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Sample records for acute leukemia patients

  1. Allogeneic Transplantation for Patients With Acute Leukemia or Chronic Myelogenous Leukemia (CML)

    2016-06-14

    Leukemia, Lymphocytic, Acute; Leukemia; Leukemia Acute Promyelocytic Leukemia (APL); Leukemia Acute Lymphoid Leukemia (ALL); Leukemia Chronic Myelogenous Leukemia (CML); Leukemia Acute Myeloid Leukemia (AML); Leukemia Chronic Lymphocytic Leukemia (CLL)

  2. Acute myeloid leukemia in the older patient.

    Godwin, John E; Smith, Scott E

    2003-10-15

    Acute myeloid leukemia (AML) is an extremely heterogeneous disorder. The biology of AML is incompletely understood, but much data indicates that older patients have a more biologically diverse and chemotherapy resistant form of AML that is quite different from that seen in the younger patients. Approximately 60% of AML cases are in patients greater than 60 years of age, so the predominant burden is in older patients. This problem will be magnified in the future, because the US population is both growing and aging. When one examines the treatment outcomes of older AML patients over the last three decades, there is little progress in long-term survival. Nine major published randomized placebo controlled trials of myeloid growth factors given during induction for AML have been conducted. All of these trials with one exception demonstrated no significant impact on the clinical outcomes of complete response (CR) rate, disease-free, and overall survival. However, the duration of neutropenia was consistently and uniformly reduced by the use of growth factor in all nine of these trials. Because of the favorable impact of the colony-stimulating factors (CSFs) on resource use, antibiotic days, hospital days, etc., it can be more economical and beneficial to use CSFs in AML than to withhold use. The overall dismal outlook for the older AML patient can only be altered by clinical trials with new therapeutic agents. New cellular and molecularly targeted agents are entering clinical trials and bring hope for progress to this area of cancer therapy. PMID:14563517

  3. Diagnosis of large granular lymphocytic leukemia in a patient previously treated for acute myeloblastic leukemia

    Sinem Civriz Bozdag; Sinem Namdaroglu; Omur Kayikci; Gülsah Kaygusuz; Itir Demiriz; Murat Cinarsoy; Emre Tekgunduz; Fevzi Altuntas

    2013-01-01

    Large granular lymphocytic (LGL) leukemia is a lymphoproliferative disease characterized by the clonal expansion of cytotoxic T or natural killer cells. We report on a patient diagnosed with T-cell LGL leukemia two years after the achievement of hematologic remission for acute myeloblastic leukemia.

  4. Risk-Based Classification System of Patients With Newly Diagnosed Acute Lymphoblastic Leukemia

    2016-04-07

    Adult B Acute Lymphoblastic Leukemia; Adult T Acute Lymphoblastic Leukemia; Childhood B Acute Lymphoblastic Leukemia; Childhood T Acute Lymphoblastic Leukemia; Untreated Adult Acute Lymphoblastic Leukemia; Untreated Childhood Acute Lymphoblastic Leukemia

  5. Acute myelogenous leukemia (AML) - children

    Acute myelogenous leukemia - children; AML; Acute myeloid leukemia - children; Acute granulocytic leukemia - children; Acute myeloblastic leukemia - children; Acute non-lymphocytic leukemia (ANLL) - children

  6. Amifostine Treatment of a Patient with Refractory Acute Myeloid Leukemia

    Tekgündüz, Emre; ERİKÇİ, ALEV AKYOL; Ahmet ÖZTÜRK

    2009-01-01

    The prognosis for the majority of acute myeloid leukemia (AML) patients without a donor is dismal whether conventional salvage chemotherapy regimens or investigational strategies are used, and most of these patients will eventually die of their disease. There is no standard chemotherapy regimen that provides durable complete remission in patients with refractory AML. Beneficial effects of amifostine, either alone or in combination with conventional chemotherapy, was demonstrated in patients w...

  7. Monoclonal Antibody Therapy in Treating Patients With Chronic Lymphocytic Leukemia, Lymphocytic Lymphoma, Acute Lymphoblastic Leukemia, or Acute Myeloid Leukemia

    2013-06-03

    Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Nodal Marginal Zone B-cell Lymphoma; Noncontiguous Stage II Marginal Zone Lymphoma; Noncontiguous Stage II Small Lymphocytic Lymphoma; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Marginal Zone Lymphoma; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Splenic Marginal Zone Lymphoma; Stage III Marginal Zone Lymphoma; Stage III Small Lymphocytic Lymphoma; Stage IV Marginal Zone Lymphoma; Stage IV Small Lymphocytic Lymphoma

  8. Studying Biomarkers in Samples From Younger Patients With Acute Myeloid Leukemia

    2016-05-17

    Childhood Acute Monoblastic Leukemia (M5a); Childhood Acute Monocytic Leukemia (M5b); Childhood Acute Myeloblastic Leukemia Without Maturation (M1); Childhood Acute Myeloid Leukemia/Other Myeloid Malignancies; Childhood Acute Myelomonocytic Leukemia (M4)

  9. Mixed phenotype acute leukemia

    Ye Zixing; Wang Shujie

    2014-01-01

    Objective To highlight the current understanding of mixed phenotype acute leukemia (MPAL).Data sources We collected the relevant articles in PubMed (from 1985 to present),using the terms "mixed phenotype acute leukemia","hybrid acute leukemia","biphenotypic acute leukemia",and "mixed lineage leukemia".We also collected the relevant studies in WanFang Data base (from 2000 to present),using the terms "mixed phenotype acute leukemia" and "hybrid acute leukemia".Study selection We included all relevant studies concerning mixed phenotype acute leukemia in English and Chinese version,with no limitation of research design.The duplicated articles are excluded.Results MPAL is a rare subgroup of acute leukemia which expresses the myeloid and lymphoid markers simultaneously.The clinical manifestations of MPAL are similar to other acute leukemias.The World Health Organization classification and the European Group for Immunological classification of Leukaemias 1998 cdteria are most widely used.MPAL does not have a standard therapy regimen.Its treatment depends mostly on the patient's unique immunophenotypic and cytogenetic features,and also the experience of individual physician.The lack of effective treatment contributes to an undesirable prognosis.Conclusion Our understanding about MPAL is still limited.The diagnostic criteria have not been unified.The treatment of MPAL remains to be investigated.The prognostic factor is largely unclear yet.A better diagnostic cdteria and targeted therapeutics will improve the therapy effect and a subsequently better prognosis.

  10. High Throughput Drug Sensitivity Assay and Genomics- Guided Treatment of Patients With Relapsed or Refractory Acute Leukemia

    2016-05-19

    Acute Leukemia of Ambiguous Lineage; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Refractory Adult Acute Lymphoblastic Leukemia; Refractory Childhood Acute Lymphoblastic Leukemia

  11. Comorbidity and performance status in acute myeloid leukemia patients

    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 World Health Organization Performance Status (PS......) on achievement of complete remission and mortality in all Danish AML patients treated between 2000 and 2012 overall and stratified by age. Comorbidity was measured using a modified version of the Charlson Comorbidity Index, with separate adjustment for pre-leukemic conditions. Of 2792 patients, 1467...

  12. Expression of Heparanase Gene in Egyptian Acute Leukemia Patients

    Samir Attia Mohamed Zaahkouk. a, Seham Omar Mohamed Ibrahim b; Amira Ahmed Hammam b ; Hesham Fathy Hedifa

    2014-04-01

    Full Text Available Background: Heparanase is an endoglycosidase that degrades heparin sulfate, the main polysaccharide constituent of the extracellular matrix and basement membrane. Expression of the heparanase gene is associated with the invasive, angiogenic, and metastatic potential of diverse malignant tumors and cell lines. Aim of the study: to investigate possible relation/correlation between Heparanase gene expression and quantitation in pediatric Acute leukemia patients and clinicopathologic variables as well as patients outcome in an attempt to determine it′s prognostic value and the possibility of using it as a new target for treatment. Patients and methods: Forty pediatric acute leukemia patients (20 acute myeloid leukemia (AML&20 acute lymphoblastic leukemia(ALL as well as 11 normal volunteers were analyzed for the expression and level of Heparanase gene using real time quantitative reverse transcriptase polymerase chain reaction (RTQ-PCR to investigate a possible relation, association, or correlation with the clinical and laboratory features of patients at diagnosis, and patient outcome after treatment and follow up. Results: Comparing the 3 groups as regards the Heparanase gene level there was high statistical significant difference (p<0.001 being maximum in AML and minimum in controls, with mean Relative quantitation (RQ level 2336.2± 10405.2 in AML ,median 8.0 and range (3.1-46543.0 , while mean RQ in ALL was 1.7±1.0 ,median 1.7 and range (0.1-3.1 and in controls mean was 0.8±0.3, median 0.8 and range (0.4-1.4.Comparison between each 2 groups as regards heparanase level was of high statistically significant difference, p value being (p<0.001 when comparing AML/ALL and AML/controls and (p=0.035 when comparing ALL/controls. Cut off value for heparanase gene was calculated using Roc curve and was found to be 1.413 with 80% sensitivity and 100% specificity. According to this cut off level, 20/20 (100% AML cases were heparanase positive, 12

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

    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

  14. Prevalence of transient hyperglycemia and diabetes mellitus in pediatric patients with acute leukemia

    Banihashem, A; Ghasemi, A.; N. Ghaemi; Moazzen, N; Amirabadi, A

    2014-01-01

    Background The most common malignancy of children is Leukemia, accounting approximately one third of cancer diagnosis. Available data demonstrate improvement in survival of pediatric leukemia, so evaluation of side effects of treatment is very important. This study investigates hyperglycemia and diabetes mellitus prevalence in pediatric patients with acute leukemia. Materials and Methods This study was performed in children with acute leukemia. At the first admission, demographic data was col...

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

    2016-03-16

    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

  16. Entinostat and Clofarabine in Treating Patients With Newly Diagnosed, Relapsed, or Refractory Poor-Risk Acute Lymphoblastic Leukemia or Bilineage/Biphenotypic Leukemia

    2014-07-16

    Acute Leukemias of Ambiguous Lineage; Philadelphia Chromosome Negative Adult Precursor Acute Lymphoblastic Leukemia; Recurrent Adult Acute Lymphoblastic Leukemia; Untreated Adult Acute Lymphoblastic Leukemia

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

    2013-07-03

    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

  18. Splenic microabscesses in patients with acute myelogenous leukemia

    Eight patients with acute myelogenous leukemia in complete remission after induction chemotherapy got septic fever. Fever was unresponsive to broad-spectrum antibiotic therapy. Ultrasonography showed multiple 0,5-2 cm in diameter, anechoic densities and some 1-3 cm ''target'' appearances in spleen and liver. Computed tomography demonstrated multiple, round, 0,5-2 cm areas of diminished attenuation in spleen and liver, which did not enhance like the surrounding parenchyma. These microabscesses increased in size and number of lesions without equivalent antifungal therapy and decreased or disappeared after specific treatment. Candida-infection was assured by histologic liver specimen in four patients, fungal organisms were seen microscopically in liver-biopsy in one patient and at autopsy one patient was found to have candida disseminated to the spleen, liver, kidneys, lungand CNS. (orig.)

  19. Invasive fungal diseases in patients with acute lymphoid leukemia.

    Nicolato, Andrea; Nouér, Simone A; Garnica, Marcia; Portugal, Rodrigo; Maiolino, Angelo; Nucci, Marcio

    2016-09-01

    Invasive fungal disease (IFD) represents an important complication in patients with acute lymphoid leukemia (ALL). The objectives of this study were to determine the prevalence of IFD in ALL patients with neutropenia, identify factors associated with IFD, and estimate the impact of IFD on the outcome. All patients with ALL who developed febrile neutropenia from 1987 to 2013 were evaluated. Cases of IFD were classified as proven or probable. Factors associated with IFD were evaluated by comparing episodes with and without a diagnosis of IFD. Among 350 episodes of febrile neutropenia, 31 IFDs were diagnosed (8.8%). Prolonged neutropenia was the only factor associated with IFD caused by yeasts. Factors associated with IFD caused by molds by multivariate analysis were the period after 2008, receipt of allogeneic transplant, relapsed ALL and prolonged neutropenia. Patients in relapse should receive induction chemotherapy in rooms with HEPA filter and receive antifungal prophylaxis. PMID:26949001

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

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

    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

  2. Individualized leukemia cell-population profiles in common B-cell acute lymphoblastic leukemia patients

    Jian-Hua Yu; Jing-Tao Dong; Yong-Qian Jia; Neng-Gang Jiang; Ting-Ting Zeng; Hong Xu; Xian-Ming Mo

    2013-01-01

    Immunophenotype is critical for diagnosing common B-cell acute lymphoblastic leukemia (common ALL) and detecting minimal residual disease.We developed a protocol to explore the immunophenotypic profiles of common ALL based on the expression levels of the antigens associated with B lymphoid development,including IL-7Rα (CD127),cytoplasmic CD79a (cCD79a),CD19,VpreB (CD179a),and slgM,which are successive and essential for progression of B cells along their developmental pathway.Analysis of the immunophenotypes of 48 common ALL cases showed that the immunophenotypic patterns were highly heterogeneous,with the leukemic cell population differing from case to case.Through the comprehensive analysis of immunophenotypic patterns,the profiles of patient-specific composite leukemia cell populations could provide detailed information helpful for the diagnosis,therapeutic monitoring,and individualized therapies for common ALL.

  3. Clofarabine and Cytarabine in Treating Patients With Acute Myeloid Leukemia With Minimal Residual Disease

    2013-05-07

    Adult Acute Myeloid Leukemia in Remission; 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

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

    2013-09-13

    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(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

  5. Identification of de Novo Fanconi Anemia in Younger Patients With Newly Diagnosed Acute Myeloid Leukemia

    2016-05-13

    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; Chronic Myelomonocytic Leukemia; de Novo Myelodysplastic Syndromes; Fanconi Anemia; Refractory Anemia; Refractory Anemia With Excess Blasts; Refractory Anemia With Excess Blasts in Transformation; Refractory Anemia With Ringed Sideroblasts; Secondary Myelodysplastic Syndromes; Untreated Childhood Acute Myeloid Leukemia and Other Myeloid Malignancies

  6. FLT3 and NPM-1 mutations in a cohort of acute promyelocytic leukemia patients from India

    Suchitra Swaminathan; Swati Garg; Manisha Madkaikar; Maya Gupta; Farah Jijina; Kanjaksha Ghosh

    2014-01-01

    Background: Acute promyelocytic leukemia (APL) with t (15;17) is a distinct category of acute myeloid leukemia (AML) and is reported to show better response to anthracyclin based chemotherapy. A favorable overall prognosis over other subtypes of AML has been reported for APL patients but still about 15% patients relapse. Methods: This study evaluated the presence of Famus like tyrosine kinase-3 (FLT3) and nucleophosmin-1 (NPM1) gene mutations in a cohort of 40 APL patients. Bone marrow/pe...

  7. Invasive Pulmonary Aspergillosis in a Patient with Acute Lymphoblastic Leukemia

    Orhan Ayyıldız

    2004-01-01

    Full Text Available Fungal infections are common and life-threatening among immunosupressive patients.Invasive pulmonar aspergilloz (IPA generally occurs when Aspergillus inhaled, but rarelywith the hematogen spread of dermal or gastrointestinal Aspergillus. We present here, IPA ina 58 year-old male patient with acute lymphoblastic leukemia (ALL. He was admitted to ourclinic with fatigue, weakness, pansitopenia, and with petechia. Supportive treatment,vincristine and prednisone was initiated. Chest roentgenogram was normal. Dyspnea andfever (39.5’C were seen after 1 month of therapy. Thorax high resolution computerizedtomography was obtained and cavitary lesion was seen in the left upper-anterior segment oflung. Sputum and blood culture were negative. In spite of the empiric use of Meropenem 3gr/d, Vancomycin 2 gr/d and fluconazole 200 mg/d, fever was not turned to normal andclinical symptoms were not healed. On the fifth days of therapy amphotericin-B was initiatedand the other antibiotics were stopped after 3 days. General symptoms were healed on the 8thdays. Radiologic findings were improved partially after 20 days. The patient clinically is welland remains in remission and radiologic findings were turn to near normal after 10 monthsof treatment. We aimed to emphasis about treatment of empirical Amphotericin-B incritically ill patient with ALL.

  8. Lithium Carbonate and Tretinoin in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia

    2015-10-19

    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); Recurrent Adult Acute Myeloid Leukemia

  9. Donor Umbilical Cord Blood Transplant With or Without Ex-vivo Expanded Cord Blood Progenitor Cells in Treating Patients With Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia, Chronic Myelogenous Leukemia, or Myelodysplastic Syndromes

    2016-08-10

    Acute Biphenotypic Leukemia; Acute Lymphoblastic Leukemia in Remission; Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome; Acute Myeloid Leukemia in Remission; Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Mixed Phenotype Acute Leukemia; Myelodysplastic Syndrome; Pancytopenia; Refractory Anemia; Refractory Anemia With Excess Blasts; Refractory Anemia With Excess Blasts in Transformation; Secondary Acute Myeloid Leukemia

  10. Imaging of liver and spleen candidiasis in patients with acute leukemia

    Seino, Yasuo; Tamakawa, Y.; Kato, T.; Kimura, Y.; Miyazaki, S.; Miura, R.; Ishida, H.

    1988-01-01

    Four patients with acute leukemia were found to have candidal abscess of liver and spleen. CT and US showed hepatosplenomegaly and microabscess. These findings might be useful in diagnosis of visceral candidiasis.

  11. Imaging of liver and spleen candidiasis in patients with acute leukemia

    Four patients with acute leukemia were found to have candidal abscess of liver and spleen. CT and US showed hepatosplenomegaly and microabscess. These findings might be useful in diagnosis of visceral candidiasis. (author)

  12. Treatment of Acute Myeloid Leukemia in Adolescent and Young Adult Patients

    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.

  13. Levofloxacin in Preventing Infection in Young Patients With Acute Leukemia Receiving Chemotherapy or Undergoing Stem Cell Transplantation

    2016-04-08

    Acute Leukemias of Ambiguous Lineage; Bacterial Infection; Diarrhea; Fungal Infection; Musculoskeletal Complications; Neutropenia; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia; Untreated Childhood Acute Myeloid Leukemia and Other Myeloid Malignancies

  14. Mixed Phenotype Acute Leukemia with Low Hypodiploidy in a Pediatric Patient

    Salazar, Elizabeth G.; Wertheim, Gerald B.; Biegel, Jaclyn A.; Hwang, William; Tasian, Sarah K.; Rheingold, Susan R.

    2015-01-01

    We describe the case of a 16 year-old female with mixed phenotype acute leukemia B/myeloid, NOS (formerly biphenotypic leukemia) with masked hypodiploidy and somatic TP53 and CDKN2A/B deletions. She achieved morphologic remission with lymphoid-directed multi-agent chemotherapy, but experienced an early medullary relapse 11 months from initial diagnosis. Her case details the unusual finding of hypodiploidy in a patient with ambiguous lineage leukemia and highlights the complexity of therapy se...

  15. Effect of therapy-related acute myeloid leukemia on the outcome of patients with acute myeloid leukemia

    ESPíRITO SANTO, ANA ESPÍRITO; CHACIM, SÉRGIO; FERREIRA, ISABEL; LEITE, LUÍS; MOREIRA, CLAUDIA; PEREIRA, DULCINEIA; DANTAS BRITO, MARGARIDA DANTAS; NUNES, MARTA; DOMINGUES, NELSON; OLIVEIRA, ISABEL; MOREIRA, ILÍDIA; MARTINS, ANGELO; VITERBO, LUÍSA; MARIZ, JOSÉ MÁRIO; MEDEIROS, RUI

    2016-01-01

    Therapy-related acute myeloid leukemia (t-AML) is a rare and almost always fatal late side effect of antineoplastic treatment involving chemotherapy, radiotherapy or the two combined. The present retrospective study intended to characterize t-AML patients that were diagnosed and treated in a single referral to an oncological institution in North Portugal. Over the past 10 years, 231 cases of AML were diagnosed and treated at the Portuguese Institute of Oncology of Porto, of which 38 t-AML cases were identified. Data regarding the patient demographics, primary diagnosis and treatment, age at onset of therapy-related myeloid neoplasm, latency time of the neoplasm, cytogenetic characteristics, AML therapy and outcome were collected from medical records. A previous diagnosis with solid tumors was present in 28 patients, and 10 patients possessed a history of hematological conditions, all a lymphoproliferative disorder. Breast cancer was the most frequent solid tumor identified (39.5% of all solid tumors diagnosed). The mean latency time was 3 years. In the present study, t-AML patients were older (PAML patients. The overall survival time was observed to be significantly poorer among individuals with t-AML (PAML and those with de novo AML (P=0.983). Additionally, patients with promyelocytic leukemia possess a good prognosis, even when AML occurs as a secondary event (P=0.98). To the best of our knowledge, the present study is the first to evaluate t-AML in Portugal and the results are consistent with the data published previously in other populations. The present study concludes that although t-AML demonstrates a poor prognosis, this is not observed among younger patients or promyelocytic leukemia patients.

  16. Acute promyelocytic leukemia in a hemophilia A patient:a case report

    张磊; 李洪强; 赵辉; 王婷婷; 季林祥; 杨仁池; 韩忠朝

    2004-01-01

    @@ Acute promyelocytic leukemia (APL) is the M3 subtype of the French-American-British (FAB) classification of acute myeloid leukemia (AML). Hemophilia is a congenital bleeding disorder characterized by a deficiency of coagulation factor VIII or IX. In our center, more than one thousand patients with haemophilia A have been treated since 1980.1 In June 2002, APL was first diagnosed in one person with haemophilia (PWH). The coincidence of these two diseases led to challenges in developing a treatment strategy.

  17. /sup 32/P and acute leukemia: development of leukemia in a patient with hemoglobin Yakima

    Bagby, G.C. Jr.; Richert-Boe, K.; Koler, R.D.

    1978-08-01

    In 1954 a then 31-yr-old male was found to have erythrocytosis. Over the ensuing decade he received 72 mCi /sup 32/P. In 1964 his daughters were found to have erythrocytosis. Further investigation led to the discovery of hemoglobin Yakima, a variant with high oxygen affinity. He received no further therapy and was well until 1975, when he developed the preleukemic syndrome. Within 12 mo he developed acute nonlymphocytic leukemia accompanied by fetal erythropoiesis. Because the initial discovery of this type of hemoglobinopathy came 27 yr after the introduction of /sup 32/P for use in the treatment of polycythemia vera, and because there are now known to be more than 39 different high-oxygen-affinity hemoglobins, we anticipate that more patients such as ours have been exposed to /sup 32/P. The exposed population should be closely followed, since this will likely permit assessment of the risk of /sup 32/P-induced leukemia in a nonneoplastic condition.

  18. Total Marrow and Lymphoid Irradiation and Chemotherapy Before Donor Transplant in Treating Patients With Myelodysplastic Syndrome or Acute Leukemia

    2016-08-10

    Adult Acute Lymphoblastic Leukemia in Complete Remission; Acute Myeloid Leukemia in Remission; Previously Treated Myelodysplastic Syndrome; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Childhood Acute Lymphoblastic Leukemia in Complete Remission

  19. Allogeneic Hematopoietic Cell Transplantation for Patients with Mixed Phenotype Acute Leukemia.

    Munker, Reinhold; Brazauskas, Ruta; Wang, Hai Lin; de Lima, Marcos; Khoury, Hanna J; Gale, Robert Peter; Maziarz, Richard T; Sandmaier, Brenda M; Weisdorf, Daniel; Saber, Wael

    2016-06-01

    Acute biphenotypic leukemias or mixed phenotype acute leukemias (MPAL) are rare and considered high risk. The optimal treatment and the role of allogeneic hematopoietic stem cell transplantation (alloHCT) are unclear. Most prior case series include only modest numbers of patients who underwent transplantation. We analyzed the outcome of 95 carefully characterized alloHCT patients with MPAL reported to the Center for International Blood and Marrow Transplant Research between 1996 and 2012. The median age was 20 years (range, 1 to 68). Among the 95 patients, 78 were in first complete remission (CR1) and 17 were in second complete remission (CR2). Three-year overall survival (OS) of 67% (95% confidence interval [CI], 57 to 76), leukemia-free survival of 56% (95% CI, 46 to 66), relapse incidence of 29% (95% CI, 20 to 38), and nonrelapse mortality of 15% (95% CI, 9 to 23) were encouraging. OS was best in younger patients (acute myelogenous leukemia or 359 acute lymphoblastic leukemia cases. MPAL patients had more acute and a trend for more chronic graft-versus-host disease. No difference was observed between patients who underwent transplantation in CR1 versus those who underwent transplantation in CR2. AlloHCT is a promising treatment option for pediatric and adult patients with MPAL with encouraging long-term survival. PMID:26903380

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

    2016-02-22

    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

  1. General Information about Adult Acute Myeloid Leukemia

    ... Treatment Childhood AML Treatment Research Adult Acute Myeloid Leukemia Treatment (PDQ®)–Patient Version General Information About Adult Acute Myeloid Leukemia Go to Health Professional Version Key Points Adult ...

  2. Treatment Option Overview (Adult Acute Lymphoblastic Leukemia)

    ... Treatment Childhood AML Treatment Research Adult Acute Lymphoblastic Leukemia Treatment (PDQ®)–Patient Version General Information About Adult Acute Lymphoblastic Leukemia Go to Health Professional Version Key Points Adult ...

  3. Treatment Option Overview (Adult Acute Myeloid Leukemia)

    ... Treatment Childhood AML Treatment Research Adult Acute Myeloid Leukemia Treatment (PDQ®)–Patient Version General Information About Adult Acute Myeloid Leukemia Go to Health Professional Version Key Points Adult ...

  4. General Information about Adult Acute Lymphoblastic Leukemia

    ... Treatment Childhood AML Treatment Research Adult Acute Lymphoblastic Leukemia Treatment (PDQ®)–Patient Version General Information About Adult Acute Lymphoblastic Leukemia Go to Health Professional Version Key Points Adult ...

  5. Stages of Adult Acute Myeloid Leukemia

    ... Treatment Childhood AML Treatment Research Adult Acute Myeloid Leukemia Treatment (PDQ®)–Patient Version General Information About Adult Acute Myeloid Leukemia Go to Health Professional Version Key Points Adult ...

  6. Stages of Adult Acute Lymphoblastic Leukemia

    ... Treatment Childhood AML Treatment Research Adult Acute Lymphoblastic Leukemia Treatment (PDQ®)–Patient Version General Information About Adult Acute Lymphoblastic Leukemia Go to Health Professional Version Key Points Adult ...

  7. Treatment Options for Adult Acute Myeloid Leukemia

    ... Treatment Childhood AML Treatment Research Adult Acute Myeloid Leukemia Treatment (PDQ®)–Patient Version General Information About Adult Acute Myeloid Leukemia Go to Health Professional Version Key Points Adult ...

  8. Treatment Options for Adult Acute Lymphoblastic Leukemia

    ... Treatment Childhood AML Treatment Research Adult Acute Lymphoblastic Leukemia Treatment (PDQ®)–Patient Version General Information About Adult Acute Lymphoblastic Leukemia Go to Health Professional Version Key Points Adult ...

  9. 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

    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

  10. The Relationship between Clinical Feature, Complex Immunophenotype, Chromosome Karyotype, and Outcome of Patients with Acute Myeloid Leukemia in China

    Bingjie Ding; Lanlan Zhou; Xuejie Jiang; Xiaodong Li; Qingxiu Zhong; Zhixiang Wang; Zhengshan Yi; Zhongxin Zheng; Changxin Yin; Rui Cao; Libin Liao; Fanyi Meng

    2015-01-01

    Mixed phenotype acute leukemia (MPAL) is a complex entity expressing both lymphoid and myeloid immunophenotyping. In the present study, 47 MPAL, 60 lymphoid antigen-positive acute myeloid leukemia (Ly+AML), and 90 acute myeloid leukemia with common myeloid immunophenotype (Ly−AML) patients were investigated. We found that, in MPAL patients, there were high proportions of blast cells in bone marrow and incidence of hepatosplenomegaly, lymphadenopathy, and Philadelphia chromosome. The overall s...

  11. Clinical and microbiological characteristics of perianal infections in adult patients with acute leukemia.

    Chien-Yuan Chen

    Full Text Available BACKGROUND: Perianal infection is a common problem for patients with acute leukemia. However, neutropenia and bleeding tendency are relatively contraindicated to surgical intervention. The epidemiology, microbiology, clinical manifestations and outcomes of perianal infection in leukemic patients are also rarely discussed. METHOD: The medical records of 1102 adult patients with acute leukemia at a tertiary medical center in Taiwan between 2001 and 2010 were retrospectively reviewed and analyzed. RESULT: The prevalence of perianal infection was 6.7% (74 of 1102 in adult patients with acute leukemia. Twenty-three (31% of the 74 patients had recurrent episodes of perianal infections. Patients with acute myeloid leukemia had higher recurrent rates than acute lymphoblastic leukemia patients (p = 0.028. More than half (n = 61, 53% of the perianal infections were caused by gram-negative bacilli, followed by gram-positive cocci (n = 36, 31%, anaerobes (n = 18, 15% and Candida (n = 1, 1% from pus culture. Eighteen patients experienced bacteremia (n = 24 or candidemia (n = 1. Overall 41 (68% of 60 patients had polymicrobial infection. Escherichia coli (25% was the most common micro-organism isolated, followed by Enterococcus species (22%, Klebsiella pneumoniae (13%, and Bacteroides species (11%. Twenty-five (34% of 74 patients received surgical intervention. Acute leukemia patients with surgically managed anal fistulas tended to have fewer recurrences (p = 0.067. Four (5% patients died within 30 days after diagnosis of perianal infection. Univariate analysis of 30-day survival revealed the elderly (≧ 65 years (p = 0.015 and patients with shock (p<0.001 had worse outcome. Multivariate analysis showed septic shock to be the independent predictive factor of 30-day crude mortality of perianal infections (p = 0.016. CONCLUSION: Perianal infections were common and had high recurrence rate in adult patients with acute

  12. Drug screen in patient cells suggests quinacrine to be repositioned for treatment of acute myeloid leukemia

    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 μM drug concentration. Only one of these compounds, quinacrine, showed low activity in normal PBMCs and was therefore selected for further preclinical evaluation. Mining the NCI-60 and the NextBio databases demonstrated leukemia sensitivity and the ability of quinacrine to reverse myeloid leukemia gene expression. Mechanistic exploration was performed using the NextBio bioinformatic software using gene expression analysis of drug exposed acute myeloid leukemia cultures (HL-60) in the database. Analysis of gene enrichment and drug correlations revealed strong connections to ribosomal biogenesis nucleoli and translation initiation. The highest drug–drug correlation was to ellipticine, a known RNA polymerase I inhibitor. These results were validated by additional gene expression analysis performed in-house. Quinacrine induced early inhibition of protein synthesis supporting these predictions. The results suggest that quinacrine have repositioning potential for treatment of acute myeloid leukemia by targeting of ribosomal biogenesis

  13. Polyradiculoneuritis revealing an acute monoblastic leukemia 5

    Wafa Allam; Hassan Errihani; Yahya Hsaini

    2010-01-01

    Acute polyradiculoneuritis has been frequently reported in association with malignant disorders, especially those of the lymphoid system. To date, there have been no reported cases of acute monoblastic leukemia associated with this polyradiculopathy. The authors tell us about a very rare case of leukemia presenting as acute monoblastic leukemia 5 (AML5) in a 28 years old patient from Morroco

  14. 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

    2016-02-12

    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

  15. Assessing Compliance With Mercaptopurine Treatment in Younger Patients With Acute Lymphoblastic Leukemia in First Remission | Division of Cancer Prevention

    This randomized phase III trial studies compliance to a mercaptopurine treatment intervention compared to standard of care in younger patients with acute lymphoblastic leukemia in remission. Assessing ways to help patients who have acute lymphoblastic leukemia to take their medications as prescribed may help them in taking their medications more consistently and may improve treatment outcomes. |

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

    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

  17. Study of nucleophosmin (NPM) gene mutation in patients with acute myeloid leukemia and myelodysplastic syndromes

    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. Clofarabine and Melphalan Before Donor Stem Cell Transplant in Treating Patients With Myelodysplasia or Acute Leukemia in Remission

    2016-06-09

    Adult Acute Lymphoblastic Leukemia in Remission; 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); Previously Treated Myelodysplastic Syndromes; Secondary Acute Myeloid Leukemia

  19. Etoposide, Prednisone, Vincristine Sulfate, Cyclophosphamide, and Doxorubicin Hydrochloride With Asparaginase in Treating Patients With Acute Lymphoblastic Leukemia or Lymphoblastic Lymphoma

    2016-04-26

    B Acute Lymphoblastic Leukemia; B Lymphoblastic Lymphoma; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent B Lymphoblastic Lymphoma; Recurrent T Lymphoblastic Leukemia/Lymphoma; Refractory B Lymphoblastic Lymphoma; Refractory T Lymphoblastic Lymphoma; T Acute Lymphoblastic Leukemia; T Lymphoblastic Lymphoma

  20. The mortality and response rate after FLANG regimen in patients with refractory/relapsed acute leukemia

    Vali A Mehrzad

    2012-01-01

    Full Text Available Background: Oncologists today are greatly concerned about the treatment of relapsed/refractory acute leukemia. FLANG regimen, combination of novantron, cytarabine, fludarabine, and granulocyte-colony stimulating factor, has been used in treatment of refractory/relapsed acute leukemia since 1990s. The present study has evaluated mortality and response rate of this regimen. Materials and Methods: In this study, 25 patients with refractory/relapsed acute leukemia aged 15-55 years underwent FLANG regimen at Seyed-Al-Shohada Hospital, Isfahan, Iran during 2008-2009. One month later, bone marrow samples were taken to evaluate the responsiveness to treatment. Participants were followed for a year. The data was analyzed by student-t and chi-square tests, logistic, and Cox regression analysis, and Kaplan-Meier curves in SPSS 19. Results: Out of the 25 patients, 8 patients (32% had acute lymphoblastic leukemia (5 refractory and 3 relapsed cases and 17 subjects had acute myeloid leukemia (7 refractory and 10 relapsed cases. According to the bone marrow biopsies taken one month after FLANG regimen, 10 patients (40% had responded to treatment. Five patients of the 10 responders underwent successful bone marrow transplantation (BMT. On the other hand, 13 patients (52%, who had not entered the CR period, died during the follow-up. Logistic regression analysis did not reveal any significant associations between disease type and responsiveness to treatment. Conclusion: This study indicated higher rates of unresponsiveness to treatment while its mortality rate was comparable with other studies. Overall, according to limitations for BMT (as the only chance for cure in Iran, it seems that FLANG therapy is an acceptable choice for these patients.

  1. Oral idarubicin plus cytosine arabinoside in the treatment of acute non lymphoblastic leukemia in elderly patients.

    Pagano, L; Sica, S; Marra, R; Voso, M T; Storti, S; Di Mario, A; Leone, G

    1991-01-01

    Eighteen acute nonlymphoblastic leukemia patients greater than 60 yr., 12 at diagnosis and 6 in first relapse, were treated with the association of oral Idarubicin and subcutaneous Aracytin. One patient was not evaluable. Eight out of 17 patients achieved complete remission (47%), 4 patients died in induction and 5 proved resistant to treatments. Mucocutaneous and gastrointestinal toxicity was mild. The most frequent extra-hematological complications were infections. We observed an important hepatic toxicity in 1 case. PMID:1820991

  2. Development of Acute Promyelocytic Leukemia in a Patient With Gouty Arthritis on Long Term Colchicine.

    Buyukkurt, Nurhilal; Korur, Asli; Boga, Can

    2016-06-01

    Colchicine is a frequently used drug in rheumatological diseases. Acute promyelocytic leukemia developed in a patient who used colchicine for gouty arthritis since 10 years is presented and the possible relation between the long term use of colchicine and hematological malignancies is discussed. PMID:27408362

  3. Relapsing and difficult to control hypokalemia in a patient with acute lymphoid leukemia

    Nieto-Ríos, John Fredy; Serna-Higuita, Lina María; Valencia-Chicué, Libardo Humberto; Ocampo-Kohn, Catalina; Aristizábal-Alzate, Arbey; Zuluaga-Valencia, Gustavo Adolfo

    2015-01-01

    Hypokalemia is an electrolytic disorder, in some occasions difficult to control. When severe, it may be life-threatening. We report the case of a patient with relapse of acute lymphoid leukemia, who presented to the hospital with flaccid paralysis associated with severe hypokalemia. The cause was a tubulopathy associated with leukemic infiltration of the kidneys.

  4. Hemophagocytic syndrome in patients with acute myeloid leukemia undergoing intensive chemotherapy

    Delavigne, Karen; Bérard, Emilie; Bertoli, Sarah; Corre, Jill; Duchayne, Eliane; Demur, Cécile; Mas, Véronique Mansat-De; Borel, Cécile; Picard, Muriel; Alvarez, Muriel; Sarry, Audrey; Huguet, Françoise; Récher, Christian

    2014-01-01

    Hemophagocytic lymphohistiocytosis is a condition of immune dysregulation characterized by severe organ damage induced by a hyperinflammatory response and uncontrolled T-cell and macrophage activation. Secondary hemophagocytic lymphohistiocytosis typically occurs in association with severe infections or malignancies. Patients with acute myeloid leukemia may be prone to develop hemophagocytic lymphohistiocytosis because of an impaired immune response and a high susceptibility to severe infecti...

  5. Chromosome abnormalities in Down's syndrome patients with acute leukemia

    Kaneko, Y. (Univ. of Chicago, IL); Rowley, J.D.; Variakojis, D; Chilcote, R.R.; Moohr, J.W.; Patel, D.

    1981-09-01

    Chromosome and cytologic studies were performed on three Down's syndrome (DS) patients with acute nonlymphocytic leukemia (ANLL). All three patients had an aneuploid clone in their leukemic cells: 50,XX, +6, +19, +21, +22, 48,XX, +8, +21, and 47,XY, +8, -21, +dic(21;21)(p13;p11). Every patient appeared to have acute undifferentiated leukemia when the blast cells were examined with Wright-Giemsa stain; cytochemistry studies, however, showed that the leukemic blasts were in an early stage of myeloid differentation. The two patients with +8 had a preleukemic phase; the blast cells of the patient with an extra no. 19 and no. 22 could not be differentiated morphologically from those of the two patients with an extra no. 8. Our findings and a review of data on 40 other patients suggest that most DS children with ANLL have hyperdiploidy, which is usually related to gains of C, F, and/or G chromosomes.

  6. Tretinoin and Arsenic Trioxide in Treating Patients With Untreated Acute Promyelocytic Leukemia

    2015-12-30

    Adult Acute Promyelocytic Leukemia With t(15;17)(q22;q12); PML-RARA; Childhood Acute Promyelocytic Leukemia With t(15;17)(q22;q12); PML-RARA; Untreated Adult Acute Myeloid Leukemia; Untreated Childhood Myeloid Neoplasm

  7. Individualized leukemia cell-population profiles in common B-cell acute lymphoblastic leukemia patients

    Xian-Ming Mo; Hong Xu; Ting-Ting Zeng; Neng-Gang Jiang; Yong-Qian Jia; Jing-Tao Dong; Jian-Hua Yu; Wen-Tong Meng

    2013-01-01

    Immunophenotype is critical for diagnosing common B-cell acute lymphoblastic leukemia (common ALL) and detecting minimal residual disease. We developed a protocol to explore the immunophenotypic profiles of common ALL based on the expression levels of the antigens associated with B lymphoid development, including IL-7R alpha (CD127), cytoplasmic CD79a (cCD79a), CD19, VpreB (CD179a), and sIgM, which are successive and essential for progression of B cells along their developmental pathway. Anal...

  8. Concanavalin A receptors on the surface membrane of lymphocytes from patients with acute leukemia.

    Ben-Bassat, H; Anor, E; Penchas, S; Shlomai, Z; Prokocimer, M; Or, R; Polliack, A

    1984-01-01

    Peripheral blood mononuclear cells (PBM) isolated from 23 patients with acute lymphoblastic leukemia (ALL) and 24 with acute non-lymphoblastic leukemia (ANLL) were studied for binding and mobility of Concanavalin A (Con A) receptors, using fluorescent Con A (F-Con-A). The cap forming ability of PBM from all patients was 18.7 (+/- 9.3%) and 18.9 (+/- 9.9%) for ANLL patients at the time of diagnosis or during relapse. During clinical complete remission the cap forming ability of the PBM did not change significantly. No correlation was observed between the percentage of blasts present in the peripheral blood at the time of examination and the extent of cap formation, for both types of leukemia. The pattern of F-Con-A binding to PBM in ANLL patients was different compared to that seen in ALL. In ANLL, the fluorescent stain was concentrated in a round body on the cell ("button form") after binding to the membrane, while the rest of the cell showed almost no fluorescence. The present results indicate that PBM cells from patients with acute leukemia are characterized by a high degree of Con-A receptor mobility. PMID:6471903

  9. Ultrasound and MR Findings of Aleukemic Leukemia Cutis in a Patient with Complete Remission of Acute Lymphoblastic Leukemia: A Case Report

    Kim, Min Sung; Jee, Won Hee; Kim, Sun Ki; Lee, So Yeon; Lim, Gye Yeon; Park, Gyeong Sin; Lee, Seok [Catholic University of Korea College of Medicine, Seoul (Korea, Republic of)

    2010-12-15

    Aleukemic leukemia cutis is an extremely rare condition characterized by the infiltration of leukemic cells in skin without blasts in the peripheral blood. Leukemia cutis is considered a grave prognostic sign, thus early diagnosis is important. Leukemia cutis usually occurs in patients with myeloid leukemia. To the best of our knowledge, there has been no report regarding the radiological findings of aleukemic leukemia cutis, which is probably due to the presence of the skin changes in most patients. We report the ultrasound and MR findings of aleukemic leukemia cutis, even without the skin manifestation in patients with a history of complete remission of the acute lymphoblastic leukemia following an allogeneic peripheral blood stem cell transplantation

  10. Cytogenetic Findings of Patients with Acute Lymphoblastic Leukemia in Fars Province

    Akbar Safaei; Jahanbanoo Shahryari; Mohamad Reza Farzaneh; Narjes Tabibi; Marzieh Hosseini

    2013-01-01

    Background: Acute lymphoblastic leukemia (ALL) is the sixth most common malignancy in Iran. Cytogenetic analysis of leukemic blasts plays an important role in classification and prognosis in ALL patients. The purpose of this study was to define the frequency of chromosomal abnormalities of ALL patients in adults and children in Fars province, Iran. Methods: In this cross-sectional study, we evaluated karyotype results of bone marrow specimens in 168 Iranian patients with ALL (154 B-ALL and...

  11. CRUSTED SCABIES IN A PATIENT WITH ACUTE LYMPHOCYTIC LEUKEMIA

    Mamatha

    2015-06-01

    Full Text Available A 17 year s old male patient presented with diffuse, ill defined, hyperpigmented, scaly plaques on the body, for the past 15 days. Lesions were more over the groin and also on both elbows and wrists. Patient is a known case of acute lymphocytic leukaemia, diagnosed a t the age of 13 years and has been on treatment ever since. A KOH ( 10% mount of the scales showed the presence of sarcoptes scabiei and skin biopsy with haematoxylin and eosin showed fragments of mite in the excised skin.

  12. Congenital acute megakaryocytic leukemia

    N B Mathur

    2011-01-01

    Full Text Available Congenital leukemia (CL is an extremely rare disorder in the newborn, significant proportion of which is of myeloid origin, primarily of M4 or M5 morphology. As compared to pediatric leukemia, CL is a more aggressive disease. Acute myeloid leukemia (AML-M7 or acute megakaryocytic leukemia is a rare type of AML with an incidence of 0.5 per million per year. Median age of presentation is 6 years, and children may present with a broad variety of symptoms including low-grade fever, diarrhea, easy bruising, failure to gain weight and life-threatening conditions.

  13. Fludarabine Phosphate and Total-Body Irradiation Followed by Donor Peripheral Blood Stem Cell Transplant in Treating Patients With Acute Lymphoblastic Leukemia or Chronic Myelogenous Leukemia That Has Responded to Treatment With Imatinib Mesylate, Dasatinib, or Nilotinib

    2015-07-20

    Adult Acute Lymphoblastic Leukemia in Remission; Blastic Phase Chronic Myelogenous Leukemia; Childhood Acute Lymphoblastic Leukemia in Remission; Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Chronic Phase Chronic Myelogenous Leukemia; Philadelphia Chromosome Positive Adult Precursor Acute Lymphoblastic Leukemia; Philadelphia Chromosome Positive Childhood Precursor Acute Lymphoblastic Leukemia; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Lymphoblastic Leukemia; Relapsing Chronic Myelogenous Leukemia

  14. Patient Activation through Counseling and Exercise – Acute Leukemia (PACE-AL) – a randomized controlled trial

    Jarden, Mary; Møller, Tom; Kjeldsen, Lars;

    2013-01-01

    treatment related symptoms and side effects. To date, there are no clinical practice exercise guidelines for patients with acute leukemia undergoing induction and consolidation chemotherapy. A randomized controlled trial is needed to determine if patients with acute leukemia can benefit by a structured and...... supervised counseling and exercise program.Methods/design: This paper presents the study protocol: Patient Activation through Counseling and Exercise -- Acute Leukemia (PACE-AL) trial, a two center, randomized controlled trial of 70 patients with acute leukemia (35 patients/study arm) following induction...... chemotherapy in the outpatient setting. Eligible patients will be randomized to usual care or to the 12 week exercise and counseling program. The intervention includes 3 hours + 30 minutes per week of supervised and structured aerobic training (moderate to high intensity 70 - 80%) on an ergometer cycle...

  15. Cyclophosphamide and Busulfan Followed by Donor Stem Cell Transplant in Treating Patients With Myelofibrosis, Acute Myeloid Leukemia, or Myelodysplastic Syndrome

    2014-04-03

    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); Childhood Acute Myeloid Leukemia in Remission; Childhood Myelodysplastic Syndromes; de Novo Myelodysplastic Syndromes; Essential Thrombocythemia; Myelodysplastic Syndrome With Isolated Del(5q); Polycythemia Vera; Previously Treated Myelodysplastic Syndromes; Primary Myelofibrosis; Recurrent Adult Acute Myeloid Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndromes; Secondary Myelofibrosis; Untreated Adult Acute Myeloid Leukemia; Untreated Childhood Acute Myeloid Leukemia and Other Myeloid Malignancies

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

    2015-02-24

    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

  17. Granulomatous rosacea: Like leukemid in a patient with acute myeloid leukemia

    Škiljević Dušan

    2008-01-01

    Full Text Available Introduction. Skin findings in leukemias may be divided into specific lesions (leukemia cutis and non-specific lesions (leukemids which may be found in up to 80% of all patients with leukemias. The leukemids vary clinically and they are usually a manifestation of bone marrow or immunologic impairment, but also Sweet syndrome, pyoderma gangrenosum, erythroderma, maculopapular exanthema, prurigo-like papules, generalized pigmentation, follicular mucinosis, generalized pruritus may be found during the course of leukemia. Case report. We report a 70-year-old male with a 3-month history of erythema, papules and pustules on the face, ears and neck and over a month history of refractory anemia, anorexia, weight loss, malaise, and fever. Physical examination revealed symmetric erythematous, violaceous papules, papulo-nodules and plaques with slate scale and sparse, small pustules on the face, earlobes and neck. Histopathologic findings of involved skin showed diffuse mixed inflammatory cell infiltrate with perifollicular accentuation and focal granulomatous inflammation in the papillary and upper reticular dermis. Extensive checkup revealed the presence of acute myeloid leukemia French- American-British (FAB classification subtype M2, with signs of three-lineage dysplasia. The patient was treated by L6 protocol which led to complete remission, both in bone marrow and skin, but after seven months he had relapse of leukemia with the fatal outcome. Conclusion. This case indicates the importance of skin eruptions in the context of hematological malignancies.

  18. Arsenic speciation in saliva of acute promyelocytic leukemia patients undergoing arsenic trioxide treatment

    Chen, Baowei; Cao, Fenglin; Yuan, Chungang; Lu, Xiufen; Shen, Shengwen; Zhou, Jin; Le, X Chris

    2013-01-01

    Arsenic trioxide has been successfully used as a therapeutic in the treatment of acute promyelocytic leukemia (APL). Detailed monitoring of the therapeutic arsenic and its metabolites in various accessible specimens of APL patients can contribute to improving treatment efficacy and minimizing arsenic-induced side effects. This article focuses on the determination of arsenic species in saliva samples from APL patients undergoing arsenic treatment. Saliva samples were collected from nine APL pa...

  19. Patient Activation through Counseling and Exercise – Acute Leukemia (PACE-AL) – a randomized controlled trial

    Jarden, Mary; Møller, Tom; Kjeldsen, Lars; Birgens, Henrik; Christensen, Jesper Frank; Bang Christensen, Karl; Diderichsen, Finn; Hendriksen, Carsten; Adamsen, Lis

    2013-01-01

    Background Patients with acute leukemia experience a substantial symptom burden and are at risk of developing infections throughout the course of repeated cycles of intensive chemotherapy. Physical activity in recent years has been a strategy for rehabilitation in cancer patients to remedy disease and treatment related symptoms and side effects. To date, there are no clinical practice exercise guidelines for patients with acute leukemia undergoing induction and consolidation chemotherapy. A r...

  20. Characterization of a pediatric T-cell acute lymphoblastic leukemia patient with simultaneous LYL1 and LMO2 rearrangements

    Homminga, Irene; Vuerhard, Maartje J.; Langerak, Anton W; Buijs-Gladdines, Jessica; Pieters, Rob; Meijerink, Jules P. P.

    2012-01-01

    Translocation of the LYL1 oncogene are rare in T-cell acute lymphoblastic leukemia, whereas the homologous TAL1 gene is rearranged in approximately 20% of patients. Previous gene-expression studies have identified an immature T-cell acute lymphoblastic leukemia subgroup with high LYL1 expression in the absence of chromosomal aberrations. Molecular characterization of a t(7;19)(q34;p13) in a pediatric T-cell acute lymphoblastic leukemia patient led to the identification of a translocation betw...

  1. Distinguishing the Causes of Pulmonary Infiltrates in Patients With Acute Leukemia.

    Nucci, Marcio; Nouér, Simone A; Anaissie, Elias

    2015-06-01

    Pulmonary infiltrates are commonly observed in patients with acute leukemia (AL), particularly acute myeloid leukemia, who undergo remission induction therapy. The mortality rate is unacceptably high and depends on 3 factors: the host (performance status, comorbidities, and frailty), the etiology of the infiltrates and the type of response to antileukemic therapy. The approach to the diagnosis of pulmonary infiltrates in patients with AL includes a medical history, thorough physical examination, radiologic pattern of the infiltrates (focal vs. diffuse), and timing of their appearance in relation to the start of antileukemic therapy (early, ie, within the first 2 weeks or late). Localized infiltrates are most commonly caused by bacterial (early) and fungal infections (late). Diffuse early infiltrates might be caused by leukemic infiltration of the lungs, pulmonary hemorrhage and/or edema, diffuse alveolar damage, viral pneumonia, and rarely transfusion-related acute lung injury (TRALI) or the differentiation syndrome. Similar to the early phase, pulmonary edema, viral pneumonia, and rarely TRALI might cause diffuse infiltrates during the late phase, in addition to immune reconstitution and pneumocystosis, particularly among patients with acute lymphoblastic leukemia. Diagnostic tests, invasive and noninvasive, can be particularly useful to establish the diagnosis. Early intervention is critical and is based on the most likely diagnosis with modification when the etiology is confirmed. PMID:26297289

  2. Aberrant Phenotype in Iranian Patients with Acute Myeloid Leukemia

    Mehdi Jahedi

    2014-03-01

    Full Text Available Purpose: The aim of this study was to evaluate the incidence of aberrant phenotypes and possible prognostic value in peripheral and bone marrow blood mononuclear cells of Iranian patients with AML. Methods: 56 cases of de novo AML (2010-2012 diagnosed by using an acute panel of monoclonal antibodies by multiparametric flowcytometry. Immunophenotyping was done on fresh bone marrow aspirate and/or peripheral blood samples using the acute panel of MoAbs is stained with Phycoerythrin (PE /fluorescein isothiocyanate (FITC, Allophycocyanin (APC and Peridinin-chlorophyll protein complex (perCP. We investigated Co-expression of lymphoid-associated markers CD2, CD3, CD7, CD 10, CD19, CD20 and CD22 in myeloblasts. Results: Out of the 56 cases, 32 (57.1% showed AP. CD7 was positive in 72.7% of cases in M1 and 28.5% in M2 but M3 and M4 cases lacked this marker. We detected CD2 in 58.35 of M1cases, 21.40% of M2 cases, 33.3 of M3 and 20% of M5; but M4 patients lacked this marker. The CBC analysis demonstrated a wide range of haemoglobin concentration, Platelet and WBC count which varied from normal to anaemia, thrombocytopenia to thrombocytosis and leukopenia to hyper leukocytosis. Conclusions: Our findings showed that CD7 and CD2 were the most common aberrant marker in Iranian patients with AML. However, we are not find any significant correlation between aberrant phenotype changing and MRD in our population. Taken together, this findings help to provide new insights in to the investigation of other aberrant phenotypes that may play roles in diagnosis and therapeutic of AML.

  3. Acute lymphoblastic leukemia (ALL)

    Jeha S, Pui CH. Clinical manifestations and treatment of acute lymphoblastic leukemia in children. In: Hoffman R, Benz EJ Jr, Silberstein LE, Weitz JI, Anastasi J, eds. Hematology: Basic Principles and Practice. 6th ed. ...

  4. The study on relationship between age and cytogenetic subgroups in 640 patients with de novo acute myeloid leukemia

    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

  5. Risk of acute leukemia and myelodysplastic syndromes in patients with monoclonal gammopathy of undetermined significance (MGUS): a population-based study of 17 315 patients

    Roeker, LE; Larson, DR; Kyle, RA; Kumar, S; Dispenzieri, A; Rajkumar, SV

    2013-01-01

    The purpose of this study was to determine if there is an increased risk of acute leukemia and myelodysplastic syndromes (MDS) in persons with monoclonal gammopathy of undetermined significance (MGUS). We used a large population-based cohort of individuals systematically screened for the presence or absence of MGUS. MGUS status was then linked to the diagnosis of acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL) and MDS. A total of 17 315 patients age 50 and older (605 MGUS and...

  6. Acute lymphocytic Leukemia masquerading as acute osteomyelitis

    Two children each developed a focal destructive bone lesion accompanied by intermittent fever, swelling, tenderness and elevated ESR. Blood counts were normal; bone marrow aspiration showed acute leukemia. The bone lesions healed in both patients after anti-leukemic therapy. We suggest that the similar roentgenographic appearance of osteomyelitis, bone infarction and focal destructive lesions in leukemia probably reflects a common, basically ischemic process of bone. (orig.)

  7. Kinetics of indium-111-labeled leukemic cells in patients with acute non-lymphocytic leukemia

    The kinetics of autologous leukemic cells labeled with In-111 oxine were studied in 5 patients with acute myeloblastic leukemia (AML) and one patient with acute premyelocytic leukemia (APL), and kinetics of OKM1 monoclonal antibody-treated leukemic cells were studied in one patient with acute monoblastic leukemia (AMoL). Recoveries of 33.7 +- 23.3%(range, 22.0 to 48.1%) were achieved at 10min after injection of In-111 oxine labeled leukemic cells in AML and APL patients. However, in a patient with AMoL recovery of 12.3% was only achieved at 10min after injection of OKM1-treated leukemic cells. Clearance of the activity from blood was rapid up to one in all patients. The clearance curve of the activity in 5 AML patients showed a hump or a plateau from one to 5hr after injection of labeled leukemic cells. In APL patient and AMoL patient, however, this hump or plateau was not noted. In AML and APL patients the activity over the spleen was higher than that of over the liver at from 30min to 3hr after and showed a plateau or gradual rising thereafter. In a patient with AMoL, the hepatic activity was higher than the splenic activity at 30min after, but thereafter the latter became higher than the former. Liver activity curves showed transient fall at 3hr after and then gradual uprising in all patients. In a patient with APL, high activity was noted over the kidneys. This rose to a maximum after 3hr and then decreased rapidly. Since In-111 oxine stays firmly attached to the cells in spite of the possibility of radiation damage in a long-term survey, it seems an ideal label for studying leukemic cell kinetics

  8. Characterization of Common Chromosomal Translocations and Their Frequencies in Acute Myeloid Leukemia Patients of Northwest Iran

    Elnaz Amanollahi Kamaneh; Karim Shams Asenjan; Aliakbar Movassaghpour Akbari; Parvin Akbarzadeh Laleh; Hadi Chavoshi; Jamal Eivazi Ziaei; Alireza Nikanfar; Iraj Asvadi Kermani; Ali Esfahani

    2016-01-01

    Objective: Detection of chromosomal translocations has an important role in diagnosis and treatment of hematological disorders. We aimed to evaluate the 46 new cases of de novo acute myeloid leukemia (AML) patients for common translocations and to assess the effect of geographic and ethnic differences on their frequencies. Materials and Methods: In this descriptive study, reverse transcriptase-polymerase chain reaction (RT-PCR) was used on 46 fresh bone marrow or peripheral blo...

  9. Development of therapeutic agents for elderly patients with acute myelogenous leukemia

    Hourigan, Christopher S.; Judith E Karp

    2010-01-01

    Acute myelogenous leukemia (AML) is a disease more common in the elderly than the young. It is increasingly recognized that conventional cytotoxic chemotherapies used in children and young adults may not be appropriate in older adults because of diverse host- and disease-biology factors. This review highlights some of the most promising new treatment options that are being evaluated for older patients with AML. These options include CPX-351 (Celator Pharmaceuticals Inc), a unique liposomal fo...

  10. HAG regimen improves survival in adult patients with hypocellular acute myeloid leukemia

    Hu, Xiaoxia; Fu, Weijun; Wang, Libing; Gao, Lei; Lü, Shuqin; Xi, Hao; Qiu, Huiying; Chen, Li; Chen, Jie; Ni, Xiong; Xu, Xiaoqian; Zhang, Weiping; Yang, Jianmin; Wang, Jianmin; Song, Xianmin

    2015-01-01

    Background Hypocellular acute myeloid leukemia (Hypo-AML) is a rare disease entity. Studies investigating the biological characteristics of hypo-AML have been largely lacking. We examined the clinical and biological characteristics, as well as treatment outcomes of hypo-AML in our institutes over a seven years period. Design and Methods We retrospectively analyzed data on 631 adult AML patients diagnosed according to the French-American-British (FAB) classification and WHO classification of t...

  11. Fluorescence in situ hybridization analysis of the hTERC region in acute myeloid leukemia patients

    Özge Özer; Tuğçe Bulakbaşı Balcı; Zerrin Yılmaz; Feride İffet Şahin

    2011-01-01

    Objective: The telomerase RNA component (hTERC) gene is located at 3q26. Increased hTERC gene expression has been frequently observed and amplification was shown using fluorescence in situ hybridization (FISH) in different cancers. The aim of this study was to determine whether hTERC gene amplification is detectable by FISH in acute myeloid leukemia (AML) cells. Material and Methods: FISH and karyotype results at the time of diagnosis of 23 adult AML patients were retrospectively evaluated. A...

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

    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.

  13. Morbidity associated to the transfusion support in pediatric patients with acute leukemia in the National Cancer Institute

    Acute leukemia represents the most common cancer in pediatrics. The current treatments made necessary a hematological support which increases the risks of complications, like fever, immunologic reaction, infections and, graft versus host disease. The objective of the present study was to determine the morbidity associated with transfusion support in pediatric patients with acute leukemia. In the pediatric population with diagnosis of acute leukemia in the INC during one and half year, the morbidity associated with transfusions was low and couldn't be related to the treatment given to the transfused products

  14. Wilms Tumor 1 Gene Mutations in Patients with Cytogenetically Normal Acute Myeloid Leukemia

    Salah Aref; Solafa El Sharawy; Mohamed Sabry; Emad Azmy; Dalia Abdel Raouf; Nadia El Menshawy

    2014-01-01

    Objective: This study aimed to assess the prognostic impact of Wilms tumor 1 (WT1) mutations in cytogenetically normal acute myeloid leukemia (CN-AML) among Egyptian patients. Materials and Methods: Exons 1, 2, 3, 7, 8, and 9 of WT1 were screened for mutations in samples from 82 CN-AML patients out of 203 newly diagnosed AML patients, of age ranging from 21 to 74 years, using high-resolution capillary electrophoresis. Results: Eleven patients out of 82 (13.41%) harbored WT1 mutations. Mutatio...

  15. Acute lymphoblastic leukemia as second primary tumor in a patient with retinoblastoma.

    Ganguly, Anasua; Kaliki, Swathi; Mohammad, Faraz Ali; Mishra, Dilip K; Vanajakshi, S; Reddy, Vijay Anand

    2016-01-01

    Second primary tumor (SPT) is defined as a second tumor that presents either simultaneously or after the diagnosis of an index tumor. Second primary malignancies are the leading cause of death in patients with heritable retinoblastoma (RB). Acute lymphoblastic leukemia (ALL), as SPT in RB patients, is extremely rare. To the best of our knowledge, only five cases of ALL as SPT in patients with RB has been documented in the literature. Herein, we report a case of a 6-year-old girl with bilateral RB, who developed ALL during the course of treatment of RB. This case highlights the importance of reviewing blood investigations regularly to diagnose leukemia as SPT in RB and also the necessity for proper counseling and lifelong follow-up in these patients. PMID:27433042

  16. Prognostic Significance of Lymphoid Enhancer-Binding Factor-1 Expression in Egyptian Adult B-Acute Lymphocytic Leukemia Patients

    Aly, Rabab M.; Ansaf B. Yousef

    2015-01-01

    Objective: Lymphoid enhancer-binding factor-1 (LEF-1) is a key transcription factor of wingless-type (Wnt) signaling in various tumors and it is associated with a number of malignant diseases such as leukemia. We explored the expression profile of LEF-1 in acute lymphoblastic leukemia (ALL) and determined its specific prognostic significance in this disease. Materials and Methods: We studied LEF-1 expression in 56 newly diagnosed B-acute ALL adult patients using real-time quantitative polymer...

  17. Acute acalculous cholecystitis complicating chemotherapy for acute myeloblastic leukemia

    Olfa Kassar

    2015-01-01

    Full Text Available Acute acalculous cholecystitis is a rare complication in the treatment of acute myeloblastic leukemia. Diagnosis of acute acalculous cholecystitis remains difficult during neutropenic period. We present two acute myeloblastic leukemia patients that developed acute acalculous cholecystitis during chemotherapy-induced neutropenia. They suffered from fever, vomiting and acute pain in the epigastrium. Ultrasound demonstrated an acalculous gallbladder. Surgical management was required in one patient and conservative treatment was attempted in the other patient. None treatment measures were effective and two patients died. Acute acalculous cholecystitis is a serious complication in neutropenic patients. Earlier diagnosis could have expedited the management of these patients.

  18. Acute appendicitis caused by acute myeloid leukemia

    Zhang, Shanxiang; Chen, Shaoxiong

    2014-01-01

    Key Clinical Message A case of appendiceal involvement by acute myeloid leukemia (AML) in an adult with recent history of AML transformed from myelodysplastic syndrome (MDS) was presented. Being aware of this rare presentation in particular in a patient with history of MDS and/or AML is important for prompt clinical diagnosis and management.

