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Sample records for acute basophilic leukemia

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

    ClinicalTrials.gov

    2016-07-20

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

  2. Flavopiridol in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia, or Chronic Myelogenous Leukemia

    ClinicalTrials.gov

    2013-06-03

    Adult Acute Basophilic Leukemia; Adult Acute Eosinophilic Leukemia; Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(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); Blastic Phase Chronic Myelogenous Leukemia; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Relapsing Chronic Myelogenous Leukemia

  3. Biomarkers in Bone Marrow Samples From Pediatric Patients With High-Risk Acute Myeloid Leukemia

    ClinicalTrials.gov

    2016-05-17

    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); Recurrent Childhood Acute Myeloid Leukemia; Untreated Childhood Acute Myeloid Leukemia and Other Myeloid Malignancies

  4. Sorafenib in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia, or Chronic Myelogenous Leukemia

    ClinicalTrials.gov

    2013-01-08

    Adult Acute Basophilic Leukemia; Adult Acute Eosinophilic Leukemia; Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); 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 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 Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia

  5. Tipifarnib and Bortezomib in Treating Patients With Acute Leukemia or Chronic Myelogenous Leukemia in Blast Phase

    ClinicalTrials.gov

    2015-04-14

    Adult Acute Basophilic Leukemia; Adult Acute Eosinophilic Leukemia; 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; Blastic Phase; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Disease; Untreated Adult Acute Lymphoblastic Leukemia; Untreated Adult Acute Myeloid Leukemia

  6. Lenalidomide in Treating Older Patients With Acute Myeloid Leukemia

    ClinicalTrials.gov

    2014-07-25

    Adult Acute Basophilic Leukemia; Adult Acute Eosinophilic Leukemia; Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(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

  7. Bortezomib and Combination Chemotherapy in Treating Younger Patients With Recurrent, Refractory, or Secondary Acute Myeloid Leukemia

    ClinicalTrials.gov

    2014-05-13

    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 t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myelomonocytic Leukemia (M4); 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); Recurrent Adult Acute Myeloid Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia

  8. Tipifarnib in Treating Older Patients With Previously Untreated Acute Myeloid Leukemia

    ClinicalTrials.gov

    2013-03-22

    Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome; Adult Acute Basophilic Leukemia; Adult Acute Eosinophilic Leukemia; Adult Acute Erythroid Leukemia (M6); Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monoblastic Leukemia and Acute Monocytic Leukemia (M5); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Cellular Diagnosis, Adult Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

  9. Azacitidine, Mitoxantrone Hydrochloride, and Etoposide in Treating Older Patients With Poor-Prognosis Acute Myeloid Leukemia

    ClinicalTrials.gov

    2015-08-18

    Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome; Adult Acute Basophilic Leukemia; Adult Acute Eosinophilic Leukemia; Adult Acute Megakaryoblastic Leukemia; Adult Acute Monoblastic Leukemia; Adult Acute Monocytic Leukemia; Adult Acute Myeloid Leukemia in Remission; 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; Alkylating Agent-Related Acute Myeloid Leukemia; Recurrent Adult Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

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

    ClinicalTrials.gov

    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

  11. Eltrombopag Olamine in Improving Platelet Recovery in Older Patients With Acute Myeloid Leukemia Undergoing Chemotherapy

    ClinicalTrials.gov

    2016-02-17

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

  12. Tanespimycin and Cytarabine in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia, Chronic Myelogenous Leukemia, Chronic Myelomonocytic Leukemia, or Myelodysplastic Syndromes

    ClinicalTrials.gov

    2013-09-27

    Accelerated Phase Chronic Myelogenous Leukemia; Adult Acute Basophilic Leukemia; Adult Acute Eosinophilic Leukemia; Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(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); Blastic Phase Chronic Myelogenous Leukemia; Chronic Myelomonocytic Leukemia; de Novo Myelodysplastic Syndromes; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Refractory Anemia With Excess Blasts in Transformation; Relapsing Chronic Myelogenous Leukemia; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndromes

  13. Idarubicin, Cytarabine, and Tipifarnib in Treating Patients With Newly Diagnosed Myelodysplastic Syndromes or Acute Myeloid Leukemia

    ClinicalTrials.gov

    2014-05-09

    Adult Acute Basophilic Leukemia; Adult Acute Eosinophilic Leukemia; Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(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 Myelodysplastic Syndromes; Chronic Myelomonocytic Leukemia; de Novo Myelodysplastic Syndromes; Refractory Anemia With Excess Blasts; Refractory Anemia With Excess Blasts in Transformation; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndromes; Untreated Adult Acute Myeloid Leukemia

  14. Alvocidib, Cytarabine, and Mitoxantrone in Treating Patients With Newly Diagnosed Acute Myeloid Leukemia

    ClinicalTrials.gov

    2015-07-14

    Adult Acute Basophilic Leukemia; Adult Acute Eosinophilic Leukemia; Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(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

  15. Eltrombopag Olamine in Treating Patients With Relapsed/Refractory Acute Myeloid Leukemia

    ClinicalTrials.gov

    2016-04-04

    Adult Acute Basophilic Leukemia; Adult Acute Eosinophilic Leukemia; 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

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

    ClinicalTrials.gov

    2013-06-03

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

  17. Acute basophilic leukaemia in a three-month-old calf.

    PubMed

    Laabs, Eva-Maria; Mischke, Reinhard; Dziallas, Peter; Maiolini, Arianna; Tipold, Andrea; Raddatz, Barbara; Puff, Christina; Rehage, Jürgen

    2015-09-03

    A three-month-old female Holstein-Friesian calf was presented with acute tetraparesis. After neurological examination a multifocal lesion in the central nervous system was suspected with the most pronounced lesions between the third thoracic and the third lumbar vertebrae. Haematological examination revealed moderate anaemia as well as severe thrombocytopenia, neutropenia and leucocytosis. A blood smear and bone marrow aspirate exhibited predominantly blasts with basophilic granulation leading to a diagnosis of acute (myeloid) leukaemia with involvement of the basophilic lineage or an acute basophilic leukaemia. Magnetic resonance imaging revealed spinal cord compression; at necropsy, extensive localised haemorrhages extending into the thoracic vertebral canal were found. Histopathology revealed a large population of blast cells in several tissues including the meninges. Due to multifocal detection of neoplastic cells in the vascular system, neoplasia of the haematopoietic system was assumed in agreement with haematological findings. Signs of paresis could be explained by intramedullary spinal cord haemorrhage and myeloid infiltrations of meningeal vessels. In conclusion, despite its rarity, acute myeloid leukaemia with involvement of the basophilic lineage may be considered in diagnosing calves with progressive deteriorating general condition, paresis, leucocytosis with moderate basophilic differentiation or haemorrhagic disorders.

  18. Entinostat and Sorafenib Tosylate in Treating Patients With Advanced or Metastatic Solid Tumors or Refractory or Relapsed Acute Myeloid Leukemia

    ClinicalTrials.gov

    2013-09-18

    Adult Acute Basophilic Leukemia; Adult Acute Eosinophilic Leukemia; 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); Blastic Phase Chronic Myelogenous Leukemia; Recurrent Adult Acute Myeloid Leukemia; Unspecified Adult Solid Tumor, Protocol Specific

  19. Acute Lymphocytic Leukemia

    MedlinePlus

    ... hard for blood to do its work. In acute lymphocytic leukemia (ALL), also called acute lymphoblastic leukemia, there are too ... of white blood cells called lymphocytes or lymphoblasts. ALL is the most common type of cancer in ...

  20. Sorafenib in Treating Patients With Refractory or Relapsed Acute Leukemia, Myelodysplastic Syndromes, or Blastic Phase Chronic Myelogenous Leukemia

    ClinicalTrials.gov

    2015-04-27

    Adult Acute Basophilic Leukemia; Adult Acute Eosinophilic Leukemia; 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 Acute Promyelocytic Leukemia With t(15;17)(q22;q12); PML-RARA; Adult Erythroleukemia; Adult Pure Erythroid Leukemia; Alkylating Agent-Related Acute Myeloid Leukemia; Blastic Phase; de Novo Myelodysplastic Syndrome; Previously Treated Myelodysplastic Syndrome; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndrome

  1. What Is Acute Myeloid Leukemia?

    MedlinePlus

    ... about acute myeloid leukemia? What is acute myeloid leukemia? Cancer starts when cells in a part of ... the body from doing their jobs. Types of leukemia Not all leukemias are the same. There are ...

  2. Flavopiridol, Cytarabine, and Mitoxantrone in Treating Patients With Acute Leukemia

    ClinicalTrials.gov

    2013-10-07

    Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia; Untreated Adult Acute Lymphoblastic Leukemia; Untreated Adult Acute Myeloid Leukemia

  3. Vorinostat, Cytarabine, and Etoposide in Treating Patients With Relapsed and/or Refractory Acute Leukemia or Myelodysplastic Syndromes or Myeloproliferative Disorders

    ClinicalTrials.gov

    2013-05-01

    Accelerated Phase Chronic Myelogenous Leukemia; Adult Acute Basophilic Leukemia; Adult Acute Eosinophilic Leukemia; Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Acute Promyelocytic Leukemia (M3); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Atypical Chronic Myeloid Leukemia, BCR-ABL1 Negative; Blastic Phase Chronic Myelogenous Leukemia; Chronic Eosinophilic Leukemia; Chronic Myelomonocytic Leukemia; Chronic Neutrophilic Leukemia; de Novo Myelodysplastic Syndromes; Essential Thrombocythemia; Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable; Polycythemia Vera; Previously Treated Myelodysplastic Syndromes; Primary Myelofibrosis; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Relapsing Chronic Myelogenous Leukemia; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndromes

  4. Thrombosis and acute leukemia.

    PubMed

    Crespo-Solís, Erick

    2012-04-01

    Thrombosis is a common complication in patients with acute leukemia. While the presence of central venous lines, concomitant steroids, the use of Escherichia coli asparaginase and hereditary thrombophilic abnormalities are known risk factors for thrombosis in children, information on the pathogenesis, risk factors, and clinical outcome of thrombosis in adult patients with acute lymphoid leukemia (ALL) or acute myeloid leukemia (AML) is still scarce. Expert consensus and guidelines regarding leukemia-specific risk factors, thrombosis prevention, and treatment strategies, as well as optimal type of central venous catheter in acute leukemia patients are required. It is likely that each subtype of acute leukemia represents a different setting for the development of thrombosis and the risk of bleeding. This is perhaps due to a combination of different disease-specific pathogenic mechanisms of thrombosis, including the type of chemotherapy protocol chosen, the underlying patients health, associated risk factors, as well as the biology of the disease itself. The risk of thrombosis may also vary according to ethnicity and prevalence of hereditary risk factors for thrombosis; thus, it is advisable for Latin American, Asian, and African countries to report on their specific patient population. PMID:22507812

  5. Targeted Therapy in Treating Patients With Relapsed or Refractory Acute Lymphoblastic Leukemia or Acute Myelogenous Leukemia

    ClinicalTrials.gov

    2016-07-28

    Chronic Myelomonocytic Leukemia; Myelodysplastic Syndrome; Recurrent Acute Myeloid Leukemia With Myelodysplasia-Related Changes; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Refractory Adult Acute Lymphoblastic Leukemia

  6. What Is Acute Lymphocytic Leukemia (ALL)?

    MedlinePlus

    ... key statistics about acute lymphocytic leukemia? What is acute lymphocytic leukemia? Cancer starts when cells in the body begin ... leukemias). The rest of this document focuses on acute lymphocytic leukemia (ALL) in adults. For information on ALL in ...

  7. IMMUNOTHERAPY IN ACUTE LEUKEMIA

    PubMed Central

    Leung, Wing

    2010-01-01

    Recent advances in immunotherapy of cancer may represent a successful example in translational research, in which progress in knowledge and technology in immunology has lead to new strategies of immunotherapy, and even past failure in many clinical trials have led to a better understanding of basic cancer immunobiology. This article reviews the latest concepts in antitumor immunology and its application in the treatment of cancer, with particular focus on acute leukemia. PMID:19100371

  8. [Infant acute leukemia].

    PubMed

    Brethon, Benoît; Cavé, Hélène; Fahd, Mony; Baruchel, André

    2016-03-01

    If acute leukemia is the most frequent cancer in childhood (33%), it remains a very rare diagnosis in infants less than one year old, e.g. less than 5% of cases. At this age, the frequency of acute lymphoblastic leukemia (ALL) (almost all of B-lineage) is quite similar to the one of myeloblastic forms (AML). Infant leukemia frequently presents with high hyperleucocytosis, major tumoral burden and numerous extra-hematological features, especially in central nervous system and skin. Whatever the lineage, the leukemic cell is often very immature cytologically and immunologically. Rearrangements of the Mixed Lineage Leukemia (MLL) gene, located on band 11q23, are the hallmark of these immature leukemias and confer a particular resistance to conventional approaches, corticosteroids and chemotherapy. The immaturity of infants less than 1-year-old is associated to a decrease of the tolerable dose-intensity of some drugs (anthracyclines, alkylating agents) or asks questions about some procedures like radiotherapy or high dose conditioning regimen, responsible of inacceptable acute and late toxicities. The high level of severe infectious diseases and other high-grade side effects limits also the capacity to cure these infants. The survival of infants less than 1-year-old with AML is only 50% but similar to older children. On the other hand, survival of those with ALL is the same, then quite limited comparing the 80% survival in children over one year. Allogeneic stem cell transplantations are indicated in high-risk subgroups of infant ALL (age below 6 months, high hyperleucocytosis >300.10(9)/L, MLL-rearrangement, initial poor prednisone response). However, morbidity and mortality remain very important and these approaches cannot be extended to all cases. During the neonatal period, the dismal prognosis linked to the high number of primary failures or very early relapses and uncertainties about the late toxicities question physicians about ethics. It is an emergency to

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

    ClinicalTrials.gov

    2016-07-26

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

  10. Acute Promyelocytic Leukemia

    PubMed Central

    Kingsley, Edwin C.; Durie, Brian G. M.; Garewal, Harinder S.

    1987-01-01

    Acute promyelocytic leukemia (APL) is a subtype of acute myelogenous leukemia frequently associated with disseminated intravascular coagulation (DIC). Data on 11 patients with APL treated at our institution were analyzed and compared with those of 147 published cases. Most had a bleeding diathesis at presentation and evidence of DIC eventually developed in all. Seven patients (64%) showed the t(15;17)(q22;q21) karyotype or a similar translocation. Using a chemotherapy induction regimen containing an anthracycline, complete remission, requiring a total of 14 courses of treatment, was achieved in six patients (55%). The median duration of response and median survival for complete responders were 10 and 15 months, respectively. Three patients (27%) died of bleeding complications during induction therapy. The tritiated-thymidine labeling index of leukemia cells predicted which patients would achieve a complete remission. Review of six studies of 147 patients with APL from the past 12 years supports the use of a chemotherapy induction regimen containing anthracycline or amsacrine and heparin for the treatment of DIC. PMID:3472414

  11. Acute Leukemias in Children

    PubMed Central

    Pai, Mohan K. R.

    1979-01-01

    With combination chemotherapy approximately 50% of children with lymphoblastic leukemia survive for five or more years and it is now realistic to hope for a cure. Development of sophisticated cytochemical and immunological techniques have enabled us to recognize the factors that predispose to treatment failures. The survival in acute non-lymphocytic leukemia continues to be poor despite the introduction of several innovative treatment regimens. Current research is focused on the manipulation of the host-tumor immune response to eradicate the disease by treatment modalities such as immunotherapy and bone marrow transplantation. Since the treatment regimens are becoming more complex, the initial diagnosis and treatment is best carried out at centres specialized in the management of childhood malignancies. ImagesFig. 1Fig. 2Fig. 3 PMID:21297755

  12. Genetically Modified T-cell Immunotherapy in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia

    ClinicalTrials.gov

    2016-08-10

    Adult Acute Myeloid Leukemia in Remission; Donor; Early Relapse of Acute Myeloid Leukemia; Late Relapse of Acute Myeloid Leukemia; Recurrent Adult Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia

  13. Engineered Nanostructures of Haptens Lead to Unexpected Formation of Membrane Nanotubes Connecting Rat Basophilic Leukemia Cells

    DOE PAGES

    Li, Jie-Ren; Ross, Shailise S.; Liu, Yang; Liu, Ying X.; Wang, Kang-hsin; Chen, Huan-Yuan; Liu, Fu-Tong; Laurence, Ted A.; Liu, Gang-yu

    2015-06-09

    We report here on a recent finding that co-stimulation of the high-affinity immunoglobulin E (IgE) receptor (FcεRI) and the chemokine receptor 1 (CCR1) triggered formation of membrane nanotubes among bone-marrow-derived mast cells. The co-stimulation was attained using corresponding ligands: IgE binding antigen and macrophage inflammatory protein 1α (MIP1 α), respectively. However, this approach failed to trigger formation of nanotubes among rat basophilic leukemia (RBL) cells due to the lack of CCR1 on the cell surface (Int. Immunol. 2010, 22 (2), 113–128). RBL cells are frequently used as a model for mast cells and are best known for antibody-mediated activation viamore » FcεRI. This work reports the successful formation of membrane nanotubes among RBLs using only one stimulus, a hapten of 2,4-dinitrophenyl (DNP) molecules, which are presented as nanostructures with our designed spatial arrangements. This observation underlines the significance of the local presentation of ligands in the context of impacting the cellular signaling cascades. In the case of RBL, certain DNP nanostructures suppress antigen-induced degranulation and facilitate the rearrangement of the cytoskeleton to form nanotubes. We conclude that these results demonstrate an important scientific concept; engineered nanostructures enable cellular signaling cascades, where current technologies encounter great difficulties. More importantly, nanotechnology offers a new platform to selectively activate and/or inhibit desired cellular signaling cascades.« less

  14. Engineered Nanostructures of Haptens Lead to Unexpected Formation of Membrane Nanotubes Connecting Rat Basophilic Leukemia Cells

    SciTech Connect

    Li, Jie-Ren; Ross, Shailise S.; Liu, Yang; Liu, Ying X.; Wang, Kang-hsin; Chen, Huan-Yuan; Liu, Fu-Tong; Laurence, Ted A.; Liu, Gang-yu

    2015-06-09

    We report here on a recent finding that co-stimulation of the high-affinity immunoglobulin E (IgE) receptor (FcεRI) and the chemokine receptor 1 (CCR1) triggered formation of membrane nanotubes among bone-marrow-derived mast cells. The co-stimulation was attained using corresponding ligands: IgE binding antigen and macrophage inflammatory protein 1α (MIP1 α), respectively. However, this approach failed to trigger formation of nanotubes among rat basophilic leukemia (RBL) cells due to the lack of CCR1 on the cell surface (Int. Immunol. 2010, 22 (2), 113–128). RBL cells are frequently used as a model for mast cells and are best known for antibody-mediated activation via FcεRI. This work reports the successful formation of membrane nanotubes among RBLs using only one stimulus, a hapten of 2,4-dinitrophenyl (DNP) molecules, which are presented as nanostructures with our designed spatial arrangements. This observation underlines the significance of the local presentation of ligands in the context of impacting the cellular signaling cascades. In the case of RBL, certain DNP nanostructures suppress antigen-induced degranulation and facilitate the rearrangement of the cytoskeleton to form nanotubes. We conclude that these results demonstrate an important scientific concept; engineered nanostructures enable cellular signaling cascades, where current technologies encounter great difficulties. More importantly, nanotechnology offers a new platform to selectively activate and/or inhibit desired cellular signaling cascades.

  15. Nilotinib and Imatinib Mesylate After Donor Stem Cell Transplant in Treating Patients With Acute Lymphoblastic Leukemia or Chronic Myelogenous Leukemia

    ClinicalTrials.gov

    2014-12-09

    Accelerated Phase Chronic Myelogenous Leukemia; Adult Acute Lymphoblastic Leukemia in Remission; Blastic Phase Chronic Myelogenous Leukemia; Childhood Acute Lymphoblastic Leukemia in Remission; Childhood Chronic Myelogenous Leukemia; 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; Untreated Adult Acute Lymphoblastic Leukemia; Untreated Childhood Acute Lymphoblastic Leukemia

  16. Acute Myeloid Leukemia

    MedlinePlus

    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 ...

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

    ClinicalTrials.gov

    2013-01-22

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

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

    ClinicalTrials.gov

    2014-11-06

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

  19. Decitabine in Treating Patients With Previously Untreated Acute Myeloid Leukemia

    ClinicalTrials.gov

    2016-05-18

    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); Secondary Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

  20. Gemtuzumab Ozogamicin in Treating Patients With Acute Myeloid Leukemia

    ClinicalTrials.gov

    2013-09-23

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

  1. Flavopiridol and Vorinostat in Treating Patients With Relapsed or Refractory Acute Leukemia or Chronic Myelogenous Leukemia or Refractory Anemia

    ClinicalTrials.gov

    2013-04-01

    Blastic Phase Chronic Myelogenous Leukemia; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Refractory Anemia With Excess Blasts; Relapsing Chronic Myelogenous Leukemia; Untreated Adult Acute Lymphoblastic Leukemia; Untreated Adult Acute Myeloid Leukemia

  2. General Information about Adult Acute Lymphoblastic Leukemia

    MedlinePlus

    ... Acute Lymphoblastic Leukemia Treatment (PDQ®)–Patient Version General Information About Adult Acute Lymphoblastic Leukemia Go to Health ... the PDQ Adult Treatment Editorial Board . Clinical Trial Information A clinical trial is a study to answer ...

  3. General Information about Adult Acute Myeloid Leukemia

    MedlinePlus

    ... Acute Myeloid Leukemia Treatment (PDQ®)–Patient Version General Information About Adult Acute Myeloid Leukemia Go to Health ... the PDQ Adult Treatment Editorial Board . Clinical Trial Information A clinical trial is a study to answer ...

  4. General Information about Childhood Acute Lymphoblastic Leukemia

    MedlinePlus

    ... Acute Lymphoblastic Leukemia Treatment (PDQ®)–Patient Version General Information About Childhood Acute Lymphoblastic Leukemia Go to Health ... the PDQ Pediatric Treatment Editorial Board . Clinical Trial Information A clinical trial is a study to answer ...

  5. Targeted Therapy for Acute Lymphocytic Leukemia

    MedlinePlus

    ... Monoclonal antibodies to treat acute lymphocytic leukemia Targeted therapy for acute lymphocytic leukemia In recent years, new ... These drugs are often referred to as targeted therapy. Some of these drugs can be useful in ...

  6. Treatment Options for Adult Acute Myeloid Leukemia

    MedlinePlus

    ... 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 ...

  7. Stages of Adult Acute Myeloid Leukemia

    MedlinePlus

    ... 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 Option Overview (Adult Acute Myeloid Leukemia)

    MedlinePlus

    ... 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 ...

  9. How Is Acute Lymphocytic Leukemia Classified?

    MedlinePlus

    ... How is acute lymphocytic leukemia treated? How is acute lymphocytic leukemia classified? Most types of cancers are assigned numbered ... ALL are now named as follows: B-cell ALL Early pre-B ALL (also called pro-B ...

  10. Progress in acute myeloid leukemia.

    PubMed

    Kadia, Tapan M; Ravandi, Farhad; O'Brien, Susan; Cortes, Jorge; Kantarjian, Hagop M

    2015-03-01

    Significant progress has been made in the treatment of acute myeloid leukemia (AML). Steady gains in clinical research and a renaissance of genomics in leukemia have led to improved outcomes. The recognition of tremendous heterogeneity in AML has allowed individualized treatments of specific disease entities within the context of patient age, cytogenetics, and mutational analysis. The following is a comprehensive review of the current state of AML therapy and a roadmap of our approach to these distinct disease entities. PMID:25441110

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

    ClinicalTrials.gov

    2016-10-24

    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

  12. Tipifarnib in Treating Older Patients With Acute Myeloid Leukemia

    ClinicalTrials.gov

    2015-03-19

    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; Alkylating Agent-Related Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

  13. Acute myeloid leukemia

    MedlinePlus

    ... a low number of platelets. A white blood cell count ( WBC ) can be high, low, or normal. Bone ... and overall health How high your white blood cell count was Certain genetic changes in the leukemia cells ...

  14. Acute lymphoblastic leukemia (ALL)

    MedlinePlus

    ... be found for ALL. The following factors may play a role in the development of all types of leukemia: Certain chromosome problems Exposure to radiation, including x-rays before birth Past treatment with chemotherapy drugs ...

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

    ClinicalTrials.gov

    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

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

    ClinicalTrials.gov

    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

  17. Rebeccamycin Analog in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia, Myelodysplastic Syndrome, Acute Lymphoblastic Leukemia, or Chronic Myelogenous Leukemia

    ClinicalTrials.gov

    2013-01-22

    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; Chronic Myelomonocytic Leukemia; de Novo Myelodysplastic Syndromes; 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; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndromes

  18. Traumatic stress in acute leukemia

    PubMed Central

    Rodin, Gary; Yuen, Dora; Mischitelle, Ashley; Minden, Mark D; Brandwein, Joseph; Schimmer, Aaron; Marmar, Charles; Gagliese, Lucia; Lo, Christopher; Rydall, Anne; Zimmermann, Camilla

    2013-01-01

    Objective Acute leukemia is a condition with an acute onset that is associated with considerable morbidity and mortality. However, the psychological impact of this life-threatening condition and its intensive treatment has not been systematically examined. In the present study, we investigate the prevalence and correlates of post-traumatic stress symptoms in this population. Methods Patients with acute myeloid, lymphocytic, and promyelocytic leukemia who were newly diagnosed, recently relapsed, or treatment failures were recruited at a comprehensive cancer center in Toronto, Canada. Participants completed the Stanford Acute Stress Reaction Questionnaire, Memorial Symptom Assessment Scale, CARES Medical Interaction Subscale, and other psychosocial measures. A multivariate regression analysis was used to assess independent predictors of post-traumatic stress symptoms. Results Of the 205 participants, 58% were male, mean age was 50.1 ± 15.4 years, 86% were recently diagnosed, and 94% were receiving active treatment. The mean Stanford Acute Stress Reaction Questionnaire score was 30.2 ± 22.5, with 27 of 200 (14%) patients meeting criteria for acute stress disorder and 36 (18%) for subsyndromal acute stress disorder. Post-traumatic stress symptoms were associated with more physical symptoms, physical symptom distress, attachment anxiety, and perceived difficulty communicating with health-care providers, and poorer spiritual well-being (all p <0.05). Conclusions The present study demonstrates that clinically significant symptoms of traumatic stress are common in acute leukemia and are linked to the degree of physical suffering, to satisfaction with relationships with health-care providers, and with individual psychological characteristics. Longitudinal study is needed to determine the natural history, but these findings suggest that intervention may be indicated to alleviate or prevent traumatic stress in this population. PMID:22081505

  19. SB-715992 in Treating Patients With Acute Leukemia, Chronic Myelogenous Leukemia, or Advanced Myelodysplastic Syndromes

    ClinicalTrials.gov

    2013-01-10

    Acute Undifferentiated Leukemia; Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Acute Promyelocytic Leukemia (M3); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Blastic Phase Chronic Myelogenous Leukemia; de Novo Myelodysplastic Syndromes; 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; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndromes; Untreated Adult Acute Myeloid Leukemia

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

    ClinicalTrials.gov

    2016-03-14

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

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

    ClinicalTrials.gov

    2013-10-29

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

  2. Genomic characterization of acute leukemias.

    PubMed

    Chiaretti, Sabina; Gianfelici, Valentina; Ceglie, Giulia; Foà, Robin

    2014-01-01

    Over the past two decades, hematologic malignancies have been extensively evaluated due to the introduction of powerful technologies, such as conventional karyotyping, FISH analysis, gene and microRNA expression profiling, array comparative genomic hybridization and SNP arrays, and next-generation sequencing (including whole-exome sequencing and RNA-seq). These analyses have allowed for the refinement of the mechanisms underlying the leukemic transformation in several oncohematologic disorders and, more importantly, they have permitted the definition of novel prognostic algorithms aimed at stratifying patients at the onset of disease and, consequently, treating them in the most appropriate manner. Furthermore, the identification of specific molecular markers is opening the door to targeted and personalized medicine. The most important findings on novel acquisitions in the context of acute lymphoblastic leukemia of both B and T lineage and de novo acute myeloid leukemia are described in this review.

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

    ClinicalTrials.gov

    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

  4. Combination Chemotherapy With or Without Donor Stem Cell Transplant in Treating Patients With Acute Lymphoblastic Leukemia

    ClinicalTrials.gov

    2016-09-09

    Adult Acute Lymphoblastic Leukemia in Remission; Adult B Acute Lymphoblastic Leukemia; Adult B Acute Lymphoblastic Leukemia With t(9;22)(q34;q11.2); BCR-ABL1; Adult L1 Acute Lymphoblastic Leukemia; Adult L2 Acute Lymphoblastic Leukemia; Adult T Acute Lymphoblastic Leukemia; Recurrent Adult Acute Lymphoblastic Leukemia; Untreated Adult Acute Lymphoblastic Leukemia

  5. Genetics Home Reference: core binding factor acute myeloid leukemia

    MedlinePlus

    ... acute myeloid leukemia core binding factor acute myeloid leukemia Enable Javascript to view the expand/collapse boxes. ... Close All Description Core binding factor acute myeloid leukemia (CBF-AML) is one form of a cancer ...

