD aberrations were found in patients with FAB M1 (50%, and fewer were found in patients with FAB M2 (8%, M4 (8%, and M5 (8%. Although less frequent in patients with cytogenetic aberrations, FLT3/ITDs were found in 17% of patients with t(15;17. Although the study was powered to 80%, patients with FLT3/ITD mutation did not show shorter complete remission duration or a higher relapse rate.Conclusion: The data confirm that FLT3/ITD mutations represent a common alteration in adult acute myeloid leukemia, mainly with normal karyotype (83% and de novo acute myeloid leukemia (75%, as compared to secondary acute myeloid leukemia (25% (p<0.001. It also showed that half of the M1-FAB subtype is FLT3/ITD positive. Therefore, FLT3/ITD is a therapeutic target, and thus inhibition of FLT3 tyrosine kinase activity may provide a new approach in

  20. Thymoquinone Induces Mitochondria-Mediated Apoptosis in Acute Lymphoblastic Leukaemia in Vitro

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    Bassem Y. Sheikh

    2013-09-01

    Full Text Available There has been a growing interest in naturally occurring compounds from traditional medicine with anti-cancer potential. Nigella sativa (black seed is one of the most widely studied plants. This annual herb grows in countries bordering the Mediterranean Sea and India. Thymoquinone (TQ is an active ingredient isolated from Nigella sativa. The anti-cancer effect of TQ, via the induction of apoptosis resulting from mitochondrial dysfunction, was assessed in an acute lymphocyte leukemic cell line (CEMss with an IC50 of 1.5 µg/mL. A significant increase in chromatin condensation in the cell nucleus was observed using fluorescence analysis. The apoptosis was then confirmed by Annexin V and an increased number of cellular DNA breaks in treated cells were observed as a DNA ladder. Treatment of CEMss cells with TQ encouraged apoptosis with cell death-transducing signals by a down-regulation of Bcl-2 and up-regulation of Bax. Moreover, the significant generation of cellular ROS, HSP70 and activation of caspases 3 and 8 were also observed in the treated cells. The mitochondrial apoptosis was clearly associated with the S phase cell cycle arrest. In conclusion, the results from the current study indicated that TQ could be a promising agent for the treatment of leukemia.

  1. Impact of graft-versus-host disease after reduced-intensity conditioning allogeneic stem cell transplantation for acute myeloid leukemia

    DEFF Research Database (Denmark)

    Baron, F; Labopin, M; Niederwieser, D;

    2012-01-01

    This report investigated the impact of graft-versus-host disease (GVHD) on transplantation outcomes in 1859 acute myeloid leukemia patients given allogeneic peripheral blood stem cells after reduced-intensity conditioning (RIC allo-SCT). Grade I acute GVHD was associated with a lower risk of rela...... of relapse (hazards ratio (HR)=0.7, P=0.02) translating into a trend for better overall survival (OS; HR=1.3; P=0.07). Grade II acute GVHD had no net impact on OS, while grade III-IV acute GVHD was associated with a worse OS (HR=0.4, P...

  2. All-trans retinoic acid with daunorubicin or idarubicin for risk-adapted treatment of acute promyelocytic leukaemia : a matched-pair analysis of the PETHEMA LPA-2005 and IC-APL studies

    NARCIS (Netherlands)

    Sanz, Miguel A.; Montesinos, Pau; Kim, Haesook T.; Ruiz-Argueelles, Guillermo J.; Undurraga, Maria S.; Uriarte, Maria R.; Martinez, Lem; Jacomo, Rafael H.; Gutierrez-Aguirre, Homero; Melo, Raul A. M.; Bittencourt, Rosane; Pasquini, Ricardo; Pagnano, Katia; Fagundes, Evandro M.; Vellenga, Edo; Holowiecka, Alexandra; Gonzalez-Huerta, Ana J.; Fernandez, Pascual; De la Serna, Javier; Brunet, Salut; De Lisa, Elena; Gonzalez-Campos, Jose; Ribera, Jose M.; Krsnik, Isabel; Ganser, Arnold; Berliner, Nancy; Ribeiro, Raul C.; Lo-Coco, Francesco; Lowenberg, Bob; Rego, Eduardo M.