  19. Medical costs of treatment and survival of patients with acute myeloid leukemia in Belgium.

    Van de Velde, A L; Beutels, P; Smits, E L; Van Tendeloo, V F; Nijs, G; Anguille, S; Verlinden, A; Gadisseur, A P; Schroyens, W A; Dom, S; Cornille, I; Goossens, H; Berneman, Z N

    2016-07-01

    The advent of new cell-based immunotherapies for leukemia offers treatment possibilities for certain leukemia subgroups. The wider acceptability of these new technologies in clinical practice will depend on its impact on survival and costs. Due to the small patient groups who have received it, these aspects have remained understudied. This non-randomized single-center study evaluated medical costs and survival for acute myeloid leukemia between 2005 and 2010 in 50 patients: patients treated with induction and consolidation chemotherapy (ICT) alone; patients treated with ICT plus allogeneic hematopoietic stem cell transplantation (HCT), which is the current preferred post-remission therapy in patients with intermediate- and poor-risk AML with few co-morbidities, and patients treated with ICT plus immunotherapy using autologous dendritic cells (DC) engineered to express the Wilms' tumor protein (WT1). Total costs including post- consolidation costs on medical care at the hematology ward and outpatient clinic, pharmaceutical prescriptions, intensive care ward, laboratory tests and medical imaging were analyzed. Survival was markedly better in HCT and DC. HCT and DC were more costly than ICT. The median total costs for HCT and DC were similar. These results need to be confirmed to enable more thorough cost-effectiveness analyses, based on observations from multicenter, randomized clinical trials and preferably using quality-adjusted life-years as an outcome measure. PMID:27111858

  20. FLT3 and NPM1 mutations in Chinese patients with acute myeloid leukemia and normal cytogenetics

    Wang, Lei; Xu, Wei-lai; Meng, Hai-tao; Qian, Wen-bin; Mai, Wen-yuan; Tong, Hong-yan; Mao, Li-Ping; Tong, Yin; Qian, Jie-jing; Lou, Yin-jun; Chen, Zhi-mei; Wang, Yun-Gui; Jin, Jie

    2010-01-01

    Mutations of fms-like tyrosine kinase 3 (FLT3) and nucleophosmin (NPM1) exon 12 genes are the most common abnormalities in adult acute myeloid leukemia (AML) with normal cytogenetics. To assess the prognostic impact of the two gene mutations in Chinese AML patients, we used multiplex polymerase chain reaction (PCR) and capillary electrophoresis to screen 76 AML patients with normal cytogenetics for mutations in FLT3 internal tandem duplication (FLT3/ITD) and exon 12 of the NPM1 gene. FLT3/ITD...

  1. Invasive fungal infection (IFI) in two pediatric patients with acute leukemia. Case report

    At present over 70% of children with malignancies can be successfully cured although this is achieved at the cost of increased incidence of major complications. Fungal infections account for some 10% of all infections and, in severely immunosuppressed patients, they are still the cause of a high mortality rate (50-95%). As a result the prevention and treatment of adverse effects of antineoplastic therapy is of the most importance and can be a factor determining the success of such treatment. This paper contains two case reports of adolescent female patients diagnosed with acute leukemia who developed invasive fungal infections (IFI) in the course of intensive chemotherapy. (authors)

  2. Herpetic geometric glossitis: Acyclovir resistant case in a patient with acute myelogenous leukemia

    Pereira Claudio

    2010-01-01

    Full Text Available Herpes simplex virus (HSV infections in an immunocompromised host may be atypical in location and morphology. Lesions are more extensive and aggressive, slow healing or nonhealing and extremely painful. Intraoral lesions are ulcerative and may involve any intraoral, oropharyngeal, or esophageal site. Herpetic geometric glossitis is a recently described form of lingual HSV infection in an immunocompromised patient. It was described as ulcer on the dorsum of the tongue sensitive for acyclovir therapy. A patient is presented with acute myelogenous leukemia that developed herpetic geometric glossitis which was acyclovir resistant.

  3. Clinical Presentations of Acute Leukemia

    Objective: To document the clinical presentation and epidemiology of various types of acute leukemia with their respective referral source at a tertiary level centre in Peshawar. Study Design: An observational study. Place and Duration of Study: Department of Pathology, Hayatabad Medical Complex (HMC), Peshawar, from January 2011 to May 2012. Methodology: A total of 618 bone marrow biopsy reports were reviewed. All biopsy reports labeled as acute leukemia were reviewed for age, gender, address, referring unit, diagnosis on bone marrow examination, presenting complaints, duration of illness and findings of clinical examination. Results: Ninety-two patients were diagnosed as suffering from acute leukemias (15%). ALL was most prevalent (46%), followed by AML (38%) and undifferentiated acute leukemia (16%). Males were affected more compared to females (60% vs. 40%). ALL and AML were predominant in pediatric (64%) and adults (77%) patients respectively. Patients from Afghanistan accounted for 33% of all cases followed by Peshawar (14%). Fever (77%), pallor (33%) and bleeding disorders (23%) were the main presenting complaints. Enlargement of liver, spleen and lymph nodes together was associated with ALL compared with AML (p = 0.004). Conclusion: ALL-L1 and AML-M4 were the most common sub-types. Fever, pallor and bleeding disorders were the main presenting complaints. Enlargement of liver, spleen and lymph nodes was more frequently associated with ALL compared to AML. (author)

  4. ALL (Acute Lymphoblastic Leukemia) Guide: Information for Patients and Caregivers

    ... you plan questions to ask your doctor about treatment. Induction Therapy. Induction therapy is the first round of treatment with chemotherapy. ... patients need to start induction chemotherapy right away. Induction therapy is done in the hospital. Patients are often ...

  5. CHARACTERISTICS OF PHAGOCYTIC CELLS IN PATIENTS WITH ACUTE LEUKEMIA WITH AN INFECTIOUS SYNDROME

    S. V. Plotnikova

    2013-01-01

    Full Text Available Abstract. The aim of this study was to investigate some characteristics of neutrophils and monocytes in patients with acute leukemia, depending on presence of an infectious syndrome, as based on studying of CD16, CD64, HLA-DR receptors, along with assaying myeloperoxidase (MPO and functional activity of the cells. Infectious syndrome in acute leukemia patients was accompanied by changes in antibody-dependent cytotoxicity against neutrophils (decreased CD16 and increase in CD64 expression, lower phagocytic capacity of the cells, and myeloperoxidase deficiency of neutrophils and monocytes. In patients with inflammatory manifestations of infectious syndrome (i.e., acute tonsillitis, bronchitis, pneumonia, etc., the signs of neutrophilic insussiciency were more pronounced, i.e., CD16+ neutrophils comprised 24.36±7.43%, as compared with 74.21±5.43% in controls, p < 0.001; MPO positivity was detected in 29.15±12.6% of the cells against 96.1±1.94% in controls, p < 0.01; MPO expression: 5.34±3.07 MFI, with 32.9±10.76 in controls, p < 0,05. These data suggest significant disturbances of anti-infectious elimination mechanisms.

  6. Effect of Acupressure on Nausea-Vomiting in Patients With Acute Myeloblastic Leukemia.

    Avc, Hatice Sevil; Ovayolu, Nimet; Ovayolu, Özlem

    2016-01-01

    The aim of this study was to assess the effect of acupressure, applied at P6 (Neiguan) acupuncture point, on chemotherapy-induced nausea and vomiting in patients with acute myeloblastic leukemia. This was a randomized controlled trial conducted on patients with myeloblastic leukemia. A total of 90 patients, who received the same chemotherapy regimen and antiemetic therapy, were included in the study as 30 patients in the control group, 30 patients in the band group, and 30 patients in the pressure group. Although acupressure was applied by placing wristbands at P6 acupuncture point of both wrists in patients of the band group for totally 4 days, acupressure was applied with the use of finger pressure in patients of the pressure group for totally 4 days. No intervention was made in patients of the control group other than the routine antiemetic therapy. The data of the study were collected by using a questionnaire and nausea-vomiting chart. Severity of nausea-vomiting was assessed by using the visual analog scale on this chart. It was determined that the acupressure band applied to the patients included in the study reduced number and severity of nausea-vomiting (P acupressure applied with pressure did not affect number and severity of nausea-vomiting (P > .05). It was found that the acupressure band was effective for reducing the chemotherapy-induced nausea and vomiting. PMID:27501207

  7. Acute leukemia in early childhood

    M. Emerenciano

    2007-06-01

    Full Text Available Acute leukemia in early childhood is biologically and clinically distinct. The particular characteristics of this malignancy diagnosed during the first months of life have provided remarkable insights into the etiology of the disease. The pro-B, CD10 negative immunophenotype is typically found in infant acute leukemia, and the most common genetic alterations are the rearrangements of the MLL gene. In addition, the TEL/AML1 fusion gene is most frequently found in children older than 24 months. A molecular study on a Brazilian cohort (age range 0-23 months has detected TEL/AML1+ve (N = 9, E2A/PBX1+ve (N = 4, PML/RARA+ve (N = 4, and AML1/ETO+ve (N = 2 cases. Undoubtedly, the great majority of genetic events occurring in these patients arise prenatally. The environmental exposure to damaging agents that give rise to genetic changes prenatally may be accurately determined in infants since the window of exposure is limited and known. Several studies have shown maternal exposures that may give rise to leukemogenic changes. The Brazilian Collaborative Study Group of Infant Acute Leukemia has found that mothers exposed to dipyrone, pesticides and hormones had an increased chance to give birth to babies with infant acute leukemia [OR = 1.48 (95%CI = 1.05-2.07, OR = 2.27 (95%CI = 1.56-3.31 and OR = 9.08 (95%CI = 2.95-27.96], respectively. This review aims to summarize recent clues that have facilitated the elucidation of the biology of early childhood leukemias, with emphasis on infant acute leukemia in the Brazilian population.

  8. Childhood Acute Lymphoblastic Leukemia

    Pui, Ching-Hon; Yang, Jun J; Hunger, Stephen P;

    2015-01-01

    PURPOSE: To review the impact of collaborative studies on advances in the biology and treatment of acute lymphoblastic leukemia (ALL) in children and adolescents. METHODS: A review of English literature on childhood ALL focusing on collaborative studies was performed. The resulting article was...

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

    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

  10. Mitochondrial DNA alterations of peripheral lymphocytes in acute lymphoblastic leukemia patients undergoing total body irradiation therapy

    2011-01-01

    Background Mitochondrial DNA (mtDNA) alterations, including mtDNA copy number and mtDNA 4977 bp common deletion (CD), are key indicators of irradiation-induced damage. The relationship between total body irradiation (TBI) treatment and mtDNA alterations in vivo, however, has not been postulated yet. The aim of this study is to analyze mtDNA alterations in irradiated human peripheral lymphocytes from acute lymphoblastic leukemia (ALL) patients as well as to take them as predictors for radiatio...

  11. Pathologic rupture of the spleen in a patient with acute myelogenous leukemia and leukostasis

    Gil Cunha De Santis

    2014-07-01

    Full Text Available Rupture of the spleen can be classified as spontaneous, traumatic, or pathologic. Pathologic rupture has been reported in infectious diseases such as infectious mononucleosis, and hematologic malignancies such as acute and chronic leukemias. Splenomegaly is considered the most relevant factor that predisposes to splenic rupture. A 66-year-old man with acute myeloid leukemia evolved from an unclassified myeloproliferative neoplasm, complaining of fatigue and mild upper left abdominal pain. He was pale and presented fever and tachypnea. Laboratory analyses showed hemoglobin 8.3 g/dL, white blood cell count 278 × 109/L, platelet count 367 × 109/L, activated partial thromboplastin time (aPTT ratio 2.10, and international normalized ratio (INR 1.60. A blood smear showed 62% of myeloblasts. The immunophenotype of the blasts was positive for CD117, HLA-DR, CD13, CD56, CD64, CD11c and CD14. Lactate dehydrogenase was 2384 U/L and creatinine 2.4 mg/dL (normal range: 0.7-1.6 mg/dL. Two sessions of leukapheresis were performed. At the end of the second session, the patient presented hemodynamic instability that culminated in circulatory shock and death. The post-mortem examination revealed infiltration of the vessels of the lungs, heart, and liver, and massive infiltration of the spleen by leukemic blasts. Blood volume in the peritoneal cavity was 500 mL. Acute leukemia is a rare cause of splenic rupture. Male gender, old age and splenomegaly are factors associated with this condition. As the patient had leukostasis, we hypothesize that this, associated with other factors such as lung and heart leukemic infiltration, had a role in inducing splenic rupture. Finally, we do not believe that leukapheresis in itself contributed to splenic rupture, as it is essentially atraumatic.

  12. Cytosine arabinoside and daunorubicin induction therapy in a patient with acute myeloid leukemia on chronic hemodialysis.

    Krashin, Eilon; Dolberg, Osnat J; Hellmann, Ilana; Huitema, Alwin D R; Rosing, Hilde; Ellis, Martin

    2016-09-01

    The combination of daunorubicin and cytarabine is the cornerstone of induction therapy for acute myeloid leukemia (AML). Little data are available on the optimal chemotherapy regimen for patients with AML and advanced renal failure, with some authors recommending administration of reduced daunorubicin doses. We report the case of a 54-year-old AML patient on chronic hemodialysis who was treated with a modified induction regimen with reduced-dose daunorubin. Daunorubicin levels were measured during the treatment schedule. Although daunorubicin terminal t1/2 appears to be unaffected in hemodialysis patients, the estimated 0-23 h area under the curve was comparable with that of patients receiving full-dose daunorubicin. Therefore, dose adjustment in this patient group may be prudent. PMID:27254285

  13. Minimal Residual Disease in Acute Myeloid Leukemia

    Ommen, Hans Beier; Nederby, Line; Toft-Petersen, Marie;

    2014-01-01

    This chapter discusses how minimal residual disease (MRD) is detected and managed in acute myeloid leukemia (AML) patients. The most commonly used techniques to detect residual leukemia in patients in complete remission (CR) are quantitative PCR (qPCR) and multicolor flow cytometry (MFC). While q...

  14. Secondary acute non lymphoid leukemia in patients treated for non Hodgkin's lymphoma

    The present study was undertaken to evaluate the frequency, characteristics and actual risk of secondary acute non lymphoid leukemia (s-ANLL) in 141 patients treated for non Hodgkin's lymphoma with different modalities. One hundred and twenty-four patients received chemotherapy according to PROVECIP protocol (9). Of these, 15 also received as induction treatment a local nodal irradiation and 33 an extended field radiotherapy. Seventeen out of 141 were treated by total body irradiation. Of these, 15 relapsed and received salvage chemotherapy. Sixteen of the 124 patients trated with PROVECIP also underwent different chemotherapeutic programs as salvage treatment. Of the entire population studied, 2 patients significantly affected the occurrence of s-ANLL, since both leukemias occurred in patients treated with total body irradiation, given alone or followed by chemotherapy. The actuarial risk at 8 years was 5.24% in the whole group, whereas it greatly increased in the group of patients treated with total body irradiation (24%). Conversely, no risk was found in the group treated with PROVECIP, alone, with additional chemotherapy, or with associated local or extended field radiotherapy

  15. Mixed Pulmonary Infection with Penicillium notatum and Pneumocystis jiroveci in a Patient with Acute Myeloid Leukemia

    Tehrani, Shabnam; Hemmatian, Marjan

    2016-01-01

    Penicillium notatum is a fungus that widely exists in the environment and is often non-pathogenic to humans. However, in immunocompromised hosts it may be recognized as a cause of systemic mycosis. A 44-year-old man with acute myeloid leukemia (AML) was admitted to our hospital with fever and neutropenia. Due to no improvement after initial treatment, he underwent bronchoscopy. The patient was found to have P. notatum and Pneumocystis jiroveci infection, and therefore was given voriconazole, primaquine and clindamycin. The patient was successfully treated and suffered no complications. Conclusion: This case highlights P. notatum as a cause of infection in immunocompromised patients. To the best of our knowledge, mixed lung infection with P. notatum and P. jiroveci in a patient with AML has not been previously reported.

  16. Busulfan and Etoposide Followed by Peripheral Blood Stem Cell Transplant and Low-Dose Aldesleukin in Treating Patients With Acute Myeloid Leukemia

    2015-08-04

    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); Childhood Acute Myeloid Leukemia in Remission; Recurrent Adult Acute Myeloid Leukemia; Recurrent Childhood Acute Myeloid Leukemia

  17. Total Marrow and Lymphoid Irradiation and Chemotherapy Before Donor Stem Cell Transplant in Treating Patients With High-Risk Acute Lymphocytic or Myelogenous Leukemia

    2016-04-07

    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 Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia

  18. Clofarabine or Daunorubicin Hydrochloride and Cytarabine Followed By Decitabine or Observation in Treating Older Patients With Newly Diagnosed Acute Myeloid Leukemia

    2014-09-16

    Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome; 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); Secondary Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

  19. Two Elderly Patients with Philadelphia Chromosome Positive Mixed Phenotype Acute Leukemia Who Were Successfully Treated with Dasatinib and Prednisolone.

    Takata, Hiroyuki; Ikebe, Taichi; Sasaki, Hitohiro; Miyazaki, Yasuhiko; Ohtsuka, Eiichi; Saburi, Yoshio; Ogata, Masao; Shirao, Kuniaki

    2016-01-01

    Philadelphia chromosome positive (Ph+) mixed phenotype acute leukemia (MPAL) is a rare type of acute leukemia having both myeloid and lymphoid features for which no optimal treatment has yet been established. We herein describe two elderly Ph+MPAL patients who achieved molecular remission without any serious adverse events by treatment with dasatinib and prednisolone. Although dasatinib induction therapy combined with prednisolone is known to be a highly effective treatment for Ph+ acute lymphoblastic leukemia, its efficacy for Ph+MPAL has not been shown. The clinical courses of the present cases suggest that combination therapy with dasatinib and prednisolone is a safe and effective therapeutic modality in elderly Ph+MPAL patients. PMID:27150875

  20. Novel management options for adult patients with progressive acute lymphoblastic leukemia: introduction.

    Wang, Eunice S

    2015-06-01

    Acute lymphoblastic leukemia (ALL) is a heterogeneous hematologic malignancy characterized by highly proliferative immature lymphoid cells in the bone marrow and peripheral blood. In adults, ALL accounts for approximately 20% of all adult leukemias. ALL carries a poor prognosis in adults. The 5-year overall survival is 24% in patients ages 40 to 59 years and 18% in patients ages 60 to 69 years. ALL can be grouped into different categories according to its cell lineage (B cell or T cell), the presence or absence of the Philadelphia chromosome, and various cytogenetic and molecular classifications. A main goal of treatment is to allow the patient to achieve a complete remission and to consolidate this remission with either a maintenance regimen or an allogeneic stem cell transplant. Although the overall rate of complete remission following frontline therapy for newly diagnosed ALL is high, the majority of patients experience a disease relapse. In general, the duration of initial complete remission impacts the patient’s prognosis and response to further therapies. Subsequent treatments must balance the goal of achieving a remission with the need for the patient to maintain or improve quality of life. Recently approved agents, such as blinatumomab and vincristine sulfate liposome injection, offer the promise of a second remission that can serve as a bridge to allogeneic stem cell transplant while still maintaining quality of life. A novel approach using adoptive cellular immunotherapy with chimeric antigen receptor (CAR) T cells is associated with extremely robust responses. PMID:26431322

  1. Reduced-intensity conditioning allogeneic hematopoietic-cell transplantation for older patients with acute myeloid leukemia.

    Goyal, Gaurav; Gundabolu, Krishna; Vallabhajosyula, Saraschandra; Silberstein, Peter T; Bhatt, Vijaya Raj

    2016-06-01

    Elderly patients (>60 years) with acute myeloid leukemia have a poor prognosis with a chemotherapy-alone approach. Allogeneic hematopoietic-cell transplantation (HCT) can improve overall survival (OS). However, myeloablative regimens can have unacceptably high transplant-related mortality (TRM) in an unselected group of older patients. Reduced-intensity conditioning (RIC) or nonmyeloablative (NMA) conditioning regimens preserve the graft-versus-leukemia effects but reduce TRM. NMA regimens result in minimal cytopenia and may not require stem cell support for restoring hematopoiesis. RIC regimens, intermediate in intensity between NMA and myeloablative regimens, can cause prolonged myelosuppresion and usually require stem cell support. A few retrospective and prospective studies suggest a possibility of lower risk of relapse with myeloablative HCT in fit older patients with lower HCT comorbidity index; however, RIC and NMA HCTs have an important role in less-fit patients and those with significant comorbidities because of lower TRM. Whether early tapering of immunosuppression, monitoring of minimal residual disease, and post-transplant maintenance therapy can improve the outcomes of RIC and NMA HCT in elderly patients will require prospective trials. PMID:27247754

  2. Metagenomic analysis of bloodstream infections in patients with acute leukemia and therapy-induced neutropenia.

    Gyarmati, P; Kjellander, C; Aust, C; Song, Y; Öhrmalm, L; Giske, C G

    2016-01-01

    Leukemic patients are often immunocompromised due to underlying conditions, comorbidities and the effects of chemotherapy, and thus at risk for developing systemic infections. Bloodstream infection (BSI) is a severe complication in neutropenic patients, and is associated with increased mortality. BSI is routinely diagnosed with blood culture, which only detects culturable pathogens. We analyzed 27 blood samples from 9 patients with acute leukemia and suspected BSI at different time points of their antimicrobial treatment using shotgun metagenomics sequencing in order to detect unculturable and non-bacterial pathogens. Our findings confirm the presence of bacterial, fungal and viral pathogens alongside antimicrobial resistance genes. Decreased white blood cell (WBC) counts were associated with the presence of microbial DNA, and was inversely proportional to the number of sequencing reads. This study could indicate the use of high-throughput sequencing for personalized antimicrobial treatments in BSIs. PMID:26996149

  3. Prognostic Significance of the Lymphoblastic Leukemia-Derived Sequence 1 (LYL1 Gene Expression in Egyptian Patients with Acute Myeloid Leukemia

    Nadia El Menshawy

    2014-06-01

    Full Text Available OBJECTIVE: Aberrant activation of transcription factor genes is the most frequent target of genetic alteration in lymphoid malignancies. The lymphoblastic leukemia-derived sequence 1 (LYL1 gene, which encodes a basic helix-loop helix, was first identified with human T-cell acute leukemia. Recent studies suggest its involvement in myeloid malignancies. We aimed to study the expression percent of oncogene LYL1 in primary and secondary high-risk myeloid leukemia and the impact on prognostic significance in those patients. METHODS: Using quantitative real-time polymerase chain reaction for detection of LYL1 oncogenes, our study was carried out on 39 myeloid leukemia patients including de novo cases, myelodysplastic syndrome (MDS with transformation, and chronic myelogenous leukemia (CML in accelerated and blast crisis, in addition to 10 healthy individuals as the reference control. RESULTS: LYL1 expression was increased at least 2 times compared to the controls. The highest expression of this transcription factor was observed in the MDS cases transformed to acute leukemia at 7.3±3.1, p=0.0011. LYL1 expression was found in 68.2%, 75%, and 77.8% of cases of acute myeloid leukemia, CML crisis, and MDS, respectively. Significant correlation of LYL1 overexpression with some subtypes of French-American-British classification was found. There was, for the first time, significant correlation between the blood count at diagnosis and LYL1 expression (p=0.023, 0.002, and 0.031 for white blood cells, hemoglobin, and platelets, respectively. The rate of complete remission was lower with very high levels of LYL1 expression and the risk of relapse increased with higher levels of LYL1 expression, suggesting an unfavorable prognosis for cases with enhanced expression. CONCLUSION: Overexpression of LYL1 is highly associated with acute myeloid leukemia and shows more expression in MDS with unfavorable prognosis in response to induction chemotherapy. These

  4. Veliparib and Topotecan With or Without Carboplatin in Treating Patients With Relapsed or Refractory Acute Leukemia, High-Risk Myelodysplasia, or Aggressive Myeloproliferative Disorders

    2016-04-05

    Adult Acute Megakaryoblastic Leukemia; Adult Acute Monoblastic Leukemia; Adult Acute Monocytic Leukemia; Adult Acute Myeloid Leukemia With Inv(16)(p13.1q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With Maturation; Adult Acute Myeloid Leukemia With Minimal Differentiation; 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 Myeloid Leukemia Without Maturation; Adult Acute Myelomonocytic Leukemia; Adult Erythroleukemia; Adult Pure Erythroid Leukemia; Chronic Myelomonocytic Leukemia; de Novo Myelodysplastic Syndrome; Essential Thrombocythemia; Hematopoietic and Lymphoid Cell Neoplasm; Philadelphia Chromosome Negative, BCR-ABL1 Positive Chronic Myelogenous Leukemia; Polycythemia Vera; Previously Treated Myelodysplastic Syndrome; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Disease; Secondary Myelodysplastic Syndrome

  5. Addition of Arsenic Trioxide into Induction Regimens Could Not Accelerate Recovery of Abnormality of Coagulation and Fibrinolysis in Patients with Acute Promyelocytic Leukemia.

    Ye Zhang

    Full Text Available All-trans retinoic acid combined to anthracycline-based chemotherapy is the standard regimen of acute promyelocytic leukemia. The advent of arsenic trioxide has contributed to improve the anti-leukemic efficacy in acute promyelocytic leukemia. The objectives of the current study were to evaluate if dual induction by all-trans retinoic acid and arsenic trioxide could accelerate the recovery of abnormality of coagulation and fibrinolysis in patients with acute promyelocytic leukemia.Retrospective analysis was performed in 103 newly-diagnosed patients with acute promyelocytic leukemia. Hemostatic variables and the consumption of component blood were comparably analyzed among patients treated by different induction regimen with or without arsenic trioxide.Compared to patients with other subtypes of de novo acute myeloid leukemia, patients with acute promyelocytic leukemia had lower platelet counts and fibrinogen levels, significantly prolonged prothrombin time and elevated D-dimers (P<0.001. Acute promyelocytic leukemia patients with high or intermediate risk prognostic stratification presented lower initial fibrinogen level than that of low-risk group (P<0.05. After induction treatment, abnormal coagulation and fibrinolysis of patients with acute promyelocytic leukemia was significantly improved before day 10. The recovery of abnormal hemostatic variables (platelet, prothrombin time, fibrinogen and D-dimer was not significantly accelerated after adding arsenic trioxide in induction regimens; and the consumption of transfused component blood (platelet and plasma did not dramatically change either. Acute promyelocytic leukemia patients with high or intermediate risk prognostic stratification had higher platelet transfusion demands than that of low-risk group (P<0.05.Unexpectedly, adding arsenic trioxide could not accelerate the recovery of abnormality of coagulation and fibrinolysis in acute promyelocytic leukemia patients who received all

  6. Influence of Chemotherapy on the Lipid Peroxidation and Antioxidant Status in Patients with Acute Myeloid Leukemia

    Zohreh Sanaat

    2012-07-01

    Full Text Available Chemotherapeutic agents used in patients with cancer cause to generate the enormous amounts of free radicals associated with cell injury. In this study we assess the effects of chemotherapy regimen on oxidant/antioxidant status in patients with acute myeloid leukemia (AML. 38 newly diagnosed patients with acute myeloid leukemia were recruited in this study. All patients received cytarabine and daunorubicin as chemotherapy regimen. Plasma levels of malondialdehyde (MDA, total antioxidant status (TAS, and the levels of erythrocyte activity of superoxide dismutase (SOD and glutathione peroxidase (GPx were determined before chemotherapy and 14 days after chemotherapy with cytarabine and daunorubicin. Plasma MDA concentrations increased significantly (from 2.68±0.89 nmol/L to 3.14±1.29 nmol/L during the 14days post-chemotherapy period (P=0.04. Plasma TAS concentrations changed with chemotherapy from 1.09±0.15 mmol/L to 1.02±0.14 mmol/L with P=0.005. Erythrocyte SOD and GPX activity decreased overtime from 1157.24±543.61 U/g Hb to 984.01±419.09 U/g Hb (P=0.04 and 46.96±13.70 U/g Hb to 41.40±6.44 U/g Hb (P=0.02 respectively. We report here that there is an increase in malondialdehyde levels and a decrease in the levels of antioxidant enzymes and total antioxidant status. This suggests that chemotherapy causes these changes as a result of enormous production of reactive oxygen species in the patients with AML. Antioxidant supplementation must be approached with caution because of the probability of reduction the therapeutic efficacy of these cytotoxic drugs.

  7. CLAG-based induction therapy in previously untreated high risk acute myeloid leukemia patients.

    Seiter, Karen; Ahmed, Nasir; Shaikh, Azfar; Baskind, Paul; Liu, Delong

    2016-07-01

    The CLAG regimen is highly active in patients with relapsed and/or refractory acute myeloid leukemia (AML). We administered CLAG-based chemotherapy to 20 previously untreated AML patients who were poor candidates for standard induction therapy. Responding patients received further CLAG as post-remission therapy followed by additional therapy that was tailored to their AML subtype. Patients were considered poor candidates for standard therapy due to either cardiac disease, prior chemotherapy for another malignancy, prior myeloproliferative disease, or myelodysplastic syndrome that had progressed after hypomethylator therapy. Overall, thirteen patients had a complete response (CR) to the first cycle of therapy (65%), one patient had a CR without platelet recovery, and 3 patients had a partial response (PR). Two of the patients with PR converted to CR after further therapy. The median duration of response has not been reached; the mean duration of response is 36.8 months (95% CI 28.8-44.8 months). Median overall survival (including deaths from all causes) is 29.0 months (95% CI 18.0-46.0 months). Patients with de novo AML had a CR rate of 90.9% and a median overall survival of 38.5 months. CLAG-based therapy is a well-tolerated, efficacious induction strategy in previously-untreated patients with high risk AML. CLAG-based regimens should be studied in a broader group of newly diagnosed AML patients. PMID:27151544

  8. Bacillus cereus septicemia in a patient with acute lymphoblastic leukemia: A case report and review of the literature.

    Chou, Ya-Ling; Cheng, Shin-Nan; Hsieh, Kao-Hsian; Wang, Chih-Chien; Chen, Shyi-Jou; Lo, Wen-Tsung

    2013-08-01

    Bacillus cereus is an aerobic Gram-positive, spore-forming, rod-shaped bacterium that is responsible for foodborne illnesses. We report on a 15-year-old girl with B-cell acute lymphoblastic leukemia, who fell into a somnolent state after presenting with a 12-hour history of fever, muscle soreness, myalgia in both calves, sore throat, and vomiting. Fulminant septicemic syndrome caused by B. cereus was finally identified. The aim of this work is the introduction of B. cereus as a differential diagnosis of sepsis in patients with acute leukemia in induction chemotherapy, to prevent delayed treatment. PMID:23927823

  9. CCAAT/enhancer binding protein a gene expression in Egyptian patients with acute myeloid leukemia

    Background: Transcription factors play a crucial role in myeloid differentiation and lineage determination. Tumor suppressor protein C/EBPa is a key regulator of granulocytic differentiation whose functional inactivation has become a pathophysiological signature of myeloid leukemia. Given the role that CCAAT/enhancer binding protein α (C/EBP α) plays in myelopoiesis, we anticipated that their expression might be disrupted in myeloid neoplasms. Purpose: To estimate the expression of C/EBP α mRNA in patients with acute myeloid leukemia and correlate its expression with the pathogenesis of the disease. Patients and methods: Forty AML patients and 20 age and sex matched healthy controls were included in the study. Blood samples of patients and controls were analyzed for CEBP α mRNA expression by quantitative RT-real time PCR using TaqMan technology and δδct method for calculation of gene expression. Results: Twenty-nine (72.5%) patients out of the 40 showed low expression levels of CEBP α mRNA below the cutoff value with median of 0.19 (range:0-0.87). While eleven (27.5%) patients out of the 40 showed higher expression levels of CEBP α above the cutoff value with median of 1.52 (range: 1.07-2). Seven patients out of the 11 showed higher expression levels of CEBP α mRNA belong to the M3 subtype of AML harboring the t(15;17) PML-RARa translocation. Conclusion: We conclude that the majority of the AML patients analyzed, express low levels of C/EBPa mRN. However, a subset of patients represented by the M3 subtype, express higher levels of C/EBPa

  10. Immunology of infusion reactions in the treatment of patients with acute lymphoblastic leukemia.

    Asselin, Barbara

    2016-07-01

    Infusion reactions are potentially dose-limiting adverse events associated with intravenous administration of several common agents used to treat patients with acute lymphoblastic leukemia. True clinical hypersensitivity reactions are antibody-mediated and can occur only after repeated exposure to an antigen. Conversely, anaphylactoid infusion reactions are nonantibody-mediated and often occur on the initial exposure to a drug. Cytokine-release syndrome comprises a subset of nonantibody-mediated infusion reactions associated with the use of monoclonal antibodies and immune therapies. Clinical symptoms of hypersensitivity reactions and nonantibody-mediated infusion reactions heavily overlap and can be difficult to distinguish in practice. Regardless of the underlying mechanism, any infusion reaction can negatively affect treatment efficacy and patient safety. These events require prompt response, and potentially, modification of subsequent therapy. PMID:27086555

  11. Septic arthritis as the first sign of Candida tropicalis fungaemia in an acute lymphoid leukemia patient

    Vicari Perla

    2003-01-01

    Full Text Available Fungal infections caused by Candida species have increased in incidence during the past two decades in England, North America and Europe. Candidal arthritis is rare in patients who are not intravenous drug users or are who not using a prostheses. We report the case of a 24-year-old man with acute lymphoid leukemia, who developed Candida tropicalis arthritis during an aplastic period after chemotherapy. This is the eighth case described in the literature of C. tropicalis causing arthritis without intra-articular inoculation. We call attention to an unusual first sign of fungal infection: septic arthritis without intra-articular inoculation. However, this case differs from the other seven, since despite therapy a fast and lethal evolution was observed. We reviewed reported cases, incidence, risk factors, mortality and treatment of neutropenic patients with fungal infections.

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

    2016-07-08

    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

  13. Azathioprine-associated acute myeloid leukemia in a patient with Crohn's disease and thiopurine S-methyltransferase deficiency

    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, and...

  14. BAALC and ERG Expression in Egyptian Patients with Acute Myeloid Leukemia, Relation to Survival and Response to Treatment

    Soliman, Aml; Aal, Asmaa Abdel; Afify, Reham; Ibrahim, Noha

    2016-01-01

    AIM: Aim was to detect Brain and Acute Leukemia, Cytoplasmic (BAALC) and ETS-related gene (ERG) expression in patients with acute myeloid leukemia (AML) as well as to study their biologic and prognostic impact on the disease outcome and survival. PATIENTS AND METHODS: The current study was carried out on 44 patients with denovo acute myeloid leukemia, as well as 44 age and sex matched controls. The quantitative real-time reverse transcription-polymerase chain reaction (RT-PCR) assay was performed for estimation of BAALC and ERG expression. RESULTS: The current study was carried out on 44 patients with denovo acute myeloid leukemia, as well as 44 age and sex matched controls. The quantitative real-time reverse transcription-polymerase chain reaction (RT-PCR) assay was performed for estimation of BAALC and ERG expression. BAALC was expressed in 36 (81.82%) of AML cases versus 10 (22.72%) of the control group which was highly statistically significant (P AML. PMID:27335598

  15. Wilms Tumor 1 Gene Mutations in Patients with Cytogenetically Normal Acute Myeloid Leukemia

    Salah Aref

    2014-03-01

    Full Text Available OBJECTIVE: This study aimed to assess the prognostic impact of Wilms tumor 1 (WT1 mutations in cytogenetically normal acute myeloid leukemia (CN-AML among Egyptian patients. METHODS: Exons 1, 2, 3, 7, 8, and 9 of WT1 were screened for mutations in samples from 82 CNAML patients out of 203 newly diagnosed AML patients, of age ranging from 21 to 74 years, using high-resolution capillary electrophoresis. RESULTS: Eleven patients out of 82 (13.41% harbored WT1 mutations. Mutations were detected in exon 7 (n=7, exon 9 (n=2, exon 8 (n=1, and exon 3 (n=1, but not in exons 1 or 2. There was no statistically significant difference between the WT1 mutants and wild types as regards age, sex, French-American-British subtypes, and the prevalence of success of induction remission therapy (p=0.966; 28.6% vs. 29.3%. Patients with WT1 mutations had overall survival lower than patients with the wild type (HR=1.38; 95% CI 4.79-6.86; p=0.004. CONCLUSION: CN-AML patients with WT1 mutations have poor clinical outcome. We recommend molecular testing for WT1 mutations in patients with CN-AML at diagnosis in order to improve risk stratification of those patients.

  16. An Adult Patient with Systemic Mastocytosis and B-Acute Lymphoblastic Leukemia

    Theodoros Iliakis

    2014-01-01

    Full Text Available Mastocytosis is a myeloproliferative neoplasm characterized by clonal expansion of abnormal mast cells, ranging from the cutaneous forms of the disease to mast cell leukemia. In a significant proportion of patients, systemic mastocytosis (SM coexists with another hematologic malignancy, termed systemic mastocytosis with an associated hematologic nonmast cell lineage disorder (SM-AHNMD. Despite the pronounced predominance of concomitant myeloid neoplasms, the much more unusual coexistence of lymphoproliferative diseases has also been reported. Imatinib mesylate (IM has a role in the treatment of SM in the absence of the KITD816V mutation. In the setting of SM-AHNMD, eradicating the nonmast cell malignant clone greatly affects prognosis. We report a case of an adult patient with SM associated with B-lineage acute lymphoblastic leukemia (B-ALL. Three cases of concurrent adult ALL and mastocytosis have been reported in the literature, one concerning SM and two concerning cutaneous mastocytosis (CM, as well as six cases of concomitant CM and ALL in children.

  17. Retrospective review of pediatric patients with acute lymphoblastic leukemia: A single center experience

    Khalid Safoorah

    2010-10-01

    Full Text Available Objective: We reviewed the clinical details and treatment outcome of children with newly diagnosed acute lymphoblastic leukemia (ALL to determine the significance of already established prognostic factors in our patients. Setting: A tertiary care hospital in Karachi, Pakistan. Study Design: This is a retrospective study. Materials and Methods: Children diagnosed with ALL were evaluated over a period of 17 years (January 1, 1989 to December 31, 2006. Data was collected by reviewing the medical records of the patients and the prognostic factors analyzed by us include age, gender, white blood cell count, central nervous system and mediastinal involvement at presentation, morphology and immunophenotype of the blast cells, and response to induction therapy. Results: There were 46 patients diagnosed during the study period and on regular follow-up. Forty five (97.8% of these were in complete remission after 28 days of induction therapy. Thirty patients (65.2% were alive and doing well at the time of study. Of these 30 patients, 26 (86.6% remained relapse free while only four (13.3% had relapsed. The remaining 16 patients (34.7% did not survive including 11 (68.7% who had a relapse. Only significant variables in terms of prognosis were age and ALL phenotype with a P value 0.04 and 0.03 respectively. Conclusion: We found that ALL is a frequent childhood hematological malignancy in our setting and is more prevalent in males and children less than ten years of age. Age and leukemia phenotype emerged as the important prognostic factors in pediatric ALL in our patients.

  18. Favorable outcome of hepatosplenic candidiasis in a patient with acute leukemia

    Čolović Nataša

    2015-01-01

    Full Text Available Introduction. Acute leukemias treatment requires strong chemotherapy. Patients that develop bone marrow aplasia become immunocompromised, thus becoming liable to bacterial and fungal infections. Fungal infections caused by Candida are frequent. Hepatosplenic candidiasis (HSC is a frequent consequence of invasive candidiasis which is clinically presented with prolonged febrility unresponsive to antibiotics. Case Outline. A 53-year-old patient with acute myeloid leukemia was submitted to standard chemotherapy “3+7” regimen (daunoblastine 80 mg i.v. on days 1 to 3, cytarabine 2Ч170 mg i.v. during 7 days and achieved complete remission. However, during remission he developed febrility unresponsive to antibiotics. Computerised tomography (CT of the abdomen showed multiple hypodense lesions within the liver and spleen. Haemocultures on fungi were negative. However, seroconversion of biomarkers for invasive fungal infection (IFI (Candida and Aspergillus antigen/Ag and antibody/Ab indicated possible HSC. Only high positivity of anti-Candida IgG antibodies, positivity of mannan and CT finding we regarded sufficient for the diagnosis and antimycotic therapy. Three months of treatment with different antimycotics were necessary for complete disappearance of both clinical symptoms and CT findings. Conclusion. In patients with prolonged febrile neutropenia IFI has to be strongly suspected. If imaging techniques show multiple hypodense lesions within liver and spleen, HSC has to be taken seriously into consideration. We believe that, along with CT finding, positive laboratory Candida biomarkers (mannan and IgG antibodies should be considered sufficient for “probable HSC” and commencement of antifungal therapy, which must be long enough, i.e. until complete disappearance of clinical symptoms and CT findings are achieved. [Projekat Ministarstva nauke Republike Srbije, br. OI 175034

  19. Transient Appearance of Blasts in Peripheral Smear in Paediatric Patient with Acute Aleukemic Leukemia

    Vaghasiya Viren L; Parikh Hina S; Patel Divyesh V; Taviad Dilip S

    2012-01-01

    Acute leukemia can present as leukemic blast in peripheral blood & bone marrow or in some cases in only in bone marrow. Here we present unique case of paediatric acute leukaemia which shows blast cells in peripheral blood transiently and without any definitive treatment blast cell disappear from peripheral blood. So diagnosis made previously was questioned, but later on when bone marrow examination was performed it turn out to be acute leukaemia. We haven’t found any reference o...

  20. CEBPA mutations in patients with de novo acute myeloid leukemia: data analysis in a Chinese population

    Su L

    2016-06-01

    Full Text Available Long Su, SuJun Gao, XiaoLiang Liu, YeHui Tan, Lu Wang, Wei Li Cancer Center, The First Hospital, Jilin University, Changchun, People’s Republic of China Background: This study was aimed to explore the clinical characteristics and prognoses of acute myeloid leukemia (AML patients with CEBPA mutations. Patients and methods: Three hundred and forty-five patients with de novo AML were retrospectively analyzed with regard to CEBPA mutations, clinical characteristics, therapeutic responses, and long-term outcomes. Results: CEBPA mutations were detected in 59 patients (17.10%, with 47 cases harboring double mutations and 12 cases harboring single mutations. In those with a normal karyotype (NK, 44 cases (25.29% were detected with CEBPA mutations. The following characteristics were observed in CEBPA-mutated patients: most (66.10% of them were M1 or M2; they presented with higher peripheral white blood cell counts (23.71 [12.6, 60.02] ×109/L versus 7.34 [2.38, 26.63] ×109/L; u=4.944, P<0.001 and higher hemoglobin levels (89.64±23.05 g/L versus 75.65±23.65 g/L; t=4.156, P<0.001 than those observed in patients without the mutation; and the expression of CD7 and HLA-DR was higher, whereas that of CD34 and CD56 was lower in patients with the mutation than in those without the mutation. Compared with those without the mutation, patients with CEBPA mutations had a superior complete remission rate (75.0% versus 56.54%; χ2=6.185, P=0.013 and superior overall survival (P=0.034. Conclusion: The frequency of CEBPA mutations may be higher in Chinese patients with AML than has been reported in populations of western countries, and the presence of CEBPA mutations is an indication of favorable prognoses for these patients. Keywords: acute myeloid leukemia, CEBPA mutations, immunophenotype, complete remission, long-term prognoses

  1. Radiolabeled BC8 Antibody, Busulfan, Cyclophosphamide Followed by Donor Stem Cell Transplant in Treating Patients With Acute Myelogenous Leukemia in First Remission

    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)

  2. Acute promyelocytic leukemia after whole brain irradiation of primary brain lymphomainan HIV-infected patient

    Boban A

    2009-01-01

    Full Text Available Abstract The occurrence of acute promyelocytic leukemia (APL in HIV-infected patients has been reported in only five cases. Due to a very small number of reported HIV/APL patients who have been treated with different therapies with the variable outcome, the prognosis of APL in the setting of the HIV-infection is unclear. Here, we report a case of an HIV-patient who developed APL and upon treatment entered a complete remission. A 25-years old male patient was diagnosed with HIV-infection in 1996, but remained untreated. In 2004, the patient was diagnosed with primary central nervous system lymphoma. We treated the patient with antiretroviral therapy and whole-brain irradiation, resulting in complete remission of the lymphoma. In 2006, prompted by a sudden neutropenia, we carried out a set of diagnostic procedures, revealing APL. Induction therapy consisted of standard treatment with all-trans-retinoic-acid (ATRA and idarubicin. Subsequent cytological and molecular analysis of bone marrow demonstrated complete hematological and molecular remission. Due to the poor general condition, consolidation treatment with ATRA was given in March and April 2007. The last follow-up 14 months later, showed sustained molecular APL remission. In conclusion, we demonstrated that a complete molecular APL remission in an HIV-patient was achieved by using reduced-intensity treatment.

  3. Allogeneic hematopoietic stem cell transplantation for adult patients with mixed phenotype acute leukemia: results of a matched-pair analysis.

    Shimizu, Hiroaki; Saitoh, Takayuki; Machida, Shinichiro; Kako, Shinichi; Doki, Noriko; Mori, Takehiko; Sakura, Toru; Kanda, Yoshinobu; Kanamori, Heiwa; Miyawaki, Shuichi; Okamoto, Shinichiro

    2015-11-01

    Adult patients with mixed phenotype acute leukemia (MPAL) have a poor prognosis, and the therapeutic role of allogeneic stem cell transplantation (allo-SCT) for MPAL remains to be elucidated. Thus, we retrospectively assessed the efficacy of allo-SCT for MPAL. Eighteen patients with MPAL were identified from the transplant outcome database of Kanto Study Group for Cell Therapy (KSGCT). We also selected 215 patients with acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) as control cohorts using an optimal matching method. The 5-yr overall survival (OS) rate of patients with MPAL was 48.1%, and patients in remission at the time of transplant showed significantly better survival than those not in remission (5-yr OS: 71.8% vs. 0%, P = 0.001). No significant differences were seen in OS when stratifying patients according to immunophenotype, cytogenetic abnormalities, or the type of induction therapy. The 5-yr OS rate of patients with MPAL was not significantly different compared with AML control patients (48.1% vs. 48.1%; P = 0.855) or ALL control patients (48.1% vs. 37.8%; P = 0.426). These results suggested that allo-SCT is an effective treatment for MPAL, especially early in the disease course, and innovative transplant approaches are warranted to improve the transplant outcome of patients with MPAL who are not in remission. PMID:25605541

  4. Clofarabine doubles the response rate in older patients with acute myeloid leukemia but does not improve survival

    Burnett, Alan K.; RUSSELL, NIGEL H; Hunter, Ann E.; Milligan, Donald; Knapper, Steven; Wheatley, Keith; Yin, John; McMullin, Mary F.; Ali, Sahra; Bowen, David; Hills, Robert K.

    2013-01-01

    Better treatment is required for older patients with acute myeloid leukemia (AML) not considered fit for intensive chemotherapy. We report a randomized comparison of lowdose Ara-C (LDAC) vs the novel nucleoside, clofarabine, in untreated older patients with AML and high-risk myelodysplastic syndrome (MDS). A total of 406 patients with de novo (62%), secondary disease (24%), or high-risk MDS (>10% marrow blasts) (15%), median age 74 years, were randomized to LDAC 20 mg twice daily for 10 da...

  5. Clinical characteristics and outcomes of patients with acute myelogenous leukemia admitted to intensive care: a case-control study

    Roze des Ordons, Amanda L; Chan, Kris; Mirza, Imran; Townsend, Derek R; Bagshaw, Sean M

    2010-01-01

    Background There is limited epidemiologic data on patients with acute myelogenous (myeloid) leukemia (AML) requiring life-sustaining therapies in the intensive care unit (ICU). Our objectives were to describe the clinical characteristics and outcomes in critically ill AML patients. Methods This was a retrospective case-control study. Cases were defined as adult patients with a primary diagnosis of AML admitted to ICU at the University of Alberta Hospital between January 1st 2002 and June 30th...

  6. 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

    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

  7. Frequency and Prognostic Relevance of FLT3 Mutations in Saudi Acute Myeloid Leukemia Patients

    Ghaleb Elyamany

    2014-01-01

    Full Text Available The Fms-like tyrosine kinase-3 (FLT3 is a receptor tyrosine kinase that plays a key role in cell survival, proliferation, and differentiation of hematopoietic stem cells. Mutations of FLT3 were first described in 1997 and account for the most frequent molecular mutations in acute myeloid leukemia (AML. AML patients with FLT3 internal tandem duplication (ITD mutations have poor cure rates the prognostic significance of point mutations; tyrosine kinase domain (TKD is still unclear. We analyzed the frequency of FLT3 mutations (ITD and D835 in patients with AML at diagnosis; no sufficient data currently exist regarding FLT3 mutations in Saudi AML patients. This study was aimed at evaluating the frequency of FLT3 mutations in patients with AML and its significance for prognosis. The frequency of FLT3 mutations in our study (18.56% was lower than many of the reported studies, FLT3-ITD mutations were observed in 14.4%, and FLT3-TKD in 4.1%, of 97 newly diagnosed AML patients (82 adult and 15 pediatric. Our data show significant increase of FLT3 mutations in male more than female (13 male, 5 female. Our results support the view that FLT3-ITD mutation has strong prognostic factor in AML patients and is associated with high rate of relapse, and high leucocytes and blast count at diagnosis and relapse.

  8. Treatment of Acute Myeloid Leukemia in Elderly Patients-A Therapeutic Dilemma.

    Mamdani, Hirva; Santos, Cedric Dos; Konig, Heiko

    2016-07-01

    Older adults represent the majority of approximately 20,000 new patients diagnosed with acute myeloid leukemia (AML) in the United States each year. While the treatment goal for younger patients is to achieve a cure with intensive therapeutic protocols, including standard chemotherapy and hematopoietic stem cell transplantation, these goals are less well defined in the elderly population. This is in part due to the continuous decline in treatment outcomes with increasing age secondary to a number of patient-related and disease-specific factors, ranging from the presence of comorbid conditions to the higher frequency of adverse cytogenetic and unfavorable molecular markers. Although best supportive care, low-dose cytarabine, and epigenetic drugs represent well recognized treatment concepts, no universally accepted strategy for the management of elderly patients with AML exists. Therapeutic decisions are widely based on the patient's age, general health, the disease features, as well as the patient's personal wishes. The predicament of treating AML in the elderly population is the central theme of this review. PMID:27073039

  9. Immunocompetent cell functions in Ph+ acute lymphoblastic leukemia patients on prolonged Imatinib maintenance treatment.

    Maggio, Roberta; Peragine, Nadia; De Propris, Maria Stefania; Vitale, Antonella; Elia, Loredana; Calabrese, Elisabetta; Della Starza, Irene; Intoppa, Stefania; Milani, Maria Laura; Guarini, Anna; Foà, Robin

    2011-04-01

    Imatinib mesylate (Imatinib) is a potent inhibitor of defined tyrosine kinases and is effectively used for the treatment of malignancies characterized by the constitutive activation of these tyrosine kinases, such as Philadelphia chromosome-positive (Ph(+)) leukemias and gastrointestinal stromal tumors. Suppressive as well as stimulating effects of this drug on T lymphocytes or dendritic cells (DC), which play a major role in immune tumor surveillance, have been reported. For this reason, we questioned whether Imatinib could also affect the phenotypic and functional properties of these subpopulations in Ph(+) acute lymphoblastic leukemia (ALL) patients on prolonged Imatinib maintenance treatment. Circulating T lymphocytes and NK cells from Imatinib-treated Ph(+) ALL patients showed a subset distribution comparable to that of healthy donors. In addition, T-cell immunomodulant cytokine production (IFN-γ, TNF-α) and proliferative responses were not impaired. A normal monocyte-derived DC differentiation and apoptotic body loading capacity was also observed in the majority of Imatinib-treated patients. In contrast, an impairment in the DC intracellular production of IL-12 was recorded, although this was not observed when normal DC were exposed in vitro to Imatinib. Finally, in vivo Imatinib treatment did not affect the T-lymphocyte proliferation and IFN-γ production induced by leukemic apoptotic body-loaded DC, underling the potential capability of these cells to generate a specific immune response against tumoral antigens. Taken together, these findings provide evidence that immunotherapeutic approaches aimed at controlling residual disease in Ph(+) ALL patients in hematologic remission are not jeopardized by the long-term administration of Imatinib. PMID:21240485

  10. Antigen Expression on Blast Cells and Hematological Parameters at Presentation in Acute Lymphoblastic Leukemia Patients

    Objective: To analyze the expression of various antigens on the leukemic blasts and to determine the hematological parameters, in Acute Lymphoblastic Leukemia (ALL) patients at presentation. Study Design: Observational study. Place and Duration of Study: King Edward Medical University, Lahore and Hameed Latif Hospital, Lahore, from February 2013 to March 2014. Methodology: A total of 50 newly diagnosed and untreated patients of ALL were selected from Mayo Hospital and Hameed Latif Hospital. These patients included both genders and all age groups. Hemoglobin, total leukocyte count and platelet count were determined on hematology analyser-Sysmex-Kx-2I. Blast cell percentage was estimated on Giemsa stained blood smears. Immuno phenotyping was done on bone marrow samples by 5 colour flow cytometery on Beckman Counter Navious Flow cytometer. An acute leukemia panel of 23 antibodies was used. The data was entered and analyzed in SPSS version 22. Results: Of the 50 ALL patients, 36 (72 percentage) were B-ALL and 14 (28 percentage) T-ALL. There were 18 (36 percentage) children and 32 (64 percentage) adults. T-ALL included 22 percentage of the childhood and 31 percentage of the adult cases. Immuno phenotypic analysis showed that CD19, CD79a and CD20 were B-lineage specific markers whereas cCD3, CD3 and CD5 were T-lineage specific. CD10 was the most sensitive marker for B-ALL and CD7 was the most sensitive marker of T-ALL. TdT was expressed in 92 percentage B-ALL and 71 percentage T-ALL cases, CD34 in 58 percentage and 43 percentage cases and CD45 in 83 percentage and 100 percentage respectively. High leukocyte count (> 50 x 109/L) was present in 58 percentage cases. Hemoglobin was < 10 g/dl in 74 percentage patients and platelet count was below 20 x 109/Lin 12 percentage patients. Leukocyte count, hemoglobin, platelet count and blast cell percentage did not show a significant difference in the two ALL immuno types. Conclusion: The frequency of T-ALL is higher in childhood

  11. Acute Myeloid Leukemia Presenting as Acute Appendicitis

    Sherri Rauenzahn

    2013-01-01

    Full Text Available Appendicitis in leukemic patients is uncommon but associated with increased mortality. Additionally, leukemic cell infiltration of the appendix is extremely rare. While appendectomy is the treatment of choice for these patients, diagnosis and management of leukemia have a greater impact on remission and survival. A 59-year-old Caucasian female was admitted to the surgical service with acute right lower quadrant pain, nausea, and anorexia. She was noted to have leukocytosis, anemia, and thrombocytopenia. Abdominal imaging demonstrated appendicitis with retroperitoneal and mesenteric lymphadenopathy for which she underwent laparoscopic appendectomy. Peripheral smear, bone marrow biopsy, and surgical pathology of the appendix demonstrated acute myeloid leukemia (AML with nonsuppurative appendicitis. In the setting of AML, prior cases described the development of appendicitis with active chemotherapy. Of these cases, less than ten patients had leukemic infiltration of the appendix, leading to leukostasis and nonsuppurative appendicitis. Acute appendicitis with leukemic infiltration as the initial manifestation of AML has only been described in two other cases in the literature with an average associated morbidity of 32.6 days. The prompt management in this case of appendicitis and AML resulted in an overall survival of 185 days.

  12. Thyroid-Like Follicular Carcinoma of the Kidney in a Young Patient with History of Pediatric Acute Lymphoblastic Leukemia

    William W. Wu

    2014-01-01

    Full Text Available Thyroid-like follicular carcinoma of the kidney (TLFCK is a rare histological variant of renal cell carcinoma not currently included in the World Health Organization classification of renal tumors. Only 24 previous cases of TLFCK have been reported to date. We report a case of TLFCK in a 19-year-old woman with history of pediatric acute lymphoblastic leukemia. This patient is the youngest with TLFCK to be reported to date and the first with history of lymphoblastic leukemia. The development of TLFCK in a young patient with history of lymphoblastic leukemia is interesting and suggests that genes involved in leukemogenesis may also be important for TLFCK pathogenesis. Recognition of TLFCK is important to distinguish it from other conditions that show thyroid-like features, as a misdiagnosis can result in adverse patient care.

  13. Psychological Impact of Chemotherapy for Childhood Acute Lymphoblastic Leukemia on Patients and Their Parents.

    Sherief, Laila M; Kamal, Naglaa M; Abdalrahman, Hadel M; Youssef, Doaa M; Abd Alhady, Mohamed A; Ali, Adel S A; Abd Elbasset, Maha Aly; Hashim, Hiatham M

    2015-12-01

    To assess the self-esteem of pediatric patients on chemotherapy for acute lymphoblastic leukemia (ALL) and psychological status of their parents.The psychological status of 178 children receiving chemotherapy for ALL and their parents was assessed using parenting stress index (PSI) to determine the degree of stress the parents are exposed to using parent's and child's domains. Self-esteem Scale was used to determine the psychological status of patients.The study revealed significant low level of self-esteem in 84.83% of patients. Their parents had significant psychological stress. PSI was significantly associated with parents' low sense of competence, negative attachment to their children, feeling of high restriction, high depression, poor relation to spouse, high social isolation variables of parent's domains. It was significantly associated with low distraction, negative parents' reinforcement, low acceptability, and high demanding variables of child's domains. Long duration of disease was the most detrimental factor among demographic data of the patients.Chemotherapy for ALL has a significant impact on the psychological status of both patients and their parents with high prevalence of low self-esteem in children and high degree of stress in their parents. PMID:26705211

  14. Outpatient care of patients with acute myeloid leukemia: Benefits, barriers, and future considerations.

    Vaughn, Jennifer E; Buckley, Sarah A; Walter, Roland B

    2016-06-01

    Patients with acute myeloid leukemia (AML) who receive intensive induction or re-induction chemotherapy with curative intent typically experience prolonged cytopenias upon completion of treatment. Due to concerns regarding infection and bleeding risk as well as significant transfusion and supportive care requirements, patients have historically remained in the hospital until blood count recovery-a period of approximately 30 days. The rising cost of AML care has prompted physicians to reconsider this practice, and a number of small studies have suggested the safety and feasibility of providing outpatient supportive care to patients following intensive AML (re-) induction therapy. Potential benefits include a significant reduction of healthcare costs, improvement in quality of life, and decreased risk of hospital-acquired infections. In this article, we will review the currently available literature regarding this practice and discuss questions to be addressed in future studies. In addition, we will consider some of the barriers that must be overcome by institutions interested in implementing an "early discharge" policy. While outpatient management of selected AML patients appears safe, careful planning is required in order to provide the necessary support, education and rapid management of serious complications that occur among this very vulnerable patient population. PMID:27101148

  15. Prognostic factors in acute promyelocytic leukemia: strategies to define high-risk patients.

    Testa, Ugo; Lo-Coco, Francesco

    2016-04-01

    All trans retinoic acid (ATRA) has revolutionized the therapy of acute promyelocytic leukemia (APL). Treatment of this leukemia with ATRA in combination with chemotherapy has resulted in complete remission rates >90 % and long-term remission rates above 80 %. Furthermore, the combination of ATRA and arsenic trioxide (ATO) was shown to be safe and effective in frontline treatment and, for patients with low and intermediate risk disease, possibly superior to the standard ATRA and anthracycline-based regimen. However, in spite of this tremendous progress, APL still remains associated with a high incidence of early death due to the frequent occurrence of an abrupt bleeding diathesis. This hemorrhagic syndrome more frequently develops in high-risk APL patients, currently defined as those exhibiting >10 × 10(9)/L WBC at presentation. In addition to high WBC count, other molecular and immunophenotypic features have been associated with high-risk APL. Among them, the expression in APL blasts of the stem/progenitor cell antigen CD34, the neural adhesion molecule (CD56), and the T cell antigen CD2 help to identify a subset of patients at higher risk of relapse and often the expression of these markers is associated with high WBC count. At the molecular level, the short PML/RARA isoform and FLT3-internal tandem duplication (ITD) mutations have been associated with increased relapse risk. These observations indicate that extended immunophenotypic and molecular characterization of APL at diagnosis including evaluation of CD2, CD56, and CD34 antigens and of FLT3 mutations may help to better design risk-adapted treatment in this disease. PMID:26920716

  16. Comparison of Newly Diagnosed and Relapsed Patients with Acute Promyelocytic Leukemia Treated with Arsenic Trioxide: Insight into Mechanisms of Resistance

    Ezhilarasi Chendamarai; Saravanan Ganesan; Ansu Abu Alex; Vandana Kamath; Nair, Sukesh C.; Arun Jose Nellickal; Nancy Beryl Janet; Vivi Srivastava; Kavitha M Lakshmi; Auro Viswabandya; Aby Abraham; Mohammed Aiyaz; Nandita Mullapudi; Raja Mugasimangalam; Rose Ann Padua

    2015-01-01

    There is limited data on the clinical, cellular and molecular changes in relapsed acute promyeloytic leukemia (RAPL) in comparison with newly diagnosed cases (NAPL). We undertook a prospective study to compare NAPL and RAPL patients treated with arsenic trioxide (ATO) based regimens. 98 NAPL and 28 RAPL were enrolled in this study. RAPL patients had a significantly lower WBC count and higher platelet count at diagnosis. IC bleeds was significantly lower in RAPL cases (P=0.022). The ability of...

  17. Speciation of arsenic trioxide metabolites in peripheral blood and bone marrow from an acute promyelocytic leukemia patient

    Iriyama Noriyoshi; Yoshino Yuta; Yuan Bo; Horikoshi Akira; Hirabayashi Yukio; Hatta Yoshihiro; Toyoda Hiroo; Takeuchi Jin

    2012-01-01

    Abstract Background Speciation of arsenic trioxide (ATO) metabolites in clinical samples such as peripheral blood (PB) from acute promyelocytic leukemia (APL) patients has been conducted. However, speciation of arsenicals in bone marrow (BM) has not yet been performed. Profiles of arsenic speciation in plasma of BM were thus investigated and compared with those of PB plasma from a relapsed APL patient. The total arsenic concentrations in high molecular weight fraction (HMW-F) of BM and PB pla...

  18. Impact of invasive fungal disease on the chemotherapy schedule and event-free survival in acute leukemia patients who survived fungal disease: a case-control study

    Even, Caroline; Bastuji-Garin, Sylvie; Hicheri, Yosr; Pautas, Cécile; Botterel, Francoise; Maury, Sébastien; Cabanne, Ludovic; Bretagne, Stéphane; Cordonnier, Catherine

    2010-01-01

    Patients with acute leukemia who initially survive invasive fungal disease must receive chemotherapy or go on to transplant. Many centers change subsequent chemotherapy to decrease the risk of fungal reactivation. This case-control study compared acute leukemia patients (n=28) who developed a proven or probable fungal disease and survived four weeks later, to patients who did not (n=78), and assessed the impact of fungal disease on the chemotherapy regimens, and overall and event-free survival.

  19. Hematopoietic stem cell transplantation with conditioning regimens containing melphalan in pediatric patients with acute lymphoblastic leukemia

    A multicenter comparative study was carried out to investigate the efficacy and safety of hematopoietic stem cell transplantation with conditioning regimens containing melphalan in pediatric patients with acute lymphoblastic leukemia. One hundred twenty three patients at a variety of remission stages were eligible for study participation. Eighty-nine were transplanted with allogeneic grafts and 34 patients with autologous grafts (23 cases with bone marrow and 11 cases with peripheral blood stem cells). Conditioning regimens used were as follows: melphalan and busulfan for 40 patients, melphalan, busulfan and TBI for 44 patients, other regimens for 39 patients. To accelerate engraftment G-CSF (lenograstim) was administered as a 1-hour or 24-hour drip infusion daily at 5 μg/kg from day 5 until hematological recovery. The five year disease free survival (DFS) was 63% for 42 patients at CR1, 41% for 41 patients at CR2 and 33% for 40 patients at other stages. There was no significant difference in the DFS between allogeneic-transplantation and autologous-transplantation in all disease stages. In patients at remission stage for CR1 and CR2, the 5-year DFS by conditioning regimen was 63% for regimen with melphalan and busulfan, 54% for regimen with melphalan, busulfan and TBI and 54% for regimens with melphalan and TBI. There was no significant difference in the DFS between the groups. Serious complications such as renal failure were observed in 11%, veno-occlusive disease in 9%, and interstitial pneumonia in 9%. The most dominating cause of death was relapse in the disease (48% of deaths) which was most commonly observed in autologous transplantation. Contrary to that, treatment related toxic death was the most frequent cause of deaths in allogeneic-transplantation. (author)

  20. Hematopoietic stem cell transplantation with conditioning regimens containing melphalan in pediatric patients with acute lymphoblastic leukemia

    Matsuyama, Takaharu; Kato, Koji [Nagoya First Red Cross Hospital (Japan). Children' s Medical Center; Hanada, Ryoji [Saitama Children' s Medical Center, Iwatsuki (Japan)] [and others

    2002-07-01

    A multicenter comparative study was carried out to investigate the efficacy and safety of hematopoietic stem cell transplantation with conditioning regimens containing melphalan in pediatric patients with acute lymphoblastic leukemia. One hundred twenty three patients at a variety of remission stages were eligible for study participation. Eighty-nine were transplanted with allogeneic grafts and 34 patients with autologous grafts (23 cases with bone marrow and 11 cases with peripheral blood stem cells). Conditioning regimens used were as follows: melphalan and busulfan for 40 patients, melphalan, busulfan and TBI for 44 patients, other regimens for 39 patients. To accelerate engraftment G-CSF (lenograstim) was administered as a 1-hour or 24-hour drip infusion daily at 5 {mu}g/kg from day 5 until hematological recovery. The five year disease free survival (DFS) was 63% for 42 patients at CR1, 41% for 41 patients at CR2 and 33% for 40 patients at other stages. There was no significant difference in the DFS between allogeneic-transplantation and autologous-transplantation in all disease stages. In patients at remission stage for CR1 and CR2, the 5-year DFS by conditioning regimen was 63% for regimen with melphalan and busulfan, 54% for regimen with melphalan, busulfan and TBI and 54% for regimens with melphalan and TBI. There was no significant difference in the DFS between the groups. Serious complications such as renal failure were observed in 11%, veno-occlusive disease in 9%, and interstitial pneumonia in 9%. The most dominating cause of death was relapse in the disease (48% of deaths) which was most commonly observed in autologous transplantation. Contrary to that, treatment related toxic death was the most frequent cause of deaths in allogeneic-transplantation. (author)

  1. Cytokines, growth, and environment factors in bone marrow plasma of acute lymphoblastic leukemia pediatric patients

    Kováč, M.; Vášková, M.; Petráčková, Denisa; Pelková, V.; Mejstříková, E.; Kalina, T.; Žaliová, M.