  6. MS-275 and Azacitidine in Treating Patients With Myelodysplastic Syndromes, Chronic Myelomonocytic Leukemia, or Acute Myeloid Leukemia

    ClinicalTrials.gov

    2016-07-20

    Chronic Myelomonocytic Leukemia; de Novo Myelodysplastic Syndrome; Leukemia; Previously Treated Myelodysplastic Syndrome; Recurrent Adult Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndrome; Untreated Adult Acute Myeloid Leukemia

  7. Alemtuzumab and Combination Chemotherapy in Treating Patients With Untreated Acute Lymphoblastic Leukemia

    ClinicalTrials.gov

    2014-03-20

    Acute Undifferentiated Leukemia; B-cell Adult Acute Lymphoblastic Leukemia; B-cell Childhood Acute Lymphoblastic Leukemia; L1 Adult Acute Lymphoblastic Leukemia; L1 Childhood Acute Lymphoblastic Leukemia; L2 Adult Acute Lymphoblastic Leukemia; L2 Childhood Acute Lymphoblastic Leukemia; Philadelphia Chromosome Negative Adult Precursor Acute Lymphoblastic Leukemia; Philadelphia Chromosome Positive Adult Precursor Acute Lymphoblastic Leukemia; Philadelphia Chromosome Positive Childhood Precursor Acute Lymphoblastic Leukemia; T-cell Adult Acute Lymphoblastic Leukemia; T-cell Childhood Acute Lymphoblastic Leukemia; Untreated Adult Acute Lymphoblastic Leukemia; Untreated Childhood Acute Lymphoblastic Leukemia

  8. Vosaroxin and Infusional Cytarabine in Treating Patients With Untreated Acute Myeloid Leukemia

    ClinicalTrials.gov

    2016-03-10

    Acute Myeloid Leukemia; Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome; Acute Myeloid Leukemia With Multilineage Dysplasia; Myeloid Sarcoma; Secondary Acute Myeloid Leukemia; Therapy-Related Acute Myeloid Leukemia; Therapy-Related Myelodysplastic Syndrome

  9. Combination Chemotherapy and Imatinib Mesylate in Treating Children With Relapsed Acute Lymphoblastic Leukemia

    ClinicalTrials.gov

    2013-10-07

    L1 Childhood Acute Lymphoblastic Leukemia; L2 Childhood Acute Lymphoblastic Leukemia; Non-T, Non-B Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Lymphoblastic Leukemia; T-cell Childhood Acute Lymphoblastic Leukemia

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

    ClinicalTrials.gov

    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)

  11. Nivolumab and Dasatinib in Treating Patients With Relapsed or Refractory Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia

    ClinicalTrials.gov

    2016-08-25

    B Acute Lymphoblastic Leukemia With t(9;22)(q34;q11.2); BCR-ABL1; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Lymphoblastic Leukemia; Refractory Adult Acute Lymphoblastic Leukemia; Refractory Childhood Acute Lymphoblastic Leukemia

  12. CCI-779 in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia, Myelodysplastic Syndromes, or Chronic Myelogenous Leukemia in Blastic Phase

    ClinicalTrials.gov

    2013-01-22

    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; Chronic Myelomonocytic Leukemia; de Novo Myelodysplastic Syndromes; 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; Secondary Myelodysplastic Syndromes

  13. Genetics Home Reference: acute promyelocytic leukemia

    MedlinePlus

    ... acute myeloid leukemia, a cancer of the blood-forming tissue ( bone marrow ). In normal bone marrow, hematopoietic ... 7186-203. Review. Citation on PubMed de Thé H, Chen Z. Acute promyelocytic leukaemia: novel insights into ...

  14. Screening antiallergic components from Carthamus tinctorius using rat basophilic leukemia 2H3 cell membrane chromatography combined with high-performance liquid chromatography and tandem mass spectrometry.

    PubMed

    Han, Shengli; Huang, Jing; Cui, Ronghua; Zhang, Tao

    2015-02-01

    Carthamus tinctorius, used in traditional Chinese medicine, has many pharmacological effects, such as anticoagulant effects, antioxidant effects, antiaging effects, regulation of gene expression, and antitumor effects. However, there is no report on the antiallergic effects of the components in C. tinctorius. In the present study, we investigated the antiallergic components of C. tinctorius and its mechanism of action. A rat basophilic leukemia 2H3/cell membrane chromatography coupled online with high-performance liquid chromatography and tandem mass spectrometry method was developed to screen antiallergic components from C. tinctorius. The screening results showed that Hydroxysafflor yellow A, from C. tinctorius, was the targeted component that retained on the rat basophilic leukemia 2H3/cell membrane chromatography column. We measured the amount of β-hexosaminidase and histamine released in mast cells and the key markers of degranulation. The release assays showed that Hydroxysafflor yellow A could attenuate the immunoglobulin E induced release of allergic cytokines without affecting cell viability from 1.0 to 50.0 μM. In conclusion, the established rat basophilic leukemia 2H3 cell membrane chromatography coupled with online high-performance liquid chromatography and tandem mass spectrometry method successfully screened and identified Hydroxysafflor yellow A from C. tinctorius as a potential antiallergic component. Pharmacological analysis elucidated that Hydroxysafflor yellow A is an effective natural component for inhibiting immunoglobulin E-antigen-mediated degranulation.

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

    MedlinePlus

    ... leukemia? What should you ask your doctor about acute lymphocytic leukemia? It is important to have frank, honest discussions ... answer many of your questions. What kind of acute lymphocytic leukemia (ALL) do I have? Do I have any ...

  16. What Are the Key Statistics about Acute Lymphocytic Leukemia?

    MedlinePlus

    ... lymphocytic leukemia? What are the key statistics about acute lymphocytic leukemia? The American Cancer Society’s estimates for acute lymphocytic leukemia (ALL) in the United States for 2016 (including ...

  17. Immunotherapy for acute myeloid leukemia.

    PubMed

    Jurcic, Joseph G

    2005-09-01

    Immunotherapeutic strategies have become part of standard cancer treatment. Chimeric and humanized antibodies have demonstrated activity against a variety of tumors. Although the humanized anti-CD33 antibody HuM195 has only modest activity against overt acute myeloid leukemia (AML), it can eliminate minimal residual disease in acute promyelocytic leukemia. High-dose radioimmunotherapy with b-particle-emitting isotopes targeting CD33, CD45, and CD66 can potentially allow intensification of antileukemic therapy before hematopoietic stem cell transplantation. Conversely, a-particle immunotherapy with isotopes such as bismuth-213 or actinium-225 offers the possibility of selective tumor cell kill while sparing surrounding normal tissues. Targeted chemotherapy with the anti-CD33- calicheamicin construct gemtuzumab ozogamicin has produced remissions in relapsed AML and appears promising when used in combination with standard chemotherapy for newly diagnosed AML. T-cell recognition of peptide antigens presented on the cell surface in combination with major histocompatibility complex antigen provides another potentially promising approach for the treatment of AML. PMID:16091194

  18. The structure at 2.5 Å resolution of human basophilic leukemia-expressed protein BLES03

    PubMed Central

    Bitto, Eduard; Bingman, Craig A.; Robinson, Howard; Allard, Simon T. M.; Wesenberg, Gary E.; Phillips, George N.

    2005-01-01

    The crystal structure of the human basophilic leukemia-expressed protein (BLES03, p5326, Hs.433573) was determined by single-wavelength anomalous diffraction and refined to an R factor of 18.8% (R free = 24.5%) at 2.5 Å resolution. BLES03 shows no detectable sequence similarity to any functionally characterized proteins using state-of-the-art sequence-comparison tools. The structure of BLES03 adopts a fold similar to that of eukaryotic transcription initiation factor 4E (eIF4E), a protein involved in the recognition of the cap structure of eukaryotic mRNA. In addition to fold similarity, the electrostatic surface potentials of BLES03 and eIF4E show a clear conservation of basic and acidic patches. In the crystal lattice, the acidic amino-terminal helices of BLES03 monomers are bound within the basic cavity of symmetry-related monomers in a manner analogous to the binding of mRNA by eIF4E. Interestingly, the gene locus encoding BLES03 is located between genes encoding the proteins DRAP1 and FOSL1, both of which are involved in transcription initiation. It is hypothesized that BLES03 itself may be involved in a biochemical process that requires recognition of nucleic acids. PMID:16511166

  19. The effects of thermal stimuli on intracellular calcium change and histamine releases in rat basophilic leukemia mast cells

    NASA Astrophysics Data System (ADS)

    Wu, Zu-Hui; Zhu, Dan; Chen, Ji-Yao; Zhou, Lu-Wei

    2012-05-01

    The effects of thermal stimuli on rat basophilic leukemia mast cells were studied. The cells in calcium-contained or calcium-free buffers were thermally stimulated in the temperature range of 25-60 °C. The corresponding calcium ion concentration in cells [Ca2+]i as well as the released histamine from cells was measured with fluorescence staining methods. The ruthenium red (RR), a block of membrane calcium channels (transient receptor potential family V (TRPV)), was used in experiments. Under the stimulus of 25-50 °C, no significant difference on [Ca2+]i was found between these three groups of the cells in calcium-contained buffer without or with RR and cells in calcium-free saline, indicating that the increased calcium in cytosol did not result from the extracellular buffer but came from the intracellular calcium stores. The [Ca2+]i continuously increased under the temperature of 50-60 °C, but the RR and calcium-free saline can obviously diminish the [Ca2+]i increase at these high temperatures, reflecting that the opening of the TRPV2 channels leads to a calcium influx resulting in the [Ca2+]i increment. The histamine release also became significant in these cases. Since the released histamine is a well-known mediator for the microcirculation promotion, the histamine release from mast cells could be one of the mechanisms of thermal therapy.

  20. Distribution and dynamics of rat basophilic leukemia immunoglobulin E receptors (FcepsilonRI) on planar ligand-presenting surfaces.

    PubMed

    Spendier, Kathrin; Carroll-Portillo, Amanda; Lidke, Keith A; Wilson, Bridget S; Timlin, Jerilyn A; Thomas, James L

    2010-07-21

    There is considerable interest in the signaling mechanisms of immunoreceptors, especially when triggered with membrane-bound ligands. We have quantified the spatiotemporal dynamics of the redistribution of immunoglobulin E-loaded receptors (IgE-FcepsilonRI) on rat basophilic leukemia-2H3 mast cells in contact with fluid and gel-phase membranes displaying ligands for immunoglobulin E, using total internal reflection fluorescence microscopy. To clearly separate the kinetics of receptor redistribution from cell spreading, and to precisely define the initial contact time (+/-50 ms), micropipette cell manipulation was used to bring individual cells into contact with surfaces. On ligand-free surfaces, there are micron-scale heterogeneities in fluorescence that likely reflect regions of the cell that are more closely apposed to the substrate. When ligands are present, receptor clusters form with this same size scale. The initial rate of accumulation of receptors into the clusters is consistent with diffusion-limited trapping with D approximately 10(-1) microm2/s. These results support the hypothesis that clusters form by diffusion to cell-surface contact regions. Over longer timescales (>10 s), individual clusters moved with both diffusive and directed motion components. The dynamics of the cluster motion is similar to the dynamics of membrane fluctuations of cells on ligand-free fluid membranes. Thus, the same cellular machinery may be responsible for both processes.

  1. Distribution and Dynamics of Rat Basophilic Leukemia Immunoglobulin E Receptors (FcɛRI) on Planar Ligand-Presenting Surfaces

    PubMed Central

    Spendier, Kathrin; Carroll-Portillo, Amanda; Lidke, Keith A.; Wilson, Bridget S.; Timlin, Jerilyn A.; Thomas, James L.

    2010-01-01

    Abstract There is considerable interest in the signaling mechanisms of immunoreceptors, especially when triggered with membrane-bound ligands. We have quantified the spatiotemporal dynamics of the redistribution of immunoglobulin E-loaded receptors (IgE-FcɛRI) on rat basophilic leukemia-2H3 mast cells in contact with fluid and gel-phase membranes displaying ligands for immunoglobulin E, using total internal reflection fluorescence microscopy. To clearly separate the kinetics of receptor redistribution from cell spreading, and to precisely define the initial contact time (±50 ms), micropipette cell manipulation was used to bring individual cells into contact with surfaces. On ligand-free surfaces, there are micron-scale heterogeneities in fluorescence that likely reflect regions of the cell that are more closely apposed to the substrate. When ligands are present, receptor clusters form with this same size scale. The initial rate of accumulation of receptors into the clusters is consistent with diffusion-limited trapping with D ∼10−1μm2/s. These results support the hypothesis that clusters form by diffusion to cell-surface contact regions. Over longer timescales (>10 s), individual clusters moved with both diffusive and directed motion components. The dynamics of the cluster motion is similar to the dynamics of membrane fluctuations of cells on ligand-free fluid membranes. Thus, the same cellular machinery may be responsible for both processes. PMID:20643056

  2. Effects of shear stress on intracellular calcium change and histamine release in rat basophilic leukemia (RBL-2H3) cells.

    PubMed

    Yang, Wenzhong; Chen, Jiyao; Zhou, Luwei

    2009-01-01

    Massage, one form of physical therapy, is widely used for a large number of musculoskeletal disorders, but its exact mechanism still remains to be elucidated. One hypothesis is that the shear stress caused by massage may induce cutaneous mast cells to release histamine, thereby improving the local tissue microcirculation of blood. In the present work, a mast cell line (rat basophilic leukemia cells, RBL-2H3) was used in vitro to study cellular responses to the stimulus of shear stress generated by a rotating rotor in a cell dish. The intracellular calcium ([Ca2+]c) was studied by confocal fluorescence microscopy with Fluo-3/AM staining and the released histamine was measured with a fluorescence spectrometer using o-phthalaldehyde (OPA) staining. An elevation of [Ca2+]c occurred immediately after the shear stress, followed by histamine release. However, both [Ca2+]c increase and histamine release disappeared when a Ca2+-free saline was used, indicating that the rise in the [Ca2+]c is due to a Ca2+ influx from the extracellular buffer. Furthermore, Ruthenium red, a transient receptor potential vanilloid (TRPV) inhibitor, could effectively block the shear stressinduced histamine release, suggesting that TRPV membrane proteins are the likely targets of the shear stress. Because histamine is a well-known mediator of microvascular tissue dilation, these results may have an important impact on understanding the mechanism involved in massage therapy. PMID:19888909

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

    ClinicalTrials.gov

    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

  4. Veliparib and Temozolomide in Treating Patients With Acute Leukemia

    ClinicalTrials.gov

    2016-07-20

    Accelerated Phase of Disease; Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome; Adult Acute Myeloid Leukemia With Inv(16)(p13.1q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With t(16;16)(p13.1;q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); RUNX1-RUNX1T1; Adult Acute Myeloid Leukemia With t(9;11)(p22;q23); MLLT3-MLL; Adult Acute Promyelocytic Leukemia With t(15;17)(q22;q12); PML-RARA; Adult B Acute Lymphoblastic Leukemia; Adult B Acute Lymphoblastic Leukemia With t(9;22)(q34;q11.2); BCR-ABL1; Adult T Acute Lymphoblastic Leukemia; Alkylating Agent-Related Acute Myeloid Leukemia; Blastic Phase; Chronic Myelomonocytic Leukemia; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Disease; Secondary Acute Myeloid Leukemia; Untreated Adult Acute Lymphoblastic Leukemia; Untreated Adult Acute Myeloid Leukemia

  5. Dasatinib, Cytarabine, and Idarubicin in Treating Patients With High-Risk Acute Myeloid Leukemia

    ClinicalTrials.gov

    2016-04-08

    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; Untreated Adult Acute Myeloid Leukemia

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

    ClinicalTrials.gov

    2016-09-12

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

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

    ClinicalTrials.gov

    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

  8. 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

    ClinicalTrials.gov

    2016-09-09

    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

  9. Acute myeloid leukemia presenting as galactorrhea

    PubMed Central

    Nambiar, K. Rakul; Devi, R. Nandini

    2016-01-01

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

  10. Acute myeloid leukemia presenting as galactorrhea

    PubMed Central

    Nambiar, K. Rakul; Devi, R. Nandini

    2016-01-01

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

  11. Treatment Option Overview (Childhood Acute Lymphoblastic Leukemia)

    MedlinePlus

    ... recovery) and treatment options. Childhood acute lymphoblastic leukemia (ALL) is a type of cancer in which the ... genetic conditions affect the risk of having childhood ALL. Anything that increases your risk of getting a ...

  12. Stages of Adult Acute Lymphoblastic Leukemia

    MedlinePlus

    ... recovery) and treatment options. Adult acute lymphoblastic leukemia (ALL) is a type of cancer in which the ... to radiation may increase the risk of developing ALL. Anything that increases your risk of getting a ...

  13. Risk Groups for Childhood Acute Lymphoblastic Leukemia

    MedlinePlus

    ... recovery) and treatment options. Childhood acute lymphoblastic leukemia (ALL) is a type of cancer in which the ... genetic conditions affect the risk of having childhood ALL. Anything that increases your risk of getting a ...

  14. Treatment Options for Adult Acute Lymphoblastic Leukemia

    MedlinePlus

    ... recovery) and treatment options. Adult acute lymphoblastic leukemia (ALL) is a type of cancer in which the ... to radiation may increase the risk of developing ALL. Anything that increases your risk of getting a ...

  15. Treatment Options for Childhood Acute Lymphoblastic Leukemia

    MedlinePlus

    ... recovery) and treatment options. Childhood acute lymphoblastic leukemia (ALL) is a type of cancer in which the ... genetic conditions affect the risk of having childhood ALL. Anything that increases your risk of getting a ...

  16. Treatment Option Overview (Adult Acute Lymphoblastic Leukemia)

    MedlinePlus

    ... recovery) and treatment options. Adult acute lymphoblastic leukemia (ALL) is a type of cancer in which the ... to radiation may increase the risk of developing ALL. Anything that increases your risk of getting a ...

  17. Passive electrical properties of the membrane and cytoplasm of cultured rat basophil leukemia cells. II. Effects of osmotic perturbation.

    PubMed

    Irimajiri, A; Asami, K; Ichinowatari, T; Kinoshita, Y

    1987-01-26

    The effects of osmotic perturbation on the dielectric behavior of cultured rat basophilic leukemia (RBL-1) cells were examined. Cells exposed to osmolalities (pi) of 145-650 mosmolal showed dielectric dispersions of the following characteristics: Permittivity increment delta epsilon(= epsilon l - epsilon h where epsilon l and epsilon h refer to the low- and high-frequency limit values) for a fixed volume concentration increased with pi; gross permittivity behavior was apparently of a typical Cole-Cole type; however, frequency dependence of conductivity was undulant and could be simulated by a superposition of two separate Cole-Cole type dispersions; separation of these subdispersions along the frequency axis was an increasing function of pi, and so was conductivity increment in the high-frequency region. As examined by light microscopy, the cells were spherical in spite of imposed anisotonic stresses and behaved as osmometers at 200-410 mosmolal. When normalized by dividing by number (not volume) concentration, delta epsilon remained relatively constant irrespective of pi. Apparent membrane capacities (Cm), analyzed by applying a single-shell model, increased systematically from a hypotonic value of approx. 1 microF/cm2 up to 5 microF/cm2 at 650 mosmolal. This increase was interpreted as due to increased cellular 'surface/volume' ratios that were confirmed by scanning electron microscopy. Cole-Cole's beta parameter, which culminated around 0.9 for isotonic cells and declined to approx. 0.8 for anisotonic cells, did not parallel the broadening of cell volume distribution but appeared to reflect changes in the intracellular conductivity caused by the anisotonic challenge. The results indicate that the dispersion method can probe changes in surface morphology as well as subcellular organelles' constitution of living cells.

  18. Acute Appendicitis Secondary to Acute Promyelocytic Leukemia

    PubMed Central

    Rodriguez, Eduardo A.; Lopez, Marvin A.; Valluri, Kartik; Wang, Danlu; Fischer, Andrew; Perdomo, Tatiana

    2015-01-01

    Patient: Female, 43 Final Diagnosis: Myeloid sarcoma appendicitis Symptoms: Abdominal pain • chills • fever Medication: — Clinical Procedure: Laparoscopic appendectomy, bone marrow biopsy Specialty: Gastroenterology and Hepatology Objective: Rare disease Background: The gastrointestinal tract is a rare site for extramedullary involvement in acute promyelocytic leukemia (APL). Case Report: A 43-year-old female with no past medical history presented complaining of mild abdominal pain, fever, and chills for the past day. On examination, she was tachycardic and febrile, with mild tenderness of her right lower quadrant and without signs of peritoneal irritation. Laboratory examination revealed pancytopenia and DIC, with a fibrinogen level of 290 mg/dL. CT of the abdomen showed a thickened and hyperemic appendix without perforation or abscess, compatible with acute appendicitis. The patient was given IV broad-spectrum antibiotics and was transfused with packed red blood cells and platelets. She underwent uncomplicated laparoscopic appendectomy and bone marrow biopsy, which revealed neo-plastic cells of 90% of the total bone marrow cellularity. Flow cytometry indicated presence of 92.4% of immature myeloid cells with t (15: 17) and q (22: 12) mutations, and FISH analysis for PML-RARA demonstrated a long-form fusion transcript, positive for APL. Appendix pathology described leukemic infiltration with co-expression of myeloperoxidase and CD68, consistent with myeloid sarcoma of the appendix. The patient completed a course of daunorubicin, cytarabine, and all trans-retinoic acid. Repeat bone marrow biopsy demonstrated complete remission. She will follow up with her primary care physician and hematologist/oncologist. Conclusions: Myeloid sarcoma of the appendix in the setting of APL is very rare and it might play a role in the development of acute appendicitis. Urgent management, including bone marrow biopsy for definitive diagnosis and urgent surgical intervention

  19. S1312, Inotuzumab Ozogamicin and Combination Chemotherapy in Treating Patients With Relapsed or Refractory Acute Leukemia

    ClinicalTrials.gov

    2016-04-14

    Acute Leukemias of Ambiguous Lineage; B-cell Adult Acute Lymphoblastic Leukemia; Philadelphia Chromosome Positive Adult Precursor Acute Lymphoblastic Leukemia; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Burkitt Lymphoma

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

    ClinicalTrials.gov

    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

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

    ClinicalTrials.gov

    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

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

    ClinicalTrials.gov

    2015-12-03

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

  3. Selinexor and Chemotherapy in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia

    ClinicalTrials.gov

    2016-09-29

    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

  4. Lenalidomide in Treating Older Patients With Acute Myeloid Leukemia Who Have Undergone Stem Cell Transplant

    ClinicalTrials.gov

    2015-03-02

    Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome; Adult Acute Megakaryoblastic Leukemia; Adult Acute Monoblastic Leukemia; Adult Acute Monocytic Leukemia; Adult Acute Myeloid Leukemia in Remission; 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; Alkylating Agent-Related Acute Myeloid Leukemia; Recurrent Adult Acute Myeloid Leukemia

  5. Choline Magnesium Trisalicylate and Combination Chemotherapy in Treating Patients With Acute Myeloid Leukemia

    ClinicalTrials.gov

    2016-07-08

    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); Recurrent Adult Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

  6. Tipifarnib and Etoposide in Treating Older Patients With Newly Diagnosed, Previously Untreated Acute Myeloid Leukemia

    ClinicalTrials.gov

    2014-10-01

    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

  7. Alvocidib, Cytarabine, and Mitoxantrone in Treating Patients With Newly Diagnosed Acute Myeloid Leukemia

    ClinicalTrials.gov

    2015-06-03

    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

  8. Omacetaxine Mepesuccinate, Cytarabine, and Decitabine in Treating Older Patients With Newly Diagnosed Acute Myeloid Leukemia

    ClinicalTrials.gov

    2016-04-05

    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

  9. Blinatumomab and Combination Chemotherapy or Dasatinib, Prednisone, and Blinatumomab in Treating Older Patients With Acute Lymphoblastic Leukemia

    ClinicalTrials.gov

    2016-10-19

    B Acute Lymphoblastic Leukemia; B Acute Lymphoblastic Leukemia With t(9;22)(q34;q11.2); BCR-ABL1; Recurrent Adult Acute Lymphoblastic Leukemia; Refractory Adult Acute Lymphoblastic Leukemia; Untreated Adult Acute Lymphoblastic Leukemia

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

    ClinicalTrials.gov

    2016-10-14

    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

  11. GTI-2040 in Treating Patients With Relapsed, Refractory, or High-Risk Acute Leukemia, High-Grade Myelodysplastic Syndromes, or Refractory or Blastic Phase Chronic Myelogenous Leukemia

    ClinicalTrials.gov

    2015-12-03

    Acute Undifferentiated 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); Blastic Phase Chronic Myelogenous Leukemia; de Novo Myelodysplastic Syndromes; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Relapsing Chronic Myelogenous Leukemia; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndromes; Untreated Adult Acute Lymphoblastic Leukemia; Untreated Adult Acute Myeloid Leukemia

  12. Bortezomib and Combination Chemotherapy in Treating Young Patients With Relapsed Acute Lymphoblastic Leukemia or Lymphoblastic Lymphoma

    ClinicalTrials.gov

    2014-09-30

    B-cell Adult Acute Lymphoblastic Leukemia; B-cell Childhood Acute Lymphoblastic Leukemia; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Lymphoblastic Lymphoma; T-cell Adult Acute Lymphoblastic Leukemia; T-cell Childhood Acute Lymphoblastic Leukemia

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

    ClinicalTrials.gov

    2014-10-30

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

  14. Bioelectrical Impedance Measurement for Predicting Treatment Outcome in Patients With Newly Diagnosed Acute Leukemia

    ClinicalTrials.gov

    2016-07-26

    Acute Undifferentiated Leukemia; 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); Mast Cell Leukemia; Myeloid/NK-cell Acute Leukemia; Untreated Adult Acute Lymphoblastic Leukemia; Untreated Adult Acute Myeloid Leukemia

  15. The Effects of Electrical Stimuli on Calcium Change and Histamine Release in Rat Basophilic Leukemia Mast Cells

    NASA Astrophysics Data System (ADS)

    Zhu, Dan; Wu, Zu-Hui; Chen, Ji-Yao; Zhou, Lu-Wei

    2013-06-01

    We apply electric fields at different frequencies of 0.1, 1, 10 and 100 kHz to the rat basophilic leukemia (RBL) mast cells in calcium-containing or calcium-free buffers. The stimuli cause changes of the intracellular calcium ion concentration [Ca2+]i as well as the histamine. The [Ca2+]i increases when the frequency of the external electric field increases from 100 Hz to 10 kHz, and then decreases when the frequency further increases from 10 kHz to 100 kHz, showing a peak at 100 kHz. A similar frequency dependence of the histamine release is also found. The [Ca2+]i and the histamine releases at 100 Hz are about the same as the values of the control group with no electrical stimulation. The ruthenium red (RR), an inhibitor to the TRPV (transient receptor potential (TRP) family V) channels across the cell membrane, is used in the experiment to check whether the electric field stimuli act on the TRPV channels. Under an electric field of 10 kHz, the [Ca2+]i in a calcium-concentration buffer is about 3.5 times as much as that of the control group with no electric stimulation, while the [Ca2+]i in a calcium-free buffer is only about 2.2 times. Similar behavior is also found for the histamine release. RR blockage effect on the [Ca2+]i decrease is statistically significant (~75%) when mast cells in the buffer with calcium are stimulated with a 10 kHz electric field in comparison with the result without the RR treatment. This proves that TRPVs are the channels that calcium ions inflow through from the extracellular environment under electrical stimuli. Under this condition, the histamine is also released following a similar way. We suggest that, as far as an electric stimulation is concerned, an application of ac electric field of 10 kHz is better than other frequencies to open TRPV channels in mast cells, and this would cause a significant calcium influx resulting in a significant histamine release, which could be one of the mechanisms for electric therapy.

  16. What's New in Adult Acute Myeloid Leukemia Research and Treatment?

    MedlinePlus

    ... Topic Additional resources for acute myeloid leukemia What’s new in acute myeloid leukemia research and treatment? Researchers ... benefit from current treatments. Researchers are studying many new chemo drugs for use in AML, including: Sapacitabine, ...

  17. Nilotinib and Combination Chemotherapy in Treating Patients With Newly Diagnosed Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia or Blastic Phase Chronic Myelogenous Leukemia

    ClinicalTrials.gov

    2015-10-29

    B-cell Adult Acute Lymphoblastic Leukemia; Blastic Phase Chronic Myelogenous Leukemia; Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Philadelphia Chromosome Positive Adult Precursor Acute Lymphoblastic Leukemia; Untreated Adult Acute Lymphoblastic Leukemia

  18. Trebananib With or Without Low-Dose Cytarabine in Treating Patients With Acute Myeloid Leukemia

    ClinicalTrials.gov

    2016-07-25

    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; Untreated Adult Acute Myeloid Leukemia

  19. 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

    ClinicalTrials.gov

    2016-09-29

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

  20. Actual biological diagnosis of acute myeloblastic leukemia in children

    PubMed Central

    Buga Corbu, V; Glűck, A; Arion, C

    2014-01-01

    Abstract Acute myeloblastic leukemia accounts for approximately 20% of acute leukemias in children. The days the microscope represented the main tool in the diagnosis and classification of Acute Myeloblastic Leukemia seem to be very far. This review summarizes the current diagnosis of this malignancy, where the morphological, cytochemical, immunophenotyping, cytogenetic and molecular characterization represents the basement of a risk group related therapy. PMID:25408742

  1. Actual biological diagnosis of acute myeloblastic leukemia in children.

    PubMed

    Buga Corbu, V; Glűck, A; Arion, C

    2014-06-15

    Acute myeloblastic leukemia accounts for approximately 20% of acute leukemias in children. The days the microscope represented the main tool in the diagnosis and classification of Acute Myeloblastic Leukemia seem to be very far. This review summarizes the current diagnosis of this malignancy, where the morphological, cytochemical, immunophenotyping, cytogenetic and molecular characterization represents the basement of a risk group related therapy.

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

    ClinicalTrials.gov

    2016-03-16

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

  3. Phase I Combination of Midostaurin, Bortezomib, and Chemo in Relapsed/Refractory Acute Myeloid Leukemia

    ClinicalTrials.gov

    2016-07-04

    Acute Myeloid Leukemia; Acute Myeloid Leukemia With Multilineage Dysplasia Following; Myelodysplastic Syndrome; 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

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

    ClinicalTrials.gov

    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

  5. The biology of pediatric acute megakaryoblastic leukemia

    PubMed Central

    Downing, James R.