    2015-01-01

    Front-line treatment of acute promyelocytic leukaemia (APL) consists of all-trans retinoic acid (ATRA) and anthracycline-based chemotherapy. In this setting, a comparison of idarubicin and daunorubicin has never been carried out. Two similar clinical trials using ATRA and chemotherapy for newly diag

  3. Prognostic value of immunophenotyping and gene mutations in elderly patients with acute myeloid leukemia with normal karyotype.

    Science.gov (United States)

    Dang, Harry; Jiang, Allan; Kamel-Reid, Suzanne; Brandwein, Joseph; Chang, Hong

    2013-01-01

    Elderly patients with acute myeloid leukemia generally have a poor prognosis and a highly heterogeneous clinical outcome. Prognostic indicators are required for and aid in patient stratification. However, the prognostic value of genetic mutations and immunophenotypic features in elderly normal karyotype acute myeloid leukemia, the largest cytogenetic risk group, remains unclear. We investigated the genetic mutations NPM1, FLT3-ITD, and FLT3-TKD and expression of the membrane antigens CD7, CD15, CD34, and CD56 in 144 elderly patients with de novo normal karyotype acute myeloid leukemia to retrospectively analyze the prognostic and clinical relevance of these parameters. CD7, CD15, CD34, and CD56 were expressed in 24%, 47%, 52%, and 15% of patients, respectively. NPM1 and FLT3-ITD mutations were detected in 51% and 17% of patients, respectively. Complete remission was obtained in 94 patients (65%), and the median overall survival was 16.5 months. Univariate analysis detected 5 markers with prognostic relevance: high leukocyte count, FLT3-ITD mutations, NPM1 mutations, CD34 expression, and CD56 expression in acute myeloid leukemia blasts. In multivariate analysis, patients with NPM1 predicted a higher complete remission (CR) rate (P = .016), longer event-free survival (P = .008), and longer overall survival (P = .049). FLT3-ITD mutations predicted a shorter event-free survival (P = .002) and shorter overall survival (P acute myeloid leukemia. By combining genetic and immunophenotypic markers, we can divide patients into distinct prognostic groups with important implications for prognostic stratification and risk-adapted therapy.

  4. Ciprofloxacin versus colistin prophylaxis during neutropenia in acute myeloid leukemia: two parallel patient cohorts treated in a single center

    Science.gov (United States)

    Pohlen, Michele; Marx, Julia; Mellmann, Alexander; Becker, Karsten; Mesters, Rolf M.; Mikesch, Jan-Henrik; Schliemann, Christoph; Lenz, Georg; Müller-Tidow, Carsten; Büchner, Thomas; Krug, Utz; Stelljes, Matthias; Karch, Helge; Peters, Georg; Gerth, Hans U.; Görlich, Dennis; Berdel, Wolfgang E.

    2016-01-01

    Patients undergoing intensive chemotherapy for acute myeloid leukemia are at high risk for bacterial infections during therapy-related neutropenia. However, the use of specific antibiotic regimens for prophylaxis in afebrile neutropenic acute myeloid leukemia patients is controversial. We report a retrospective evaluation of 172 acute myeloid leukemia patients who received 322 courses of myelosuppressive chemotherapy and had an expected duration of neutropenia of more than seven days. The patients were allocated to antibiotic prophylaxis groups and treated with colistin or ciprofloxacin through 2 different hematologic services at our hospital, as available. The infection rate was reduced from 88.6% to 74.2% through antibiotic prophylaxis (vs. without prophylaxis; P=0.04). A comparison of both antibiotic drugs revealed a trend towards fewer infections associated with ciprofloxacin prophylaxis (69.2% vs. 79.5% in the colistin group; P=0.07), as determined by univariate analysis. This result was confirmed through multivariate analysis (OR: 0.475, 95%CI: 0.236–0.958; P=0.041). The prophylactic agents did not differ with regard to the microbiological findings (P=0.6, not significant). Of note, the use of ciprofloxacin was significantly associated with an increased rate of infections with pathogens that are resistant to the antibiotic used for prophylaxis (79.5% vs. 9.5% in the colistin group; P<0.0001). The risk factors for higher infection rates were the presence of a central venous catheter (P<0.0001), mucositis grade III/IV (P=0.0039), and induction/relapse courses (vs. consolidation; P<0.0001). In conclusion, ciprofloxacin prophylaxis appears to be of particular benefit during induction and relapse chemotherapy for acute myeloid leukemia. To prevent and control drug resistance, it may be safely replaced by colistin during consolidation cycles of acute myeloid leukemia therapy. PMID:27470601