    2014-01-01

    Roč. 25, č. 1 (2014), s. 8-13. ISSN 1148-5493 R&D Projects: GA MZd NR9531 Institutional support: RVO:61388971 Keywords : pediatric acute lymphoblastic leukemia * bone marrow plasma * cytokine Subject RIV: CE - Biochemistry Impact factor: 1.960, year: 2014

  2. Pretransplant HLA mistyping in diagnostic samples of acute myeloid leukemia patients due to acquired uniparental disomy

    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

  3. DNA methylation for subtype classification and prediction of treatment outcome in patients with childhood acute lymphoblastic leukemia

    Milani, Lili; Lundmark, Anders; Kiialainen, Anna; Nordlund, Jessica; Flaegstad, Trond; Forestier, Erik; Heyman, Mats; Jonmundsson, Gudmundur; Kanerva, Jukka; Schmiegelow, Kjeld; Söderhäll, Stefan; Gustafsson, Mats; Lönnerholm, Gudmar; Syvänen, Ann-Christine

    2010-01-01

    Despite improvements in the prognosis of childhood acute lymphoblastic leukemia (ALL), subgroups of patients would benefit from alternative treatment approaches. Our aim was to identify genes with DNA methylation profiles that could identify such groups. We determined the methylation levels of 1320...... ALL and gene sets that discriminated between subtypes of ALL and between ALL and controls in pairwise classification analyses. We also identified 20 individual genes with DNA methylation levels that predicted relapse of leukemia. Thus, methylation analysis should be explored as a method to improve...

  4. HLA-G expression on blasts and tolerogenic cells in patients affected by acute myeloid leukemia.

    Locafaro, Grazia; Amodio, Giada; Tomasoni, Daniela; Tresoldi, Cristina; Ciceri, Fabio; Gregori, Silvia

    2014-01-01

    Human Leukocyte Antigen-G (HLA-G) contributes to cancer cell immune escape from host antitumor responses. The clinical relevance of HLA-G in several malignancies has been reported. However, the role of HLA-G expression and functions in Acute Myeloid Leukemia (AML) is still controversial. Our group identified a subset of tolerogenic dendritic cells, DC-10 that express HLA-G and secrete IL-10. DC-10 are present in the peripheral blood and are essential in promoting and maintaining tolerance via the induction of adaptive T regulatory (Treg) cells. We investigated HLA-G expression on blasts and the presence of HLA-G-expressing DC-10 and CD4(+) T cells in the peripheral blood of AML patients at diagnosis. Moreover, we explored the possible influence of the 3' untranslated region (3'UTR) of HLA-G, which has been associated with HLA-G expression, on AML susceptibility. Results showed that HLA-G-expressing DC-10 and CD4(+) T cells are highly represented in AML patients with HLA-G positive blasts. None of the HLA-G variation sites evaluated was associated with AML susceptibility. This is the first report describing HLA-G-expressing DC-10 and CD4(+) T cells in AML patients, suggesting that they may represent a strategy by which leukemic cells escape the host's immune system. Further studies on larger populations are required to verify our findings. PMID:24741612

  5. The prognostic value of hematogones in patients with acute myeloid leukemia.

    Chantepie, Sylvain P; Parienti, Jean-Jacques; Salaun, Véronique; Benabed, Khaled; Cheze, Stéphane; Gac, Anne-Claire; Johnson-Ansah, Hyacinthe; Macro, Margaret; Damaj, Gandhi; Vilque, Jean-Pierre; Reman, Oumedaly

    2016-06-01

    In acute myeloid leukemia (AML), new prognostic tools are needed to assess the risk of relapse. Hematogones (HGs) are normal B-lymphocyte precursors that increase in hematological diseases and may influence remission duration in AML. HG detection was prospectively investigated in 262 AML patients to determine its prognostic value. Flow cytometric HG detection was performed in bone marrow aspiration after intensive chemotherapy at the time of hematological recovery. Patients with HGs in bone marrow samples had a significantly better relapse-free survival (RFS) and overall survival (OS) than patients without HGs (P = 0.0021, and P = 0.0016). Detectable HGs independently predicted RFS (HR = 0.61, 95%CI: 0.42 - 0.89, P = 0.012) and OS (HR = 0.59, 95%CI: 0.38 - 0.92, 0.019) controlling for age, ELN classification, the number of chemotherapy cycles to achieve CR, performance status, secondary AML and flow cytometric minimal residual disease (MRD). In intensively treated AML, individual determination of HGs could be useful to stratify the optimal risk-adapted therapeutic strategy after induction chemotherapy. Am. J. Hematol. 91:566-570, 2016. © 2016 Wiley Periodicals, Inc. PMID:26934680

  6. Patient-derived acute myeloid leukemia (AML) bone marrow cells display distinct intracellular kinase phosphorylation patterns

    Multiparametric analyses of phospho-protein activation in patients with acute myeloid leukemia (AML) offers a quantitative measure to monitor the activity of novel intracellular kinase (IK) inhibitors. As recent clinical investigation with FMS-like tyrosine-3 inhibitors demonstrated, targeting IK with selective inhibitors can have a modest clinical benefit. Because multiple IKs are active in patients with AML, multikinase inhibitors may provide the necessary inhibition profile to achieve a more sustained clinical benefit. We here describe a method of assessing the activation of several IKs by flow cytometry. In 40 different samples of patients with AML we observed hyper-activated phospho-proteins at baseline, which is modestly increased by adding stem cell factor to AML cells. Finally, AML cells had a significantly different phospho-protein profile compared with cells of the lymphocyte gate. In conclusion, our method offers a way to determine the activation status of multiple kinases in AML and hence is a reliable assay to evaluate the pharmacodynamic activity of novel multikinase inhibitors

  7. Clinical significance of P53 and Bcl-2 in acute myeloid leukemia patients of Eastern India

    Geetaram Sahu

    2011-11-01

    Full Text Available The frequency of p53 and Bcl-2 protein expression in 100 newly diagnosed and 10 relapsed acute myeloid leukemia (AML patients was analyzed by immunocytochemistry (ICC. The Kaplan-Meier method was used for univariate and multivariate statistical analysis to assess the relationship between p53, Bcl-2 and clinico-hematologic feature with respect to overall survival (OS using SPSS statistical software. No statistical significance was found in univariate analysis (P=0.60. However, when the subgroups of patients (+1, +2, +3 and +4 were compared, expression of p53 and Bcl-2 protein (1-10%, 11- 30%, 31-50% and >50% was statistically significant (P<0.05. However, in multivariate analysis, p53, immunopositivity was independently associated with a shorter overall survival (OS (P=0.038 while Bcl-2 immunopositivity was associated with longer overall survival (OS (P=0.002. Our finding shows that p53 and Bcl-2 protein overexpression is a strong indicator of response to chemotherapy and overall survival. This study reports for the first time AML in patients from Eastern India.

  8. HLA-G Expression on Blasts and Tolerogenic Cells in Patients Affected by Acute Myeloid Leukemia

    Grazia Locafaro

    2014-01-01

    Full Text Available Human Leukocyte Antigen-G (HLA-G contributes to cancer cell immune escape from host antitumor responses. The clinical relevance of HLA-G in several malignancies has been reported. However, the role of HLA-G expression and functions in Acute Myeloid Leukemia (AML is still controversial. Our group identified a subset of tolerogenic dendritic cells, DC-10 that express HLA-G and secrete IL-10. DC-10 are present in the peripheral blood and are essential in promoting and maintaining tolerance via the induction of adaptive T regulatory (Treg cells. We investigated HLA-G expression on blasts and the presence of HLA-G-expressing DC-10 and CD4+ T cells in the peripheral blood of AML patients at diagnosis. Moreover, we explored the possible influence of the 3′ untranslated region (3′UTR of HLA-G, which has been associated with HLA-G expression, on AML susceptibility. Results showed that HLA-G-expressing DC-10 and CD4+ T cells are highly represented in AML patients with HLA-G positive blasts. None of the HLA-G variation sites evaluated was associated with AML susceptibility. This is the first report describing HLA-G-expressing DC-10 and CD4+ T cells in AML patients, suggesting that they may represent a strategy by which leukemic cells escape the host’s immune system. Further studies on larger populations are required to verify our findings.

  9. Persistent complete molecular remission after nilotinib and graft-versus-leukemia effect in an acute lymphoblastic leukemia patient with cytogenetic relapse after allogeneic stem cell transplantation

    Farnsworth Paul

    2012-09-01

    Full Text Available Abstract We report the successful treatment and sustained molecular remission using single agent nilotinib in a relapsed Philadelphia chromosome positive (Ph+ acute lymphoblastic leukemia patient after allogeneic hematopoietic stem cell transplantation. Compared to previously published studies, this is the first report where a patient did not receive additional chemotherapy after relapse, nor did she receive donor lymphocyte infusions. With nilotinib, the patient reverted back to normal blood counts and 100% donor reconstitution by single tandem repeat (STR chimerism analysis in the bone marrow and in peripheral blood, granulocytes, T and B-lymphocytes. This report also highlights the use of nilotinib in combination with extracorporeal photopheresis (ECP for concomitant graft-versus-host disease. Our data suggests that ECP, together with nilotinib, did not adversely affect the overall Graft-versus-leukemia (GVL effect.

  10. Characterization of Common Chromosomal Translocations and Their Frequencies in Acute Myeloid Leukemia Patients of Northwest Iran

    Elnaz Amanollahi Kamaneh

    2016-04-01

    Full Text Available Objective: Detection of chromosomal translocations has an important role in diagnosis and treatment of hematological disorders. We aimed to evaluate the 46 new cases of de novo acute myeloid leukemia (AML patients for common translocations and to assess the effect of geographic and ethnic differences on their frequencies. Materials and Methods: In this descriptive study, reverse transcriptase-polymerase chain reaction (RT-PCR was used on 46 fresh bone marrow or peripheral blood samples to detect translocations t (8; 21, t (15; 17, t (9; 11 and inv (16. Patients were classified using the French-American-British (FAB criteria in to eight sub-groups (M0-M7. Immunophenotyping and biochemical test results of patients were compared with RT-PCR results. Results: Our patients were relatively young with a mean age of 44 years. AML was relatively predominant in female patients (54.3% and most of patients belonged to AML-M2. Translocation t (8; 21 had the highest frequency (13% and t (15; 17 with 2.7% incidence was the second most frequent. CD19 as an immunophenotypic marker was at a relatively high frequency (50% in cases with t (8; 21, and patients with this translocation had a specific immunophenotypic pattern of complete expression of CD45, CD38, CD34, CD33 and HLA-DR. Conclusion: Similarities and differences of results in Iran with different parts of the world can be explained with ethnic and geographic factors in characterizations of AML. Recognition of these factors especially in other comprehensive studies may aid better diagnosis and management of this disease.

  11. An efficient computational approach to evaluate the expression profile of individual acute leukemia patients

    Hansen, Marcus Celik; Nyvold, Charlotte Guldborg; Haferlach, Torsten;

    Microarray and sequencing studies have been instrumental in the mapping of genome wide associations in hematological diseases. Thus, the MILE Study has taught us that it is possible to robustly classify and predict leukemia subgroups. Several factors have impeded the general use of such data and...... that combining data from MILE Study and data mining at the single patient level by novel scripts could help delineate the leukemia subtype and profile the unique expression signature....

  12. Outcome and medical costs of patients with invasive aspergillosis and acute myelogenous leukemia-myelodysplastic syndrome treated with intensive chemotherapy: An observational study

    Slobbe, Lennert; Polinder, Suzanne; Doorduijn, Jeanette; Lugtenburg, Pieternella; Barzouhi, Abdelilah; Steyerberg, Ewout; Rijnders, Bart

    2008-01-01

    textabstractBackground. Invasive aspergillosis (IA) is a leading cause of mortality in patients with acute leukemia. Management of IA is expensive, which makes prevention desirable. Because hospital resources are limited, prevention costs have to be compared with treatment costs and outcome. Methods. In 269 patients treated for acute myelogenous leukemia-myelodysplastic syndrome (AML-MDS) during 2002-2007, evidence of IA was collected using high-resolution computed tomography and galactomanna...

  13. Impact of postremission consolidation chemotherapy on outcome after reduced-intensity conditioning allogeneic stem cell transplantation for patients with acute myeloid leukemia in first complete remission

    Yeshurun, Moshe; Labopin, Myriam; Blaise, Didier;

    2014-01-01

    The objective of the current study was to investigate the role of postremission consolidation chemotherapy before reduced-intensity conditioning (RIC) allogeneic stem cell transplantation (alloSCT) for patients with acute myeloid leukemia (AML) in first complete remission (CR1).......The objective of the current study was to investigate the role of postremission consolidation chemotherapy before reduced-intensity conditioning (RIC) allogeneic stem cell transplantation (alloSCT) for patients with acute myeloid leukemia (AML) in first complete remission (CR1)....

  14. "HLA Class II Allele and Haplotype Frequencies in Iranian Patients with Acute Myelogenous Leukemia and Control Group "

    Abdolfattah Sarafnejad

    2006-09-01

    Full Text Available Previous studies have demonstrated some significant differences in HLA allele frequencies in leukemic patients and normal subjects. We have analyzed HLA class II alleles and haplotypes in 60 Iranian patients with acute myelogenous leukemia (AML and 180 unrelated normal subjects. Blood samples were collected after obtaining informed consents. From the patients and control DNA extraction and HLA typing were performed using PCR-SSP method. Significant positive association with the disease was found for HLA-DRB1*11 allele (35% vs. 24.7%, p=0.033. Two alleles including HLA-DRB4 and –DQB1*0303 were found to be significantly decreased in patients compared to controls. Regarding haplotype analysis, no significant association was found between case and control groups. It is suggested that HLA-DRB1*11 allele plays as a presumptive predisposing factor while the HLA-DRB4 and –DQB1*0303 alleles are suggested as protective genetic factors against acute myelogenous leukemia. Larger studies are needed to confirm and establish the role of these associations with acute myelogenous leukemia.

  15. Temsirolimus, Dexamethasone, Mitoxantrone Hydrochloride, Vincristine Sulfate, and Pegaspargase in Treating Young Patients With Relapsed Acute Lymphoblastic Leukemia or Non-Hodgkin Lymphoma

    2015-07-09

    Childhood B Acute Lymphoblastic Leukemia; Childhood T Acute Lymphoblastic Leukemia; Mature T-Cell and NK-Cell Non-Hodgkin Lymphoma; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Lymphoblastic Lymphoma

  16. A phase I trial of the aurora kinase inhibitor, ENMD-2076, in patients with relapsed or refractory acute myeloid leukemia or chronic myelomonocytic leukemia.

    Yee, Karen W L; Chen, Hsiao-Wei T; Hedley, David W; Chow, Sue; Brandwein, Joseph; Schuh, Andre C; Schimmer, Aaron D; Gupta, Vikas; Sanfelice, Deborah; Johnson, Tara; Le, Lisa W; Arnott, Jamie; Bray, Mark R; Sidor, Carolyn; Minden, Mark D

    2016-10-01

    ENMD-2076 is a novel, orally-active molecule that inhibits Aurora A kinase, as well as c-Kit, FLT3 and VEGFR2. A phase I study was conducted to determine the maximum tolerated dose (MTD), recommended phase 2 dose (RP2D) and toxicities of ENMD-2076 in patients with acute myeloid leukemia (AML) and chronic myelomonocytic leukemia (CMML). Patients received escalating doses of ENMD-2076 administered orally daily [225 mg (n = 7), 375 mg (n = 6), 325 mg (n = 9), or 275 mg (n = 5)]. Twenty-seven patients were treated (26 AML; 1 CMML-2). The most common non-hematological toxicities of any grade, regardless of association with drug, were fatigue, diarrhea, dysphonia, dyspnea, hypertension, constipation, and abdominal pain. Dose-limiting toxicities (DLTs) consisted of grade 3 fatigue, grade 3 typhilitis, grade 3 syncope and grade 3 QTc prolongation). Of the 16 evaluable patients, one patient achieved a complete remission with incomplete count recovery (CRi), three experienced a morphologic leukemia-free state (MLFS) with a major hematologic improvement in platelets (HI-P), and 5 other patients had a reduction in marrow blast percentage (i.e. 11-65 %). The RP2D in this patient population is 225 mg orally once daily. PMID:27406088

  17. Mitochondrial DNA alterations of peripheral lymphocytes in acute lymphoblastic leukemia patients undergoing total body irradiation therapy

    Mitochondrial DNA (mtDNA) alterations, including mtDNA copy number and mtDNA 4977 bp common deletion (CD), are key indicators of irradiation-induced damage. The relationship between total body irradiation (TBI) treatment and mtDNA alterations in vivo, however, has not been postulated yet. The aim of this study is to analyze mtDNA alterations in irradiated human peripheral lymphocytes from acute lymphoblastic leukemia (ALL) patients as well as to take them as predictors for radiation toxicity. Peripheral blood lymphocytes were isolated from 26 ALL patients 24 hours after TBI preconditioning (4.5 and 9 Gy, respectively). Extracted DNA was analyzed by real-time PCR method. Average 2.31 times mtDNA and 0.53 fold CD levels were observed after 4.5 Gy exposure compared to their basal levels. 9 Gy TBI produced a greater response of both mtDNA and CD levels than 4.5 Gy. Significant inverse correlation was found between mtDNA content and CD level at 4.5 and 9 Gy (P = 0.037 and 0.048). Moreover, mtDNA content of lymphocytes without irradiation was found to be correlated to age. mtDNA and CD content may be considered as predictive factors to radiation toxicity

  18. Mitochondrial DNA alterations of peripheral lymphocytes in acute lymphoblastic leukemia patients undergoing total body irradiation therapy

    Ji Fuyun

    2011-10-01

    Full Text Available Abstract Background Mitochondrial DNA (mtDNA alterations, including mtDNA copy number and mtDNA 4977 bp common deletion (CD, are key indicators of irradiation-induced damage. The relationship between total body irradiation (TBI treatment and mtDNA alterations in vivo, however, has not been postulated yet. The aim of this study is to analyze mtDNA alterations in irradiated human peripheral lymphocytes from acute lymphoblastic leukemia (ALL patients as well as to take them as predictors for radiation toxicity. Methods Peripheral blood lymphocytes were isolated from 26 ALL patients 24 hours after TBI preconditioning (4.5 and 9 Gy, respectively. Extracted DNA was analyzed by real-time PCR method. Results Average 2.31 times mtDNA and 0.53 fold CD levels were observed after 4.5 Gy exposure compared to their basal levels. 9 Gy TBI produced a greater response of both mtDNA and CD levels than 4.5 Gy. Significant inverse correlation was found between mtDNA content and CD level at 4.5 and 9 Gy (P = 0.037 and 0.048. Moreover, mtDNA content of lymphocytes without irradiation was found to be correlated to age. Conclusions mtDNA and CD content may be considered as predictive factors to radiation toxicity.

  19. Serum Adiponectin and Resistin Levels in de Novo and Relapsed Acute Lymphoblastic Leukemia Children Patients

    Hatim A El-Baz

    2013-05-01

    Full Text Available Background: Adipose tissue secretes a large number of adipocytokines such as leptin, resistin, and adiponectin. Many of these hormones and cytokines are altered in obese individuals and may lead to disruption of the normal balance between cell proliferation, differentiation, and apoptosis. The aim of our work was to investigate the disturbance of secretion of adiponectin and resistin in de novo and relapsed acute lymphoblastic leukemia (ALL in Egyptian children and determine whether adiponectin and resistin are implicated in increased risk relapse compared to healthy individuals.Methods: Measurements of adiponectin and resistin were performed at diagnosis, in 32 patients with de novo ALL aged 3 to 18 years (mean 9.8 y and 19 children with relapsed ALL aged 5 to 17 (mean 9.9 yr. 10 apparently healthy children with matched age and sex were used as controls.Results: Mean adiponectin levels were low (P < 0.05, whereas mean resistin levels were high (P<0.05 at diagnosis and relapsed ALL (compared to healthy controls. A significant decrease of adiponectin levels was observed in relapsed ALL compared to de novo ALL. In contrast resistin was significantly increased in relapsed ALL compared to de novo patients. Adiponectin in ALL subjects inversely correlated with resistin level (r = -0.51, P < 0.001.Conclusion: Low adiponectin and high resistin level at diagnosis suggest their implication in ALL pathogenesis and may serve as potential clinically significant diagnostic markers to detect leukemic relapse.

  20. Cytogenetic profiles of 2806 patients with acute myeloid leukemia-a retrospective multicenter nationwide study.

    Byun, Ja Min; Kim, Young Jin; Yoon, Hwi-Joong; Kim, Si-Young; Kim, Hee-Je; Yoon, Jaeho; Min, Yoo Hong; Cheong, Jun-Won; Park, Jinny; Lee, Jae Hoon; Hong, Dae Sik; Park, Seong Kyu; Kim, Hyeoung-Joon; Ahn, Jae-Sook; Shin, Ho-Jin; Chung, Joo Seop; Lee, Won Sik; Lee, Sang Min; Park, Yong; Kim, Byung Soo; Lee, Je-Hwan; Lee, Kyoo-Hyung; Jung, Chul Won; Jang, Jun Ho; Min, Woo-Sung; Park, Tae Sung

    2016-08-01

    The cytogenetic and molecular data is recognized as the most valuable prognostic factor in acute myeloid leukemia (AML). Our aim was to systemically analyze the cytogenetics of Korean AML patients and to compare the cytogenetic profiles of various races to identify possible geographic heterogeneity. We retrospectively reviewed medical records of 2806 AML patients diagnosed at 11 tertiary teaching hospitals in Korea between January 2007 and December 2011. The most common recurrent chromosomal abnormality was t(8;21) (8.8 %, 238/2717), but t(15;17) showed an almost same number (8.6 %,235/2717). Among de novo AML, the most frequent aberrations were t(15;17), observed in 229 (10.7 %). The most common French-American-British (FAB) classification type was M2 (32.2 %), and recurrent cytogenetic abnormalities correlated with the FAB subtypes. Among 283 secondary AML cases, myelodysplastic syndrome was the most common predisposing factor. About 67.1 % of the secondary AML cases were associated with chromosomal aberrations, and chromosome 7 abnormalities (n = 45, 15.9 %) were most common. The incidence of FLT3 internal tandem duplication mutation was relatively low at 15 %. Our study reports certain similarities and differences in comparison to previous reports. Such discrepancies call for extensive epidemiological studies to clarify the role of genetic as well as geographic heterogeneity in the pathogenesis of AML. PMID:27230620

  1. Cytogenetic Findings of Patients with Acute Lymphoblastic Leukemia in Fars Province

    Akbar Safaei

    2013-12-01

    Full Text Available Background: Acute lymphoblastic leukemia (ALL is the sixth most common malignancy in Iran. Cytogenetic analysis of leukemic blasts plays an important role in classification and prognosis in ALL patients. The purpose of this study was to define the frequency of chromosomal abnormalities of ALL patients in adults and children in Fars province, Iran. Methods: In this cross-sectional study, we evaluated karyotype results of bone marrow specimens in 168 Iranian patients with ALL (154 B-ALL and 14 T-ALL in Fars Province using the conventional cytogenetic G-banding method. Results: The frequency of cytogenetic abnormalities, including numerical and/or structural changes, was 61.7% and 53.8% in the B-ALL and T-ALL patients, respectively. Hyperdiploidy was the most common (32% cytogenetic abnormality. Among structural abnormalities, the most common was t(9;22 in 11% of the patients. The children showed a higher incidence of hyperdiploidy and lower incidence of t(9;22 than adults (P<0.05. We found a lower incidence of recurrent abnormalities such as 11q23, t(1;19, and t(12;21 than those reported in previous studies. Conclusion: Normal karyotype was more frequent in our study. The frequencies of some cytogenetic abnormalities such as hyperdiploidy and t(9;22 in our study were comparable to those reported in the literature. The results of this study in Fars Province can be used as baseline information for treatment decision and research purposes in ALL patients. We recommend the use of advanced molecular techniques in the future to better elucidate cryptic cytogenetic abnormalities.

  2. Acute myelogenous leukemia (AML) -- children

    ... Leung WH, Pounds S, Cao X, e t al. Definition of cure in childhood acute myeloid leukemia. Cancer . ... M. is also a founding member of Hi-Ethics and subscribes to the principles of the Health ...

  3. Radioimmunotherapy for Treatment of Acute Leukemia.

    Bodet-Milin, Caroline; Kraeber-Bodéré, Françoise; Eugène, Thomas; Guérard, François; Gaschet, Joëlle; Bailly, Clément; Mougin, Marie; Bourgeois, Mickaël; Faivre-Chauvet, Alain; Chérel, Michel; Chevallier, Patrice

    2016-03-01

    Acute leukemias are characterized by accumulation of immature cells (blasts) and reduced production of healthy hematopoietic elements. According to the lineage origin, two major leukemias can be distinguished: acute myeloid leukemia (AML) and acute lymphoid leukemia (ALL). Although the survival rate for pediatric ALL is close to 90%, half of the young adults with AML or ALL and approximately 90% of older patients with AML or ALL still die of their disease, raising the need for innovative therapeutic approaches. As almost all leukemic blasts express specific surface antigens, targeted immunotherapy appears to be particularly promising. However, published results of immunotherapy alone are generally modest. Radioimmunotherapy (RIT) brings additional therapeutic mechanisms using radiolabeled monoclonal antibodies (mAbs) directed to tumor antigens, thus adding radiobiological cytotoxicity to immunologic cytotoxicity. Because of the high radiosensitivity of tumor cells and the diffuse widespread nature of the disease, making it rapidly accessible to circulating radiolabeled mAbs, acute leukemias represent relevant indications for RIT. With the development of recombinant and humanized mAbs, innovative radionuclides, and more efficient radiolabeling and pretargeting techniques, RIT has significantly improved over the last 10 years. Different approaches of α and β RIT targeting CD22, CD33, CD45, or CD66 antigens have already been evaluated or are currently being developed in the treatment of acute leukemia. This review summarizes the preclinical and clinical studies demonstrating the potential of RIT in treatment of AML and ALL. PMID:26897718

  4. Impact of cytomegalovirus reactivation on relapse and survival in patients with acute leukemia who received allogeneic hematopoietic stem cell transplantation in first remission.

    Yoon, Jae-Ho; Lee, Seok; Kim, Hee-Je; Jeon, Young-Woo; Lee, Sung-Eun; Cho, Byung-Sik; Lee, Dong-Gun; Eom, Ki-Seong; Kim, Yoo-Jin; Min, Chang-Ki; Cho, Seok-Goo; Min, Woo-Sung; Lee, Jong Wook

    2016-03-29

    Cytomegalovirus (CMV)-reactivation is associated with graft-vs-leukemia (GVL) effect by stimulating natural-killer or T-cells, which showed leukemia relapse prevention after hematopoietic stem cell transplantation (HSCT). We enrolled patients with acute myeloid leukemia (n = 197) and acute lymphoid leukemia (n = 192) who underwent allogeneic-HSCT in first remission. We measured RQ-PCR weekly to detect CMV-reactivation and preemptively used ganciclovir (GCV) when the titer increased twice consecutively, but GCV was sometimes delayed in patients without significant graft-vs-host disease (GVHD) by reducing immunosuppressive agents. In the entire group, CMV-reactivation showed poor overall survival (OS). To evaluate subsequent effects of CMV-reactivation, we excluded early relapse and deaths within 100 days, during which most of the CMV-reactivation occurred. Untreated CMV-reactivated group (n = 173) showed superior OS (83.8% vs. 61.7% vs. 74.0%, p acute leukemia. PMID:26883100

  5. Clofarabine Does Not Negatively Impact the Outcomes of Patients With Acute Myeloid Leukemia Undergoing Allogeneic Stem Cell Transplantation

    Mathisen, Michael S.; Kantarjian, Hagop; Jabbour, Elias; Garcia-Manero, Guillermo; Ravandi, Farhad; Faderl, Stefan; Borthakur, Gautam; Cortes, Jorge E.; Quintás-Cardama, Alfonso

    2012-01-01

    We evaluated whether clofarabine-containing chemotherapy predisposed patients to hepatic toxicity (particularly venoocclusive disease [VOD]) after allogeneic stem cell transplantation (allo-SCT). In the group who received clofarabine and subsequent transplantation, there were no cases of VOD, and liver toxicity was comparable to a control group who received standard acute myeloid leukemia (AML) chemotherapy. Other transplant-specific outcomes, including overall survival (OS), were also simila...

  6. Examination of the FLT3 and NPM1 mutational status in patients with acute myeloid leukemia from southeastern Poland

    Koczkodaj, Dorota; Zmorzyński, Szymon; Michalak-Wojnowska, Małgorzata; Wąsik-Szczepanek, Ewa; Filip, Agata A.

    2016-01-01

    Introduction Acute myeloid leukemia (AML) is a genetically heterogeneous disease at both the cytogenetic and molecular levels. In AML cells many chromosomal aberrations are observed, some of them being characteristic of a particular subtype of patients, and others being less significant. Besides chromosomal abnormalities, the leukemic cells can have a variety of mutations involving individual genes. The aim of this work was to investigate the frequencies of molecular alterations with the focu...

  7. Clofarabine and Cytarabine in Treating Older Patients With Acute Myeloid Leukemia or High-Risk Myelodysplastic Syndromes That Have Relapsed or Not Responded to Treatment

    2013-08-06

    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); Myelodysplastic Syndrome With Isolated Del(5q); Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Myeloid Leukemia

  8. Criteria and Classification of Hybrid Acute Leukemia in 72 Acute Leukemias Based Mainly on Flow Cytometric Analysis

    Aoki, Sadao; Nomoto, Nobuhiko; Maruyama, Souichi; Shinada, Shoji; Shibata, Akira

    1991-01-01

    Phenotypes of leukemic cells can be determined through dual staining with pairs of FITC-labeled and PE-labeled monoclonal antibodies using a laser flow cytometer. Hybrid acute leukemia (HAL) was diagnosed when leukemic cells expressed 2 or more lymphoid markers and at least on myeloid marker simultaneously. Based on this criteria, nineteen out of 72 cases with untreated acute leukemia were diagnosed as HAL, 15 of 29 (51%) patients with acute lymphoblastic leukemia and 4 of 43 (9%) patients wi...

  9. Aleukemic leukemia cutis in a patient with Philadelphia chromosome-positive biphenotypic leukemia.

    Onozawa, Masahiro; Hashino, Satoshi; Kanamori, Hiroe; Izumiyama, Koh; Yonezumi, Masakatsu; Chiba, Koji; Kondo, Takeshi; Fukuhara, Takashi; Tanaka, Junji; Imamura, Masahiro; Asaka, Masahiro

    2004-01-01

    Aleukemic leukemia cutis is a rare condition characterized by the invasion of leukemic blasts into the skin before their appearance in the peripheral blood. Leukemia cutis usually occurs in patients with myeloid leukemia, especially the myelomonocytic and monocytic types of acute myeloblastic leukemia. We describe the case of a 62-year-old woman with aleukemic leukemia cutis who developed Philadelphia-positive acute leukemia 1 month after skin involvement. Leukemic cells expressed both myeloi...

  10. Acute Lymphocytic Leukemia

    Leukemia is cancer of the white blood cells. White blood cells help your body fight infection. Your blood cells form in your bone marrow. In leukemia, however, the bone marrow produces abnormal white blood ...

  11. Acute Myeloid Leukemia

    Leukemia is cancer of the white blood cells. White blood cells help your body fight infection. Your blood cells form in your bone marrow. In leukemia, however, the bone marrow produces abnormal white blood ...

  12. MDM4 Overexpressed in Acute Myeloid Leukemia Patients with Complex Karyotype and Wild-Type TP53

    Li Li; Yanhong Tan; Xiuhua Chen; Zhifang Xu; Siyao Yang; Fanggang Ren; Haixiu Guo; Xiaojuan Wang; Yi Chen; Guoxia Li; Hongwei Wang

    2014-01-01

    Acute myeloid leukemia patients with complex karyotype (CK-AML) account for approximately 10-15% of adult AML cases, and are often associated with a poor prognosis. Except for about 70% of CK-AML patients with biallelic inactivation of TP53, the leukemogenic mechanism in the nearly 30% of CK-AML patients with wild-type TP53 has remained elusive. In this study, 15 cases with complex karyotype and wild-type TP53 were screened out of 140 de novo AML patients and the expression levels of MDM4, a ...

  13. Whole brain magnetization transfer histogram analysis of pediatric acute lymphoblastic leukemia patients receiving intrathecal methotrexate therapy

    Yamamoto, Akira [Department of Diagnostic Imaging and Nuclear Medicine, Graduate School of Medicine, Kyoto University, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto-shi Kyoto 606-8507 (Japan)]. E-mail: yakira@kuhp.kyoto-u.ac.jp; Miki, Yukio [Department of Diagnostic Imaging and Nuclear Medicine, Graduate School of Medicine, Kyoto University, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto-shi Kyoto 606-8507 (Japan)]. E-mail: mikiy@kuhp.kyoto-u.ac.jp; Adachi, Souichi [Department of Pediatrics, Graduate School of Medicine, Kyoto University, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto-shi Kyoto 606-8507 (Japan)]. E-mail: sadachi@kuhp.kyoto-u.ac.jp (and others)

    2006-03-15

    Background and purpose: The purpose of this prospective study was to evaluate the hypothesis that magnetization transfer ratio (MTR) histogram analysis of the whole brain could detect early and subtle brain changes nonapparent on conventional magnetic resonance imaging (MRI) in children with acute lymphoblastic leukemia (ALL) receiving methotrexate (MTX) therapy. Materials and methods: Subjects in this prospective study comprised 10 children with ALL (mean age, 6 years; range, 0-16 years). In addition to conventional MRI, magnetization transfer images were obtained before and after intrathecal and intravenous MTX therapy. MTR values were calculated and plotted as a histogram, and peak height and location were calculated. Differences in peak height and location between pre- and post-MTX therapy scans were statistically analyzed. Conventional MRI was evaluated for abnormal signal area in white matter. Results: MTR peak height was significantly lower on post-MTX therapy scans than on pre-MTX therapy scans (p = 0.002). No significant differences in peak location were identified between pre- and post-chemotherapy imaging. No abnormal signals were noted in white matter on either pre- or post-MTX therapy conventional MRI. Conclusions: This study demonstrates that MTR histogram analysis allows better detection of early and subtle brain changes in ALL patients who receive MTX therapy than conventional MRI.

  14. Successful voriconazole treatment of invasive pulmonary aspergillosis in a patient with acute biphenotypic leukemia

    Hirano,Teiichi

    2009-08-01

    Full Text Available A 23-year old woman with acute biphenotypic leukemia (ABL complained of chest pain with cough, high fever and hemoptysis during induction chemotherapy, although she had been treated with anti-biotics and micafungin. We made a clinical diagnosis of invasive pulmonary aspergillosis (IPA based on a consolidation in the right upper lung field on a chest radiograph as well as a high level of serum beta-D-glucan (with no evidence of tuberculosis and candidiasis. We changed her treatment from micafungin to voriconazole. Later, we discovered an air-crescent sign by CT scan that supported the diagnosis of IPA. Following voriconazole treatment, clinical symptoms ceased and abnormal chest shadows improved gradually and concurrently with a recovery of neutrophils. IPA must be considered in immunocompromised patients with pulmonary infiltrates who do not respond to broad-spectrum antibiotics. Serological tests and CT findings can aid in early diagnosis of IPA, which, along with treatment for IPA, will improve clinical outcomes.

  15. The prognostic significance of minimal residual disease in adult Egyptian patients with precursor acute lymphoblastic leukemia

    Background: Minimal residual disease (MRD) studies in adult acute lymphoblastic leukemia (ALL) give highly significant prognostic information superior to other standard criteria as Minimal residual disease; age, gender and total leucocytic count (TLC) in distinguishing patients at high and low risk of Flow cytometry relapse. Objectives: We aimed to determine the value of MRD monitoring by flow cytometry (FCM) in predicting outcome in adult Precursor ALL patients. Patients and methods: Bone marrow (BM) samples were analyzed by 4-color FCM collected at diagnosis and after induction therapy (MRD1) to correlate MRD positivity with disease free survival (DFS) and overall survival (OS). Results: Study included 57 adult ALL patients (44 males and 13 females) with a median age of 22 years (18-49). DFS showed no significant difference with age, gender and initial TLC (p = 0.838, 0.888 and 0.743, respectively). Cumulative DFS at 2 years was 34% for B-lineage ALL (n: 35) and 57% for T-lineage ALL (n: 18) (p = 0.057). Cumulative DFS at 2 years was M.A. Samra et al. 136 7% for MRD1 positive (high risk, HR) versus 57% for MRD1 negative patients (Low risk, LR) (p < 0.001). Cumulative DFS at 2 years was 29% for HR patients (n: 26) versus 55% for LR (n: 27) according to GMALL classification (p = 0.064). Cumulative OS did not differ according to age, gender and TLC (p = 0.526, 0.594 and 0.513, respectively). Cumulative OS at 2 years was 36% for B ALL (n: 39) versus 77% for TALL (n: 18) (p = 0.016) and was 49% for Philadelphia chromosome (Ph) negative patients versus 0% for Ph-positive patients (p < 0.001). Regarding MRD1, OS at 2 years was 18% for MRD1 HR (n:17) versus 65% for MRD1 LR (n: 38) (p < 0.001). OS was 35% for high-risk patients (n: 30) and 62% for low-risk patients (n: 27) classified according to GMALL risk stratification (p = 0.017). Conclusion: MRD by FCM is a strong independent predictor of outcome in terms of DFS and OS and is a powerful informative parameter in

  16. Acute Lymphoblastic Leukemia Associated with Brucellosis in Two Patients with Fever and Pancytopenia

    Eser, Bulent; Altuntas, Fevzi; Soyuer, Isin; Er, Ozlem; Canoz, Ozlem; COSKUN, HASAN SENOL; Cetin, Mustafa; Unal, Ali

    2006-01-01

    Brucellosis is a disease involving the lymphoproliferative system, which may lead to changes in the hematological parameters; however, pancytopenia is a rare finding. However, malignant diseases in association with brucellosis are rarely the cause of pancytopenia. Herein, two cases with fever and pancytopenia, diagnosed as simultaneous acute lymphoblastic leukemia and brucellosis are presented. Anti-leukemic therapy and brucellosis treatment were administered simultaneously, and normal blood ...

  17. Leukemoid reaction in a patient with acute lymphoblastic leukemia following the

    Osman Yokuş

    2013-06-01

    Full Text Available The occurrence of persistent neutrophilic leukocytosisabove 50,000 cells/μL for reasons other thanleukemia is defined as leukemoid reaction. Chronicmyelogenous leukemia (CML and chronic neutrophilicleukemia (CNL should be excluded, and underlyingdiseases or causes should be examined,in differential diagnosis. The most commonly observedcauses of leukemoid reactions are severeinfections, intoxications, malignancies, severe hemorrhage,or acute hemolysis [1]. J Clin Exp Invest2013; 4 (2: 258-259

  18. Brown sequard syndrome secondary of soft tissue infection in a patient with acute lymphocyte leukemia

    A 42-year-old Latin American female with acute lymphocytic leukemia in second relapse developed a small ecthymic lesion around the entrance site of a left subclavian line. This was followed by development of left-sided hemiparesis with contralateral loss of pain and temperature sensation. CT of the neck revealed a diffuse inflammatory process with soft tissue involvement and several bubbles of air in the anterior paraspinal muscles and within the spinal canal in the epidural location. (orig.)

  19. Prognostic Value of AML1/ETO Fusion Transcripts in Patients with Acute Myelogenous Leukemia

    Cho, Eun Kyung; Bang, Soo Mee; Ahn, Jeong Yeal; Yoo, Seung Min; Park, Pil Whan; Seo, Yieh Hea; Shin, Dong Bok; Lee, Jae Hoon

    2003-01-01

    Background The t (8;21) (q22;q22), which produces the fusion gene AML1/ETO, is associated with relatively good prognosis and, in particular, with a good response to cytosine arabinoside. Analysis of t (8;21) positive leukemic blasts has shown characteristic morphological and immunological features. We performed this study to investigate the incidence of AML1/ETO rearrangement in adult acute myelogenous leukemia (AML), especially in M2 subtype, to make a comparison of clinical, morphological a...

  20. Bilateral breast involvement in acute myeloid leukemia

    Hakeem A, Mandakini BT, Asif K, Firdaus, Shagufta RC

    2013-04-01

    Full Text Available Breast involvement by leukemic infiltration is usually bilateral, but may be unilateral. Clinically patients can present with either single or multiple masses, or with diffuse breast engorgement, with or without nodularity. The affected patients are predominantly young adults. We present a case of an adolescent girl with acute myeloid leukemia having bilateral breast infiltration by leukemic cells.

  1. Acute childhood leukemia: Nursing care

    Modern therapy for childhood acute leukemia has provided a dramatically improved prognosis over that of just 30 years ago. In the early 1960's survival rates for acute lymphocytic leukemia (ALL) and acute myelogenous leukemia (AML) were 4% and 3%, respectively. By the 1980's survival rates had risen to 72% for all and 25% to 40% for AML. Today, a diagnosis of all carries an 80% survival rate and as high as a 90% survival rate for some low-risk subtypes. Such high cure rates depend on intense and complex, multimodal therapeutic protocols. Therefore, nursing care of the child with acute leukemia must meet the demands of complicated medical therapies and balance those with the needs of a sick child and their concerned family. An understanding of disease process and principles of medical management guide appropriate and effective nursing interventions. Leukemia is a malignant disorder of the blood and blood- forming organs (bone marrow, lymph nodes and spleen). Most believe that acute leukemia results from a malignant transformation of a single early haematopoietic stem cell that is capable of indefinite self-renewal. These immature cells of blasts do not respond to normal physiologic stimuli for differentiation and gradually become the predominant cell in the bone marrow

  2. Efficacy of Exercise Interventions in Patients with Acute Leukemia: A Meta-Analysis

    Zhu, Jinjie; Gu, Zejuan; Yin, Xiangguang

    2016-01-01

    Background Decreased physical performance and impaired physiological and psychological fitness have been reported in patients with acute leukemia (AL). We performed a meta-analysis to assess the efficacy of exercise in patients with AL. Methods In this meta-analysis, the electronic databases MEDLINE, Embase, Cochrane, Web of Science, SPORTDiscus, CINAHL and PEDro were searched through November 2015. Three authors participated in the study selection, data extraction and quality assessment. The instrument used for quality assessment was derived from the Cochrane Handbook for Systematic Reviews of Interventions. Analyses were performed according to the recommendations of The Cochrane Collaboration using Review Manager 5.3. Results Nine trials (8 randomized controlled trials and 1 quasi-experimental design trial) with 314 AL participants were included in this meta-analysis. The pooled standardized mean differences between the exercise and control groups were 0.45 (95% confidence interval (CI): 0.09 to 0.80, P value = 0.01, P for heterogeneity = 0.23, I2 = 28%) for cardiorespiratory fitness and 0.67 (95% CI: 0.28 to 1.06, P value = 0.0007, P for heterogeneity = 0.14, I2 = 43%) for muscle strength. Based on the data for fatigue, anxiety, and depression, there were no significant differences in these parameters between the exercise and control groups. Conclusions Exercise has beneficial effects on cardiorespiratory fitness, muscle strength and functional mobility; however, no significant improvements in fatigue, anxiety, depression or quality of life were observed. Further large-scale randomized trials are needed to assess the safety, feasibility and efficacy of exercise programs for AL patients. PMID:27463234

  3. Prognostic impact of high ABC transporter activity in 111 adult acute myeloid leukemia patients with normal cytogenetics when compared to FLT3, NPM1, CEBPA and BAALC

    Hirsch, Pierre; Tang, Ruoping; Marzac, Christophe; Perrot, Jean-Yves; FAVA, FANNY; Bernard, Chantal; Jeziorowska, Dorota; MARIE, JEAN PIERRE; Legrand, Ollivier

    2012-01-01

    ATP-binding cassette transporter (and specially P-glycoprotein) activity is a well known prognostic factor in acute myeloid leukemia, but when compared to other molecular markers its prognostic value has not been well studied. Here we study relationships between this activity, fms-like tyro-sine kinase 3(FLT3/ITD), nucleophosmin(NPM1), CAAT-enhancer binding protein alpha(CEBPα), and brain and acute leukemia cytoplasmic protein (BAALC), in 111 patients with normal cytogenetics who underwent th...

  4. Clofarabine, Cytarabine, and Filgrastim in Treating Patients With Newly Diagnosed Acute Myeloid Leukemia, Advanced Myelodysplastic Syndrome, and/or Advanced Myeloproliferative Neoplasm

    2015-12-28

    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; Refractory Anemia With Excess Blasts; Untreated Adult Acute Myeloid Leukemia; Myeloproliferative Neoplasm With 10% Blasts or Higher

  5. Acute nonlymphocytic leukemia following bladder instillations with thiotepa.

    Easton, D. J.; Poon, M. A.

    1983-01-01

    A case of therapy-related leukemia is described. Other cases of acute nonlymphocytic leukemia have been associated with the intramuscular administration of thiotepa (an alkylating agent), but this patient received only intravesical instillations of the drug. The interval between the start of chemotherapy and the onset of leukemia was 56 months.

  6. Molecular Detection of BCR/ ABL Fusion Gene in Saudi Acute Lymphoblastic Leukemia Patients

    Background: Molecular cytogenetics is becoming one of the most useful tools targeting some genes which are generally considered to lead to leukemic transformation (as well as for numerical abnormalities). A fraction of acute lymphoblastic leukemia (ALL) cases carry the translocation t(9;22) (q34;ql1.2) which juxtaposes the ABL proto-oncogene to the BCR gene generating a chimeric gene, BCR/ABL. This aberration is more frequent in adult ALL (20%-40%) than in pediatric ALL >)5%), and predicts poor clinical outcome. Aim of our Work: Is to study BCR/ A BL fusion gene in ALL cases using fluorescent in situ hybridization. Patients and Methods: Twenty newly diagnosed ALL patients, 16 adult and 4 paediatric cases, were included in the study, 11 cases (55%) were of precursor B phenotype, S cases (40%) belonged to T lineage, while one case was bi phenotypic expressing mainly precursor B cell markers tether with CD13, CD33, CD117, Detection of BCR/ABL fusion gene was done using interphase FISH technique and was confirmed molecularly using the RT-PCR technique. Results: BCR/ ABL fusion gene was negative in all the examined cases, yet abnormality involving 9q34, ABL gene, either by addition or deletion was detected in three cases (15%). Two of these cases were associated with BCR gene extra copies (three and four copies, respectively). Conclusion: This may reflect the frequency of association of ABL gene and BCR gene abnormality in our cases, and that absence of fusion gene BCR/ABL does not exclude their role in the leukomogenic process, yet a larger study is required to confirm and detect the prevalence of these gene disturbances in ALL and their association

  7. Frank hematuria as the presentation feature of acute leukemia

    Suriya Owais

    2010-01-01

    Full Text Available Muco-cutaneous bleeding is a common presenting feature of acute leukemias. Mucosal bleeding usually manifests as gum bleeding and/or epistaxis but may occur in any mucosal surface of the body. Hematuria as an isolated or main presenting feature of acute leukemia is rare. We describe two cases of acute leukemia, a 19 year old male with acute lymphoblastic leukemia and a 52 year old male with acute myeloid leukemia, both presenting with gross hematuria. There was no demonstrable leukemic infiltration of the urinary tract on imaging studies. Hematuria in these patients was likely to be due to occult leukemic infiltration of the urinary system, aggravated by thrombocytopenia, as it subsided after starting chemotherapy. Our cases highlight that hematuria should be remembered as a rare presenting feature of acute leukemia.

  8. P-GLYCOPROTEIN QUANTITATION IN ACUTE LEUKEMIA

    Mali in Nikougoftar

    2003-06-01

    Full Text Available Multi drug resistance(MDR is a major problem in the treatment of cancer and hemalological malignancies. This resistance is multi factorial and is the result of decreased intra cellular drug accumulation. This is partly due to the presence of a 170KD intra membranous protein termed P-glycoprotein(P-gp that is an energy-dependent efflux pump which has increased expression on drug-resistance cells. In this study we identified the presence of P-gp by staining with Fluorescent Iso Thio Cyanate (FITC conjugated anti P-gp in acute leukemia patients and flow cytometry in addition to performing immunophenotype analysis and French, American British (FAB classification. Results revealed that one fifth of leuke¬mic patients expressed P-gp and this phenotype was more prevalent in Acute Undifferentiated Leukemia(AUL and Acute Myelogenous Leukemia (AML than in Acute Lymphoblastic Leukemia(ALL. Other findings showed a logical rela¬tionship between this phenotype and age groups. There was not any association between P-gp+ phenotype and FAB and Immunophenotyping sub classification, but there was a linear relationship between CD34 and CD7 expression and P-gp+ phenotype. The accumulation of P-gp molecule that was stated as Mean Fluores¬cence Intensity (MFI on the blasts1 membrane of AUL and AML patients showed marked increase in comparison to ALL. Furthermore MFI in P-gp+ relapsed patients was much more than P-gp+ pretreatment patients.

  9. Psychological Risk Factors in Acute Leukemia

    Gouva M.

    2009-04-01

    Full Text Available Several theoretical models have been occasionally proposed to account for the involvement of psychological factors in cancer genesis. Family environment and relations as well as certain personality traits were correlated to cancer onset. However, little is known in the case of acute leukemia. The present study examined family environment, state-trait anxiety, hostility and the direction of hostility as well as alexithymia in 41 acute leukemia patients and their first degree relatives (70. In accordance with previous findings, the present results showed that family cohesion, conflict and organization as well as guilt, state anxiety and alexithymia were significant risk factors for the development of the disease.

  10. Prognostic Significance of the Lymphoblastic Leukemia-Derived Sequence 1 (LYL1) GeneExpression in Egyptian Patients with AcuteMyeloid Leukemia

    Nadia El Menshawy; Doaa Shahin; Hayam Fathi Ghazi

    2014-01-01

    Objective: Aberrant activation of transcription factor genes is the most frequent target of genetic alteration in lymphoid malignancies. The lymphoblastic leukemia-derived sequence 1 (LYL1) gene, which encodes a basic helix-loop helix, was first identified with human T-cell acute leukemia. Recent studies suggest its involvement in myeloid malignancies. We aimed to study the expression percent of oncogene LYL1 in primary and secondary high-risk myeloid leukemia and the impact on prognostic sig...

  11. Chromosomal changes detected by fluorescence in situ hybridization in patients with acute lymphoblastic leukemia

    ZHANG Lijun 张丽君; PARKHURST JB; KERN WF; SCOTT KV; NICCUM D; MULVIHILL JJ; LI Shibo 李师伯

    2003-01-01

    Objectives To investigate patients with acute lymphoblastic leukemia (ALL) for TEL/AML1 fusion, BCR/ABL fusion, MLL gene rearrangements, and numerical changes of chromosomes 4, 10, 17 and 21 by fluorescence in situ hybridization (FISH) and to determine the relationship and the significance of those findings.Methods Fifty-one American patients (34 men and 17 women) were included in this study. Of them there were 41 patients with pro-B cell type ALL, 9 with B cell type ALL and 1 with T cell type ALL. Chromosome metaphases of each sample were prepared according to standard protocols. Fluorescence in situ hybridization was performed using commercially available DNA probes, including whole chromosome painting probes, locus specific probes, specific chromosome centromere probes and dual color/multiple color translocation fusion probes. The digital image analysis was carried out using Cytovision and Quips FISH programs.Results An overall incidence of chromosomal anomalies, including t (9;22), MLL gene rearrangements, t (12;21), and numerical chromosomal anomalies of chromosomes 4, 10, 17 and 21 was found in 33 patients (65%). Thirty-one of them were pediatric patients and two adults. The t (12;21) was the commonest chromosomal anomaly detected in this population; 14 out of the 45 pediatric patients (31%) were positive for TEL/AML1 fusion, among which three had an additional derivative 21 [t (12;21)], four had a deletion of 12p and two had an extra copy of chromosome 21. All 14 patients with positive TEL/AML1 fusion had ALL pre-B cell or B-cell lineage according to standard immunotyping. The percentage of cells with fusion signals ranged from 20% to 80%. All fourteen patients positive for TEL/AML1 gene fusion were mosaic. Three out of the 14 patients positive for the TEL/AML1 gene fusion were originally reported to be culture failures and none of the remaining eleven samples had been found to have chromosome 12 abnormalities by conventional cytogenetic techniques. All

  12. The emerging role of exercise and health counseling in patients with acute leukemia undergoing chemotherapy during outpatient management

    Jarden, Mary; Adamsen, Lis; Kjeldsen, Lars;

    2013-01-01

    This study investigates the feasibility, safety and benefits of a 6-week exercise and health counseling intervention in patients with acute leukemia undergoing consolidation chemotherapy during outpatient management. Seventeen of twenty patients completed study requirements (85%), adherence to...... exercise was 73% and for health counseling 92%. There were improvements in the 6-min-walk-distance (p=0.0013), sit-to-stand test (p=0.0062), the right and left biceps arm-curl tests p=0.0002 and p=0.0002, respectively; health-related quality of life (p=0.0209) (FACT-An), vitality (p=0.0015), mental health...

  13. Nucleophosmin (NPM1) gene variants in Egyptian patients with acute myeloid leukemia

    To the editor Kassem et al. [1] described a novel mutational deletion [del 1178 (A)] in the 30 untranslated region of NPM1 gene detected in a heterozygous form in seven de novo acute myeloid leukemia (AML) patients of their study population. The described nucleotide deletion is an NPM1 gene polymorphism recorded in db SNP database (rs34351976; g28027: Genbank accession number NG016018.1) (http://www.ncbi.nlm.nih.gov/projects/SNP/) and was described previously by Do hner et al. [2] and Chou et al. [3]. This variant accounted for 60-70% of AML patients with normal karyotype [2]. The putative deletion was also identified in healthy volunteers and persisted at complete remission and also at relapse of AML patients [3]. This deletion had no effect on the predicted amino acid sequence and is not in linkage disequilibrium with any previously identified NPM1 mutations [2,3]. Analysis of RNA folding at the region surrounding the rs34351976 in the presence or absence of the deletion using Mfold analysis software (http://www.mfold.rna.albany.edu) revealed no RNA folding change that may alter RNA splicing and subsequently gene expression. Furthermore, splicing motifs analysis using Human Splicing Finder software version 2.4.1 showed that the presence of the deletion does not abolish any recognition site of exonic or intronic enhancers or silencer motifs. In general, it seems that the impact of NMP1 polymorphisms on the molecular pathogenesis of AML is not clear yet and needs further investigation. Kassem et al. [1] describes the molecular aspect of de novo AML in the Egyptian population. The previously known NPM1 mutations mentioned in their study are less frequent compared to the figures recorded worldwide. Moreover, the authors wondered whether the NPM1 variants identified in their patients may confer a better outcome of AML. According to the previously mentioned data, one can speculate that the presence of NPM1 gene polymorphism (rs34351976) should not be mistaken as being

  14. Methylation of Gene CHFR Promoter in Acute Leukemia Cells

    GONG Hui; LIU Wengli; ZHOU Jianfeng; XU Huizhen

    2005-01-01

    Summary: In order to explore whether gene CHFR was inactivated by methylation in leukemia cells, the expression of CHFR was examined before and after treatment with demethylation agent in Molt-4, Jurkat and U937 leukemia cell lines by means of RT-PCR. The methylation of promoter in Molt-4, Jurkat and U937 cells as well as 41 acute leukemia patients was analyzed by MS-PCR. The results showed that methylation of CHFR promoter was inactivated and could be reversed by treatment with a demethylating agent in Molt-4, Jurkat and U937. CHFR promoter methylation was detected in 39 % of acute leukemia patients. There was no difference in incidence of CHFR promoter methylation between acute myelocytic leukemia and acute lymphocytic leukemia. In conclusion, CHFR is frequently inactivated in acute leukemia and is a good candidate for the leukemia supper gene. By affecting mitotic checkpoint function, CHFR inactivation likely plays a key role in tumorigenesis in acute leukemia. Moreover, the methylation of gene CHFR appears to be a good index with which to predict the sensitivity of acute leukemia to microtubule inhibitors.

  15. Fatal Cyberlindnera fabianii fungemia in a patient with mixed phenotype acute leukemia after umbilical cord blood transplantation.

    Katagiri, Seiichiro; Gotoh, Moritaka; Tone, Kazuya; Akahane, Daigo; Ito, Yoshikazu; Ohyashiki, Kazuma; Makimura, Koichi

    2016-05-01

    We report a case of Cyberlindnera fabianii fungemia after umbilical cord blood transplantation (CBT). A 69-year-old woman was diagnosed as having mixed phenotype acute leukemia. The patient received CBT for primary refractory disease. After preconditioning chemotherapy, the patient's condition deteriorated, leading to acute respiratory failure from capillary leak syndrome and consequent admittance to the intensive care unit. The patient recovered temporarily following the administration of noninvasive positive pressure ventilation and continuous hemodiafiltration, but died of fungemia with the presence of yeast-like cells 15 days post-CBT. The yeast-like cells were analyzed by sequencing of the D1/D2 domain of the large subunit and the internal transcribed spacer domain, and were identified as C. fabianii. This case shows that molecular genetic-based methods may be effective for detecting undetermined invasive fungal infections in stem cell transplantation settings. PMID:26879198

  16. Leukemia Stem Cells and Human Acute Lymphoblastic Leukemia

    Bernt, Kathrin M.; Armstrong, Scott A.

    2009-01-01

    Leukemias and other cancers have been proposed to contain a subpopulation of cells that display characteristics of stem cells, and which maintain tumor growth. That most anti-cancer therapy is directed against the bulk of the tumor, and possibly spares the cancer stem cells, may lie at the heart of treatment failures with conventional modalities. Leukemia stem cells are fairly well described for acute myeloid leukemia (AML), but their existence and relevance for acute lymphoblastic leukemia (...

  17. Efficacy and effects of palifermin for the treatment of oral mucositis in patients affected by acute lymphoblastic leukemia.

    Lucchese, Alessandra; Matarese, Giovanni; Ghislanzoni, Luis Huanca; Gastaldi, Giorgio; Manuelli, Maurizio; Gherlone, Enrico

    2016-04-01

    This randomized-controlled trial studied the efficacy of palifermin, administered as a dose during hematopoietic stem cell transplant (HSCT) therapy, as primary prophylaxis on pediatric patients with acute lymphoblastic leukemia in order to reduce oral mucositis (OM). Patients in the palifermin group were randomly assigned to receive palifermin, 60 μg/kg, intravenously as a single dose 3 days before and 0, +1, and +2 post autologous HSCT infusion. The patients in the control group received only a placebo treatment. OM-related assessments were the WHO oral-toxicity scale and the patient-reported outcomes. There was a statistically significant reduction in the incidence of OM grade 3 and 4 in the palifermin group compared to the control group. There was also a reduction in the degree of severity of OM in the palifermin group (1.65 grade respect to 2.33 in the control group). Palifermin could prevent the recurrence of severe OM and improve the quality of life in patients with acute lymphoblastic leukemia (ALL). PMID:26428409

  18. Next-generation-sequencing of recurrent childhood high hyperdiploid acute lymphoblastic leukemia reveals mutations typically associated with high risk patients.

    Chen, Cai; Bartenhagen, Christoph; Gombert, Michael; Okpanyi, Vera; Binder, Vera; Röttgers, Silja; Bradtke, Jutta; Teigler-Schlegel, Andrea; Harbott, Jochen; Ginzel, Sebastian; Thiele, Ralf; Husemann, Peter; Krell, Pina F I; Borkhardt, Arndt; Dugas, Martin; Hu, Jianda; Fischer, Ute

    2015-09-01

    20% of children suffering from high hyperdiploid acute lymphoblastic leukemia develop recurrent disease. The molecular mechanisms are largely unknown. Here, we analyzed the genetic landscape of five patients at relapse, who developed recurrent disease without prior high-risk indication using whole-exome- and whole-genome-sequencing. Oncogenic mutations of RAS pathway genes (NRAS, KRAS, FLT3, n=4) and deactivating mutations of major epigenetic regulators (CREBBP, EP300, each n=2 and ARID4B, EZH2, MACROD2, MLL2, each n=1) were prominent in these cases and virtually absent in non-recurrent cases (n=6) or other pediatric acute lymphoblastic leukemia cases (n=18). In relapse nucleotide variations were detected in cell fate determining transcription factors (GLIS1, AKNA). Structural genomic alterations affected genes regulating B-cell development (IKZF1, PBX1, RUNX1). Eleven novel translocations involved the genes ART4, C12orf60, MACROD2, TBL1XR1, LRRN4, KIAA1467, and ELMO1/MIR1200. Typically, patients harbored only single structural variations, except for one patient who displayed massive rearrangements in the context of a germline tumor suppressor TP53 mutation and a Li-Fraumeni syndrome-like family history. Another patient harbored a germline mutation in the DNA repair factor ATM. In summary, the relapse patients of our cohort were characterized by somatic mutations affecting the RAS pathway, epigenetic and developmental programs and germline mutations in DNA repair pathways. PMID:26189108

  19. Prognostic value of IDH1 mutations identified with PCR-RFLP assay in acute myeloid leukemia patients

    Background: Somatic mutations in isocitrate dehydrogenase 1 (1DH1) gene occur frequently in primary brain tumors. Recently theses mutations were demonstrated in acute myeloid leukemia (AML). So far, assessment of these mutations relied on the DNA sequencing technique. Aim of the work: The aim of this study was to detect somatic mutations in IDH1 gene using mismatched primers suitable for endonuclease based detection, without the need for DNA sequencing, and to estimate its prognostic value, on patients with de novo AML. Methods: Residual DNA extracted from pretreatment bone marrow (BM) samples of 100 patients with de novo AML was used. The polymerase chain reaction-restriction fragment length polymorphism method (PCR-RFLP) was adapted to IDHl gene, codon 132 mutations screening. Results: The frequency of IDH1 mutations was 13%. In the non-acute promyelocytic leukemia group (non-APL), IDH1 mutations were significantly associated with FLT3-ITD negative patients (p = 0.03). Patients with 1DH1 mutations did not achieve complete remission (CR). There was a trend for shorter overall survival (OS) in patients with IDH1 mutation compared to those with wild type (p = 0.08). Conclusion: IDH1 mutations are recurring genetic alterations in AML and they may have unfavorable impact on clinical outcome in adult AML. The PCR-RFLP method allows for a fast, inexpensive, and sensitive method for the detection of IDF11 mutations in AML.