    2015-01-01

    Acute megakaryoblastic leukemia (AMKL) comprises between 4% and 15% of newly diagnosed pediatric acute myeloid leukemia patients. AMKL in children with Down syndrome (DS) is characterized by a founding GATA1 mutation that cooperates with trisomy 21, followed by the acquisition of additional somatic mutations. In contrast, non–DS-AMKL is characterized by chimeric oncogenes consisting of genes known to play a role in normal hematopoiesis. CBFA2T3-GLIS2 is the most frequent chimeric oncogene identified to date in this subset of patients and confers a poor prognosis. PMID:26186939

  6. Targeting of leukemia-initiating cells in acute promyelocytic leukemia

    PubMed Central

    Lo-Coco, Francesco

    2015-01-01

    Acute promyelocytic leukemia (APL) is a subtype of acute myeloid leukemia (AML) with peculiar molecular, phenotypic and clinical features and unique therapeutic response to specific treatments. The disease is characterized by a single, pathognomonic molecular event, consisting of the translocation t(15;17) which gives rise to the PML/retinoic acid receptor α (RARα) hybrid protein. The development of this leukemia is mainly related to the fusion oncoprotein PML/RARα, acting as an altered RAR mediating abnormal signalling and repression of myeloid differentiation, with consequent accumulation of undifferentiated promyelocytes. The prognosis of APL has dramatically been improved with the introduction in therapy of all-trans retinoic acid (ATRA) and arsenic trioxide (ATO). The main effect of these two drugs is linked to the targeting of either RAR moiety of the PML/RARα molecule and induction of cell differentiation (ATRA) or of the PML moiety of the fusion protein and induction of leukemic cell apoptosis, including leukemic progenitors (mostly induced by ATO). These two drugs exhibited excellent synergism and determine a very high rate of durable remissions in low/intermediate-risk APLs, when administered in the absence of any chemotherapeutic drug. The strong synergism and the marked clinical efficacy of these two agents when administered together seem to be related to their capacity to induce PML/RARα degradation and complete eradication of leukemia stem cells. PMID:27358876

  7. Idarubicin, Cytarabine, and Pravastatin Sodium in Treating Patients With Acute Myeloid Leukemia or Myelodysplastic Syndromes

    ClinicalTrials.gov

    2015-03-03

    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); Chronic Myelomonocytic Leukemia; de Novo Myelodysplastic Syndromes; Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable; Refractory Anemia With Excess Blasts; Untreated Adult Acute Myeloid Leukemia

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

    ClinicalTrials.gov

    2016-09-16

    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 in Remission; Chronic Myelomonocytic Leukemia

  9. Filgrastim, Cladribine, Cytarabine, and Mitoxantrone Hydrochloride in Treating Patients With Newly Diagnosed or Relapsed/Refractory Acute Myeloid Leukemia or High-Risk Myelodysplastic Syndromes

    ClinicalTrials.gov

    2016-09-26

    Acute Biphenotypic Leukemia; de Novo Myelodysplastic Syndrome; Previously Treated Myelodysplastic Syndrome; Recurrent Adult Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndrome; Untreated Adult Acute Myeloid Leukemia

  10. 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

    ClinicalTrials.gov

    2016-07-18

    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

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

    ClinicalTrials.gov

    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

  12. Vaccine Therapy and Basiliximab in Treating Patients With Acute Myeloid Leukemia in Complete Remission

    ClinicalTrials.gov

    2016-06-27

    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)

  13. CPI-613, Cytarabine, and Mitoxantrone Hydrochloride in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia

    ClinicalTrials.gov

    2016-07-26

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

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

    ClinicalTrials.gov

    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

  15. Cancer Statistics: Acute Lymphocytic Leukemia (ALL)

    MedlinePlus

    ... at a Glance Show More At a Glance Estimated New Cases in 2016 6,590 % of All New Cancer Cases 0.4% Estimated Deaths in 2016 1,430 % of All Cancer ... of This Cancer : In 2013, there were an estimated 77,855 people living with acute lymphocytic leukemia ...

  16. Ixazomib in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia

    ClinicalTrials.gov

    2016-10-18

    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

  17. Vorinostat and Gemtuzumab Ozogamicin in Treating Older Patients With Previously Untreated Acute Myeloid Leukemia

    ClinicalTrials.gov

    2011-11-03

    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); Untreated Adult Acute Myeloid Leukemia

  18. Cytarabine With or Without SCH 900776 in Treating Adult Patients With Relapsed Acute Myeloid Leukemia

    ClinicalTrials.gov

    2016-07-20

    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; Alkylating Agent-Related Acute Myeloid Leukemia; Recurrent Adult Acute Myeloid Leukemia

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

    ClinicalTrials.gov

    2016-10-04

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

  20. Flavopiridol, Cytarabine, and Mitoxantrone in Treating Patients With Relapsed or Refractory Acute Leukemia

    ClinicalTrials.gov

    2013-09-27

    Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(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); Malignant Neoplasm; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia

  1. Tipifarnib and Etoposide in Treating Older Patients With Newly Diagnosed Acute Myeloid Leukemia

    ClinicalTrials.gov

    2013-01-08

    Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(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

  2. Bortezomib, Daunorubicin, and Cytarabine in Treating Older Patients With Previously Untreated Acute Myeloid Leukemia

    ClinicalTrials.gov

    2014-09-04

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

  3. Vaccine Therapy Plus Immune Adjuvant in Treating Patients With Chronic Myeloid Leukemia, Acute Myeloid Leukemia, or Myelodysplastic Syndrome

    ClinicalTrials.gov

    2013-01-04

    Accelerated Phase Chronic Myelogenous Leukemia; Adult Acute Myeloid Leukemia in Remission; Chronic Phase Chronic Myelogenous Leukemia; Previously Treated Myelodysplastic Syndromes; Refractory Anemia With Excess Blasts; Refractory Anemia With Excess Blasts in Transformation; Relapsing Chronic Myelogenous Leukemia

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

    ClinicalTrials.gov

    2016-08-23

    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

  5. Regulation of rat basophilic leukemia-2H3 mast cell secretion by a constitutive Lyn kinase interaction with the high affinity IgE receptor (Fc epsilon RI).

    PubMed

    Vonakis, Becky M; Gibbons, Scott P; Rotté, Masashi J; Brothers, Elizabeth A; Kim, Seok C; Chichester, Kristin; MacDonald, Susan M

    2005-10-01

    Signaling through the high affinity IgE receptor is initiated by noncovalently associated Lyn kinase, resulting in the secretion of inflammatory mediators from mast cells. A fraction of the total cellular Lyn is associated via its N-terminal unique domain with the cytoplasmic domain of the Fc epsilonRI beta subunit before receptor aggregation. In the current study, we stably transfected the unique domain of Lyn into rat basophilic leukemia-2H3 mast cells and examined the consequences on Fc epsilonRI-induced signal transduction and mediator secretion to further define the role of the unique domain of Lyn in mast cell secretion. Tyrosine phosphorylation of Fc epsilonRI beta and gamma subunits was partially inhibited in the Lyn unique domain transfectants after Ag stimulation. Ag stimulation of Lyn unique domain transfectants was accompanied by enhanced phosphorylation of MEK and ERK-2, which are required for leukotriene C4 (LTC4) release, and production of LTC4 was increased 3- to 5-fold, compared with cells transfected with vector alone. Conversely, tyrosine phosphorylation of the adaptor protein Gab2, which is essential for mast cell degranulation, was inhibited after Ag stimulation of Lyn unique domain transfectants, and Ag-induced release of histamine was inhibited up to 48%. In rat basophilic leukemia-2H3 cells, Lyn thus plays a dual role by positively regulating Fc epsilonRI phosphorylation and degranulation while negatively regulating LTC4 production. This study provides further evidence that the constitutive interaction between the unique domain of Lyn and the Fc epsilonRI beta subunit is a crucial step in the initiation of Fc epsilonRI signaling and that Lyn is limiting for Fc epsilonRI-induced secretion of inflammatory mediators.

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

    ClinicalTrials.gov

    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

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

    MedlinePlus

    ... lymphocytic leukemia? What are the risk factors for acute lymphocytic leukemia? A risk factor is something that affects your ... this is unknown. Having an identical twin with ALL Someone who has an identical twin who develops ...

  8. Targeting MTHFD2 in acute myeloid leukemia.

    PubMed

    Pikman, Yana; Puissant, Alexandre; Alexe, Gabriela; Furman, Andrew; Chen, Liying M; Frumm, Stacey M; Ross, Linda; Fenouille, Nina; Bassil, Christopher F; Lewis, Caroline A; Ramos, Azucena; Gould, Joshua; Stone, Richard M; DeAngelo, Daniel J; Galinsky, Ilene; Clish, Clary B; Kung, Andrew L; Hemann, Michael T; Vander Heiden, Matthew G; Banerji, Versha; Stegmaier, Kimberly

    2016-06-27

    Drugs targeting metabolism have formed the backbone of therapy for some cancers. We sought to identify new such targets in acute myeloid leukemia (AML). The one-carbon folate pathway, specifically methylenetetrahydrofolate dehydrogenase-cyclohydrolase 2 (MTHFD2), emerged as a top candidate in our analyses. MTHFD2 is the most differentially expressed metabolic enzyme in cancer versus normal cells. Knockdown of MTHFD2 in AML cells decreased growth, induced differentiation, and impaired colony formation in primary AML blasts. In human xenograft and MLL-AF9 mouse leukemia models, MTHFD2 suppression decreased leukemia burden and prolonged survival. Based upon primary patient AML data and functional genomic screening, we determined that FLT3-ITD is a biomarker of response to MTHFD2 suppression. Mechanistically, MYC regulates the expression of MTHFD2, and MTHFD2 knockdown suppresses the TCA cycle. This study supports the therapeutic targeting of MTHFD2 in AML. PMID:27325891

  9. Sirolimus, Idarubicin, and Cytarabine in Treating Patients With Newly Diagnosed Acute Myeloid Leukemia

    ClinicalTrials.gov

    2016-06-03

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

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

    ClinicalTrials.gov

    2015-06-18

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

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

    ClinicalTrials.gov

    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

  12. Azacitidine and Gemtuzumab Ozogamicin in Treating Older Patients With Previously Untreated Acute Myeloid Leukemia

    ClinicalTrials.gov

    2016-09-20

    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 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; Secondary Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

  13. Comparing Three Different Combination Chemotherapy Regimens in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia

    ClinicalTrials.gov

    2015-07-02

    Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(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

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

    ClinicalTrials.gov

    2013-09-27

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

  15. Diagnosis of acute leukemia in cerebrospinal fluid (CSF-acute leukemia).

    PubMed

    Crespo-Solis, Erick; López-Karpovitch, Xavier; Higuera, Jesús; Vega-Ramos, Beatriz

    2012-10-01

    Cerebrospinal fluid-acute leukemia (CSF-acute leukemia) is a frequent and serious complication in patients with acute leukemia. One of the major problems of this complication is the diagnosis process itself. CSF cytology is currently considered the gold standard for establishing the diagnosis, a technique which presents various processing limitations, seriously impacting the predictive values. In the last 11 years, studies of CSF flow cytometry analysis done in patients with acute leukemia have demonstrated superiority in comparison with CSF cytology. Although comparative studies between these two techniques have been reported since 2001, no new consensus or formal changes to the gold standard have been established for the CSF acute leukemia diagnosis. The evidence suggests that positive flow cytometry cases, considered as indeterminate cases, will behave like disease in the central nervous system (CNS). Nevertheless, we think there are some variables and considerations that must be first evaluated under research protocols before CNS relapse can be established with only one positive flow cytometry analysis in the setting of indeterminate CSF samples. This paper proposes a diagnostic algorithm and complementary strategies. PMID:22639108

  16. Global Characteristics of Childhood Acute Promyelocytic Leukemia

    PubMed Central

    Zhang, L; Samad, A; Pombo-de-Oliveira, MS; Scelo, G; Smith, MT; Feusner, J; Wiemels, JL; Metayer, C

    2014-01-01

    Acute promyelocytic leukemia (APL) comprises approximately 5–10% of childhood acute myeloid leukemia (AML) cases in the US. While variation in this percentage among other populations was noted previously, global patterns of childhood APL have not been thoroughly characterized. In this comprehensive review of childhood APL, we examined its geographic pattern and the potential contribution of environmental factors to observed variation. In 142 studies (spanning >60 countries) identified, variation was apparent—de novo APL represented from 2% (Switzerland) to >50% (Nicaragua) of childhood AML in different geographic regions. Because a limited number of previous studies addressed specific environmental exposures that potentially underlie childhood APL development, we gathered 28 childhood cases of therapy-related APL, which exemplified associations between prior exposures to chemotherapeutic drugs/radiation and APL diagnosis. Future population-based studies examining childhood APL patterns and the potential association with specific environmental exposures and other risk factors are needed. PMID:25445717

  17. Leukemia.

    PubMed

    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

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

    ClinicalTrials.gov

    2016-10-10

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

  19. Brain Function in Young Patients Receiving Methotrexate for Acute Lymphoblastic Leukemia

    ClinicalTrials.gov

    2016-04-08

    Childhood B Acute Lymphoblastic Leukemia; Childhood T Acute Lymphoblastic Leukemia; Cognitive Side Effects of Cancer Therapy; Long-Term Effects Secondary to Cancer Therapy in Children; Neurotoxicity Syndrome; Psychological Impact of Cancer; Untreated Childhood Acute Lymphoblastic Leukemia

  20. Therapy Related Acute Myeloid Leukemia with t(8;16) Mimicking Acute Promyelocytic Leukemia.

    PubMed

    Chharchhodawala, Taher; Gajendra, Smeeta; Tiwari, Priya; Gogia, Ajay; Gupta, Ritu

    2016-06-01

    Acute myeloid leukemia (AML) with t(8;16)(p11;q13) is a distinct clinical and morphological entity with poor prognosis, which is characterized by a high frequency of extramedullary involvement, most commonly leukemia cutis; association with therapy related AML; frequent coagulopathy and morphologic features overlapping acute promyelocytic leukemia(APL). Herein, we present a case of 47 year-old post-menopausal woman developing secondary AML with t(8;16)(p11;q13) after 1 year of completion of therapy for breast carcinoma. Blasts were granulated with few showing clefted nucleus resembling promyelocytes and immnuophenotyping showed high side scatter with MPO positivity and CD 34 and HLA-DR negativity. In view of promyelocyte like morphology and immunophenotyping of blasts, possibility of APL was considered but, reverse transcription polymerase chain reaction (RT-PCR) for PML-RARα fusion transcript came out to be negative. Conventional cytogenetics showed t(8;16)(p11;q13). So, we should keep possibility of t(8;16) (p11;q13) in therapy related acute myeloid leukemia in patient showing clinical and morphological features of acute promyelocytic leukemia. PMID:27408347

  1. 7-Hydroxystaurosporine and Perifosine in Treating Patients With Relapsed or Refractory Acute Leukemia, Chronic Myelogenous Leukemia or High Risk Myelodysplastic Syndromes

    ClinicalTrials.gov

    2013-09-27

    Accelerated Phase Chronic Myelogenous Leukemia; Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Acute Promyelocytic Leukemia (M3); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Blastic Phase Chronic Myelogenous Leukemia; Myelodysplastic/Myeloproliferative Neoplasms; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Relapsing Chronic Myelogenous Leukemia; Secondary Acute Myeloid Leukemia; T-cell Adult Acute Lymphoblastic Leukemia; Untreated Adult Acute Lymphoblastic Leukemia; Untreated Adult Acute Myeloid Leukemia

  2. Vorinostat and Azacitidine in Treating Patients With Myelodysplastic Syndromes or Acute Myeloid Leukemia

    ClinicalTrials.gov

    2016-06-27

    Acute Erythroid Leukemia; Acute Megakaryoblastic Leukemia; Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome; Chronic Myelomonocytic Leukemia; Myelodysplastic Syndrome; Recurrent Adult Acute Myeloid Leukemia; Refractory Anemia; Refractory Anemia With Excess Blasts; Refractory Anemia With Excess Blasts in Transformation; Refractory Anemia With Ring Sideroblasts

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

    ClinicalTrials.gov

    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

  4. Combination Chemotherapy and Dasatinib in Treating Patients With Newly Diagnosed Acute Myeloid Leukemia

    ClinicalTrials.gov

    2016-07-19

    Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome; Adult Acute Myeloid Leukemia With Inv(16)(p13.1q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With t(16;16)(p13.1;q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); RUNX1-RUNX1T1; Secondary Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

  5. Tretinoin, Cytarabine, and Daunorubicin Hydrochloride With or Without Arsenic Trioxide Followed by Tretinoin With or Without Mercaptopurine and Methotrexate in Treating Patients With Acute Promyelocytic Leukemia

    ClinicalTrials.gov

    2013-06-04

    Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Promyelocytic Leukemia (M3); Childhood Acute Promyelocytic Leukemia (M3); Untreated Adult Acute Myeloid Leukemia; Untreated Childhood Acute Myeloid Leukemia and Other Myeloid Malignancies

  6. Leukemia

    MedlinePlus

    ... Acute leukemia in adults. In: Niederhuber JE, Armitage JO, Doroshow JH, Kastan MB, Tepper JE, eds. Abeloff's ... Pui CH. Childhood leukemia. In: Niederhuber JE, Armitage JO, Doroshow JH, Kastan MB, Tepper JE, eds. Abeloff's ...

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

    ClinicalTrials.gov

    2014-12-19

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

  8. Ipilimumab in Treating Patients With Relapsed or Refractory High-Risk Myelodysplastic Syndrome or Acute Myeloid Leukemia

    ClinicalTrials.gov

    2016-09-16

    Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome; Chronic Myelomonocytic Leukemia; Previously Treated Myelodysplastic Syndrome; Recurrent Adult Acute Myeloid Leukemia; Secondary Myelodysplastic Syndrome

  9. WEE1 Inhibitor AZD1775 With or Without Cytarabine in Treating Patients With Advanced Acute Myeloid Leukemia or Myelodysplastic Syndrome

    ClinicalTrials.gov

    2016-09-12

    Chronic Myelomonocytic Leukemia; Myelodysplastic Syndrome With Isolated Del(5q); Myelodysplastic/Myeloproliferative Neoplasm; Previously Treated Myelodysplastic Syndrome; Recurrent Adult Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

  10. Genetics Home Reference: cytogenetically normal acute myeloid leukemia

    MedlinePlus

    ... one form of a cancer of the blood-forming tissue (bone marrow) called acute myeloid leukemia. In ... 1 link) PubMed Sources for This Page Döhner H. Implication of the molecular characterization of acute myeloid ...

  11. [Acute monoblastic leukemia with tetrasomy 8].

    PubMed

    Kameoka, Junichi; Horiuchi, Takahiro; Miyamura, Koichi; Miura, Ikuo; Okuda, Mitsutaka; Nomura, Jun; Hirokawa, Makoto; Sawada, Kenichi; Sasaki, Takeshi

    2006-08-01

    Tetrasomy 8 is a rare chromosomal abnormality in acute leukemia, and it has recently been considered as a poor prognostic factor. A 20-year-old woman was admitted because of purpura on the upper and lower limbs in February 2002. On admission, her leukocyte count was 6.5 x 10(9)/l with 66% of blasts, the hemoglobin level was 11.2 g/dl, and the platelet count was 101 x 10(9)/l. The bone marrow aspirate contained 85.6% of peroxidase-negative, alpha-naphthyl-butyrate esterase-positive, and CD4+ CD56+ blast cells. Karyotypic analysis of the bone marrow cells showed 48, XY, + 8, + 8[17]/47, XY, +8[3]. The patient was diagnosed as having AML (M5a), and treatment with daunorubicin (70 mg x 5 days) and cytosine arabinoside (150 mg x 7 days) resulted in a complete remission. She relapsed four months later, however, with an extramedullary tumor in T12. Remission could not be achieved, and the patient underwent allogeneic peripheral blood stem cell transplantation from her HLA-identical mother. Her clinical course was almost uneventful except for a phlegmon in the right leg, but on day 49 a relapse occurred, and she died of acute renal failure on day 73. This case strongly illustrates the characteristic of tetrasomy 8 as a poor prognostic factor in acute leukemia. PMID:16986717

  12. Does hematopoietic stem cell transplantation benefit infants with acute leukemia?

    PubMed Central

    Sison, Edward Allan R.; Brown, Patrick

    2015-01-01

    A 6-month-old girl was diagnosed with acute lymphoblastic leukemia (ALL). She has completed induction therapy and is currently in first complete remission (CR1). You are asked by your resident if hematopoietic stem cell transplantation (HSCT) would benefit infants with acute leukemia. PMID:24319238

  13. Donor Peripheral Blood Stem Cell Transplant and Pretargeted Radioimmunotherapy in Treating Patients With High-Risk Advanced Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia, or Myelodysplastic Syndrome

    ClinicalTrials.gov

    2016-03-01

    Chronic Myelomonocytic Leukemia; Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable; Previously Treated Myelodysplastic Syndrome; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Refractory Anemia With Excess Blasts; Refractory Cytopenia With Multilineage Dysplasia; Refractory Cytopenia With Multilineage Dysplasia and Ringed Sideroblasts; Secondary Acute Myeloid Leukemia

  14. Alvocidib, Cytarabine, and Mitoxantrone Hydrochloride or Cytarabine and Daunorubicin Hydrochloride in Treating Patients With Newly Diagnosed Acute Myeloid Leukemia

    ClinicalTrials.gov

    2014-10-10

    Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome; 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

  15. Early Discharge and Outpatients Care in Patients With Myelodysplastic Syndrome or Acute Myeloid Leukemia Previously Treated With Intensive Chemotherapy

    ClinicalTrials.gov

    2015-02-05

    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; Recurrent Adult Acute Myeloid Leukemia

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

    ClinicalTrials.gov

    2016-10-24

    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

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

    ClinicalTrials.gov

    2013-09-27

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

  18. Chalcone glycosides isolated from aerial parts of Brassica rapa L. 'hidabeni' suppress antigen-stimulated degranulation in rat basophilic leukemia RBL-2H3 cells.

    PubMed

    Itoh, Tomohiro; Ninomiya, Masayuki; Nozawa, Yoshinori; Koketsu, Mamoru

    2010-10-01

    We isolated three chalcone glycosides along with other glycoside constituents from the aerial parts of Brassica rapa L. 'hidabeni' and examined the effects of these compounds on the antigen-stimulated degranulation in rat basophilic leukemia RBL-2H3 cells. Treatments with both 4'-O-β-D-glucopyranosyl-4-hydroxy-3'-methoxychalcone (C1) and 4'-O-β-D-glucopyranosyl-3',4-dimethoxychalcone (C2) markedly inhibited antigen (Ag)-stimulated degranulation. To gain further insight into the inhibitory mechanisms by C1 and C2, we examined early intracellular signaling events, Ca(2+) mobilization and intracellular reactive oxygen species (ROS) production. Both C1 and C2 did not affect early intracellular signaling events but exhibited the suppression of intracellular ROS production through NADPH oxidase (NOX) inactivation. From these results, we proposed that the inhibitory effects of C1 and C2 on Ag-stimulated degranulation were mainly due to suppression of intracellular Ca(2+) elevation by suppression of intracellular ROS production through NOX inactivation. Our findings suggest that C1 and C2 would be beneficial to alleviate symptoms of type I allergy.

  19. OM-X®, Fermented Vegetables Extract Suppresses Antigen-Stimulated Degranulation in Rat Basophilic Leukemia RBL-2H3 Cells and Passive Cutaneous Anaphylaxis Reaction in Mice.

    PubMed

    Itoh, Tomohiro; Miyake, Yasuyoshi; Kasashima, Takuya; Shimomiya, Yoshie; Nakamura, Yuki; Ando, Masashi; Tsukamasa, Yasuyuki; Takahata, Muneaki

    2015-09-01

    OM-X® is a hand-made and naturally manufactured probiotic supplement. This fermented food product is made from vegetables, fruits, seaweeds and mushrooms, using 12 strains of lactic acid bacteria and bifidobacteria. OM-X® is also known to have beneficial health properties, and some of its components show effects on antigen (Ag)-stimulated degranulation activity, indicating that OM-X® may be useful in the treatment of allergy responses and symptoms. In this study, we evaluated the inhibitory effects of OM-X® on Ag-stimulated degranulation in rat basophilic leukemia RBL-2H3 cells, clarified the underlying mechanisms, and determined the active compounds in OM-X® for suppression of degranulation. Treatment with OM-X® gradually suppressed Ag-stimulated degranulation throughout the maturation period. OM-X® also gradually produced melanoidins by lactic acid bacterial fermentation during the maturation process. There was a high correlation between the suppression levels of Ag-stimulated degranulation and the browning of OM-X®. Furthermore, the inhibition of Ag-stimulated degranulation by OM-X® was found to be partially due to the direct inactivation of NADPH oxidase. To elucidate the in vivo effects of OM- X®, type I allergy model mice were orally administered with OM-X®, and the passive cutaneous anaphylaxis (PCA) reaction was measured. OM-X® intake remarkably suppressed the PCA reaction. Taken together, our findings suggest that OMX® could be a beneficial food to ameliorate allergic reactions.

  20. Controlled-release formulation of antihistamine based on cetirizine zinc-layered hydroxide nanocomposites and its effect on histamine release from basophilic leukemia (RBL-2H3) cells

    PubMed Central

    Hasan, Samer; Ali, Hussein Al; Al-Qubaisi, Mothanna; Hussein, Mohd Zobir; Ismail, Maznah; Zainal, Zulkarnain; Hakim, Muhammad Nazrul

    2012-01-01

    A controlled-release formulation of an antihistamine, cetirizine, was synthesized using zinc-layered hydroxide as the host and cetirizine as the guest. The resulting well-ordered nanolayered structure, a cetirizine nanocomposite “CETN,” had a basal spacing of 33.9 Å, averaged from six harmonics observed from X-ray diffraction. The guest, cetirizine, was arranged in a horizontal bilayer between the zinc-layered hydroxide (ZLH) inorganic interlayers. Fourier transform infrared spectroscopy studies indicated that the intercalation takes place without major change in the structure of the guest and that the thermal stability of the guest in the nanocomposites is markedly enhanced. The loading of the guest in the nanocomposites was estimated to be about 49.4% (w/w). The release study showed that about 96% of the guest could be released in 80 hours by phosphate buffer solution at pH 7.4 compared with about 97% in 73 hours at pH 4.8. It was found that release was governed by pseudo-second order kinetics. Release of histamine from rat basophilic leukemia cells was found to be more sensitive to the intercalated cetirizine in the CETN compared with its free counterpart, with inhibition of 56% and 29%, respectively, at 62.5 ng/mL. The cytotoxicity assay toward Chang liver cells line show the IC50 for CETN and ZLH are 617 and 670 μg/mL, respectively. PMID:22848164

  1. High-Risk Childhood Acute Lymphoblastic Leukemia

    PubMed Central

    Bhojwani, Deepa; Howard, Scott C.; Pui, Ching-Hon

    2009-01-01

    Although most children with acute lymphoblastic leukemia (ALL) are cured, certain subsets have a high risk of relapse. Relapse risk can be predicted by early response to therapy, clinical and pharmacogenetic features of the host, and genetic characteristics of leukemic cells. Though early treatment response can be assessed by the peripheral blast cell count after 1 week of single-agent glucocorticoid treatment or percent of bone marrow blasts by morphology after 1 or 2 weeks of multiagent induction treatment, determination of minimal residual disease by polymerase chain reaction (PCR) or flow cytometry after 2 to 6 weeks of induction is the most precise and useful measure. Augmented therapy has improved outcome for the poor responders to initial treatment. Infants with mixed-lineage leukemia (MLL)–rearranged ALL comprise a very poor-risk group wherein further intensification of chemotherapy causes significant toxicity. Hybrid protocols incorporating drugs effective for acute myeloid leukemia could improve survival, a strategy being tested in international trials. Studies on the biology of MLL-induced leukemogenesis have prompted the development of novel targeted agents, currently under evaluation in clinical trials. Short-term outcomes of patients with Philadelphia chromosome (Ph)–positive ALL have improved significantly by adding tyrosine kinase inhibitors to standard chemotherapy regimens. New agents and methods to overcome resistance are under investigation, and allogeneic stem cell transplantation is recommended for certain subsets of patients, for example those with Ph+ and T-cell ALL with poor early response. Genome-wide interrogation of leukemic cell genetic abnormalities and germline genetic variations promise to identify new molecular targets for therapy. PMID:19778845

  2. Molecular Genetic Markers in Acute Myeloid Leukemia

    PubMed Central

    Yohe, Sophia

    2015-01-01

    Genetics play an increasingly important role in the risk stratification and management of acute myeloid leukemia (AML) patients. Traditionally, AML classification and risk stratification relied on cytogenetic studies; however, molecular detection of gene mutations is playing an increasingly important role in classification, risk stratification, and management of AML. Molecular testing does not take the place of cytogenetic testing results, but plays a complementary role to help refine prognosis, especially within specific AML subgroups. With the exception of acute promyelocytic leukemia, AML therapy is not targeted but the intensity of therapy is driven by the prognostic subgroup. Many prognostic scoring systems classify patients into favorable, poor, or intermediate prognostic subgroups based on clinical and genetic features. Current standard of care combines cytogenetic results with targeted testing for mutations in FLT3, NPM1, CEBPA, and KIT to determine the prognostic subgroup. Other gene mutations have also been demonstrated to predict prognosis and may play a role in future risk stratification, although some of these have not been confirmed in multiple studies or established as standard of care. This paper will review the contribution of cytogenetic results to prognosis in AML and then will focus on molecular mutations that have a prognostic or possible therapeutic impact. PMID:26239249

  3. Nanomedicine approaches in acute lymphoblastic leukemia.

    PubMed

    Tatar, Andra-Sorina; Nagy-Simon, Timea; Tomuleasa, Ciprian; Boca, Sanda; Astilean, Simion

    2016-09-28

    Acute lymphoblastic leukemia (ALL) is the malignancy with the highest incidence amongst children (26% of all cancer cases), being surpassed only by the cancers of the brain and of the nervous system. The most recent research on ALL is focusing on new molecular therapies, like targeting specific biological structures in key points in the cell cycle, or using selective inhibitors for transmembranary proteins involved in cell signalling, and even aiming cell surface receptors with specifically designed antibodies for active targeting. Nanomedicine approaches, especially by the use of nanoparticle-based compounds for the delivery of drugs, cancer diagnosis or therapeutics may represent new and modern ways in the near future anti-cancer therapies. This review offers an overview on the recent role of nanomedicine in the detection and treatment of acute lymphoblastic leukemia as resulting from a thorough literature survey. A short introduction on the basics of ALL is presented followed by the description of the conventional methods used in the ALL detection and treatment. We follow our discussion by introducing some of the general nano-strategies used for cancer detection and treatment. The detailed role of organic and inorganic nanoparticles in ALL applications is further presented, with a special focus on gold nanoparticle-based nanocarriers of antileukemic drugs. PMID:27460684

  4. Nanomedicine approaches in acute lymphoblastic leukemia.

    PubMed

    Tatar, Andra-Sorina; Nagy-Simon, Timea; Tomuleasa, Ciprian; Boca, Sanda; Astilean, Simion

    2016-09-28

    Acute lymphoblastic leukemia (ALL) is the malignancy with the highest incidence amongst children (26% of all cancer cases), being surpassed only by the cancers of the brain and of the nervous system. The most recent research on ALL is focusing on new molecular therapies, like targeting specific biological structures in key points in the cell cycle, or using selective inhibitors for transmembranary proteins involved in cell signalling, and even aiming cell surface receptors with specifically designed antibodies for active targeting. Nanomedicine approaches, especially by the use of nanoparticle-based compounds for the delivery of drugs, cancer diagnosis or therapeutics may represent new and modern ways in the near future anti-cancer therapies. This review offers an overview on the recent role of nanomedicine in the detection and treatment of acute lymphoblastic leukemia as resulting from a thorough literature survey. A short introduction on the basics of ALL is presented followed by the description of the conventional methods used in the ALL detection and treatment. We follow our discussion by introducing some of the general nano-strategies used for cancer detection and treatment. The detailed role of organic and inorganic nanoparticles in ALL applications is further presented, with a special focus on gold nanoparticle-based nanocarriers of antileukemic drugs.