  5. The MDM-2 Antagonist Nutlin-3 Promotes the Maturation of Acute Myeloid Leukemic Blasts

    Directory of Open Access Journals (Sweden)

    Paola Secchiero

    2007-10-01

    Full Text Available The small-molecule inhibitor of murine double minute (MDM-2, Nutlin-3, induced variable apoptosis in primary acute myeloid leukemia (AML blasts, promoted myeloid maturation of surviving cells, as demonstrated by analysis of CD11 b, CD14 surface antigens, by morphologic examination. Although the best-characterized activity of Nutlin-3 is activation of the p53 pathway, Nutlin-3 induced maturation also in one AML sample characterized by p53 deletion, as well as in the p53-/- human myeloblastic HL-60 cell line. At the molecular level, the maturational activity of Nutlin-3 in HL-60 cells was accompanied by the induction of E2F1 transcription factor, it was significantly counteracted by specific gene knockdown with small interfering RNA for E2F1. Moreover, Nutlin-3, as well as tumor necrosis factor (TNF α, potentiated the maturational activity of recombinant TNF-related apoptosis-inducing lig, (TRAIL in HL-60 cells. However, although TNF-α significantly counteracted the proapoptotic activity of TRAIL, Nutlin-3 did not interfere with the proapoptotic activity of TRAIL. Taken together, these data disclose a novel, potentially relevant therapeutic role for Nutlin-3 in the treatment of both p53 wild-type, p53-/- AML, possibly in association with recombinant TRAIL.

  6. Matrine induces apoptosis in human acute myeloid leukemia cells via the mitochondrial pathway and Akt inactivation.

    Directory of Open Access Journals (Sweden)

    Shenghui Zhang

    Full Text Available Acute myeloid leukemia (AML is a hematological malignancy characterized by a rapid increase in the number of immature myeloid cells in bone marrow. Despite recent advances in the treatment, AML remains an incurable disease. Matrine, a major component extracted from Sophora flavescens Ait, has been demonstrated to exert anticancer effects on various cancer cell lines. However, the effects of matrine on AML remain largely unknown. Here we investigated its anticancer effects and underlying mechanisms on human AML cells in vitro and in vivo. The results showed that matrine inhibited cell viability and induced cell apoptosis in AML cell lines as well as primary AML cells from patients with AML in a dose- and time-dependent manner. Matrine induced apoptosis by collapsing the mitochondrial membrane potential, inducing cytochrome c release from mitochondria, reducing the ratio of Bcl-2/Bax, increasing activation of caspase-3, and decreasing the levels of p-Akt and p-ERK1/2. The apoptotic effects of matrine on AML cells were partially blocked by a caspase-3 inhibitor Z-DEVD-FMK and a PI3K/Akt activator IGF-1, respectively. Matrine potently inhibited in vivo tumor growth following subcutaneous inoculation of HL-60 cells in SCID mice. These findings indicate that matrine can inhibit cell proliferation and induce apoptosis of AML cells and may be a novel effective candidate as chemotherapeutic agent against AML.

  7. In vitro evaluation of triazenes: DNA cleavage, antibacterial activity and cytotoxicity against acute myeloid leukemia cells

    Energy Technology Data Exchange (ETDEWEB)

    Domingues, Vanessa O.; Hoerner, Rosmari; Reetz, Luiz G.B.; Kuhn, Fabio, E-mail: rosmari.ufsm@gmail.co [Universidade Federal de Santa Maria (UFSM), RS (Brazil). Dept. de Analises Clinicas e Toxicologicas; Coser, Virginia M.; Rodrigues, Jacqueline N.; Bauchspiess, Rita; Pereira, Waldir V. [Hospital Universitario de Santa Maria, RS (Brazil). Dept. de Hematologia-Oncologia; Paraginski, Gustavo L.; Locatelli, Aline; Fank, Juliana de O.; Giglio, Vinicius F.; Hoerner, Manfredo, E-mail: hoerner.manfredo@gmail.co [Universidade Federal de Santa Maria (UFSM), RS (Brazil). Dept. de Quimica