  20. FLT3 INTERNAL TANDEM DUPLICATION AND D835 MUTATIONS IN PATIENTS WITH ACUTE LYMPHOBLASTIC LEUKEMIA AND ITS CLINICAL SIGNIFICANCE

    Ghaleb Elyamany

    2014-05-01

    Full Text Available The fms-like tyrosine kinase 3 (FLT3 gene is a member of the class III receptor tyrosine kinase family, mutations of FLT3 were first described in 1997 and account for the most frequent molecular mutations in acute myeloid leukemia. No data currently exist regarding FLT3 mutations in Saudi acute lymphoblastic leukemia (ALL patients as no study has reported for FLT3 mutations in Saudi ALL patients. In this retrospective study, we have examined a cohort of 77 ALL patients, to determine the prevalence of FLT3 mutations and the possible prognostic relevance of these mutations in ALL patients and did correlations to other biologic factors, such as karyotype, molecular mutations, and leukocyte count. FLT3 internal tandem duplication (ITD mutations and point mutation in tyrosine kinase domain (D835 mutations were analyzed in ALL patients at diagnosis by polymerase chain reaction (PCR. 2 cases (2.6%, 2/77 were positive for FLT3 mutations, one was found to have FLT3/ITD and other was found to have FLT3/D835. Our findings suggest that FLT3 mutations were not common in Saudi ALL and did not affect clinical outcome.

  1. An Adult Patient with Systemic Mastocytosis and B-Acute Lymphoblastic Leukemia

    Theodoros Iliakis; Niki Rougkala; Diamantopoulos, Panagiotis T; Vasiliki Papadopoulou; Fani Kalala; Konstantinos Zervakis; Nefeli Giannakopoulou; Polixeni Chatzinikolaou; Georgia Levidou; Eleftheria Lakiotaki; Penelope Korkolopoulou; Efstratios Patsouris; Eleni Variami; Nora-Athina Viniou

    2014-01-01

    Mastocytosis is a myeloproliferative neoplasm characterized by clonal expansion of abnormal mast cells, ranging from the cutaneous forms of the disease to mast cell leukemia. In a significant proportion of patients, systemic mastocytosis (SM) coexists with another hematologic malignancy, termed systemic mastocytosis with an associated hematologic nonmast cell lineage disorder (SM-AHNMD). Despite the pronounced predominance of concomitant myeloid neoplasms, the much more unusual coexistence of...

  2. Acute myeloid leukemia in patients older than 75: prognostic impact of FLT3-ITD and NPM1 mutations.

    Hirsch, Pierre; Qassa, Ghazi; Marzac, Christophe; Tang, Ruoping; Perrot, Jean-Yves; Isnard, Françoise; Mohty, Mohamad; Marie, Jean Pierre; Legrand, Ollivier

    2015-01-01

    The benefit associated with chemotherapy in older patients with acute myeloid leukemia (AML) is debated. The prognostic impact of molecular mutations in these patients is unknown. We identified 79 patients with AML aged 75 years or over. Forty-two received chemotherapy and 37 supportive care only. In intensively treated patients, overall survival was longer (p < 0.001). Achieving complete remission was associated with longer survival (p < 0.001). NPM1 mutations tended to be associated with a higher complete remission rate (p = 0.12). In multivariate analysis, FLT3-ITD was associated with poorer survival (p = 0.049). Patients harboring FLT3-ITD and no NPM1 mutation had a poorer prognosis than others (p = 0.02). Intensive treatments can benefit a portion of elderly patients. FLT3-ITD and NPM1 mutational status might be useful for prognosis stratification. PMID:24724782

  3. CT and MR imaging findings of appendiceal and hepatic mucormycosis in a patient with acute T-lymphoblastic leukemia

    Choi, Seo Youn; Lee, Min Hee; Lee, Hae Kyung; Yi, Boem Ha; Chin, Su Sie; Park, Seong Kyu; Chung, Jun Chul [Soonchunhyang University Bucheon Hospital, Bucheon (Korea, Republic of)

    2015-11-15

    Fungal infections occur in severely immunocompromised patients having profound and prolonged neutropenia. Here, we report a case of a 41-year-old female who, at the conclusion of induction chemotherapy for acute T-lymphoblastic leukemia, developed angioinvasive mucormycosis involving the appendix and liver, which presented as abdominal pain. This case is the first to provide detailed computed tomography and magnetic resonance imaging findings of angioinvasive appendiceal and hepatic mucormycosis. The implications of these findings as well as the diagnosis and management of mucormycosis, is further discussed.

  4. FLT3 and NPM1 mutations in Chinese patients with acute myeloid leukemia and normal cytogenetics.

    Wang, Lei; Xu, Wei-lai; Meng, Hai-tao; Qian, Wen-bin; Mai, Wen-yuan; Tong, Hong-yan; Mao, Li-ping; Tong, Yin; Qian, Jie-jing; Lou, Yin-jun; Chen, Zhi-mei; Wang, Yun-gui; Jin, Jie

    2010-10-01

    Mutations of fms-like tyrosine kinase 3 (FLT3) and nucleophosmin (NPM1) exon 12 genes are the most common abnormalities in adult acute myeloid leukemia (AML) with normal cytogenetics. To assess the prognostic impact of the two gene mutations in Chinese AML patients, we used multiplex polymerase chain reaction (PCR) and capillary electrophoresis to screen 76 AML patients with normal cytogenetics for mutations in FLT3 internal tandem duplication (FLT3/ITD) and exon 12 of the NPM1 gene. FLT3/ITD mutation was detected in 15 (19.7%) of 76 subjects, and NPM1 mutation in 20 (26.3%) subjects. Seven (9.2%) cases were positive for both FLT3/ITD and NPM1 mutations. Significantly more FLT3/ITD aberration was detected in subjects with French-American-British (FAB) M1 (42.8%). NPM1 mutation was frequently detected in subjects with M5 (47.1%) and infrequently in subjects with M2 (11.1%). FLT3 and NPM1 mutations were significantly associated with a higher white blood cell count in peripheral blood and a lower CD34 antigen expression, but not age, sex, or platelet count. Statistical analysis revealed that the FLT3/ITD-positive group had a lower complete remission (CR) rate (53.3% vs. 83.6%). Survival analysis showed that the FLT3/ITD-positive/NPM1 mutation-negative group had worse overall survival (OS) and relapse-free survival (RFS). The FLT3/ITD-positive/NPM1 mutation-positive group showed a trend towards favorable survival compared with the FLT3/ITD-positive/NPM1 mutation-negative group (P=0.069). Our results indicate that the FLT3/ITD mutation might be a prognostic factor for an unfavorable outcome in Chinese AML subjects with normal cytogenetics, while NPM1 mutation may be a favorable prognostic factor for OS and RFS in the presence of FLT3/ITD. PMID:20872983

  5. The Superiority of Allogeneic Hematopoietic Stem Cell Transplantation Over Chemotherapy Alone in the Treatment of Acute Myeloid Leukemia Patients with Mixed Lineage Leukemia (MLL) Rearrangements

    Yang, Hua; Huang, Sai; Zhu, Cheng-Ying; Gao, Li; Zhu, Hai-Yan; Lv, Na; Jing, Yu; Yu, Li

    2016-01-01

    Background Acute myeloid leukemia (AML) patients with mixed lineage leukemia (MLL) gene rearrangements always had a very poor prognosis. In this study, we report the incidence of MLL rearrangements in AML patients using gene analysis, as well as the clinical significance and prognostic features of these rearrangements. Material/Methods This retrospective study took place from April 2008 to November 2011 in the People’s Liberation Army General Hospital. A total 433 AML patients were screened by multiple nested reverse transcription polymerase chain reaction (RT-PCR) to determine the incidence of the 11 MLL gene rearrangements. There were 68 cases of MLL gene rearrangements, for a positive rate of 15.7%. A total of 24 patients underwent allogeneic hematopoietic stem cell transplantation (Allo-HSCT), and 34 patients received at least 4 cycles of chemotherapy. Ten patients were lost to follow-up. Results The median follow-up was 29 months. The complete remission (CR) rate was 85.4%. The overall survival (OS) was 57.4±5.9 months for the Allo-HSCT group and 21.0±2.1 months for the chemotherapy group. The Allo-HSCT group had superior survival compared with the chemotherapy group (5-year OS: 59±17% vs. 13±8%, P0.05). Multivariate analysis showed that transplantation, platelets >50×109/L at onset, and CR are associated with a better OS in MLL rearranged AML patients. Patients with thrombocytopenia and extramedullary involvement were prone to relapse. Conclusions Our results suggest that Allo-HSCT is superior to chemotherapy alone for treating MLL rearranged AML patients. Patients treated with Allo-HSCT have a better prognosis and a longer survival. CR is an independent prognostic factor for OS, and extramedullary involvement is an independent prognostic factor for DFS. MLL rearranged AML patients with thrombocytopenia at onset <50×109 had very bad OS and DFS. PMID:27373985

  6. Differentiation Therapy of Acute Myeloid Leukemia

    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.

  7. Differentiation Therapy of Acute Myeloid Leukemia

    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

  8. Differentiation Therapy of Acute Myeloid Leukemia

    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.

  9. Use of clofarabine for acute childhood leukemia

    A Pession

    2010-06-01

    Full Text Available A Pession, R Masetti, K Kleinschmidt, A MartoniPediatric Oncology and Hematology “Lalla Seràgnoli”, University of Bologna, ItalyAbstract: A second-generation of purine nucleoside analogs, starting with clofarabine, has been developed in the course of the search for new therapeutic agents for acute childhood leukemia, especially for refractory or relapsed disease. Clofarabine is a hybrid of fludarabine and cladribine, and has shown to have antileukemic activity in acute lymphoblastic leukemia as well as in myeloid disorders. As the only new antileukemic chemotherapeutic agent to enter clinical use in the last 10 years, clofarabine was approved as an orphan drug with the primary indication of use in pediatric patients. Toxicity has been tolerable in a heavily pretreated patient population, and clofarabine has been demonstrated to be safe, both as a single agent and in combination therapies. Liver dysfunction has been the most frequently observed adverse event, but this is generally reversible. Numerous Phase I and II trials have recently been conducted, and are still ongoing in an effort to find the optimal role for clofarabine in various treatment strategies. Concomitant use of clofarabine, cytarabine, and etoposide was confirmed to be safe and effective in two independent trials. Based on the promising results when used as a salvage regimen, clofarabine is now being investigated for its potential to become part of frontline protocols.Keywords: clofarabine, pediatric acute lymphoblastic leukemia, pediatric acute myeloid leukemia

  10. Brain damage after treatment for acute lymphoblastic leukemia. A report on 34 patients with special regard to MRI findings

    Biti, G.P.; Magrini, S.M.; Villari, N.; Caramella, D.; Guazzelli, G.; Rosi, A.; Lippi, A.

    1989-01-01

    In 34 patients treated for acute lymphoblastic leukemia (ALL), central nervous system (CNS) damage was assessed by clinical evaluation and brain magnetic resonance imaging (MRI). Twenty-seven of them had been off therapy from 5 to 109 months (median 64 months) while 7 had not completed the maintenance phase of their treatment. All the patients were disease-free when evaluated. None of the 3 patients who showed clinical CNS damage during the follow-up was symptomatic when submitted to MRI, while periventricular hyperintensity in T2-weighted images, suggestive of leukoencephalopathy, was present in 8 of the 34 patients. These subclinical abnormalities appear to be more frequent, transient in nature and treatment-related in patients evaluated shortly after the induction phase. Similar MRI findings seem, on the contrary, to be consequences of the disease on the CNS when appearing in long-term survivors. (orig.).

  11. Expression of CD133 in acute leukemia.

    Tolba, Fetnat M; Foda, Mona E; Kamal, Howyda M; Elshabrawy, Deena A

    2013-06-01

    There have been conflicting results regarding a correlation between CD133 expression and disease outcome. To assess CD133 expression in patients with acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) and to evaluate its correlation with the different clinical and laboratory data as well as its relation to disease outcome, the present study included 60 newly diagnosed acute leukemic patients; 30 ALL patients with a male to female ratio of 1.5:1 and their ages ranged from 9 months to 48 years, and 30 AML patients with a male to female ratio of 1:1 and their ages ranged from 17 to 66 years. Flow cytometric assessment of CD133 expression was performed on blast cells. In ALL, no correlations were elicited between CD133 expression and some monoclonal antibodies, but in AML group, there was a significant positive correlation between CD133 and HLA-DR, CD3, CD7 and TDT, CD13 and CD34. In ALL group, patients with negative CD133 expression achieved complete remission more than patients with positive CD133 expression. In AML group, there was no statistically significant association found between positive CD133 expression and treatment outcome. The Kaplan-Meier curve illustrated a high significant negative correlation between CD133 expression and the overall survival of the AML patients. CD133 expression is an independent prognostic factor in acute leukemia, especially ALL patients and its expression could characterize a group of acute leukemic patients with higher resistance to standard chemotherapy and relapse. CD133 expression was highly associated with poor prognosis in acute leukemic patients. PMID:23532815

  12. Treosulfan, Fludarabine Phosphate, and Total Body Irradiation Before Donor Stem Cell Transplant in Treating Patients With Myelodysplastic Syndrome or Acute Myeloid Leukemia

    2016-06-20

    Acute Myeloid Leukemia in Remission; Chronic Myelomonocytic Leukemia; Minimal Residual Disease; Myelodysplastic Syndrome; Myelodysplastic/Myeloproliferative Neoplasm; Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable

  13. Fatal lymphoproliferation and acute monocytic leukemia-like disease following infectious mononucleosis in the elderly

    Hehlmann, R.; Walther, B; ZÖLLNER, N.; Wolf, Hans J.; Deinhardt, F; Schmid, M.

    1981-01-01

    Three elderly patients are reported, in whom serologically confirmed recent infectious mononucleosis is followed by fatal lymphoproliferation (case 1), by acute monocytic leukemia (case 2), and by acute probably monocytic leukemia (case 3).

  14. Phase I Dose-Escalation Trial of Clofarabine Followed by Escalating Doses of Fractionated Cyclophosphamide in Children With Relapsed or Refractory Acute Leukemias

    2010-09-21

    Myelodysplastic Syndrome; Acute Myeloid Leukemia; Myeloproliferative Disorders; Acute Lymphocytic Leukemia; Acute Promyelocytic Leukemia; Acute Leukemia; Chronic Myelogenous Leukemia; Myelofibrosis; Chronic Myelomonocytic Leukemia; Juvenile Myelomonocytic Leukemia

  15. Clinical Research of Compound Zhebei Granules for Increasing the Therapeutic Effect of Chemotherapy in Refractory Acute Leukemia Patients

    LU Dian-rong; LI Dong-yun; CHEN Xin-yi; YE Pei-zhi; TIAN Shao-dan

    2009-01-01

    Objective:To observe the effects of Compound Zhebei Granules (复方浙贝颗粒 CZG) in chemotherapy for refractory acute leukemia.Method:Using a randomized, double-blind and multi-central concurrent control clinical research project, the patients conformed with the diagnostic criteria, according to the drug randomized method, were divided into a CZG group and a control group.The patients of the two groups respectively took the observation drug or a placebo 3 days before chemotherapy, and the therapeutic effects were evaluated after one course of chemotherapy.According to the clinical research project, 137 patients were enrolled, including 71 cases in the CZG group and 66 cases in the control group.Results:The clinical complete remission (CR)rate was 42.3% in the CZG group with a total effective rate of 73.2%, and it was 25.8% in the control group with a total effective rate of 53.0%, showing a statistically significant difference between the two groups (P<0.05).Conclusion:CZG can increase the clinical remission rate for refractory acute leukemia during chemotherapy.

  16. A combination of temsirolimus, an allosteric mTOR inhibitor, with clofarabine as a new therapeutic option for patients with acute myeloid leukemia

    Chiarini, Francesca; Lonetti, Annalisa; Teti, Gabriella; Orsini, Ester; Bressanin, Daniela; Cappellini, Alessandra; Ricci, Francesca; Tazzari, Pier Luigi; Ognibene, Andrea; Falconi, Mirella; Pagliaro, Pasqualepaolo; Iacobucci, Ilaria; Martinelli, Giovanni; Amadori, Sergio; McCubrey, James A.

    2012-01-01

    Signaling through the phosphatidylinositol 3-kinase (PI3K) pathway and its downstream effectors, Akt and mechanistic target of rapamycin (mTOR), is aberrantly activated in acute myeloid leukemia (AML) patients, where it contributes to leukemic cell proliferation, survival, and drug-resistance. Thus, inhibiting mTOR signaling in AML blasts could enhance their sensitivity to cytotoxic agents. Preclinical data also suggest that allosteric mTOR inhibition with rapamycin impaired leukemia initiati...

  17. Phase II Trial of Reduced-Intensity Busulfan/Clofarabine Conditioning with Allogeneic Hematopoietic Stem Cell Transplantation for Patients with Acute Myeloid Leukemia, Myelodysplastic Syndromes, and Acute Lymphoid Leukemia.

    El-Jawahri, Areej; Li, Shuli; Ballen, Karen K; Cutler, Corey; Dey, Bimalangshu R; Driscoll, Jessica; Hunnewell, Chrisa; Ho, Vincent T; McAfee, Steven L; Poliquin, Cathleen; Saylor, Meredith; Soiffer, Robert J; Spitzer, Thomas R; Alyea, Edwin; Chen, Yi-Bin

    2016-01-01

    Clofarabine has potent antileukemia activity and its inclusion in reduced-intensity conditioning (RIC) allogeneic hematopoietic stem cell transplantation (HSCT) for acute leukemia could potentially improve outcomes. We conducted a phase II study of busulfan (.8 mg/kg i.v. twice daily on days -5, -4, -3, and -2) with clofarabine (40 mg/m(2) i.v. daily on days -5, -4, -3, and -2) conditioning before allogeneic 8/8 HLA-matched related or unrelated HSCT. The primary endpoint was donor neutrophil engraftment by day +40. Secondary endpoints included nonrelapse mortality (NRM), acute and chronic graft-versus-host disease (GVHD), progression-free survival (PFS), and overall survival (OS). Thirty-four patients (acute myeloid leukemia [AML], n = 25; myelodysplastic syndromes, n = 5; and acute lymphoid leukemia, n = 4) were enrolled. Day 40+ engraftment with donor chimerism was achieved in 33 of 34 patients with 1 patient dying before count recovery. Day 100 and 1-year NRM were 5.9% (95% confidence interval [CI], 1.0 to 17.4) and 24% (95% CI, 11 to 39), respectively. The 2-year relapse rate was 26% (95% CI, 13 to 42). Cumulative incidences of acute and chronic GVHD were 21% and 44%, respectively. The 2-year PFS was 50% (95% CI, 32 to 65) and OS was 56% (95% CI, 38 to 71). For patients with AML in first complete remission, 2-year PFS and OS were both 82% (95% CI, 55 to 94). RIC with busulfan and clofarabine leads to successful engraftment with acceptable rates of NRM and GVHD. PMID:26260679

  18. Systemic mastocytosis with associated acute myelogenous leukemia

    Zhrebker, Leah; Cooper, Barry; Krause, John R.

    2014-01-01

    Systemic mastocytosis (SM) is a condition associated with a clonal neoplastic proliferation of mast cells. Approximately 40% of patients with SM present with an associated clonal hematological non–mast cell lineage disorder. Patients presenting with SM–acute myeloid leukemia (AML) have the worst prognosis. We present a case of a 62-year-old woman who was diagnosed with SM-AML. After initial treatment with a standard regimen of cytosine arabinoside (Ara-C)/idarubicin, her bone marrow showed re...

  19. Cytogenetic studies of Acute Myeloid Leukemia

    Tarek Abd -Alla Atia

    2010-01-01

    Acute myeloid leukemia (AML) describes as a group of hematopoietic stem cell disorders characterized by expansion of undifferentiated myeloid progenitors. Acquired chromosomal anomaly particularly reciprocal translocations constitute one of the major events contribute to leukemogenesis. Patient and Methods: 45 untreated, newly diagnosed patients with de novo AML were enrolled in the present study and subjected to cytogenetic analysis. Four ml of heparinized peripheral blood were collected for...

  20. Free-radical oxidation of lipids in erythrocyte membranes and endogenous alpha-tocopherol dynamics in blood plasma of acute leukemia patients

    Karagezyan, K.G.; Bilyan, L.F.; Osipova, E.N.; Porosyan, A.S.

    1985-12-01

    Interaction between free-radical oxidation of lipids and dynamics of the endogenous alpha-tocopherol level in membrane erythrocytes was studied in healthy blood donors (14), acute leukemia patients before treatment (27) and persons in remission (11) after appropriate treatment by the commonly known VAMP, AVAMP and TsAMP procedures and, in some cases, by use of combinations of prednisolone and 6-mercaptopurine. Free-radical oxidation of lipids was determined by the malonic dialdehyde yield in ascorbate- and NADPH-independent oxidation systems. The studies showed an inversely proportional dependence between reduction of the alpha-tocopherol level in the acute leukemia patients blood plasma and the intensity of free radical oxidation of lipids in the erythrocyte membranes. The combined therapy recommended in the study inhibited the peroxide formation process in the erythrocyte membranes significantly and promoted restoration of the endogenous alpha-tocopherol level which facilitated a favorable course of acute leukemia and promoted possible remission.

  1. Dose Escalation of Total Marrow Irradiation With Concurrent Chemotherapy in Patients With Advanced Acute Leukemia Undergoing Allogeneic Hematopoietic Cell Transplantation

    Wong, Jeffrey Y.C., E-mail: jwong@coh.org [Department of Radiation Oncology, City of Hope National Medical Center, Duarte, California (United States); Forman, Stephen; Somlo, George [Department of Hematology/Hematopoietic Cell Transplantation, City of Hope National Medical Center, Duarte, California (United States); Rosenthal, Joseph [Department of Hematology/Hematopoietic Cell Transplantation, City of Hope National Medical Center, Duarte, California (United States); Department of Pediatrics, City of Hope National Medical Center, Duarte, California (United States); Liu An; Schultheiss, Timothy; Radany, Eric [Department of Radiation Oncology, City of Hope National Medical Center, Duarte, California (United States); Palmer, Joycelynne [Department of Biostatistics, City of Hope National Medical Center, Duarte, California (United States); Stein, Anthony [Department of Hematology/Hematopoietic Cell Transplantation, City of Hope National Medical Center, Duarte, California (United States)

    2013-01-01

    Purpose: We have demonstrated that toxicities are acceptable with total marrow irradiation (TMI) at 16 Gy without chemotherapy or TMI at 12 Gy and the reduced intensity regimen of fludarabine/melphalan in patients undergoing hematopoietic cell transplantation (HCT). This article reports results of a study of TMI combined with higher intensity chemotherapy regimens in 2 phase I trials in patients with advanced acute myelogenous leukemia or acute lymphoblastic leukemia (AML/ALL) who would do poorly on standard intent-to-cure HCT regimens. Methods and Materials: Trial 1 consisted of TMI on Days -10 to -6, etoposide (VP16) on Day -5 (60 mg/kg), and cyclophosphamide (CY) on Day -3 (100 mg/kg). TMI dose was 12 (n=3 patients), 13.5 (n=3 patients), and 15 (n=6 patients) Gy at 1.5 Gy twice daily. Trial 2 consisted of busulfan (BU) on Days -12 to -8 (800 {mu}M min), TMI on Days -8 to -4, and VP16 on Day -3 (30 mg/kg). TMI dose was 12 (n=18) and 13.5 (n=2) Gy at 1.5 Gy twice daily. Results: Trial 1 had 12 patients with a median age of 33 years. Six patients had induction failures (IF), and 6 had first relapses (1RL), 9 with leukemia blast involvement of bone marrow ranging from 10%-98%, 5 with circulating blasts (24%-85%), and 2 with chloromas. No dose-limiting toxicities were observed. Eleven patients achieved complete remission at Day 30. With a median follow-up of 14.75 months, 5 patients remained in complete remission from 13.5-37.7 months. Trial 2 had 20 patients with a median age of 41 years. Thirteen patients had IF, and 5 had 1RL, 2 in second relapse, 19 with marrow blasts (3%-100%) and 13 with peripheral blasts (6%-63%). Grade 4 dose-limiting toxicities were seen at 13.5 Gy (stomatitis and hepatotoxicity). Stomatitis was the most frequent toxicity in both trials. Conclusions: TMI dose escalation to 15 Gy is possible when combined with CY/VP16 and is associated with acceptable toxicities and encouraging outcomes. TMI dose escalation is not possible with BU/VP16 due to

  2. Dose Escalation of Total Marrow Irradiation With Concurrent Chemotherapy in Patients With Advanced Acute Leukemia Undergoing Allogeneic Hematopoietic Cell Transplantation

    Purpose: We have demonstrated that toxicities are acceptable with total marrow irradiation (TMI) at 16 Gy without chemotherapy or TMI at 12 Gy and the reduced intensity regimen of fludarabine/melphalan in patients undergoing hematopoietic cell transplantation (HCT). This article reports results of a study of TMI combined with higher intensity chemotherapy regimens in 2 phase I trials in patients with advanced acute myelogenous leukemia or acute lymphoblastic leukemia (AML/ALL) who would do poorly on standard intent-to-cure HCT regimens. Methods and Materials: Trial 1 consisted of TMI on Days −10 to −6, etoposide (VP16) on Day −5 (60 mg/kg), and cyclophosphamide (CY) on Day −3 (100 mg/kg). TMI dose was 12 (n=3 patients), 13.5 (n=3 patients), and 15 (n=6 patients) Gy at 1.5 Gy twice daily. Trial 2 consisted of busulfan (BU) on Days −12 to −8 (800 μM min), TMI on Days −8 to −4, and VP16 on Day −3 (30 mg/kg). TMI dose was 12 (n=18) and 13.5 (n=2) Gy at 1.5 Gy twice daily. Results: Trial 1 had 12 patients with a median age of 33 years. Six patients had induction failures (IF), and 6 had first relapses (1RL), 9 with leukemia blast involvement of bone marrow ranging from 10%-98%, 5 with circulating blasts (24%-85%), and 2 with chloromas. No dose-limiting toxicities were observed. Eleven patients achieved complete remission at Day 30. With a median follow-up of 14.75 months, 5 patients remained in complete remission from 13.5-37.7 months. Trial 2 had 20 patients with a median age of 41 years. Thirteen patients had IF, and 5 had 1RL, 2 in second relapse, 19 with marrow blasts (3%-100%) and 13 with peripheral blasts (6%-63%). Grade 4 dose-limiting toxicities were seen at 13.5 Gy (stomatitis and hepatotoxicity). Stomatitis was the most frequent toxicity in both trials. Conclusions: TMI dose escalation to 15 Gy is possible when combined with CY/VP16 and is associated with acceptable toxicities and encouraging outcomes. TMI dose escalation is not possible

  3. The MLL recombinome of acute leukemias in 2013

    Meyer, C; Hofmann, Julian; Burmeister, T;

    2013-01-01

    Chromosomal rearrangements of the human MLL (mixed lineage leukemia) gene are associated with high-risk infant, pediatric, adult and therapy-induced acute leukemias. We used long-distance inverse-polymerase chain reaction to characterize the chromosomal rearrangement of individual acute leukemia...... patients. We present data of the molecular characterization of 1590 MLL-rearranged biopsy samples obtained from acute leukemia patients. The precise localization of genomic breakpoints within the MLL gene and the involved translocation partner genes (TPGs) were determined and novel TPGs identified. All...... patients were classified according to their gender (852 females and 745 males), age at diagnosis (558 infant, 416 pediatric and 616 adult leukemia patients) and other clinical criteria. Combined data of our study and recently published data revealed a total of 121 different MLL rearrangements, of which 79...

  4. Successful Control of Disseminated Intravascular Coagulation by Recombinant Thrombomodulin during Arsenic Trioxide Treatment in Relapsed Patient with Acute Promyelocytic Leukemia

    Motohiro Shindo

    2012-01-01

    Full Text Available Disseminated intravascular coagulation (DIC frequently occurs in patients with acute promyelocytic leukemia (APL. With the induction of therapy in APL using all-trans retinoic acid (ATRA, DIC can be controlled in most cases as ATRA usually shows immediate improvement of the APL. However, arsenic trioxide (ATO which has been used for the treatment of relapse in APL patients has shown to take time to suppress APL cells, therefore the control of DIC in APL with ATO treatment is a major problem. Recently, the recombinant soluble thrombomodulin fragment has received a lot of attention as the novel drug for the treatment of DIC with high efficacy. Here, we present a relapsed patient with APL in whom DIC was successfully and safely controlled by rTM during treatment with ATO.

  5. Early warning and prevention of pneumonia in acute leukemia by patient education, spirometry, and positive expiratory pressure

    Møller, Tom; Moser, Claus; Adamsen, Lis;

    2016-01-01

    intervention versus control group (2.17 per 1000 days vs. 6.52 per 1000 days, P = 0.021, respectively). A cross point at 80-76% of the personal FEV1 reference value showed high sensitivity and specificity on pneumonia development. Our data demonstrate the feasibility of educating AML patients in their......Long-lasting neutropenia associated with acute myeloid leukemia (AML) and its treatment gives rise to a high risk of pneumonia. The use of broad-spectrum antibiotic prophylaxis during outpatient management has not completely protected patients against admission due to infections and neutropenic...... fever, emphasizing the need to approach infection protection with complementary efforts. In a randomized controlled design, we examined the applicability of patient-performed daily spirometry [forced expiratory volume in one second (FEV1)] as an early warning tool and explored the effectiveness of...

  6. Quantitative analysis of human herpesvirus-6 genome in blood and bone marrow samples from Tunisian patients with acute leukemia: a follow-up study

    Faten Nefzi

    2012-11-01

    Full Text Available Abstract Background Infectious etiology in lymphoproliferative diseases has always been suspected. The pathogenic roles of human herpesvirus-6 (HHV-6 in acute leukemia have been of great interest. Discordant results to establish a link between HHV-6 activation and the genesis of acute leukemia have been observed. The objective of this study was to evaluate a possible association between HHV-6 infection and acute leukemia in children and adults, with a longitudinal follow-up at diagnosis, aplasia, remission and relapse. Methods HHV-6 load was quantified by a quantitative real-time PCR in the blood and bone marrow samples from 37 children and 36 adults with acute leukemia: 33 B acute lymphoblastic leukemia (B-ALL, 6 T acute lymphoblastic leukemia (T-ALL, 34 acute myeloid leukemia (AML. Results HHV-6 was detected in 15%, 8%, 30% and 28% of the blood samples at diagnosis, aplasia, remission and relapse, respectively. The median viral loads were 138, 244, 112 and 78 copies/million cells at diagnosis, aplasia, remission and relapse, respectively. In the bone marrow samples, HHV-6 was detected in 5%, 20% and 23% of the samples at diagnosis, remission and relapse, respectively. The median viral loads were 34, 109 and 32 copies/million cells at diagnosis, remission and relapse, respectively. According to the type of leukemia at diagnosis, HHV-6 was detected in 19% of the blood samples and in 7% of the bone marrow samples (with median viral loads at 206 and 79 copies/million cells, respectively from patients with B-ALL. For patients with AML, HHV-6 was present in 8% of the blood samples and in 4% of the bone marrow samples (with median viral loads at 68 and 12 copies/million cells, respectively. HHV-6 was more prevalent in the blood samples from children than from adults (25% and 9%, respectively and for the bone marrow (11% and 0%, respectively. All typable HHV-6 were HHV-6B species. No link was shown between neither the clinical symptoms nor the

  7. Phase II trial of clofarabine and daunorubicin as induction therapy for acute myeloid leukemia patients greater than or equal to 60 years of age

    Vigil, Carlos E; Tan, Wei; Deeb, George; Sait, Sheila; Block, AnneMarie W; Starostik, Petr; Griffiths, Elizabeth A.; Thompson, James E.; Greene, Jessica D.; Ford, Laurie A.; Wang, Eunice S.; Wetzler, Meir

    2013-01-01

    We designed a phase II study evaluating the upfront combination of clofarabine and daunorubicin in acute myeloid leukemia (AML) patients ≥60 years old. The median age of the 21 patients was 69 (range 60–85) years. Fourteen patients (67%) had unfavorable risk features. The principal toxicities were grade ≥3 infections and prolonged myelosuppression. Three (14%) deaths occurred from infectious complications. Six (28.6%) patients achieved complete remission including three (21.4%) of 14 patients...

  8. The clinical importance of myeloid antigen coexpression and TEL-AML1 mutation in patients with childhood acute lymphoblastic leukemia

    Ayşen Türedi Yıldırım

    2013-03-01

    Full Text Available Objective: In this study, we aim to investigate the relationship,if any, between clinical features, prognosis, and thecoexpressions and TEL-AML1 mutation in patients withacute lymphoblastic leukemia (ALL.Methods: Eigthy-three patients with acute lymphoblasticleukemia were retrospectively examined. Age, gender,White blood cell count, hemoglobin level, platelet count,ALL subtypei (B or T ALL, risk groups, surface antigensdeteceted by flow cytometry, existence of TEL-AML1 mutations,response, remission and relapse status at 8., 15.ve 33. Days of treatment were recorded and analyzed.Results: 15 (18% out of 83 were identified with aberrantantigen expression. Of these patients, twelve (14.4%had myeloid antigen coexpression (CD13 and/or CD33,two with B cell ALL had CD2 and CD7 coexpressions respectively,one with T cell ALL had CD19 coexpression.No significant differences were found between patientswith and without myeloid antigen coexpression in terms ofhemoglobin levels, white blood cells and platelet counts,responses given on the 8th, 15th, and 30th days on the treatment,risk groups, and relapse (p>0.05. Myeloid antigencoexpression was found in 4 of 13 patients who were identifiedwith TEL-AML1 mutation. No significant relationshipwas found between this mutation and coexpressions. Norelapse and exitus were observed in four patients with coexpressionand TEL-AML1.Conclusion: The prognosis and clinical features showsno statistically significant relationship with the presence ofneither Myeloid antigen expression nor TEL-AML1 mutation.We believe, however, the future studies involving biggersample sizes will prove to be useful in terms of moreconvincing results. J Clin Exp Invest 2013; 4(1: 90-94Key words: Acute lenfoblastic leukemia, coexpression,TEL-AML1 mutation, prognosis

  9. Hematopoietic Stem Cell Transplantation in Children with Acute Lymphoblastic Leukemia

    Ibrahim Bayram

    2014-01-01

    In children patients with acute lymphoblastic leukemia, according to the European bone marrow transplant handbook, the indications for stem cell transplantation, conditioning regimen, donor selection and information about sources of stem cells will be evaluated.

  10. Novel Therapies for Relapsed Acute Lymphoblastic Leukemia

    Fullmer, Amber; O’Brien, Susan; Kantarjian, Hagop; Jabbour, Elias

    2009-01-01

    The outcome of salvage therapy for relapsed acute lymphoblastic leukemia (ALL) remains poor. Salvage therapy mimics regimens with activity in newly diagnosed ALL. Novel strategies under investigation as monotherapy or in combination with chemotherapy improve the treatment of relapsed disease. For some ALL subsets, specific therapies are indicated. The addition of targeted therapy in Philadelphia chromosome–positive ALL has improved responses in relapsed patients without resistance to availabl...

  11. MINIMAL RESIDUAL DISEASE IN ACUTE LYMPHOBLASTIC LEUKEMIA

    Campana, Dario

    2009-01-01

    In patients with acute lymphoblastic leukemia (ALL), monitoring of minimal residual disease (MRD) offers a way to precisely assess early treatment response and detect relapse. Established methods to study MRD are flow cytometric detection of abnormal immunophenotypes, polymerase chain reaction (PCR) amplification of antigen-receptor genes, and PCR amplification of fusion transcripts. The strong correlation between MRD levels and risk of relapse in childhood ALL is well established; studies in...

  12. Effectiveness and safety of different azacitidine dosage regimens in patients with myelodysplastic syndromes or acute myeloid leukemia.

    García-Delgado, Regina; de Miguel, Dunia; Bailén, Alicia; González, José Ramón; Bargay, Joan; Falantes, José F; Andreu, Rafael; Ramos, Fernando; Tormo, Mar; Brunet, Salut; Figueredo, Antonio; Casaño, Javier; Medina, Angeles; Badiella, Llorenç; Jurado, Antonio Fernández; Sanz, Guillermo

    2014-07-01

    We investigated the effectiveness and tolerability of azacitidine in patients with World Health Organization-defined myelodysplastic syndromes, or acute myeloid leukemia with 20-30% bone marrow blasts. Patients were treated with azacitidine, with one of three dosage regimens: for 5 days (AZA 5); 7 days including a 2-day break (AZA 5-2-2); or 7 days (AZA 7); all 28-day cycles. Overall response rates were 39.4%, 67.9%, and 51.3%, respectively, and median overall survival (OS) durations were 13.2, 19.1, and 14.9 months. Neutropenia was the most common grade 3-4 adverse event. These results suggest better effectiveness-tolerability profiles for 7-day schedules. PMID:24795069

  13. Acute myelogenous leukemia switch lineage upon relapse to acute lymphoblastic leukemia: a case report

    Dorantes-Acosta, Elisa; Arreguin-Gonzalez, Farina; Rodriguez-Osorio, Carlos A; Sadowinski, Stanislaw; Pelayo, Rosana; Medina-Sanson, Aurora

    2009-01-01

    Acute leukemia, the most common form of cancer in children, accounts for approximately 30% of all childhood malignancies, with acute lymphoblastic leukemia being five times more frequent than acute myeloid leukemia. Lineage switch is the term that has been used to describe the phenomenon of acute leukemias that meet the standard French-American-British system criteria for a particular lineage (either lymphoid or myeloid) upon initial diagnosis, but meet the criteria for the opposite lineage a...

  14. Acute myocardial infarction during induction chemotherapy for acute MLL t(4;11) leukemia with lineage switch and extreme leukocytosis

    Čolović Nataša; Bogdanović Andrija; Virijević Marijana; Vidović Ana; Tomin Dragica

    2015-01-01

    Introduction. In patients with acute leukemias hemorrhage is the most frequent problem. Vein thrombotic events may appear rarely but arterial thromboses are exceptionally rare. We present a patient with acute leukemia and bilateral deep leg vein thrombosis who developed an acute myocardial infarction (AMI) during induction chemotherapy. The etiology and treatment of AMI in patients with acute leukemia, which is a rare occurrence, is discussed. Case Outline....

  15. Bone scintigraphy in acute myeloid leukemia patient with fungal vertebral osteomyelitis

    Zekiye Hasbek

    2013-09-01

    Full Text Available The result of the magnetic resonance imaging (MRI study was reported as “metastasis of primary disease on L2-L3 vertebrae” in a 63-year-old male patient, who developed a back pain after receiving four courses of treatment for AML. The patient, who did not respond to pain medication, was sent to nuclear medicine department for a bone scintigraphy. Diffuse increased osteoblastic activity was reported on L2-L3 vertebrae with a suspicion about infection or fracture, together with a focal osteoblastic activity involvement in the right sacroiliac joint in the bone scintigraphy which was made with Tc99m-MDP. In the mean time, the patient complained about progressive loss of strength on bilateral lower extremities and numbness in legs. Repeated MRI was reported as “irregularities in L2-L3 vertebral disc region concordant with infection, prominent thecal pressure, loss of height in L2-L3 vertebrae associated with osteomyelitis and a mass concordant with paravertebral abscess and granulation tissue”. The patient was operated and necrotic tissue was removed by curettage, relieving the compression on L2-L3 and on the disc distance. In culture examination of the sample “candida albicans” was isolated. Antifungal treatment with Amphotericin B was started. Patient's pain was reduced and MRI findings showed some regression in abscess following the treatment. There was improvement in neurological examination. However, relapse in AML was observed in bone marrow aspiration, performed during follow-up and chemotherapy was started again. On the second day of chemotherapy high fever started and cellulitis developed on the right leg. The patient received hemodialysis treatment due to increase in BUN and creatinine levels. Pulmonary edema and associated respiratory insufficiency was developed and the patient died. Fungal infections are one of the most important clinical problems in leukemia patients. However, vertebral osteomyelitis secondary to fungal

  16. Low expression of Toll-like receptors in peripheral blood mononuclear cells of pediatric patients with acute lymphoblastic leukemia.

    Sánchez-Cuaxospa, María; Contreras-Ramos, Alejandra; Pérez-Figueroa, Erandi; Medina-Sansón, Aurora; Jiménez-Hernández, Elva; Torres-Nava, José R; Rojas-Castillo, Emilio; Maldonado-Bernal, Carmen

    2016-08-01

    Cancer is the second most common cause of death among children aged 1-14 years. Leukemia accounts for one-third of all childhood cancers, 78% of which is acute lymphoblastic leukemia (ALL). The development of cancer has been associated with malignant cells that express low levels of immunogenic molecules, which facilitates their escape from the antineoplastic immune response. It is thought that it may be possible to rescue the antineoplastic immune response through the activation of recognition receptors, such as Toll-like receptors (TLRs), which activate the innate immune system. TLRs are type I membrane glycoproteins expressed mainly in immune system cells such as monocytes, neutrophils, macrophages, dendritic cells, T, B and natural killer cells. The aim of the present study was to evaluate the expression of TLR1, TLR3, TLR4, TLR7 and TLR9 in peripheral blood mononuclear cells (PBMCs) in patients with ALL and prior to any treatment. PBMCs were obtained from 50 pediatric patients diagnosed with ALL and from 20 children attending the ophthalmology and orthopedics services. The mean fluorescence intensity was obtained by analysis of immunofluorescence. We found lower expression levels of TLR1, TLR3, TLR4, TLR7 and TLR9 in PBMCs from patients with ALL compared with those from control patients. We also observed that the PBMCs from patients with Pre-B and B ALL had lower TLR4 expression than controls and patients with Pro-B, Pre-B, B and T ALL had lower TLR7 expression than controls. The present study is the first to demonstrate reduced expression of TLRs in PBMCs from pediatric patients with ALL. This finding is of great relevance and may partly explain the reduction in the antineoplastic immune response in patients with ALL. PMID:27277333

  17. Advances in Management of Acute Promyelocytic Leukemia with Arsenic Trioxide

    MA Jun

    2007-01-01

    @@ Acute promyelocytic leukemia (APL), with specific features in cell morphology, is classified as M3 by French-American-British (FAB).Among M3, 95% of patients show specific chromosome translocation t(15;17)q(22;21) with PML-RAR α fusion gene, and 5% of patients show other subtypes. According to the statistical analysis of 2 540 adult acute myeloid leukemia (AML)cases in Harbin Institute of Hematology & Oncology, APL accounted for 23%.

  18. Vosaroxin and vosaroxin plus low-dose Ara-C (LDAC) vs low-dose Ara-C alone in older patients with acute myeloid leukemia

    Dennis, Mike; Russell, Nigel; Hills, Robert K;

    2015-01-01

    The development of new treatments for older patients with acute myeloid leukemia is an active area, but has met with limited success. Vosaroxin, a quinolone-derived intercalating agent has several properties that could prove beneficial. Initial clinical studies showed it to be well-tolerated in o...

  19. Frequent ASXL2 mutations in acute myeloid leukemia patients with t(8;21)/RUNX1-RUNX1T1 chromosomal translocations

    Micol, Jean-Baptiste; Duployez, Nicolas; Boissel, Nicolas; Petit, Arnaud; Geffroy, Sandrine; Nibourel, Olivier; Lacombe, Catherine; Lapillonne, Helene; Etancelin, Pascaline; Figeac, Martin; Renneville, Aline; Castaigne, Sylvie; Leverger, Guy; Ifrah, Norbert; Dombret, Hervé

    2014-01-01

    ASXL2 was mutated in 22.7% (25/110) of adult and pediatric t(8;21)/RUNX1-RUNX1T1 acute myeloid leukemia patients.ASXL2 mutations are mutually exclusive with ASXL1 mutations and occur in t(8;21) but not inv(16)/t(16;16) or RUNX1-mutant AML.

  20. Differentiation syndrome in patients with acute promyelocytic leukemia treated with all- trans retinoic acid and anthracycline chemotherapy: Characteristics, outcome, and prognostic factors

    P. Montesinos (Pau); J.M. Bergua (Juan Miguel); E. Vellenga (Edo); C. Rayón (Chelo); R. Parody (Ricardo); J. de Serna (Javier); A. León (Angel); J. Esteve (Jordi); G. Milone (Gustavo); G. Debén (Guillermo); C. Rivas (Concha); M. González (Marcos); M. Tormo (Mar); D.M. Joaquín; J.D. González (José David); S. Negri (Silvia); E. Amutio (Elena); S. Brunet (Salut); B. Löwenberg (Bob); M.A. Sanz (Miguel Angel)

    2009-01-01

    textabstractDifferentiation syndrome (DS) can be a life-threatening complication in patients with acute promyelocytic leukemia (APL) undergoing induction therapy with all- trans retinoic acid (ATRA). Detailed knowl- edge about DS has remained limited. We present an analysis of the incidence, char- a

  1. The Prognostic Impact of K-RAS Mutations in Adult Acute Myeloid Leukemia Patients Treated with High Dose Cytarabine

    Activating point mutation of the RAS gene has been generally accepted as an oncogenic event in a variety of malignancies. It represents one of the most common genetic alterations in acute myeloid leukemia (AML). However there is still controversy about its clinical relevance on the treatment outcome of this leukemia. Objective: This study aimed to clarify the biologic and prognostic impact of K-RAS mutations in relation to the dose of cytarabine (ara-C) used in post induction consolidation chemotherapy in adult AML patients. Patients and Methods: The study comprised 71de novo AML patients with a male: Female ratio of 1.4: 1; their ages ranged from 21-59 years with a median of 37 years. They were subjected to full clinical evaluation, routine laboratory investigations, cytogenetic studies by G banding and K-RAS mutation detection using realtime PCR. The patients were randomized into 2 groups (gps) according to the ara-C dose used in consolidation treatment, HDAC gp receiving 400 mg ara-C and LDAC gp receiving 100 mg ara-C. They were followed over a period of 5 years. Results: Mutations in the K-RAS gene (mutRAS) were detected in 23 patients (32%) with the remaining 48 patients (68%) having wild type RAS (wtRAS). Blast cell percentage was significantly lower in mutRAS compared to wtRAS patients (p=<0.001). The M4 subtype of AML and cases with Inv 16 showed significantly higher frequencies in mutRAS compared to wtRAS patients, (p=0.015, 0.003, respectively). The patients were followed up for a median of 43 months (range 11-57 months). There was no significant difference in overall survival (OS) between mutRAS and wtRAS patients (p=0.326). Within the mutRAS patients treated with HDAC, cumulative OS was significantly higher than those treated with LDAC (p=0.001). This was not the case in the wtRAS group (p=0.285). There was no significant difference in disease The Prognostic Impact of K-RAS Mutations in Adult Acute Myeloid Leukemia Patients Treated with High Dose

  2. Relapsed childhood acute lymphoblastic leukemia in the Nordic countries

    Oskarsson, Trausti; Söderhäll, Stefan; Arvidson, Johan;

    2016-01-01

    Relapse is the main reason for treatment failure in childhood acute lymphoblastic leukemia. Despite improvements in the up-front therapy, survival after relapse is still relatively poor, especially for high-risk relapses. The aims of this study were to assess outcomes following acute lymphoblastic...... leukemia relapse after common initial Nordic Society of Paediatric Haematology and Oncology protocol treatment; to validate currently used risk stratifications, and identify additional prognostic factors for overall survival. Altogether, 516 of 2735 patients (18.9%) relapsed between 1992 and 2011 and were...... development of novel approaches is urgently needed to increase survival in relapsed childhood acute lymphoblastic leukemia....

  3. A high BMI is a risk factor in younger patients with de novo acute myelogenous leukemia.

    Crysandt, Martina; Kramer, Michael; Ehninger, Gerhard; Bornhäuser, Martin; Berdel, Wolfgang E; Serve, Hubert; Röllig, Christoph; Kaifie, Andrea; Jost, Edgar; Brummendorf, Tim H; Wilop, Stefan

    2016-07-01

    Overweight and obese patients have an increased risk to develop several malignancies and, additionally, body mass index (BMI) impacts on outcome in several solid tumors. However, little is known for AML. We analyzed a cohort of 3526 patients with AML treated in three prospective multicenter trials within the German Study Alliance Leukemia. In multivariate analyses, we identified BMI as an independent risk factor for both DFS (HR 1.014, P = 0.0217) and OS (HR 1.015, P AML younger than 65 yr with intermediate risk and adverse cytogenetics. Overweight with a BMI ≥25 kg/m² best discriminated the worse outcome and led to an absolute reduction in long-term survival of 5-7% in the group of all younger patients (3-yr OS 39.9% vs. 47.3%; 10-yr OS 28.7% vs. 33.8%, P = 0.0002). Additionally, response to induction therapy was significantly reduced in these patients (76.9% vs. 82.8%, P AML, overweight and obesity are risk factors for impaired response to induction therapy, DFS and OS. This effect is, in part but not fully, explained by dose reduction such as dose-capping at a body surface area of 2 m². PMID:26277604

  4. CHP2 gene expression and quantitation in Egyptian patients with acute leukemia

    Amira Ahmed Hammam; Hisham Hasan Eissa; Mohamed Roshdy El Masry; Sarah Mahmoud

    2014-01-01

    Aim: CHP2 (calcineurin B homologous protein 2) is identified as a tumor-associated antigen highly expressed in different malignancies. It plays a critical role in cancer cell development, proliferation, motility and survival. It is suggested that the human tumor related gene CHP2 expression in leukemia primary cells and leukemia cell lines significantly increase, which may play an important role in growth process of leukemia cells. Methods: In this study, the expression of CHP2 gene was an...

  5. Cytomegalovirus induces strong antileukemic effect in acute myeloid leukemia patients following sibling HSCT without ATG-containing regimen.

    Bao, Xiebing; Zhu, Qian; Xue, Shengli; Hu, Xiaohui; Ma, Xiao; Chen, Feng; Chen, Suning; Sun, Aining; Wu, Depei; Yu, Jianhua; Wu, Xiaojin; Qiu, Huiying

    2016-01-01

    A considerable number of studies have demonstrated that cytomegalovirus (CMV) reactivation after allogeneic hematopoietic stem cell transplantation (Allo-HSCT) could enforce graft-versus leukemia (GVL) effect in acute myeloid leukemia (AML) patients. However, the use of antithymocyte globulin (ATG) as part of graft-versus-host disease (GVHD) prophylaxis may dampen this beneficial effect of CMV replication. In this context, we retrospectively analyzed the effect of CMV reactivation on relapse, survival and prognosis in a total of 227 AML patients who received a myeloablative (MA) conditioning regimen at a single research center between January 2010 and April 2013. Of these 227 patients, 110 cases received non-ATG-containing regimens and 117 cases received ATG-containing regimens. CMV reactivation occurred in 45 patients (41%) among non-ATG regimen group and 73 patients (62%) among ATG regimen group (P = 0.001). At a median time to follow-up of 27.5 months, a lower risk of cumulative relapse incidence associated with CMV reactivation was observed in non-ATG group in multivariate analyses (OR 0.28, 95% CI 0.10-0.79; P = 0.016). However, CMV reactivation after transplantation did not significantly decrease the cumulative incidence of relapse in our ATG group (OR 0.28, 95% CI 0.10-0.79; P = 0.016). Collectively, our results demonstrate that in AML patients following sibling HSCT, the CMV-induced beneficial effect on relapse occurs only in the MA regimens containing no ATG, although ATG promotes CMV reactivation. PMID:27158357

  6. Acute Lymphoblastic Leukemia (ALL) (For Parents)

    ... of WBC) are produced, a child will develop acute lymphoblastic, or lymphoid, leukemia (ALL). This is the most common type of childhood leukemia, affecting about 75% of kids with this cancer of the blood cells. Kids ... (AML) Chronic Myelogenous Leukemia (CML) Cancer ...

  7. Brachial Plexopathy due to Myeloid Sarcoma in a Patient With Acute Myeloid Leukemia After Allogenic Peripheral Blood Stem Cell Transplantation.

    Ha, Yumi; Sung, Duk Hyun; Park, Yoonhong; Kim, Du Hwan

    2013-04-01

    Myeloid sarcoma is a solid, extramedullary tumor comprising of immature myeloid cells. It may occur in any organ; however, the invasion of peripheral nervous system is rare. Herein, we report the case of myeloid sarcoma on the brachial plexus. A 37-year-old woman with acute myelogenous leukemia achieved complete remission after chemotherapy. One year later, she presented right shoulder pain, progressive weakness in the right upper extremity and hypesthesia. Based on magnetic resonance images (MRI) and electrophysiologic study, a provisional diagnosis of brachial plexus neuritis was done and hence steroid pulse therapy was carried out. Three months later the patient presented epigastric pain. After upper gastrointestinal endoscopy, myeloid sarcoma of gastrointestinal tract was confirmed pathologically. Moreover, 18-fluoride fluorodeoxyglucose positron emission tomography showed a fusiform shaped mass lesion at the brachial plexus overlapping with previous high signal lesion on the MRI. Therefore, we concluded the final diagnosis as brachial plexopathy due to myeloid sarcoma. PMID:23705126

  8. Arsenic in the cerebrospinal fluid of a patient receiving arsenic trioxide for relapsed acute promyelocytic leukemia with CNS involvement.

    Knipp, Sabine; Gattermann, Norbert; Schapira, Marc; Käferstein, Herbert; Germing, Ulrich

    2007-11-01

    We report on a 42-year-old patient whose relapse of acute promyelocytic leukaemia (APL) included meningeal infiltration. Since he had previously experienced ATRA syndrome, he received arsenic trioxide (ATO) plus intrathecal therapy with cytarabine, prednisone, and methotrexate. We measured the concentration of arsenic in his cerebrospinal fluid (CSF). Arsenic showed a peak CSF concentration of 0.008 mg/l (0.11 micromol/l) and a nadir of 0.002 mg/l (0.027 micromol/l), both representing about 14% of blood levels. ATO thus crosses the blood-CSF-barrier when administered intravenously, but the concentration in CSF is probably not sufficient for treatment of meningeal leukemia. PMID:17416415

  9. Epidemiology of acute lymphoblastic leukemia

    Although the etiology of acute leukemia is largely unknown, some facets of the puzzle are becoming clarified. Recognition of important patterns in age-specific mortality rates has suggested that events early in life, perhaps even prenatally, may have an influence on developing leukemia in childhood. The racial differences evident in mortality, incidence, and immunologic subtype of ALL suggest either differences in exposures to certain factors or differences in responses to those factors by white children. Hereditary factors appear to play a role. Familial and hereditary conditions exist that have high incidences of acute leukemia. Chromosomal anomalies are common in these conditions. Viral infections may play a role by contributing to alteration in genetic material through incorporation of the viral genome. How that virus is dealt with after primary infection seems important. The presence of immunodeficiency may allow wider dissemination or enhanced replication of such viruses, thereby increasing the likelihood of cellular transformation to an abnormal cell. Proliferation of that malignant cell to a clone may depend on other cofactors. Perhaps prolonged exposure to substances like benzene or alkylating agents may enhance these interactions between virus and genetic material. Does this change DNA repair mechanisms. Are viral infections handled differently. Is viral genomic information more easily integrated into host cells. Ionizing radiation has multiple effects. Alteration in genetic material occurs both at the molecular and chromosomal levels. DNA may be altered, lost, or added in the cell's attempt to recover from the injury

  10. The prognostic impact of K-RAS mutations in adult acute myeloid leukemia patients treated with high-dose cytarabine

    Ahmad EI

    2011-07-01

    Full Text Available Ebtesam I Ahmad, Heba H Gawish, Nashwa MA Al Azizi, Ashraf M ElhefniClinical Pathology Department, Hematology and Oncology Unit of Internal Medicine Department, Faculty of Medicine, Zagazig University, Sharkia, EgyptBackground: Activating point mutation of the RAS gene has been generally accepted as an oncogenic event in a variety of malignancies. It represents one of the most common genetic alterations in acute myeloid leukemia (AML. However, little is known about its clinical relevance in the treatment outcome for this leukemia.Objective: This study aimed to clarify the biologic and prognostic impact of K-RAS mutations in relation to the dose of cytarabine (ara-C used in postinduction consolidation chemotherapy in adult AML patients.Patients and methods: The study comprised of 71 de novo AML patients with male/female ratio 1.4:1; their ages ranged from 21–59 years with a median of 37 years. They were subjected to full clinical evaluation, routine laboratory investigations, cytogenetic studies by G-banding (Giemsa staining, and K-RAS mutation detection using real-time polymerase chain reaction. The patients were randomized into two groups according to the ara-C dose used in consolidation treatment, the high the dose ara-C (HDAC group receiving 400 mg ara-C and-low-dose ara-C (LDAC group receiving 100 mg ara-C; they were followed over a period of five years.Results: Mutations in the K-RAS gene (mutRAS were detected in 23 patients (32% with the remaining 48 patients (68% having wild-type RAS (wtRAS. The percent of blast cells was significantly lower in mutRAS compared to wtRAS patients (P ≤ 0.001 while M4 subtype of AML and Inv(16 frequencies were significantly higher in mutRAS compared to wtRAS patients (P = 0.015 and (P = 0.003, respectively. The patients were followed up for a median of 43 months (range 11–57 months. There was no significant difference in overall survival (OS between mutRAS and wtRAS (P = 0.326. Within the mut

  11. Phase 1 study of clofarabine in pediatric patients with relapsed/refractory acute lymphoblastic leukemia in Japan.

    Koh, Katsuyoshi; Ogawa, Chitose; Okamoto, Yasuhiro; Kudo, Kazuko; Inagaki, Jiro; Morimoto, Tsuyoshi; Mizukami, Hideya; Ecstein-Fraisse, Evelyne; Kikuta, Atsushi

    2016-08-01

    A phase 1 study was conducted to evaluate the safety, pharmacokinetics (PK), efficacy and pharmacogenetic characteristics of clofarabine in seven Japanese pediatric patients with relapsed/refractory acute lymphoblastic leukemia (ALL). Patients in Cohort 1 received clofarabine 30 mg/m(2)/day for 5 days, followed by 52 mg/m(2)/day for 5 days in subsequent cycles. Cohort 2 patients were consistently treated with 52 mg/m(2)/day for 5 days. No more than six cycles were performed. Every patient had at least one ≥Grade 3 adverse event (AE). AEs (≥Grade 3) related to clofarabine were anaemia, neutropenia, febrile neutropenia, thrombocytopenia, alanine aminotransferase increased, aspartate aminotransferase increased, haemoglobin decreased, and platelet (PLT) count decreased. C max and AUC of clofarabine increased in a dose-dependent fashion, but its elimination half-life (T 1/2) did not appear to be dependent on dose or duration of treatment. Clofarabine at 52 mg/m(2)/day shows similarly tolerable safety and PK profiles compared to those in previous studies. No complete remission (CR), CR without PLT recovery, or partial remission was observed. Since clofarabine is already used as a key drug for relapsed/refractory ALL patients in many countries, the efficacy of clofarabine in Japanese pediatric patients should be evaluated in larger study including more patients, such as by post-marketing surveillance. PMID:27086352

  12. Acute megakaryoblastic leukemia, unlike acute erythroid leukemia, predicts an unfavorable outcome after allogeneic HSCT.

    Ishiyama, Ken; Yamaguchi, Takuhiro; Eto, Tetsuya; Ohashi, Kazuteru; Uchida, Naoyuki; Kanamori, Heiwa; Fukuda, Takahiro; Miyamura, Koichi; Inoue, Yoshiko; Taguchi, Jun; Mori, Takehiko; Iwato, Koji; Morishima, Yasuo; Nagamura-Inoue, Tokiko; Atsuta, Yoshiko; Sakamaki, Hisashi; Takami, Akiyoshi

    2016-08-01

    Acute erythroid leukemia (FAB-M6) and acute megakaryoblastic leukemia (FAB-M7) exhibit closely related properties in cells regarding morphology and the gene expression profile. Although allogeneic hematopoietic stem cell transplantation (allo-HSCT) is considered the mainstay of the treatment for both subtypes of leukemia due to their refractoriness to chemotherapy and high rates of relapse, it remains unclear whether allo-HSCT is curative in such cases due to their scarcity. We retrospectively examined the impact of allo-HSCT in 382 patients with M6 and 108 patients with M7 using nationwide HSCT data and found the overall survival (OS) and relapse rates of the M6 patients to be significantly better than those of the M7 patients after adjusting for confounding factors and statistically comparable with those of the patients with M0/M1/M2/M4/M5 disease. Consequently, the factors of age, gender, performance status, karyotype, disease status at HSCT and development of graft-vs.-host disease predicted the OS for the M6 patients, while the performance status and disease status at HSCT were predictive of the OS for the M7 patients. These findings substantiate the importance of distinguishing between M6 and M7 in the HSCT setting and suggest that unknown mechanisms influence the HSCT outcomes of these closely related subtypes of leukemia. PMID:27244257

  13. Myeloablative allogeneic versus autologous stem cell transplantation in adult patients with acute lymphoblastic leukemia in first remission: A prospective sibling donor versus no-donor comparison

    Cornelissen, Jan; Holt, Bronno; Verhoef, Gregor; Veer, Mars; Oers, Marinus; Ossenkoppele, Gert; Sonneveld, Pieter; Maertens, Johan; Marwijk Kooy, Marinus; Schaafsma, Martijn; Wijermans, Pierre; Biesma, Douwe; Wittebol, Shulamit; Voogt, Paul; Baars, Joke

    2009-01-01

    textabstractWhile commonly accepted in poor-risk acute lymphoblastic leukemia (ALL), the role of allogeneic hematopoietic stem cell transplantation (allo-SCT) is still disputed in adult patients with standard-risk ALL. We evaluated outcome of patients with ALL in first complete remission (CR1), according to a sibling donor versus no-donor comparison. Eligible patients (433) were entered in 2 consecutive, prospective studies, of whom 288 (67%) were younger than 55 years, in CR1, and eligible t...

  14. Prognosis of acute myeloid leukemia harboring monosomal karyotype in patients treated with or without allogeneic hematopoietic cell transplantation after achieving complete remission

    Yanada, Masamitsu; Kurosawa, Saiko; Yamaguchi, Takuhiro; Yamashita, Takuya; Moriuchi, Yukiyoshi; Ago, Hiroatsu; Takeuchi, Jin; Nakamae, Hirohisa; Taguchi, Jun; Sakura, Toru; Takamatsu, Yasushi; Waki, Fusako; Yokoyama, Hiroki; Watanabe, Masato; Emi, Nobuhiko

    2012-01-01

    To evaluate the prognostic impact of monosomal karyotype on post-remission outcome in acute myeloid leukemia, we retrospectively analyzed 2,099 patients who had achieved complete remission. Monosomal karyotype was noted in 73 patients (4%). Of these, the probability of overall survival from first complete remission was 14% at four years, which was significantly lower than that reported in patients without monosomal karyotype, primarily due to a high relapse rate (86%). Monosomal karyotype rem...

  15. Autonomous growth potential of leukemia blast cells is associated with poor prognosis in human acute leukemias

    Jakubowski Ann A

    2009-12-01

    Full Text Available Abstract We have described a severe combined immunodeficiency (SCID mouse model that permits the subcutaneous growth of primary human acute leukemia blast cells into a measurable subcutaneous nodule which may be followed by the development of disseminated disease. Utilizing the SCID mouse model, we examined the growth potential of leukemic blasts from 133 patients with acute leukemia, (67 acute lymphoblastic leukemia (ALL and 66 acute myeloid leukemia (AML in the animals after subcutaneous inoculation without conditioning treatment. The blasts displayed three distinct growth patterns: "aggressive", "indolent", or "no tumor growth". Out of 133 leukemias, 45 (33.8% displayed an aggressive growth pattern, 14 (10.5% displayed an indolent growth pattern and 74 (55.6% did not grow in SCID mice. The growth probability of leukemias from relapsed and/or refractory disease was nearly 3 fold higher than that from patients with newly diagnosed disease. Serial observations found that leukemic blasts from the same individual, which did not initiate tumor growth at initial presentation and/or at early relapse, may engraft and grow in the later stages of disease, suggesting that the ability of leukemia cells for engraftment and proliferation was gradually acquired following the process of leukemia progression. Nine autonomous growing leukemia cell lines were established in vitro. These displayed an aggressive proliferation pattern, suggesting a possible correlation between the capacity of human leukemia cells for autonomous proliferation in vitro and an aggressive growth potential in SCID mice. In addition, we demonstrated that patients whose leukemic blasts displayed an aggressive growth and dissemination pattern in SClD mice had a poor clinical outcome in patients with ALL as well as AML. Patients whose leukemic blasts grew indolently or whose leukemia cells failed to induce growth had a significantly longer DFS and more favorable clinical course.