  5. Cancer procoagulant in acute lymphoblastic leukemia.

    PubMed

    Alessio, M G; Falanga, A; Consonni, R; Bassan, R; Minetti, B; Donati, M B; Barbui, T

    1990-08-01

    In a previous study we characterized cancer procoagulant (CP), a 68 kd cysteine proteinase which directly activates coagulation factor X in various subtypes (from M1 to M5) of acute non-lymphoblastic leukemia (ANLL). The aim of this study was to determine whether CP is also expressed by acute lymphoblastic leukemia (ALL) cells. Blasts from 25 ALL patients were extracted and tested for their procoagulant properties. 16 samples (64%) shortened the recalcification time of normal human plasma, and 9 (36%) did not. 8 of the 16 active samples showed properties compatible with CP, i.e. independence from factor VII in triggering blood coagulation and sensitivity to cysteine proteinase inhibitors. Selected samples also cross-reacted with a polyclonal antibody raised against purified CP. The specific activity of CP in ALL extracts was significantly lower than in most ANLL types previously studied (all but M4). These finding indicate that CP can be a property of the lymphoid phenotype although its expression may be lower than in the myeloid phenotype.

  6. Dasatinib and Combination Chemotherapy in Treating Young Patients With Newly Diagnosed Acute Lymphoblastic Leukemia

    ClinicalTrials.gov

    2016-09-08

    Adult B Acute Lymphoblastic Leukemia With t(9;22)(q34;q11.2); BCR-ABL1; Childhood B Acute Lymphoblastic Leukemia With t(9;22)(q34;q11.2); BCR-ABL1; Untreated Adult Acute Lymphoblastic Leukemia; Untreated Childhood Acute Lymphoblastic Leukemia

  7. Sorafenib Tosylate and Chemotherapy in Treating Older Patients With Acute Myeloid Leukemia

    ClinicalTrials.gov

    2016-07-05

    Acute Myeloid Leukemia (Megakaryoblastic) With t(1;22)(p13;q13); RBM15-MKL1; Acute Myeloid Leukemia With a Variant RARA Translocation; Acute Myeloid Leukemia With Inv(3)(q21q26.2) or t(3;3)(q21;q26.2); RPN1-EVI1; Acute Myeloid Leukemia With t(6;9)(p23;q34); DEK-NUP214; Acute Myeloid Leukemia With t(9;11)(p22;q23); MLLT3-MLL; Acute Myeloid Leukemia With Variant MLL Translocations; Untreated Adult Acute Myeloid Leukemia

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

    PubMed

    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

  9. Cyclosporine, Pravastatin Sodium, Etoposide, and Mitoxantrone Hydrochloride in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia

    ClinicalTrials.gov

    2012-06-18

    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

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

    ClinicalTrials.gov

    2014-12-22

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

  11. 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

    ClinicalTrials.gov

    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

  12. New Strategies in Acute Myelogenous Leukemia: Leukemogenesis and Personalized Medicine

    PubMed Central

    Gojo, Ivana; Karp, Judith E.

    2014-01-01

    Recent advances in molecular technology have unraveled the complexity of leukemogenesis and provided the opportunity to design more personalized and pathophysiology-targeted therapeutic strategies. Despite the use of intensive chemotherapy, relapse remains the most common cause for therapeutic failure in acute myelogenous leukemia (AML). The interactions between leukemia stem cells (LSC) and marrow microenvironment appear to be critical in promoting therapeutic resistance through progressive acquisition of genetic and epigenetic changes within leukemia cells and immune evasion, resulting in leukemia cell survival. With advances in genomic sequencing efforts, epigenetic and phenotypic characterization, personalized therapeutic strategies aimed at critical leukemia survival mechanisms may be feasible in the near future. Here, we review select novel approaches to therapy of AML such as targeting LSC, altering leukemia/marrow microenvironment interactions, inhibiting DNA repair or cell cycle checkpoints, and augmenting immune-based anti-leukemia activity. PMID:25324141

  13. Is Acute Myeloid Leukemia a Liquid Tumor?

    PubMed Central

    Ohanian, Maro; Faderl, Stefan; Ravandi, Farhad; Pemmaraju, Naveen; Garcia-Manero, Guillermo; Cortes, Jorge; Estrov, Zeev

    2014-01-01

    Extramedullary manifestations of acute myeloid leukemia (AML) were described as early as the 19th century. However, the incidence, clinical significance, and pathobiology of extramedullary AML remain ill defined. We reviewed case reports, retrospective case series, pilot studies, and imaging studies of extramedullary leukemia (EML) to determine its frequency, characteristics, clinical presentation, and significance. EML precedes or accompanies development of AML and occurs during or following treatment, even during remission. Although imaging studies are rarely conducted and the true incidence of EML has yet to be verified, authors have reported several estimates based on retrospective and autopsy studies. The incidence of EML in patients with AML of all ages is estimated to be about 9% and EML in children with AML was detected in 40% of patients at diagnosis. The combination of positron emission tomography and computed tomography were the most sensitive and reliable techniques of detecting and monitoring EML. Based on our literature review, the frequency of EML is likely underreported. The well-documented nature of EML in AML patients suggests that AML can manifest as a solid tumor. The extent to which EML accompanies AML and whether EML is derived from bone marrow are unknown. Furthermore, questions remain regarding the role of the microenvironment, which may or may not facilitate the survival and proliferation of EML, and the implications of these interactions with regard to minimal residual disease, tumor cell quiescence, and relapse. Therefore, prospective studies of detection and characterization of EML in AML patients are warranted. PMID:23280377

  14. MINIMAL RESIDUAL DISEASE IN ACUTE LYMPHOBLASTIC LEUKEMIA

    PubMed Central

    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 adult patients also support its prognostic value. Hence, results of MRD studies can be used to select treatment intensity and duration, and 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, 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 clarifying the cellular and biologic features of leukemic cells that resist chemotherapy in vivo. PMID:19100372

  15. Acute lymphoblastic leukemia and developmental biology

    PubMed Central

    Campos-Sanchez, Elena; Toboso-Navasa, Amparo; Romero-Camarero, Isabel; Barajas-Diego, Marcos

    2011-01-01

    The latest scientific findings in the field of cancer research are redefining our understanding of the molecular and cellular basis of the disease, moving the emphasis toward the study of the mechanisms underlying the alteration of the normal processes of cellular differentiation. The concepts best exemplifying this new vision are those of cancer stem cells and tumoral reprogramming. The study of the biology of acute lymphoblastic leukemias (ALLs) has provided seminal experimental evidence supporting these new points of view. Furthermore, in the case of B cells, it has been shown that all the stages of their normal development show a tremendous degree of plasticity, allowing them to be reprogrammed to other cellular types, either normal or leukemic. Here we revise the most recent discoveries in the fields of B-cell developmental plasticity and B-ALL research and discuss their interrelationships and their implications for our understanding of the biology of the disease. PMID:22031225

  16. Minimal residual disease in acute promyelocytic leukemia.

    PubMed

    Weil, S C

    2000-03-01

    In the last decade our understanding of acute promyelocytic leukemia (APL) has advanced tremendously. The recognition of all-trans retinoic acid (ATRA) as a powerful therapeutic agent paralleled the cloning of the t(15;17) breakpoint. RtPCR for the PML-RARA hybrid mRNA has become the hallmark of molecular diagnosis and molecular monitoring in APL. Current techniques are useful in predicting complete remission and a possible cure in many patients who repeatedly test negative by PCR. Standardizing techniques and improving the sensitivity of the assay are important. Doing this in a way so that clinically relevant minimal residual disease can be distinguished from "indolent disease" remains among the future challenges in APL. PMID:10702899

  17. Pharmacogenetics of childhood acute lymphoblastic leukemia.

    PubMed

    Lopez-Lopez, Elixabet; Gutierrez-Camino, Angela; Bilbao-Aldaiturriaga, Nerea; Pombar-Gomez, Maria; Martin-Guerrero, Idoia; Garcia-Orad, Africa

    2014-07-01

    Acute lymphoblastic leukemia (ALL) is the major pediatric cancer in developed countries. Although treatment outcome has improved owing to advances in chemotherapy, there is still a group of patients for which therapy fails while some patients experience severe toxicity. In the last few years, several pharmacogenetic studies have been performed to search for markers of outcome and toxicity in pediatric ALL. However, to date, TPMT is the only pharmacogenetic marker in ALL with clinical guidelines for drug dosing. In this article, we will provide an overview of the most important findings carried out in pharmacogenetics for pediatric ALL, such as the interest drawn by methotrexate transporters in the context of methotrexate treatment. Even if most of the studies are centered on coding genes, we will also point to new approaches focusing on noncoding regions and epigenetic variation that could be interesting for consideration in the near future.

  18. Perinatal risk factors for acute myeloid leukemia.

    PubMed

    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 < 0.001), with peak risk among persons born in winter. Relative to persons born in summer (June-August), incidence rate ratios for AML were 1.72 (95 % CI 1.25-2.38; P = 0.001) for winter (December-February), 1.37 (95 % CI 0.99-1.90; P = 0.06) for spring (March-May), and 1.27 (95 % CI 0.90-1.80; P = 0.17) for fall (September-November). Other risk factors for AML included high fetal growth, high gestational age at birth, and low maternal education level. These findings did not vary by sex or age at diagnosis. Sex, 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.

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

    ClinicalTrials.gov

    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

  20. Adult Acute Myeloid Leukemia Long-term Survivors

    PubMed Central

    Cheng, M. Jennifer; Hourigan, Christopher S.; Smith, Thomas J.

    2014-01-01

    The number of leukemia patients and survivors is growing. This review summarizes what is known regarding the health related quality of life (HRQOL) and medical complications associated with acute myeloid leukemia (AML) disease and treatment and highlights understudied aspects of adult AML survivorship care, and potential novel areas for intervention. PMID:25243197

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

    ClinicalTrials.gov

    2016-07-26

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

  2. Binding of monoclonal antibody AA4 to gangliosides on rat basophilic leukemia cells produces changes similar to those seen with Fc epsilon receptor activation

    PubMed Central

    1992-01-01

    The mAb AA4 binds to novel derivatives of the ganglioside Gd1b on rat basophilic leukemia (RBL-2H3) cells. Some of the gangliosides are located close to the high affinity IgE receptor (Fc epsilon RI), and binding of mAb AA4 inhibits Fc epsilon RI-mediated histamine release. In the present study, mAb AA4 was found to bind exclusively to mast cells in all rat tissues examined. In vitro, within 1 min of mAb AA4 binding, the cells underwent striking morphologic changes. They lost their normal spindle shaped appearance, increased their ruffling, and spread over the surface of the culture dish. These changes were accompanied by a redistribution of the cytoskeletal elements, actin, tubulin, and vimentin, but only the actin was associated with the membrane ruffles. Binding of mAb AA4 also induces a rise in intracellular calcium, stimulates phosphatidyl inositol breakdown, and activates PKC. However, the extent of these changes was less than that observed when the cells were stimulated with antigen or antibody directed against the Fc epsilon RI. None of these changes associated with mAb AA4 binding were seen when the cells were exposed to nonspecific IgG, IgE, or four other anti-cell surface antibodies, nor were the changes induced by binding mAb AA4 at 4 degrees C or in the absence of extracellular calcium. Although mAb AA4 does not stimulate histamine release, it enhances the effect of the calcium ionophore A23187 mediated release. The morphological and biochemical effects produced by mAb AA4 are similar to those seen following activation of the cell through the IgE receptor. Therefore, the surface gangliosides which bind mAb AA4 may function in modulating secretory events. PMID:1370498

  3. Evaluation of an in vitro method for the measurement of specific IgE antibody responses: the rat basophilic leukemia (RBL) cell assay.

    PubMed

    Dearman, R J; Skinner, R A; Deakin, N; Shaw, D; Kimber, I

    2005-01-15

    The evaluation of allergenic potential is a key parameter in the safety assessment of novel proteins, including those expressed in genetically modified crops and foodstuffs. The majority of allergic reactions to food proteins are immediate type hypersensitivity reactions in which the principal biological effector is IgE antibody; the accurate measurement of specific IgE antibody is therefore a critical factor in experimental systems designed to characterize protein allergenic potential. Due to the presence of much higher concentrations of other immunoglobulin isotypes, the assessment of specific serum IgE antibody poses substantial technical challenges. We have examined the utility of the rat basophilic leukemia (RBL) cell line for the measurement of murine IgE responses. RBL cells were sensitized with mouse monoclonal anti-dinitrophenyl (DNP) IgE antibody and challenged with DNP-albumin conjugates with various hapten substitution ratios (SR). Polyclonal anti-OVA IgE antisera were also assessed for activity in the RBL assay. Results were compared with titers measured in homologous passive cutaneous anaphylaxis (PCA) assay. Marked degranulation of RBL cells was induced by conjugates with SRs of between 16 and 32, whereas conjugates with lower SRs (of 10 or 3) failed to elicit significant serotonin release. All conjugates were able to induce mast cell degranulation in vivo in a PCA assay. Anti-OVA antisera with PCA titers of 1/32 to 1/64 failed to stimulate RBL cell degranulation, whereas high titer antibody (1/2048 to 1/4096 by PCA) induced a positive RBL cell response. Successful stimulation of RBL cell degranulation requires not only appropriate epitope densities but also high affinity antibody. These data indicate that this assay is inappropriate for the routine analysis of specific polyclonal IgE antibody responses such as those that are induced by exposure to complex protein allergens.

  4. Combination Chemotherapy in Treating Young Patients With Newly Diagnosed High-Risk B Acute Lymphoblastic Leukemia and Ph-Like TKI Sensitive Mutations

    ClinicalTrials.gov

    2016-11-02

    B Acute Lymphoblastic Leukemia; Bone Necrosis; Central Nervous System Leukemia; Cognitive Side Effects of Cancer Therapy; Neurotoxicity Syndrome; Pain; Testicular Leukemia; Therapy-Related Toxicity; Untreated Adult Acute Lymphoblastic Leukemia; Untreated Childhood Acute Lymphoblastic Leukemia

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

    PubMed Central

    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

  6. Endometrial and acute myeloid leukemia cancer genomes characterized

    Cancer.gov

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

  7. Agents for refractory/relapsed acute lymphocytic leukemia in adults.

    PubMed

    Qian, L-R; Fu, W; Shen, J-L

    2014-01-01

    Although treatment results for adult acute lymphoblastic leukemia (ALL) have improved considerably in the past decades, treating adult patients with relapsed/refractory acute lymphocytic leukemia (ALL) is still difficult. Adults with refractory/relapsed acute lymphocytic leukemia (ALL) processed to death rapidly associated with chemotherapy resistance, high mortality by reinduction, etc. Only 20% to 30% of those patients acquired complete remission (CR). Those patients are always of short duration unless an allogeneic stem cell transplant is feasible. Median survival is only ranging from 2 to 12 months. Therapeutic strategy on relapsed/refractory acute lymphocytic leukemia (ALL) is always a major therapeutic challenge bothering hematological researchers. Novel agents and unique therapeutic strategies have been developed in recent years. This review focuses on major clinical advances in the agents for refractory/relapsed ALL.

  8. Genetics Home Reference: familial acute myeloid leukemia with mutated CEBPA

    MedlinePlus

    ... N. A family harboring a germ-line N-terminal C/EBPalpha mutation and development of acute myeloid leukemia with an additional somatic C-terminal C/EBPalpha mutation. Genes Chromosomes Cancer. 2010 Mar; ...

  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

    ClinicalTrials.gov

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

    ClinicalTrials.gov

    2013-10-09

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

  11. Novel and Emerging Drugs for Acute Myeloid Leukemia

    PubMed Central

    Stein, E.M.; Tallman, M.S.

    2014-01-01

    Acute myeloid leukemia (AML) is a challenging disease to treat with the majority of patients dying from their illness. While overall survival has been markedly prolonged in acute promyelocytic leukemia (APL), survival in younger adults with other subtypes of AML has only modestly improved over the last twenty years. Physicians who treat AML eagerly await drugs like Imatinib for chronic myeloid leukemia, Cladribine for hairy cell leukemia, and Rituximab for non-Hodgkin Lymphoma which have had an important impact on improving outcome. Recent research efforts have focused on refining traditional chemotherapeutic agents to make them more active in AML, targeting specific genetic mutations in myeloid leukemia cells, and utilizing novel agents such as Lenalidomide that have shown activity in other hematologic malignancies. Here, we focus on reviewing the recent literature on agents that may assume a role in clinical practice for patients with AML over the next five years. PMID:22483153

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

    ClinicalTrials.gov

    2016-07-19

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

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

    ClinicalTrials.gov

    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

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

    ClinicalTrials.gov

    2016-09-07

    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

  15. Reduced Intensity Donor Peripheral Blood Stem Cell Transplant in Treating Patients With De Novo or Secondary Acute Myeloid Leukemia in Remission

    ClinicalTrials.gov

    2016-01-19

    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 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); Secondary Acute Myeloid Leukemia

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

    ClinicalTrials.gov

    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

  17. Tacrolimus and Methotrexate With or Without Sirolimus in Preventing Graft-Versus-Host Disease in Young Patients Undergoing Donor Stem Cell Transplant for Acute Lymphoblastic Leukemia in Complete Remission

    ClinicalTrials.gov

    2014-01-23

    B-cell Childhood Acute Lymphoblastic Leukemia; Childhood Acute Lymphoblastic Leukemia in Remission; Graft Versus Host Disease; L1 Childhood Acute Lymphoblastic Leukemia; L2 Childhood Acute Lymphoblastic Leukemia; T-cell Childhood Acute Lymphoblastic Leukemia

  18. Childhood Acute Lymphoblastic Leukemia: Progress Through Collaboration

    PubMed Central

    Yang, Jun J.; Hunger, Stephen P.; Pieters, Rob; Schrappe, Martin; Biondi, Andrea; Vora, Ajay; Baruchel, André; Silverman, Lewis B.; Schmiegelow, Kjeld; Escherich, Gabriele; Horibe, Keizo; Benoit, Yves C.M.; Izraeli, Shai; Yeoh, Allen Eng Juh; Liang, Der-Cherng; Downing, James R.; Evans, William E.; Relling, Mary V.; Mullighan, Charles G.

    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 reviewed and revised by the committee chairs of the major ALL study groups. Results With long-term survival rates for ALL approaching 90% and the advent of high-resolution genome-wide analyses, several international study groups or consortia were established to conduct collaborative research to further improve outcome. As a result, treatment strategies have been improved for several subtypes of ALL, such as infant, MLL-rearranged, Philadelphia chromosome–positive, and Philadelphia chromosome–like ALL. Many recurrent genetic abnormalities that respond to tyrosine kinase inhibitors and multiple genetic determinants of drug resistance and toxicities have been identified to help develop targeted therapy. Several genetic polymorphisms have been recognized that show susceptibility to developing ALL and that help explain the racial/ethnic differences in the incidence of ALL. Conclusion The information gained from collaborative studies has helped decipher the heterogeneity of ALL to help improve personalized treatment, which will further advance the current high cure rate and the quality of life for children and adolescents with ALL. PMID:26304874

  19. The Epigenetic Landscape of Acute Myeloid Leukemia

    PubMed Central

    Conway O'Brien, Emma

    2014-01-01

    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. PMID:24778653

  20. Acute myeloid leukemia masquerading as hepatocellular carcinoma

    PubMed Central

    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

  1. Epigenetic deregulation in pediatric acute lymphoblastic leukemia

    PubMed Central

    Chatterton, Zac; Morenos, Leah; Mechinaud, Francoise; Ashley, David M; Craig, Jeffrey M; Sexton-Oates, Alexandra; Halemba, Minhee S; Parkinson-Bates, Mandy; Ng, Jane; Morrison, Debra; Carroll, William L; Saffery, Richard; Wong, Nicholas C

    2014-01-01

    Similar to most cancers, genome-wide DNA methylation profiles are commonly altered in pediatric acute lymphoblastic leukemia (ALL); however, recent observations highlight that a large portion of malignancy-associated DNA methylation alterations are not accompanied by related gene expression changes. By analyzing and integrating the methylome and transcriptome profiles of pediatric B-cell ALL cases and primary tissue controls, we report 325 genes hypermethylated and downregulated and 45 genes hypomethylated and upregulated in pediatric B-cell ALL, irrespective of subtype. Repressed cation channel subunits and cAMP signaling activators and transducers are overrepresented, potentially indicating a reduced cellular potential to receive and propagate apoptotic signals. Furthermore, we report specific DNA methylation alterations with concurrent gene expression changes within individual ALL subtypes. The ETV6-RUNX1 translocation was associated with downregulation of ASNS and upregulation of the EPO-receptor, while Hyperdiploid patients (>50 chr) displayed upregulation of B-cell lymphoma (BCL) members and repression of PTPRG and FHIT. In combination, these data indicate genetically distinct B-cell ALL subtypes contain cooperative epimutations and genome-wide epigenetic deregulation is common across all B-cell ALL subtypes. PMID:24394348

  2. Acute lymphoblastic leukemia: age and biology.

    PubMed

    Foà, Robin

    2011-06-22

    Acute lymphoblastic leukemia (ALL) is the most frequent neoplasm in children, while being relatively rare in adults. The outcome of children with ALL is far superior than that observed in adults, whose survival rates generally do not exceed 40%. A retrospective analysis recently carried out on a large series of cases enrolled in the AIEOP and GIMEMA protocols for the treatment of pediatric and adult ALL has documented specific differences among the various age cohorts examined, particularly in terms of incidence of molecular rearrangements, with the BCR/ABL rearrangement being detected in more than half of patients in the 6(th) decade of life. These findings highlight the importance of a precise diagnostic screening at all ages, since elderly patients might benefit more from targeted approaches, that are associated with less toxic effects. Furthermore, extended biologic approaches aimed at identifying novel therapeutic targets should be regarded as a main goal to refine our therapeutic armamentarium.Finally, the introduction of pediatric-like protocols is progressively changing the outcome of young adult patients, although an important caveat is represented by the comorbidities and toxic effects associated with more aggressive chemotherapy; therefore, patients' fitness should always be carefully considered.

  3. Diffuse Alveolar Hemorrhage in Acute Myeloid Leukemia.

    PubMed

    Nanjappa, Sowmya; Jeong, Daniel K; Muddaraju, Manjunath; Jeong, Katherine; Hill, Ebone D; Greene, John N

    2016-07-01

    Diffuse alveolar hemorrhage is a potentially fatal pulmonary disease syndrome that affects individuals with hematological and nonhematological malignancies. The range of inciting factors is wide for this syndrome and includes thrombocytopenia, underlying infection, coagulopathy, and the frequent use of anticoagulants, given the high incidence of venous thrombosis in this population. Dyspnea, fever, and cough are commonly presenting symptoms. However, clinical manifestations can be variable. Obvious bleeding (hemoptysis) is not always present and can pose a potential diagnostic challenge. Without prompt treatment, hypoxia that rapidly progresses to respiratory failure can occur. Diagnosis is primarily based on radiological and bronchoscopic findings. This syndrome is especially common in patients with hematological malignancies, given an even greater propensity for thrombocytopenia as a result of bone marrow suppression as well as the often prolonged immunosuppression in this patient population. The syndrome also has an increased incidence in individuals with hematological malignancies who have received a bone marrow transplant. We present a case series of 5 patients with acute myeloid leukemia presenting with diffuse alveolar hemorrhage at our institution. A comparison of clinical manifestations, radiographic findings, treatment course, and outcomes are described. A review of the literature and general overview of the diagnostic evaluation, differential diagnoses, pathophysiology, and treatment of this syndrome are discussed. PMID:27556667

  4. Laboratory-Treated T Cells in Treating Patients With High-Risk Relapsed Acute Myeloid Leukemia, Myelodysplastic Syndrome, or Chronic Myelogenous Leukemia Previously Treated With Donor Stem Cell Transplant

    ClinicalTrials.gov

    2016-08-08

    Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome; Adult Myelodysplastic Syndrome; Childhood Myelodysplastic Syndrome; Previously Treated Myelodysplastic Syndrome; Recurrent Adult Acute Myeloid Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Recurrent Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Secondary Acute Myeloid Leukemia; Therapy-Related Acute Myeloid Leukemia

  5. Acute Myeloid Leukemia Presenting as Intracerebral Granulocytic Sarcoma.

    PubMed

    Dhandapani, E; Thirumavalavan; Sowrirajan

    2015-10-01

    The CNS involvement of acute myeloid leukemia (AML) is more commonly manifest as meningeal involvement. Rarely it may present as intravascular tumor aggregates called granulocytic sarcoma which presents as intracranial hemorrhage. We are presenting a case of intracranial, intra-parenchymal granulocytic sarcoma (other names: chloroma, extramedullary myeloblastoma), presenting as acute hemiplegia without cerebral hemorrhage. PMID:27608697

  6. Bacillus cereus bacteremia in an adult with acute leukemia.

    PubMed

    Funada, H; Uotani, C; Machi, T; Matsuda, T; Nonomura, A

    1988-03-01

    Bacillus cereus, which used to be considered non-pathogenic, was isolated from the blood of a patient with acute leukemia who was receiving intensive chemotherapy. Fatal bacteremia developed with a clinical syndrome of acute gastroenteritis, followed by both meningoencephalitis with subarachnoid hemorrhage and multiple liver abscesses probably caused by infective vasculitis. Surveillance stool cultures revealed colonization with the organism prior to the onset of diarrhea, and repetitive blood cultures were found to be positive. Thus, this case suggested some new important clinicopathologic features of true B. cereus bacteremia complicating acute leukemia.

  7. Acute lymphoblastic leukemia in a pygmy hippopotamus (Hexaprotodon liberiensis).

    PubMed

    McCurdy, Paul; Sangster, Cheryl; Lindsay, Scott; Vogelnest, Larry

    2014-12-01

    A captive, 31-yr-old, intact male pygmy hippopotamus presented with nonspecific signs of weight loss, inappetence, diarrhea, and lethargy. After 5 wk of diagnostic investigation and symptomatic treatment, an acute leukemic process with concurrent polycystic kidney disease was suspected. The animal's condition continued to deteriorate prompting euthanasia. Necropsy, histopathologic, and immunohistochemical examination confirmed acute T-cell lymphoblastic leukemia and polycystic kidneys. Acute T-cell lymphoblastic leukemia has not previously been documented in this species; however, polycystic kidney disease has been reported. This case report adds to the increasing number of pygmy hippopotamuses diagnosed with polycystic kidney disease and describes acute T-cell lymphoblastic leukemia, a previously unreported disease of this species.