    2010-07-01

    The asymmetric diazoamines 1-(2-chlorophenyl)-3-(4-carboxyphenyl)triazene (1), 1-(2-fluorophenyl)-3-(4-carboxyphenyl)triazene (2) and 1-(2-fluorophenyl)-3-(4-amidophenyl) triazene (3) were evaluated for their ability to cleave pUC18 and pBSKII plasmid DNA, antibacterial activity and in vitro cytotoxicity against acute myeloid leukemia cells and normal leukocytes using the bioassay of reduction of 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyltetrazolium bromide (MTT). The triazenes showed ability to cleave the two types of plasmid DNA: triazene 1 at pH 8.0 and 50 deg C; triazene 2 at pH 6.5 and 37 and 50 deg C; triazene 3 at pH 6.5 and 37 deg C. The compounds presented cytotoxic activity against myeloid leukemia cells. Compound 1 showed high activity against B. cereus (MIC = 32 {mu}g mL{sup -1}). The observation of intermolecular hydrogen bonding in the solid state of compound 3, based on the structural analysis by X-ray crystallography, as well as the results of IR and UV-Vis spectroscopic analyses of compounds 1, 2 and 3 are discussed in the present work. (author)

  8. Lack of noncanonical RAS mutations in cytogenetically normal acute myeloid leukemia.

    Science.gov (United States)

    Reuter, Christoph W M; Krauter, Jürgen; Onono, Fredrick O; Bunke, Tania; Damm, Frederik; Thol, Felicitas; Wagner, Katharina; Göhring, Gudrun; Schlegelberger, Brigitte; Heuser, Michael; Ganser, Arnold; Morgan, Michael A

    2014-06-01

    Transforming mutations in RAS genes are commonly found in human malignancies, including myeloid leukemias. To investigate the incidence, spectrum, and distribution of activating K- and N-RAS mutations in cytogenetically normal acute myeloid leukemia (CN-AML) patients, 204 CN-AML patients were screened. Activating K- and N-RAS mutations were detected in 3 of 204 (1.5 %) and 22 of 204 (10.8 %) CN-AML samples, respectively. RAS mutated patients presented with a lower percentage of bone marrow blasts (65 vs 80 %, P = 0.022). RAS mutations tended to occur with nucleophosmin-1 (NPM1) mutations (P = 0.079), and all three samples containing K-RAS mutations had concomitant NPM1 mutations. There was no significant overlap between K-RAS mutations and N-RAS, FLT3, CEBPA, IDH1/2, WT1 or MLL mutations. RAS mutation status did not impact relapse-free or overall survival of CN-AML patients. In contrast to reports of noncanonical RAS mutations in other cancers, including some leukemia subtypes, we only observed K- and N-RAS mutations in codons 12, 13, or 61 in CN-AML samples. Our findings suggest that while K-RAS mutations are infrequent in CN-AML, activating K-RAS mutations may cooperate with mutated NPM1 to induce leukemia.

  9. Therapeutic reactivation of protein phosphatase 2A in acute myeloid leukemia

    Directory of Open Access Journals (Sweden)

    Kavitha eRamaswamy

    2015-02-01

    Full Text Available Protein phosphatase 2A (PP2A is a serine/threonine phosphatase that is required for normal cell growth and development. PP2A is a potent tumor suppressor, which is inactivated in cancer cells as a result of genetic deletions and mutations. In myeloid leukemias, genes encoding PP2A subunits are generally intact. Instead, PP2A is functionally inhibited by post-translational modifications of its catalytic C subunit, and interactions with negative regulators by its regulatory B and scaffold A subunits. Here, we review the molecular mechanisms of genetic and functional inactivation of PP2A in human cancers, with a particular focus on human acute myeloid leukemias (AML. By analyzing expression of genes encoding PP2A subunits using transcriptome sequencing, we find that PP2A dysregulation in AML is characterized by silencing and overexpression of distinct A scaffold and B regulatory subunits, respectively. We review the mechanisms of functional PP2A activation by drugs such as fingolimod, forskolin, OP449, and perphenazine. This analysis yields two non-mutually exclusive mechanisms for therapeutic PP2A re-activation: i allosteric activation of the phosphatase activity, and ii stabilization of active holo-enzyme assembly and displacement of negative regulatory factors from A and B subunits. Future studies should allow the development of specific and potent pharmacologic activators of PP2A, and definition of susceptible disease subsets based on specific mechanisms of PP2A dysregulation.