  16. An adult patient who developed malignant fibrous histiocytoma 9 years after radiation therapy for childhood acute lymphoblastic leukemia

    Kato, Yasuhiro [National Hiroshima Hospital, Higashi-Hiroshima (Japan); Ohno, Norioki; Horikawa, Yoko; Nishimura, Shin-ichiro; Ueda, Kazuhiro; Shimose, Shoji [Hiroshima Univ. (Japan). School of Medicine

    2002-12-01

    A 24-year-old Japanese man with a history of acute lymphoblastic leukemia, which occurred during childhood, developed malignant fibrous histiocytoma of his left knee. His past history revealed that he had undergone leukemic blast cell invasion of the left knee and subsequent radiation therapy 9 years ago. The total radiation doses for the upper part of the left tibia and the lower part of the left femur were 60 Gy and 40 Gy, respectively. Neither distant metastasis nor a relapse of leukemia occurred. A curative resection of the left femur with a noninvasive margin was performed. Adjuvant chemotherapy including high-dose methotrexate was given successfully before and after surgery; this was followed by relapse-free survival for 3 years. The nature of postirradiation malignant fibrous histiocytoma is highly aggressive. When a patient complains of persistent symptoms in a previously irradiated field, the possibility of this tumor must be taken into account. The importance of early diagnosis cannot be over-emphasized. (author)

  17. A case of multiple hepatic abscesses detected by CT scan in the patient with acute lymphoblastic leukemia

    A 34 years old man admitted to a hospital on 21 Feb. 1983 and was diagnosed acute lymphoblastic leukemia. A hematological complete remission was achieved by combination therapy of vincristine, prednisolone and L-asparaginase. However, he had complaining of high fever and right hypochondralgia since early in Apr. 1983, and it was revealed that elevation of right diaphragm on chest X-ray. Therefore, he was also given several antibiotics (CPZ, TOB, LMOX, PIPC, LCM, AMK, MINO and GM) for complication of probable liver abscess. Remittent fever was persisted in spite of as mentioned above various antibiotics. The multiple hepatic abscesses were found by CT scan of the mid-abdomen as the low density lesions, but bacterial cultures detected no any pathogens. His complaining of remittent fever and right hypochondralgia were improved by treated with Miconazole during about one month, and decreasing in size and number of multiple hepatic abscesses were found by CT scan. Though we could not determined clearly, but suspected that, multiple hepatic abscesses were due to fungus infection, by reason of therapeutic result. Regarding the complication of hepatic abscesses with leukemia, 5 cases have been reported in Japan, and one case out of 5 cases were detected by CT scan. We thought that CT scan were useful procedure for a early diagnosis of hepatic abscesses. In recently, the patient has continued of complete remission hematologically. (author)

  18. Serum metabonomics of acute leukemia using nuclear magnetic resonance spectroscopy

    Musharraf, Syed Ghulam; Siddiqui, Amna Jabbar; Shamsi, Tahir; Choudhary, M. Iqbal; Rahman, Atta-ur

    2016-01-01

    Acute leukemia is a critical neoplasm of white blood cells. In order to differentiate between the metabolic alterations associated with two subtypes of acute leukemia, acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML), we investigated the serum of ALL and AML patients and compared with two controls (healthy and aplastic anemia) using 1H NMR (nuclear magnetic resonance) spectroscopy. Thirty-seven putative metabolites were identified using Carr-Purcell-Meiboom-Gill (CPMG) sequence. The use of PLS-DA and OPLS-DA models gave results with 84.38% and 90.63% classification rate, respectively. The metabolites responsible for classification are mainly lipids, lactate and glucose. Compared with controls, ALL and AML patients showed serum metabonomic differences involving aberrant metabolism pathways including glycolysis, TCA cycle, lipoprotein changes, choline and fatty acid metabolisms. PMID:27480133

  19. Helical tomotherapy targeting total bone marrow after total body irradiation for patients with relapsed acute leukemia undergoing an allogeneic stem cell transplant

    Background and purpose: To report our clinical experience in planning and delivering total marrow irradiation (TMI) after total body irradiation (TBI) in patients with relapsed acute leukemia undergoing an allogeneic stem-cell transplant (SCT). Materials and Methods: Patients received conventional TBI as 2 Gy BID/day for 3 days boosted the next day by TMI (2 Gy in a single fraction) and followed by cyclophosphamide (Cy) 60 mg/kg for 2 days. While TBI was delivered with linear accelerator, TMI was performed with helical tomotherapy (HT). Results: Fifteen patients were treated from July 2009 till May 2010, ten with acute myeloid leukemia, and five with acute lymphoid leukemia. At the time of radiotherapy eight patients were in relapse and seven in second or third complete remission (CR) after relapse. The donor was a matched sibling in 7 cases and an unrelated donor in 8 cases. Median organ-at-risk dose reduction with TMI ranged from 30% to 65% with the largest reduction (-50%-65%) achieved for brain, larynx, liver, lungs and kidneys. Target areas (bone marrow sites and spleen in selected cases) were irradiated with an optimal conformity and an excellent homogeneity. Follow-up is short ranging from 180 to 510 days (median 310 days). However, tolerance was not different from a conventional TBI-Cy. All patients treated with TBI/TMI reached CR after SCT. Three patients have died (2 for severe GvHD, 1 for infection) and 2 patients showed relapsed leukemia. Twelve patients are alive with ten survivors in clinical remission of disease. Conclusions: This study confirms the clinical feasibility of using HT to deliver TMI as selective dose boost modality after TBI. For patients with advanced leukemia targeted TMI after TBI may be a novel approach to increase radiation dose with low risk of severe toxicity.

  20. Cytogenetics Does Not Impact Outcomes in Adult Patients with Acute Lymphoblastic Leukemia Undergoing Allogeneic Hematopoietic Cell Transplantation.

    Aldoss, Ibrahim; Tsai, Ni-Chun; Slovak, Marilyn L; Palmer, Joycelynne; Alvarnas, Joseph; Marcucci, Guido; Forman, Stephen J; Pullarkat, Vinod

    2016-07-01

    The prognostic relevance of cytogenetics at diagnosis on the outcome of allogeneic hematopoietic stem cell transplantation (alloHCT) for adult acute lymphoblastic leukemia (ALL) remains unclear. We retrospectively analyzed outcomes of 333 adult ALL patients who underwent alloHCT at our institution over a 10-year period. Patients were classified according to disease status at transplantation (complete response [CR] 1 [n = 202] or > CR1) and according to cytogenetic risk, defined as good (2%), intermediate (42%), poor (46%), or unknown (10%) based on available outcome data for each of the cytogenetic abnormalities. Three-year overall survival (OS), leukemia-free survival (LFS), and relapse incidence (RI) were 55.7%, 47.9% and 27.5%, respectively; 1-year nonrelapse mortality (NRM) was 17.3%. For patients undergoing alloHCT in CR1, 3-year OS, LFS, and RI were 69.8%, 62.3%, and 17.1%, respectively. In multivariable analysis, cytogenetic risk did not impact OS or LFS for the whole cohort or for patients who underwent transplantation in CR1. Disease status at alloHCT was an independent predictor for LFS (CR1 versus others: hazard ratio [HR], 3.17; P OS (CR1 versus others: HR, 2.90; P < .01). Graft-versus-host disease prophylaxis with tacrolimus/sirolimus was associated with a low NRM of 11.5% in the alloHCT recipients in CR1. Our data indicate that cytogenetic risk is not an independent predictor of outcomes in alloHCT performed to treat adult ALL. PMID:27044907

  1. Epigenetic regulators as promising therapeutic targets in acute myeloid leukemia

    Gallipoli, Paolo; Giotopoulos, George; Huntly, Brian J. P.

    2015-01-01

    Acute myeloid leukemia (AML), the most prevalent acute leukemia in adults, is an aggressive hematological malignancy arising in hematopoietic stem and progenitor cells. With the exception of a few specific AML subtypes, the mainstays of treatment have not significantly changed over the last 20 years, and are still based on standard cytotoxic chemotherapy. As a result, clinical outcome remains poor for the majority of patients, with overall long-term survival in the region of 20?30%. Recent su...

  2. Congenital acute lymphocytic leukemia associated with hyperleucocytic leukemia syndrome

    A two-month-old female infant had congenital acute lymphocytic leukemia 39 days after birth. Cranial CT showed many small high dense spots over the whole brain. The mechanism of occurrence of central neurologic symptoms and the association of hyperleucocytic leukemia are discussed with a review of the literature. (Namekawa, K.)

  3. Retinoic Acid Syndrome in Patients following the Treatment of Acute Promyelocytic Leukemia with All-trans Retinoic Acid

    Yung-Cheng Su

    2009-10-01

    Full Text Available Background: Retinoic acid syndrome (RAS is a potentially lethal complication during alltransretinoic acid (ATRA treatment of acute promyelocytic leukemia(APL. The incidence and risk factors have been shown to vary in differentseries. In this study we want to establish the incidence of RAS in our hospitaland try to elucidate factors that increase its risk.Methods: We retrospectively analyzed 102 patients diagnosed with APL betweenAugust 1993 and December 2007 at Chang Gung Memorial Hospital,Taiwan. All patients received ATRA as an induction regimen with or withoutconventional chemotherapy.Results: Eight of the 102 patients (7.8% experienced RAS which developed after amedian of 9 days (range: 2 to 23 days of ATRA treatment. Respiratory distressand fever were the most common presentations, occurring in 7 of 8patients (87.5%. Age, gender, morphological or molecular subtypes, an initialwhite blood cell (WBC count of more than 10 x 109/L and concurrentchemotherapy did not statistically attribute to the occurrence of RAS. Onepatient developed RAS manifesting with pulmonary hemorrhage but experienceda complete recovery after administration of high-dose dexamethasone.The RAS-related mortality was 12.5% (1 out of 8 patients.Conclusion: The incidence of RAS in this study was similar to those of other series withATRA and concurrent chemotherapy. Age, gender, morphological or molecularsubtypes, an initial leukocyte count of more than 10 x 109/L or the presenceof concurrent chemotherapy is not significantly associated with theoccurrence of the RAS.

  4. Mixed Phenotypic Acute Leukemia Presenting as Mediastinal Mass-2 Cases.

    Vardhan, Rig; Kotwal, Jyoti; Ganguli, Prosenjit; Ahmed, Rehan; Sharma, Ajay; Singh, Jasjit

    2016-06-01

    Mixed phenotype acute leukemia symbolizes a very small subset of acute leukemia that simply cannot be allocated as lymphoid or myeloid lineage. The 2008 World Health Organisation classification established stringent standard for diagnosis of mixed phenotype acute leukemia, accentuating myeloperoxidase for myeloid lineage, cytoplasmic CD3 for T lineage and CD19 with other B markers for B lineage obligation. Mixed phenotype leukemia is rare and 3-5 % of acute leukmias of all age groups, is associated with poor outcome with overall survival of 18 months. We wish to present two cases of mixed phenotypic acute leukemia who presented with mediastinal masses, were suspected to be T cell lymphoma/leukemia clinically and radiologically. In one case, tissue diagnosis was given as lymphoma for which treatment was given. These cases show that patients diagnosed as lymphoma on histopathology can be cases of mixed phenotype acute leukemia and varying specific treatment protocols and follow up are required. Awareness of these entities will help in proper diagnosis and treatment. PMID:27408360

  5. Novel mutations of the nucleophosmin (NPM-1) gene in Egyptian patients with acute myeloid leukemia: A pilot study

    Mutations of the nucleophosmin (NPM-1) gene have been reported in 50-60% of acute myeloid leukemia (AML) patients with normal karyotype. This work was designed to study the prevalence and nature of NPM1 gene mutations in a group of Egyptian patients with AML to get an idea about the profile of NPM1 gene mutations in our society. In 45 previously untreated patients with de novo AML, peripheral blood and/or bone marrow samples from all patients were subjected to microscopic morphologic examination, cytochemical analysis, immuno phenotyping and karyotyping. Patients with normal cytogenetic results were selected for molecular analysis of NPM1 exon 12 by PCR amplification followed by DNA sequencing of the amplified product. Twenty-one patients (46.7%) had abnormal karyotype: six cases with ;(15;17), five cases with (8;21), five cases had trisomy 8, two cases carrying inv(3) and three cases had monosomy 7. The remaining 24 patients (53.3%) had normal karyotype. These patients were then subjected to molecular analysis. Out of these 24 patients with normal karyotype, mutant NPM-1 was detected in 11 patients (45.8%) by DNA sequencing; 2 cases showed type A mutation, 2 cases were harboring [ins 1015-4019 (CACG)], with point mutation [1006C→G], while the remaining 7 cases showed heterozygous deletion of nt A [del 1178 (A)]. Conclusion: Two novel NPM1 gene mutations were detected among our study population of AML patients identified as: the insertion CACG associated with point mutation, deletion of one base, or associated with point mutation. NPM1 gene mutations may become a new tool for monitoring minimal residual disease in AML with normal karyotype. Whether these previously unreported NPM-1 mutations will confer the same better outcome as previously reported mutations is currently unknown and warrants a larger study.

  6. DIAGNOSIS AND SUBCLASSIFICATION OF ACUTE LYMPHOBLASTIC LEUKEMIA

    Sabina Chiaretti

    2014-10-01

    Full Text Available Acute lymphoblastic leukemia (ALL is a disseminated malignancy of B- or T-lymphoblasts which imposes a rapid and accurate diagnostic process to support an optimal risk-oriented therapy and thus increase the curability rate. The need for a precise diagnostic algorithm is underlined by the awareness that both ALL therapy and related success rates may vary greatly in function of ALL subset, from standard chemotherapy in patients with standard-risk ALL, to allotransplantation (SCT and targeted therapy in high-risk patients and cases expressing suitable biological targets, respectively. This review offers a glimpse on how best identify ALL and the most relevant ALL subsets.

  7. Clofarabine Combined with Busulfan Provides Excellent Disease Control in Adult Patients with Acute Lymphoblastic Leukemia Undergoing Allogeneic Hematopoietic Stem Cell Transplantation

    Kebriaei, P.; Basset, Roland; Ledesma, C.; Ciurea, S; Parmar, S.; Shpall, EJ; Hosing, C.; Khouri, Issa; Qazilbash, M; Popat, U; Alousi, A.; Nieto, Y; Jones, RB; Lima, M.; Champlin, RE

    2012-01-01

    We investigated the safety and early disease-control data obtained with intravenous busulfan (Bu) combined with clofarabine (Clo) in patients with acute lymphoblastic leukemia (ALL) undergoing allogeneic hematopoietic stem cell transplantation (SCT). Fifty-one patients with median age 36 years (range 20–64) received a matched sibling (n=24), syngeneic (n=2) or matched unrelated donor transplant (n=25) for ALL in first complete remission (n=30), second complete remission (n=13), or with active...

  8. Association between the methylation status of the MGMT promoter in bone marrow specimens and chemotherapy outcomes of patients with acute myeloid leukemia

    Hong, Qingxiao; Chen, Xiaoying; Ye, Huadan; ZHOU, ANNAN; GAO, YUTING; Jiang, Danjie; Wu, Xiaodong; TIAN, BINGRU; CHEN, YOUFEN; Wang, Ming; Xie, JiPing; XIA, YONGMING; Duan, Shiwei

    2016-01-01

    The O(6)-methylguanine-DNA methyltransferase (MGMT) gene is a tumor suppressor gene that is associated with the risk of developing acute myeloid leukemia (AML). However, the association between the methylation status of the MGMT promoter and the chemotherapeutic outcomes of patients with AML remains unknown. In the present study, 30 bone marrow samples derived from patients with AML were collected prior and subsequent to chemotherapy. The methylation status of the MGMT promoter in the bone ma...

  9. The prognostic impact of FLT3-ITD and NPM1 mutations in patients with relapsed acute myeloid leukemia and intermediate-risk cytogenetics

    How, J; Sykes, J.; Minden, M D; Gupta, V.; Yee, K W L; Schimmer, A D; Schuh, A C; Kamel-Reid, S; Brandwein, J M

    2013-01-01

    Internal tandem duplication of the fms-like tyrosine kinase-3 gene (FLT3-ITD) and nucleophosmin-1 (NPM1) mutations have prognostic importance in acute myeloid leukemia (AML) patients with intermediate-risk karyotype at diagnosis, but less is known about their utility to predict outcomes at relapse. We retrospectively analysed outcomes of 70 patients with relapsed, intermediate-risk karyotype AML who received a uniform reinduction regimen, with respect to FLT3-ITD and NPM1 mutation status and ...

  10. Deficiency of complement factor MBL in a patient required cardiac surgery after an acute myocardial infarction with underlining chronic lymphocytic leukemia

    Lai, Lawrence T.; Lee, Daniel C.; Ko, Wilson; Shevde, Ketan; Zhang, Ming

    2008-01-01

    Increasing evidence suggests that Mannan-binding lectin (MBL), the initial factor of the lectin pathway of complement, plays a role in cardiovascular diseases, i.e. inversely associated with risk of myocardial infarction (MI). In the present case, a patient with MBL deficiency underwent coronary artery bypass grafting (CABG) after an acute MI with underlining chronic lymphocytic leukemia (CLL). Post-operatively, the patient had a cerebral vascular accident and eventually expired. Analysis of ...

  11. Defining Molecular Phenotypes of Mesenchymal and hematopoietic Stem Cells derived from Peripheral blood of Acute Lymphocytic Leukemia patients for regenerative stem cell therapy

    Pravin D. Potdar; Rambhadur P Subedi

    2011-01-01

    Acute Lymphocytic Leukemia (ALL) is a clonal myeloid disorder affecting all age groups, characterized by accumulation of immature blast cells in bone marrow and in peripheral blood. Autologous Bone Marrow Transplantation is a present treatment for cure of ALL patients, which is very expensive, invasive process and may have possibility of transplantation of malignant stem cells to patients. In the present study, we hypothesized to isolate large number of normal Mesenchymal & Hematopoietic stem...

  12. Recurrent gastrointestinal hemorrhage in treatment with dasatinib in a patient showing SMAD4 mutation with acute lymphoblastic leukemia Philadelphia positive and juvenile polyposis hereditary hemorrhagic telangiectasia syndrome

    Chiara Sartor

    2013-07-01

    Full Text Available We report a case of a patient affected by juvenile polyposis and hereditary hemorrhagic telangiectasia linked to a SMAD4 mutation who developed acute lymphoblastic leukemia positive for the Philadelphia chromosome translocation and with a complex karyotype. During the treatment with the tyrosine kinase inhibitor dasatinib the patient presented recurrent severe gastrointestinal hemorrhages linked to the genetic background and aggravated by thrombocytopenia.

  13. Similar Survival for Patients Undergoing Reduced-Intensity Total Body Irradiation (TBI) Versus Myeloablative TBI as Conditioning for Allogeneic Transplant in Acute Leukemia

    Purpose: Hematopoietic stem cell transplantation (HSCT) is the mainstay of treatment for adults with acute leukemia. Total body irradiation (TBI) remains an important part of the conditioning regimen for HCST. For those patients unable to tolerate myeloablative TBI (mTBI), reduced intensity TBI (riTBI) is commonly used. In this study we compared outcomes of patients undergoing mTBI with those of patients undergoing riTBI in our institution. Methods and Materials: We performed a retrospective review of all patients with acute leukemia who underwent TBI-based conditioning, using a prospectively acquired database of HSCT patients treated at our institution. Patient data including details of the transplantation procedure, disease status, Karnofsky performance status (KPS), response rates, toxicity, survival time, and time to progression were extracted. Patient outcomes for various radiation therapy regimens were examined. Descriptive statistical analysis was performed. Results: Between June 1985 and July 2012, 226 patients with acute leukemia underwent TBI as conditioning for HSCT. Of those patients, 180 had full radiation therapy data available; 83 had acute lymphoblastic leukemia and 94 had acute myelogenous leukemia; 45 patients received riTBI, and 135 received mTBI. Median overall survival (OS) was 13.7 months. Median relapse-free survival (RFS) for all patients was 10.2 months. Controlling for age, sex, KPS, disease status, and diagnosis, there were no significant differences in OS or RFS between patients who underwent riTBI and those who underwent mTBI (P=.402, P=.499, respectively). Median length of hospital stay was shorter for patients who received riTBI than for those who received mTBI (16 days vs 23 days, respectively; P<.001), and intensive care unit admissions were less frequent following riTBI than mTBI (2.22% vs 12.69%, respectively, P=.043). Nonrelapse survival rates were also similar (P=.186). Conclusions: No differences in OS or RFS were seen between

  14. Similar Survival for Patients Undergoing Reduced-Intensity Total Body Irradiation (TBI) Versus Myeloablative TBI as Conditioning for Allogeneic Transplant in Acute Leukemia

    Mikell, John L., E-mail: jmikell@emory.edu [Department of Radiation Oncology, Winship Cancer Institute, Emory University, Atlanta, Georgia (United States); Waller, Edmund K. [Department of Hematology and Oncology, Winship Cancer Institute, Emory University, Atlanta, Georgia (United States); Switchenko, Jeffrey M. [Department of Biostatistics and Bioinformatics, Winship Cancer Institute, Emory University, Atlanta, Georgia (United States); Rangaraju, Sravanti; Ali, Zahir; Graiser, Michael [Department of Hematology and Oncology, Winship Cancer Institute, Emory University, Atlanta, Georgia (United States); Hall, William A. [Department of Radiation Oncology, Winship Cancer Institute, Emory University, Atlanta, Georgia (United States); Langston, Amelia A. [Department of Hematology and Oncology, Winship Cancer Institute, Emory University, Atlanta, Georgia (United States); Esiashvili, Natia [Department of Radiation Oncology, Winship Cancer Institute, Emory University, Atlanta, Georgia (United States); Khoury, H. Jean [Department of Hematology and Oncology, Winship Cancer Institute, Emory University, Atlanta, Georgia (United States); Khan, Mohammad K. [Department of Radiation Oncology, Winship Cancer Institute, Emory University, Atlanta, Georgia (United States)

    2014-06-01

    Purpose: Hematopoietic stem cell transplantation (HSCT) is the mainstay of treatment for adults with acute leukemia. Total body irradiation (TBI) remains an important part of the conditioning regimen for HCST. For those patients unable to tolerate myeloablative TBI (mTBI), reduced intensity TBI (riTBI) is commonly used. In this study we compared outcomes of patients undergoing mTBI with those of patients undergoing riTBI in our institution. Methods and Materials: We performed a retrospective review of all patients with acute leukemia who underwent TBI-based conditioning, using a prospectively acquired database of HSCT patients treated at our institution. Patient data including details of the transplantation procedure, disease status, Karnofsky performance status (KPS), response rates, toxicity, survival time, and time to progression were extracted. Patient outcomes for various radiation therapy regimens were examined. Descriptive statistical analysis was performed. Results: Between June 1985 and July 2012, 226 patients with acute leukemia underwent TBI as conditioning for HSCT. Of those patients, 180 had full radiation therapy data available; 83 had acute lymphoblastic leukemia and 94 had acute myelogenous leukemia; 45 patients received riTBI, and 135 received mTBI. Median overall survival (OS) was 13.7 months. Median relapse-free survival (RFS) for all patients was 10.2 months. Controlling for age, sex, KPS, disease status, and diagnosis, there were no significant differences in OS or RFS between patients who underwent riTBI and those who underwent mTBI (P=.402, P=.499, respectively). Median length of hospital stay was shorter for patients who received riTBI than for those who received mTBI (16 days vs 23 days, respectively; P<.001), and intensive care unit admissions were less frequent following riTBI than mTBI (2.22% vs 12.69%, respectively, P=.043). Nonrelapse survival rates were also similar (P=.186). Conclusions: No differences in OS or RFS were seen between

  15. PROGNOSTIC SIGNIFICANCE OF EXPRESSION OF SURVIVIN IN ACUTE LEUKEMIA

    王晓娟; 戴国仪; 曹利民; 王国华; 朱慧芬; 张悦; 沈关心

    2002-01-01

    Objective: To investigate the expression of survivin gene and its significance in acute leukemia. Methods: The expression of surviving in 134 acute leukemia patients and 4 leukemia cell lines was detected by RT-PCR and immunofluorescence analysis. Results: We detected survivin expression in 78 of 134 acute leukemia patients and all the cell lines but not in normal controls and anemia patients. Survivin gene expression correlated with a lower white blood cell count, which was 11×109/L and 48×109/L in the positive and negative group respectively (P<0.01 by the Mann-Whitney test). In 55 cases of FAB M1/M2/M3, it was associated with leukemic cell maturation(P<0.01 by the Fisher test). Survivin expression was strongly related to survival time of acute leukemia patients (P<0.05). Conclusion: These data suggest that survivin expression may be considered as a new unfavorable prognostic factor for acute leukemia due to its important role in apoptosis inhibition that influences disease outcome.

  16. Temozolomide and cisplatin in relapsed/refractory acute leukemia

    Rasul Muhammad

    2009-05-01

    Full Text Available Abstract Cisplatin depletes MGMT and increases the sensitivity of leukemia cells to temozolomide. We performed a phase I study of cisplatin and temozolomide in patients with relapsed and refractory acute leukemia. Fifteen patients had AML, 3 had ALL, and 2 had biphenotypic leukemia. The median number of prior chemotherapy regimens was 3 (1–5. Treatment was well tolerated up to the maximal doses of temozolomide 200 mg/m2/d times 7 days and cisplatin 100 mg/m2 on day 1. There was one complete remission in this heavily pretreated patient population. Five of 20 (25% patients demonstrated a significant reduction in bone marrow blasts.

  17. Selecting Sample Preparation Workflows for Mass Spectrometry-Based Proteomic and Phosphoproteomic Analysis of Patient Samples with Acute Myeloid Leukemia

    Maria Hernandez-Valladares

    2016-08-01

    Full Text Available Global mass spectrometry (MS-based proteomic and phosphoproteomic studies of acute myeloid leukemia (AML biomarkers represent a powerful strategy to identify and confirm proteins and their phosphorylated modifications that could be applied in diagnosis and prognosis, as a support for individual treatment regimens and selection of patients for bone marrow transplant. MS-based studies require optimal and reproducible workflows that allow a satisfactory coverage of the proteome and its modifications. Preparation of samples for global MS analysis is a crucial step and it usually requires method testing, tuning and optimization. Different proteomic workflows that have been used to prepare AML patient samples for global MS analysis usually include a standard protein in-solution digestion procedure with a urea-based lysis buffer. The enrichment of phosphopeptides from AML patient samples has previously been carried out either with immobilized metal affinity chromatography (IMAC or metal oxide affinity chromatography (MOAC. We have recently tested several methods of sample preparation for MS analysis of the AML proteome and phosphoproteome and introduced filter-aided sample preparation (FASP as a superior methodology for the sensitive and reproducible generation of peptides from patient samples. FASP-prepared peptides can be further fractionated or IMAC-enriched for proteome or phosphoproteome analyses. Herein, we will review both in-solution and FASP-based sample preparation workflows and encourage the use of the latter for the highest protein and phosphorylation coverage and reproducibility.

  18. Identification of fungal pathogens in a patient with acute myelogenic leukemia using a pathogen detection array technology.

    Banerjee, Sagarika; Peck, Kristen N; Feldman, Michael D; Schuster, Mindy G; Alwine, James C; Robertson, Erle S

    2016-04-01

    Invasive zygomycosis in immunocompromised patients results in a high mortality rate, and early identification is crucial to optimize therapy and to reduce morbidity. However, diagnosing specific species of zygomycetes fungi possess challenge in the clinical laboratories. A need for a rapid and sensitive diagnostic tool for early recognition of a zygomycetes fungus in clinical samples to the species level will lead to prompt and accurate therapy and the PathoChip provides one such platform. We utilized a pathogen array technology referred to as PathoChip, comprised of oligonucleotide probes that can detect all the sequenced viruses as well as known pathogenic bacteria, fungi and parasites and family-specific conserved probes, thus providing a means for detecting previously uncharacterized members of a family. We rapidly identified a zygomycetous fungus, Rhizomucor pusillus, an otherwise challenge for the clinical laboratories, predominantly in a patient with acute myelogenous leukemia. This report highlights the value of PathoChip as a diagnostic tool to identify micro-organisms to the species level, especially for those difficult to identify in most clinical laboratories. It will also help clinicians to obtain a critical snapshot of the infection profile of a patient to plan treatment strategies. PMID:26619325

  19. Eradication of Pulmonary Aspergillosis in an Adolescent Patient Undergoing Three Allogeneic Stem Cell Transplantations for Acute Lymphoblastic Leukemia

    Michaela Döring

    2012-01-01

    Full Text Available Systemic fungal infections are a major cause of infection-related mortality in patients with hematologic malignancies. This report addresses the case of an adolescent patient with acute lymphoblastic leukemia who underwent three allogeneic hematopoietic stem cell transplantations and developed pulmonary aspergillosis. Combination therapy with liposomal amphotericin B (L-AmB, 3 mg/kg bw/day and caspofungin (CAS, 50 mg/day during the first allogeneic hematopoietic stem cell transplantation (HSCT improved the pulmonary situation. After shifting the antifungal combination therapy to oral voriconazole (2 × 200 mg/day and CAS, a new pulmonal lesion occurred alongside the improvements in the existing pulmonary aspergillosis. An antifungal combination during a second HSCT with L-AmB (3 mg/kg bw/day and CAS showed an improvement in the pulmonary aspergillosis. A combination therapy with CAS and L-AmB (1 mg/kg bw/day during the third HSCT led once again to progress the pulmonary aspergillosis, after increasing the L-AMB to 3 mg/kg bw/day for recovery. The presented case provides an example of how, despite severe immunosuppression, a combination of antifungal drugs administered intravenously at therapeutic dosages may be more efficient than either intravenous monotherapy or combinations of intravenous and oral antifungals in selecting pediatric and adolescent patients with proven fungal infections.

  20. Histone H4 acetylation by immunohistochemistry and prognosis in newly diagnosed adult acute lymphoblastic leukemia (ALL) patients

    Histone deacetylase (HDAC) inhibitors are a novel anti-tumor therapy. To determine whether HDAC inhibitors may be useful in the treatment of adult acute lymphoblastic leukemia (ALL), we examined the acetylation of histone H4 by immunohistochemistry in newly diagnosed ALL patients and evaluated the impact of acetylation on complete remission (CR) rate, relapse-free survival (RFS), and overall survival (OS). Patients ≥18 years of age and an available diagnostic bone marrow biopsy were evaluated. Cox proportional hazards analysis was used to identify univariate and multivariate correlates of CR, RFS, and OS. The variables histone H4 acetylation (positive or negative), white blood count, cytogenetic (CG) risk group (CALGB criteria), and age were used in multivariate analysis. On multivariate analysis, histone acetylation was associated with a trend towards an improved OS (for all CG risk groups) (HR = 0.51, p = 0.09). In patients without poor risk CG, there was an impressive association between the presence of histone acetylation and an improved CR rate (OR 3.43, p = 0.035), RFS (HR 0.07, p = 0.005), and OS (HR 0.24, p = 0.007). This association remained statistically significant in multivariate analysis. These data provide a rationale for the design of novel regimens incorporating HDAC inhibitors in ALL

  1. CLINICAL FEATURES AND CLINICAL OUTCOME OF ACUTE PROMYELOCYTIC LEUKEMIA PATIENTS TREATED AT CAIRO NATIONAL CANCER INSTITUTE IN EGYPT

    Tamer M Fouad

    2011-01-01

    Full Text Available

    The current study reports the clinical features and treatment outcome of 67 patients with acute promyelocytic leukemia (APL presented to National Cancer Institute (NCI-Cairo, in Egypt from January 2007 to January 2011. The median follow-up time was 36 months. All patients were treated with the simultaneous administration of all-trans retinoic acid (ATRA and anthracyclin. The treatment protocol was modified due to resource limitations at the NCI-Cairo by replacing of idarubicin with doxorubicin in most of the cases and the inclusion of cytarbine during the consolidation phase only in pediatric patients. All patients who achieved molecular complete remission (CRm after consolidation received two-year maintenance treatment with low dose chemotherapy composed of 6 mercaptopurine, methotrexate and intermittent ATRA courses. The median age at presentation was 29 years. There was a slight male predominance (53%.  Bleeding was the most common presenting symptom (79%. Most patients had an intermediate risk Sanz score (49% and 34% had a high risk score.  All patients achieved molecular CR at end of consolidation therapy with a median duration of 100 days. The main therapeutic complications during the induction phase were febrile neutropenia (42%, bleeding (18% and differentiation syndrome (11%. Five patients died at diagnosis due to bleeding, three died during induction chemotherapy due to febrile neutropenia (n=2 and bleeding (n=1 and one patient died during consolidation therapy due to febrile neutropenia.  The 3-year OS was 89% and relapse rate was 3%. Adapting standard AIDA treatment protocols to limited resources by reducing dose-intensity during treatment consolidation, using ATRA in the consolidation phase and alternative anthracyclin (doxorubicin may be a valid treatment option in developing countries. In spite of the increased incidence of high and intermediate risk score APL in our sample, we reported an acceptable CR rate

  2. CLINICAL FEATURES AND CLINICAL OUTCOME OF ACUTE PROMYELOCYTIC LEUKEMIA PATIENTS TREATED AT CAIRO NATIONAL CANCER INSTITUTE IN EGYPT

    Ola Khorshid

    2011-12-01

    Full Text Available The current study reports the clinical features and treatment outcome of 67 patients with acute promyelocytic leukemia (APL presented to National Cancer Institute (NCI-Cairo, in Egypt from January 2007 to January 2011. The median follow-up time was 36 months. All patients were treated with the simultaneous administration of all-trans retinoic acid (ATRA and anthracyclin. The treatment protocol was modified due to resource limitations at the NCI-Cairo by replacing of idarubicin with doxorubicin in most of the cases and the inclusion of cytarbine during the consolidation phase only in pediatric patients. All patients who achieved molecular complete remission (CRm after consolidation received two-year maintenance treatment with low dose chemotherapy composed of 6 mercaptopurine, methotrexate and intermittent ATRA courses. The median age at presentation was 29 years. There was a slight male predominance (53%.  Bleeding was the most common presenting symptom (79%. Most patients had an intermediate risk Sanz score (49% and 34% had a high risk score.  All patients achieved molecular CR at end of consolidation therapy with a median duration of 100 days. The main therapeutic complications during the induction phase were febrile neutropenia (42%, bleeding (18% and differentiation syndrome (11%. Five patients died at diagnosis due to bleeding, three died during induction chemotherapy due to febrile neutropenia (n=2 and bleeding (n=1 and one patient died during consolidation therapy due to febrile neutropenia.  The 3-year OS was 89% and relapse rate was 3%. Adapting standard AIDA treatment protocols to limited resources by reducing dose-intensity during treatment consolidation, using ATRA in the consolidation phase and alternative anthracyclin (doxorubicin may be a valid treatment option in developing countries. In spite of the increased incidence of high and intermediate risk score APL in our sample, we reported an acceptable CR rate, toxicity and OS.

  3. Risk stratification of T-cell Acute Lymphoblastic Leukemia patients based on gene expression, mutations and copy number variation.

    Mirji, Gauri; Bhat, Jaydeep; Kode, Jyoti; Banavali, Shripad; Sengar, Manju; Khadke, Prashant; Sait, Osama; Chiplunkar, Shubhada

    2016-06-01

    Gene expression, copy number variations (CNV), mutations and survival were studied to delineate TCRγδ+T-cell acute lymphoblastic leukemia (T-ALL) as a distinct subgroup from TCRαβ+T-ALL. Gene Ontology analysis showed that differential regulation of genes involved in pathways for leukemogenesis, apoptosis, cytokine-cytokine receptor interaction and antigen processing/presentation may offer a survival benefit to TCRγδ+T-ALL patients. Genes involved in disease biology and having equal expression in both the subgroups, were further analysed for mutations and CNV using droplet digital PCR. TCRγδ+T-ALL patients exhibited differential level of mutations for NOTCH1 and IKZF3; however BRAF mutations were detected at equal levels in both the subgroups. Although TCRγδ+T-ALL patients with these mutations demonstrated improved disease-free survival (DFS) as compared TCRαβ+T-ALL patients, it was not statistically significant. Patients with homozygous deletion of CDKN2A/CDKN2B showed poor DFS in each subgroup. TCRγδ+T-ALL patients with wild type/heterozygous deletion of CDKN2A/CDKN2B possess significantly better DFS over TCRαβ+T-ALL patients (p=0.017 and 0.045, respectively). Thus, the present study has for the first time demonstrated TCRγδ clonality and CDKN2A/CDKN2B CNV together as potential prognostic markers in management of T-ALL. Further understanding the functional significance of differentially regulated genes in T-ALL patients would aid in designing risk based treatment strategies in subset specific manner. PMID:27070758

  4. Frequency of p190 and p210 BCR-ABL rearrangements and survival in Brazilian adult patients with acute lymphoblastic leukemia

    Ilana de França Azevedo

    2014-10-01

    Full Text Available Objective: This study investigated the occurrence of the p190 and p210 break point clusterregion-Abelson (BCR-ABL rearrangements in adults with acute lymphoblastic leukemia and possible associations with clinical and laboratory characteristics and survival. Methods: Forty-one over 18-year-old patients with acute lymphoblastic leukemia of both genders followed-up between January 2008 and May 2012 were included in this study. Clinical and laboratory data were obtained from the medical charts of the patients. Reverse transcription polymerase chain reaction (RT-PCR using specific primers was employed to identify molecular rearrangements. Results: At diagnosis, the median age was 33 years, and there was a predominance of males (61%. The most common immunophenotype was B lineage (76%. BCR-ABL rearrangements was detected in 14 (34% patients with the following distribution: p190 (28%, p210 (50% and double positive (22%. Overall survival of patients with a mean/median of 331/246 days of follow up was 39%, respectively, negative BCR-ABL (44% and positive BCR-ABL (28%. Conclusion: These results confirm the high frequency of BCR-ABL rearrangements and the low survival rate of adult Brazilian patients with acute lymphoblastic leukemia.

  5. Mixed-phenotype acute leukemia: clinical and laboratory features and outcome in 100 patients defined according to the WHO 2008 classification.

    Matutes, Estella; Pickl, Winfried F; Van't Veer, Mars; Morilla, Ricardo; Swansbury, John; Strobl, Herbert; Attarbaschi, Andishe; Hopfinger, Georg; Ashley, Sue; Bene, Marie Christine; Porwit, Anna; Orfao, Alberto; Lemez, Petr; Schabath, Richard; Ludwig, Wolf-Dieter

    2011-03-17

    The features of 100 mixed-phenotype acute leukemias (MPALs), fulfilling WHO 2008 criteria, are documented. Myeloid and T-lineage features were demonstrated by cytoplasmic myeloperoxidase and CD3; B-lineage features were demonstrated by at least 2 B-lymphoid markers. There were 62 men and 38 women; 68% were adults. Morphology was consistent with acute lymphoblastic leukemia (ALL; 43%), acute myeloid leukemia (AML; 42%), or inconclusive (15%). Immunophenotyping disclosed B + myeloid (59%), T + myeloid (35%), B + T (4%), or trilineage (2%) combinations. Cytogenetics evidenced t(9;22)/(Ph(+)) (20%), 11q23/MLL rearrangements (8%), complex (32%), aberrant (27%), or normal (13%) karyotypes. There was no correlation between age, morphology, immunophenotype, or cytogenetics. Response to treatment and outcome were available for 67 and 70 patients, respectively; 27 received ALL, 34 AML, 5 a combination of ALL + AML therapy, and 1 imatinib. ALL treatment induced a response in 85%, AML therapy in 41%; 3 of 5 patients responded to the combination therapy. Forty (58%) patients died, 33 of resistant disease. Overall median survival was 18 months and 37% of patients are alive at 5 years. Age, Ph(+), and AML therapy were predictors for poor outcome (P < .001; P = .002; P = .003). MPAL is confirmed to be a poor-risk disease. Adults and Ph(+) patients should be considered for transplantation in first remission. PMID:21228332

  6. Lack of Correlation Between the CCR5-Δ32 Mutation and Acute Myeloid Leukemia in Iranian Patients

    Khorramdelazad, Hossein; Mortazavi, Yousef; Momeni, Mohammad; Arababadi, Mohammad Kazemi; Khandany, Behjat Kalantary; Moogooei, Mozhgan; Hassanshahi, Gholamhossein

    2014-01-01

    Chemokines and their receptors are crucially important in the pathogenesis of acute myeloblastic leukemia (AML). The CC chemokine receptor 5 (CCR5) is a specific chemokine receptor for CC chemokine ligand 3 (CCL3), CCL4 and CCL5 which all play key roles in identifying cancer properties and localization of leukemia cells. It has been demonstrated that the known mutation in CCR5 gene (CCR5-Δ32) leads to mal-expression of the receptor and affect its function. The aim of this study was to determi...

  7. Acute Myeloid Leukemia: Focus on Novel Therapeutic Strategies

    Lin, Tara L.; M. Yair Levy

    2012-01-01

    Acute myeloid leukemia (AML) is a heterogeneous disease with variable clinical outcomes. Cytogenetic analysis reveals which patients may have favorable risk disease, but 5-year survival in this category is only approximately 60%, with intermediate and poor risk groups faring far worse. Advances in our understanding of the biology of leukemia pathogenesis and prognosis have not been matched with clinical improvements. Unsatisfactory outcomes persist for the majority of patients with AML, parti...

  8. Karyotype complexity and prognosis in acute myeloid leukemia

    Stölzel, F.; Mohr, B.; Kramer, M.; Oelschlägel, U; Bochtler, T; Berdel, W E; Kaufmann, M; Baldus, C D; Schäfer-Eckart, K; R. Stuhlmann; Einsele, H; Krause, S W; Serve, H; Hänel, M.; Herbst, R.

    2016-01-01

    A complex aberrant karyotype consisting of multiple unrelated cytogenetic abnormalities is associated with poor prognosis in patients with acute myeloid leukemia (AML). The European Leukemia Net classification and the UK Medical Research Council recommendation provide prognostic categories that differ in the definition of unbalanced aberrations as well as the number of single aberrations. The aim of this study on 3526 AML patients was to redefine and validate a cutoff for karyotype complexity...

  9. Esophageal strictures during treatment for acute lymphoblastic leukemia.

    Kelly, Kevin

    2012-02-01

    Esophageal stricture is a rare complication of paediatric cancer treatment that usually occurs after esophageal exposure to radiotherapy. We describe 4 cases of esophageal stricture during chemotherapy for acute lymphoblastic leukemia. All patients presented with refractory vomiting and were diagnosed with radiologic contrast studies. None of the patients had received radiotherapy. Esophageal candidiasis was seen in 2 patients but the remaining 2 patients had earlier systemic candidiasis. High-dose dexamethasone may predispose these children to both esophageal candidiasis and peptic esophagitis. The etiology of esophageal strictures during treatment for acute leukemia is likely to be multifactorial but systemic candidiasis may play a significant role.

  10. Prognostic relevance of Wilms tumor 1 (WT1) gene Exon 7 mutations in-patient with cytogenetically normal acute myeloid leukemia

    Aref, Salah; El Sharawy, Solafa; Sabry, Mohamed; Azmy, Emad; Raouf, Dalia Abdel

    2013-01-01

    This study aimed to assess the prognostic influences of Wilms tumor 1 (WT1) gene mutations in cytogenetically normal acute myeloid leukemia (CN-AML) among Egyptian patients. Exon 7 of WT1 was screened for mutations in samples from 82 CN-AML patients out of 203 newly diagnosed AML patients, using a high-resolution capillary electrophoresis. Seven out of 82 AML patients (8.3 %) harbored WT1 mutations. There was no significant difference between the mutant WT1 and wild type AML patients as regar...

  11. Acute Leukemia: Diagnosis, Management, and Potential for Cure

    Stewart, Keith; Keating, Armand

    1988-01-01

    Acute leukemia is an uncommon malignant disorder resulting from the clonal proliferation of hematopoietic precursors of the myeloid or lymphoid lineages. Of the two major subgroups, acute lymphoblastic leukemia is more common in children, while acute myelogenous leukemia predominates in adults. With modern chemotherapy 60%-70% of all children with acute lymphoblastic leukemia can be long-term survivors and are potentially cured. Although the prognosis in acute myelogenous leukemia is less fav...

  12. Detection of MYC gene rearrangements by conventional cytogenetics and fluorescent in situ hybridization in patients with acute lymphoblastic leukemia cases

    Seda Eren

    2015-03-01

    Full Text Available Objective: The aim of this study is to investigate rearrangements at the region of MYC gene by conventional cytogenetics and interphase FISH methods in patients with acute lymphoblastic leukemia (ALL. Methods: The study was carried out on bone marrow specimens of 25 ALL patients who were referred to our laboratory. Fourteen children and 11 adult ALL cases were examined. Conventional cytogenetic analysis was performed using G banding technique and fluorescence in situ hybridization technique was applied using MYC breakapart probe (Cytocell. Results: Totally, in 2 of 25 cases available metaphases were not obtained. While in 9 of 23 cases were found to have normal karyotype (39.1%, numerical chromosomal abnormalities were detected in 6 cases, structural abnormalities in 4 and both numerical and structural abnormalities were found in 4 cases. In one case (4% t(8;14(q24;q32 was found as a cytogenetic aberration in which MYC gene locus involved.FISH analysis was performed successfully in all cases and MYC rearrangements were found in 3 cases (12% by FISH method. Conclusion: By comparing two techniques, it was observed that FISH method showed more sensitivity, however conventional cytogenetic techniques were also effective to reveal all changes of the chromosomes. Therefore, we concluded that it would be more efficient to useof these two techniques together.J Clin Exp Invest 2015;6 (1: 21-26

  13. Identification of a Novel P190-Derived Breakpoint Peptide Suitable for Peptide Vaccine Therapeutic Approach in Ph+ Acute Lymphoblastic Leukemia Patients

    Micaela Ippoliti

    2012-01-01

    Full Text Available Ph+ acute lymphoblastic leukemia (Ph+ ALL is a high-risk acute leukemia with poor prognosis, in which the specific t(9;22(q34;q11 translocation results in a chimeric bcr-abl (e1a2 breakpoint and in a 190 KD protein (p190 with constitutive tyrosine kinase activity. The advent of first- and second-generation tyrosine kinase inhibitors (TKIs improved the short-term outcome of Ph+ ALL patients not eligible for allo-SCT; yet disease recurrence is almost inevitable. Peptides derived from p190-breakpoint area are leukemia-specific antigens that may mediate an antitumor response toward p190+ leukemia cells. We identified one peptide named p190-13 able to induce in vitro peptide-specific CD4+ T cell proliferation in Ph+ ALL patients in complete remission during TKIs. Thus this peptide appears a good candidate for developing an immune target vaccine strategy possibly synergizing with TKIs for remission maintenance.

  14. Speciation of arsenic trioxide metabolites in peripheral blood and bone marrow from an acute promyelocytic leukemia patient

    Iriyama Noriyoshi

    2012-01-01

    Full Text Available Abstract Background Speciation of arsenic trioxide (ATO metabolites in clinical samples such as peripheral blood (PB from acute promyelocytic leukemia (APL patients has been conducted. However, speciation of arsenicals in bone marrow (BM has not yet been performed. Profiles of arsenic speciation in plasma of BM were thus investigated and compared with those of PB plasma from a relapsed APL patient. The total arsenic concentrations in high molecular weight fraction (HMW-F of BM and PB plasma were also determined. Methods Response assessment was evaluated by BM aspirate examination and fluorescence in situ hybridization analysis. The analyses of total arsenic concentrations and speciation were preformed by inductively coupled plasma mass spectrometry (ICP-MS, and high-performance liquid chromatography (HPLC/ICP-MS, respectively. Results Response assessment showed that the patient achieved complete remission. The total arsenic concentrations in BM plasma increased with time during the consecutive administration. The PB plasma concentrations of methylated arsenic metabolites substantially increased after the start of administration, while those of inorganic arsenic were still kept at a low level, followed by substantially increase from day-14 after administration. The arsenic speciation profiles of PB plasma were very similar to those of BM plasma. Furthermore, the total arsenic concentrations of HMW-F in BM plasma were much higher than those in PB plasma. Conclusions The behaviors of arsenic speciation suggested for the first time that arsenic speciation analysis of PB plasma could be predicative for BM speciation, and showed relatively higher efficiency of drug metabolism in the patient. These results may further provide not only significance of clinical application of ATO, but also a new insight into host defense mechanisms in APL patients undergoing ATO treatment, since HMW proteins-bound arsenic complex could be thought to protect BM from the

  15. A phase 3 study of gemtuzumab ozogamicin during induction and postconsolidation therapy in younger patients with acute myeloid leukemia.

    Petersdorf, Stephen H; Kopecky, Kenneth J; Slovak, Marilyn; Willman, Cheryl; Nevill, Thomas; Brandwein, Joseph; Larson, Richard A; Erba, Harry P; Stiff, Patrick J; Stuart, Robert K; Walter, Roland B; Tallman, Martin S; Stenke, Leif; Appelbaum, Frederick R

    2013-06-13

    This randomized phase 3 clinical trial evaluated the potential benefit of the addition of gemtuzumab ozogamicin (GO) to standard induction and postconsolidation therapy in patients with acute myeloid leukemia. Patients were randomly assigned to receive daunorubicin (45 mg/m(2) per day on days 1, 2, and 3), cytarabine (100 mg/m(2) per day by continuous infusion on days 1-7), and GO (6 mg/m(2) on day 4; DA+GO) vs standard induction therapy with daunorubicin (60 mg/m(2) per day on days 1, 2, and 3) and cytarabine alone (DA). Patients who achieved complete remission (CR) received 3 courses of high-dose cytarabine. Those remaining in CR after consolidation were randomly assigned to receive either no additional therapy or 3 doses of GO (5 mg/m(2) every 28 days). From August 2004 until August 2009, 637 patients were registered for induction. The CR rate was 69% for DA+GO and 70% for DA (P = .59). Among those who achieved a CR, the 5-year relapse-free survival rate was 43% in the DA+GO group and 42% in the DA group (P = .40). The 5-year overall survival rate was 46% in the DA+GO group and 50% in the DA group (P = .85). One hundred seventy-four patients in CR after consolidation underwent the postconsolidation randomization. Disease-free survival was not improved with postconsolidation GO (HR, 1.48; P = .97). In this study, the addition of GO to induction or postconsolidation therapy failed to show improvement in CR rate, disease-free survival, or overall survival. PMID:23591789

  16. Continued improvement in survival of acute myeloid leukemia patients: an application of the loss in expectation of life.

    Bower, H; Andersson, T M-L; Björkholm, M; Dickman, P W; Lambert, P C; Derolf, Å R

    2016-01-01

    We evaluated temporal trends in survival of Swedish acute myeloid leukemia (AML) patients diagnosed between 1973 and 2011 using relative survival ratios (RSRs) and a measure called the loss in expectation of life (LEL). RSRs increased most for patients <60 years at diagnosis during the first calendar periods, but between 1997-2005 and 2006-2011 the most pronounced increase was for those aged 61-70 years at diagnosis; RSR changed from 0.16 (95% confidence interval (CI): 0.13-0.19) to 0.28 (95% CI: 0.23-0.33), respectively. The LEL for males aged 35 years at diagnosis was 41.0 (95% CI: 40.1-41.8) years in 1975 and 19.5 (95% CI: 16.4-22.5) years in 2011. For males aged 65 years, the corresponding figures were 13.8 (95% CI: 13.7-14.0) and 12.0 (95% CI: 11.3-12.8). Conditional LEL estimates suggested that patients who survive 5 years postdiagnosis have shorter remaining lifespan than the general population. The proportion of expected life lost (PELL) suggested that male 65-year-old patients lost 75% of their life expectancy in 2005 and 66% if they were diagnosed in 2011. Survival continued to increase to 2011, with larger improvements in those aged 61-70 years at diagnosis. The LEL and PELL are intuitive measures that may be useful in communicating survival statistics to patients, clinicians and health-care providers. PMID:26849011

  17. Overexpression of miR-378 is frequent and may affect treatment outcomes in patients with acute myeloid leukemia.

    Qian, Jun; Lin, Jiang; Qian, Wei; Ma, Ji-chun; Qian, Si-xuan; Li, Yun; Yang, Jing; Li, Jian-yong; Wang, Cui-zhu; Chai, Hai-yan; Chen, Xing-xing; Deng, Zhao-qun

    2013-07-01

    MicroRNA miR-378 plays important roles in tumorigenesis by enhancing cell survival, reducing apoptosis, promoting tumor growth, angiogenesis and promoting cell migration and invasion. Abnormal expression of miR-378 has been observed in various types of cancers. The aim of this study was to investigate the expression status of miR-378 and its clinical significance in patients with acute myeloid leukemia (AML) using real-time quantitative PCR. miR-378 overexpression was identified in 26 of 84 (31%) AML patients. The patients with miR-378 overexpression had lower hemoglobin level than those without miR-378 overexpression (66 versus 78 g/L, respectively, P=0.010). The frequency of miR-378 overexpression in FAB-M2 subtype was higher than other subtypes (44% versus 20%, P=0.032). Moreover, the frequency of miR-378 overexpression was higher in patients with t(8;21) than in others (64% versus 24%, P=0.012). The status of miR-378 expression was not correlated with the mutations of eight genes (FLT3-ITD, NPM1, C-KIT, IDH1/IDH2, DNMT3A, C/EBPA and U2AF1). The difference in relapse-free survival was observed between patients with and without miR-378 overexpression (P=0.049). These findings suggest that miR-378 up-regulation is a common event and might have an adverse impact on prognosis in AML. PMID:23582927

  18. Unrelated Hematopoietic Stem Cell Transplantation for Children with Acute Leukemia: Experience at a Single Institution

    Lee, Jae Hee; Yoon, Hoi Soo; Song, Joon Sup; Choi, Eun Seok; Moon, Hyung Nam; Seo, Jong Jin; Im, Ho Joon

    2009-01-01

    We evaluate the outcomes in children with acute leukemia who received allogeneic hematopoietic stem cell transplantation (HCT) using unrelated donor. Fifty-six children in complete remission (CR) received HCT from unrelated donors between 2000 and 2007. Thirty-five had acute myeloid leukemia, and 21 had acute lymphoid leukemia. Stem cell sources included bone marrow in 38, peripheral blood in 4, and cord blood (CB) in 14. Four patients died before engraftment and 52 engrafted. Twenty patients...

  19. Quantitative analysis of human herpesvirus-6 genome in blood and bone marrow samples from Tunisian patients with acute leukemia: a follow-up study

    Faten, Nefzi; Agnès, Gautheret-Dejean; Nadia, Ben Fredj; Nabil, Abid Ben Salem; Monia, Zaier; Abderrahim, Khelif; Henri, Agut; Salma, Feki; Mahjoub, Aouni

    2012-01-01

    Background Infectious etiology in lymphoproliferative diseases has always been suspected. The pathogenic roles of human herpesvirus-6 (HHV-6) in acute leukemia have been of great interest. Discordant results to establish a link between HHV-6 activation and the genesis of acute leukemia have been observed. The objective of this study was to evaluate a possible association between HHV-6 infection and acute leukemia in children and adults, with a longitudinal follow-up at diagnosis, aplasia, rem...

  20. Leukemia cutis with lymphoglandular bodies: a clue to acute lymphoblastic leukemia cutis

    Obiozor, Cynthia; Ganguly, Siddhartha; Fraga, Garth R.

    2015-01-01

    Leukemia cutis describes cutaneous lesions produced by infiltrates of leukemic cells. It usually manifests contemporaneously with the initial diagnosis of systemic leukemia, but may also precede or follow systemic leukemia. Most cases are associated with acute myeloid leukemia. Adult B-cell lymphoblastic leukemia cutis is very rare. We report a 59-year-old woman with a history of B-cell acute lymphoblastic leukemia who relapsed with aleukemic lymphoblastic leukemia cutis. Lymphoglandular bodi...

  1. Spectrum of acute and chronic leukemia at a tertiary care hospital, Haryana, India

    Gajender Singh; Padam Parmar; Sant Prakash Kataria; Sunita Singh; Rajeev Sen

    2016-01-01

    Background: Leukemias are primary neoplasms arising from the malignant proliferations of blood cells or their precursors. Leukemias are classified into acute/chronic myeloid and lymphoid subtype. Typing of leukemia is essential for effective therapy because prognosis and survival rate are different for each type and sub-type. Methods: A total of 356 patients diagnosed to have acute/chronic leukemia were included in our study. Only newly diagnosed cases were included in this study and patie...

  2. Dronabinol has preferential antileukemic activity in acute lymphoblastic and myeloid leukemia with lymphoid differentiation patterns

    Kampa-Schittenhelm, Kerstin Maria; Salitzky, Olaf; Akmut, Figen; Illing, Barbara; Kanz, Lothar; Salih, Helmut Rainer; Schittenhelm, Marcus Matthias

    2016-01-01

    Background It has been previously demonstrated in several cancer models, that Dronabinol (THC) may have anti-tumor activity – however, controversial data exists for acute leukemia. We have anecdotal evidence that THC may have contributed to disease control in a patient with acute undifferentiated leukemia. Methods To test this hypothesis, we evaluated the antileukemic efficacy of THC in several leukemia cell lines and native leukemia blasts cultured ex vivo. Expression analysis for the CB1/2 ...

  3. Philadelphia Chromosome-positive Acute Lymphoblastic Leukemia or Chronic Myeloid Leukemia in Lymphoid Blast Crisis.

    Kolenova, Alexandra; Maloney, Kelly W; Hunger, Stephen P

    2016-08-01

    The clinical characteristics of chronic myeloid leukemia (CML) in lymphoid blast crisis (BC) can resemble those of Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph ALL). Because of this, there can be concern as to whether a patient with newly diagnosed Ph leukemia has Ph ALL or CML in lymphoid BC. This distinction has significant potential therapeutic implications because most children with Ph ALL are now treated with chemotherapy plus a tyrosine kinase inhibitor, whereas allogeneic stem cell transplant is usually recommended for any patient with CML that presents in or later develops BC. PMID:27164534

  4. The JAK2V617F activating mutation occurs in chronic myelomonocytic leukemia and acute myeloid leukemia, but not in acute lymphoblastic leukemia or chronic lymphocytic leukemia

    Levine, Ross L.; Loriaux, Marc; Huntly, Brian J. P.; Loh, Mignon L.; Beran, Miroslav; Stoffregen, Eric; Berger, Roland; Clark, Jennifer J.; Willis, Stephanie G.; Nguyen, Kim T.; Flores, Nikki J.; Estey, Elihu; Gattermann, Norbert; Armstrong, Scott; Look, A. Thomas; Griffin, James D.; Bernard, Olivier A.; Heinrich, Michael C.; Gilliland, D. Gary; Druker, Brian; Deininger, Michael W. N.

    2005-01-01

    Activating mutations in tyrosine kinases have been identified in hematopoietic and nonhematopoietic malignancies. Recently, we and others identified a single recurrent somatic activating mutation (JAK2V617F) in the Janus kinase 2 (JAK2) tyrosine kinase in the myeloproliferative disorders (MPDs) polycythemia vera, essential thrombocythemia, and myeloid metaplasia with myelofibrosis. We used direct sequence analysis to determine if the JAK2V617F mutation was present in acute myeloid leukemia (AML), chronic myelomonocytic leukemia (CMML)/atypical chronic myelogenous leukemia (aCML), myelodysplastic syndrome (MDS), B-lineage acute lymphoblastic leukemia (ALL), T-cell ALL, and chronic lymphocytic leukemia (CLL). Analysis of 222 patients with AML identified JAK2V617F mutations in 4 patients with AML, 3 of whom had a preceding MPD. JAK2V617F mutations were identified in 9 (7.8%) of 116 CMML/a CML samples, and in 2 (4.2%) of 48 MDS samples. We did not identify the JAK2V617F disease allele in B-lineage ALL (n = 83), T-cell ALL (n = 93), or CLL (n = 45). These data indicate that the JAK2V617F allele is present in acute and chronic myeloid malignancies but not in lymphoid malignancies. PMID:16081687

  5. Cancer Statistics: Acute Lymphocytic Leukemia (ALL)

    ... population data for older age groups are available. Statistics at a Glance Show More At a Glance ... acute lymphocytic leukemia in the United States. Survival Statistics Show More How Many People Survive 5 Years ...

  6. Glutathione S transferase (GSTP 1, GSTM 1, and GSTT 1 gene polymorphisms in Egyptian patients with acute myeloid leukemia

    Aml S Nasr

    2015-01-01

    Full Text Available BACKGROUND: The super family of glutathione S-transferases (GSTs is composed of multiple isoenzymes with significant evidence of functional polymorphic variation. GSTs detoxify potentially mutagenic and toxic DNA-reactive electrophiles, including metabolites of several chemotherapeutic agents, some of which are suspected human carcinogens. Polymorphisms within the phase II metabolizer enzymes GST T1, GST M1, and GST P1 affect the body's ability to detoxify a range of potential leukemogens encountered in the environment. AIM OF WORK: To address how differences in the human GST isoenzyme expression patterns influence cancer susceptibility, prognosis, and treatment. PATIENTS AND METHODS: A total of 50 patients with acute myeloid leukemia (AML, as well as 50 age and sex matched apparently healthy volunteers were genotyped for GSTP 1, GSTM 1, and GSTT 1 gene polymorphisms using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP and conventional polymerase chain reaction (PCR, respectively. RESULTS: For GSTP1 313 A → G (GSTP1 Ile105Val polymorphism, It was found that the wild genotype (AA was significantly higher among control subjects (P value = 0.0277, while the frequency of heteromutant genotype (AG and mutant G allele (AG + GG was significantly higher among patients (P value = 0.0402, P value = 0.0277, respectively. For GSTM1 and GSTT1gene, we found statistically significantly higher frequency among patients regarding homozygous gene deletion (P value = 0.0005. CONCLUSION: We demonstrated that GSTM1 null or GSTT1 null genotypes may be considered independent risk factors for AML with no impact on prognosis and GSTP1 * 105 genotype is a prognostic factor, adding independent information to the routine laboratory parameters and cytogenetic and molecular alterations of the tumor cells.

  7. Bone marrow infiltration in patients with acute leukemia: dynamic contrast-enhanced MRI and its clinical significance

    Objective: Using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) to evaluate the hemodynamic perfusion characteristics of bone marrow infiltration in patients with acute leukemia (AL). Methods: Forty-seven patients with AL received coronal pelvic T1WI DCE-MRI with fast low angle shot (FLASH) sequence. Among them, 25 were initial onset untreated (IOU) patients, 22 were treated AL patients, including 14 with complete remission (CR) and 8 with non-remission (NR). The hemodynamic perfusion parameters including maximum percentage of enhancement (Emax) and slope were determined based on enhancement-time curves (ETCs) of iliac and lumbar vertebra. The proportion of marrow myeloblasts was recorded. For all patients, quantitative perfusion parameters of bone marrow infiltration in ilium were compared with those in lumbar. The values of Emax and ES were compared among IOU, CR and NR patients. Correlations between perfusion parameters and histopathological results were assessed. Results: In all the 47 patients, the Emax values of bilateral iliac bone marrow (15.70±7.06) were slightly higher than that of lumbar bone marrow (11.28±5.52), and the difference was statistically significant (P0.05). In the 25 untreated patients, the Emax and slop values were 17.15±5.75 and 0.98±0.13, respectively; in the 14 CR patients, they were 8.76±3.93 and 0.26±0.04, respectively, and in the 8 NR patients, they were 21.62±6.50 and 1.38±0.02, respectively. There was significant difference in the Emax and slop values among the three groups (P0.05). A significant positive correlation was found between Emax value of iliac bone marrow and the proportion of marrow myeloblasts (r=0.501, P 0.05). Conclusions: DCE-MRI can be used for evaluating the hemodynamic characteristics of microcirculation of bone marrow infiltration in patients with AL, which can provide useful information in evaluating prognosis and monitoring therapeutic effect. (authors)

  8. Brachial Plexopathy due to Myeloid Sarcoma in a Patient With Acute Myeloid Leukemia After Allogenic Peripheral Blood Stem Cell Transplantation

    Ha, Yumi; Sung, Duk Hyun; Park, Yoonhong; Kim, Du Hwan

    2013-01-01

    Myeloid sarcoma is a solid, extramedullary tumor comprising of immature myeloid cells. It may occur in any organ; however, the invasion of peripheral nervous system is rare. Herein, we report the case of myeloid sarcoma on the brachial plexus. A 37-year-old woman with acute myelogenous leukemia achieved complete remission after chemotherapy. One year later, she presented right shoulder pain, progressive weakness in the right upper extremity and hypesthesia. Based on magnetic resonance images ...