  8. Acute lymphoblastic leukemia in a pygmy hippopotamus (Hexaprotodon liberiensis).

    PubMed

    McCurdy, Paul; Sangster, Cheryl; Lindsay, Scott; Vogelnest, Larry

    2014-12-01

    A captive, 31-yr-old, intact male pygmy hippopotamus presented with nonspecific signs of weight loss, inappetence, diarrhea, and lethargy. After 5 wk of diagnostic investigation and symptomatic treatment, an acute leukemic process with concurrent polycystic kidney disease was suspected. The animal's condition continued to deteriorate prompting euthanasia. Necropsy, histopathologic, and immunohistochemical examination confirmed acute T-cell lymphoblastic leukemia and polycystic kidneys. Acute T-cell lymphoblastic leukemia has not previously been documented in this species; however, polycystic kidney disease has been reported. This case report adds to the increasing number of pygmy hippopotamuses diagnosed with polycystic kidney disease and describes acute T-cell lymphoblastic leukemia, a previously unreported disease of this species. PMID:25632680

  9. Tosedostat in Combination With Cytarabine or Decitabine in Treating Patients With Newly Diagnosed Acute Myeloid Leukemia or High-Risk Myelodysplastic Syndrome

    ClinicalTrials.gov

    2014-06-09

    Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome; 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); de Novo Myelodysplastic Syndromes; Previously Treated Myelodysplastic Syndromes; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndromes; Untreated Adult Acute Myeloid Leukemia

  10. Combination Chemotherapy With or Without Bone Marrow Transplantation in Treating Children With Acute Myelogenous Leukemia or Myelodysplastic Syndrome

    ClinicalTrials.gov

    2013-01-15

    Childhood Acute Erythroleukemia (M6); Childhood Acute Megakaryocytic Leukemia (M7); 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; 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

  11. Cediranib Maleate in Treating Patients With Relapsed, Refractory, or Untreated Acute Myeloid Leukemia or High-Risk Myelodysplastic Syndrome

    ClinicalTrials.gov

    2014-09-18

    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); de Novo Myelodysplastic Syndromes; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndromes; Untreated Adult Acute Myeloid Leukemia

  12. ADCY7 supports development of acute myeloid leukemia

    PubMed Central

    Li, Chunling; Xie, Jingjing; Lu, Zhigang; Chen, Chen; Li, Yancun; Zhan, Renhui; Fang, Yi; Hu, Xuemei; Zhang, Cheng Cheng

    2015-01-01

    Acute myeloid leukemia (AML) is the most common adult acute leukemia. Despite treatment, the majority of the AML patients relapse within 5 years. In silico analysis of several available databases of AML patients showed that the expression of adenylate cyclase 7 (ADCY7) significantly inversely correlates with the overall survival of AML patients. To determine whether ADCY7 supports AML development, we employed an shRNA-encoding lentivirus system to inhibit adcy7 expression in human AML cells including U937, MV4-11, and THP-1 cells. The ADCY7 deficiency resulted in decreased cell growth, elvated apoptosis, and lower c-Myc expression of these leukemia cells. This indicates that G protein-coupled receptor signaling contributes to AML pathogenesis. Our study suggests that inhibition of ADCY7 may be novel strategy for treating leukemia. PMID:26220344

  13. Leukomogenic factors downregulate heparanase expression in acute myeloid leukemia cells

    SciTech Connect

    Eshel, Rinat; Ben-Zaken, Olga; Vainas, Oded; Nadir, Yona; Minucci, Saverio; Polliack, Aaron; Naparstek, Ella; Vlodavsky, Israel; Katz, Ben-Zion; E-mail: bkatz@tasmc.healt.gov.il

    2005-10-07

    Heparanase is a heparan sulfate-degrading endoglycosidase expressed by mature monocytes and myeloid cells, but not by immature hematopoietic progenitors. Heparanase gene expression is upregulated during differentiation of immature myeloid cells. PML-RAR{alpha} and PLZF-RAR{alpha} fusion gene products associated with acute promyelocytic leukemia abrogate myeloid differentiation and heparanase expression. AML-Eto, a translocation product associated with AML FAB M2, also downregulates heparanase gene expression. The common mechanism that underlines the activity of these three fusion gene products involves the recruitment of histone deacetylase complexes to specific locations within the DNA. We found that retinoic acid that dissociates PML-RAR{alpha} from the DNA, and which is used to treat acute promyelocytic leukemia patients, restores heparanase expression to normal levels in an acute promyelocytic leukemia cell line. The retinoic acid effects were also observed in primary acute promyelocytic leukemia cells and in a retinoic acid-treated acute promyelocytic leukemia patient. Histone deacetylase inhibitor reverses the downregulation of heparanase expression induced by the AML-Eto fusion gene product in M2 type AML. In summary, we have characterized a link between leukomogenic factors and the downregulation of heparanase in myeloid leukemic cells.

  14. What's New in Adult Acute Lymphocytic Leukemia (ALL) in Adults Research?

    MedlinePlus

    ... Topic Additional resources for acute lymphocytic leukemia What’s new in acute lymphocytic leukemia research and treatment? Researchers ... have the Philadelphia chromosome. Gene expression profiling This new lab technique is being studied to help identify ...

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

    ClinicalTrials.gov

    2016-08-23

    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

  16. Acute promyelocytic leukemia: a curable disease.

    PubMed

    Lo Coco, F; Nervi, C; Avvisati, G; Mandelli, F

    1998-12-01

    The Second International Symposium on Acute Promyelocytic Leukemia (APL) was held in Rome in 12-14 November 1997. Clinical and basic investigators had the opportunity to discuss in this meeting the important advances in the biology and treatment of this disease achieved in the last 4 years, since the First Roman Symposium was held in 1993. The first part of the meeting was dedicated to relevant aspects of laboratory research, and included the following topics: molecular mechanisms of leukemogenesis and of response/resistance to retinoids, biologic and therapeutic effects of new agents such as arsenicals and novel synthetic retinoids; characterization of APL heterogeneity at the morphological, cytogenetic and immunophenotypic level. The updated results of large cooperative clinical trials using variable combinations of all-trans retinoic acid (ATRA) and chemotherapy were presented by the respective group chairmen, and formed the 'core' part of the meeting. These studies, which in most cases integrated the molecular assessment of response to treatment, provided a stimulating framework for an intense debate on the most appropriate frontline treatment options to be adopted in the future. The last day was dedicated to special entities such as APL in the elderly and in the child, as well as the role of bone marrow transplantation. The prognostic value of molecular monitoring studies was also discussed in the final session of the meeting. In this article, we review the major advances and controversial issues in APL biology and treatment discussed in this symposium and emerging from very recent publications. We would like to credit the successful outcome of this meeting to the active and generous input of all invited speakers and to participants from all over the world who provided constructive and fruitful discussions.

  17. Survival after intestinal mucormycosis in acute myelogenous leukemia.

    PubMed

    Parra, R; Arnau, E; Julia, A; Lopez, A; Nadal, A; Allende, E

    1986-12-15

    A young woman with acute myelocytic leukemia developed acute lower gastrointestinal bleeding immediately after a first remission induction of her leukemia. After the site of bleeding was located in the descending colon, a necrotic bleeding ulcer was resected. Histologic examination of the ulcer established the diagnosis of gastrointestinal mucormycosis. Treatment with amphotericin B was administered because of the high risk of dissemination. The patient has been followed for 9 months with no evidence of relapse of infection. Survival after gastrointestinal mucormycosis in acute leukemia has not previously been reported in the English language literature. Success in managing mucormycosis depends on the adherence to the recommended principles of early aggressive diagnostic measures, excisional surgery, amphotericin B therapy, and control of the underlying predisposing condition.

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

    ClinicalTrials.gov

    2016-07-08

    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

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

    ClinicalTrials.gov

    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

  20. Medullary allotransplant in acute myeloblastic leukemia in a child.

    PubMed

    Buga Corbu, V; Glűck, A; Arion, C

    2014-09-15

    Although acute myeloblastic leukemia (AML) is more resistant to chemotherapy than acute lymphoblastic leukemia (ALL), significant progresses have been achieved over the last 20 years with an improvement in the long-term survival up to 50-60%. This may be attributed to the intensification of chemotherapy, including the increased use of stem-cell transplantation (HSCT) in well-defined subgroups. Allo-HSCT represents an extremely effective alternative in pediatric AML treatment panel, but its efficiency is limited both by the toxic effects and by the difficulty of finding a matched HLA donor.

  1. Medullary allotransplant in acute myeloblastic leukemia in a child

    PubMed Central

    Buga Corbu, V; Glűck, R; Arion, C

    2014-01-01

    Abstract Although acute myeloblastic leukemia (AML) is more resistant to chemotherapy than acute lymphoblastic leukemia (ALL), significant progresses have been achieved over the last 20 years with an improvement in the long-term survival up to 50-60%. This may be attributed to the intensification of chemotherapy, including the increased use of stem-cell transplantation (HSCT) in well-defined subgroups. Allo-HSCT represents an extremely effective alternative in pediatric AML treatment panel, but its efficiency is limited both by the toxic effects and by the difficulty of finding a matched HLA donor. PMID:25408774

  2. Neutropenic enterocolitis: a rare presenting complication of acute leukemia.

    PubMed

    Quigley, M M; Bethel, K; Nowacki, M; Millard, F; Sharpe, R

    2001-03-01

    Neutropenic enterocolitis is a necrotizing inflammatory process with intramural infection that occurs predominantly in neutropenic patients. This syndrome is most frequently observed after chemotherapy for hematologic and solid tissue malignancies, but it can also be observed in a number of other clinical settings as well. Neutropenic enterocolitis can be a rare presenting complication of acute leukemia. We report a case of acute lymphoblastic leukemia that presented with abdominal pain due to neutropenic enterocolitis. The diagnostic and treatment challenges associated with this manner of presentation are discussed.

  3. High frequency of acute promyelocytic leukemia among Latinos with acute myeloid leukemia.

    PubMed

    Douer, D; Preston-Martin, S; Chang, E; Nichols, P W; Watkins, K J; Levine, A M

    1996-01-01

    A high frequency (24%) of acute promyelocytic leukemia (APL) was noted among acute myelocytic leukemia (AML) cases at the Los Angeles County-University of Southern California (LAC-USC) Medical Center, in comparison with the expected frequency of 5% to 15%. Because of the high proportion of Latinos in this center, we questioned if APL is more common in this ethnic group. The proportion of APL among the 80 AML patients of Latino origin was significantly higher (30; 37.5%) when compared with the 62 non-Latinos (4; 6.5%) (P = .00001). In an attempt to verify this finding on a larger group of patients, we analyzed 276 pathologically verified cases of AML in patients aged 30 to 69 years from the entire County of Los Angeles, registered on an ongoing population-based epidemiologic study of AML. APL was more frequent among the 47 Latinos (24.3%) than in the 229 non-Latinos (8.3%) (P = .0075). APL is seen in younger patients with AML, but Latino AML patients also had a higher frequency of APL after accounting for their younger age (age-adjusted odds ratio for APL among Latinos in LAC-USC Medical Center, 9.4 [95% confidence interval (CI) 2.9, 30] P = .0002; among Latinos in the population-based study, 3.0 [95% CI 1.3 to 6.9] P = .01). The different ethnic distribution of AML was found to be due to a higher proportion of APL cases per se, and not to a lower proportion of any other French-American-British subtype (P = .0004). These results, from two different populations of AML patients, indicate that Latinos with AML have a higher likelihood of the APL subtype of disease, which may suggest a genetic predisposition to APL and/or exposure to distinct environmental factor(s).

  4. Optimizing asparaginase therapy for acute lymphoblastic leukemia.

    PubMed

    Rizzari, Carmelo; Conter, Valentino; Starý, Jan; Colombini, Antonella; Moericke, Anja; Schrappe, Martin

    2013-03-01

    Asparaginases are important agents used in the treatment of children with acute lymphoblastic leukemia (ALL). Three types of asparaginase are currently available: two are derived from Escherichia coli [native asparaginase and pegylated asparaginase (PEG-asparaginase)] and one from Erwinia chrysanthemi (crisantaspase). All three products share the same mechanism of action but have different pharmacokinetic properties, which do not make them easily interchangeable. Among the known toxicities and side-effects, allergic reactions and silent inactivation represent the most important limitations to the prolonged use of any asparaginase product, with associated reduced therapeutic effects and poorer outcomes. Routine real time monitoring can help to identify patients with silent inactivation and facilitate a switch to a different product to ensure continued depletion of asparagine, completion of the treatment schedule and maintenance of outcomes. However, the most appropriate second-line treatment is still a matter of debate. PEG-asparaginase has lower immunogenicity and a longer half-life than native Escherichia coli (E. coli) asparaginase, which makes it useful for both first-line and second-line use with a reduced number of doses. However, PEG-asparaginase displays cross-reactivity with native E. coli asparaginase that may harm its therapeutic effects. Crisantaspase does not display cross-reactivity to either of the E. coli-derived products, which has made crisantaspase the second-line treatment option in a number of recent protocols. As crisantaspase has a much shorter biological half-life than the E. coli-derived products, the appropriate dosage and administration schedule are of paramount importance in delivering treatment with this product. In the ongoing trial AIEOP-BFM ALL 2009 (Associazione Italiana Ematologia Oncologia Pediatrica - Berlin-Franklin-Munster), in which PEG-asparaginase is used first-line, one dose of PEG-asparaginase is substituted by seven doses

  5. The MLL recombinome of acute leukemias in 2013

    PubMed Central

    Meyer, C; Hofmann, J; Burmeister, T; Gröger, D; Park, T S; Emerenciano, M; Pombo de Oliveira, M; Renneville, A; Villarese, P; Macintyre, E; Cavé, H; Clappier, E; Mass-Malo, K; Zuna, J; Trka, J; De Braekeleer, E; De Braekeleer, M; Oh, S H; Tsaur, G; Fechina, L; van der Velden, V H J; van Dongen, J J M; Delabesse, E; Binato, R; Silva, M L M; Kustanovich, A; Aleinikova, O; Harris, M H; Lund-Aho, T; Juvonen, V; Heidenreich, O; Vormoor, J; Choi, W W L; Jarosova, M; Kolenova, A; Bueno, C; Menendez, P; Wehner, S; Eckert, C; Talmant, P; Tondeur, S; Lippert, E; Launay, E; Henry, C; Ballerini, P; Lapillone, H; Callanan, M B; Cayuela, J M; Herbaux, C; Cazzaniga, G; Kakadiya, P M; Bohlander, S; Ahlmann, M; Choi, J R; Gameiro, P; Lee, D S; Krauter, J; Cornillet-Lefebvre, P; Te Kronnie, G; Schäfer, B W; Kubetzko, S; Alonso, C N; zur Stadt, U; Sutton, R; Venn, N C; Izraeli, S; Trakhtenbrot, L; Madsen, H O; Archer, P; Hancock, J; Cerveira, N; Teixeira, M R; Lo Nigro, L; Möricke, A; Stanulla, M; Schrappe, M; Sedék, L; Szczepański, T; Zwaan, C M; Coenen, E A; van den Heuvel-Eibrink, M M; Strehl, S; Dworzak, M; Panzer-Grümayer, R; Dingermann, T; Klingebiel, T; Marschalek, R

    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 TPGs are now characterized at the molecular level. However, only seven rearrangements seem to be predominantly associated with illegitimate recombinations of the MLL gene (∼90%): AFF1/AF4, MLLT3/AF9, MLLT1/ENL, MLLT10/AF10, ELL, partial tandem duplications (MLL PTDs) and MLLT4/AF6, respectively. The MLL breakpoint distributions for all clinical relevant subtypes (gender, disease type, age at diagnosis, reciprocal, complex and therapy-induced translocations) are presented. Finally, we present the extending network of reciprocal MLL fusions deriving from complex rearrangements. PMID:23628958

  6. Childhood acute leukemias are frequent in Mexico City: descriptive epidemiology

    PubMed Central

    2011-01-01

    Background Worldwide, acute leukemia is the most common type of childhood cancer. It is particularly common in the Hispanic populations residing in the United States, Costa Rica, and Mexico City. The objective of this study was to determine the incidence of acute leukemia in children who were diagnosed and treated in public hospitals in Mexico City. Methods Included in this study were those children, under 15 years of age and residents of Mexico City, who were diagnosed in 2006 and 2007 with leukemia, as determined by using the International Classification of Childhood Cancer. The average annual incidence rates (AAIR), and the standardized average annual incidence rates (SAAIR) per million children were calculated. We calculated crude, age- and sex-specific incidence rates and adjusted for age by the direct method with the world population as standard. We determined if there were a correlation between the incidence of acute leukemias in the various boroughs of Mexico City and either the number of agricultural hectares, the average number of persons per household, or the municipal human development index for Mexico (used as a reference of socio-economic level). Results Although a total of 610 new cases of leukemia were registered during 2006-2007, only 228 fit the criteria for inclusion in this study. The overall SAAIR was 57.6 per million children (95% CI, 46.9-68.3); acute lymphoblastic leukemia (ALL) was the most frequent type of leukemia, constituting 85.1% of the cases (SAAIR: 49.5 per million), followed by acute myeloblastic leukemia at 12.3% (SAAIR: 6.9 per million), and chronic myeloid leukemia at 1.7% (SAAIR: 0.9 per million). The 1-4 years age group had the highest SAAIR for ALL (77.7 per million). For cases of ALL, 73.2% had precursor B-cell immunophenotype (SAAIR: 35.8 per million) and 12.4% had T-cell immunophenotype (SAAIR 6.3 per million). The peak ages for ALL were 2-6 years and 8-10 years. More than half the children (58.8%) were classified as high

  7. [Tumor lysis syndrome in a pregnancy complicated with acute lymphoblastic leukemia].

    PubMed

    Álvarez-Goris, M P; Sánchez-Zamora, R; Torres-Aguilar, A A; Briones Garduño, J C

    2016-04-01

    Acute leukemia is rare during pregnancy, affects about 1 in 75,000 pregnancies, of all leukemias diagnosed only 28% are acute lymphoblastic leukemia, this is a risk factor to develop spontaneous tumor lysis syndrome, it's a oncologic complication potentially deadly if the prophylactic treatment its avoided. Cases of acute lymphoblastic leukemia associated with pregnancy has been poorly documented in the literature the association of these two entities to pregnancy is the first report published worldwide, so the information is limited. PMID:27443101

  8. Use of a rat basophil leukemia (RBL) cell-based immunological assay for allergen identification, clinical diagnosis of allergy, and identification of anti-allergy agents for use in immunotherapy.

    PubMed

    Sun, Na; Zhou, Cui; Zhou, Xin; Sun, Lu; Che, Huilian

    2015-01-01

    Food allergy is an important public health problem that affects an estimated 8% of young children and 2% of adults. With an increasing interest in genetically-engineered foods, there is a growing need for development of sensitive and specific tests to evaluate potential allergenicity of foods and novel proteins as well as to determine allergic responses to ensure consumer safety. This review covers progress made in the field of development of cell models, specifically that involving a rat basophil leukemia (RBL) cell-based immunoassay, for use in allergen identification, diagnosis, and immunotherapy. The RBL assay has been extensively employed for determining biologically relevant cross-reactivities of food proteins, assessing the effect of processing on the allergenicity of food proteins, diagnosing allergic responses to whole-food products, and identifying anti-allergy food compounds. From the review of the literature, one might conclude the RBL cell-based assay is a better test system when compared to wild-type mast cell and basophil model systems for use in allergen identification, diagnosis, and analyses of potential immunotherapeutics. However, it is important to emphasize that this assay will only be able to identify those allergens to which the human has already been exposed, but will not identify a truly novel allergen, i.e. one that has never been encountered as in its preferred (humanized) configuration.

  9. Use of humanized rat basophilic leukemia reporter cell lines as a diagnostic tool for detection of allergen-specific IgE in allergic patients: time for a reappraisal?

    PubMed

    Falcone, Franco H; Alcocer, Marcos J C; Okamoto-Uchida, Yoshimi; Nakamura, Ryosuke

    2015-11-01

    The interaction between allergens and specific IgE is at the heart of the allergic response and as such lies at the center of techniques used for diagnosis of allergic sensitization. Although serological tests are available, in vivo tests such as double-blind placebo-controlled food challenges (DBPCFC) and skin prick test (SPT) associated to the patients' clinical history are still the main guides to clinicians in many practices around the world. More recently, complex protein arrays and basophil activation tests, requiring only small amounts of whole blood, have been developed and refined, but are yet to enter clinical practice. Similarly, the use of rat basophilic leukemia (RBL) cell lines for detection of allergen-specific IgE has been made possible by stable transfection of the human FcεRI α chain into this cell line more than 20 years ago, but has not found widespread acceptance among clinicians. Here, we review the perceived limitations of diagnostic applications of humanized RBL systems. Furthermore, we illustrate how the introduction of reporter genes into humanized RBL cells is able to overcome most of these limitations, and has the potential to become a new powerful tool to complement the armamentarium of allergists. A demonstration of the usefulness of humanized RBL reporter systems for elucidation of complex IgE sensitization patterns against wheat proteins and a section on the use of fluorescence-based reporter systems in combination with allergen arrays close the review. PMID:26452547

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

    ClinicalTrials.gov

    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)

  11. Hypocellular acute myeloid leukemia in adults: analysis of the clinical outcome of 123 patients

    PubMed Central

    Al-Kali, Aref; Konoplev, Sergej; Lin, Erpei; Kadia, Tapan; Faderl, Stefan; Ravandi, Farhad; Ayoubi, Mohamad; Brandt, Mark; Cortes, Jorge E.; Kantarjian, Hagop; Borthakur, Gautam

    2012-01-01

    Background The hypocellular variant of acute myeloid leukemia accounts for less than 10% of all cases of adult acute myeloid leukemia. It is defined by having less than 20 percent of cellular bone marrow in a biopsy at presentation. It is unclear in the literature whether the outcome of hypocellular acute myeloid leukemia differs from that of non-hypocellular acute myeloid leukemia. Design and Methods We retrospectively analyzed all the cases reported to be hypocellular acute myeloid leukemia between 2000 and 2009. A second pathology review was conducted and the diagnosis was confirmed in all cases. Results One hundred twenty-three (9%) patients were identified: patients with hypocellular acute myeloid leukemia were older than those with non-hypocellular acute myeloid leukemia (P=0.009) and more frequently presented with cytopenias (P<0.001). Forty-one patients with hypocellular acute myeloid leukemia had an antecedent hematologic disorder and 11 patients had received prior chemo-radiotherapy for non-hematopoietic neoplasms. On multivariate analysis, overall survival, remission duration and event-free survival were comparable to those of other patients with acute myeloid leukemia. Conclusions The outcome of hypocellular acute myeloid leukemia does not differ from that of non-hypocellular acute myeloid leukemia. PMID:22058194

  12. Upregulation of Leukocytic Syncytin-1 in Acute Myeloid Leukemia Patients

    PubMed Central

    Sun, Yi; Zhu, Hongyan; Song, Jianxin; Jiang, Yaxian; Ouyang, Hongmei; Huang, Rongzhong; Zhang, Guiqian; Fan, Xin; Tao, Rui; Jiang, Jie; Niu, Hua

    2016-01-01

    Background Syncytin-1, a cell membrane-localizing fusogen, is abnormally expressed in several cancers, including endometrial cancer, breast cancer, and leukemia. Although abnormal syncytin-1 expression has been detected in two-thirds of leukemia blood samples, its expression profile in acute leukemia patients has not yet been analyzed. Material/Methods Bone marrow samples from 50 acute myelogenous leukemia (AML) cases and 14 B-cell acute lymphocytic leukemia (B-cell ALL) patients were subjected to flow cytometry to assess leukocyte type distributions and leukocytic syncytin-1 surface expression. RT-PCR was applied to assess leukocytic syncytin-1 mRNA expression. Statistical analysis was applied to compare syncytin-1 expression between AML and B-cell ALL patients across blasts, granulocytes, lymphocytes, and monocytes as well as to determine clinical factors statistically associated with changes in syncytin-1 expression. Results The leukocyte type distributions of the AML and B-cell ALL cohorts highly overlapped, with an observable difference in blast distribution between the 2 cohorts. The AML cohort displayed significantly greater syncytin-1 surface and mRNA expression (p<0.05). Syncytin-1 surface and mRNA expression was significantly increased across all 4 leukocyte types (p<0.05). The percentage of syncytin-1-expressing blasts was significantly greater in AML patients (p<0.05), with blasts showing the largest fold-change in syncytin-1 expression (p<0.05). M5, M5a, and M5b AML patients displayed significantly higher syncytin-1 surface expression relative to all other AML French-American-British (FAB) classifications (p<0.05). Conclusions These findings suggest leukocytic syncytin-1 expression may play a role in the development and/or maintenance of the AML phenotype and the acute monocytic leukemia phenotype in particular. PMID:27393911

  13. Bendamustine Hydrochloride and Idarubicin in Treating Older Patients With Previously Untreated Acute Myeloid Leukemia or Myelodysplastic Syndrome

    ClinicalTrials.gov

    2012-12-07

    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); de Novo Myelodysplastic Syndromes; Myelodysplastic Syndrome With Isolated Del(5q); Untreated Adult Acute Myeloid Leukemia

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

    ClinicalTrials.gov

    2016-08-23

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

  15. Neurodevelopmental Sequelae of Pediatric Acute Lymphoblastic Leukemia and Its Treatment

    ERIC Educational Resources Information Center

    Janzen, Laura A.; Spiegler, Brenda J.

    2008-01-01

    This review will describe the neurocognitive outcomes associated with pediatric acute lymphoblastic leukemia (ALL) and its treatment. The literature is reviewed with the aim of addressing methodological issues, treatment factors, risks and moderators, special populations, relationship to neuroimaging findings, and directions for future research.…

  16. [Acute leukemia in Jehovah's Witnesses: difficulties in its management].

    PubMed

    Gómez-Almaguer, D; Ruiz-Argüelles, G; Lozano de la Vega, A; García-Guajardo, B M

    1990-01-01

    The Witnesses of Jehovah is a religious community posing special problems because of their religions conviction which objects to transfusions of blood or blood products. Six patients with acute lymphoblastic leukemia (one adult and 5 children) are presented. We obtained permission for blood transfusion in four children without resorting to legal pressures which, on the hand, are non-existent in Mexico. PMID:2091183

  17. Acute non-lymphocytic leukemia following multimodality therapy for retinoblastoma

    SciTech Connect

    White, L.; Ortega, J.A.; Ying, K.L.

    1985-02-01

    The genetic form of retinoblastoma carries a high risk of secondary malignant neoplasm, apparently not related to the use of chemotherapy. A child with unilateral non-genetic retinoblastoma who had received chemotherapy and radiation therapy and developed acute non-lymphocytic leukemia (ANLL) is reported. The occurrence of ANLL and retinoblastoma has not been previously reported.

  18. Acute myelogenous leukemia treated with daunomycin associated with nephrotic syndrome.

    PubMed

    Thomson, M; de Arriba, G; Ordi, J; Oliva, H; Hernando, L

    1989-01-01

    We report a 33-year-old patient with a diagnosis of acute myelogenous leukemia that developed a nephrotic syndrome 9 days after starting treatment with daunomycin. Pathological studies of the kidneys revealed minimal change disease with IgM deposits. Possible pathogenetic mechanisms are discussed.

  19. Epidemiology and Treatment of Acute Promyelocytic Leukemia in Latin America

    PubMed Central

    Rego, E.M.; Jácomo, R.H.

    2011-01-01

    Distinct epidemiological characteristics have been described in Acute Promielocytic Leukemia (APL). Populations from Latin America have a higher incidence of APL and in some geographic areas a distinct distribution of the PML-RARA isoforms is present. Here, we review the main differences in APL epidemilogy in Latin America as well as treatment outcomes. PMID:22110899

  20. Cannabis Extract Treatment for Terminal Acute Lymphoblastic Leukemia with a Philadelphia Chromosome Mutation

    PubMed Central

    Singh, Yadvinder; Bali, Chamandeep

    2013-01-01

    Acute lymphoblastic leukemia (ALL) is a cancer of the white blood cells and is typically well treated with combination chemotherapy, with a remission state after 5 years of 94% in children and 30–40% in adults. To establish how aggressive the disease is, further chromosome testing is required to determine whether the cancer is myeloblastic and involves neutrophils, eosinophils or basophils, or lymphoblastic involving B or T lymphocytes. This case study is on a 14-year-old patient diagnosed with a very aggressive form of ALL (positive for the Philadelphia chromosome mutation). A standard bone marrow transplant, aggressive chemotherapy and radiation therapy were revoked, with treatment being deemed a failure after 34 months. Without any other solutions provided by conventional approaches aside from palliation, the family administered cannabinoid extracts orally to the patient. Cannabinoid resin extract is used as an effective treatment for ALL with a positive Philadelphia chromosome mutation and indications of dose-dependent disease control. The clinical observation in this study revealed a rapid dose-dependent correlation. PMID:24474921

  1. Phase I Trial of AZD1775 and Belinostat in Treating Patients With Relapsed or Refractory Myeloid Malignancies or Untreated Acute Myeloid Leukemia

    ClinicalTrials.gov

    2016-07-20

    Blast Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Previously Treated Myelodysplastic Syndrome; Recurrent Adult Acute Myeloid Leukemia; Refractory Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Secondary Acute Myeloid Leukemia; Therapy-Related Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

  2. Family history of autoimmune thyroid disease and childhood acute leukemia.

    PubMed

    Perillat-Menegaux, Florence; Clavel, Jacqueline; Auclerc, Marie-Françoise; Baruchel, André; Leverger, Guy; Nelken, Brigitte; Philippe, Noël; Sommelet, Danièle; Vilmer, Etienne; Hémon, Denis

    2003-01-01

    The association between a familial history of autoimmune disease and childhood acute leukemia was investigated in a French case-control study that, overall, was designed to assess the role of perinatal, infectious, environmental, and genetic factors in the etiology of childhood acute leukemia. Familial histories of autoimmune disease in first- and second-degree relatives were compared in 279 incident cases, 240 cases of acute lymphocytic leukemia (ALL) and 39 cases of acute non-lymphoblastic leukemia (ANLL), and 285 controls. Recruitment was frequency matched by age, gender, hospital, and ethnic origin. Odds ratios (OR) were estimated using an unconditional regression model taking into account the stratification variables, socioeconomic status, and familial structure. A statistically significant association between a history of autoimmune disease in first- or second-degree relatives and ALL (OR, 1.7; 95% confidence interval (CI), 1.0-2.8) was found. A relationship between thyroid diseases overall and ALL (OR, 2.0; 95% CI, 1.0-3.9) was observed. This association was more pronounced for potentially autoimmune thyroid diseases (Grave's disease and/or hyperthyroidism and Hashimoto's disease and/or hypothyroidism) (OR, 3.5; 95% CI, 1.1-10.7 and OR, 5.6; 95% CI, 1.0-31.1, respectively for ALL and ANLL), whereas it was not statistically significant for the other thyroid diseases (thyroid goiter, thyroid nodule, and unspecified thyroid disorders) (OR, 1.6; 95% CI, 0.7-3.5 and OR, 1.3; 95% CI, 0.2-7.0, respectively, for ALL and ANLL). The results suggest that a familial history of autoimmune thyroid disease may be associated with childhood acute leukemia.