  10. U2AF1 mutations in Chinese patients with acute myeloid leukemia and myelodysplastic syndrome.

    Directory of Open Access Journals (Sweden)

    Jun Qian

    Full Text Available Somatic mutations of U2AF1 gene have recently been identified in myelodysplastic syndrome (MDS and acute myeloid leukemia (AML. In this study, we analyzed the frequency and clinical impact of U2AF1 mutations in a cohort of 452 Chinese patients with myeloid neoplasms. Mutations in U2AF1 were found in 2.5% (7/275 of AML and 6.3% (6/96 of MDS patients, but in none of 81 CML. All mutations were heterozygous missense mutations affecting codon S34 or Q157. There was no significant association of U2AF1 mutation with blood parameters, FAB subtypes, karyotypes and other gene mutations in AML. The overall survival (OS of AML patients with U2AF1 mutation (median 3 months was shorter than those without mutation (median 7 months (P = 0.035. No difference in the OS was observed between MDS patients with and without U2AF1 mutations. Our data show that U2AF1 mutation is a recurrent event at a low frequency in AML and MDS.

  11. Concurrent acute myeloid leukemia and T lymphoblastic lymphoma in a patient with rearranged PDGFRB genes

    Directory of Open Access Journals (Sweden)

    Chang Hung

    2012-02-01

    Full Text Available Abstract Concurrent hematologic malignancies are relatively rare. We encountered a case of concurrent acute myeloid leukemia (AML and T lymphoblastic lymphoma. The bone marrow chromosome analysis showed the karyotype 46, XY, t(5;12(q33;p13, which indicated presence of PDGFRB gene translocations. Therefore, this disease belongs to the new WHO category of myeloid and lymphoid neoplasms with abnormalities in PDGFRA, PDGFRB and FGFR1 genes. Although such genetic mutations are prone to multi-lineage differentiation, the present case is in fact the first report of concurrent AML and T lymphoblastic lymphoma involving PDGFRB mutations. The patient was treated with cytarabine and daunomycin in combination with high dose dexamethasone. Allogeneic stem cell transplantation was performed after successful remission induction for both entities. The patient eventually died of chronic graft-versus-host-disease related infection. Based on such an experience, we suggest the decision of stem cell transplantation should be weighed carefully against the risks, especially when tyrosine kinase inhibitors are safe and potentially effective in dealing with such entities.

  12. Minimal PU.1 reduction induces a preleukemic state and promotes development of acute myeloid leukemia.

    Science.gov (United States)

    Will, Britta; Vogler, Thomas O; Narayanagari, Swathi; Bartholdy, Boris; Todorova, Tihomira I; da Silva Ferreira, Mariana; Chen, Jiahao; Yu, Yiting; Mayer, Jillian; Barreyro, Laura; Carvajal, Luis; Neriah, Daniela Ben; Roth, Michael; van Oers, Johanna; Schaetzlein, Sonja; McMahon, Christine; Edelmann, Winfried; Verma, Amit; Steidl, Ulrich

    2015-10-01

    Modest transcriptional changes caused by genetic or epigenetic mechanisms are frequent in human cancer. Although loss or near-complete loss of the hematopoietic transcription factor PU.1 induces acute myeloid leukemia (AML) in mice, a similar degree of PU.1 impairment is exceedingly rare in human AML; yet, moderate PU.1 inhibition is common in AML patients. We assessed functional consequences of modest reductions in PU.1 expression on leukemia development in mice harboring DNA lesions resembling those acquired during human stem cell aging. Heterozygous deletion of an enhancer of PU.1, which resulted in a 35% reduction of PU.1 expression, was sufficient to induce myeloid-biased preleukemic stem cells and their subsequent transformation to AML in a DNA mismatch repair-deficient background. AML progression was mediated by inhibition of expression of a PU.1-cooperating transcription factor, Irf8. Notably, we found marked molecular similarities between the disease in these mice and human myelodysplastic syndrome and AML. This study demonstrates that minimal reduction of a key lineage-specific transcription factor, which commonly occurs in human disease, is sufficient to initiate cancer development, and it provides mechanistic insight into the formation and progression of preleukemic stem cells in AML.