  9. [Expression of HoxA10 in acute leukemia and its significance].

    Huang, Ying; Li, Wei-Jia; Wei, Cai-Xia; Zhou, Zhi; Nie, Bo

    2005-12-01

    To investigate the expression of HoxA(10) mRNA in acute leukemia patients and its significance, HoxA(10) level was detected by reverse transcription polymerase chain reaction (RT-PCR) in 50 patients with acute leukemias, 7 healthy volunteers and 3 patients with ITP (idiopathic thrombocytopenic purpura). The regularity of the expression of HoxA(10) gene in acute leukemia and the relationship between HoxA(10) level and the prognosis of leukemia was explored. The results showed that HoxA(10) was expressed in all types of acute myelogenous leukemia; HoxA(10) message was also observed in acute lymphoblastic leukemia patients and part of control groups. 3 normal donors were found not to express HoxA(10). The level of HoxA(10) mRNA of acute myelogenous leukemia patients was significantly higher than that of acute lymphoblastic leukemia patients and controls (P acute promyelocytic leukemia. The number of blast and promyeloid cells in the bone marrow was positive related with the level of HoxA (r = 0.635, P acute myelogenous leukemia. It is concluded that HoxA(10) is a major transcription factor regulating hematopoiesis and a mark to differentiate lymphoid leukemia and myelogenous leukemia, but not a specific gene of cancer. The level of HoxA(10) is related with load of leukemic cells and curative effect, and can affect occurrence and development of leukemia in combination with many cytokines, HoxA(10) may facilitate the leukemia progression with another cofactors. PMID:16403259

  10. Support for social rehabilitation of childhood acute lymphoblastic leukemia patients. Psychological and educational assessment by the K-ABC

    Intellectual impairment in pediatric acute lymphoblastic leukemia (ALL) is thought to be caused by the effect of treatment on the central nervous system. We therefore assessed the characteristics and tendencies of patients' cognitive ability by using the K-ABC (Kaufman Assessment Battery for Children), an intelligence test. The subjects were 28 patients treated for ALL (males 18, females 10, age 4.7-12.0 years). The patients who took the K-ABC test were divided into irradiation group (15 patients who received brain irradiation as prophylactic treatment) and a non-irradiation group (13 patients whose brain was not irradiated), and evaluated the results. The K-ABC consists of a cognition processing scale and an acquisition level, and the cognition processing scale consists of a sequential processing scale and simultaneous processing scale. Patients were assessed in regard to various factors: 1. sex, 2. age of onset, 3. length of hospital stay, 4. age at the time of irradiation, 5. radiation dose, 6. score on the cognition processing scale, and multiple comparisons were made based on analysis of variance, least significant differences (1, 2, 3, 6), and the t-test (4, 5). Sequential processing ability was impaired in the patients with impaired cognitive processing in both groups. Part of simultaneous processing ability (ability to understand spatial relationships) tended to be reduced in the irradiation group in addition to the impairment in sequential processing ability, and factors 1 and 4 influenced cognitive ability in the irradiation group. The ability of girls decreased more than in boys. When children were irradiated below 4 years of age, their ability decreased even more. Regardless of whether they had received radiation therapy, all of the patients had received chemotherapy, including methotrexate, etc., and the anticancer drugs may have reduced their cognitive ability. The reduction of simultaneous processing ability may have been caused by the addition of

  11. Support for social rehabilitation of childhood acute lymphoblastic leukemia patients. Psychological and educational assessment by the K-ABC

    Izumi, Mayuko [Ochanomizu Univ., Tokyo (Japan); Hosoya, Ryouta; Oohira, Mutsuro; Kaneko, Takashi; Matsushita, Taketsugu

    2000-10-01

    Intellectual impairment in pediatric acute lymphoblastic leukemia (ALL) is thought to be caused by the effect of treatment on the central nervous system. We therefore assessed the characteristics and tendencies of patients' cognitive ability by using the K-ABC (Kaufman Assessment Battery for Children), an intelligence test. The subjects were 28 patients treated for ALL (males 18, females 10, age 4.7-12.0 years). The patients who took the K-ABC test were divided into irradiation group (15 patients who received brain irradiation as prophylactic treatment) and a non-irradiation group (13 patients whose brain was not irradiated), and evaluated the results. The K-ABC consists of a cognition processing scale and an acquisition level, and the cognition processing scale consists of a sequential processing scale and simultaneous processing scale. Patients were assessed in regard to various factors: 1. sex, 2. age of onset, 3. length of hospital stay, 4. age at the time of irradiation, 5. radiation dose, 6. score on the cognition processing scale, and multiple comparisons were made based on analysis of variance, least significant differences (1, 2, 3, 6), and the t-test (4, 5). Sequential processing ability was impaired in the patients with impaired cognitive processing in both groups. Part of simultaneous processing ability (ability to understand spatial relationships) tended to be reduced in the irradiation group in addition to the impairment in sequential processing ability, and factors 1 and 4 influenced cognitive ability in the irradiation group. The ability of girls decreased more than in boys. When children were irradiated below 4 years of age, their ability decreased even more. Regardless of whether they had received radiation therapy, all of the patients had received chemotherapy, including methotrexate, etc., and the anticancer drugs may have reduced their cognitive ability. The reduction of simultaneous processing ability may have been caused by the addition

  12. Genomic profiling of thousands of candidate polymorphisms predicts risk of relapse in 778 Danish and German childhood acute lymphoblastic leukemia patients

    Wesolowska, Agata; Borst, L.; Dalgaard, Marlene Danner;

    2015-01-01

    Childhood acute lymphoblastic leukemia survival approaches 90%. New strategies are needed to identify the 10–15% who evade cure. We applied targeted, sequencing-based genotyping of 25 000 to 34 000 preselected potentially clinically relevant singlenucleotide polymorphisms (SNPs) to identify host...... genome profiles associated with relapse risk in 352 patients from the Nordic ALL92/2000 protocols and 426 patients from the German Berlin–Frankfurt–Munster (BFM) ALL2000 protocol. Patients were enrolled between 1992 and 2008 (median follow-up: 7.6 years). Eleven cross-validated SNPs were significantly...... associated with risk of relapse across protocols. SNP and biologic pathway level analyses associated relapse risk with leukemia aggressiveness, glucocorticosteroid pharmacology/response and drug transport/metabolism pathways. Classification and regression tree analysis identified three distinct risk groups...

  13. Double CEBPA mutations are prognostically favorable in non-M3 acute myeloid leukemia patients with wild-type NPM1 and FLT3-ITD

    Wen, Xiang-Mei; Lin, Jiang; YANG Jing; Yao, Dong-Ming; Deng, Zhao-Qun; Tang, Chun-Yan; Xiao, Gao-fei; Lei YANG; Ma, Ji-chun; Hu, Jia-Bo; Qian, Wei; Qian, Jun

    2014-01-01

    This study is aimed to investigate the pattern of CEBPA mutations and its clinical significance in Chinese non-M3 acute myeloid leukemia (AML) patients. The entire coding region of CEBPA gene was amplified by PCR and then sequenced in samples from 233 non-M3 AML patients. Fifty mutations were identified in 37 (15.8%) patients with eleven (4.7%) double mutated CEBPA (dmCEBPA) and twenty-six (11.1%) single mutated CEBPA (smCEBPA). dmCEBPA was exclusively observed in M1 and M2 subtypes of FAB cl...

  14. Phase 2 clinical trial of 5-azacitidine, valproic acid, and all-trans retinoic acid in patients with high-risk acute myeloid leukemia or myelodysplastic syndrome

    Raffoux, Emmanuel; Cras, Audrey; Recher, Christian; Boëlle, Pierre-Yves; de Labarthe, Adrienne; Turlure, Pascal; Marolleau, Jean-Pierre; Reman, Oumedaly; Gardin, Claude; Victor, Maud; Maury, Sébastien; Rousselot, Philippe; Malfuson, Jean-Valère; Maarek, Odile; Daniel, Marie-Thérèse

    2010-01-01

    In this Phase 2 study, we evaluated the efficacy of combination of 5-azacitidine (AZA), valproic acid (VPA), and all-trans retinoic acid (ATRA) in patients with high-risk acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS). Treatment consisted of six cycles of AZA and VPA for 7 days, followed by ATRA for 21 days. Sixty-five patients were enrolled (median age, 72 years; 55 AML including 13 relapsed/refractory patients, 10 MDS; 30 unfavorable karyotypes). Best responses included 14 C...

  15. Radiation treatment of testicular relapse in acute lymphoblastic leukemia

    Ten patients with testicular relapse among 128 cases of acute lymphoblastic leukemia are reported. At the time of the initial diagnosis of leukemia all patients with later testicular relapse showed one or more risk factors as predictive for leukemic infiltration of the testicles. All patients except one, who underwent orchiectomy and died 11 weeks after surgical intervention, received radiation therapy with doses ranging from 12 to 20 Gy and chemotherapy. The local control was excellent. Average survival time from testicular relapse to death was 68 weeks in 8 of 9 patients treated by irradiation and chemotherapy. One patient is still alive without signs of disease after 6 years. (orig.)

  16. Protracted Administration of L-Asparaginase in Maintenance Phase Is the Risk Factor for Hyperglycemia in Older Patients with Pediatric Acute Lymphoblastic Leukemia.

    Hideki Yoshida

    Full Text Available Although L-asparaginase related hyperglycemia is well known adverse event, it is not studied whether the profile of this adverse event is affected by intensification of L-asparaginase administration. Here, we analyzed the profile of L-asparaginase related hyperglycemia in a 1,176 patients with pediatric acute lymphoblastic leukemia treated according to the Japan Association of Childhood Leukemia Study ALL-02 protocol using protracted L-asparaginase administration in maintenance phase. We determined that a total of 75 L-asparaginase related hyperglycemia events occurred in 69 patients. Although 17 events (17/1176, 1.4% developed in induction phase, which was lower incidence than those (10-15% in previous reports, 45 events developed during the maintenance phase with protracted L-asparaginase administration. Multivariate analysis showed that older age at onset (≥ 10 years was a sole independent risk factor for L-asparaginase-related hyperglycemia (P<0.01, especially in maintenance phase. Contrary to the previous reports, obesity was not associated with L-asparaginase-related hyperglycemia. These findings suggest that protracted administration of L-asparaginase is the risk factor for hyperglycemia when treating adolescent and young adult acute lymphoblastic leukemia patients.

  17. Image-Guided Total-Marrow Irradiation Using Helical Tomotherapy in Patients With Multiple Myeloma and Acute Leukemia Undergoing Hematopoietic Cell Transplantation

    Purpose: Total-body irradiation (TBI) has an important role in patients undergoing hematopoietic cell transplantation (HCT), but is associated with significant toxicities. Targeted TBI using helical tomotherapy results in reduced doses to normal organs, which predicts for reduced toxicities compared with standard TBI. Methods and Materials: Thirteen patients with multiple myeloma were treated in an autologous tandem transplantation Phase I trial with high-dose melphalan, followed 6 weeks later by total-marrow irradiation (TMI) to skeletal bone. Dose levels were 10, 12, 14, and 16 Gy at 2 Gy daily/twice daily. In a separate allogeneic HCT trial, 8 patients (5 with acute myelogenous leukemia, 1 with acute lymphoblastic leukemia, 1 with non-Hodgkin's lymphoma, and 1 with multiple myeloma) were treated with TMI plus total lymphoid irradiation plus splenic radiotherapy to 12 Gy (1.5 Gy twice daily) combined with fludarabine/melphalan. Results: For the 13 patients in the tandem autologous HCT trial, median age was 54 years (range, 42-66 years). Median organ doses were 15-65% that of the gross target volume dose. Primarily Grades 1-2 acute toxicities were observed. Six patients reported no vomiting; 9 patients, no mucositis; 6 patients, no fatigue; and 8 patients, no diarrhea. For the 8 patients in the allogeneic HCT trial, median age was 52 years (range, 24-61 years). Grades 2-3 nausea, vomiting, mucositis, and diarrhea were observed. In both trials, no Grade 4 nonhematologic toxicity was observed, and all patients underwent successful engraftment. Conclusions: This study shows that TMI using helical tomotherapy is clinically feasible. The reduced acute toxicities observed compare favorably with those seen with standard TBI. Initial results are encouraging and warrant further evaluation as a method to dose escalate with acceptable toxicity or to offer TBI-containing regimens to patients unable to tolerate standard approaches

  18. Wilms Tumor 1 Expression and Pre-emptive Immunotherapy in Patients with Acute Myeloid Leukemia Undergoing an Allogeneic Hemopoietic Stem Cell Transplantation.

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

    2016-07-01

    Minimal residual disease (MRD) was monitored by Wilms tumor 1 (WT1) expression in 207 patients with acute myeloid leukemia (AML) after an allogeneic hemopoietic stem cell transplantation (HSCT) as a trigger to initiate pre-emptive immunotherapy (IT) with cyclosporin discontinuation and/or donor lymphocyte infusion. The trigger for IT was WT1 ≥ 180 copies/10(4) Abelson cells in marrow cells in the first group of 122 patients (WT1-180) and ≥ 100 copies in a subsequent group of 85 patients (WT1-100). Forty patients received IT. The cumulative incidence (CI) of relapse was 76% in WT1-180 (n = 17) versus 29% in WT1-100 patients (n = 23) receiving IT (P = .006); the leukemia-free survival from MRD positivity was 23% versus 74%, respectively (P = .003). We then looked at the entire AML patient population (n = 207). WT1-180 and WT1-100 patients were comparable for disease phase and age. The overall 4-year CI of transplantation-related mortality was 13% in both groups; the CI of leukemia relapse was 38% in the WT1-180 and 28% in the WT1-100 patients (P = .05) and leukemia-free survival was 56% versus 48%, respectively (P = .07). In conclusion, we suggests that WT1-based pre-emptive immunotherapy is feasible in patients with undergoing an allogeneic HSCT. The protective effect on relapse is greater when IT is triggered at lower levels of WT1. PMID:26970379

  19. Outcome of conditioning intensity in acute myeloid leukemia with monosomal karyotype in patients over 45 year-old : A study from the acute leukemia working party (ALWP) of the European group of blood and marrow transplantation (EBMT)

    Poire, Xavier; Labopin, Myriam; Cornelissen, Jan J.; Volin, Liisa; Richard Espiga, Carlos; Veelken, J. Hendrik; Milpied, Noel; Cahn, Jean-Yves; Yacoub-Agha, Ibrahim; van Imhoff, Gustaaf W.; Michallet, Mauricette; Michaux, Lucienne; Nagler, Arnon; Mohty, Mohamad

    2015-01-01

    Acute myeloid leukemia with monosomal karyotype (MK AML) carries a very poor prognosis, even after allogeneic stem cell transplantation (SCT). However, SCT remains the only curative option in this high-risk population. Because myeloablative conditioning regimen (MAC) is associated with less relapse,

  20. Phase 2 trial of clofarabine in combination with etoposide and cyclophosphamide in pediatric patients with refractory or relapsed acute lymphoblastic leukemia

    Hijiya, Nobuko; Thomson, Blythe; Isakoff, Michael S.; Silverman, Lewis B.; Steinherz, Peter G.; Borowitz, Michael J.; Kadota, Richard; Cooper, Todd; Shen, Violet; Dahl, Gary; Thottassery, Jaideep V.; Jeha, Sima; Maloney, Kelly; Paul, Jo-Anne; Barry, Elly

    2011-01-01

    The outcomes in children with refractory/relapsed (R/R) acute lymphoblastic leukemia (ALL) are dismal. The efficacy and safety of intravenous clofarabine 40 mg/m2 per day, cyclophosphamide 440 mg/m2 per day, and etoposide 100 mg/m2 per day for 5 consecutive days in pediatric patients with R/R ALL was evaluated in this phase 2 study. The primary endpoint was overall response rate (complete remission [CR] plus CR without platelet recovery [CRp]). Among the 25 patients (median age, 14 years; pre...

  1. The Costs and Cost-Effectiveness of Allogeneic Peripheral Blood Stem Cell Transplantation versus Bone Marrow Transplantation in Pediatric Patients with Acute Leukemia

    LIN Yu-feng; Lairson, David R.; Chan, Wenyaw; Du, Xianglin L.; Leung, Kathryn S.; Kennedy-Nasser, Alana A.; Martinez, Caridad A; Gottschalk, Stephen M; Bollard, Catherine M.; Heslop, Helen E.; Brenner, Malcolm K; Krance, Robert A.

    2010-01-01

    In a retrospective study, we evaluated the cost and cost-effectiveness of allogeneic peripheral blood stem cell transplantation (PBSCT) (n=30) compared with bone marrow transplantation (BMT) (n=110) in children with acute leukemia at 1 year of follow up. Treatment success was defined as disease free survival at one year post transplant. For standard risk disease patients the treatment success rate was 57.1% for PBSCT patients and 80.3% for recipients of BMT (P=NS). The average total cost per ...

  2. Polymorphisms of Dectin-1 and TLR2 Predispose to Invasive Fungal Disease in Patients with Acute Myeloid Leukemia.

    Mike Fischer

    Full Text Available Patients with acute myeloid leukemia (AML who undergo induction chemotherapy are at high risk for invasive fungal disease (IFD. Dectin-1, a C-type lectin family member represents one of the most important pattern recognition receptors of the innate immune system and single nucleotide polymorphisms (SNPs in the Dectin-1 gene have been associated with an increased risk of infectious complications. We sought to investigate the impact of three different Dectin-1 SNPs and one TLR2 SNP on developing IFD in 186 adult patients with newly diagnosed AML following anthracycline-based induction chemotherapy.Genotyping of Dectin-1 SNPs (rs16910526, rs3901533 and rs7309123 and TLR2 SNP (rs5743708 was performed by TaqMan method and pyrosequencing. IFD was defined according to the EORTC/MSG consensus guidelines. Multiple logistic regression analyses were applied to evaluate the association between the polymorphisms and the occurrence of pulmonary infections. Dectin-1 expression studies with SNP genotyped human monocytes were performed to elucidate susceptibility to IFD following chemotherapy.We could demonstrate that patients carrying the Dectin-1 SNP rs7309123 G/G (n = 47 or G/G and C/G (n = 133 genotype revealed a significant higher risk for developing both pneumonia in general (adjusted odds ratio (OR: 2.5; p = 0.014 and OR: 3.0, p = 0.004 and pulmonary IFD (OR: 2.6; p = 0.012 and OR: 2.4, p = 0.041, respectively. Patients carrying the TLR2 SNP rs5743708 (R753Q, GA/AA genotype, n = 12 also revealed a significantly higher susceptibility to pneumonia including IFD. Furthermore, Dectin-1 mRNA expression in human monocytes was lower following chemotherapy.To our best knowledge, this study represents the first analysis demonstrating that harbouring polymorphisms of Dectin-1 (rs7309123 or TLR2 (rs5743708 represents an independent risk factor of developing IFD in patients with AML undergoing induction chemotherapy.

  3. Pre-chemotherapy risk factors for invasive fungal diseases: prospective analysis of 1,192 patients with newly diagnosed acute myeloid leukemia (SEIFEM 2010-a multicenter study).

    Caira, Morena; Candoni, Anna; Verga, Luisa; Busca, Alessandro; Delia, Mario; Nosari, Annamaria; Caramatti, Cecilia; Castagnola, Carlo; Cattaneo, Chiara; Fanci, Rosa; Chierichini, Anna; Melillo, Lorella; Mitra, Maria Enza; Picardi, Marco; Potenza, Leonardo; Salutari, Prassede; Vianelli, Nicola; Facchini, Luca; Cesarini, Monica; De Paolis, Maria Rosaria; Di Blasi, Roberta; Farina, Francesca; Venditti, Adriano; Ferrari, Antonella; Garzia, Mariagrazia; Gasbarrino, Cristina; Invernizzi, Rosangela; Lessi, Federica; Manna, Annunziata; Martino, Bruno; Nadali, Gianpaolo; Offidani, Massimo; Paris, Laura; Pavone, Vincenzo; Rossi, Giuseppe; Spadea, Antonio; Specchia, Giorgina; Trecarichi, Enrico Maria; Vacca, Adriana; Cesaro, Simone; Perriello, Vincenzo; Aversa, Franco; Tumbarello, Mario; Pagano, Livio

    2015-02-01

    Correct definition of the level of risk of invasive fungal infections is the first step in improving the targeting of preventive strategies. We investigated the potential relationship between pre-hospitalization exposure to sources of fungi and the development of invasive fungal infections in adult patients with newly diagnosed acute myeloid leukemia after their first course of chemotherapy. From January 2010 to April 2012, all consecutive acute myeloid leukemia patients in 33 Italian centers were prospectively registered. Upon first admission, information about possible pre-chemotherapy risk factors and environmental exposure was collected. We recorded data regarding comorbid conditions, employment, hygienic habits, working and living environment, personal habits, hobbies, and pets. All invasive fungal infections occurring within 30 days after the first course of chemotherapy were recorded. Of the 1,192 patients enrolled in this study, 881 received intensive chemotherapy and were included in the present analysis. Of these, 214 developed an invasive fungal infection, including 77 proven/probable cases (8.7%). Of these 77 cases, 54 were proven/probable invasive mold infections (6.1%) and 23 were proven yeast infections (2.6%). Upon univariate analysis, a significant association was found between invasive mold infections and age, performance status, diabetes, chronic obstructive pulmonary disease, smoking, cocaine use, job, hobbies, and a recent house renovation. Higher body weight resulted in a reduced risk of invasive mold infections. Multivariate analysis confirmed the role of performance status, job, body weight, chronic obstructive pulmonary disease, and house renovation. In conclusion, several hospital-independent variables could potentially influence the onset of invasive mold infections in patients with acute myeloid leukemia. Investigation of these factors upon first admission may help to define a patient's risk category and improve targeted prophylactic

  4. Minimal residual disease in acute lymphoblastic leukemia.

    Campana, Dario

    2009-01-01

    In patients with acute lymphoblastic leukemia (ALL), monitoring of minimal residual disease (MRD) offers a way to precisely assess early treatment response and detect relapse. Established methods to study MRD are flow cytometric detection of abnormal immunophenotypes, polymerase chain reaction (PCR) amplification of antigen-receptor genes, and PCR amplification of fusion transcripts. The strong correlation between MRD levels and risk of relapse in childhood ALL is well demonstrated; studies in adult patients also support its prognostic value. Hence, results of MRD studies can be used to select treatment intensity and duration, and to estimate the optimal timing for hematopoietic stem cell transplantation. Practical issues in the implementation of MRD assays in clinical studies include determining the most informative time point to study MRD and the levels of MRD that will trigger changes in treatment intensity, as well as the relative cost and informative power of different methodologies. The identification of new markers of leukemia and the use of increasingly refined assays should further facilitate routine monitoring of MRD and help to clarify the cellular and biologic features of leukemic cells that resist chemotherapy in vivo. PMID:19100372

  5. Rearrangement of the breakpoint cluster region in Philadelphia chromosome positive acute leukemia.

    Takahashi, Isao; Sekito,Noriko; Takeuchi, Makoto; Osada, Ken; Matsuzaki,Toshiro; Fukuda, Shunichi; Lai,Minyu; Uchida, Kozaburo; Kimura,Ikuro; Miyamoto,Kanji; Kitajima,Koichi; Sanada, Hiroshi

    1988-01-01

    The rearrangement of breakpoint cluster region (ber) was examined in leukemic cells obtained from 3 patients initially diagnosed as having Ph+ acute leukemia, 2 with acute lymphocytic leukemia (ALL) and one with acute mixed leukemia. DNA was digested with Bgl II and BamH I. The ber rearrangement was present in the case of acute mixed leukemia (Case 1), but was absent in the 2 cases of ALL (Cases 2 and 3). These results suggest that Case 1 represented a type of blast crisis of chronic myelocyt...

  6. Successful management of pulmonary hemorrhage and aspergillosis in a patient with acute myeloid leukemia (AML-M3

    Hulya Gunbatar

    2015-01-01

    Full Text Available A 35-year-old man presented with a one month history of gingival bleeding. He was diagnosed with Acute Myeloid Leukemia (AML-M3. During treatment he developed alveolar hemorrhage for which he was treated with a steroid. After the steroid treatment he developed a nodule, a cavitary lesion and atelectasia in the left lung. He was treated with voriconazole. After therapy with voriconazole his lesion significantly decreased. This case illustrates the efficacy and safety of antifungal therapy with voriconazole for aspergillosis complicated by AML.

  7. All-trans retinoic acid as a single agent induces complete remission in a patient with acute leukemia of M2a subtype

    陈子兴; 王阳; 王玮; 贡静霞; 薛永权

    2002-01-01

    Objective To present a special case with the karyotype and molecular marker of acute myeloid leukemia (AML)-M2 who was induced to complete remission by all-trans retinoic acid (ATRA) alone.Methods A recently hospitalized young female patient with acute leukemia was initially diagnosed as M3 subtype based on morphological French-American-British (FAB) classification. Karyotype analysis using standard G and R banding techniques and RT-PCR were applied to further define the diagnosis. After primarily cultured bone marrow cells from the iliac aspiration were tested for in vitro induced differentiation, the patient was treated with oral all-trans retinoic acid alone, 60?mg per day until complete remission was achieved. Peripheral blood and bone marrow changes were monitored over the whole treatment course.Results The characteristic chromosomal aberration for M3, the t(15;17) reciprocal translocation, was not found while a t(8;21) translocation was verified. Furthermore, an amplified product of the AML-1/ETO fusion gene instead of the PML/RARα fusion gene was detected by RT-PCR and the diagnosis was corrected from M3 to M2. Primary cultured bone marrow cells can be fully induced to terminal differentiation after 4 days exposure to ATRA. A hematological complete remission was achieved after 40 days treatment with ATRA as a single therapeutic agent, suggesting an alternative pathway mediating ATRA-induced myeloid differentiation. Conclusion A leukemia patient with a subtype other than M3, such as M2 in this case, may also be induced to complete remission by the mechanism of ATRA-induced terminal differentiation. This implies that there may be a pathway other than PML/RARα fusion gene product which mediates ATRA-induced myeloid maturation in leukemia cells.

  8. Pre-chemotherapy risk factors for invasive fungal diseases: prospective analysis of 1,192 patients with newly diagnosed acute myeloid leukemia (SEIFEM 2010-a multicenter study)

    Caira, Morena; Candoni, Anna; Verga, Luisa; Busca, Alessandro; Delia, Mario; Nosari, Annamaria; Caramatti, Cecilia; Castagnola, Carlo; Cattaneo, Chiara; Fanci, Rosa; Chierichini, Anna; Melillo, Lorella; Mitra, Maria Enza; Picardi, Marco; Potenza, Leonardo; Salutari, Prassede; Vianelli, Nicola; Facchini, Luca; Cesarini, Monica; De Paolis, Maria Rosaria; Di Blasi, Roberta; Farina, Francesca; Venditti, Adriano; Ferrari, Antonella; Garzia, Mariagrazia; Gasbarrino, Cristina; Invernizzi, Rosangela; Lessi, Federica; Manna, Annunziata; Martino, Bruno; Nadali, Gianpaolo; Offidani, Massimo; Paris, Laura; Pavone, Vincenzo; Rossi, Giuseppe; Spadea, Antonio; Specchia, Giorgina; Trecarichi, Enrico Maria; Vacca, Adriana; Cesaro, Simone; Perriello, Vincenzo; Aversa, Franco; Tumbarello, Mario; Pagano, Livio

    2015-01-01

    Correct definition of the level of risk of invasive fungal infections is the first step in improving the targeting of preventive strategies. We investigated the potential relationship between pre-hospitalization exposure to sources of fungi and the development of invasive fungal infections in adult patients with newly diagnosed acute myeloid leukemia after their first course of chemotherapy. From January 2010 to April 2012, all consecutive acute myeloid leukemia patients in 33 Italian centers were prospectively registered. Upon first admission, information about possible pre-chemotherapy risk factors and environmental exposure was collected. We recorded data regarding comorbid conditions, employment, hygienic habits, working and living environment, personal habits, hobbies, and pets. All invasive fungal infections occurring within 30 days after the first course of chemotherapy were recorded. Of the 1,192 patients enrolled in this study, 881 received intensive chemotherapy and were included in the present analysis. Of these, 214 developed an invasive fungal infection, including 77 proven/probable cases (8.7%). Of these 77 cases, 54 were proven/probable invasive mold infections (6.1%) and 23 were proven yeast infections (2.6%). Upon univariate analysis, a significant association was found between invasive mold infections and age, performance status, diabetes, chronic obstructive pulmonary disease, smoking, cocaine use, job, hobbies, and a recent house renovation. Higher body weight resulted in a reduced risk of invasive mold infections. Multivariate analysis confirmed the role of performance status, job, body weight, chronic obstructive pulmonary disease, and house renovation. In conclusion, several hospital-independent variables could potentially influence the onset of invasive mold infections in patients with acute myeloid leukemia. Investigation of these factors upon first admission may help to define a patient’s risk category and improve targeted prophylactic

  9. What Are the Risk Factors for Acute Lymphocytic Leukemia?

    ... both ALL and acute myeloid leukemia (AML). Japanese atomic bomb survivors had a greatly increased risk of developing ... cell acute lymphocytic leukemia. Most cases occur in Japan and the Caribbean area. This disease is not ...

  10. Do We Know What Causes Acute Myeloid Leukemia?

    ... Topic Can acute myeloid leukemia be prevented? Do we know what causes acute myeloid leukemia? Some people ... genes – the instructions for how our cells function. We tend to look like our parents because they ...

  11. What Should You Ask Your Doctor about Acute Lymphocytic Leukemia?

    ... treatment for acute lymphocytic leukemia? What should you ask your doctor about acute lymphocytic leukemia? It is ... with your doctor. You should feel free to ask any question that’s on your mind, no matter ...

  12. Age Difference in Immunophenotype of Acute Leukemia

    Kazunori Nakase

    2006-01-01

    Full Text Available We examined the immunophenotype of 880 cases with acute leukemia and analyzed their age difference in relation to the morphological subtype and the karyotype. We divided the patients into 3 age groups: child (0-15 years, adult (16-59 years and elderly (60 years and older group. The diagnoses based on the French-American-British (FAB criteria and the immunophenotype as follows: 453 patients as acute myeloid leukemia (AML, 366 as precursor B-cell acute lymphoblastic leukemia (ALL (24 CD10- cases and 342 CD10+ cases, 10 B-cell ALL and 51 T-cell ALL. In AML, there were no significant age differences in the frequency of FAB subtypes. Karyotypically, the frequencies of t(8;21 and 11q23 decreased with age and that of 5/7/8 abnormality increased with age. As for the immunophenotype in each FAB subtype, CD11b in M2 (0% and CD34 in M3 (0% were less commonly expressed in the child group than in the other age groups. Whereas Both CD11b (100% and CD34 (60% in M4 were more predominantly expressed in the child group than in the other age groups. Lymphoid antigen, CD19 showed a higher frequency (38.5% in the child M2 than did other age M2 groups, reflecting the distribution pattern of t(8;21 among the 3 age groups. Additionally, the child group more frequently expressed this antigen (33.3% than the older groups among CD7+ AML. In ALL, the frequency of CD10+ precursor B ALL was more common in the child group (84% than in the adult group. On the other hand, B-cell ALL showed a lower frequency (0.7% in the child group and T-cell ALL did a higher frequency (18.3% in the adult group than any other age groups, respectively. Although the frequency of t(9;22 increased with age in CD10+ precursor-B ALL, myeloid antigen (CD13/CD33 expression evenly distributed among the 3 age groups. Our results suggest that phenotypic heterogeneity gradually emerged with age irrespective of the pattern of karyotype.

  13. Recurrent Self-Limited Fungemia Caused by Yarrowia lipolytica in a Patient with Acute Myelogenous Leukemia

    Chang, Chulhun Ludgerus; Park, Tae Hee; Lee, Eun Yup; Lim, Young Tak; Son, Han Chul

    2001-01-01

    Yarrowia lipolytica is a weakly pathogenic yeast that is rarely isolated from the blood. We observed transient recurrent catheter-related fungemia attributable to this organism in a leukemic patient. The fungemia and accompanying fever subsided spontaneously. The data suggest that it might be possible to withhold specific treatment for Y. lipolytica fungemia even in an immunocompromised patient.

  14. MORPHOLOGIC & FLOWCYTOMETRIC ANALYSIS OF ACUTE LEUKEMIAS IN A TEACHING HOSPITAL IN CHHATTISGARH

    Rabia Parveen

    2015-10-01

    Full Text Available BACKGROUND : Immunophenotyping of leukemi a by flowcytometry offers a better classification of the hematopoietic lineage of malignant cells as compared to morphology. AIM : To determine the immunophenotypic subtypes of acute leukemia in a tertiary care teaching hospital. MATERIAL & METHODS : A one y ear study of morphologic & flowcytometric data of patients with acute leukemia. RESULTS : Total numbers of acute leukemia patients diagnosed morphologically were 45, out of which 20 patients underwent immunophenotyping by flowcytometry. Maximum patients wer e in the age group of 0 - 10 yrs followed by 11 - 20 yrs with males outnumbering female. Immunophenotypically they belonged to ALL - B cell lineage, ALL - T cell lineage, AML, biphenotypic, inconclusive. CONCLUSION : Immunophenotyping of acute leukemias by flowcyto metry, not only helps to confirm the morphologic diagnosis but also helps in assigning specific lineage to the blasts, particularly in acute lymphoid leukemia

  15. Secondary Solid Organ Neoplasm in Patients with Acute Lymphoblastic Leukemia: A Nationwide Population-Based Study in Taiwan

    Teng, Chung-Jen; Huon, Leh-Kiong; Hu, Yu-Wen; Yeh, Chiu-Mei; Chien, Sheng-Hsuan

    2016-01-01

    Background Acute lymphoblastic leukemia (ALL) is more common in children than in adults. Secondary neoplasms (SNs) in childhood ALL have been widely reported. However, only one study has demonstrated SNs in adult ALL. Because of the poorer survival of adult ALL, the incidence might be underestimated. Objective To evaluate the incidence and risk factors of secondary solid organ neoplasms among adult and child ALL patients. Methods Newly diagnosed ALL patients between 1997 and 2011 were recruited from the Taiwan National Health Insurance database. Those who had antecedent or combined malignancies were excluded. Standardized incidence ratios (SIRs) were analyzed to compare the risk of our cohort to general population in the same age, sex and calendar year. Risk factors for SN development were analyzed by Cox proportional hazards models. Effects of treatments were treated as time-dependent variables. Results The 15-year cumulative incidence of SN was 1.9% and 8.4% in 1,381 child and 2,154 adult ALL patients, respectively. The SIR was significantly increased in child ALL (SIR 6.06), but not in adult ALL (SIR 1.16). The SIRs of follow-up periods were 5.14, 2.24, .87 and .71 at ≥ 10 years, 5–10 years, 1–5 years and 0–1, respectively. Overall, 15 SNs developed, and CNS tumors (SIR 11.56) were the most common type. Multivariate analysis showed that age ≥ 20 years (hazard ratio [HR] 5.04), end-stage renal disease (HR 18.98) and cranial irradiation (HR 8.12) were independent risk factors for cancer development. Conclusions When compared with the general population, child ALL shows a increased risk of developing SNs. CNS tumors are the most common type, and cranial irradiation is an independent risk factor. With longer follow-up, the risk of SNs increases. Hence, physicians need to pay more attention on the risk of developing SNs in long-term ALL survivors with risk factors. PMID:27035574

  16. Vascular endothelial growth factor signaling in acute myeloid leukemia

    Kampen, Kim R.; ter Elst, Arja; de Bont, Eveline S. J. M.

    2013-01-01

    This review is designed to provide an overview of the current literature concerning vascular endothelial growth factor signaling (VEGF) in acute myeloid leukemia (AML). Aberrant VEGF signaling operates in the bone marrow of AML patients and is related to a poor prognosis. The altered signaling pathw

  17. Second Malignant Neoplasms After Treatment of Childhood Acute Lymphoblastic Leukemia

    Schmiegelow, K.; Levinsen, Mette Frandsen; Attarbaschi, Andishe;

    2013-01-01

    PURPOSE: Second malignant neoplasms (SMNs) after diagnosis of childhood acute lymphoblastic leukemia (ALL) are rare events. PATIENTS AND METHODS: We analyzed data on risk factors and outcomes of 642 children with SMNs occurring after treatment for ALL from 18 collaborative study groups between 1980...

  18. Prognostic significance of serum vascular endothelial growth factor levels in patients with acute myelogenous leukemia (AML)

    Objective: To measure the expression of vascular endothelial growth factor (VEGF) protein levels in various leukemic cell line cultures and serum of patients with AMI and assess its prognostic significance. Methods: VEGF levels in serum of 49 newly diagnosed AML patients, 10 AML patients in relapse and cultural supernatants of five leukemic cell lines (U937, K562, HL-60, TF-1 and NB4 for 48 hours) were determined by enzyme linked-immunosorbent assay (ELISA). Results: VEGF protein levels of cultural supernatants were high in all of the five leukemic cell lines (cultures), Serum VEGF levels in newly diagnosed and relapsed AML patients were 201.17 ± 110.93 pg/ml and 232.59 ±118.62 pg/ml respectively, obviously higher than those in the controls (p<0.05). In newly diagnosed patients with VEGF levels above and below the mean value 201.17 pg/ml, the complete remission (CR) rates were 48% and 77% respectively (p<0.05). Conclusion: VEGF plays a major role in the growth, proliferation and migration of hematopoietic malignancies cells. Serum VEGF levels have prognostic significance in patients with AML

  19. 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

    2015-11-16

    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

  20. 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

    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

  1. Health related quality of life and impact of infectious comorbidity in outpatient management of patients with acute leukemia

    Møller, Tom; Adamsen, Lis; Appel, Charlotte;

    2012-01-01

    longitudinal HRQOL evaluation (European Organisation for Research and Treatment of Cancer core 30-item questionnaire; EORTC-QLQ C-30) and the impact of infectious comorbidity among 60 patients with leukemia (median age 47) treated in an outpatient management program at Copenhagen University Hospital....... Significant improvement was seen on several HRQOL scores during follow-up. Explorative general linear models (GLMs) suggest that high cumulative severity of infectious comorbidity significantly reduces physical functioning and overall quality of life at treatment completion....

  2. ERYTHEMA NODOSUM REVEALING ACUTE MYELOID LEUKEMIA

    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

  3. Complicated septic shock caused by Achromobacter xylosoxidans bacteremia in a patient with acute lymphoblastic leukemia

    Al-Jasser A M

    2007-01-01

    Full Text Available Infections caused by Achromobacter xylosoxidans cause significant morbidity and mortality in debilitated individuals. Eradication of these infections requires prolonged therapy with antimicrobial agents and removal of any infected central venous catheter. The outcome is usually poor in patients with high risk malignancy, septic complications, and/or multi-organ dysfunction

  4. Marijuana Smoking in Patients With Leukemia.

    Khwaja, Sara; Yacoub, Abraham; Cheema, Asima; Rihana, Nancy; Russo, Robin; Velez, Ana Paula; Nanjappa, Sowmya; Sandin, Ramon L; Bohra, Chandrashekar; Gajanan, Ganesh; Greene, John N

    2016-07-01

    Worldwide, marijuana (cannabis) is a widely used drug. The incidence of marijuana smoking is increasing and is second only to tobacco as the most widely smoked substance in the general population. It is also the second most commonly used recreational drug after alcohol. Some adverse effects of marijuana smoking have been documented; however, the number of studies on the pulmonary effects of marijuana in individuals with leukemia is limited. In our case series, we report on 2 men with acute myeloid leukemia with miliary nodular lung patterns on computed tomography of the chest due to heavy marijuana use. We also report on 2 patients with acute lymphocytic leukemia who had a history of smoking marijuana and then developed lung opacities consistent with mold infection. PMID:27556668

  5. Clinical, cytogenetic and dual-color FISH studies on five cases of myelodysplastic syndrome or acute myeloid leukemia patients with 1;7 translocation

    申咏梅; 薛永权; 李建勇; 潘金兰; 吴亚芳

    2003-01-01

    Objective To study the clinical and cytogenetic characteristics of four patients with myel odysplastic syndrome (MDS) and one with acute myeloid leukemia experiencing t(1; 7).Methods Five patients seen in our hospital from 1992 to 2001 were diagnosed as MDS and acute myelocytic leukemia (AML) according to the French-American-British (FAB) criteria. Chromosomes were prepared using the direct method as well as 24-hou r unstimulated cultures of fresh heparinized bone marrow for each subject, while R-banding was used to analyze karyotypes. Dual-color fluorescence in situ hy bridization (FISH) using SpectrumRed and SpectrumGreen directly labeled chromoso me 1-specific α-satellite DNA probe (red) and chromosome 7- specific α-sat ellite DNA probe (green) was performed for three cases. Results Of the five patients, three had 1;7 translocation due to along history of expos ure to benzene. In three cases, dual-color FISH resulted in three red signals and two green ones, in which one red signal adjoining one green signal in 27.6% , 84% and 18.5% metaphases, respectively. Conclusions Exposure to benzene may be the cause for Chinese MDS and AML patients with t(1;7 ) translocation. The result of dual-color FISH convincingly confirmed that the centromere of the derivative chromosome 7p/1q resulting from 1;7 translocation was made up of centromeres from both chromosomes 1 and 7.

  6. Defining Molecular Phenotypes of Mesenchymal and hematopoietic Stem Cells derived from Peripheral blood of Acute Lymphocytic Leukemia patients for regenerative stem cell therapy

    Potdar, PD; Subedi, RP

    2011-01-01

    Acute Lymphocytic Leukemia (ALL) is a clonal myeloid disorder affecting all age groups, characterized by accumulation of immature blast cells in bone marrow and in peripheral blood. Autologous Bone Marrow Transplantation is a present treatment for cure of ALL patients, which is very expensive, invasive process and may have possibility of transplantation of malignant stem cells to patients. In the present study, we hypothesized to isolate large number of normal Mesenchymal & Hematopoietic stem cells from peripheral blood of ALL patients, which will be further characterized for their normal phenotypes by using specific molecular stem cell markers. This is the first study, which defines the existing phenotypes of isolated MSCs and HSCs from peripheral blood of ALL patients. We have established three cell lines in which two were Mesenchymal stem cells designated as MSCALL and MSCnsALL and one was suspension cell line designated as HSCALL. The HSCALL cell line was developed from the lymphocyte like cells secreted by MSCALL cells. Our study also showed that MSCALL from peripheral blood of ALL patient secreted hematopoietic stem cells in vitro culture. We have characterized all three-cell lines by 14 specific stem cell molecular markers. It was found that both MSC cell lines expressed CD105, CD13, and CD73 with mixed expression of CD34 and CD45 at early passage whereas, HSCALL cell line expressed prominent feature of hematopoietic stem cells such as CD34 and CD45 with mild expression of CD105 and CD13. All three-cell lines expressed LIF, OCT4, NANOG, SOX2, IL6, and DAPK. These cells mildly expressed COX2 and did not express BCR-ABL. Overall it was shown that isolated MSCs and HSCs can be use as a model system to study the mechanism of leukemia at stem cell level and their use in stem cell regeneration therapy for Acute Lymphocytic Leukemia. PMID:24693170

  7. Defining Molecular Phenotypes of Mesenchymal and hematopoietic Stem Cells derived from Peripheral blood of Acute Lymphocytic Leukemia patients for regenerative stem cell therapy

    Pravin D. Potdar

    2011-01-01

    Full Text Available Acute Lymphocytic Leukemia (ALL is a clonal myeloid disorder affecting all age groups, characterized by accumulation of immature blast cells in bone marrow and in peripheral blood. Autologous Bone Marrow Transplantation is a present treatment for cure of ALL patients, which is very expensive, invasive process and may have possibility of transplantation of malignant stem cells to patients. In the present study, we hypothesized to isolate large number of normal Mesenchymal & Hematopoietic stem cells from peripheral blood of ALL patients, which will be further characterized for their normal phenotypes by using specific molecular stem cell markers. This is the first study, which defines the existing phenotypes of isolated MSCs and HSCs from peripheral blood of ALL patients. We have established three cell lines in which two were Mesenchymal stem cells designated as MSCALL and MSCnsALL and one was suspension cell line designated as HSCALL. The HSCALL cell line was developed from the lymphocyte like cells secreted by MSCALL cells. Our study also showed that MSCALL from peripheral blood of ALL patient secreted hematopoietic stem cells in vitro culture. We have characterized all three-cell lines by 14 specific stem cell molecular markers. It was found that both MSC cell lines expressed CD105, CD13, and CD73 with mixed expression of CD34 and CD45 at early passage whereas, HSCALL cell line expressed prominent feature of hematopoietic stem cells such as CD34 and CD45 with mild expression of CD105 and CD13. All three-cell lines expressed LIF, OCT4, NANOG, SOX2, IL6, and DAPK. These cells mildly expressed COX2 and did not express BCR-ABL. Overall it was shown that isolated MSCs and HSCs can be use as a model system to study the mechanism of leukemia at stem cell level and their use in stem cell regeneration therapy for Acute Lymphocytic Leukemia.

  8. Long-term follow-up of imatinib plus combination chemotherapy in patients with newly diagnosed Philadelphia chromosome-positive acute lymphoblastic leukemia.

    Lim, Sung-Nam; Joo, Young-Don; Lee, Kyoo-Hyung; Kim, Dae-Young; Lee, Je-Hwan; Lee, Jung-Hee; Chi, Hyun-Sook; Yun, Sung-Cheol; Lee, Won Sik; Lee, Sang Min; Park, Seonyang; Kim, Inho; Sohn, Sang Kyun; Moon, Joon Ho; Ryoo, Hun-Mo; Bae, Sung Hwa; Hyun, Myung Soo; Kim, Min Kyoung; Kim, Hyeoung Joon; Yang, Deok-Hwan; Eom, Hyeon-Seok; Lee, Gyeong-Won; Jung, Chul Won; Won, Jong-Ho; Kim, Hawk; Lee, Jae-Hoon; Shin, Ho-Jin; Jang, Dae-Young

    2015-11-01

    The effects of imatinib plus chemotherapy were assessed in 87 patients with newly diagnosed Philadelphia chromosome-positive (Ph(+) ) acute lymphoblastic leukemia (ALL). Imatinib was administered continuously, starting from the eighth day of remission induction chemotherapy, then through five courses of consolidation or until allogeneic hematopoietic cell transplantation (HCT). Patients who were not transplanted were maintained on imatinib for 2 years. Eighty-two patients (94.3%) achieved complete remission (CR). Among these 82 CR patients, 40 experienced recurrence of leukemia. The 5-year relapse free survival (RFS) rate and overall survival (OS) rates were 39.0% and 33.4%, respectively. In total, 56 patients underwent allogeneic HCT in first CR. The 5-year cumulative incidence of relapse and OS rate of them were 59.1% and 52.6%, respectively. Six of seven patients who were maintained on imatinib after completion of consolidation relapsed and the median time of RFS was 40.7 months. In total patient, cumulative molecular CR rate was 88.5% and median time of molecular CR duration was 13 months. Initial imatinib dose intensity was significantly associated with median CR duration (P treatment of patients with Ph(+) ALL, it is important to maintain imatinib dose intensity. PMID:26228525

  9. MORPHOLOGIC & FLOWCYTOMETRIC ANALYSIS OF ACUTE LEUKEMIAS IN A TEACHING HOSPITAL IN CHHATTISGARH

    Rabia Parveen; Minal; Vanita; Patra; Swati

    2015-01-01

    BACKGROUND : Immunophenotyping of leukemi a by flowcytometry offers a better classification of the hematopoietic lineage of malignant cells as compared to morphology. AIM : To determine the immunophenotypic subtypes of acute leukemia in a tertiary care teaching hospital. MATERIAL & METHODS : A one y ear study of morphologic & flowcytometric data of patients with acute leukemia. RESULTS : Total numbers ...

  10. A Rare Case of Adult Acute Lymphoblastic Leukemia Presenting with Paraparesis and Multiple Osteolytic Lesions

    Verma, S P; Dubashi, B.; Basu, D; Dutta, T. K.; Kar, R.

    2013-01-01

    Acute lymphoblastic leukemia presenting with bone involvement and multiple osteolytic lesions has been commonly reported in pediatric population. Various myeloid and lymphoid malignancies can rarely present with bony lesions. We are reporting an adult female patient with acute lymphoblastic leukemia who presented with paraparesis and multiple osteolytic lesions in skull initially giving false impression of multiple myeloma.

  11. Outcome of older patients with acute myeloid leukemia in first relapse.

    Sarkozy, Clémentine; Gardin, Claude; Gachard, Nathalie; Merabet, Fathia; Turlure, Pascal; Malfuson, Jean-Valère; Pautas, Cécile; Micol, Jean-Baptiste; Thomas, Xavier; Quesnel, Bruno; Celli-Lebras, Karine; Preudhomme, Claude; Terré, Christine; Fenaux, Pierre; Chevret, Sylvie; Castaigne, Sylvie; Dombret, Hervé

    2013-09-01

    To provide data for future drug evaluation, we analyzed the outcome of 393 patients aged 50 years or older (median, 64 years) with AML in first relapse after treatment in recent ALFA trials. Salvage options were retrospectively classified as follows: best supportive care (BSC), low-dose cytarabine (LDAC), gemtuzumab ozogamicin (GO), intensive chemotherapy (ICT), or ICT combined with GO. Second complete remission (CR2) rate was 31% and median post-relapse survival was 6.8 months (0, 17, 42.5, 53, and 80% and 3.2, 5.6, 8.9, 9, and 19.8 months in BSC, LDAC, GO, ICT, and ICT + GO subsets, respectively). Age, performance status, WBC, CR1 duration, and favorable AML karyotype, but not other cytogenetic or molecular features, influenced post-relapse outcome. Multivariate adjustment and propensity score matching showed that intensive salvage (ICT/ICT+GO/GO versus LDAC/BSC) was associated with longer post-relapse survival, at least in patients with CR1 duration ≥12 months (P = 0.001 and 0.0005, respectively). Of interest, GO appeared to be as effective as standard ICT, and ICT + GO combination more effective than standard ICT. In conclusion, older patients with CR1 duration ≥12 months appeared to benefit from intensive salvage and results observed with GO-containing salvage suggest that GO combination studies should be actively pursued in this setting. PMID:23749683

  12. Therapy-Related Myelodysplastic Syndrome Following Treatment for Childhood Acute Lymphoblastic Leukemia: Outcome of Patients Registered in the EWOG-MDS 98/06 Studies

    Strahm, Birgitte; Amann, Roland; De Moerloose, Barbara;

    Objective: Therapy-related myelodysplastic syndrome (tMDS) following treatment of childhood acute lymphoblastic leukemia (ALL) is one of the most frequently observed secondary malignancies in survivors of childhood cancer. Allogeneic stem cell transplantation (SCT) is the only curative treatment....... This analysis was performed to asses the outcome of patients with tMDS following treatment for childhood ALL reported to the EWOG-MDS study group. Patients and Transplant Procedure: Forty-three patients (19 male/24 female) were diagnosed with tMDS between August 1989 and August 2009. The median age at diagnosis......, cyclophosphamide and melphalan (Bu/Cy/Mel) (23), an alternative busulfan based regimen (6), a radiation based regimen (5) or others (3). Results: After a median follow up of 4.1 (0.5 – 9.4) years, 14 patients are alive in first complete remission (CR). Seventeen patients developed relapse after a median time...

  13. Phase 1 Study of Terameprocol (EM-1421) in Patients With Leukemia

    2016-02-20

    Leukemias; Acute Myeloid Leukemia (AML); Acute Lymphocytic Leukemia (ALL); Adult T Cell Leukemia (ATL); Chronic Myeloid Leukemia (CML-BP); Chronic Lymphocytic Leukemia (CLL); Myelodysplastic Syndrome (MDS); Chronic Myelomonocytic Leukemia (CMML)

  14. Allogeneic stem cell transplantation in acute myeloid leukemia

    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%.

  15. Idiopathic thrombocytopenic purpura following successful treatment of acute lymphoblastic leukemia.

    Tannir, N M; Kantarjian, H

    2001-03-01

    Thrombocytopenia is common in patients with acute lymphocytic leukemia (ALL) at diagnosis. It is a universal side effect of dose-intensive regimens employed in the treatment of adult ALL. In patients with ALL who achieve remission, thrombocytopenia frequently indicates relapse. We report three adult patients successfully treated for ALL who developed thrombocytopenia and were found to have immune-mediated thrombocytopenia (ITP). Possible pathophysiologic mechanisms underlying the association of ALL and ITP are discussed. PMID:11342378

  16. Side effects of treatment in childhood acute leukemia, 2

    We evaluated delayed neurotoxicities in treatment of childhood acute leukemia. Of 28 patients treated over 2 years who were examined on computed tomography of brain scans, 7 patients had abnormal findings. These abnormalities included two cases of leukoencephalopathy, three cases of intracranial calcifications, and two of ventricular dilatation. These patients were under 6 years old at the onset of disease, especially under 3 years old. Also, delayed neurotoxicities developed after relapse of leukemia, especially CNS relapse. It was considered that these were caused by cranial irradiation, intravenous methotrexate injection, intrathecal methotrexate, and sometimes high-dose Ara-C therapy, etc. Most of the cases of leukoencephalopathy were associated with treatment of intermediate-dose or high-dose methotrexate after relapse. These abnormalities must be carefully considered in the treatment of younger children with leukemia and patients with relapse. (author)

  17. Prognostic impact of high ABC transporter activity in 111 adult acute myeloid leukemia patients with normal cytogenetics when compared to FLT3, NPM1, CEBPA and BAALC.

    Hirsch, Pierre; Tang, Ruoping; Marzac, Christophe; Perrot, Jean-Yves; Fava, Fanny; Bernard, Chantal; Jeziorowska, Dorota; Marie, Jean Pierre; Legrand, Ollivier

    2012-02-01

    ATP-binding cassette transporter (and specially P-glycoprotein) activity is a well known prognostic factor in acute myeloid leukemia, but when compared to other molecular markers its prognostic value has not been well studied. Here we study relationships between this activity, fms-like tyro-sine kinase 3(FLT3/ITD), nucleophosmin(NPM1), CAAT-enhancer binding protein alpha(CEBPα), and brain and acute leukemia cytoplasmic protein (BAALC), in 111 patients with normal cytogenetics who underwent the same treatment, and evaluate its prognostic impact. Independent factors for survival were age (P=0.0126), ATP-binding cassette transporter activity (P=0.018) and duplications in the fms-like tyrosine kinase 3 (P=0.0273). In the 66 patients without fms-like tyrosine kinase 3 duplication and without nucleophosmin mutation, independent prognostic factors for complete remission achievement and survival were age and ATP-binding cassette transporter activity. In conclusion, ATP-binding cassette transporter activity remains an independent prognostic factor, and could assist treatment decisions in patients with no nucleophosmin mutation and no fms-like tyrosine kinase 3 duplication. PMID:22058196

  18. Use of a stop-flow programmable shunt valve to maximize CNS chemotherapy delivery in a pediatric patient with acute lymphoblastic leukemia

    Sheri K Palejwala

    2014-01-01

    Full Text Available Background: The requirement for frequent intraventricular drug delivery in the setting of shunt dependence is particularly challenging in the treatment of central nervous system infection, neoplastic disease, and hemorrhage. This is especially relevant in the pediatric population where both hematogenous malignancy requiring intrathecal drug delivery and shunt-dependent hydrocephalus are more prevalent. Intrathecal and intraventricular chemotherapy agents can be prematurely diverted in these shunt-dependent patients. Case Description: We report the use of a stop-flow programmable shunt valve to maximize delivery of intraventricular chemotherapy in a child with acute lymphoblastic leukemia and disseminated intravascular coagulation who presented with spontaneous intracerebral and intraventricular hemorrhages. The patient then developed posthemorrhagic hydrocephalus and eventually progressed to shunt dependence but still required frequent intraventricular chemotherapy administration. A ventriculoperitoneal shunt, equipped with a valve that allows for near cessation of cerebrospinal fluid flow (Certas; , Codman, Raynham, MA, and a contralateral Ommaya reservoir were inserted to maximize intraventricular dissemination of chemotherapy. Conclusions: To the best of our knowledge, this is the first reported case of the use of a high-resistance programmable valve being used to virtually cease cerebrospinal fluid flow through the distal catheter temporarily in order to maximize intraventricular drug dissemination in a pediatric patient with acute lymphoblastic leukemia.

  19. Cerebral venous thrombosis in adult patients with acute lymphoblastic leukemia or lymphoblastic lymphoma during induction chemotherapy with l-asparaginase: The GRAALL experience.

    Couturier, Marie-Anne; Huguet, Françoise; Chevallier, Patrice; Suarez, Felipe; Thomas, Xavier; Escoffre-Barbe, Martine; Cacheux, Victoria; Pignon, Jean-Michel; Bonmati, Caroline; Sanhes, Laurence; Bories, Pierre; Daguindau, Etienne; Dorvaux, Véronique; Reman, Oumedaly; Frayfer, Jamile; Orvain, Corentin; Lhéritier, Véronique; Ifrah, Norbert; Dombret, Hervé; Hunault-Berger, Mathilde; Tanguy-Schmidt, Aline

    2015-11-01

    Central nervous system (CNS) thrombotic events are a well-known complication of acute lymphoblastic leukemia (ALL) induction therapy, especially with treatments including l-asparaginase (l-ASP). Data on risk factors and clinical evolution is still lacking in adult patients. We report on the clinical evolution of 22 CNS venous thrombosis cases occurring in 708 adults treated for ALL or lymphoblastic lymphoma (LL) with the Group for Research on Adult Acute Lymphoblastic Leukemia (GRAALL)-induction protocol, which included eight L-ASP (6,000 IU/m(2) ) infusions. The prevalence of CNS thrombosis was 3.1%. CNS thrombosis occurred after a median of 18 days (range: 11-31) when patients had received a median of three l-ASP injections (range: 2-7). Patients with CNS thrombosis exhibited a median antithrombin (AT) nadir of 47.5% (range: 36-67%) at Day 17 (range: D3-D28), and 95% of them exhibited AT levels lower than 60%. There were no evident increase in hereditary thrombotic risk factors prevalence, and thrombosis occurred despite heparin prophylaxis which was performed in 90% of patients. Acquired AT deficiency was frequently detected in patients with l-ASP-based therapy, and patients with CNS thrombosis received AT prophylaxis (45%) less frequently than patients without CNS thrombosis (83%), P = 0.0002). CNS thrombosis was lethal in 5% of patients, while 20% had persistent sequelae. One patient received all planned l-ASP infusions without recurrence of CNS thrombotic whereas l-ASP injections were discontinued in 20 patients during the management of thrombosis without a significant impact on overall survival (P = 0.4). PMID:26214580

  20. Environment-mediated drug resistance in Bcr/Abl-positive acute lymphoblastic leukemia

    Feldhahn, Niklas; Arutyunyan, Anna; Stoddart, Sonia; ZHANG Bin; Schmidhuber, Sabine; Yi, Sun-ju; Kim, Yong-Mi; Groffen, John; Heisterkamp, Nora

    2012-01-01

    Although cure rates for acute lymphoblastic leukemia (ALL) have increased, development of resistance to drugs and patient relapse are common. The environment in which the leukemia cells are present during the drug treatment is known to provide significant survival benefit. Here, we have modeled this process by culturing murine Bcr/Abl-positive acute lymphoblastic leukemia cells in the presence of stroma while treating them with a moderate dose of two unrelated drugs, the farnesyltransferase i...

  1. [Lipid peroxidation and antioxidant system status in patients with acute myeloblast leukemia and toxic damage of the liver].

    Kuzieva, G Z; Kholmatova, N M; Shevchenko, L I; Khuzhakhmedov, Zh D; Zavgorodniaia, S V

    2009-01-01

    Patients with acute myelogenous leucosis with toxic damage of the liver against polychemotherapy have an expressed disbalance in the lipid peroxidation-anti-oxidant system, which is possible to correct effectively using S-adenozilmetionin (heptral) was observed. PMID:19953992

  2. Pharmacokinetic modelling of methotrexate from routine clinical data in patients with acute lymphoblastic leukemia

    Pharmacokinetic modelling was performed in NONMEM (version 6.1) using a dataset including 273 patients (aged 2 to 23 years) who received high-dose MTX (5 g/m/sup 2/ per course) in long-term treatment. Total 2582 methotrexate plasma concentrations were performed by fluorescence polarisation immunoassay (FPIA). A three compartment open model with elimination from the central compartment described the pharmacokinetics of methotrexate. The most important covariates affecting the disposition of methotrexate were age (age, year), body weight (BW, kg), and creatinine clearance (CLR, lh/sup -1/). The final model with exponential disposition of MTX was clearance (CL, Ih/sup -1/) = (6.11 + WT*6.7310/sup -2/) + (1.0810/sup -4/* CLR )* EXP(1.9510/sup -1/), (V, l) = 10,8+(AGE* 9.310/sup -2/) *EXP(9.110/sup -1/), = Q(lh/sup -1/) = 2.0410/sup -3/*WT Pharmacokinetic parameters (percentage CV) in this study were CL, 8.72 lh/sup -1/ (44 %); V1, 17.49 I (95%); V2, 6.048 l (56%); V3, 0.015 I (52%). The model predictions in the qualification group were found to have no bias and satisfactory precision. (author)

  3. Quality control of flow cytometry data analysis for evaluation of minimal residual disease in bone marrow from acute leukemia patients during treatment

    Bjorklund, E.; Matinlauri, I.; Tierens, A.;

    2009-01-01

    Low levels of leukemia cells in the bone marrow, minimal residual disease (MRD), are considered to be a powerful indicator of treatment response in acute lymphatic leukemia (ALL). A Nordic quality assurance program, aimed on standardization of the flow cytometry MRD analysis, has been established...... MRD detection can be reliably applied in international, multicenter treatment protocols Udgivelsesdato: 2009/6...

  4. Next-generation sequencing for minimal residual disease monitoring in acute myeloid leukemia patients with FLT3-ITD or NPM1 mutations.

    Thol, Felicitas; Kölking, Britta; Damm, Frederik; Reinhardt, Katarina; Klusmann, Jan-Henning; Reinhardt, Dirk; von Neuhoff, Nils; Brugman, Martijn H; Schlegelberger, Brigitte; Suerbaum, Sebastian; Krauter, Jürgen; Ganser, Arnold; Heuser, Michael

    2012-07-01

    Systematic assessment of minimal residual disease (MRD) in acute myeloid leukemia (AML) patients has been hampered by lack of a reliable, uniform MRD marker applicable to all patients. We evaluated next-generation sequencing (NGS) for MRD assessment in AML patients (n = 80 samples). The ability of NGS technologies to generate thousands of clonal sequences makes it possible to determine the allelic ratio of sequence variants. Using NGS, we were able to determine the allelic ratio of different FLT3-internal tandem duplication (ITD) clones within one patient sample, in addition to resolution of FLT3-ITD insertion site, length, and sequence in a single analysis. Furthermore, NGS allowed us to study emergence of clonal dominance. Parallel assessment of MRD by NGS and quantitative real-time polymerase chain reaction in NPM1 mutated patients was concordant in 95% of analyzed samples (n = 38). The frequency of mutated alleles was linearly quantified by NGS. As NGS sensitivity is scalable depending on sequence coverage, it reflects a highly flexible and reliable tool to assess MRD in leukemia patients. PMID:22454318

  5. FLAG-induced remission in a patient with acute mast cell leukemia (MCL exhibiting t(7;10(q22;q26 and KIT D816H

    Peter Valent

    2014-01-01

    Full Text Available Mast cell leukemia (MCL is a life-threatening disease associated with high mortality and drug-resistance. Only few patients survive more than 12 months. We report on a 55-year-old female patient with acute MCL diagnosed in May 2012. The disease was characterized by a rapid increase in white blood cells and mast cells (MC in the peripheral blood, and a rapid increase of serum tryptase levels. The KIT D816H mutation was detected in the blood and bone marrow (BM. Induction chemotherapy with high-dose ARA-C and fludarabine (FLAG was administered. Unexpectedly, the patient entered a hematologic remission with almost complete disappearance of neoplastic MC and a decrease of serum tryptase levels to normal range after 2 cycles of FLAG. Consecutively, the patient was prepared for allogeneic stem cell transplantation. However, shortly after the third cycle of FLAG, tryptase levels increased again, immature MC appeared in the blood, and the patient died from cerebral bleeding. Together, this case shows that intensive chemotherapy regimens, like FLAG, may induce remission in acute MCL. However, treatment responses are short-lived and the overall outcome remains dismal in these patients. We propose to separate this acute type of MCL from more subacute or chronic variants of MCL.