  3. Survival of patients with mixed phenotype acute leukemias: A large population-based study.

    PubMed

    Shi, Runhua; Munker, Reinhold

    2015-06-01

    Little is known about the incidence and treatment outcome of patients with acute biphenotypic leukemias. The World Health Organization (WHO) established the term of acute leukemia of ambiguous phenotype in 2001 (revised in 2008) introducing the term of mixed phenotype acute leukemias. Using the database of the Surveillance, Epidemiology, and End Results registry (SEER), we identified 313 patients with mixed phenotype acute leukemias and compared them with 14,739 patients with acute lymphoblastic leukemia and 34,326 patients with acute myelogenous leukemias diagnosed between 2001 and 2011. As a further control group, 1777 patients were included who were not classified as myeloid, lymphoid or biphenotypic (other acute leukemias). The incidence of mixed phenotype acute leukemias is 0.35 cases/1,000,000 person-years. In a multivariate analysis, the prognosis depends strongly on age (as with other leukemias) and it has the worst outcome of all four types of leukemia. However, the prognosis has improved, comparing 2001-2005 with 2006-2011. We present the first comprehensive, population-based study of acute biphenotypic or mixed phenotype acute leukemias according to the WHO classification. Especially in older patients, the prognosis is unfavorable and new treatments should be investigated.

  4. Acute myeloid leukemia cells polarize macrophages towards a leukemia supporting state in a Growth factor independence 1 dependent manner

    PubMed Central

    Al-Matary, Yahya S.; Botezatu, Lacramioara; Opalka, Bertram; Hönes, Judith M.; Lams, Robert F.; Thivakaran, Aniththa; Schütte, Judith; Köster, Renata; Lennartz, Klaus; Schroeder, Thomas; Haas, Rainer; Dührsen, Ulrich; Khandanpour, Cyrus

    2016-01-01

    The growth of malignant cells is not only driven by cell-intrinsic factors, but also by the surrounding stroma. Monocytes/Macrophages play an important role in the onset and progression of solid cancers. However, little is known about their role in the development of acute myeloid leukemia, a malignant disease characterized by an aberrant development of the myeloid compartment of the hematopoietic system. It is also unclear which factors are responsible for changing the status of macrophage polarization, thus supporting the growth of malignant cells instead of inhibiting it. We report herein that acute myeloid leukemia leads to the invasion of acute myeloid leukemia-associated macrophages into the bone marrow and spleen of leukemic patients and mice. In different leukemic mouse models, these macrophages support the in vitro expansion of acute myeloid leukemia cell lines better than macrophages from non-leukemic mice. The grade of macrophage infiltration correlates in vivo with the survival of the mice. We found that the transcriptional repressor Growth factor independence 1 is crucial in the process of macrophage polarization, since its absence impedes macrophage polarization towards a leukemia supporting state and favors an anti-tumor state both in vitro and in vivo. These results not only suggest that acute myeloid leukemia-associated macrophages play an important role in the progression of acute myeloid leukemia, but also implicate Growth factor independence 1 as a pivotal factor in macrophage polarization. These data may provide new insights and opportunities for novel therapies for acute myeloid leukemia. PMID:27390361

  5. Specificity of Heteroantisera to Human Acute Leukemia-Associated Antigens

    PubMed Central

    Baker, Michael A.; Ramachandar, K.; Taub, Robert N.

    1974-01-01

    Antisera have been raised to human leukemic blast cells from individual patients in mice rendered tolerant with cyclophosphamide to remission leukocytes from the same individual. 10 antisera were raised against acute myelogenous leukemia (AML) cells and 5 antisera were raised against acute lymphoblastic leukemia (ALL) cells. Antisera to AML cells were absorbed with ALL cells, and antisera to ALL cells were absorbed with AML cells. Unabsorbed and absorbed antisera as well as antisera raised in nontolerant mice were tested for cytotoxicity against various cells of a panel containing myeloblasts from 35 patients with AML, lymphoblasts from 7 patients with ALL, myeloblasts from 7 patients with chronic myelogenous leukemia (CML) in blast crisis, peripheral blood leukocytes from 12 patients with acute leukemia in remission and 30 nonleukemic patients, and nucleated bone marrow cells from 10 nonleukemic patients. Unabsorbed antisera to AML or ALL cells raised in tolerant mice were highly cytotoxic to leukemic blasts cells but significantly less cytotoxic to remission and control cells. Antisera to AML cells absorbed with ALL cells retained measurable cytotoxicity against AML cells but were not cytotoxic to ALL cells or control cells. Similarly, antisera to ALL cells absorbed with AML cells retained significant cytotoxicity only to ALL cells. Control antisera raised in nontolerant mice were cytotoxic to all cells tested. Although species specific, histocompatibility, differentiation, maturation, and cell cycle-associated antigens may be responsible in part for the cytotoxic activity of the unabsorbed antisera, the absorbed antisera are probably detecting antigens specific for their leukemic cell type. PMID:4140196

  6. Outcomes for patients with chronic lymphocytic leukemia and acute leukemia or myelodysplastic syndrome.

    PubMed

    Tambaro, F P; Garcia-Manero, G; O'Brien, S M; Faderl, S H; Ferrajoli, A; Burger, J A; Pierce, S; Wang, X; Do, K-A; Kantarjian, H M; Keating, M J; Wierda, W G

    2016-02-01

    Acute leukemia (AL) and myelodysplastic syndrome (MDS) are uncommon in chronic lymphocytic leukemia (CLL). We retrospectively identified 95 patients with CLL, also diagnosed with AL (n=38) or MDS (n=57), either concurrently (n=5) or subsequent (n=90) to CLL diagnosis and report their outcomes. Median number of CLL treatments prior to AL and MDS was 2 (0-9) and 1 (0-8), respectively; the most common regimen was purine analog combined with alkylating agent±CD20 monoclonal antibody. Twelve cases had no prior CLL treatment. Among 38 cases with AL, 33 had acute myelogenous leukemia (AML), 3 had acute lymphoid leukemia (ALL; 1 Philadelphia chromosome positive), 1 had biphenotypic and 1 had extramedullary (bladder) AML. Unfavorable AML karyotype was noted in 26, and intermediate risk in 7 patients. There was no association between survival from AL and number of prior CLL regimens or karyotype. Expression of CD7 on blasts was associated with shorter survival. Among MDS cases, all International Prognostic Scoring System (IPSS) were represented; karyotype was unfavorable in 36, intermediate in 6 and favorable in 12 patients; 10 experienced transformation to AML. Shorter survival from MDS correlated with higher risk IPSS, poor-risk karyotype and increased number of prior CLL treatments. Overall, outcomes for patients with CLL subsequently diagnosed with AL or MDS were very poor; AL/MDS occurred without prior CLL treatment. Effective therapies for these patients are desperately needed.

  7. Acute Lymphocytic Leukemia with Bilateral Renal Masses Masquerading as Nephroblastomatosis.

    PubMed

    Thakore, Poonam; Aljabari, Salim; Turner, Curtis; Vasylyeva, Tetyana L

    2015-01-01

    Acute lymphoblastic leukemia (ALL) is the most common malignancy in the pediatric patient population. However, renal involvement as the primary manifestation of ALL is rare. We report a case of a 4-year-old boy with bilateral renal lesions resembling nephroblastic rests as the first finding of early stage ALL preceding hematological changes and subsequent classic clinical findings by two weeks. These renal hypodensities completely resolved after one week of induction chemotherapy. This case demonstrates that renal involvement can be the only initial presenting finding of leukemia. Children with lesions resembling nephroblastic rests need appropriate surveillance due to the risk of malignant disease.

  8. Acute Lymphocytic Leukemia with Bilateral Renal Masses Masquerading as Nephroblastomatosis

    PubMed Central

    Thakore, Poonam; Aljabari, Salim; Turner, Curtis; Vasylyeva, Tetyana L.

    2015-01-01

    Acute lymphoblastic leukemia (ALL) is the most common malignancy in the pediatric patient population. However, renal involvement as the primary manifestation of ALL is rare. We report a case of a 4-year-old boy with bilateral renal lesions resembling nephroblastic rests as the first finding of early stage ALL preceding hematological changes and subsequent classic clinical findings by two weeks. These renal hypodensities completely resolved after one week of induction chemotherapy. This case demonstrates that renal involvement can be the only initial presenting finding of leukemia. Children with lesions resembling nephroblastic rests need appropriate surveillance due to the risk of malignant disease. PMID:26613060

  9. 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

    ClinicalTrials.gov

    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

  10. Low-Dose or High-Dose Conditioning Followed by Peripheral Blood Stem Cell Transplant in Treating Patients With Myelodysplastic Syndrome or Acute Myelogenous Leukemia

    ClinicalTrials.gov

    2014-10-23

    Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome; Acute Myeloid Leukemia/Transient Myeloproliferative Disorder; 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; Myelodysplastic Syndrome With Isolated Del(5q); Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Myeloid Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndromes

  11. Ovarian reserve in women treated for acute lymphocytic leukemia or acute myeloid leukemia with chemotherapy, but not stem cell transplantation.

    PubMed

    Rossi, Brooke V; Missmer, Stacey; Correia, Katharine F; Wadleigh, Martha; Ginsburg, Elizabeth S

    2012-01-01

    Purpose. It is well known that chemotherapy regimens may have a negative effect on ovarian reserve, leading to amenorrhea or premature ovarian failure. There are little data regarding the effects of leukemia chemotherapy on ovarian reserve, specifically in women who received the chemotherapy as adults and are having regular menstrual periods. Our primary objective was to determine if premenopausal women with a history of chemotherapy for leukemia, without subsequent stem cell transplantation, have decreased ovarian reserve. Materials and Methods. We measured ovarian reserve in five women who had been treated for acute lymphocytic leukemia (ALL) or acute myeloid leukemia (AML) and compared them to age-matched control women without a history of chemotherapy. Results. There appeared to be a trend towards lower antimullerian hormone and antral follicle counts and higher follicle-stimulating hormone levels in the leukemia group. Conclusion. Our results indicate that chemotherapy for AML or ALL without stem cell transplantation may compromise ovarian reserve. Although our results should be confirmed by a larger study, oncologists, infertility specialists, and patients should be aware of the potential risks to ovarian function and should be counseled on options for fertility preservation.

  12. Ovarian Reserve in Women Treated for Acute Lymphocytic Leukemia or Acute Myeloid Leukemia with Chemotherapy, but Not Stem Cell Transplantation

    PubMed Central

    Rossi, Brooke V.; Missmer, Stacey; Correia, Katharine F.; Wadleigh, Martha; Ginsburg, Elizabeth S.

    2012-01-01

    Purpose. It is well known that chemotherapy regimens may have a negative effect on ovarian reserve, leading to amenorrhea or premature ovarian failure. There are little data regarding the effects of leukemia chemotherapy on ovarian reserve, specifically in women who received the chemotherapy as adults and are having regular menstrual periods. Our primary objective was to determine if premenopausal women with a history of chemotherapy for leukemia, without subsequent stem cell transplantation, have decreased ovarian reserve. Materials and Methods. We measured ovarian reserve in five women who had been treated for acute lymphocytic leukemia (ALL) or acute myeloid leukemia (AML) and compared them to age-matched control women without a history of chemotherapy. Results. There appeared to be a trend towards lower antimullerian hormone and antral follicle counts and higher follicle-stimulating hormone levels in the leukemia group. Conclusion. Our results indicate that chemotherapy for AML or ALL without stem cell transplantation may compromise ovarian reserve. Although our results should be confirmed by a larger study, oncologists, infertility specialists, and patients should be aware of the potential risks to ovarian function and should be counseled on options for fertility preservation. PMID:23050166

  13. Acute pediatric leg compartment syndrome in chronic myeloid leukemia.

    PubMed

    Cohen, Eric; Truntzer, Jeremy; Trunzter, Jeremy; Klinge, Steve; Schwartz, Kevin; Schiller, Jonathan

    2014-11-01

    Acute compartment syndrome is an orthopedic surgical emergency and may result in devastating complications in the setting of delayed or missed diagnosis. Compartment syndrome has a variety of causes, including posttraumatic or postoperative swelling, external compression, burns, bleeding disorders, and ischemia-reperfusion injury. Rare cases of pediatric acute compartment syndrome in the setting of acute myeloid leukemia and, even less commonly, chronic myeloid leukemia have been reported. The authors report the first known case of pediatric acute compartment syndrome in a patient without a previously known diagnosis of chronic myeloid leukemia. On initial examination, an 11-year-old boy presented with a 2-week history of progressive left calf pain and swelling after playing soccer. Magnetic resonance imaging scan showed a hematoma in the left superficial posterior compartment. The patient had unrelenting pain, intermittent lateral foot parethesias, and inability to bear weight. Subsequently, he was diagnosed with acute compartment syndrome and underwent fasciotomy and evacuation of a hematoma. Laboratory results showed an abnormal white blood cell count of 440×10(9)/L (normal, 4.4-11×10(9)) and international normalized ratio of 1.3 (normal, 0.8-1.2). Further testing included the BCR-ABL1 fusion gene located on the Philadelphia chromosome, leading to a diagnosis of chronic myeloid leukemia. Monotherapy with imatinib mesylate (Gleevec) was initiated. This report adds another unique case to the growing literature on compartment syndrome in the pediatric population and reinforces the need to consider compartment syndrome, even in unlikely clinical scenarios. PMID:25361367

  14. Acute pediatric leg compartment syndrome in chronic myeloid leukemia.

    PubMed

    Cohen, Eric; Truntzer, Jeremy; Trunzter, Jeremy; Klinge, Steve; Schwartz, Kevin; Schiller, Jonathan

    2014-11-01

    Acute compartment syndrome is an orthopedic surgical emergency and may result in devastating complications in the setting of delayed or missed diagnosis. Compartment syndrome has a variety of causes, including posttraumatic or postoperative swelling, external compression, burns, bleeding disorders, and ischemia-reperfusion injury. Rare cases of pediatric acute compartment syndrome in the setting of acute myeloid leukemia and, even less commonly, chronic myeloid leukemia have been reported. The authors report the first known case of pediatric acute compartment syndrome in a patient without a previously known diagnosis of chronic myeloid leukemia. On initial examination, an 11-year-old boy presented with a 2-week history of progressive left calf pain and swelling after playing soccer. Magnetic resonance imaging scan showed a hematoma in the left superficial posterior compartment. The patient had unrelenting pain, intermittent lateral foot parethesias, and inability to bear weight. Subsequently, he was diagnosed with acute compartment syndrome and underwent fasciotomy and evacuation of a hematoma. Laboratory results showed an abnormal white blood cell count of 440×10(9)/L (normal, 4.4-11×10(9)) and international normalized ratio of 1.3 (normal, 0.8-1.2). Further testing included the BCR-ABL1 fusion gene located on the Philadelphia chromosome, leading to a diagnosis of chronic myeloid leukemia. Monotherapy with imatinib mesylate (Gleevec) was initiated. This report adds another unique case to the growing literature on compartment syndrome in the pediatric population and reinforces the need to consider compartment syndrome, even in unlikely clinical scenarios.

  15. Acute myeloid leukemia in children: Current status and future directions.

    PubMed

    Taga, Takashi; Tomizawa, Daisuke; Takahashi, Hiroyuki; Adachi, Souichi

    2016-02-01

    Acute myeloid leukemia (AML) accounts for 25% of pediatric leukemia and affects approximately 180 patients annually in Japan. The treatment outcome for pediatric AML has improved through advances in chemotherapy, hematopoietic stem cell transplantation (HSCT), supportive care, and optimal risk stratification. Currently, clinical pediatric AML studies are conducted separately according to the AML subtypes: de novo AML, acute promyelocytic leukemia (APL), and myeloid leukemia with Down syndrome (ML-DS). Children with de novo AML are treated mainly with anthracyclines and cytarabine, in some cases with HSCT, and the overall survival (OS) rate now approaches 70%. Children with APL are treated with an all-trans retinoic acid (ATRA)-combined regimen with an 80-90% OS. Children with ML-DS are treated with a less intensive regimen compared with non-DS patients, and the OS is approximately 80%. HSCT in first remission is restricted to children with high-risk de novo AML only. To further improve outcomes, it will be necessary to combine more accurate risk stratification strategies using molecular genetic analysis with assessment of minimum residual disease, and the introduction of new drugs in international collaborative clinical trials. PMID:26645706

  16. PHF6 mutations in adult acute myeloid leukemia.

    PubMed

    Van Vlierberghe, P; Patel, J; Abdel-Wahab, O; Lobry, C; Hedvat, C V; Balbin, M; Nicolas, C; Payer, A R; Fernandez, H F; Tallman, M S; Paietta, E; Melnick, A; Vandenberghe, P; Speleman, F; Aifantis, I; Cools, J; Levine, R; Ferrando, A

    2011-01-01

    Loss of function mutations and deletions encompassing the plant homeodomain finger 6 (PHF6) gene are present in about 20% of T-cell acute lymphoblastic leukemias (ALLs). Here, we report the identification of recurrent mutations in PHF6 in 10/353 adult acute myeloid leukemias (AMLs). Genetic lesions in PHF6 found in AMLs are frameshift and nonsense mutations distributed through the gene or point mutations involving the second plant homeodomain (PHD)-like domain of the protein. As in the case of T-ALL, where PHF6 alterations are found almost exclusively in males, mutations in PHF6 were seven times more prevalent in males than in females with AML. Overall, these results identify PHF6 as a tumor suppressor gene mutated in AML and extend the role of this X-linked tumor suppressor gene in the pathogenesis of hematologic tumors.

  17. Inotuzumab ozogamicin in the treatment of acute lymphoblastic leukemia.

    PubMed

    Dahl, Jenny; Marx, Kayleigh; Jabbour, Elias

    2016-01-01

    Over 90% of leukemic blasts in patients with acute lymphoblastic leukemia express the marker CD22. Inotuzumab ozogamicin (INO) is a CD22-directed humanized monoclonal antibody conjugated to the potent cytotoxin, calicheamicin, via an acid labile linker. INO has shown high rates of response in the treatment of relapsed and refractory (R/R) ALL in single-agent studies, with fewer adverse effects than traditional cytotoxic chemotherapy. Given this experience, studies are now being done to evaluate INO in combination with low-intensity chemotherapy as frontline treatment for older adults with ALL and patients with R/R disease. Herein we will discuss the use of INO in the treatment of acute lymphoblastic leukemia.

  18. Thrombo-hemorrhagic deaths in acute promyelocytic leukemia.

    PubMed

    Breccia, Massimo; Lo Coco, Francesco

    2014-05-01

    Acute promyelocytic leukemia (APL) has become the most curable form of acute myeloid leukemia after the advent of all-trans retinoic acid (ATRA). However, early deaths (ED) mostly due to the disease-associated coagulopathy remain the major cause of treatment failure. In particular, hemorrhagic events account for 40-65% of ED and several prognostic factors have been identified for such hemorrhagic deaths, including poor performance status, high white blood cell (WBC) count and coagulopathy. Occurrence of thrombosis during treatment with ATRA may be associated with differentiation syndrome (DS) or represent an isolated event. Some prognostic factors have been reported to be associated with thrombosis, including increased WBC or aberrant immunophenotype of leukemic promyelocytes. Aim of this review is to report the incidence, severity, possible pathogenesis and clinical manifestations of thrombo-haemorrhagic deaths in APL.

  19. Thrombo-hemorrhagic deaths in acute promyelocytic leukemia.

    PubMed

    Breccia, Massimo; Lo Coco, Francesco

    2014-05-01

    Acute promyelocytic leukemia (APL) has become the most curable form of acute myeloid leukemia after the advent of all-trans retinoic acid (ATRA). However, early deaths (ED) mostly due to the disease-associated coagulopathy remain the major cause of treatment failure. In particular, hemorrhagic events account for 40-65% of ED and several prognostic factors have been identified for such hemorrhagic deaths, including poor performance status, high white blood cell (WBC) count and coagulopathy. Occurrence of thrombosis during treatment with ATRA may be associated with differentiation syndrome (DS) or represent an isolated event. Some prognostic factors have been reported to be associated with thrombosis, including increased WBC or aberrant immunophenotype of leukemic promyelocytes. Aim of this review is to report the incidence, severity, possible pathogenesis and clinical manifestations of thrombo-haemorrhagic deaths in APL. PMID:24862130

  20. Elbow septic arthritis associated with pediatric acute leukemia: a case report and literature review.

    PubMed

    Uemura, Takuya; Yagi, Hirohisa; Okada, Mitsuhiro; Yokoi, Takuya; Shintani, Kosuke; Nakamura, Hiroaki

    2015-01-01

    Acute leukemia in children presents with various clinical manifestations that mimic orthopaedic conditions. The association of septic arthritis of the elbow with acute leukemia is very rare, and the correct diagnosis of acute leukemia is often established only after treatment of the septic arthritis. In this article, we present a three-year-old child patient with elbow septic arthritis related to acute leukemia, diagnosed promptly by bone marrow aspiration on the same day as emergency surgical debridement of the septic elbow joint due to the maintenance of a high index of suspicion, and treated with chemotherapy as soon as possible. The emergency physician and orthopaedist must recognize unusual patterns of presentation like this. Since delay in initiating treatment of septic arthritis may result in growth disturbance, elbow septic arthritis associated with pediatric acute leukemia must be treated promptly and appropriately. Early diagnosis is a good prognostic feature of childhood acute leukemia.

  1. Bone marrow necrosis in acute leukemia: Clinical characteristic and outcome.

    PubMed

    Badar, Talha; Shetty, Aditya; Bueso-Ramos, Carlos; Cortes, Jorge; Konopleva, Marina; Borthakur, Gautam; Pierce, Sherry; Huang, Xuelin; Chen, Hsiang-Chun; Kadia, Tapan; Daver, Naval; Dinardo, Courtney; O'Brien, Susan; Garcia-Manero, Guillermo; Kantarjian, Hagop; Ravandi, Farhad

    2015-09-01

    Bone marrow necrosis (BMN) is characterized by infarction of the medullary stroma, leading to marrow necrosis with preserved cortical bone. In reported small series, BMN in hematological malignancies is associated with poor prognosis. We sought to find the impact of BMN on clinical outcome in a relatively larger cohort of patients with acute leukemias. Overall we evaluated 1,691 patients; 1,051 with acute myeloid leukemia (AML) and 640 with acute lymphocytic leukemia referred to our institution between 2002 and 2013. Patients with AML and acute lymphoblastic leukemia (ALL) were evaluated separately to determine the incidence of BMN, associated clinical features and its prognostic significance. At initial diagnosis, BMN was observed in 25 (2.4%) patients with AML and 20 (3.2%) patients with ALL. In AML, BMN was significantly associated with French-American-British AML M5 morphology (32% vs. 10%, P = 0.002). The complete remission (CR) rate in AML with and without BMN was 32% and 59% respectively (P = 0.008). Likewise, CR rate in ALL with BMN was also inferior, 70% vs. 92% (P = 0.005). The median overall survival (OS) in AML with BMN was significantly poorer, 3.7 months compared to 14 months without BMN (P = 0.003). Similarly, the median OS in ALL with and without BMN was 61.7 and 72 months respectively (P = 0.33). BMN is not a rare entity in AML and ALL, but is infrequent. BMN in AML and in ALL is suggestive of inferior response and poor prognosis.

  2. Acute myeloid leukemia with non-specific cutaneous manifestation.

    PubMed

    Kotokey, R K; Potsangham, T; Das, R

    2008-09-01

    Acute myeloid leukemia is not uncommon in upper Assam. Primary skin manifestation in AML though very rare, may be found. The skin manifestation may be the first presentation in AML. Here such a case has been discussed which presented with primarily skin manifestation, subsequently diagnosed as AML. Therefore routine investigations are mandatory in all patients before going for a sophisticated investigation so that the diagnosis is not missed. PMID:19086364

  3. Massive Pulmonary Embolism at the Onset of Acute Promyelocytic Leukemia

    PubMed Central

    Sorà, Federica; Chiusolo, Patrizia; Laurenti, Luca; Autore, Francesco; Giammarco, Sabrina; Sica, Simona

    2016-01-01

    Life-threatening bleeding is a major and early complication of acute promyelocytic leukemia (APL), but in the last years there is a growing evidence of thromboses in APL. We report the first case of a young woman with dyspnea as the first symptom of APL due to massive pulmonary embolism (PE) successfully treated with thrombolysis for PE and heparin. APL has been processed with a combination of all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) obtaining complete remission. PMID:27413520

  4. Effect of Taurine on Febrile Episodes in Acute Lymphoblastic Leukemia

    PubMed Central

    Islambulchilar, Mina; Asvadi, Iraj; Sanaat, Zohreh; Esfahani, Ali; Sattari, Mohammadreza

    2015-01-01

    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. PMID:25789226

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

    ClinicalTrials.gov

    2016-09-26

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

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

    ClinicalTrials.gov

    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

  7. Dasatinib in Treating Young Patients With Recurrent or Refractory Solid Tumors or Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia or Chronic Myelogenous Leukemia That Did Not Respond to Imatinib Mesylate

    ClinicalTrials.gov

    2013-02-04

    Accelerated Phase Chronic Myelogenous Leukemia; Blastic Phase Chronic Myelogenous Leukemia; Childhood Chronic Myelogenous Leukemia; Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Meningeal Chronic Myelogenous Leukemia; Recurrent Childhood Acute Lymphoblastic Leukemia; Relapsing Chronic Myelogenous Leukemia; Unspecified Childhood Solid Tumor, Protocol Specific

  8. Busulfan, Fludarabine Phosphate, and Anti-Thymocyte Globulin Followed By Donor Stem Cell Transplant and Azacitidine in Treating Patients With High-Risk Myelodysplastic Syndrome and Older Patients With Acute Myeloid Leukemia

    ClinicalTrials.gov

    2016-09-26

    Adult Acute Megakaryoblastic Leukemia; Adult Acute Monoblastic Leukemia; Adult Acute Monocytic Leukemia; Adult Acute Myeloid Leukemia in Remission; 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; Alkylating Agent-Related Acute Myeloid Leukemia; de Novo Myelodysplastic Syndrome; Previously Treated Myelodysplastic Syndrome; Recurrent Adult Acute Myeloid Leukemia; Refractory Anemia With Excess Blasts; Secondary Myelodysplastic Syndrome; Untreated Adult Acute Myeloid Leukemia

  9. Delirium in acute promyelocytic leukemia patients: two case reports

    PubMed Central

    2013-01-01

    Background Delirium is a frequently misdiagnosed and inadequately treated neuropsychiatric complication most commonly observed in terminally ill cancer patients. To our knowledge this is the first report describing delirium in two patients aged less than 60 years and enrolled in an intensive chemotherapeutic protocol for acute promyelocytic leukemia. Case presentation Two female Caucasian acute promyelocytic leukemia patients aged 46 and 56 years developed delirium during their induction treatment with all-trans retinoic acid and idarubicin. In both cases symptoms were initially attributed to all-trans retinoic acid that was therefore immediately suspended. In these two patients several situations may have contribute to the delirium: in patient 1 a previous psychiatric disorder, concomitant treatments with steroids and benzodiazepines, a severe infection and central nervous system bleeding while in patient 2 steroid treatment and isolation. In patient 1 delirium was treated with short-term low-doses of haloperidol while in patient 2 non-pharmacologic interventions had a beneficial role. When the diagnosis of delirium was clear, induction treatment was resumed and both patients completed their therapeutic program without any relapse of the psychiatric symptoms. Both patients are alive and in complete remission as far as their leukemia is concerned. Conclusions We suggest that patients with acute promyelocytic leukemia eligible to intensive chemotherapy should be carefully evaluated by a multisciplinary team including psychiatrists in order to early recognize symptoms of delirium and avoid inadequate treatments. In case of delirium, both pharmacologic and non-pharmacologic interventions may be considered. PMID:24237998

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

    ClinicalTrials.gov

    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

  11. Comprehensive mutational analysis of primary and relapse acute promyelocytic leukemia.

    PubMed

    Madan, V; Shyamsunder, P; Han, L; Mayakonda, A; Nagata, Y; Sundaresan, J; Kanojia, D; Yoshida, K; Ganesan, S; Hattori, N; Fulton, N; Tan, K-T; Alpermann, T; Kuo, M-C; Rostami, S; Matthews, J; Sanada, M; Liu, L-Z; Shiraishi, Y; Miyano, S; Chendamarai, E; Hou, H-A; Malnassy, G; Ma, T; Garg, M; Ding, L-W; Sun, Q-Y; Chien, W; Ikezoe, T; Lill, M; Biondi, A; Larson, R A; Powell, B L; Lübbert, M; Chng, W J; Tien, H-F; Heuser, M; Ganser, A; Koren-Michowitz, M; Kornblau, S M; Kantarjian, H M; Nowak, D; Hofmann, W-K; Yang, H; Stock, W; Ghavamzadeh, A; Alimoghaddam, K; Haferlach, T; Ogawa, S; Shih, L-Y; Mathews, V; Koeffler, H P