  13. An operational definition of primary refractory acute myeloid leukemia allowing early identification of patients who may benefit from allogeneic stem cell transplantation

    DEFF Research Database (Denmark)

    Ferguson, Paul; Hills, Robert K; Grech, Angela

    2016-01-01

    Up to 30% of adults with acute myeloid leukemia fail to achieve a complete remission after induction chemotherapy - termed primary refractory acute myeloid leukemia. There is no universally agreed definition of primary refractory disease, nor have the optimal treatment modalities been defined. We.......0001) cohorts. The utilization of REF1 criteria permits the early identification of patients whose outcome after one course of induction chemotherapy is very poor, and informs a novel definition of primary refractory acute myeloid leukemia. Furthermore, these data demonstrate that allogeneic stem cell...

  14. Intracranial CNS Manifestations of Myeloid Sarcoma in Patients with Acute Myeloid Leukemia: Review of the Literature and Three Case Reports from the Author’s Institution

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    Gustavo M. Cervantes

    2015-05-01

    Full Text Available Myeloid sarcoma (MS of the central nervous system (CNS is a rare presentation of leukemic mass infiltration outside of the bone marrow. It may involve the subperiosteum and dura mater and, on rare occasions, can also invade the brain parenchyma. The disease is most commonly seen in children or young adults; however, it has been described in multiple age groups. MS can be seen in patients with acute myeloid leukemia (AML, chronic myeloid leukemia and other myeloproliferative disorders. This entity has the potential to be underdiagnosed if the MS appearance precedes the first diagnosis of leukemia. The main reason is that their appearance on CT and MRI has a broad differential diagnosis, and proper diagnosis of MS can only be made if the imaging findings are correlated with the clinical history and laboratory findings. Herein, we describe the intracranial CNS manifestations of MS in patients with AML on CT and MRI involving the brain and/or meninges. This study is based on a systematic review of the literature. In addition, three case reports from the author’s institution with AML and intracranial involvement of MS are included. Our aim is to enhance the awareness of this entity among both clinicians and radiologists.

  15. Hierarchy in gene expression is predictive of risk, progression, and outcome in adult acute myeloid leukemia

    Science.gov (United States)

    Tripathi, Shubham; Deem, Michael W.

    2015-02-01

    Cancer progresses with a change in the structure of the gene network in normal cells. We define a measure of organizational hierarchy in gene networks of affected cells in adult acute myeloid leukemia (AML) patients. With a retrospective cohort analysis based on the gene expression profiles of 116 AML patients, we find that the likelihood of future cancer relapse and the level of clinical risk are directly correlated with the level of organization in the cancer related gene network. We also explore the variation of the level of organization in the gene network with cancer progression. We find that this variation is non-monotonic, which implies the fitness landscape in the evolution of AML cancer cells is non-trivial. We further find that the hierarchy in gene expression at the time of diagnosis may be a useful biomarker in AML prognosis.

  16. An evidence for adhesion-mediated acquisition of acute myeloid leukemic stem cell-like immaturities

    Energy Technology Data Exchange (ETDEWEB)

    Funayama, Keiji; Shimane, Miyuki; Nomura, Hitoshi [Department of Integrative Bioscience and Biomedical Engineering, Waseda University, 4-3-1 Ohkubo, Shinjuku-ku, Tokyo 169-8555 (Japan); Asano, Shigetaka, E-mail: asgtkmd@waseda.jp [Department of Integrative Bioscience and Biomedical Engineering, Waseda University, 4-3-1 Ohkubo, Shinjuku-ku, Tokyo 169-8555 (Japan)

    2010-02-12

    For long-term survival in vitro and in vivo of acute myeloid leukemia cells, their adhesion to bone marrow stromal cells is indispensable. However, it is still unknown if these events are uniquely induced by the leukemic stem cells. Here we show that TF-1 human leukemia cells, once they have formed a cobblestone area by adhering to mouse bone marrow-derived MS-5 cells, can acquire some leukemic stem cell like properties in association with a change in the CD44 isoform-expression pattern and with an increase in a set of related microRNAs. These findings strongly suggest that at least some leukemia cells can acquire leukemic stem cell like properties in an adhesion-mediated stochastic fashion.