  6. The surface molecular signature of leukemic cells is associated with NPM1 mutations and FLT3 -ITD in patients with de novo acute myeloid leukemia.

    Su, Long; Gao, Su-Jun; Li, Wei; Tan, Ye-Hui; Cui, Jiu-Wei; Han, Wei

    2014-01-01

    Certain molecular mutations are associated with signs of cell morphology and differentiation in acute myeloid leukemia (AML). However, only limited data are available for the detailed analysis of such correlations. In this study, AML patients were classified into 4 subsets according to CD34, HLA-DR and CD11c expression levels. Significantly low CD34 antigen expression was observed in nucleophosmin (NPM1)-mutated patients and in those with FMS-like tyrosine kinase 3 internal tandem duplication (FLT3-ITD). No correlations were observed among NPM1 mutations, FLT3-ITD and monocytic morphology in patients without CD34 expression. Both NPM1 mutations and FLT3-ITD were absent in cluster IIb patients (CD34(+)CD11c(-)). The associations among NPM1 mutations, FLT3-ITD and the surface molecular signature of leukemic cells may offer beneficial information about the pathogenesis of AML. PMID:24192815

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

    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 with...

  8. Acute parotitis during induction therapy including L-asparaginase in acute lymphoblastic leukemia.

    Sica, S; Pagano, L; Salutari, P; Di Mario, A; Rutella, S; Leone, G

    1994-02-01

    In a patient affected by acute lymphoblastic leukemia (ALL) and subjected to therapy with Erwinia L-asparaginase, acute parotitis was observed. Microbiological studies excluded any infectious etiology. Regression of parotitis was spontaneous. This complication has not been previously reported and could be due to the same mechanism of pancreatic injury. The occurrence of acute parotitis needs to be promptly recognized in order to avoid the continuation of L-asparaginase. PMID:8148421

  9. Molecular Insights in MLL Rearranged Acute Leukemia

    R.W. Stam (Ronald)

    2006-01-01

    textabstractAcute lymphoblastic leukemia (ALL) in infants (<1 year of age) is characterized by a high incidence (~80%) of rearrangements of the MLL gene, resistance to several important chemotherapeutic drugs, and a poor treatment outcome. With overall survival rates for infant ALL not exceeding 50%

  10. Acute leukemia of childhood: A single institution's experience

    Slavković Bojana

    2005-01-01

    Full Text Available The aim of this study was to investigate distribution of immunophenotypic and cytogenetic features of childhood acute leukemia (AL in the cohort of 239 newly diagnosed patients registered at the leading pediatric oncohematology center in the country during a six-year period (1996-2002. With approximately 60-70% of all childhood AL cases in Serbia and Montenegro being diagnosed and treated in this institution the used data represent a valid research sample to draw conclusions for entire country. On the basis of five phenotypic markers, the distribution of immunological subtypes was as follows: 169 (70.7% expressed B-cell marker CD19 (137 were CD10 positive and 32 CD10 negative, 37 (15.5% belonged to T-lineage acute lymphoblastic leukemia (T-ALL (cyCD3 positive, and 33 (13.8% were acute myeloblastic leukemia (AML (CD13 positive and/or CD33 positive in the absence of lymphoid-associated antigens. The ratio of males and females was 1.5:1. Most of the cases were between the ages of 2 and 4, and were predominantly B-lineage acute lymphoblastic leukemia (B-ALL cases. Another peak of age distribution was observed at the age of 7. The frequency of T-ALL (18% of ALL was similar to that reported for Mediterranean countries: France (19.4%, Greece (28.1%, Southern Italy (28.3%, and Bulgaria (28.0%. Cytogenetic analyses were performed in 193 patients: 164 ALL and 29 AML. Normal karyotype was found in 57% of ALL and in 55% of AML patients, while cytogenetic abnormalities including structural, numerical, and complex chromosomal rearrangements were found in 43% of ALL and in 45% of AML patients. Our results represent a contribution to epidemiological aspects of childhood leukemia studies.

  11. The clinically relevant pharmacogenomic changes in acute myelogenous leukemia

    Emadi, Ashkan; Karp, Judith E.

    2012-01-01

    Acute myelogenous leukemia (AML) is an extremely heterogeneous neoplasm with several clinical, pathological, genetic and molecular subtypes. Combinations of various doses and schedules of cytarabine and different anthracyclines have been the mainstay of treatment for all forms of AMLs in adult patients. Although this combination, with the addition of an occasional third agent, remains effective for treatment of some young-adult patients with de novo AML, the prognosis of AML secondary to myel...

  12. Prolonged Response in Patient With Multiply Relapsed B-cell Acute Lymphoblastic Leukemia and Monosomy-7 to Bortezomib, Lenalidomide, and Dexamethasone.

    Vundamati, Divya; Bostrom, Bruce

    2016-08-01

    Isolated monosomy-7, a rare cytogenetic abnormality in patients with pediatric acute lymphoblastic leukemia (ALL), portends a worse prognosis. Despite improvements in treatment, outcomes for patients with relapsed ALL remain poor. Novel treatments adopted from the B-cell malignancy multiple myeloma may have a role in treatment of ALL. Bortezomib is one such agent currently in phase III trials for B and T ALL. This study presents a patient with B-cell ALL and monosomy-7 who relapsed off therapy. The combination of bortezomib, lenalidomide, and dexamethasone was used to attain remission before bone marrow transplant after conventional relapse therapy failed. A recurrence after bone marrow transplant was controlled for a prolonged period with the same therapy. The case supports the hypothesis that bortezomib, lenalidomide, and dexamethasone should be further explored in the treatment of B-cell ALL with monosomy-7. PMID:27299598

  13. Total body irradiation correlates with chronic graft versus host disease and affects prognosis of patients with acute lymphoblastic leukemia receiving an HLA identical allogeneic bone marrow transplant

    Purpose: To investigate whether different procedure variables involved in the delivery of fractionated total body irradiation (TBI) impact on prognosis of patients affected by acute lymphoblastic leukemia (ALL) receiving allogeneic bone marrow transplant (BMT). Methods and Materials: Ninety-three consecutive patients with ALL receiving a human leukocyte antigen (HLA) identical allogeneic BMT between 1 August 1983 and 30 September 1995 were conditioned with the same protocol consisting of cyclophosphamide and fractionated TBI. The planned total dose of TBI was 12 Gy (2 Gy, twice a day for 3 days). Along the 12-year period, variations in delivering TBI schedule occurred with regard to used radiation source, instantaneous dose rate, technical setting, and actual total dose received by the patient. We tested these different TBI variables as well as factors related to patient, state of disease, and transplant-induced disease to investigate their influence on transplant-related mortality, leukemia relapse, and survival. Results: At median follow-up of 7 years (range 3-15 years) the probabilities of leukemia-free survival (LFS) and overall survival (OS) for the 93 patients were 60% and 41%, respectively. At univariate analysis, chronic graft versus host disease (cGvHd) (p = 0.0005), age (p = 0.01), and state of disease (p 0.03) were factors affecting LFS whereas chronic GvHd (p = 0.0005), acute GvHd (p = 0.03), age (p = 0.0001), and GvHd prophylaxis (p = 0.01) were factors affecting overall survival. The occurrence of chronic GvHd was correlated with actually delivered TBI dose (p = 0.04). Combined stratification of prognostic factors showed that patients who received the planned total dose of TBI (12 Gy) and were affected by chronic GvHd had higher probabilities of LFS (p = 0.01) and OS (p = n.s.) than patients receiving less than 12 Gy and/or without occurrence of chronic GvHd. Moreover, TBI dose had a significant impact on LFS in patients transplanted in first

  14. Prognostic relevance of RUNX1 mutations in T-cell acute lymphoblastic leukemia

    Grossmann, Vera; Kern, Wolfgang; Harbich, Stefan; Alpermann, Tamara; Jeromin, Sabine; Schnittger, Susanne; Haferlach, Claudia; Haferlach, Torsten; Kohlmann, Alexander

    2011-01-01

    The runt-related transcription factor 1, RUNX1, is crucial in the development of myeloid and lymphoid cell lineages and has been reported to be mutated in myeloid malignancies in approximately 30% of cases. In this study, the mutational status of RUNX1 was investigated in 128 acute lymphoblastic leukemia patients. We detected a mutation rate of 18.3% (13 of 71) in patients with T-cell acute lymphoblastic leukemia, 3.8% (2 of 52) in patients with B-cell acute lymphoblastic leukemia and no muta...

  15. Oral health of children with acute lymphoblastic leukemia: A review

    Kadalagere Lakshmana Girish Babu

    2016-01-01

    Full Text Available Leukemia is a malignancy of the bone marrow and blood. It is the most common childhood cancer in India. Advances in the treatment regimens have greatly increased the chances of survival. Both the disease and its treatment change the oral environment. In some cases, oral manifestations are the presenting feature of the disease and it will be the dentist′s responsibility to identify the underlying disorder and guide the diagnosis of the patient. Hence, the aim of present article is to review the literature concerning the oral health of children with acute lymphoblastic leukemia (ALL.

  16. Cytogenetic studies of Acute Myeloid Leukemia

    Tarek Abd -Alla Atia

    2010-06-01

    Full Text Available Acute myeloid leukemia (AML describes as a group of hematopoietic stem cell disorders characterized by expansion of undifferentiated myeloid progenitors. Acquired chromosomal anomaly particularly reciprocal translocations constitute one of the major events contribute to leukemogenesis. Patient and Methods: 45 untreated, newly diagnosed patients with de novo AML were enrolled in the present study and subjected to cytogenetic analysis. Four ml of heparinized peripheral blood were collected for 72 hours synchronized culture, and then chromosome G- banding analysis was performed using standard methods. The karyotypes were designated according to the International System for Human Cytogenetic Nomenclature (ISCN. The collected data were analyzed statistically. Result: Cytogenetic analysis and karyotype results were obtained in 45 patients with de novo AML. Males constituted 33.3%, and females constituted 66.7% of this group. The patients' age ranged from 17-60 years. Chromosomal anomalies have been detected in 21 out of 45 patients (46.7%. However five different types of chromosome anomalies have been detected; where seven cases (33.3% carrying t(15;17( q22;q21; six cases (28.5% carrying t(8;21(q22;q22; three cases (14.3% had trisomy 8; three cases (14.3% had monosomy 7; and lastly two cases (9.5% carrying inv(3(q21q26. Conclusion: Conventional cytogenetic analysis reliability detects chromosomal abnormalities in AML patients at the time of diagnosis. Chromosomal anomalies detected in Egyptian AML patients, are similar to some extent to those recorded in other areas of the world

  17. Tracheoesophageal fistula resulting from invasive aspergillosis in acute lymphoblastic leukemia: a case report

    Tracheoesophageal fistula (TEF) in adult patients is an uncommon complication in leukemia. We present here on a case of TEF in a 46-year-old woman with ALL. The patient was asymptomatic and TEF is resulted from aspergillus bronchitis during the chemotherapy for acute lymphoblastic leukemia (ALL)

  18. Tracheoesophageal fistula resulting from invasive aspergillosis in acute lymphoblastic leukemia: a case report

    Kang, Si Won [Daejeon St. Mary' s Hospital, College of Medicine, Catholic University, Daejeon (Korea, Republic of)

    2006-04-15

    Tracheoesophageal fistula (TEF) in adult patients is an uncommon complication in leukemia. We present here on a case of TEF in a 46-year-old woman with ALL. The patient was asymptomatic and TEF is resulted from aspergillus bronchitis during the chemotherapy for acute lymphoblastic leukemia (ALL)

  19. Acute myeloid leukemia masquerading as hepatocellular carcinoma.

    Abu-Zeinah, Ghaith F; Weisman, Paul; Ganesh, Karuna; Katz, Seth S; Dogan, Ahmet; Abou-Alfa, Ghassan K; Stein, Eytan M; Jarnagin, William; Mauro, Michael J; Harding, James J

    2016-06-01

    Hepatocellular carcinoma (HCC) is often diagnosed on the basis of high quality imaging without a biopsy in the cirrhotic liver. This is a case of a 64-year-old Caucasian man with no history of liver disease or cirrhosis that presented with fatigue, weight loss, and abdominal distension and was found to have a large, isolated liver mass with arterial enhancement and portal venous washout on triple-phase computed tomography (CT) suspicious for HCC. The patient was initially referred for a surgical evaluation. Meanwhile, he developed fevers, pancytopenia, and worsening back pain, and a subsequent spinal MRI revealed a heterogeneous bone marrow signal suspicious for metastatic disease. A bone marrow biopsy that followed was diffusely necrotic. A core biopsy of the patient's liver mass was then performed and was diagnostic of acute monocytic-monoblastic leukemia. Findings from peripheral flow cytometry and a repeat bone marrow biopsy were also consistent with this diagnosis, and induction chemotherapy with cytarabine and idarubicin was initiated. This case describes a rare presentation of myeloid sarcoma (MS) as an isolated, hypervascular liver mass that mimics HCC in its radiographic appearance. Due to the broad differential for a liver mass, a confirmatory biopsy should routinely be considered prior to surgical intervention. PMID:27284485

  20. Genetic abnormalities associated with acute lymphoblastic leukemia.

    Yokota, Takafumi; Kanakura, Yuzuru

    2016-06-01

    Acute lymphoblastic leukemia (ALL) occurs with high frequency in childhood and is associated with high mortality in adults. Recent technical advances in next-generation sequencing have shed light on genetic abnormalities in hematopoietic stem/progenitor cells as the precursor to ALL pathogenesis. Based on these genetic abnormalities, ALL is now being reclassified into newly identified subtypes. Philadelphia chromosome-like B-lineage ALL is one of the new high-risk subtypes characterized by genetic alterations that activate various signaling pathways, including those involving cytokine receptors, tyrosine kinases, and epigenetic modifiers. Philadelphia chromosome-like ALL is essentially heterogeneous; however, deletion mutations in the IKZF1 gene encoding the transcription factor IKAROS underlie many cases as a key factor inducing aggressive phenotypes and poor treatment responses. Whole-genome sequencing studies of ALL patients and ethnically matched controls also identified inherited genetic variations in lymphoid neoplasm-related genes, which are likely to increase ALL susceptibility. These findings are directly relevant to clinical hematology, and further studies on this aspect could contribute to accurate diagnosis, effective monitoring of residual disease, and patient-oriented therapies. PMID:26991355

  1. Acute lymphoblastic leukemia of childhood presenting as aplastic anemia: report of two cases

    Laura Villarreal-Martínez; José Carlos Jaime-Pérez; Marisol Rodríguez-Martínez; Oscar González-Llano; David Gómez-Almaguer

    2012-01-01

    Acute lymphoblastic leukemia is the most common malignancy in pediatric patients; its diagnosis is usually easy to establish as malignant lymphoblasts invade the bone marrow and peripheral blood. Some acute lymphoblastic leukemia patients may initially present with pancytopenia and a hypoplastic bone marrow leading to the initial diagnosis of aplastic anemia. In most of these patients clinical improvement occurs, with normalization of the complete blood count within six months, although recov...

  2. Identification of homogeneously staining regions in leukemia patients

    Mohammad Heydarian Moghadam

    2013-01-01

    Full Text Available Homogeneously staining regions (HSR or double minute chromosomes (dmin are autonomously replicating extra-chromosomal elements that are frequently associated with gene amplification in a variety of cancers. The diagnosis of leukemia patients was based on characterization of the leukemic cells obtained from bone marrow cytogenetics. This study report two cases, one with Acute Myeloblastic Leukemia without maturation (AML-M1, aged 23-year-old female, and the other with chronic myelogenous leukemia (CML-blast crisis, a 28-year-old female associated with double minute chromosomes. Most cases of acute myeloid leukemia with dmin in the literature (including our cases have been diagnosed as having acute myeloid leukemia.

  3. Prognostic significance of FLT3 internal tandem duplication and NPM1 mutations in acute myeloid leukemia in an unselected patient population.

    Suzuki, Rikio; Onizuka, Makoto; Kojima, Minoru; Shimada, Masako; Okamura, Kaori; Fukagawa, Satomi; Tsuboi, Kosuke; Kikuchi, Ako; Kobayashi, Hiroyuki; Shintani, Ayumi; Ogawa, Yoshiaki; Kawada, Hiroshi; Hotta, Tomomitsu; Ando, Kiyoshi

    2007-12-01

    Mutations in the fms-like tyrosine kinase 3 (FLT3) gene containing an internal tandem duplication (FLT3/ITD) or mutations in the nucleophosmin 1 gene (NPM1) are thought to be prognostic indicators in acute myeloid leukemia (AML). Previous studies suggested that FLT3/ITD mutation indicates a poor prognosis and that NPM1 mutation indicates a more favorable one, but these studies were often performed with selected patient populations. We investigated the clinical significance of these mutations at our institution with an unselected group of patients with newly diagnosed AML. This group included patients > or =60 years old and those with a poor performance status. Using polymerase chain reaction and sequencing analyses, we detected FLT3/ITD mutations in 12 patients (20.0%) and NPM1 mutations in 7 patients (11.7%) among a group of 60 patients. There was a nonsignificant trend for FLT3/ITD mutation to be associated with a poorer predicted overall survival (OS) probability in this population. In contrast, OS was significantly higher in patients with wild-type NPM1 than in patients with NPM1 mutation, both for all AML patients and for AML patients with a normal karyotype. In this general and unselected AML patient population, NPM1 mutation was not a prognostic indicator of a favorable outcome. PMID:18192111

  4. Genomic, immunophenotypic, and NPM1/FLT3 mutational studies on 17 patients with normal karyotype acute myeloid leukemia (AML) followed by aberrant karyotype AML at relapse.

    Wang, Eunice S; Sait, Sheila N J; Gold, David; Mashtare, Terry; Starostik, Petr; Ford, Laurie Ann; Wetzler, Meir; Nowak, Norma J; Deeb, George

    2010-10-15

    Normal karyotype (NK) is the most common cytogenetic group in acute myeloid leukemia (AML) diagnosis; however, up to 50% of these patients at relapse will have aberrant karyotype (AK) AML. To determine the etiology of relapsed AK AML cells, we evaluated cytogenetic, immunophenotypic, and molecular results of 17 patients with diagnostic NK AML and relapsed AK AML at our institute. AK AML karyotype was diverse, involving no favorable and largely (8 of 17) complex cytogenetics. Despite clear cytogenetic differences, immunophenotype and NPM1/FLT3 gene mutation status did not change between presentation and relapse in 83% (10 of 12) and 94% (15 of 16) cases, respectively. High-resolution array-based comparative genomic hybridization (aCGH) performed via paired aCGH on NK AML and AK AML samples from the same patient confirmed cytogenetic aberrations only in the relapse sample. Analysis of 16 additional diagnostic NK AML samples revealed no evidence of submicroscopic aberrations undetected by conventional cytogenetics in any case. These results favor evolution of NK AML leukemia cells with acquisition of novel genetic changes as the most common etiology of AK AML relapse as opposed to secondary leukemogenesis. Additional studies are needed to confirm whether AK AML cells represent selection of rare preexisting clones below aCGH detection and to further characterize the molecular lesions found at time of AK AML relapse. PMID:20875872

  5. CD25 expression on residual leukemic blasts at the time of allogeneic hematopoietic stem cell transplant predicts relapse in patients with acute myeloid leukemia without complete remission.

    Ikegawa, Shuntaro; Doki, Noriko; Kurosawa, Shuhei; Yamaguchi, Tsukasa; Sakaguchi, Masahiro; Harada, Kaito; Yamamoto, Keita; Hino, Yutaro; Shingai, Naoki; Senoo, Yasushi; Hattori, Keiichiro; Igarashi, Aiko; Najima, Yuho; Kobayashi, Takeshi; Kakihana, Kazuhiko; Sakamaki, Hisashi; Haraguchi, Kyoko; Okuyama, Yoshiki; Ohashi, Kazuteru

    2016-06-01

    Recent studies have shown that CD25 expression at the time of diagnosis of acute myeloid leukemia (AML) may be associated with an unfavorable outcome. We focus on patients with AML without complete remission (CR) and examine the clinical correlation between surface CD25 expression at the time of transplant and subsequent transplant outcomes. We observed a significant difference in overall survival (OS), disease-free survival (DFS) and cumulative incidence of relapse (CIR) between CD25 positive (+) (n = 22) and negative (-) groups (n = 44) (2-year OS; CD25 (+) group: 5% vs. CD25 (-) group: 40%, p expression was an independent adverse factor for OS (p = 0.002) and relapse (p = 0.001). Patients with AML with residual CD25 positive blasts at the time of transplant may require additional therapy before or after transplant to improve survival. PMID:26422713

  6. Two-Stage Priming of Allogeneic Natural Killer Cells for the Treatment of Patients with Acute Myeloid Leukemia: A Phase I Trial.

    Panagiotis D Kottaridis

    Full Text Available Human Natural Killer (NK cells require at least two signals to trigger tumor cell lysis. Absence of ligands providing either signal 1 or 2 provides NK resistance. We manufactured a lysate of a tumour cell line which provides signal 1 to resting NK cells without signal 2. The tumor-primed NK cells (TpNK lyse NK resistant Acute Myeloid Leukemia (AML blasts expressing signal 2 ligands. We conducted a clinical trial to determine the toxicity of TpNK cell infusions from haploidentical donors. 15 patients with high risk AML were screened, 13 enrolled and 7 patients treated. The remaining 6 either failed to respond to re-induction chemotherapy or the donor refused to undergo peripheral blood apheresis. The conditioning consisted of fludarabine and total body irradiation. This was the first UK trial of a cell therapy regulated as a medicine. The complexity of Good Clinical Practice compliance was underestimated and led to failures requiring retrospective independent data review. The lessons learned are an important aspect of this report. There was no evidence of infusional toxicity. Profound myelosuppression was seen in the majority (median neutrophil recovery day 55. At six months follow-up, three patients treated in Complete Remission (CR remained in remission, one patient infused in Partial Remission had achieved CR1, two had relapsed and one had died. One year post-treatment one patient remained in CR. Four patients remained in CR after treatment for longer than their most recent previous CR. During the 2 year follow-up six of seven patients died; median overall survival was 400 days post infusion (range 141–910. This is the first clinical trial of an NK therapy in the absence of IL-2 or other cytokine support. The HLA-mismatched NK cells survived and expanded in vivo without on-going host immunosuppression and appeared to exert an anti-leukemia effect in 4/7 patients treated.ISRCTN trial registry ISRCTN11950134.

  7. Prognostic impact of day 15 blast clearance in risk-adapted remission induction chemotherapy for younger patients with acute myeloid leukemia: long-term results of the multicenter prospective LAM-2001 trial by the GOELAMS study group

    Bertoli, Sarah; Bories, Pierre; Béné, Marie C.; Daliphard, Sylvie; Lioure, Bruno; Pigneux, Arnaud; Vey, Norbert; Delaunay, Jacques; Leymarie, Vincent; Luquet, Isabelle; Blanchet, Odile; Cornillet-Lefebvre, Pascale; Hunault, Mathilde; Bouscary, Didier; Fegueux, Nathalie

    2014-01-01

    Early response to chemotherapy has a major prognostic impact in acute myeloid leukemia patients treated with a double induction strategy. Less is known about patients treated with standard-dose cytarabine and anthracycline. We designed a risk-adapted remission induction regimen in which a second course of intermediate-dose cytarabine was delivered after standard “7+3” only if patients had 5% or more bone marrow blasts 15 days after chemotherapy initiation (d15-blasts). Of 823 included patient...

  8. The value of the MDR1 reversal agent PSC-833 in addition to daunorubicin and cytarabine in the treatment of elderly patients with previously untreated acute myeloid leukemia (AML), in relation to MDR1 status at diagnosis

    van der Holt, B; Lowenberg, B; Burnett, AK; Knauf, WU; Shepherd, J; Piccaluga, PP; Ossenkoppele, GJ; Verhoef, GEG; Ferrant, A; Crump, M; Selleslag, D; Theobald, M; Fey, MF; Vellenga, E; Dugan, M; Sonneveld, P

    2005-01-01

    To determine whether MDR1 reversal by the addition of the P-glycoprotein (P-gp) inhibitor PSC-833 to standard induction chemotherapy would improve event-free survival (EFS), 419 untreated patients with acute myeloid leukemia (AML) aged 60 years and older were randomized to receive 2 induction cycles

  9. Association between the methylation status of the MGMT promoter in bone marrow specimens and chemotherapy outcomes of patients with acute myeloid leukemia

    HONG, QINGXIAO; CHEN, XIAOYING; YE, HUADAN; ZHOU, ANNAN; GAO, YUTING; JIANG, DANJIE; WU, XIAODONG; TIAN, BINGRU; CHEN, YOUFEN; WANG, MING; XIE, JIPING; XIA, YONGMING; DUAN, SHIWEI

    2016-01-01

    The O(6)-methylguanine-DNA methyltransferase (MGMT) gene is a tumor suppressor gene that is associated with the risk of developing acute myeloid leukemia (AML). However, the association between the methylation status of the MGMT promoter and the chemotherapeutic outcomes of patients with AML remains unknown. In the present study, 30 bone marrow samples derived from patients with AML were collected prior and subsequent to chemotherapy. The methylation status of the MGMT promoter in the bone marrow specimens was determined by methylation-specific polymerase chain reaction. The results indicated that the methylation status of the MGMT promoter was influenced by different chemotherapeutic regimens. The MGMT methylation status of M4 patients (3 out of 6) were more chemosensitive, compared with that of patients with other AML subtypes (M1, 1 out of 3; M2, 0 out of 8; M3, 3 out of 7; M5, 0 out of 3; and M6, 1 out of 3). Age-based analysis revealed that the group aged ≤60 years (7 out of 24 patients) exhibited more methylation changes than patients aged >60 years (1 out of 6). Male patients (4 out of 13) were more susceptible to chemotherapy-induced methylation changes than female patients (4 out of 17). Thus, the methylation status of the MGMT promoter may serve as a potential biomarker to predict the therapeutic outcomes in male AML patients. However, further studies in larger sample sets are required to confirm the present findings. PMID:27073563

  10. Recurrent isochromosome 21 and multiple abnormalities in a patient suspected of having acute myeloid leukemia with eosinophilic differentiation-a rare case from South India

    Sangeetha Vijay; Santhi Sarojam; Sureshkumar Raveendran; Vani Syamala; Sreeja Leelakumari; Geetha Narayanan; Sreedharan Hariharan

    2012-01-01

    Acute myeloid leukemia (AML) is a phenotypically heterogeneous disorder.The M4 subtype of AML is frequently associated with the cytogenetic marker inversion 16 and/or the presence of eosinophilia.Blast crisis is the aggressive phase of the triphasic chronic myeloid leukemia (CML),which is a disease with Philadelphia (Ph) chromosome as the major abnormality.In the present study,we report a 76-year-old patient suspected of having AML with eosinophilic differentiation (AML-M4),which in clinical tests resembles CML blast crisis with multiple chromosomal abnormalities.Isochromosome 21 [i(21)(q10)] was the most recurrent feature noted in metaphases with 46 chromosomes.Ring chromosome,tetraploid endoreduplication,recurrent aneuploid clones with loss of X chromosome,monosomy 17,monosomy 7,and structural variation translocation (9;14) were also observed in this patient.Fluorescent in situ hybridization (FISH) confirmed the absence of Ph chromosome.This report shows how cytogenetic analyses revealed atypical structural aberrations in the M4 subtype of AML.

  11. An advanced preclinical mouse model for acute myeloid leukemia using patients' cells of various genetic subgroups and in vivo bioluminescence imaging.

    Vick, Binje; Rothenberg, Maja; Sandhöfer, Nadine; Carlet, Michela; Finkenzeller, Cornelia; Krupka, Christina; Grunert, Michaela; Trumpp, Andreas; Corbacioglu, Selim; Ebinger, Martin; André, Maya C; Hiddemann, Wolfgang; Schneider, Stephanie; Subklewe, Marion; Metzeler, Klaus H; Spiekermann, Karsten; Jeremias, Irmela

    2015-01-01

    Acute myeloid leukemia (AML) is a clinically and molecularly heterogeneous disease with poor outcome. Adequate model systems are required for preclinical studies to improve understanding of AML biology and to develop novel, rational treatment approaches. Xenografts in immunodeficient mice allow performing functional studies on patient-derived AML cells. We have established an improved model system that integrates serial retransplantation of patient-derived xenograft (PDX) cells in mice, genetic manipulation by lentiviral transduction, and essential quality controls by immunophenotyping and targeted resequencing of driver genes. 17/29 samples showed primary engraftment, 10/17 samples could be retransplanted and some of them allowed virtually indefinite serial transplantation. 5/6 samples were successfully transduced using lentiviruses. Neither serial transplantation nor genetic engineering markedly altered sample characteristics analyzed. Transgene expression was stable in PDX AML cells. Example given, recombinant luciferase enabled bioluminescence in vivo imaging and highly sensitive and reliable disease monitoring; imaging visualized minimal disease at 1 PDX cell in 10000 mouse bone marrow cells and facilitated quantifying leukemia initiating cells. We conclude that serial expansion, genetic engineering and imaging represent valuable tools to improve the individualized xenograft mouse model of AML. Prospectively, these advancements enable repetitive, clinically relevant studies on AML biology and preclinical treatment trials on genetically defined and heterogeneous subgroups. PMID:25793878

  12. Bone marrow transplantation in aplastic anemia, acute leukemia and solid tumors

    Results of bone marrow transplantation for the treatment of aplastic anemia, acute leukemia and solid tumors in the first 141 patients treated between September 1973 and January 1980 are reviewed. Preparation for transplantation with total body irradiation is described. (Auth.)

  13. Frequent genomic abnormalities in acute myeloid leukemia/myelodysplastic syndrome with normal karyotype

    Akagi, Tadayuki; Ogawa, Seishi; Dugas, Martin; KAWAMATA, NORIHIKO; Yamamoto, Go; Nannya, Yasuhito; Sanada, Masashi; Miller, Carl W.; Yung, Amanda; Schnittger, Susanne; Haferlach, Torsten; Haferlach, Claudia; Koeffler, H. Phillip

    2009-01-01

    In this study, single-nucleotide polymorphism microarray analysis was employed to identify hidden genomic abnormalities in patients with acute myeloid leukemia. The findings suggest that at least one half of cases with normal karyotype have readily identifiable genomic abnormalities.

  14. Prognostic significance of cell surface phenotype in acute lymphoblastic leukemia

    Shiek Aejaz Aziz; Susheel Kumar Sharma; Iram Sabah; M Aleem Jan

    2015-01-01

    Context: To find out the phenotypic character of lymphoblasts of acute lymphoblastic leukemia (ALL) patients in our study cohort and their possible effect on the prognosis. Aims: To investigate the phenotype in ALL in our demographic population and to prognosticate various upfront current protocols employed in our hospital. Settings and Design: The study spanned over a period of 4 years with retrospective and prospective data of January 2008 through December 2011. Materials and Methods: 159 p...

  15. Functional Integration of Acute Myeloid Leukemia into the Vascular Niche

    Cogle, Christopher R.; Goldman, Devorah C.; Madlambayan, Gerard J; Leon, Ronald P.; Masri, Azzah Al; Clark, Hilary A.; Asbaghi, Steven A.; Tyner, Jeffrey W.; Dunlap, Jennifer; Fan, Guang; Kovacsovics, Tibor; Liu, Qiuying; Meacham, Amy; Hamlin, Kimberly L.; Hromas, Robert A.

    2014-01-01

    Vascular endothelial cells are a critical component of the hematopoietic microenvironment that regulates blood cell production. Recent studies suggest the existence of functional cross-talk between hematologic malignancies and vascular endothelium. Here, we show that human acute myeloid leukemia (AML) localizes to the vasculature in both patients and in a xenograft model. A significant number of vascular tissue-associated AML cells (V-AML) integrate into vasculature in vivo and can fuse with ...

  16. Recent advances in the treatment of acute myeloid leukemia

    Abdel-Wahab, Omar; Levine, Ross L.

    2010-01-01

    Acute myeloid leukemia (AML) is a disorder with significant molecular and clinical heterogeneity. Although there have been clear advances in the identification of somatic genetic and epigenetic alterations present in the malignant cells of patients with AML, translating this knowledge into an integrated view with an impact on the clinical treatment of AML has been slower to evolve. Recent clinical advances in the treatment of AML include studies demonstrating the benefit of dose-intense dauno...

  17. Acute myeloid leukemia masquerading as hepatocellular carcinoma

    Abu-Zeinah, Ghaith F.; Weisman, Paul; Ganesh, Karuna; Katz, Seth S.; Dogan, Ahmet; Abou-Alfa, Ghassan K.; Stein, Eytan M.; Jarnagin, William; Mauro, Michael J.

    2016-01-01

    Hepatocellular carcinoma (HCC) is often diagnosed on the basis of high quality imaging without a biopsy in the cirrhotic liver. This is a case of a 64-year-old Caucasian man with no history of liver disease or cirrhosis that presented with fatigue, weight loss, and abdominal distension and was found to have a large, isolated liver mass with arterial enhancement and portal venous washout on triple-phase computed tomography (CT) suspicious for HCC. The patient was initially referred for a surgical evaluation. Meanwhile, he developed fevers, pancytopenia, and worsening back pain, and a subsequent spinal MRI revealed a heterogeneous bone marrow signal suspicious for metastatic disease. A bone marrow biopsy that followed was diffusely necrotic. A core biopsy of the patient’s liver mass was then performed and was diagnostic of acute monocytic-monoblastic leukemia. Findings from peripheral flow cytometry and a repeat bone marrow biopsy were also consistent with this diagnosis, and induction chemotherapy with cytarabine and idarubicin was initiated. This case describes a rare presentation of myeloid sarcoma (MS) as an isolated, hypervascular liver mass that mimics HCC in its radiographic appearance. Due to the broad differential for a liver mass, a confirmatory biopsy should routinely be considered prior to surgical intervention. PMID:27284485

  18. The Epigenetic Landscape of Acute Myeloid Leukemia

    Emma Conway O’Brien

    2014-01-01

    Full Text Available Acute myeloid leukemia (AML is a genetically heterogeneous disease. Certain cytogenetic and molecular genetic mutations are recognized to have an impact on prognosis, leading to their inclusion in some prognostic stratification systems. Recently, the advent of high-throughput whole genome or exome sequencing has led to the identification of several novel recurrent mutations in AML, a number of which have been found to involve genes concerned with epigenetic regulation. These genes include in particular DNMT3A, TET2, and IDH1/2, involved with regulation of DNA methylation, and EZH2 and ASXL-1, which are implicated in regulation of histones. However, the precise mechanisms linking these genes to AML pathogenesis have yet to be fully elucidated as has their respective prognostic relevance. As massively parallel DNA sequencing becomes increasingly accessible for patients, there is a need for clarification of the clinical implications of these mutations. This review examines the literature surrounding the biology of these epigenetic modifying genes with regard to leukemogenesis and their clinical and prognostic relevance in AML when mutated.

  19. Use of clofarabine for acute childhood leukemia

    Masetti, Riccardo

    2010-01-01

    A Pession, R Masetti, K Kleinschmidt, A MartoniPediatric Oncology and Hematology “Lalla Seràgnoli”, University of Bologna, ItalyAbstract: A second-generation of purine nucleoside analogs, starting with clofarabine, has been developed in the course of the search for new therapeutic agents for acute childhood leukemia, especially for refractory or relapsed disease. Clofarabine is a hybrid of fludarabine and cladribine, and has shown to have antileukemic activity i...

  20. Pathogenesis and prognostication in acute lymphoblastic leukemia

    Zuckerman, Tsila; Rowe, Jacob M.

    2014-01-01

    The process of lymphoid maturation is tightly controlled by the hierarchical activation of transcription factors and selection through functional signal transduction. Acute lymphoblastic leukemia (ALL) represents a group of B/T-precursor-stage lymphoid cell malignancies arising from genetic alterations that block lymphoid differentiation and drive aberrant cell proliferation and survival. With recent advances in next-generation sequencing, we are discovering new mutations affecting normal lym...

  1. Biological, functional and genetic characterization of bone marrow-derived mesenchymal stromal cells from pediatric patients affected by acute lymphoblastic leukemia.

    Antonella Conforti

    Full Text Available Alterations in hematopoietic microenvironment of acute lymphoblastic leukemia patients have been claimed to occur, but little is known about the components of marrow stroma in these patients. In this study, we characterized mesenchymal stromal cells (MSCs isolated from bone marrow (BM of 45 pediatric patients with acute lymphoblastic leukemia (ALL-MSCs at diagnosis (day+0 and during chemotherapy treatment (days: +15; +33; +78, the time points being chosen according to the schedule of BM aspirates required by the AIEOP-BFM ALL 2009 treatment protocol. Morphology, proliferative capacity, immunophenotype, differentiation potential, immunomodulatory properties and ability to support long-term hematopoiesis of ALL-MSCs were analysed and compared with those from 41 healthy donors (HD-MSCs. ALL-MSCs were also genetically characterized through array-CGH, conventional karyotyping and FISH analysis. Moreover, we compared ALL-MSCs generated at day+0 with those isolated during chemotherapy. Morphology, immunophenotype, differentiation potential and in vitro life-span did not differ between ALL-MSCs and HD-MSCs. ALL-MSCs showed significantly lower proliferative capacity (p<0.001 and ability to support in vitro hematopoiesis (p = 0.04 as compared with HD-MSCs, while they had similar capacity to inhibit in vitro mitogen-induced T-cell proliferation (p = N.S.. ALL-MSCs showed neither the typical translocations carried by the leukemic clone (when present, nor other genetic abnormalities acquired during ex vivo culture. Our findings indicate that ALL-MSCs display reduced ability to proliferate and to support long-term hematopoiesis in vitro. ALL-MSCs isolated at diagnosis do not differ from those obtained during treatment.

  2. Biological, functional and genetic characterization of bone marrow-derived mesenchymal stromal cells from pediatric patients affected by acute lymphoblastic leukemia.

    Conforti, Antonella; Biagini, Simone; Del Bufalo, Francesca; Sirleto, Pietro; Angioni, Adriano; Starc, Nadia; Li Pira, Giuseppina; Moretta, Francesca; Proia, Alessandra; Contoli, Benedetta; Genovese, Silvia; Ciardi, Claudia; Avanzini, Maria Antonietta; Rosti, Vittorio; Lo-Coco, Francesco; Locatelli, Franco; Bernardo, Maria Ester

    2013-01-01

    Alterations in hematopoietic microenvironment of acute lymphoblastic leukemia patients have been claimed to occur, but little is known about the components of marrow stroma in these patients. In this study, we characterized mesenchymal stromal cells (MSCs) isolated from bone marrow (BM) of 45 pediatric patients with acute lymphoblastic leukemia (ALL-MSCs) at diagnosis (day+0) and during chemotherapy treatment (days: +15; +33; +78), the time points being chosen according to the schedule of BM aspirates required by the AIEOP-BFM ALL 2009 treatment protocol. Morphology, proliferative capacity, immunophenotype, differentiation potential, immunomodulatory properties and ability to support long-term hematopoiesis of ALL-MSCs were analysed and compared with those from 41 healthy donors (HD-MSCs). ALL-MSCs were also genetically characterized through array-CGH, conventional karyotyping and FISH analysis. Moreover, we compared ALL-MSCs generated at day+0 with those isolated during chemotherapy. Morphology, immunophenotype, differentiation potential and in vitro life-span did not differ between ALL-MSCs and HD-MSCs. ALL-MSCs showed significantly lower proliferative capacity (p<0.001) and ability to support in vitro hematopoiesis (p = 0.04) as compared with HD-MSCs, while they had similar capacity to inhibit in vitro mitogen-induced T-cell proliferation (p = N.S.). ALL-MSCs showed neither the typical translocations carried by the leukemic clone (when present), nor other genetic abnormalities acquired during ex vivo culture. Our findings indicate that ALL-MSCs display reduced ability to proliferate and to support long-term hematopoiesis in vitro. ALL-MSCs isolated at diagnosis do not differ from those obtained during treatment. PMID:24244271

  3. Population PK/PD model of homocysteine concentrations after high-dose methotrexate treatment in patients with acute lymphoblastic leukemia.

    Hauke Rühs

    Full Text Available Elevated homocysteine concentrations have been associated with methotrexate-induced neurotoxicity. Based on methotrexate and homocysteine plasma concentrations of 494 children with acute lymphoblastic leukemia treated with high-dose methotrexate in the TOTAL XV study, a pharmacokinetic/pharmacodynamic (PK/PD model was built with NONMEM. Several compartment and indirect response models were investigated. The pharmacokinetic disposition of methotrexate was best described by a two-compartment model. Homocysteine concentrations were included by an indirect response model where methotrexate inhibition of the homocysteine elimination rate was described by an E(max model. The homocysteine baseline level was found to be age-dependent. Simulations revealed that folinate rescue therapy does not affect peak concentrations of homocysteine but leads to a modestly reduced homocysteine exposure. In conclusion, our PK/PD model describes the increase of methotrexate-induced HCY concentrations with satisfactory precision and can be applied to assess the effect of folinate regimens on the HCY concentration-time course.

  4. Aggressive chemotherapy for acute leukemia relapsed after transplantation.

    Sica, S; Salutari, P; Di Mario, A; D'Onofrio, G; Etuk, B; Leone, G

    1994-09-01

    Bone marrow transplantation procedure has emerged as an effective treatment for hematological malignancies. However, recurrence of leukemia is still the major cause of treatment failure. Subsequent treatment in this category of patients, generally considered incurable, has not been yet standardized. At our institution, 13 patients, 7 with acute non lymphoid leukemia (ANLL) and 6 with acute lymphoid leukemia (ALL), were treated at relapse after bone marrow transplantation either autologous or allogeneic (AuBMT 8, ABMT 4) performed in complete remission (CR). The interval between BMT and relapse was less than 9 months in 6 patients (2 ABMT and 4 AuBMT) and more than 9 months in 7 patients. Early relapsed patients showed no response to treatment and died at a median of 5.5 months (range 1-13) after relapse. Late relapse after BMT was characterized by a high percentage of response (5 CR and 1 PR), particularly after intensive chemotherapy and by a longer survival (median 14 months; range 2-36). Chemotherapy after transplantation should be carefully evaluated in patients relapsed after BMT in order to select a population that can achieve long term disease free survival. PMID:7858490

  5. Systemic mastocytosis with acute myelomonocytic leukemia: a case report

    Kar, Rakhee; Rao, Seema; Pati, Hara Prasad

    2008-01-01

    Bone marrow mastocytosis may be associated with many clonal non mast cell hematological neoplasms and its association with acute myeloid leukemia especially with t (8; 21) has been described. We describe an interesting case of coexistence of systemic mastocytosis with acute myelomonocytic leukemia in a young child. Diagnosis of acute myelomonocytic leukemia was based on bone marrow aspirate findings coupled with cytochemistry. Systemic mastocytosis was diagnosed on the basis of bone marrow bi...

  6. Recurrent deletions of IKZF1 in pediatric acute myeloid leukemia

    de Rooij, Jasmijn D.E.; Beuling, Eva; Marry M van den Heuvel-Eibrink; Obulkasim, Askar; Baruchel, André; Trka, Jan; Reinhardt, Dirk; Sonneveld, Edwin; Gibson, Brenda E.S.; Pieters, Rob; Zimmermann, Martin; Zwaan, C. Michel; Fornerod, Maarten

    2015-01-01

    IKAROS family zinc finger 1/IKZF1 is a transcription factor important in lymphoid differentiation, and a known tumor suppressor in acute lymphoid leukemia. Recent studies suggest that IKZF1 is also involved in myeloid differentiation. To investigate whether IKZF1 deletions also play a role in pediatric acute myeloid leukemia, we screened a panel of pediatric acute myeloid leukemia samples for deletions of the IKZF1 locus using multiplex ligation-dependent probe amplification and for mutations...

  7. Grade 4 oral mucositis and prolonged pancytopenia with high dose intravenous methotrexate in a patient of philadelphia positive acute lymphoblastic leukemia

    Vidisha M. Shah

    2012-02-01

    Full Text Available Antimetabolite drugs are rarely associated with grade 3 or 4 mucositis. However specific side effects such as bone marrow suppression, pancytopenia, hospitalization, high cost limit the use of intravenous methotrexate. Here we report a case of 25-year-old girl patient with Acute Lymphoblastic Leukemia (ALL treated with 24 hour methotrexate in her continuous phase of chemotherapy. After 12 hours of completing the treatment she developed oral mucosal pain & she was not able to speak. After a week, her White Blood Cell (WBC count was 600/cumm with fever and she could not speak and eat or drink. So she was hospitalized for few days till she can drink something. We report high grade mucositis with methotrexate. Hematologists should be aware of this possible side effect to undertake early intervention. [Int J Basic Clin Pharmacol 2012; 1(1.000: 36-38

  8. Establishment of a new cell line (MTT-95 showing basophilic differentiation from the bone marrow of a patient with acute myelogenous leukemia (M7.

    Mizobuchi N

    1999-04-01

    Full Text Available A new myeloid cell line, MTT-95, was established from the bone marrow of a patient with acute myelogenous leukemia (AML, M7. MTT-95 cells differentiate into mature basophilic cells in culture medium with no chemical component or cytokine. Surface phenotypes were as follows: CD11b 79.3%, CD13 92.4%, CD33 99.8%, CD34 87.9%, CD41a 77.6% and HLA-DR 0.3%. MTT-95 cells were strongly positive for glycoprotein IIb/IIIa by immunohistochemical staining and revealed metachromatic granules. MTT-95 cells seem to possess characteristics of both megakaryocytes and basophils. These findings suggest that MTT-95 cells are basophil progenitors. MTT-95 cells might be useful in the study not only of the biological aspects of basophils, but also of the diversities of AML (M7.

  9. 3 Tesla proton MRI for the diagnosis of pneumonia/lung infiltrates in neutropenic patients with acute myeloid leukemia: Initial results in comparison to HRCT

    Purpose: To evaluate the diagnostic accuracy of 3 Tesla proton MRI for the assessment of pneumonia/lung infiltrates in neutropenic patients with acute myeloid leukemia. Material and methods: In a prospective study, 3 Tesla MRI was performed in 19 febrile neutropenic patients (5 women, 14 men; mean age 61 years ± 14.2; range 23–77 years). All patients underwent high-resolution CT less than 24 h prior to MRI. The MRI protocol (Magnetom Tim Trio, Siemens) included a T2-weighted HASTE sequence (TE/TR: 49 ms/∞, slice thickness 6 mm) and a high-resolution 3D VIBE sequence with an ultra-short TE < 1 ms (TE/TR 0.8/2.9 ms, slice thickness 2 mm). The VIBE sequence was examined before and after intravenous injection of 0.1 mmol/kg gadoterate meglumine (Dotarem, Guerbet). The presence of pulmonary abnormalities, their location within the lung, and lesion type (nodules, consolidations, glass opacity areas) were analyzed by one reader and compared to the findings of HRCT, which was evaluated by a second independent radiologist who served as the reference standard. The findings were compared per lobe in each patient and rated as true positive (TP) findings if all three characteristics (presence, location, and lesion type) listed above were concordant to HRCT. Results: Pulmonary abnormalities were characterized by 3 Tesla MRI with a sensitivity of 82.3% and a specificity of 78.6%, resulting in an overall accuracy of 88% (NPV/PPV 66.7%/89.5%). In 51 lobes (19 of 19 patients), pulmonary abnormalities visualized by MR were judged to be concordant in their location and in the lesion type identified by both readers. In 22 lobes (11 of 19 patients), no abnormalities were present on either MR or HRCT (true negative). In 6 lobes (5 of 19 patients), ground glass opacity areas were detected on MRI but were not visible on HRCT (false positives). In 11 lobes (7 of 19 patients), MRI failed to detect ground glass opacity areas identified by HRCT. However, since the abnormalities were

  10. 3 Tesla proton MRI for the diagnosis of pneumonia/lung infiltrates in neutropenic patients with acute myeloid leukemia: Initial results in comparison to HRCT

    Attenberger, U.I., E-mail: ulrike.attenberger@umm.de [Institute of Clinical Radiology and Nuclear Medicine, University Medical Center Mannheim (Germany); Morelli, J.N. [Scott and White Hospital, Texas A and M Health Sciences Center, Temple (United States); Henzler, T. [Institute of Clinical Radiology and Nuclear Medicine, University Medical Center Mannheim (Germany); Buchheidt, D. [Department of Hematology and Oncology, University Medical Center Mannheim (Germany); Fink, C. [Institute of Clinical Radiology and Nuclear Medicine, University Medical Center Mannheim (Germany); Department of Radiology, AKH Celle, Celle (Germany); Schoenberg, S.O.; Reichert, M. [Institute of Clinical Radiology and Nuclear Medicine, University Medical Center Mannheim (Germany)

    2014-01-15

    Purpose: To evaluate the diagnostic accuracy of 3 Tesla proton MRI for the assessment of pneumonia/lung infiltrates in neutropenic patients with acute myeloid leukemia. Material and methods: In a prospective study, 3 Tesla MRI was performed in 19 febrile neutropenic patients (5 women, 14 men; mean age 61 years ± 14.2; range 23–77 years). All patients underwent high-resolution CT less than 24 h prior to MRI. The MRI protocol (Magnetom Tim Trio, Siemens) included a T2-weighted HASTE sequence (TE/TR: 49 ms/∞, slice thickness 6 mm) and a high-resolution 3D VIBE sequence with an ultra-short TE < 1 ms (TE/TR 0.8/2.9 ms, slice thickness 2 mm). The VIBE sequence was examined before and after intravenous injection of 0.1 mmol/kg gadoterate meglumine (Dotarem, Guerbet). The presence of pulmonary abnormalities, their location within the lung, and lesion type (nodules, consolidations, glass opacity areas) were analyzed by one reader and compared to the findings of HRCT, which was evaluated by a second independent radiologist who served as the reference standard. The findings were compared per lobe in each patient and rated as true positive (TP) findings if all three characteristics (presence, location, and lesion type) listed above were concordant to HRCT. Results: Pulmonary abnormalities were characterized by 3 Tesla MRI with a sensitivity of 82.3% and a specificity of 78.6%, resulting in an overall accuracy of 88% (NPV/PPV 66.7%/89.5%). In 51 lobes (19 of 19 patients), pulmonary abnormalities visualized by MR were judged to be concordant in their location and in the lesion type identified by both readers. In 22 lobes (11 of 19 patients), no abnormalities were present on either MR or HRCT (true negative). In 6 lobes (5 of 19 patients), ground glass opacity areas were detected on MRI but were not visible on HRCT (false positives). In 11 lobes (7 of 19 patients), MRI failed to detect ground glass opacity areas identified by HRCT. However, since the abnormalities were

  11. FLT3 mutations in canine acute lymphocytic leukemia

    FMS-like tyrosine kinase 3 (FLT3) is a commonly mutated protein in a variety of human acute leukemias. Mutations leading to constitutively active FLT3, including internal tandem duplications of the juxtamembrane domain (ITD), result in continuous cellular proliferation, resistance to apoptotic cell death, and a poorer prognosis. A better understanding of the molecular consequences of FLT3 activation would allow improved therapeutic strategies in these patients. Canine lymphoproliferative diseases, including lymphoma and acute leukemias, share evolutionarily conserved chromosomal aberrations and exhibit conserved mutations within key oncogenes when compared to their human counterparts. A small percentage of canine acute lymphocytic leukemias (ALL) also exhibit FLT3 ITD mutations. We molecularly characterized FLT3 mutations in two dogs and one cell line, by DNA sequencing, gene expression analysis via quantitative real-time PCR, and sensitivity to the FLT3 inhibitor lestaurtinib via in vitro proliferation assays. FLT 3 and downstream mediators of FLT3 activation were assessed by Western blotting. The canine B-cell leukemia cell line, GL-1, and neoplastic cells from 2/7 dogs diagnosed cytologically with ALL were found to have FLT3 ITD mutations and FLT3 mRNA up-regulation. Lestaurtinib, a small molecule FLT3 inhibitor, significantly inhibited the growth of GL-1 cells, while not affecting the growth of two other canine lymphoid cell lines without the FLT3 mutation. Finally, western blots were used to confirm the conserved downstream mediators of FLT3 activating mutations. These results show that ALL and FLT3 biology is conserved between canine and human patients, supporting the notion that canine ALL, in conjunction with the GL-1 cell line, will be useful in the development of a relevant large animal model to aid in the study of human FLT3 mutant leukemias

  12. Treatment of Relapsed/Refractory Acute Lymphoblastic Leukemia in Adults.

    Ronson, Aharon; Tvito, Ariella; Rowe, Jacob M

    2016-06-01

    Patients with relapsed and refractory acute lymphoblastic leukemia (ALL) have a dismal prognosis with less than 10 % of patients surviving 5 years. Most such patients cannot be rescued with currently available therapies, whatever the initial treatment they receive. Therefore, there is an urgent need for novel treatment options. Fortunately, over the past several years, an improved understanding of the biology of the disease has allowed the identification of rational molecular targets for therapeutic endeavors and the emergence of novel therapies has sparked great interest. This review will discuss the current treatment landscape for adult patients with relapsed and/or refractory ALL. PMID:27207612

  13. Early warning and prevention of pneumonia in acute leukemia by patient education, spirometry, and positive expiratory pressure: A randomized controlled trial.

    Møller, Tom; Moser, Claus; Adamsen, Lis; Rugaard, Grith; Jarden, Mary; Bøtcher, Tina S; Wiedenbein, Liza; Kjeldsen, Lars

    2016-03-01

    Long-lasting neutropenia associated with acute myeloid leukemia (AML) and its treatment gives rise to a high risk of pneumonia. The use of broad-spectrum antibiotic prophylaxis during outpatient management has not completely protected patients against admission due to infections and neutropenic fever, emphasizing the need to approach infection protection with complementary efforts. In a randomized controlled design, we examined the applicability of patient-performed daily spirometry [forced expiratory volume in one second (FEV1)] as an early warning tool and explored the effectiveness of positive expiratory pressure (PEP) in preventing pneumonia among 80 AML patients. Twenty-five incidences of pneumonia were detected among 23 patients (6 interventions, 17 controls), giving a prevalence of 28.75% during 5420 days of observation. We found a significant difference in incidence between intervention versus control group (2.17 per 1000 days vs. 6.52 per 1000 days, P = 0.021, respectively). A cross point at 80-76% of the personal FEV1 reference value showed high sensitivity and specificity on pneumonia development. Our data demonstrate the feasibility of educating AML patients in their continuous daily measurement of FEV1 and use of PEP. Daily measures of FEV1 may be an important early warning tool for assessment of pulmonary deterioration during critical phases of neutropenia. We suggest that strategic patient education in the use of spirometry and PEP should be part of standard of care for AML patients undergoing induction chemotherapy. PMID:26661344

  14. CEBPA single mutation can be a possible favorable prognostic indicator in NPM1 and FLT3-ITD wild-type acute myeloid leukemia patients with intermediate cytogenetic risk.

    Park, Sang Hyuk; Chi, Hyun-Sook; Cho, Young-Uk; Jang, Seongsoo; Park, Chan-Jeoung

    2013-11-01

    The aim of this study was to evaluate the prognostic impact of CEBPA single mutation in acute myeloid leukemia (AML) patients with intermediate cytogenetic risk. CEBPA single and double mutations were detected in 11 (9.7%) and 17 (15.1%) of 113 NPM1 wild-type patients, but no CEBPA mutations were detected in a group of 44 NPM1 mutated patients. Among patients with NPM1/FLT3-ITD wild-type, those with CEBPA double mutations (P=0.013 and 0.007 for overall survival and relapse-free survival, respectively) or a single mutation (P=0.039 and 0.020 for overall survival and relapse-free survival, respectively) demonstrated a favorable prognosis compared with CEBPA wild-type patients. Subsequent multivariate analysis confirmed the favorable prognostic impact of CEBPA single and double mutations. Despite the low statistical power of this study due to the small number of patients, our preliminary data suggest that CEBPA single mutation may be associated with favorable clinical outcomes in NPM1/FLT3-ITD wild-type AML patients with intermediate cytogenetic risk. PMID:24054719

  15. Clinical implications of non-A-type NPM1 and FLT3 mutations in patients with normal karyotype acute myeloid leukemia.

    Park, Borae G; Chi, Hyun-Sook; Park, Seo-Jin; Min, Sook Kyoung; Jang, Seongsoo; Park, Chan-Jeoung; Kim, Dae-Young; Lee, Jung-Hee; Lee, Je-Hwan; Lee, Kyoo-Hyung

    2012-01-01

    Mutations in the nucleophosmin (NPM1) and fms-like tyrosine kinase-3 (FLT3) genes are the most commonly observed mutations in patients with normal-karyotype acute myeloid leukemia (AML-NK). We analyzed the prognostic effects and interactions of these mutations in 201 AML-NK patients. NPM1 and FLT3 mutations were found in 38.3 and 24.9% of AML-NK patients, respectively. NPM1 mutations (NPM1mut), especially in patients without FLT3 mutations (FLT3mut), were associated with a favorable outcome. However, NPM1mut did not affect survival. FLT3mut tended to be associated with a poor survival outcome. FLT3mut showed no prognostic effects in patients with A-type NPM1mut. However, FLT3mut were associated with a significantly worse prognosis in patients with non-A-type NPM1mut. The prognostic interaction between the NPM1 and FLT3 mutations was significant in patients with non-A-type NPM1mut. PMID:22104247

  16. Phase 2 clinical trial of 5-azacitidine, valproic acid, and all-trans retinoic acid in patients with high-risk acute myeloid leukemia or myelodysplastic syndrome

    Raffoux, Emmanuel; Cras, Audrey; Recher, Christian; Boëlle, Pierre-Yves; de Labarthe, Adrienne; Turlure, Pascal; Marolleau, Jean-Pierre; Reman, Oumedaly; Gardin, Claude; Victor, Maud; Maury, Sébastien; Rousselot, Philippe; Malfuson, Jean-Valère; Maarek, Odile; Daniel, Marie-Thérèse; Fenaux, Pierre; Degos, Laurent; Chomienne, Christine; Chevret, Sylvie; Dombret, Hervé

    2010-01-01

    In this Phase 2 study, we evaluated the efficacy of combination of 5-azacitidine (AZA), valproic acid (VPA), and all-trans retinoic acid (ATRA) in patients with high-risk acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS). Treatment consisted of six cycles of AZA and VPA for 7 days, followed by ATRA for 21 days. Sixty-five patients were enrolled (median age, 72 years; 55 AML including 13 relapsed/refractory patients, 10 MDS; 30 unfavorable karyotypes). Best responses included 14 CR and 3 PR (26%), 75% of the responders and 36% of the non-responders achieving an erythroid response. Median overall survival (OS) was 12.4 months. Untreated patients had a longer OS than relapsed/refractory patients. In patients who fulfilled the 6 planned cycles, OS did not appear to depend on CR/PR achievement, suggesting that stable disease while on-treatment would be a surrogate for survival with this approach. During therapy, early platelet response and demethylation of the FZD9, ALOX12, HPN, and CALCA genes were associated with clinical response. Finally, there was no evidence for the restoration of an ATRA-induced differentiation during therapy. Epigenetic modulation deserves prospective comparisons to conventional care in patients with high-risk AML, at least in those presenting previously untreated disease and low blast count. PMID:21293051

  17. Acute myeloid leukemia following radioactive iodine therapy for papillary carcinoma of the thyroid

    Jain Ankit

    2009-06-01

    Full Text Available Radioactive iodine (RAI therapy plays an important role in the management of thyroid malignancies. Leukemia is a very rare complication of radioactive therapy. There are very few case reports with doses below 100 mCi causing leukemia. We report a case of papillary carcinoma of the thyroid treated with 80 mCi RAI who later developed acute myeloid leukemia. Thus, all patients with thyroid carcinoma treated with RAI should undergo periodic hematological examinations irrespective of RAI dose.

  18. Acute myeloid leukemia following radioactive iodine therapy for papillary carcinoma of the thyroid

    Jain Ankit; Premalata CS; Saini KV; Bapsy PP; Sajeevan KV; Tejinder Singh; Ullas Batra; Babu Govind; Lokanatha Dasappa; Suresh Atilli; Permeshwar R

    2009-01-01

    Radioactive iodine (RAI) therapy plays an important role in the management of thyroid malignancies. Leukemia is a very rare complication of radioactive therapy. There are very few case reports with doses below 100 mCi causing leukemia. We report a case of papillary carcinoma of the thyroid treated with 80 mCi RAI who later developed acute myeloid leukemia. Thus, all patients with thyroid carcinoma treated with RAI should undergo periodic hematological examinations irrespective of RAI dose.

  19. Successful treatment with interferon of chicken pox in children with acute leukemia.

    Kim, Byung Soo

    1984-01-01

    Childhood leukemia, especially acute lymphocytic leukemia, can now be completely cured by a multimodality approach in one out of every two patients. Since prolonged maintenance therapy with anti-cancer agents for three years is required for complete cure, a significant problem during this course of treatment is death due to secondary infection. Those with childhood leukemia receiving anti-cancer chemotherapy who became secondarily injected with chicken pox can now be treated successfully with...

  20. Leukemia.

    Juliusson, Gunnar; Hough, Rachael

    2016-01-01

    Leukemias are a group of life threatening malignant disorders of the blood and bone marrow. In the adolescent and young adult (AYA) population, the acute leukemias are most prevalent, with chronic myeloid leukemia being infrequently seen. Factors associated with more aggressive disease biology tend to increase in frequency with increasing age, whilst tolerability of treatment strategies decreases. There are also challenges regarding the effective delivery of therapy specific to the AYA group, consequences on the unique psychosocial needs of this age group, including compliance. This chapter reviews the current status of epidemiology, pathophysiology, treatment strategies and outcomes of AYA leukemia, with a focus on acute lymphoblastic leukemia and acute myeloid leukemia. PMID:27595359

  1. Development of acute leukemia in a known case of fanconi anaemia ( aplastic anaemai

    Preeti Jhaveri

    2013-01-01

    Full Text Available Fanconi anemia is an autosomal recessive disease associated with an abnormal DNA damage. Although Fanconi anemia is well known for its association of Aplastic anemia and characteristic birth defects, leukemia and solid tumors also occur at a high rate in this group of patients. A patient male / 20yrs, known case of Fanconi anemia presented with ulcer over left lower limb. On further evaluation, the patient was found to have pancytopenia and his peripheral smear revealed many atypical blast like cells. So bone marrow study was done which revealed it to be Acute leukemia probably Acute Myeloid leukemia.

  2. Acute megakaryoblastic leukemia with increased hematogones in children.

    Anton-Harisi, Marieta; Douna, Varvara; Baka, Margarita; Servitzoglou, Marina; Kosmidis, Helen V; Georgouli, Helen; Anastasiou, Theodora

    2012-11-01

    We describe 2 patients, a 4-month-old male and a 17-month-old female, with de novo acute megakaryoblastic leukemia with increased number of hematogones at diagnosis. Both children were admitted in the hospital with thrombocytopenia. The bone marrow smears in the first child revealed the presence of 60% cells with morphologic features consistent with acute megakaryoblastic leukemia. In the other, the initial bone marrow aspirate was dry tap but on the following aspirate 10% cells with lymphoblastic morphology could be seen. The bone marrow flow cytometry showed the presence of hematogones-38% in the first case and 20% in the second-with absence of blasts. Repeated bone marrow aspirates, trephines, and immunophenotypic as well as molecular studies, confirmed the diagnosis of M7. Both children were treated according to the Berlin-Frankfurt-Munster 2004 protocol. PMID:22983420

  3. [Recent Advances of Research on CEBPA Mutation in Acute Myeloid Leukemia].