    2016-08-01

    Acute promyelocytic leukemia (APL) is a subtype of myeloid leukemia characterized by differentiation block at the promyelocyte stage. Besides the presence of chromosomal rearrangement t(15;17), leading to the formation of PML-RARA (promyelocytic leukemia-retinoic acid receptor alpha) fusion, other genetic alterations have also been implicated in APL. Here, we performed comprehensive mutational analysis of primary and relapse APL to identify somatic alterations, which cooperate with PML-RARA in the pathogenesis of APL. We explored the mutational landscape using whole-exome (n=12) and subsequent targeted sequencing of 398 genes in 153 primary and 69 relapse APL. Both primary and relapse APL harbored an average of eight non-silent somatic mutations per exome. We observed recurrent alterations of FLT3, WT1, NRAS and KRAS in the newly diagnosed APL, whereas mutations in other genes commonly mutated in myeloid leukemia were rarely detected. The molecular signature of APL relapse was characterized by emergence of frequent mutations in PML and RARA genes. Our sequencing data also demonstrates incidence of loss-of-function mutations in previously unidentified genes, ARID1B and ARID1A, both of which encode for key components of the SWI/SNF complex. We show that knockdown of ARID1B in APL cell line, NB4, results in large-scale activation of gene expression and reduced in vitro differentiation potential. PMID:27063598

  12. Comprehensive mutational analysis of primary and relapse acute promyelocytic leukemia

    PubMed Central

    Madan, V; Shyamsunder, P; Han, L; Mayakonda, A; Nagata, Y; Sundaresan, J; Kanojia, D; Yoshida, K; Ganesan, S; Hattori, N; Fulton, N; Tan, K-T; Alpermann, T; Kuo, M-C; Rostami, S; Matthews, J; Sanada, M; Liu, L-Z; Shiraishi, Y; Miyano, S; Chendamarai, E; Hou, H-A; Malnassy, G; Ma, T; Garg, M; Ding, L-W; Sun, Q-Y; Chien, W; Ikezoe, T; Lill, M; Biondi, A; Larson, R A; Powell, B L; Lübbert, M; Chng, W J; Tien, H-F; Heuser, M; Ganser, A; Koren-Michowitz, M; Kornblau, S M; Kantarjian, H M; Nowak, D; Hofmann, W-K; Yang, H; Stock, W; Ghavamzadeh, A; Alimoghaddam, K; Haferlach, T; Ogawa, S; Shih, L-Y; Mathews, V; Koeffler, H P

    2016-01-01

    Acute promyelocytic leukemia (APL) is a subtype of myeloid leukemia characterized by differentiation block at the promyelocyte stage. Besides the presence of chromosomal rearrangement t(15;17), leading to the formation of PML-RARA (promyelocytic leukemia-retinoic acid receptor alpha) fusion, other genetic alterations have also been implicated in APL. Here, we performed comprehensive mutational analysis of primary and relapse APL to identify somatic alterations, which cooperate with PML-RARA in the pathogenesis of APL. We explored the mutational landscape using whole-exome (n=12) and subsequent targeted sequencing of 398 genes in 153 primary and 69 relapse APL. Both primary and relapse APL harbored an average of eight non-silent somatic mutations per exome. We observed recurrent alterations of FLT3, WT1, NRAS and KRAS in the newly diagnosed APL, whereas mutations in other genes commonly mutated in myeloid leukemia were rarely detected. The molecular signature of APL relapse was characterized by emergence of frequent mutations in PML and RARA genes. Our sequencing data also demonstrates incidence of loss-of-function mutations in previously unidentified genes, ARID1B and ARID1A, both of which encode for key components of the SWI/SNF complex. We show that knockdown of ARID1B in APL cell line, NB4, results in large-scale activation of gene expression and reduced in vitro differentiation potential. PMID:27063598

  13. Activation of a promyelocytic leukemia-tumor protein 53 axis underlies acute promyelocytic leukemia cure.

    PubMed

    Ablain, Julien; Rice, Kim; Soilihi, Hassane; de Reynies, Aurélien; Minucci, Saverio; de Thé, Hugues

    2014-02-01

    Acute promyelocytic leukemia (APL) is driven by the promyelocytic leukemia (PML)-retinoic acid receptor-α (PML-RARA) fusion protein, which interferes with nuclear receptor signaling and PML nuclear body (NB) assembly. APL is the only malignancy definitively cured by targeted therapies: retinoic acid (RA) and/or arsenic trioxide, which both trigger PML-RARA degradation through nonoverlapping pathways. Yet, the cellular and molecular determinants of treatment efficacy remain disputed. We demonstrate that a functional Pml-transformation-related protein 53 (Trp53) axis is required to eradicate leukemia-initiating cells in a mouse model of APL. Upon RA-induced PML-RARA degradation, normal Pml elicits NB reformation and induces a Trp53 response exhibiting features of senescence but not apoptosis, ultimately abrogating APL-initiating activity. Apart from triggering PML-RARA degradation, arsenic trioxide also targets normal PML to enhance NB reformation, which may explain its clinical potency, alone or with RA. This Pml-Trp53 checkpoint initiated by therapy-triggered NB restoration is specific for PML-RARA-driven APL, but not the RA-resistant promyelocytic leukemia zinc finger (PLZF)-RARA variant. Yet, as NB biogenesis is druggable, it could be therapeutically exploited in non-APL malignancies.

  14. Outcomes after Induction Failure in Childhood Acute Lymphoblastic Leukemia

    PubMed Central

    Schrappe, Martin; Hunger, Stephen P.; Pui, Ching-Hon; Saha, Vaskar; Gaynon, Paul S.; Baruchel, André; Conter, Valentino; Otten, Jacques; Ohara, Akira; Versluys, Anne Birgitta; Escherich, Gabriele; Heyman, Mats; Silverman, Lewis B.; Horibe, Keizo; Mann, Georg; Camitta, Bruce M.; Harbott, Jochen; Riehm, Hansjörg; Richards, Sue; Devidas, Meenakshi; Zimmermann, Martin

    2012-01-01

    BACKGROUND Failure of remission-induction therapy is a rare but highly adverse event in children and adolescents with acute lymphoblastic leukemia (ALL). METHODS We identified induction failure, defined by the persistence of leukemic blasts in blood, bone marrow, or any extramedullary site after 4 to 6 weeks of remission-induction therapy, in 1041 of 44,017 patients (2.4%) 0 to 18 years of age with newly diagnosed ALL who were treated by a total of 14 cooperative study groups between 1985 and 2000. We analyzed the relationships among disease characteristics, treatments administered, and outcomes in these patients. RESULTS Patients with induction failure frequently presented with high-risk features, including older age, high leukocyte count, leukemia with a T-cell phenotype, the Philadelphia chromosome, and 11q23 rearrangement. With a median follow-up period of 8.3 years (range, 1.5 to 22.1), the 10-year survival rate (±SE) was estimated at only 32±1%. An age of 10 years or older, T-cell leukemia, the presence of an 11q23 rearrangement, and 25% or more blasts in the bone marrow at the end of induction therapy were associated with a particularly poor outcome. High hyperdiploidy (a modal chromosome number >50) and an age of 1 to 5 years were associated with a favorable outcome in patients with precursor B-cell leukemia. Allogeneic stem-cell transplantation from matched, related donors was associated with improved outcomes in T-cell leukemia. Children younger than 6 years of age with precursor B-cell leukemia and no adverse genetic features had a 10-year survival rate of 72±5% when treated with chemotherapy only. CONCLUSIONS Pediatric ALL with induction failure is highly heterogeneous. Patients who have T-cell leukemia appear to have a better outcome with allogeneic stem-cell transplantation than with chemotherapy, whereas patients who have precursor B-cell leukemia without other adverse features appear to have a better outcome with chemotherapy. (Funded by Deutsche

  15. Antileukemic Efficacy of Continuous vs Discontinuous Dexamethasone in Murine Models of Acute Lymphoblastic Leukemia

    PubMed Central

    Ramsey, Laura B.; Janke, Laura J.; Payton, Monique A.; Cai, Xiangjun; Paugh, Steven W.; Karol, Seth E.; Kamdem, Landry Kamdem; Cheng, Cheng; Williams, Richard T.; Jeha, Sima; Pui, Ching-Hon; Evans, William E.; Relling, Mary V.

    2015-01-01

    Osteonecrosis is one of the most common, serious, toxicities resulting from the treatment of acute lymphoblastic leukemia. In recent years, pediatric acute lymphoblastic leukemia clinical trials have used discontinuous rather than continuous dosing of dexamethasone in an effort to reduce the incidence of osteonecrosis. However, it is not known whether discontinuous dosing would compromise antileukemic efficacy of glucocorticoids. Therefore, we tested the efficacy of discontinuous dexamethasone against continuous dexamethasone in murine models bearing human acute lymphoblastic leukemia xenografts (n = 8 patient samples) or murine BCR-ABL+ acute lymphoblastic leukemia. Plasma dexamethasone concentrations (7.9 to 212 nM) were similar to those achieved in children with acute lymphoblastic leukemia using conventional dosages. The median leukemia-free survival ranged from 16 to 59 days; dexamethasone prolonged survival from a median of 4 to 129 days in all seven dexamethasone-sensitive acute lymphoblastic leukemias. In the majority of cases (7 of 8 xenografts and the murine BCR-ABL model) we demonstrated equal efficacy of the two dexamethasone dosing regimens; whereas for one acute lymphoblastic leukemia sample, the discontinuous regimen yielded inferior antileukemic efficacy (log-rank p = 0.002). Our results support the clinical practice of using discontinuous rather than continuous dexamethasone dosing in patients with acute lymphoblastic leukemia. PMID:26252865

  16. Functional Integration of Acute Myeloid Leukemia into the Vascular Niche

    PubMed Central

    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.; Scott, Edward W.; Fleming, William H.

    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 endothelial cells. V-AML cells acquire several endothelial cell-like characteristics, including the up-regulation of CD105, a receptor associated with activated endothelium. Remarkably, endothelial-integrated V-AML shows an almost 4-fold reduction in proliferative activity compared to non-vascular associated AML. Primary AML cells can be induced to down regulate the expression of their hematopoietic markers in vitro and differentiate into phenotypically and functionally-defined endothelial-like cells. After transplantation, these leukemia-derived endothelial cells are capable of giving rise to AML. Taken together, these novel functional interactions between AML cells and normal endothelium along with the reversible endothelial cell potential of AML suggest that vascular endothelium may serve as a previously unrecognized reservoir for acute myeloid leukemia. PMID:24637335

  17. Collaborative Efforts Driving Progress in Pediatric Acute Myeloid Leukemia

    PubMed Central

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

    2015-01-01

    Diagnosis, treatment, response monitoring, and outcome of pediatric acute myeloid leukemia (AML) have made enormous progress during the past decades. Because AML is a rare type of childhood cancer, with an incidence of approximately seven occurrences per 1 million children annually, national and international collaborative efforts have evolved. This overview describes these efforts and includes a summary of the history and contributions of each of the main collaborative pediatric AML groups worldwide. The focus is on translational and clinical research, which includes past, current, and future clinical trials. Separate sections concern acute promyelocytic leukemia, myeloid leukemia of Down syndrome, and relapsed AML. A plethora of novel antileukemic agents that have emerged, including new classes of drugs, are summarized as well. Finally, an important aspect of the treatment of pediatric AML—supportive care—and late effects are discussed. The future is bright, with a wide range of emerging innovative therapies and with more and more international collaboration that ultimately aim to cure all children with AML, with fewer adverse effects and without late effects. PMID:26304895

  18. Haploidentical Transplantation in Children with Acute Leukemia: The Unresolved Issues

    PubMed Central

    Jaiswal, Sarita Rani; Chakrabarti, Suparno

    2016-01-01

    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. PMID:27110243

  19. Collaborative Efforts Driving Progress in Pediatric Acute Myeloid Leukemia.

    PubMed

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

    2015-09-20

    Diagnosis, treatment, response monitoring, and outcome of pediatric acute myeloid leukemia (AML) have made enormous progress during the past decades. Because AML is a rare type of childhood cancer, with an incidence of approximately seven occurrences per 1 million children annually, national and international collaborative efforts have evolved. This overview describes these efforts and includes a summary of the history and contributions of each of the main collaborative pediatric AML groups worldwide. The focus is on translational and clinical research, which includes past, current, and future clinical trials. Separate sections concern acute promyelocytic leukemia, myeloid leukemia of Down syndrome, and relapsed AML. A plethora of novel antileukemic agents that have emerged, including new classes of drugs, are summarized as well. Finally, an important aspect of the treatment of pediatric AML--supportive care--and late effects are discussed. The future is bright, with a wide range of emerging innovative therapies and with more and more international collaboration that ultimately aim to cure all children with AML, with fewer adverse effects and without late effects.

  20. Update on developmental therapeutics for acute lymphoblastic leukemia.

    PubMed

    Smith, Malcolm A

    2009-07-01

    This is an exciting time in drug development for acute lymphoblastic leukemia (ALL). A confluence of trends makes it likely that highly effective new agents for ALL will be identified in the coming decade. One contributory factor is the development of more representative preclinical models of ALL for testing and prioritizing novel agents. Another important trend in ALL drug development is the increasing understanding at the molecular level of the genomic changes that occur in B-precursor and T-cell ALL. A final important trend is the increasing availability of new agents against relevant molecular targets. Molecularly targeted agents of interest discussed in this review include novel antibody-based drugs targeted against leukemia surface antigens, proteasome inhibitors, mTOR inhibitors, JAK inhibitors, Aurora A kinase inhibitors, and inhibitors of Bcl-2 family proteins. PMID:20425431

  1. PHF6 mutations in T-cell acute lymphoblastic leukemia.

    PubMed

    Van Vlierberghe, Pieter; Palomero, Teresa; Khiabanian, Hossein; Van der Meulen, Joni; Castillo, Mireia; Van Roy, Nadine; De Moerloose, Barbara; Philippé, Jan; González-García, Sara; Toribio, María L; Taghon, Tom; Zuurbier, Linda; Cauwelier, Barbara; Harrison, Christine J; Schwab, Claire; Pisecker, Markus; Strehl, Sabine; Langerak, Anton W; Gecz, Jozef; Sonneveld, Edwin; Pieters, Rob; Paietta, Elisabeth; Rowe, Jacob M; Wiernik, Peter H; Benoit, Yves; Soulier, Jean; Poppe, Bruce; Yao, Xiaopan; Cordon-Cardo, Carlos; Meijerink, Jules; Rabadan, Raul; Speleman, Frank; Ferrando, Adolfo

    2010-04-01

    Tumor suppressor genes on the X chromosome may skew the gender distribution of specific types of cancer. T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematological malignancy with an increased incidence in males. In this study, we report the identification of inactivating mutations and deletions in the X-linked plant homeodomain finger 6 (PHF6) gene in 16% of pediatric and 38% of adult primary T-ALL samples. Notably, PHF6 mutations are almost exclusively found in T-ALL samples from male subjects. Mutational loss of PHF6 is importantly associated with leukemias driven by aberrant expression of the homeobox transcription factor oncogenes TLX1 and TLX3. Overall, these results identify PHF6 as a new X-linked tumor suppressor in T-ALL and point to a strong genetic interaction between PHF6 loss and aberrant expression of TLX transcription factors in the pathogenesis of this disease.

  2. [Bleeding complications in acute myeloblastic leukemia (author's transl)].

    PubMed

    Sutor, A H

    1979-03-01

    Bleeding is common in acute myeloblastic leukemia (AML). At the time of diagnosis, the danger of bleeding cannot be predicted by laboratory means. However, the following factors represent increased risks: Promyeloblastic leukemia, high blast count, low fibrinogen, low plasminogen. From coagulation studies performed at the time of bleeding complications, the pathomechanism leading to bleeding complications usually cannot be detected. The question whether impairment of production, consumption coagulopathy, or primary fibrinolysis causes the bleeding complications can only be answered by controlling frequently clinical and hemostatic criteria, which include the thrombocytic stystem as well as plasmatic coagulation and fibrinolysis. At the present time, the therapy of bleeding complications in AML is symptomatic. It consists of transfusion with thrombocytes or fresh whole blood, respectively. Coagulation factor concentrates should only be given in combination with Heparin to prevent the deterioration of consumption coagulopathy.

  3. THE GENOMIC LANDSCAPE OF HYPODIPLOID ACUTE LYMPHOBLASTIC LEUKEMIA

    PubMed Central

    Holmfeldt, Linda; Wei, Lei; Diaz-Flores, Ernesto; Walsh, Michael; Zhang, Jinghui; Ding, Li; Payne-Turner, Debbie; Churchman, Michelle; Andersson, Anna; Chen, Shann-Ching; McCastlain, Kelly; Becksfort, Jared; Ma, Jing; Wu, Gang; Patel, Samir N.; Heatley, Susan L.; Phillips, Letha A.; Song, Guangchun; Easton, John; Parker, Matthew; Chen, Xiang; Rusch, Michael; Boggs, Kristy; Vadodaria, Bhavin; Hedlund, Erin; Drenberg, Christina; Baker, Sharyn; Pei, Deqing; Cheng, Cheng; Huether, Robert; Lu, Charles; Fulton, Robert S.; Fulton, Lucinda L.; Tabib, Yashodhan; Dooling, David J.; Ochoa, Kerri; Minden, Mark; Lewis, Ian D.; To, L. Bik; Marlton, Paula; Roberts, Andrew W.; Raca, Gordana; Stock, Wendy; Neale, Geoffrey; Drexler, Hans G.; Dickins, Ross A.; Ellison, David W.; Shurtleff, Sheila A.; Pui, Ching-Hon; Ribeiro, Raul C.; Devidas, Meenakshi; Carroll, Andrew J.; Heerema, Nyla A.; Wood, Brent; Borowitz, Michael J.; Gastier-Foster, Julie M.; Raimondi, Susana C.; Mardis, Elaine R.; Wilson, Richard K.; Downing, James R.; Hunger, Stephen P.; Loh, Mignon L.; Mullighan, Charles G.

    2013-01-01

    The genetic basis of hypodiploid acute lymphoblastic leukemia (ALL), a subtype of ALL characterized by aneuploidy and poor outcome, is unknown. Genomic profiling of 124 hypodiploid ALL cases, including whole genome and exome sequencing of 40 cases, identified two subtypes that differ in severity of aneuploidy, transcriptional profile and submicroscopic genetic alterations. Near haploid cases with 24–31 chromosomes harbor alterations targeting receptor tyrosine kinase- and Ras signaling (71%) and the lymphoid transcription factor IKZF3 (AIOLOS; 13%). In contrast, low hypodiploid ALL with 32–39 chromosomes are characterized by TP53 alterations (91.2%) which are commonly present in non-tumor cells, and alterations of IKZF2 (HELIOS; 53%) and RB1 (41%). Both near haploid and low hypodiploid tumors exhibit activation of Ras- and PI3K signaling pathways, and are sensitive to PI3K inhibitors, indicating that these drugs should be explored as a new therapeutic strategy for this aggressive form of leukemia. PMID:23334668

  4. Pharmacogenetics of alkylator-associated acute myeloid leukemia.

    PubMed

    Knoche, Eric; McLeod, Howard L; Graubert, Timothy A

    2006-07-01

    Therapy-related acute myeloid leukemia (t-AML) is a lethal late complication of alkylator chemotherapy. The genetic basis of susceptibility to t-AML is poorly understood. Both t-AML and de novo AML are complex genetic diseases, requiring cooperating mutations in interacting pathways for disease initiation and progression. Germline variants of these 'leukemia pathway' genes may cooperate with somatic mutations to induce both de novo and therapy-related AML. Several cancer susceptibility syndromes have been identified that cause an inherited predisposition to de novo and t-AML. The genes responsible for these syndromes are also somatically mutated in sporadic AML. We reason that germline polymorphism in any gene somatically mutated in AML could contribute to t-AML risk in the general population. Identification of these susceptibility alleles should help clinicians develop tailored therapies that reduce the relative risk of t-AML. PMID:16886897

  5. Functional heterogeneity of genetically defined subclones in acute myeloid leukemia

    PubMed Central

    Klco, Jeffery M.; Spencer, David H.; Miller, Christopher A.; Griffith, Malachi; Lamprecht, Tamara L.; O’Laughlin, Michelle; Fronick, Catrina; Magrini, Vincent; Demeter, Ryan T.; Fulton, Robert S.; Eades, William C.; Link, Daniel C.; Graubert, Timothy A.; Walter, Matthew J.; Mardis, Elaine R.; Dipersio, John F.; Wilson, Richard K.; Ley, Timothy J.

    2014-01-01

    Summary The relationships between clonal architecture and functional heterogeneity in acute myeloid leukemia (AML) samples are not yet clear. We used targeted sequencing to track AML subclones identified by whole genome sequencing using a variety of experimental approaches. We found that virtually all AML subclones trafficked from the marrow to the peripheral blood, but some were enriched in specific cell populations. Subclones showed variable engraftment potential in immunodeficient mice. Xenografts were predominantly comprised of a single genetically-defined subclone, but there was no predictable relationship between the engrafting subclone and the evolutionary hierarchy of the leukemia. These data demonstrate the importance of integrating genetic and functional data in studies of primary cancer samples, both in xenograft models and in patients. PMID:24613412

  6. Leukemia

    MedlinePlus

    ... version of this page please turn Javascript on. Leukemia What Is Leukemia? Leukemia is a cancer of the blood cells. ... diagnosed with leukemia are over 50 years old. Leukemia Starts in Bone Marrow Click for more information ...

  7. Acute Pancreatitis and Diabetic Ketoacidosis following L-Asparaginase/Prednisone Therapy in Acute Lymphoblastic Leukemia.

    PubMed

    Quintanilla-Flores, Dania Lizet; Flores-Caballero, Miguel Ángel; Rodríguez-Gutiérrez, René; Tamez-Pérez, Héctor Eloy; González-González, José Gerardo

    2014-01-01

    Acute pancreatitis and diabetic ketoacidosis are unusual adverse events following chemotherapy based on L-asparaginase and prednisone as support treatment for acute lymphoblastic leukemia. We present the case of a 16-year-old Hispanic male patient, in remission induction therapy for acute lymphoblastic leukemia on treatment with mitoxantrone, vincristine, prednisone, and L-asparaginase. He was hospitalized complaining of abdominal pain, nausea, and vomiting. Hyperglycemia, acidosis, ketonuria, low bicarbonate levels, hyperamylasemia, and hyperlipasemia were documented, and the diagnosis of diabetic ketoacidosis was made. Because of uncertainty of the additional diagnosis of acute pancreatitis as the cause of abdominal pain, a contrast-enhanced computed tomography was performed resulting in a Balthazar C pancreatitis classification.

  8. Acute Pancreatitis and Diabetic Ketoacidosis following L-Asparaginase/Prednisone Therapy in Acute Lymphoblastic Leukemia

    PubMed Central

    Quintanilla-Flores, Dania Lizet; Flores-Caballero, Miguel Ángel; Rodríguez-Gutiérrez, René; Tamez-Pérez, Héctor Eloy; González-González, José Gerardo

    2014-01-01

    Acute pancreatitis and diabetic ketoacidosis are unusual adverse events following chemotherapy based on L-asparaginase and prednisone as support treatment for acute lymphoblastic leukemia. We present the case of a 16-year-old Hispanic male patient, in remission induction therapy for acute lymphoblastic leukemia on treatment with mitoxantrone, vincristine, prednisone, and L-asparaginase. He was hospitalized complaining of abdominal pain, nausea, and vomiting. Hyperglycemia, acidosis, ketonuria, low bicarbonate levels, hyperamylasemia, and hyperlipasemia were documented, and the diagnosis of diabetic ketoacidosis was made. Because of uncertainty of the additional diagnosis of acute pancreatitis as the cause of abdominal pain, a contrast-enhanced computed tomography was performed resulting in a Balthazar C pancreatitis classification. PMID:24716037

  9. Investigating CD99 Expression in Leukemia Propagating Cells in Childhood T Cell Acute Lymphoblastic Leukemia

    PubMed Central

    Cox, Charlotte V.; Diamanti, Paraskevi; Moppett, John P.; Blair, Allison

    2016-01-01

    A significant number of children with T-lineage acute lymphoblastic leukemia (T-ALL) fail to respond to therapy and experience early relapse. CD99 has been shown to be overexpressed on T-ALL cells and is considered to be a reliable detector of the disease. However, the relevance of CD99 overexpression in ALL has not been investigated in a functional context. The aim of this study was to investigate the functional capacity of CD99+ cells in childhood ALL and determine the suitability of CD99 as a therapeutic target. Flow cytometric analyses confirmed higher expression of CD99 in ALL blasts (81.5±22.7%) compared to normal hemopoietic stem cells (27.5±21.9%) and T cells (3.1±5.2%, P≤0.004). When ALL cells were sorted and assessed in functional assays, all 4 subpopulations (CD34+/CD99+, CD34+/CD99-, CD34-/CD99+ and CD34-/CD99-) could proliferate in vitro and establish leukemia in NSG mice. Leukemia propagating cell frequencies ranged from 1 in 300 to 1 in 7.4x104 but were highest in the CD34+/CD99- subpopulation. In addition, all four subpopulations had self-renewal ability in secondary NSG mice. Cells in each subpopulation contained patient specific TCR rearrangements and karyotypic changes that were preserved with passage through serial NSG transplants. Despite high levels of CD99 antigen on the majority of blast cells, leukemia initiating capacity in vivo was not restricted to cells that express this protein. Consequently, targeting CD99 alone would not eliminate all T-ALL cells with the ability to maintain the disease. The challenge remains to develop therapeutic strategies that can eliminate all leukemia cells with self-renewal capacity in vivo. PMID:27764235

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

    ClinicalTrials.gov

    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

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

    PubMed Central

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

    2016-01-01

    Acute myeloid leukemia originates from leukemia-initiating cells that reside in the protective bone marrow niche. CXCR4/CXCL12 interaction is crucially involved in recruitment and retention of leukemia-initiating cells within this niche. Various drugs targeting this pathway have entered clinical trials. To evaluate CXCR4 imaging in acute myeloid leukemia, we first tested CXCR4 expression in patient-derived primary blasts. Flow cytometry revealed that high blast counts in patients with acute myeloid leukemia correlate with high CXCR4 expression. The wide range of CXCR4 surface expression in patients was reflected in cell lines of acute myeloid leukemia. Next, we evaluated the CXCR4-specific peptide Pentixafor by positron emission tomography imaging in mice harboring CXCR4 positive and CXCR4 negative leukemia xenografts, and in 10 patients with active disease. [68Ga]Pentixafor-positron emission tomography showed specific measurable disease in murine CXCR4 positive xenografts, but not when CXCR4 was knocked out with CRISPR/Cas9 gene editing. Five of 10 patients showed tracer uptake correlating well with leukemia infiltration assessed by magnetic resonance imaging. The mean maximal standard uptake value was significantly higher in visually CXCR4 positive patients compared to CXCR4 negative patients. In summary, in vivo molecular CXCR4 imaging by means of positron emission tomography is feasible in acute myeloid leukemia. These data provide a framework for future diagnostic and theranostic approaches targeting the CXCR4/CXCL12-defined leukemia-initiating cell niche. PMID:27175029

  12. Ras/Raf/MEK/ERK Pathway Activation in Childhood Acute Lymphoblastic Leukemia and Its Therapeutic Targeting

    PubMed Central

    Knight, Thomas; Irving, Julie Anne Elizabeth

    2014-01-01

    Deregulation of the Ras/Raf/MEK/extracellular signal-regulated kinase pathway is a common event in childhood acute lymphoblastic leukemia and is caused by point mutation, gene deletion, and chromosomal translocation of a vast array of gene types, highlighting its importance in leukemia biology. Pathway activation can be therapeutically exploited and may guide new therapies needed for relapsed acute lymphoblastic leukemia and other high risk subgroups. PMID:25009801

  13. Novel biological insights in T-cell acute lymphoblastic leukemia.

    PubMed

    Durinck, Kaat; Goossens, Steven; Peirs, Sofie; Wallaert, Annelynn; Van Loocke, Wouter; Matthijssens, Filip; Pieters, Tim; Milani, Gloria; Lammens, Tim; Rondou, Pieter; Van Roy, Nadine; De Moerloose, Barbara; Benoit, Yves; Haigh, Jody; Speleman, Frank; Poppe, Bruce; Van Vlierberghe, Pieter

    2015-08-01

    T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive type of blood cancer that accounts for about 15% of pediatric and 25% of adult acute lymphoblastic leukemia (ALL) cases. It is considered as a paradigm for the multistep nature of cancer initiation and progression. Genetic and epigenetic reprogramming events, which transform T-cell precursors into malignant T-ALL lymphoblasts, have been extensively characterized over the past decade. Despite our comprehensive understanding of the genomic landscape of human T-ALL, leukemia patients are still treated by high-dose multiagent chemotherapy, potentially followed by hematopoietic stem cell transplantation. Even with such aggressive treatment regimens, which are often associated with considerable acute and long-term side effects, about 15% of pediatric and 40% of adult T-ALL patients still relapse, owing to acquired therapy resistance, and present with very dismal survival perspectives. Unfortunately, the molecular mechanisms by which residual T-ALL tumor cells survive chemotherapy and act as a reservoir for leukemic progression and hematologic relapse remain poorly understood. Nevertheless, it is expected that enhanced molecular understanding of T-ALL disease biology will ultimately facilitate a targeted therapy driven approach that can reduce chemotherapy-associated toxicities and improve survival of refractory T-ALL patients through personalized salvage therapy. In this review, we summarize recent biological insights into the molecular pathogenesis of T-ALL and speculate how the genetic landscape of T-ALL could trigger the development of novel therapeutic strategies for the treatment of human T-ALL. PMID:26123366

  14. Inhibitory effects of sesquiterpene lactones isolated from Eupatorium chinense L. on IgE-mediated degranulation in rat basophilic leukemia RBL-2H3 cells and passive cutaneous anaphylaxis reaction in mice.