  17. Current Approaches in the Treatment of Relapsed and Refractory Acute Myeloid Leukemia

    Directory of Open Access Journals (Sweden)

    Nestor R. Ramos

    2015-04-01

    Full Text Available The limited sensitivity of the historical treatment response criteria for acute myeloid leukemia (AML has resulted in a different paradigm for treatment compared with most other cancers presenting with widely disseminated disease. Initial cytotoxic induction chemotherapy is often able to reduce tumor burden to a level sufficient to meet the current criteria for “complete” remission. Nevertheless, most AML patients ultimately die from their disease, most commonly as clinically evident relapsed AML. Despite a variety of available salvage therapy options, prognosis in patients with relapsed or refractory AML is generally poor. In this review, we outline the commonly utilized salvage cytotoxic therapy interventions and then highlight novel investigational efforts currently in clinical trials using both pathway-targeted agents and immunotherapy based approaches. We conclude that there is no current standard of care for adult relapsed or refractory AML other than offering referral to an appropriate clinical trial.

  18. Single institute study of FLT3 mutation in acute myeloid leukemia with near tetraploidy in Serbia

    Indian Academy of Sciences (India)

    Vladimir Jurišić; Sonja Povlović; Nataša Čolović; Vesna Djordjevic; Vera Bunjevački; Gradimir Janković; Milica Čolović

    2009-08-01

    Patients with de novo acute myeloid leukemia (AML) and near-tetraploid or completely tetraploid karyotype at presentation are rare. We present four patients with near-tetraploidy/tetraploidy in a cohort of 426 consecutive AML patients (0.98%) in respect to their cytogenetic findings, immunophenotype pattern, response to chemotherapy, course of disease and molecular analyses including tyrosine kinase receptor FLT3 gene, NRAS gene, and tumour suppressor gene, p53. We have found FLT3/ITD mutation only in one patient among the four with near-tetraploidy. The main finding is that these patients had a variable clinical course, with two having a long period of remission (36 and 12 months) and two died, not having achieved remission.

  19. Partial remission of acute myeloid leukemia complicating multiple myeloma following COAP chemotherapy: A case report.

    Science.gov (United States)

    Shen, Man; Sun, Wan-Jun; Huang, Zhong-Xia; Zhang, Jia-Jia; An, Na; Li, Xin

    2015-03-01

    A 77-year-old male was admitted to hospital after complaining of fever and a cough for three days. A diagnosis of multiple myeloma was confirmed following M protein identification and a bone marrow biopsy. The patient received chemotherapy regimens of bortezomib plus dexamethasone, cyclophosphamide, thalidomide and dexamethasone, and thalidomide and dexamethasone, and was prescribed thalidomide (100 mg/d) to be taken orally for maintenance therapy. After a further two years the patient was subsequently diagnosed with acute myeloid leukemia. Chemotherapy regimens of cytarabine, aclacinomycin and daunorubicin, homoharringtonine and etoposide, and mitoxantrone and cytarabine resulted in no remission. Partial remission was obtained with a course of ifosfamide, vindesine, cytarabine and prednisone chemotherapy. This therapy may be an alternative treatment for secondary leukemia, particularly in elderly patients.

  20. Recent Advance in Antigen-Specific Immunotherapy for Acute Myeloid Leukemia

    Directory of Open Access Journals (Sweden)

    Norimitsu Kadowaki

    2011-01-01

    Full Text Available Relapse after chemotherapy is inevitable in the majority of patients with acute myeloid leukemia (AML. Thus, it is necessary to develop novel therapies that have different antileukemic mechanisms. Recent advances in immunology and identification of promising leukemia-associated antigens open the possibilities for eradicating minimal residual diseases by antigen-specific immunotherapy after chemotherapy. Several methods have been pursued as immunotherapies for AML: peptide vaccines, granulocyte-macrophage colony-stimulating factor-secreting tumor vaccines, dendritic cell vaccines, and adoptive T cell therapy. Whereas immunogenicity and clinical outcomes are improving in these trials, severe adverse events were observed in highly avid engineered T cell therapies, indicating the importance of the balance between effectiveness and side effects in advanced immunotherapy. Such progress in inducing antitumor immune responses, together with strategies to attenuate immunosuppressive factors, will establish immunotherapy as an important armament to combat AML.