    Yu, Wen-Qing; Sun, Jing-Nan; Tan, Ye-Hui; Cui, Jiu-Wei; Li, Wei

    2015-12-01

    CCAAT/enhancer binding protein alpha gene (CEBPA) is an important transcription factor in maintenance of differentiation of granulocyte series of hematopoietic system. It plays a key role in regulating cell proliferation and differentiation. CEBPA mutation easily occurs in M1 and M2 type of acute myeloid leukemia, about 5%-14% in adult acute myeloid leukemia and 7.9% in children with acute myeloid leukemia. At present, domestic CEBPA mutation research is far less than abroad. This review focuses on the structual characteristics and detection method of CEBPA, CEBPA clinical features, the effect of CEBPA mutation on the prognosis of patients and the choice of treatment. PMID:26708912

  4. Effect of Taurine on Febrile Episodes in Acute Lymphoblastic Leukemia

    Mina Islambulchilar

    2015-03-01

    Full Text Available Purpose: The purpose of our study was to evaluate the effect of oral taurine on the incidence of febrile episodes during chemotherapy in young adults with acute lymphoblastic leukemia. Methods: Forty young adults with acute lymphoblastic leukemia, at the beginning of maintenance course of their chemotherapy, were eligible for this study. The study population was randomized in a double blind manner to receive either taurine or placebo (2 gram per day orally. Life quality and side effects including febrile episodes were assessed using questionnaire. Data were analyzed using Pearson’s Chi square test. Results: Of total forty participants, 43.8% were female and 56.3 % were male. The mean age was 19.16±1.95 years (ranges: 16-23 years. The results indicated that the levels of white blood cells are significantly (P<0.05 increased in taurine treated group. There was no elevation in blasts count. A total of 70 febrile episodes were observed during study, febrile episodes were significantly (P<0.05 lower in taurine patients in comparison to the control ones. Conclusion: The overall incidence of febrile episodes and infectious complications in acute lymphoblastic leukemia patients receiving taurine was lower than placebo group. Taurine’s ability to increase leukocyte count may result in lower febrile episodes.

  5. Successful Administration of Recombinant Human Soluble Thrombomodulin α (Recomodulin for Disseminated Intravascular Coagulation during Induction Chemotherapy in an Elderly Patient with Acute Monoblastic Leukemia Involving the t(9;11(p22;q23 MLL/AF9 Translocation

    Kazutaka Takagi

    2011-01-01

    Full Text Available Patients with acute myelogenous leukemia complicate with disseminated intravascular coagulation (DIC, not only at the time of the initially leukemia diagnosis, but also during induction chemotherapy. In Japan, recently, a recombinant human soluble thrombomodulin alpha (Recomodulin has been introduced as a new type of anti-DIC agent for clinical use in patients with hematological cancer or infectious disease. We describe a 67-year-old female case in which 25,600 units of Recomodulin for 6 days were successfully administered for both initially complicating and therapy-induced DIC without any troubles of bleeding in an acute monoblastic leukemia (AML-M5a patient with the MLL gene translocation. Furthermore, the levels of DIC biomarkers recovered rapidly after the Recomodulin treatment. Our case suggests that DIC control using Recomodulin is one of the crucial support-therapies during remission induction chemotherapy in patients with acute leukemia of which type tends to complicate extramedullary or extranodal infiltration having potential to onset DIC.

  6. Chromosomal differences between acute nonlymphocytic leukemia in patients with prior solid tumors and prior hematologic malignancies. A study of 14 cases with prior breast cancer

    A cytogenetic study of 14 patients with secondary acute nonlymphocytic leukemia (S-ANLL) with prior treatment for breast cancer is reported. The chromosomes recurrently involved in numerical or structural anomalies are chromosomes 7, 5, 17, and 11, in decreasing order of frequency. The distribution of the anomalies detected in this sample of patients is similar to that observed in published cases with prior breast or other solid tumors, though anomalies of chromosome 11 were not pointed out, but it significantly differs from that of the S-ANLL with prior hematologic malignancies. This difference is principally due to a higher involvement of chromosome 7 in patients with prior hematologic malignancies and of chromosomes 11 and 17 in patients with prior solid tumors. A genetic determinism involving abnormal recessive alleles located on chromosomes 5, 7, 11, and 17 uncovered by deletions of the normal homologs may be a cause of S-ANLL. The difference between patients with prior hematologic malignancies or solid tumors may be explained by different constitutional mutations of recessive genes in the two groups of patients

  7. Normal karyotype acute myeloid leukemia patients with CEBPA double mutation have a favorable prognosis but no survival benefit from allogeneic stem cell transplant.

    Ahn, Jae-Sook; Kim, Jae-Young; Kim, Hyeoung-Joon; Kim, Yeo-Kyeoung; Lee, Seung-Shin; Jung, Sung-Hoon; Yang, Deok-Hwan; Lee, Je-Jung; Kim, Nan Young; Choi, Seung Hyun; Minden, Mark D; Jung, Chul Won; Jang, Jun-Ho; Kim, Hee Je; Moon, Joon Ho; Sohn, Sang Kyun; Won, Jong-Ho; Kim, Sung-Hyun; Kim, Dennis Dong Hwan

    2016-01-01

    Normal karyotype acute myeloid leukemia (NK-AML) with CCAAT/enhancer binding protein α (CEBPA) mutations is known to have a more favorable prognosis. However, direct comparison of the clinical significance according to consolidation therapy has not been widely performed in patients with NK-AML. A total of 404 patients with NK-AML who received intensive induction chemotherapy were included in the present study. Diagnostic samples from the patients were evaluated for CEBPA mutations by direct sequencing. CEBPA single (sm) or double mutation (dm) was observed in 27 (6.7 %) and 51 (12.6 %) patients, respectively. CEBPA (dm) was associated with GATA2 (mut), and it was less frequently associated with FLT3-ITD(pos), NPM1 (mut), and DNMT3A (mut) in comparison with CEBPA (wild) or CEBPA (sm) (all p values hematopoietic cell transplantation (HCT)) demonstrated the role of consolidation treatment in patients with CEBPA (dm). Allogeneic HCT was associated with lower EFS and RI and a trend of higher non-relapse mortality. However, there was no statistically significant difference in OS. In conclusion, CEBPA (dm) was associated with other molecular mutations. Consolidation chemotherapy alone may overcome higher relapse rates by reducing the treatment mortality and increasing survival after relapse events in patients with CEBPA (dm) in NK-AML. PMID:26537612

  8. Epidemiologic study on survival of chronic myeloid leukemia and Ph(+) acute lymphoblastic leukemia patients with BCR-ABL T315I mutation

    Nicolini, Franck E; Mauro, Michael J; Martinelli, Giovanni;

    2009-01-01

    The BCR-ABL T315I mutation represents a major mechanism of resistance to tyrosine kinase inhibitors (TKIs). The objectives of this retrospective observational study were to estimate overall and progression-free survival for chronic myeloid leukemia in chronic-phase (CP), accelerated-phase (AP), o...

  9. Management of Acute Myeloid Leukemia in the Intensive Care Setting.

    Cowan, Andrew J; Altemeier, William A; Johnston, Christine; Gernsheimer, Terry; Becker, Pamela S

    2015-10-01

    Patients with acute myeloid leukemia (AML) who are newly diagnosed or relapsed and those who are receiving cytotoxic chemotherapy are predisposed to conditions such as sepsis due to bacterial and fungal infections, coagulopathies, hemorrhage, metabolic abnormalities, and respiratory and renal failure. These conditions are common reasons for patients with AML to be managed in the intensive care unit (ICU). For patients with AML in the ICU, providers need to be aware of common problems and how to manage them. Understanding the pathophysiology of complications and the recent advances in risk stratification as well as newer therapy for AML are relevant to the critical care provider. PMID:24756309

  10. Transplantations in adult acute lymphoblastic leukemia--grounds for optimism?

    Goldstone, Anthony H

    2009-01-01

    The large MRC/ECOG Adult Acute Lymphoblastic Leukemia Study establishes the value of sibling donor allogeneic transplantation in patients with standard risk, demonstrating superior outcome to conventional chemotherapy. The small but significant number of patients having matched unrelated donor transplantations on this study protocol appear to do well and might establish the value of such an approach for those without a sibling. Reduced-intensity conditioning might begin to address the transplantation-related mortality problems of the older patients. The youngest adults might not need to undergo transplantation at all. If they are now treated on pediatric chemotherapy protocols, their outcome appears to improve significantly. PMID:19778843

  11. Tratamiento de la leucemia linfoide aguda del adulto: Experiencia de un hospital en la Ciudad de México Results of treatment of acute lymphoblastic leukemia in two cohorts of Mexican patients

    Christian Ramos

    2011-09-01

    Full Text Available Background: GIMEMA ALL 0288 trial was designed to evaluate the impact of a 7-day prednisone (PDN pretreatment on complete remission of acute lymphoblastic leukemia. We adopted this trial in 2007. Aim: To evaluate the results of treatment in two cohorts of patients with acute lymphoblastic leukemia, treated from 2007 to January 2009 and from February to December 2009. Material and Methods: We studied 99 patients treated in the first period (58 males and 54 patients treated in the second period (33 males The age of patients ranged from 16 to 60 years and 70% of patients were of high risk. BCR/ABL fusion transcript was present in 12% of patients. Results: Remission rates were 61 and 51% for patients of the first and second group of treatment, respectively. The main cause of death were infections during the induction period. There were 49 relapses, mainly detected in the blood marrow. Global and event free 34 months survival were 32 and 30% respectively. Multivariate analysis disclosed risk stratification and central nervous system infiltration as risk factors for mortality. Conclusions: The main obstacles for the treatment of acute lymphoblastic leukemia in these cohorts of patients were the high incidence of infections and the lack of use of growth stimulating factors.

  12. Clofarabine for the treatment of adult acute lymphoid leukemia: the Group for Research on Adult Acute Lymphoblastic Leukemia intergroup.

    Huguet, Françoise; Leguay, Thibaut; Raffoux, Emmanuel; Rousselot, Philippe; Vey, Norbert; Pigneux, Arnaud; Ifrah, Norbert; Dombret, Hervé

    2015-04-01

    Clofarabine, a second-generation purine analog displaying potent inhibition of DNA synthesis and favorable pharmacologic profile, is approved for the treatment of acute lymphoblastic leukemia (ALL) after failure of at least two previous regimens in patients up to 21 years of age at diagnosis. Good neurologic tolerance, synergy with alkylating agents, management guidelines defined through pediatric ALL and adult acute myeloid leukemia, have also prompted its administration in more than 100 adults with Philadelphia chromosome-positive and negative B lineage and T lineage ALL, as single agent (40 mg/m(2)/ day for 5 days), or in combination. In a Group for Research on Adult Acute Lympho- blastic Leukemia (GRAALL) retrospective study of two regimens (clofarabine ± cyclophosphamide + / - etoposide (ENDEVOL) ± mitoxantrone ± asparaginase ± dexamethasone (VANDEVOL)), remission was achieved in 50% of 55 relapsed/refractory patients, and 17-35% could proceed to allogeneic stem cell. Clofarabine warrants further exploration in advanced ALL treatment and bridge-to-transplant. PMID:24996442

  13. Frequent ASXL2 mutations in acute myeloid leukemia patients with t(8;21)/RUNX1-RUNX1T1 chromosomal translocations

    Micol, Jean-Baptiste; Duployez, Nicolas; Boissel, Nicolas; Petit, Arnaud; Geffroy, Sandrine; Nibourel, Olivier; Lacombe, Catherine; Lapillonne, Helene; Etancelin, Pascaline; Figeac, Martin; Renneville, Aline; Castaigne, Sylvie; Leverger, Guy; Ifrah, Norbert; Dombret, Hervé; Preudhomme, Claude; Jourdan, Eric

    2014-01-01

    Acute myeloid leukemia (AML) with t(8;21) (q22;q22) is considered to have favorable risk; however, nearly half of t(8;21) patients are not cured, and recent studies have highlighted remarkable genetic heterogeneity in this subset of AML. Here we identify somatic mutations in additional sex combs-like 2 (ASXL2) in 22.7% (25/110) of patients with t(8;21), but not in patients with inv(16)/t(16;16) (0/60) or RUNX1-mutated AML (0/26). ASXL2 mutations were similarly frequent in adults and children t(8;21) and were mutually exclusive with ASXL1 mutations. Although overall survival was similar between ASXL1 and ASXL2 mutant t(8;21) AML patients and their wild-type counterparts, patients with ASXL1 or ASXL2 mutations had a cumulative incidence of relapse of 54.6% and 36.0%, respectively, compared with 25% in ASXL1/2 wild-type counterparts (P = .226). These results identify a high-frequency mutation in t(8;21) AML and identify the need for future studies to investigate the clinical and biological relevance of ASXL2 mutations in this unique subset of AML. PMID:24973361

  14. The genetic signature of acute leukemia in infacy

    Chantrain, Christophe; Poirel, Hélène

    2010-01-01

    Infant leukemia is a rare malignant disease with clinical and biological features distinct from older children. It is characterized by a high incidence of mixed lineage leukemia (MLL) gene rearrangement and a poor outcome despite intensive chemotherapy. Recent genetic studies argue in favor of a unique biology of infant acute leukemia. This review describes the specific genetic signature of infant leukemia. It discusses the important insights it provides into the understanding of leukemogenes...

  15. S-1 induced secondary acute erythroid leukemia with a chromosome inv(12)(p13;q13)

    Kensuke Matsumoto; Akira Kitanaka; Makiko Uemura; Fusako Waki; Tetsuya Fukumoto; Hiroaki Ohnishi; Yoshitsugu Kubota; Toshihiko Ishida

    2011-01-01

    Adjuvant chemotherapy by S-1 following gastrectomy is considered standard treatment in Japan. Analysis of follow-up data have proved the efficacy of S-1 administration,and that hematological adverse events were relatively rare. PPyrimidine anti-metabolites, including S-1, have shown relatively lower risks for secondary hematological malignancies in comparison to alkylating agents and topoisomerase-Ⅱ inhibitors. We here report a case of therapy-related leukemia after S-1 administration. A patient who had received S-1as the sole adjuvant chemotherapy was diagnosed with acute erythroid leukemia. To the best of our knowledge, our patient represents the first report of S-1 induced acute leukemia.

  16. Overexpression of Rac1 in leukemia patients and its role in leukemia cell migration and growth

    Rac1 belongs to the Rho family that act as critical mediators of signaling pathways controlling cell migration and proliferation and contributes to the interactions of hematopoietic stem cells with their microenvironment. Alteration of Rac1 might result in unbalanced interactions and ultimately lead to leukemogenesis. In this study, we analyze the expression of Rac1 protein in leukemia patients and determine its role in the abnormal behaviours of leukemic cells. Rac1 protein is overexpressed in primary acute myeloid leukemia cells as compared to normal bone marrow mononuclear cells. siRNA-mediated silencing of Rac1 in leukemia cell lines induced inhibition of cell migration, proliferation, and colony formation. Additionally, blocking Rac1 activity by an inhibitor of Rac1-GTPase, NSC23766, suppressed cell migration and growth. We conclude that overexpression of Rac1 contributes to the accelerated migration and high proliferation potential of leukemia cells, which could be implicated in leukemia development and progression.

  17. Myeloid Sarcoma: An Unusual Presentation of Acute Promyelocytic Leukemia Causing Spinal Cord Compression

    Tay Za Kyaw; Jayaranee A.s. Maniam; Ping Chong Bee; Edmund Fui Min Chin; Veera Sekaran Nadarajan; Hemalatha Shanmugam; Khairul Azmi Abd Kadir

    2012-01-01

    Acute promyelocytic leukemia with concurrent myeloid sarcoma is a rare clinical event. Herein we describe a patient that presented with back pain and bilateral leg weakness caused by spinal cord compression due to extramedullary deposition of leukemic cells. Acute promyelocytic leukemia was suspected based on immunophenotypic findings of malignant cells in bone marrow aspirate. The diagnosis was confirmed by the presence of PML-RARα fusion copies. MRI showed multiple hyperintense changes on t...

  18. Outcome of Adult Acute Lymphoblastic Leukemia in South East of Iran (Zahedan)

    Mashhadi, Mohammad Ali; Koushyar, Mohhamad Mahdi; Mohammadi, Mehdi

    2012-01-01

    Background Acute lymphoblastic leukemia is a lymphoid malignancy, resulting from autonomous proliferation of monoclonal abnormal stem cell. The aim of this study was to evaluate the response rate and prognostic factor of adult patients suffering from acute lymphoblastic leukemia, who were treated with chemotherapy in south east of Iran and demographic methods were used for this study. Methods This study was conducted in Ali Ebne Abitaleb Hospital in south east of Iran (Zahedan) from 2003-2010...

  19. Prognostic Impact of WT-1 Gene Expression in Egyptian Children with Acute Lymphoblastic Leukemia

    Hagag, Adel A; Badraia, Ibrahim M; Hassan, Samir M; Abd El-Lateef, Amal E

    2016-01-01

    Background Acute lymphoblastic leukemia (ALL) is the most common childhood cancer representing 23% of pediatric cancers. Wilms’ tumor -1 gene is a novel prognostic factor, minimal residual disease marker and therapeutic target in acute leukemia. Aim of the work The aim of this work was to study the impact of WT-1 gene expression in the prognosis of ALL. Patients and methods This study was conducted on 40 Egyptian children with newly diagnosed ALL who were subjected to full history taking, tho...

  20. Clofarabine in combination with a standard remission induction regimen (cytosine arabinoside and idarubicin) in patients with previously untreated intermediate and bad-risk acute myelogenous leukemia (AML) or high-risk myelodysplastic syndrome (HR-MDS): phase I results of an ongoing phase I/II study of the leukemia groups of EORTC and GIMEMA (EORTC GIMEMA 06061/AML-14A trial)

    Willemze, R.; Suciu, S.; Muus, P.; Halkes, C.J.; Meloni, G.; Meert, L.; Karrasch, M.; Rapion, J.; Vignetti, M.; Amadori, S.; Witte, T.J.M. de; Marie, J.P.

    2014-01-01

    This study aims to determine the maximum tolerated dose (MTD) of clofarabine combined with the EORTC-GIMEMA 3 + 10 induction regimen (idarubicin + cytosine arabinoside) in adults with untreated acute myelogenous leukemia or high-risk myelodysplastic syndrome. In this phase I trial, 25 patients (medi

  1. Aleukemic Leukemia Cutis Manifesting with Disseminated Nodular Eruptions and a Plaque Preceding Acute Monocytic Leukemia: A Case Report

    Yonal, Ipek; Hindilerden, Fehmi; Coskun, Raif; Dogan, Oner Ibrahim; Nalcaci, Meliha

    2011-01-01

    Aleukemic leukemia cutis (ALC), a discrete tumor of leukemic cells involving the skin, may be the first manifestation of acute myeloid leukemia, preceding the onset in marrow and blood by months and years. ALC is often difficult to diagnose and is associated with a dismal prognosis. A 63-year-old male presented with nodular swellings on the face, a plaque extending over the right shoulder and multiple enlarged cervical lymph nodes. The skin biopsy of the plaque lesion showed a diffuse neoplastic infiltration extending from the dermis to subcutaneous tissue with diffuse positivity for myeloperoxidase and focal positivity for CD34 on immunohistochemical staining. The diagnosis was leukemia cutis. One month later, acute monocytic leukemia (FAB AML-M5b) was diagnosed. The patient died on the seventh month of diagnosis. PMID:22187541

  2. Fractionated gemtuzumab ozogamicin and standard dose cytarabine produced prolonged second remissions in patients over the age of 55 years with acute myeloid leukemia in late first relapse.

    Pilorge, Sylvain; Rigaudeau, Sophie; Rabian, Florence; Sarkozy, Clémentine; Taksin, Anne L; Farhat, Hassan; Merabet, Fathia; Ghez, Stéphanie; Raggueneau, Victoria; Terré, Christine; Garcia, Isabelle; Renneville, Aline; Preudhomme, Claude; Castaigne, Sylvie; Rousselot, Philippe

    2014-04-01

    Gemtuzumab ozogamicin (fGO), a humanized anti-CD33 monoclonal antibody linked to calicheamicin in combination with intensive chemotherapy gives high response rates in adult acute myeloid leukemia (AML) patients in relapse. However, reduced intensity chemotherapy in combination with fractionated GO has not been tested in aged relapsing patients. Patients from our institution with CD33+ AML aged 55 years or more in first late relapse (≥ 6 months) were proposed participation in a GO compassionate use program. Induction therapy consisted in fractionated GO (fGO; 3 mg/m², days 1, 4, 7) with standard-dose cytarabine (200 mg/m² /day, 7 days). Patients were consolidated with two courses of GO and intermediate dose cytarabine. Twenty-four patients (median age 68 years) received fGO with cytarabine. Median follow-up was 42 months. The response rate was 75%, including complete remission (CR) in 16 patients and CR with incomplete platelet recovery (CRp) in two patients. Two-year overall survival (OS) was 51% (95% CI: 28-69) and 2 years relapse-free survival (RFS) was 51% (95%CI: 25-72). Duration of second CR (CR2) was longer than first CR (CR1) in 9 out of 18 patients. Minimal residual disease (MRD) was negative in evaluable patients in CR2, particularly in NPM1 mutated cases. Toxicity was in line with that of the same fractionated single agent GO schedule. Fractionated GO with low intensity chemotherapy produced high response rates and prolonged CR2 in aged AML patients in first late relapse. PMID:24375467

  3. Retinoid Differentiation Therapy for Common Types of Acute Myeloid Leukemia

    Philip Hughes; Geoffrey Brown

    2012-01-01

    Many cancers arise in a tissue stem cell, and cell differentiation is impaired resulting in an accumulation of immature cells. The introduction of all-trans retinoic acid (ATRA) in 1987 to treat acute promyelocytic leukemia (APL), a rare subtype of acute myeloid leukemia (AML), pioneered a new approach to obtain remission in malignancies by restoring the terminal maturation of leukemia cells resulting in these cells having a limited lifespan. Differentiation therapy also offers the prospect o...

  4. Data quality in the Danish National Acute Leukemia Registry

    Ostgård, Lene Sofie Granfeldt; Nørgaard, Jan Maxwell; Severinsen, Marianne Tang;

    2013-01-01

    The Danish National Acute Leukemia Registry (DNLR) has documented coverage of above 98.5%. Less is known about the quality of the recorded data.......The Danish National Acute Leukemia Registry (DNLR) has documented coverage of above 98.5%. Less is known about the quality of the recorded data....

  5. The prognostic impact of FLT3-ITD and NPM1 mutations in patients with relapsed acute myeloid leukemia and intermediate-risk cytogenetics.

    How, J; Sykes, J; Minden, M D; Gupta, V; Yee, K W L; Schimmer, A D; Schuh, A C; Kamel-Reid, S; Brandwein, J M

    2013-01-01

    Internal tandem duplication of the fms-like tyrosine kinase-3 gene (FLT3-ITD) and nucleophosmin-1 (NPM1) mutations have prognostic importance in acute myeloid leukemia (AML) patients with intermediate-risk karyotype at diagnosis, but less is known about their utility to predict outcomes at relapse. We retrospectively analysed outcomes of 70 patients with relapsed, intermediate-risk karyotype AML who received a uniform reinduction regimen, with respect to FLT3-ITD and NPM1 mutation status and first complete remission (CR1) duration. CR1 duration, but not molecular status, was significantly correlated with CR2 rate. On univariate analysis, patients with mutated FLT3-ITD (FLT3+) had significantly worse overall survival (OS) compared with those with neither an NPM1 nor FLT3-ITD mutation (NPM1-/FLT3-). On multivariate analysis, shorter CR1 duration was significantly correlated with inferior OS at relapse (P12 months. In intermediate-risk karyotype AML patients receiving reinduction, CR1 duration remains the most important predictor of OS at relapse; FLT3-ITD and NPM1 status are not independent predictors of survival. PMID:23708641

  6. Sustaining integrating imatinib and interferon-α into maintenance therapy improves survival of patients with Philadelphia positive acute lymphoblastic leukemia ineligible for allogeneic stem cell transplantation.

    Kuang, Pu; Liu, Ting; Pan, Ling; Zhu, Huanling; Wu, Yu; Ye, Yuanxin; Xiang, Bing; Ma, Hongbing; Chang, Hong; Niu, Ting; Cui, Xu; He, Chuan; Li, Jianjun; Ji, Jie; Huang, Jie; Dong, Tian; Dai, Yang; Lu, Xiaojun; Qing, Shenglan; Wu, Huaxin; Liang, Xiaogong; Wang, Xiaoyu; Wu, Chunnong

    2016-10-01

    We report the clinical results of sustainedly integrating imatinib and interferon-α into maintenance therapy in the patients ineligible for allogeneic hematopoietic stem cell transplantation (allo-HSCT). Maintenance therapy lasted for 5 years with imatinib 400 mg daily, interferon-α 3 million units, 2∼3 doses per week, and chemotherapy including vindesine and dexamethasone scheduled monthly in first year, once every 2 months in second year, and once every 3 months in third year. The chemotherapy was discontinued after 3 years and the imatinib and interferon-α continued for another 2 years. For 41 patients without allo-HSCT with a median follow-up of 32 months, the 3-year DFS and OS were 42.7  ± 8.6% and 57.9  ± 8.4%, respectively. Our study suggests that sustaining maintenance with low-dose chemotherapy, imatinib and interferon-α improved survival of adult Philadelphia-positive acute lymphoblastic leukemia (Ph + ALL) patients ineligible for allo-HSCT, and even provided an opportunity for cure. BCR/ABL persistent negativity at 6 and 9 months may have benefit to choose suitable patients for the imatinib/interferon-α maintenance strategy. PMID:26879808

  7. Analysis of outcomes and prognostic factors of acute lymphoblastic leukemia patients treated by MCP841 protocol: A regional cancer center experience

    Akhil Kapoor

    2016-01-01

    Full Text Available Background: A dramatic improvement in the survival of acute lymphoblastic leukemia (ALL patients in the last three decades has been observed. MCP 841 protocol is an old but effective tool with tolerable toxicities. The objective of this study was to estimate the relapse-free survival of ALL patients treated uniformly with MCP 841 protocol on the basis of various prognostic factors. Materials and Methods: The study design was retrospective and it was conducted in a regional cancer center of Northwest India. Three hundred and ten ALL patients who underwent treatment with MCP 841 protocol and regular follow-up for up to 5 years were selected for this study. Relapse-free survival was calculated by Kaplan-Meier analysis and Cox regression analysis was used to calculate the hazards ratio (HR using Statistical Package for the Social Sciences (SPSS software for windows version 20.0. Results: Fifty-four percent patients were 1 lakh/cmm had 41% survival [HR 2.14 (1.76-2.48 with, P < 0.001]. Conclusion: MCP 841 protocol is a useful tool for the treatment of ALL in children when more aggressive protocols can not be used.

  8. NPM1 mutations are more stable than FLT3 mutations during the course of disease in patients with acute myeloid leukemia.

    Palmisano, Michela; Grafone, Tiziana; Ottaviani, Emanuela; Testoni, Nicoletta; Baccarani, Michele; Martinelli, Giovanni

    2007-09-01

    NPM1 mutations have been reported to be the most frequent mutations in acute myeloid leukemia (AML). They are associated with a wide spectrum of morphologic subtypes of AML, normal karyotype and FLT3 mutations. The high frequency of NPM1 mutations might provide a suitable marker for monitoring residual disease of AML. PMID:17768124

  9. Successful Outcome of Disseminated Fusarium Infection with Skin Localization Treated with Voriconazole and Amphotericin B-Lipid Complex in a Patient with Acute Leukemia

    Durand-Joly, Isabelle; Alfandari, Serge; Benchikh, Zinnédine; Rodrigue, Marion; Espinel-Ingroff, Ana; Catteau, Benoit; Cordevant, Christophe; Camus, Daniel; Dei-Cas, Eduardo; Bauters, Francis; Delhaes, Laurence; de Botton, Stéphane

    2003-01-01

    A disseminated Fusarium oxysporum infection with skin localization was diagnosed in a woman with a relapse of B-acute leukemia during induction chemotherapy. The infection was refractory to amphotericin B-lipid complex alone but responded successfully when voriconazole was added.

  10. Successful Outcome of Disseminated Fusarium Infection with Skin Localization Treated with Voriconazole and Amphotericin B-Lipid Complex in a Patient with Acute Leukemia

    Durand-Joly, Isabelle; Alfandari, Serge; Benchikh, Zinnédine; Rodrigue, Marion; Espinel-Ingroff, Ana; Catteau, Benoit; Cordevant, Christophe; Camus, Daniel; Dei-Cas, Eduardo; Bauters, Francis; Delhaes, Laurence; De Botton, Stéphane

    2003-01-01

    A disseminated Fusarium oxysporum infection with skin localization was diagnosed in a woman with a relapse of B-acute leukemia during induction chemotherapy. The infection was refractory to amphotericin B-lipid complex alone but responded successfully when voriconazole was added. PMID:14532255

  11. Identification of patients with acute myeloblastic leukemia who benefit from the addition of gemtuzumab ozogamicin: results of the MRC AML15 trial

    Burnett, Alan K; Hills, Robert K; Milligan, Donald; Kjeldsen, Lars; Kell, Jonathan; Russell, Nigel H; Yin, John A L; Hunter, Ann; Goldstone, Anthony H; Wheatley, Keith

    2011-01-01

    PURPOSE: Antibody-directed chemotherapy for acute myeloid leukemia (AML) may permit more treatment to be administered without escalating toxicity. Gemtuzumab ozogamicin (GO) is an immunoconjugate between CD33 and calicheamicin that is internalized when binding to the epitope. We previously establ...

  12. Skin changes in acute myelogenous leukemia

    Mittal R

    2000-01-01

    Full Text Available A 65-year old woman developed progressive, firm, mild to moderately itchy, erythematous, papular and nodular lesions, over cheeks, extensors of limbs, scalp and lower back without any accompanying systemic complaints except for severe backache. Initially clinical diagnosis was cutaneous sarcoidosis. However presence of myeloblasts, monoblasts, myelocytes and metamyelocytes in peripheral blood smear and typical histopathology of nodule with mixed cellular infiltrate more around blood vessels, sweat glands and hair follicles with admixture of larger polymorphonuclears (myeloblasts/myelocytes, eosinophils with double nuclei, and larger phagocytic cells confirmed the diagnosis of acute myelogenous leukemia (AML.

  13. Distinct alkaline phosphatase in serum of patients with lymphatic leukemia and infectious mononucleosis

    Neumann, H.; Moran, E.M.; Russell, R.M.; Rosenberg, I.H.

    1974-10-11

    A distinct alkaline phosphatase (phosphatase N) was demonstrated in the serum of patients with acute lymphatic leukemia, chronic lymphatic leukemia, and infectious mononucleosis. This enzyme closely resembles that extracted from the thymus of mice with lymphoma or lymphatic leukemia, both in its electrophoretic mobility and its substrate specificity. The phosphatase N activity was related to the clinical state of patients with lymphatic leukemia and disappeared with recovery from infectious mononucleosis.

  14. Phase II trial to assess the safety and efficacy of clofarabine in combination with low-dose cytarabine in elderly patients with acute myeloid leukemia.

    Martínez-Cuadrón, David; Montesinos, Pau; Oriol, Albert; Salamero, Olga; Vidriales, Belén; Bergua, Juan; Herrera, Pilar; Vives, Susanna; Sanz, Jaime; Carpio, Cecilia; Rodríguez-Veiga, Rebeca; Moscardó, Federico; Sanz, Miguel A

    2014-01-01

    Previous studies have shown that clofarabine plus low-dose cytarabine (LDAC) could induce roughly 60 % of complete remissions (CR) with acceptable toxicity and induction mortality in elderly acute myeloid leukemia (AML) patients not suitable for intensive chemotherapy. The Programa Español de Tratamientos en Hematología group conducted a trial for patients diagnosed with untreated AML aged 60 years and older, using the combination of clofarabine (20 mg/m(2) × 5 days) plus low-dose cytarabine (20 mg/m(2) × 14 days). The protocol was flexible regarding the use of antifungal and antibacterial prophylaxis, and outpatient induction therapy was allowed. Although the planned recruitment goal was 75 patients, only 11 patients were enrolled (median age, 74 years) after observing high toxicity and unacceptable mortality (46 and 73 % at 4 and 8 weeks, respectively). The response assessment showed three CR (27 %), three resistant diseases (27 %), and five induction deaths (46 %). Induction was administered in an outpatient modality in five patients, while antifungal and antibacterial prophylaxis was not given in seven and five patients, respectively. In our context, induction therapy with the combination of clofarabine (20 mg/m(2)) plus LDAC was associated with high toxicity and unacceptable mortality in elderly AML patients, leading to the early interruption of the trial. Tight patients' clinical monitoring, follow-up, and intensive supportive care seem crucial to achieve at least acceptable clinical outcomes in elderly AML patients receiving clofarabine plus LDAC. This trial is registered at www.clinicaltrials.gov as no. NCT01193400. PMID:24081577

  15. Expression of CDKN1C in the bone marrow of patients with myelodysplastic syndrome and secondary acute myeloid leukemia is associated with poor survival after conventional chemotherapy.

    Radujkovic, Aleksandar; Dietrich, Sascha; Andrulis, Mindaugas; Benner, Axel; Longerich, Thomas; Pellagatti, Andrea; Nanda, Kriti; Giese, Thomas; Germing, Ulrich; Baldus, Stefan; Boultwood, Jacqueline; Ho, Anthony D; Dreger, Peter; Luft, Thomas

    2016-09-15

    We tested the hypothesis that proliferative activity of hematopoietic stem cells has impact on survival in newly diagnosed patients with myelodysplastic syndrome (MDS) and secondary acute myeloid leukemia (AML). RNA expression profiles of CD34(+) cells were analyzed in 125 MDS patients and compared to healthy controls. Prognostic impact on overall survival (OS) of mRNA proliferation signatures established for solid tumor cells was analyzed retrospectively. For validation on the protein level, immunofluorescence and immunohistochemistry analyses in bone marrow (BM) biopsies were performed, and an independent cohort of 223 MDS and secondary AML patients was investigated. Lower proliferative activity correlated with the expression of cyclin-dependent kinase inhibitor 1C (CDKN1C) and with shorter OS (p < 0.001). In multivariable analysis, higher CDKN1C expression was associated with worse OS (p = 0.02). On the BM level, a total of 84 (38%) patients showed CDKN1C protein expression before start of treatment. Patient, disease and treatment characteristics did not differ between CDKN1C-positive and -negative patients. Positive CDKN1C BM status was associated with shorter OS in multivariable analysis (HR 1.54, p = 0.04). There was an interaction between CDKN1C BM status and subsequent treatment with negative impact on OS being most pronounced in patients receiving conventional cytotoxic chemotherapy (n = 83, 2-year OS 30% versus 58%, p = 0.002). In conclusion, low-proliferative phenotype and CDKN1C expression were associated with shorter OS. CDKN1C protein expression in the BM of newly diagnosed, treatment-naïve MDS and secondary AML patients was identified as a prognostic factor for poor survival in patients treated with antiproliferative chemotherapy. PMID:27170453

  16. Low 25(OH) Vitamin D3 Levels Are Associated with Adverse Outcome in Newly-Diagnosed Intensively-Treated Adult Acute Myeloid Leukemia Patients

    Lee, Hun Ju; Muindi, Josephia R.; Tan, Wei; Hu, Qiang; Wang, Dan; Liu, Song; Wilding, Gregory E.; Ford, Laurie A.; Sait, Sheila N.J.; Block, Annemarie W.; Adjei, Araba A.; Barcos, Maurice; Griffiths, Elizabeth A; Thompson, James E.; Wang, Eunice S.; Johnson, Candace S; Trump, Donald L.; Wetzler, Meir

    2013-01-01

    Background Several studies suggest that low 25(OH) vitamin D3 levels may be prognostic in some malignancies, but no studies have evaluated their impact on treatment outcome in acute myeloid leukemia (AML). Methods VD levels were evaluated in 97 consecutive newly diagnosed, intensively-treated AML patients. MicroRNA-expression profiles and single nucleotide polymorphisms (SNPs) in the 25(OH) vitamin D3 pathway genes were evaluated and correlated with 25(OH) vitamin D3 levels and treatment outcome. Results Thirty-four (35%) patients had normal 25(OH) vitamin D3 levels (32–100 ng/ml), 34 (35%) insufficient (20–31.9 ng/ml) and 29 (30%) deficient levels (<20 ng/ml). Insufficient/deficient 25(OH) vitamin D3 levels were associated with worse relapse-free survival (RFS) compared to normal vitamin D3 levels. In multivariate analyses, deficient 25(OH) vitamin D3, smoking, European LeukemiaNet Genetic Groups and white blood cell count retained their statistical significance for RFS. A number of microRNAs and SNPs were found to be associated with 25(OH) vitamin D3 level, although none remained significant after multiple test corrections; one 25(OH) vitamin D3 receptor SNP, rs10783219, was associated with lower complete remission rate (p=0.0442), shorter RFS (p=0.0058) and overall survival (p=0.0011). Conclusions It remains to be determined what role microRNA and SNP profiles play in contributing to low 25(OH) vitamin D3 level and/or outcome and whether supplementation will improve AML outcome. PMID:24166051

  17. Targeted Resequencing of 9p in Acute Lymphoblastic Leukemia Yields Concordant Results with Array CGH and Reveals Novel Genomic Alterations

    Sarhadi, V.K.; Lahti, L.M.; Scheinin, I.; Tyybäkinoja, A.; Savola, S.; Usvasalo, A.; Räty, R.; Elonen, E.; Saarinen-Pihkala, U.M.; Knuutila, S.

    2013-01-01

    Genetic alterations of the short arm of chromosome 9 are frequent in acute lymphoblastic leukemia. We performed targeted sequencing of 9p region in 35 adolescent and adult acute lymphoblastic leukemia patients and sought to investigate the sensitivity of detecting copy number alterations in comparis

  18. Spontaneous remission of acute myeloid leukemia relapse after hematopoietic cell transplantation in a high-risk patient with 11q23/MLL abnormality.

    Hudecek, Michael; Bartsch, Kristina; Jäkel, Nadja; Heyn, Simone; Pfannes, Roald; Al-Ali, Haifa Kathrin; Cross, Michael; Pönisch, Wolfram; Gerecke, Ulrich; Edelmann, Jeanett; Ittel, Thomas; Niederwieser, Dietger

    2008-01-01

    A 35-year-old female patient was diagnosed with acute myeloid leukemia with multiple genetic aberrations [48 XX, del(3)(q21), +6, t(11;15)(q23;q15), +21] including an 11q23/MLL abnormality. The patient achieved a complete remission after one induction chemotherapy cycle. After three courses of consolidation, a matched unrelated hematopoietic cell transplantation (HCT) was performed. Following an upper respiratory tract infection 7 years after transplant, her blood counts declined to leukocytes of 1 x 10(9)/l, platelets of 51 x 10(9)/l and hemoglobin of 7.5 g/dl. A bone marrow aspirate revealed 55% leukemic blasts carrying the unfavorable genetic aberrations seen at initial diagnosis (11q23/MLL). In the absence of any disease-specific treatment, the leukemic blasts cleared from the bone marrow within 6 days after diagnosis of relapse and peripheral blood counts returned to normal. Molecular analysis of the 11q23/MLL rearrangement was used to evaluate minimal residual disease, which became undetectable in repetitive FISH analyses. This is the first report of spontaneous remission in a patient with initially a multiaberrant leukemic cell clone and a proven 11q23/MLL abnormality at relapse after HCT. PMID:18367831

  19. Perinatal risk factors for acute myeloid leukemia.

    Crump, Casey; Sundquist, Jan; Sieh, Weiva; Winkleby, Marilyn A; Sundquist, Kristina

    2015-12-01

    Infectious etiologies have been hypothesized for acute leukemias because of their high incidence in early childhood, but have seldom been examined for acute myeloid leukemia (AML). We conducted the first large cohort study to examine perinatal factors including season of birth, a proxy for perinatal infectious exposures, and risk of AML in childhood through young adulthood. A national cohort of 3,569,333 persons without Down syndrome who were born in Sweden in 1973-2008 were followed up for AML incidence through 2010 (maximum age 38 years). There were 315 AML cases in 69.7 million person-years of follow-up. We found a sinusoidal pattern in AML risk by season of birth (P birth order, parental age, and parental country of birth were not associated with AML. In this large cohort study, birth in winter was associated with increased risk of AML in childhood through young adulthood, possibly related to immunologic effects of early infectious exposures compared with summer birth. These findings warrant further investigation of the role of seasonally varying perinatal exposures in the etiology of AML. PMID:26113060

  20. Establishment and genetic characterization of a novel mixed-phenotype acute leukemia cell line with EP300-ZNF384 fusion

    Ping, Nana; Qiu, Huiying; Wang, Qian; Dai, Haiping; Ruan, Changgeng; Ehrentraut, Stefan; Drexler, Hans G.; MacLeod, Roderick A. F.; Chen, Suning

    2015-01-01

    Herein, we describe the establishment and characterization of the first mixed-phenotype acute leukemia cell line (JIH-5). The JIH-5 cell line was established from leukemia cells with B lymphoid/myeloid phenotype from a female mixed-phenotype acute leukemia patient. JIH-5 cells exhibit an immunophenotype comprised of myeloid and B lymphoid antigens. Whole-exome sequencing revealed somatic mutations in nine genes in JIH-5 cells. Transcriptional sequencing of JIH-5 cells identified EP300-ZNF384 ...

  1. TET2 gene mutation is unfavorable prognostic factor in cytogenetically normal acute myeloid leukemia patients with NPM1+ and FLT3-ITD - mutations.

    Tian, Xiaopeng; Xu, Yang; Yin, Jia; Tian, Hong; Chen, Suning; Wu, Depei; Sun, Aining

    2014-07-01

    Cytogenetically normal acute myeloid leukemia (cn-AML) is a group of heterogeneous diseases. Gene mutations are increasingly used to assess the prognosis of cn-AML patients and guide risk-adapted treatment. In the present study, we analyzed the molecular genetics characteristics of 373 adult cn-AML patients and explored the relationship between TET2 gene mutations or different genetic mutation patterns and prognosis. We found that 16.1 % of patients had TET2 mutations, 31.6 % had FLT3 internal tandem duplications (ITDs), 6.2 % had FLT3 tyrosine kinase domain mutations, 2.4 % had c-KIT mutations, 37.8 % had NPM1 mutations, 11.3 % had WT1 mutations, 5.9 % had RUNX1 mutations, 11.5 % had ASXL1 mutations, 3.8 % had MLL-PTDs, 7.8 % had IDH1 mutations, 7.8 % had NRAS mutations, 12.3 % had IDH2 mutations, 1.6 % had EZH2 mutations, and 14.7 % had DNMT3A mutations, while none had CBL mutations. Gene mutations were detected in 76.94 % (287/373) of all patients. In the NPM1m(+) patients, those with TET2 mutations were associated with a shorter median overall survival (OS) as compared to TET2 wild-type (wt) patients (9.9 vs. 27.0 months, respectively; P = 0.023); Interestingly, the TET2 mutation was identified as an unfavorable prognostic factor and was closely associated with a shorter median OS as compared to TET2-wt (9.5 vs. 32.2 months, respectively; P = 0.013) in the NPM1m(+)/FLT3-ITDm(-) patient group. Thus, identification of TET2 combined with classic NPM1 and FLT3-ITD mutations allowed us to stratify cn-AML into distinct subtypes. PMID:24859829

  2. Side effect of cranial radiation in childhood acute leukemia, 1

    We examined the somnolence syndrome, which is one of the side effects of cranial irradiation. Out of 53 patients in acute leukemia who had received cranial irradiation, nine patients (17%) developed the somnolence syndrome. Patients with the somnolence syndrome showed slow waves on EEG. Some patients had ventricular dilatation and widening of sulci before cranial irradiation on CT findings, but these findings improved after cranial irradiation. Out of nine cases with the somnolence syndrome, 6 patients survived and did not experience difficulties in school. But one patient showed calcification on CT brain scan. It is considered that the cause of the somnolence syndrome is a trasient inhibition of myelin synthesis and most patients improved without serious sequelae. It is necessary to follow up many cases of somnolence syndrome. (author)

  3. Unilateral hypopyon in a child as a first and sole presentation in relapsing acute lymphoblastic leukemia

    Wadhwa Neeraj

    2007-01-01

    Full Text Available Ocular manifestations form a part of the spectrum of varied clinical presentations in leukemias. Most of the ophthalmic manifestations are related to central nervous system leukemia and bone marrow relapse. We report a case of acute unilateral hypopyon uveitis as an initial presenting feature of relapsing acute lymphoblastic leukemia (ALL in a pediatric patient. Anterior chamber paracentesis was performed in a four-year-old male child presenting with unilateral treatment-resistant hypopyon after remission of ALL. Examination of aqueous humor aspirate revealed presence of malignant cells. Atypical hypopyon, even unilateral can be an indication of relapsing ALL in a child.

  4. How Is Acute Myeloid Leukemia Classified?

    ... also form the basis for treating these leukemias. Markers on the leukemia cells If the leukemia cells ... no signs or symptoms of the disease. A molecular complete remission means there is no evidence of ...

  5. A comparison of discharge strategies after chemotherapy completion in pediatric patients with acute myeloid leukemia: a report from the Children's Oncology Group.

    Miller, Tamara P; Getz, Kelly D; Kavcic, Marko; Li, Yimei; Huang, Yuan-Shun V; Sung, Lillian; Alonzo, Todd A; Gerbing, Robert; Daves, Marla; Horton, Terzah M; Pulsipher, Michael A; Pollard, Jessica; Bagatell, Rochelle; Seif, Alix E; Fisher, Brian T; Gamis, Alan S; Aplenc, Richard

    2016-07-01

    While most children receive acute myeloid leukemia (AML) chemotherapy as inpatients, there is variability in timing of discharge after chemotherapy completion. This study compared treatment-related morbidity, mortality and cumulative hospitalization in children with AML who were discharged after chemotherapy completion (early discharge) and those who remained hospitalized. Chart abstraction data for 153 early discharge-eligible patients enrolled on a Children's Oncology Group trial were compared by discharge strategy. Targeted toxicities included viridans group streptococcal (VGS) bacteremia, hypoxia and hypotension. Early discharge occurred in 11% of courses post-Induction I. Re-admission occurred in 80-100%, but median hospital stay was 7 days shorter. Patients discharged early had higher rates of VGS (adjusted risk ratio (aRR) = 1.67, 95% CI = 1.11-2.51), hypoxia (aRR = 1.92, 95% CI = 1.06-3.48) and hypotension (aRR = 4.36, 95% CI = 2.01-9.46), but there was no difference in mortality. As pressure increases to shorten hospitalizations, these results have important implications for determining discharge practices in pediatric AML. PMID:26727639

  6. Bony Lesions in Pediatric Acute Leukemia: Pictorial Essay

    Makhtoom Shahnazi

    2012-03-01

    Full Text Available Acute leukemia is the most common malignancy in childhood, which mainly involves children less than 15 years of age. The growing skeleton is the main site of involvement in children. Leukemic cells proliferate within the massive red bone marrow in children. So besides the pallor, petechia, purpura and ecchymosis in the skin and mucosal surfaces, bone pain and other bony lesions are other manifestations of leukemia.On the other hand, bony lesions are more prevalent in children than adults with no poor prognosis in comparison to patients without bone lesions. These bony lesions may precede other laboratory tests so familiarity with these presentations is very important for earlier diagnosis.In this pictorial essay, we tried to gather the most common bony lesions that may be seen in acute leukemia in different cases admitted to our hospital with general malaise and localized tenderness and discomfort leading us to perform plain X-ray for further evaluation. Finding these bony lesions helps clinicians to reach the diagnosis quickly. These findings include metaphyseal lucent band and erosion, periosteal reaction, small lucent bone lesion and permeative appearance, reduced bone density and collapsed vertebra.

  7. Haploidentical Transplantation in Children with Acute Leukemia: The Unresolved Issues

    Sarita Rani Jaiswal

    2016-01-01

    Full Text Available Allogeneic hematopoietic stem cell transplantation (HSCT remains a curative option for children with high risk and advanced acute leukemia. Yet availability of matched family donor limits its use and although matched unrelated donor or mismatched umbilical cord blood (UCB are viable options, they fail to meet the global need. Haploidentical family donor is almost universally available and is emerging as the alternate donor of choice in adult patients. However, the same is not true in the case of children. The studies of haploidentical HSCT in children are largely limited to T cell depleted grafts with not so encouraging results in advanced leukemia. At the same time, emerging data from UCBT are challenging the existing paradigm of less stringent HLA match requirements as perceived in the past. The use of posttransplantation cyclophosphamide (PTCY has yielded encouraging results in adults, but data in children is sorely lacking. Our experience of using PTCY based haploidentical HSCT in children shows inadequacy of this approach in younger children compared to excellent outcome in older children. In this context, we discuss the current status of haploidentical HSCT in children with acute leukemia in a global perspective and dwell on its future prospects.

  8. Expression of surface-associated 82kDa-proMMP-9 in primary acute leukemia blast cells inversely correlates with patients' risk.

    Schmohl, Joerg; Santovito, Donato; Guenther, Thomas; Sutanto, Wishnu; Kroell, Tanja; Salih, Helmut; Pitsch, Thomas; Egea, Virginia; Weber, Christian; Schmetzer, Helga; Ries, Christian

    2016-05-01

    With its ability to degrade extracellular matrix proteins and activate growth factors and cytokines, matrix metalloproteinase (MMP)-9 is an important regulator of cell function. Previously, we reported that myeloid leukemic cells express a unique 82kDa-proMMP-9 variant on their cell surface that is not affected by its natural inhibitor. In this study, we generated monoclonal antibodies that specifically recognize 82kDa-proMMP-9. Flow cytometry analysis using these antibodies revealed significant surface expression of 82kDa-proMMP-9 in monocytes, but minimal amounts in T and B cells isolated from peripheral blood of nine healthy donors and 22 patients with acute myeloid leukemia (AML). In all AML patients, blasts expressed 82kDa-proMMP-9 at levels of 4%-46%, with significantly higher levels in patients with a better risk defined according to National Comprehensive Cancer Network (NCCN) guidelines (ρ = -0.748, p < 0.001) and favorable phenotype according to the French-American-British classification (p = 0.02) compared with patients with adverse prognoses. Receiver operating characteristic curve analysis confirmed the diagnostic accuracy of 82kDa-proMMP-9 measurement in AML blasts (area under the curve: 0.893 [0.739-1.000], p = 0.019). It led us to define a cutoff value of 11.5% for identifying patients with lower NCCN risk (p = 0.005) and with a tendency toward a higher probability of response to anthracycline-based therapy (p = 0.109) and increased event-free survival (p = 0.24). Thus, 82kDa-proMMP-9 expression on blasts may represent a novel independent marker of prognosis in patients with AML. PMID:26845021

  9. High Incidences of Invasive Fungal Infections in Acute Myeloid Leukemia Patients Receiving Induction Chemotherapy without Systemic Antifungal Prophylaxis: A Prospective Observational Study in Taiwan.

    Jih-Luh Tang

    Full Text Available Invasive fungal infections (IFIs is an important complication for acute myeloid leukemia (AML patients receiving induction chemotherapy. However, the epidemiological information is not clear in Southeastern Asia, an area of potential high incidences of IFIs. To clarify it, we enrolled 298 non-M3 adult AML patients receiving induction chemotherapy without systemic anti-fungal prophylaxis from Jan 2004 to Dec 2009, when we applied a prospective diagnostic and treatment algorithm for IFIs. Their demographic parameters, IFI characters, and treatment outcome were collected for analysis. The median age of these patients was 51 years. Standard induction chemotherapy was used for 246 (82.6% patients, and 66.8% of patients achieved complete remission (CR or partial remission. The incidence of all-category IFIs was 34.6% (5.7% proven IFIs, 5.0% probable IFIs and 23.8% possible IFIs. Candida tropicalis was the leading pathogen among yeast, and lower respiratory tract was the most common site for IFIs (75.4%, 80/106. Standard induction chemotherapy and failure to CR were identified as risk factors for IFIs. The presence of IFI in induction independently predicted worse survival (hazard ratio 1.536 (1.100-2.141, p value = 0.012. Even in those who survived from the initial IFI insults after 3 months, the presence of IFIs in induction still predicted a poor long-term survival. This study confirms high incidences of IFIs in Southeastern Asia, and illustrates potential risk factors; poor short-term and long-term outcomes are also demonstrated. This epidemiological information will provide useful perspectives for anti-fungal prophylaxis and treatment for AML patients during induction, so that best chances of cure and survival can be provided.

  10. High Incidences of Invasive Fungal Infections in Acute Myeloid Leukemia Patients Receiving Induction Chemotherapy without Systemic Antifungal Prophylaxis: A Prospective Observational Study in Taiwan

    Kung, Hsiang-Chi; Yao, Ming; Wu, Un-In; Hsu, Szu-Chun; Lin, Chien-Ting; Li, Chi-Cheng; Wu, Shang-Ju; Hou, Hsin-An; Chou, Wen-Chien; Huang, Shang-Yi; Tsay, Woei; Chen, Yao-Chang; Chen, Yee-Chun; Chang, Shan-Chwen; Ko, Bor-Sheng; Tien, Hwei-Fang

    2015-01-01

    Invasive fungal infections (IFIs) is an important complication for acute myeloid leukemia (AML) patients receiving induction chemotherapy. However, the epidemiological information is not clear in Southeastern Asia, an area of potential high incidences of IFIs. To clarify it, we enrolled 298 non-M3 adult AML patients receiving induction chemotherapy without systemic anti-fungal prophylaxis from Jan 2004 to Dec 2009, when we applied a prospective diagnostic and treatment algorithm for IFIs. Their demographic parameters, IFI characters, and treatment outcome were collected for analysis. The median age of these patients was 51 years. Standard induction chemotherapy was used for 246 (82.6%) patients, and 66.8% of patients achieved complete remission (CR) or partial remission. The incidence of all-category IFIs was 34.6% (5.7% proven IFIs, 5.0% probable IFIs and 23.8% possible IFIs). Candida tropicalis was the leading pathogen among yeast, and lower respiratory tract was the most common site for IFIs (75.4%, 80/106). Standard induction chemotherapy and failure to CR were identified as risk factors for IFIs. The presence of IFI in induction independently predicted worse survival (hazard ratio 1.536 (1.100–2.141), p value = 0.012). Even in those who survived from the initial IFI insults after 3 months, the presence of IFIs in induction still predicted a poor long-term survival. This study confirms high incidences of IFIs in Southeastern Asia, and illustrates potential risk factors; poor short-term and long-term outcomes are also demonstrated. This epidemiological information will provide useful perspectives for anti-fungal prophylaxis and treatment for AML patients during induction, so that best chances of cure and survival can be provided. PMID:26061179

  11. Immature Reticulocyte Fraction and Absolute Neutrophil Count as Predictor of Hemopoietic Recovery in Patients with Acute Lymphoblastic Leukemia on Remission Induction Chemotherapy

    Shan E. Rauf

    2016-05-01

    Full Text Available Objective: Acute lymphoblastic leukemia (ALL encompasses a group of lymphoid neoplasms that are more common in children and arise from B-and T-lineage lymphoid precursor cells. The immature reticulocyte fraction (IRF, a new routine parameter in hematology analyzers, can give an indication of hemopoietic recovery like absolute neutrophil count (ANC. The purpose of this study was to evaluate IRF in excess of 5% was considered as IRF recovery. Materials and Methods: In this descriptive study, 2.5 to 3 mL of EDTA blood of 45 ALL patients undergoing the remission induction phase of their treatment was sampled and analyzed with a Sysmex XE-5000 on day 1 and every second day thereafter until the day of recovery. ANC of >0.5x109/L on the day corresponding to the first of the three consecutive counts was considered as the day of ANC recovery. IRF recovery was an IRF in excess of 5%. Results: The mean age of the patients was 12.04±5.30 years; 25 patients (55.6% were male and 20 patients (44.4% were female. On day 1 of induction remission, the mean IRF value was 9.68±1.41, while the mean ANC value was 0.077±0.061. Mean recovery day for IRF was 11.84±7.44 and mean recovery day for ANC was 17.67±8.77 (twotailed p-value <0.0001 with 95% confidence interval. By day 28, out of 45 patients 36 (80% showed ANC recovery, while 41 (91% showed IRF recovery. The remaining patients who had not shown recovery by day 28 were further followed up and all of them showed recovery of both parameters by day 39. Conclusion: This study concluded that postinduction bone marrow hemopoietic recovery was earlier by IRF than ANC in children with ALL on chemotherapy

  12. No major cognitive impairment in young children with acute lymphoblastic leukemia using chemotherapy only : A prospective longitudinal study

    Kingma, A; Van Dommelen, RI; Mooyaart, EL; Wilmink, JT; Deelman, BG; Kamps, WA

    2002-01-01

    Purpose: To study. using serial neuropsychological assessment and evaluation of school achievement, persistent neuropsychological late effects in children treated for acute lymphoblastic leukemia (ALL) at a young age with chemotherapy only. Patients and Methods: Twenty consecutive patients underwent

  13. Low-Dose lnterleukin-2 Immunotherapy Does Not Improve Outcome of Patients Age 60 Years and Older with Acute Myeloid Leukemia in First Complete Remission%首次缓解后使用小剂量IL-2免疫治疗不能改善≥60岁老年急性髓性白血病患者预后

    马军; 吴穗晶; 杜欣

    2009-01-01

    @@ 1文献来源 Low-dose Interleukin-2 immunotherapy does not improve outcome of patients age 60 years and older with acute myeloid leukemia in first complete remission: Cancer and Leukemia Group B Study 9720. [J]. J Clin Oncol, 2008,12(26):4934-4939.

  14. Diagnostic imaging of limbs in children with acute leukemia

    Objective: To evaluate X-ray and MRI features of limbs in childhood acute leukemia. Methods: Thirteen children with acute leukemia in our pediatric hematology ward were recruited. All patients were pathologically diagnosed by bone marrow aspiration and complained of bone or joint pain in the first visit. Conventional X-ray and MRI examinations of algesic sites were performed before clinical treatment and after complete remission. MR images were obtained with SE-T1WI, SE-T2WI and T2WI-fat suppressed sequences and symmetrical bilateralism was requested while scanning. X-ray and MRI manifestations were evaluated and compared. Results: All 13 patients had received X-ray examinations. Among them, 6 had normal X-ray findings, whereas the other 7 (14 sites) showed various abnormalities including radiolucent metaphyseal bands (5 sites), periosteal reaction (3 sites), osteapenia (2 sites), mixed lesions (lysis- sclerosis, 1 site), and permeative pattern (3 sites). The number of patients for MRI examinations was 8 (11 sites). Among them, 6 (9 sites) showed bone marrow infiltration and bone marrow necrosis accompanied by normal X-ray findings, another 2 (2 sites) showed bone marrow infiltration associated with radiographic abnormalities of periosteal reaction and radiolucent metaphyseal bands. Four cases were followed up within 1 week when reached complete remission by chemotherapy. MR images features included reduced sizes of bone marrow infiltration lesions associated with increased signal intensity on T1WI, and disappearance of double-line sign on bone marrow necrosis accompanied by signal homogenization. However, the radiograph before and after treatment in the same cases did not differ significantly. Conclusions: MRI was earlier and more comprehensive in showing limbs bone marrow abnormality than radiogram in acute leukemia children with chief complaint of osteoarticular pains. MRI might be one of indicators in following up therapeutic effect for AL children with

  15. Phosphoproteomic profiling analysis in pediatric acute leukemias and in solid tumors of the adult

    We analyzed 120 pediatric patients affected with B-cell AL (B-Acute Lymphoblastic Leukemia) by Reverse Phase Protein Arrays (RPPA). Leukemia cells from bone marrow aspirates were stored in liquid nitrogen in the Bio Bank of the Laboratory of Pediatric Onco hematology in Padova. Clinical data, such as immuno phenotype, outcome, response to therapy and chromosomal translocations, were collected for all the patients

  16. THE IMPORTANCE TO RECOGNIZE ORAL MANIFESTATIONS OF ACUTE LEUKEMIA (CASE REPORT)

    Anandina Irmagita; Siti Aliyah Pradono

    2015-01-01

    Dentists could be the first health providers who detect the oral manifestation of early symptoms of leukemia. The management of three cases of acute leukemia, which had intra oral manifestations that were unnoticed by the dentists, are discussed. Before being referred to the Oral Medicine Department, these patients had undergone invasive dental treatment by their dentist, which had caused complication such as bleeding. After being referred, the patients had undergone non-invasive dental exami...

  17. Technical relapsed testicular irradiation for acute lymphoblastic leukemia

    Testicular irradiation in children suffering from acute lymphoblastic leukemia presents difficulties in relation to daily positioning, dosimetry for dose homogenization of complex geometry and volume change during irradiation thereof. This can lead to significant deviations from the prescribed doses. In addition, the usual techniques often associated with unnecessary irradiation of pelvic simphysis, anus and perineum. This, in the case of pediatric patients, is of great importance, since doses in the vicinity of 20 Gy are associated with a deviation of bone growth, low testosterone levels around 24 Gy and high rates of generation of second tumors. To overcome these problems we propose a special restraint in prone and non-coplanar irradiation.

  18. Double CEBPA mutations are prognostically favorable in non-M3 acute myeloid leukemia patients with wild-type NPM1 and FLT3-ITD.

    Wen, Xiang-Mei; Lin, Jiang; Yang, Jing; Yao, Dong-Ming; Deng, Zhao-Qun; Tang, Chun-Yan; Xiao, Gao-Fei; Yang, Lei; Ma, Ji-Chun; Hu, Jia-Bo; Qian, Wei; Qian, Jun

    2014-01-01

    This study is aimed to investigate the pattern of CEBPA mutations and its clinical significance in Chinese non-M3 acute myeloid leukemia (AML) patients. The entire coding region of CEBPA gene was amplified by PCR and then sequenced in samples from 233 non-M3 AML patients. Fifty mutations were identified in 37 (15.8%) patients with eleven (4.7%) double mutated CEBPA (dmCEBPA) and twenty-six (11.1%) single mutated CEBPA (smCEBPA). dmCEBPA was exclusively observed in M1 and M2 subtypes of FAB classification (P = 0.008), whereas smCEBPA occurred in almost all subtypes (P = 0.401). Patients with dmCEBPA had significantly younger age and higher WBC counts than those with wtCEBPA (P = 0.016 and 0.043, respectively). Both dmCEBPA and smCEBPA were mainly present in cytogenetically normal patients. Patients with dmCEBPA achieved higher rate of complete (CR) than wtCEBPA patients (88% vs. 51%, P = 0.037), whereas smCEBPA and wtCEBPA groups are similar (47% vs. 51%, P = 0.810). Patients with dmCEBPA had a superior overall survival (OS) compared with patients with wtCEBPA (P = 0.033), whereas patients with smCEBPA had a similar OS as patients with wtCEBPA (P = 0.976). dmCEBPA but not smCEBPA was also associated with favorable outcome in patients with wild-type NPM1 and FLT3-ITD (NPM1(wt)FLT3-ITD(wt) ). Our data confirm that dmCEBPA but not smCEBPA is prognostically favorable in NPM1(wt)FLT3-ITD(wt) AML, and suggest that the entity AML with mutated CEBPA should be definitely designated as AML with dmCEBPA in WHO classification and smCEBPA should be excluded from the favorable risk of molecular abnormalities. PMID:25400766

  19. Expression and clinical significance of MN1 and PTEN gene in patients with acute myeloid leukemia%MH1和PTEN基因在急性髓系白血病中的表达及临床意义

    Xueshen Yan; Fanjun Meng; Hongguo Zhao; Jie Yang

    2011-01-01

    Objective: The aim of our study was to explore the correlations between both the genes, evolution and prognosis of the disease by detecting the expression of MN1 (meningioma 1) gene and PTEN (phosphatase and tensin homolog) gene in patients with acute myeloid leukemia (AML). Method: MN1 and PTEN mRNA were detected by reverse transcription-PCR in mononuclear cells of 38 patients with AML and 13 patients with normal bone marrow. Results: Positive rates of MN1 and PTEN genes were 76.3% and 60.5% respectively in bone marrow mononuclear cells. The expression level of MN1 mRNA for the de novo group increased comparing with that for normal control group (P < 0.05), the expression level of PTEN mRNA for de novo group decreased obviously comparing with that for normal control group (P < 0.01), MN1 mRNA level decreased in remission group, while PTEN mRNA level increased comparing with that in de novo group (P < 0.05). MN1 mRNA level increased and PTEN mRNA decreased in relapsed group comparing with that in control group, and their difference was statistical significance (P < 0.05). The two genes' levels had negative correlations in acute myeloid leukemia (r = –0.314, P < 0.05). Conclusion: There is close correlations between expression of MN1 and PTEN genes and the prognosis and occurrence of acute myeloid leukemia, and their expression can be taken as significant indexes to access the de novo, relapse and prognosis of acute myeloid leukemia.

  20. Role of autophagy in acute myeloid leukemia therapy

    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.