    PubMed

    Itoh, Tomohiro; Oyama, Masayoshi; Takimoto, Norihiko; Kato, Chihiro; Nozawa, Yoshinori; Akao, Yukihiro; Iinuma, Munekazu

    2009-04-15

    Sesquiterpene lactones (SQTLs) have been shown to suppress the degranulation as inferred by histamine release in rat basophilic leukemia RBL-2H3 cells. In this study, we isolated the 9 kinds of SQTLs from Eupatorium chinense L. and examined the effects of these SQTLs on the degranulation in RBL-2H3 cells. The chemical structures of two novel compounds (SQTL-3 and 8) were determined. All the SQTLs suppressed the degranulation from Ag-stimulated RBL-2H3 cells. To disclose the inhibitory mechanism of degranulation by SQTLs, we examined the activation of intracellular signaling molecules such as Lyn, Syk, and PLCgammas and intracellular free Ca(2+) concentration ([Ca(2+)]i). None of these SQTLs showed the activation of Syk and PLCgammas. The intracellular free Ca(2+) concentration ([Ca(2+)]i) was elevated by Fc epsilonRI activation, but SQTLs treatment reduced the elevation of [Ca(2+)]i by suppressing Ca(2+) influx. Thus, it was suggested that the suppression of Ag-stimulated degranulation by these SQTLs is mainly due to the decreased Ca(2+) influx. Furthermore, in order to clarify the in vivo effect of SQTL-rich extract, we administered SQTL-rich extract to the type I allergic model mice and measured the passive cutaneous anaphylaxis (PCA) reaction induced by IgE-antigen complex. The SQTLs remarkably suppressed PCA reaction in a dose-dependent manner. Thus, it was suggested that SQTLs would be a candidate as an anti-allergic agent.

  15. Testis Scintigraphy in a Patient with Acute Lymphoblastic Leukemia

    PubMed Central

    Şencan Eren, Mine; Koç, Murat; Ören, Hale; Özkal, Şermin; Durak, Hatice

    2014-01-01

    Acute lymphoblastic leukemia (ALL) is a pediatric malignancy associated with remissions and relapses. Common relapsing sitesare meninges, testis and ovary. Testicular scintigraphy is a highly specific modality used mainly in the differential diagnosis of testicular torsion and epidydimitis/epidydimo-orchitis. There is only one interesting image on leukemic infiltration with scrotal scintigraphy in the literature. The aim of this case presentation is to report that although the scintigraphic appearance of testicular torsion was observed in a patient with the diagnosis of ALL, testicular ALL infiltration was revealed in pathologic examination. Conflict of interest:None declared. PMID:24653935

  16. Building better therapy for children with acute lymphoblastic leukemia.

    PubMed

    Carroll, William L; Raetz, Elizabeth A

    2005-04-01

    Childhood acute lymphoblastic leukemia is one of the most curable of all human cancers, but new approaches are urgently needed for children who relapse and to avoid severe side effects of curative therapy. Work from the laboratories of Rob Pieters and William Evans, including a paper in this issue of Cancer Cell, has led to the identification of genes whose expression correlates with drug crossresistance and long term outcome. The goal is now to integrate these and other findings using gene expression technology into the care of children with the most common pediatric malignancy. PMID:15837616

  17. Ecthyma gangrenosum in a patient with acute leukemia.

    PubMed

    Kryeziu, Emrush; Kryeziu, K; Bajraktari, Gjani; Abazi, M; Zylfiu, B; Rudhani, I; Sadiku, Sh; Ukimeri, A; Brovina, A; Dreshaj, Sh; Telaku, S

    2010-01-01

    Ecthymagangrenosum (EG)is a rare condition with characteristic clinical appearance of red maculae that progresses to a central area of necrosis surrounded by an erythematous halo. The most frequently it is caused by Pseudomonas bacteriaemia in neutropenic patient. The authors presents a patient with acute myloblastic leukemia M4 type in whom in relapse EG caused by Pseudomonas aeruginosa was found. The patient was treated with antibiotics and surgical debridement. The author wants to point out on clinical significance this condition with high mortality rate.

  18. [Disseminated papules in a patient with acute myeloid leukemia].

    PubMed

    Ceric-Dehdari, P; Houcinat, Y; Berger, T G

    2010-11-01

    Cryptococcosis most commonly occurs in immunosuppressed patients. The pathogen is the yeast Cryptococcus neoformans. This article reports on the case of a 20-year-old female patient with acute myeloid leukemia who suddenly developed disseminated livid red papules and papulovesicles. The clinical picture and in particular the histopathology findings led to the diagnosis of cutaneous cryptococcosis, which was successfully treated with amphotericin B. For the differential diagnosis generalized herpes zoster, erythema exudativum multiforme and disseminated molluscum contagiosum must be considered. To confirm the diagnosis attempts can also be made to culture the pathogen from skin biopsy preparations. Furthermore, fungal spores can be rapidly and simply detected with the Tzanck test. PMID:20927503

  19. Myelodysplastic Syndromes and Acute Myeloid Leukemia in the Elderly.

    PubMed

    Klepin, Heidi D

    2016-02-01

    Myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) are hematologic diseases that frequently affect older adults. Treatment is challenging. Management of older adults with MDS and AML needs to be individualized, accounting for both the heterogeneity of disease biology and patient characteristics, which can influence life expectancy and treatment tolerance. Clinical trials accounting for the heterogeneity of tumor biology and physiologic changes of aging are needed to define optimal standards of care. This article highlights key evidence related to the management of older adults with MDS and AML and highlights future directions for research.

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

    PubMed

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

    2006-09-01

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

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

    PubMed

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

    2015-01-01

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

  2. Acute Myeloid Leukemia Complicated by Giant Cell Arteritis.

    PubMed

    Tsunemine, Hiroko; Umeda, Ryosuke; Nohda, Yasuhiro; Sakane, Emiko; Akasaka, Hiroshi; Itoh, Kiminari; Izumi, Mayuko; Tsuji, Goh; Kodaka, Taiichi; Itoh, Tomoo; Takahashi, Takayuki

    2016-01-01

    Giant cell arteritis (GCA), a type of systemic arteritis, is rare in Japan. We herein report a case of acute myeloid leukemia (AML) complicated by GCA that manifested during chemotherapy for AML. A 77-year-old woman with severe back pain was diagnosed with AML. She achieved complete remission with the resolution of her back pain following induction chemotherapy. However, she developed a headache and fever after consolidation chemotherapy. A diagnosis of GCA was made based on a biopsy of the temporal artery and arterial imaging. GCA should therefore be included in the differential diagnosis in AML patients complicated with a headache and fever of unknown origin. PMID:26831026

  3. Combination Chemotherapy and Rituximab in Treating Young Patients With Recurrent or Refractory Non-Hodgkin's Lymphoma or Acute Lymphoblastic Leukemia

    ClinicalTrials.gov

    2013-10-07

    B-cell Childhood Acute Lymphoblastic Leukemia; Childhood Burkitt Lymphoma; Childhood Diffuse Large Cell Lymphoma; Childhood Immunoblastic Large Cell Lymphoma; L3 Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Large Cell Lymphoma; Recurrent Childhood Lymphoblastic Lymphoma; Recurrent Childhood Small Noncleaved Cell Lymphoma

  4. Co-operative leukemogenesis in acute myeloid leukemia and acute promyelocytic leukemia reveals C/EBPα as a common target of TRIB1 and PML/RARA

    PubMed Central

    Keeshan, Karen; Vieugué, Pauline; Chaudhury, Shahzya; Rishi, Loveena; Gaillard, Coline; Liang, Lu; Garcia, Elaine; Nakamura, Takuro; Omidvar, Nader; Kogan, Scott C.

    2016-01-01

    The PML/RARA fusion protein occurs as a result of the t(15;17) translocation in the acute promyelocytic leukemia subtype of human acute myeloid leukemia. Gain of chromosome 8 is the most common chromosomal gain in human acute myeloid leukemia, including acute promyelocytic leukemia. We previously demonstrated that gain of chromosome 8-containing MYC is of central importance in trisomy 8, but the role of the nearby TRIB1 gene has not been experimentally addressed in this context. We have now tested the hypothesis that both MYC and TRIB1 have functional roles underlying leukemogenesis of trisomy 8 by using retroviral vectors to express MYC and TRIB1 in wild-type bone marrow and in marrow that expressed a PML/RARA transgene. Interestingly, although MYC and TRIB1 readily co-operated in leukemogenesis for wild-type bone marrow, TRIB1 provided no selective advantage to cells expressing PML/RARA. We hypothesized that this lack of co-operation between PML/RARA and TRIB1 reflected a common pathway for their effect: both proteins targeting the myeloid transcription factor C/EBPα. In support of this idea, TRIB1 expression abrogated the all-trans retinoic acid response of acute promyelocytic leukemia cells in vitro and in vivo. Our data delineate the common and redundant inhibitory effects of TRIB1 and PML/RARA on C/EBPα providing a potential explanation for the lack of selection of TRIB1 in human acute promyelocytic leukemia, and highlighting the key role of C/EBPs in acute promyelocytic leukemia pathogenesis and therapeutic response. In addition, the co-operativity we observed between MYC and TRIB1 in the absence of PML/RARA show that, outside of acute promyelocytic leukemia, gain of both genes may drive selection for trisomy 8. PMID:27390356

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

    PubMed Central

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

    2012-01-01

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

  6. Acute myeloid leukemia with multilineage dysplasia in children.

    PubMed

    Adachi, Souichi; Manabe, Atsushi; Imaizumi, Masue; Taga, Takashi; Tawa, Akio; Tsurusawa, Masahito; Kikuchi, Akira; Masunaga, Atsuko; Tsuchida, Masahiro; Nakahata, Tatsutoshi

    2007-11-01

    We retrospectively surveyed pediatric acute myeloid leukemia (AML) patients with multilineage dysplasia treated with the AML 99 and the Children's Cancer and Leukemia Study Group (CCLSG) AML 9805 protocols. We found only 9 AML patients (2.6%) with multilineage dysplasia among the 341 patients with newly diagnosed de novo AML. Eight of the 9 patients obtained complete remission (CR) following the intensive AML-oriented treatments. Three of 7 patients who underwent stem cell transplantation were alive in CR for more than 4 years, and the 2 patients treated only with chemotherapy were alive in CR for more than 30 months. We did not identify any particular chromosomal abnormalities or differentiation according to the French-American-British classification in these 9 patients. No reports have described AML with multilineage dysplasia in children, and the incidence of the disease is expected to be very low. We plan to conduct a prospective pathologic review to select cases with this disease entity in the next Japanese Pediatric Leukemia/Lymphoma Study Group (JPLSG) AML-05 protocol.

  7. Nanoparticle targeted therapy against childhood acute lymphoblastic leukemia

    NASA Astrophysics Data System (ADS)

    Satake, Noriko; Lee, Joyce; Xiao, Kai; Luo, Juntao; Sarangi, Susmita; Chang, Astra; McLaughlin, Bridget; Zhou, Ping; Kenney, Elaina; Kraynov, Liliya; Arnott, Sarah; McGee, Jeannine; Nolta, Jan; Lam, Kit

    2011-06-01

    The goal of our project is to develop a unique ligand-conjugated nanoparticle (NP) therapy against childhood acute lymphoblastic leukemia (ALL). LLP2A, discovered by Dr. Kit Lam, is a high-affinity and high-specificity peptidomimetic ligand against an activated α4β1 integrin. Our study using 11 fresh primary ALL samples (10 precursor B ALL and 1 T ALL) showed that childhood ALL cells expressed activated α4β1 integrin and bound to LLP2A. Normal hematopoietic cells such as activated lymphocytes and monocytes expressed activated α4β1 integrin; however, normal hematopoietic stem cells showed low expression of α4β1 integrin. Therefore, we believe that LLP2A can be used as a targeted therapy for childhood ALL. The Lam lab has developed novel telodendrimer-based nanoparticles (NPs) which can carry drugs efficiently. We have also developed a human leukemia mouse model using immunodeficient NOD/SCID/IL2Rγ null mice engrafted with primary childhood ALL cells from our patients. LLP2A-conjugated NPs will be evaluated both in vitro and in vivo using primary leukemia cells and this mouse model. NPs will be loaded first with DiD near infra-red dye, and then with the chemotherapeutic agents daunorubicin or vincristine. Both drugs are mainstays of current chemotherapy for childhood ALL. Targeting properties of LLP2A-conjugated NPs will be evaluated by fluorescent microscopy, flow cytometry, MTS assay, and mouse survival after treatment. We expect that LLP2A-conjugated NPs will be preferentially delivered and endocytosed to leukemia cells as an effective targeted therapy.

  8. Aleukemic Leukemia Cutis Manifesting with Disseminated Nodular Eruptions and a Plaque Preceding Acute Monocytic Leukemia: A Case Report

    PubMed Central

    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

  9. Treatment of Childhood Acute Lymphoblastic Leukemia Without Prophylactic Cranial Irradiation

    PubMed Central

    Pui, Ching-Hon; Campana, Dario; Pei, Deqing; Bowman, W. Paul; Sandlund, John T.; Kaste, Sue C.; Ribeiro, Raul C.; Rubnitz, Jeffrey E.; Raimondi, Susana C.; Onciu, Mihaela; Coustan-Smith, Elaine; Kun, Larry E.; Jeha, Sima; Cheng, Cheng; Howard, Scott C.; Simmons, Vickey; Bayles, Amy; Metzger, Monika L.; Boyett, James M.; Leung, Wing; Handgretinger, Rupert; Downing, James R.; Evans, William E.; Relling, Mary V.

    2009-01-01

    Background We conducted a clinical trial to test whether prophylactic cranial irradiation could be omitted in all children with newly diagnosed acute lymphoblastic leukemia. Methods A total of 498 evaluable patients were enrolled. Treatment intensity was based on presenting features and the level of minimal residual disease after remission induction treatment. Continuous complete remission was compared between the 71 patients who previously would have received prophylactic cranial irradiation and the 56 historical controls who received it. Results The 5-year event-free and overall survival probabilities (95% confidence interval) for all 498 patients were 85.6% (79.9% to 91.3%) and 93.5% (89.8% to 97.2%), respectively. The 5-year cumulative risk of isolated central-nervous-system (CNS) relapse was 2.7% (1.1% to 4.2%), and that of any CNS relapse (isolated plus combined) was 3.9% (1.9% to 5.9%). The 71 patients had significantly better continuous complete remission than the 56 historical controls (P=0.04). All 11 patients with isolated CNS relapse remain in second remission for 0.4 to 5.5 years. CNS leukemia (CNS-3 status) or a traumatic lumbar puncture with blasts at diagnosis and a high level of minimal residual disease (≥ 1%) after 6 weeks of remission induction were significantly associated with poorer event-free survival. Risk factors for CNS relapse included the presence of the t(1;19)[TCF3-PBX1], any CNS involvement at diagnosis, and T-cell immunophenotype. Common adverse effects included allergic reactions to L-asparaginase, osteonecrosis, thrombosis, and disseminated fungal infection. Conclusions With effective risk-adjusted chemotherapy, prophylactic cranial irradiation can be safely omitted in the treatment of childhood acute lymphoblastic leukemia. PMID:19553647

  10. Early Complications of Hyperleukocytosis and Leukapheresis in Childhood Acute Leukemias.

    PubMed

    Abla, Oussama; Angelini, Paola; Di Giuseppe, Giancarlo; Kanani, Mohamed F; Lau, Wendy; Hitzler, Johann; Sung, Lillian; Naqvi, Ahmed

    2016-03-01

    Hyperleukocytosis in children with acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) is associated with early morbidity and mortality. The benefit from leukapheresis is controversial, and its complications are not well defined. We analyzed the frequency of early complications in children with ALL and AML presenting with white blood cell (WBC) count >100 × 10(9)/L, and the type and frequency of complications related to leukapheresis. During a 12-year period, 84 of 634 (13%) ALL and 18 of 143 (12.5%) AML patients presented with hyperleukocytosis. Leukapheresis was performed in 18 ALL and 12 AML patients. The median initial WBC was 474 × 10(9)/L in the leukapheresis group compared with 175 × 10(9)/L in the nonleukapheresis group. Neurological leukostasis occurred in 6 ALL (7.1%) and 4 AML (22.2%) patients. Pulmonary leukostasis occurred in 16 ALL (19%) and 4 AML patients (22.2%). Neurological symptoms improved in few patients after leukapheresis, except in patients with very high WBC (>650 × 10(9)/L in ALL and >400 × 10(9)/L in AML). Leukapheresis improved respiratory symptoms in some patients but caused worsening symptoms in others. Early death was associated with neurological complications, AML diagnosis, and coagulopathy. Leukapheresis did not delay initiation of chemotherapy, nor did it impact early response to chemotherapy or long-term survival. Complications included femoral vein thrombosis, electrolyte imbalances, and hemodynamic instability, which were all reversible. The role of leukapheresis as a cytoreductive procedure in childhood hyperleukocytic leukemia remains to be well defined.

  11. Evolving Therapies in Acute Myeloid Leukemia: Progress at Last?

    PubMed

    DeAngelo, Daniel J; Stein, Eytan M; Ravandi, Farhad

    2016-01-01

    Acute myeloid leukemia (AML) is an acquired disease characterized by chromosomal translocations and somatic mutations that lead to leukemogenesis. Systemic combination chemotherapy with an anthracycline and cytarabine remains the standard induction regimen for "fit" adults. Patients who achieve complete remission generally receive postinduction therapy with cytarabine-based chemotherapy or an allogeneic bone marrow transplant. Those unfit for induction chemotherapy are treated with hypomethylating agents (HMAs), low-dose cytarabine, or they are offered supportive care alone with transfusions and prophylactic antimicrobials. The revolution in understanding the genetics of AML, facilitated by next-generation sequencing, has led to many new drugs against driver mutations. Better methods of identification of leukemic blasts have provided us with better means to detect the disease left behind after cytotoxic chemotherapy regimens. This measurable residual disease has been correlated with poorer relapse-free survival, demonstrating the need for novel strategies to eradicate it to improve the outcome of patients with acute leukemias. In this article, we discuss adapting and improving AML therapy by age and comorbidities, emerging targeted therapies in AML, and minimal residual disease (MRD) assessment in AML. PMID:27249736

  12. Lymphocyte aromatic hydrocarbon responsiveness in acute leukemia of childhood

    SciTech Connect

    Blumer, J.L.; Dunn, R.; Esterhay, M.D.; Yamashita, T.S.; Gross, S.

    1981-12-01

    Aryl hydrocarbon hydroxylase (AHH) activity and inducibility were examined in mitogen-stimulated cultured lymphocytes from children with acute leukemia in remission, with nonleukemic malignancies, and with no family or personal history of malignant disease. Neither morphological differences nor differences in mitogen responsivelness were observed among the three sources of cells studied. Levels of constitutive and dibenzanthracene-induced AHH activity were found to be similar among the three groups by analysis of variance. However, when results were analyzed in terms of inducibility ratios, it was found that cells from leukemic children were significantly less inducible (p < 0.005) than cells from unaffected children or children with nonleukemic malignancies. The reason for this difference became apparent when statistical criteria were employed for the phenotypic separation of individuals who were highly aromatic hydrocarbon responsive and minimally responsive. A significantly larger proportion (p < 0.001) of leukemic children than unaffected children or children with nonleukemic malignancy were found to be minimally aromatic hydrocarbon responsive. Moreover, in patients with acute lymphoblastic leukemia relapsing while on therapy, longer durations of the first remission were correlated (r = 0.63, p < 0.05) with the highly inducible AHH phenotype.

  13. Fanconi Syndrome: A Rare Initial Presentation of Acute Lymphoblastic Leukemia.

    PubMed

    Sahu, Kamal Kant; Law, Arjun Datt; Jain, Nidhi; Khadwal, Alka; Suri, Vikas; Malhotra, Pankaj; Varma, Subhash Chander

    2016-06-01

    A-14-year old boy, presented with a short history of excessive thirst and increased urine output. Clinical examination showed pallor, generalized lymphadenopathy and hepatosplenomegaly. For evaluation of his polyuric state he underwent routine laboratory investigations, including renal function test, acid-base studies, urine analysis. Blood tests suggested hypokalemia, hypouricemia, hypocalcemia and hyperchloremia with normal liver and kidney function tests. The arterial blood gas analysis was suggestive of normal anion gap metabolic acidosis. Urine analysis was suggestive of hyperuricosuria, hypercalciuria and glycosuria with a positive urine anion gap. His hemogram showed pancytopenia with differential count showing 88% blasts. Bone marrow examination and flowcytometry confirmed the diagnosis of B cell acute lymphoblastic leukemia. Hence this case was atypical and very interesting in the sense that the Fanconi syndrome is very rare to be an initial presenting feature of acute lymphoblastic leukemia. The patient was started on oral as well intravenous supplementation with potassium, bicarbonate, calcium and phosphorus. Simultaneously, as per the modified BFM -90 protocol (four drug based regimen-Prednisolone, vincristine, daunorubicin, cyclophosphamide along with l-asparaginase), he was started on induction protocol. By the end of 3rd week of induction therapy, his urine output started normalizing and finally settled at the end of induction therapy. At present he is in the maintenance phase of chemotherapy. PMID:27408343

  14. Targeting signaling pathways in acute lymphoblastic leukemia: new insights.

    PubMed

    Harrison, Christine J

    2013-01-01

    The genetics of acute lymphoblastic leukemia are becoming well understood and the incidence of individual chromosomal abnormalities varies considerably with age. Cytogenetics provide reliable risk stratification for treatment: high hyperdiploidy and ETV6-RUNX1 are good risk, whereas BCR-ABL1, MLL rearrangements, and hypodiploidy are poor risk. Nevertheless, some patients within the good- and intermediate-risk groups will unpredictably relapse. With advancing technologies in array-based approaches (single nucleotide polymorphism arrays) and next-generation sequencing to study the genome, increasing numbers of new genetic changes are being discovered. These include deletions of B-cell differentiation and cell cycle control genes, as well as mutations of genes in key signaling pathways. Their associations and interactions with established cytogenetic subgroups and with each other are becoming elucidated. Whether they have a link to outcome is the most important factor for refinement of risk factors in relation to clinical trials. For several newly identified abnormalities, including intrachromosomal amplification of chromosome 21 (iAMP21), that are associated with a poor prognosis with standard therapy, appropriately modified treatment has significantly improved outcome. After the successful use of tyrosine kinase inhibitors in the treatment of BCR-ABL1-positive acute lymphoblastic leukemia, patients with alternative ABL1 translocations and rearrangements involving PDGFRB may benefit from treatment with tyrosine kinase inhibitors. Other aberrations, for example, CRLF2 overexpression and JAK2 mutations, are also providing potential novel therapeutic targets with the prospect of reduced toxicity.

  15. Advancing the Minimal Residual Disease Concept in Acute Myeloid Leukemia.

    PubMed

    Hokland, Peter; Ommen, Hans B; Mulé, Matthew P; Hourigan, Christopher S

    2015-07-01

    The criteria to evaluate response to treatment in acute myeloid leukemia (AML) have changed little in the past 60 years. It is now possible to use higher sensitivity tools to measure residual disease burden in AML. Such minimal or measurable residual disease (MRD) measurements provide a deeper understanding of current patient status and allow stratification for risk of subsequent clinical relapse. Despite these obvious advantages, and after over a decade of laboratory investigation and preclinical validation, MRD measurements are not currently routinely used for clinical decision-making or drug development in non-acute promyelocytic leukemia (non-APL) AML. We review here some potential constraints that may have delayed adoption, including a natural hesitancy of end users, economic impact concerns, misperceptions regarding the meaning of and need for assay sensitivity, the lack of one single MRD solution for all AML patients, and finally the need to involve patients in decision-making based on such correlates. It is our opinion that none of these issues represent insurmountable barriers and our hope is that by providing potential solutions we can help map a path forward to a future where our patients will be offered personalized treatment plans based on the amount of AML they have left remaining to treat. PMID:26111465

  16. [Acute myeloid leukemia. Genetic diagnostics and molecular therapy].

    PubMed

    Schlenk, R F; Döhner, K; Döhner, H

    2013-02-01

    Acute myeloid leukemia (AML) is a genetically heterogeneous disease. The genetic diagnostics have become an essential component in the initial work-up for disease classification, prognostication and prediction. More and more promising molecular targeted therapeutics are becoming available. A prerequisite for individualized treatment strategies is a fast pretherapeutic molecular screening including the fusion genes PML-RARA, RUNX1-RUNX1T1 and CBFB-MYH11 as well as mutations in the genes NPM1, FLT3 and CEBPA. Promising new therapeutic approaches include the combination of all- trans retinoic acid and arsentrioxid in acute promyelocytic leukemia, the combination of intensive chemotherapy with KIT inhibitors in core-binding factor AML and FLT3 inhibitors in AML with FLT3 mutation, as well as gemtuzumab ozogamicin therapy in patients with low and intermediate cytogenetic risk profiles. With the advent of the next generation sequencing technologies it is expected that new therapeutic targets will be identified. These insights will lead to a further individualization of AML therapy.

  17. Minimally differentiated acute myelogenous leukemia (AML-M0) granulocytic sarcoma presenting in the oral cavity.

    PubMed

    Amin, Kay S; Ehsan, Aamir; McGuff, H Stan; Albright, Steven C

    2002-07-01

    Acute myelogenous leukemia with minimal differentiation (AML-M0) is a rare subtype of acute leukemia in which blasts fail to show morphologic differentiation and conventional cytochemical stains and myeloid markers are negative. Acute myelogenous leukemia (AML) presents primarily with peripheral blood and/or bone marrow involvement. Presentation in extramedullary sites, including the head and neck region, is not uncommon. Acute myelomonocytic leukemia (AML-M4) and acute monocytic leukemia (AML-M5) have had the highest incidence of associated oral infiltrates. We report a case of a 58-year-old gentleman, with no prior history of acute leukemia, presenting with a solitary palatal swelling. Initial morphologic examination favored high-grade non-Hodgkin's lymphoma (NHL). Conventional cytochemical and immunohistochemical stains were negative for lymphoid and myeloid markers. Subsequent immunophenotyping via flow cytometry performed on peripheral blood and bone marrow aspirate demonstrated myeloid lineage without lymphoid differentiation, confirming the diagnosis of AML-M0.To our knowledge, this subtype of AML-M0 has not been previously reported involving the oral cavity. With absence of morphologic differentiation, and negative findings on conventional cytochemical and immunohistochemical stains, this subtype of leukemia may be misdiagnosed as non-Hodgkin's lymphoma (NHL). Flow cytometry is useful in detecting the myeloid lineage of this leukemia. PMID:12110349

  18. MLL-MLLT10 fusion gene in pediatric acute megakaryoblastic leukemia.

    PubMed

    Morerio, Cristina; Rapella, Annamaria; Tassano, Elisa; Rosanda, Cristina; Panarello, Claudio

    2005-10-01

    The occurrence of MLL gene rearrangement in acute megakaryoblastic leukemia (AML-M7, acute myeloid leukemia, French-American-British type M7) is very rare and limited to pediatric age: in particular, MLL-MLLT10 fusion, previously reported as characteristic of monocytic leukemia, has been reported in only one case of pediatric megakaryoblastic leukemia. We describe the second case with this association in light of the few reported cases of AML-M7 with MLL and/or 11q23 involvement.

  19. Risk-Adapted Chemotherapy in Treating Younger Patients With Newly Diagnosed Standard-Risk Acute Lymphoblastic Leukemia or Localized B-Lineage Lymphoblastic Lymphoma

    ClinicalTrials.gov

    2016-09-23

    Adult B Lymphoblastic Lymphoma; Childhood B Acute Lymphoblastic Leukemia; Childhood B Acute Lymphoblastic Leukemia With t(9;22)(q34;q11.2); BCR-ABL1; Childhood B Lymphoblastic Lymphoma; Down Syndrome; Stage I B Lymphoblastic Lymphoma; Stage II B Lymphoblastic Lymphoma; Untreated Adult Acute Lymphoblastic Leukemia; Untreated Childhood Acute Lymphoblastic Leukemia

  20. Sirolimus and Azacitidine in Treating Patients With High Risk Myelodysplastic Syndrome or Acute Myeloid Leukemia That is Recurrent or Not Eligible for Intensive Chemotherapy

    ClinicalTrials.gov

    2016-10-18

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

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

    PubMed Central

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

    2014-01-01

    Acute myocardial infarction and acute myeloid leukemia are rarely reported as concomitant conditions. The management of ST-elevation myocardial infarction (STEMI) in patients who have acute myeloid leukemia is challenging: the leukemia-related thrombocytopenia, platelet dysfunction, and systemic coagulopathy increase the risk of bleeding, and the administration of thrombolytic agents can be fatal. We report the case of a 76-year-old man who presented emergently with STEMI, myelodysplastic syndrome, and newly recognized acute myeloid leukemia transformation. Standard antiplatelet and anticoagulation therapy were contraindicated by the patient's thrombocytopenia and by his reported ecchymosis and gingival bleeding upon admission. He declined cardiac catheterization, was provided palliative care, and died 2 hours after hospital admission. We searched the English-language medical literature, found 8 relevant reports, and determined that the prognosis for patients with concomitant STEMI and acute myeloid leukemia is clearly worse than that for either individual condition. No guidelines exist to direct the management of STEMI and concomitant acute myeloid leukemia. In 2 reports, dual antiplatelet therapy, anticoagulation, and drug-eluting stent implantation were used without an increased risk of bleeding in the short term, even in the presence of thrombocytopenia. However, we think that a more conservative approach—balloon angioplasty with the provisional use of bare-metal stents—might be safer. Simultaneous chemotherapy for the acute myeloid leukemia is crucial. Older age seems to be a major risk factor: patients too frail for emergent treatment can die within hours or days. PMID:24808792

  2. Laboratory Treated T Cells in Treating Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia, Non-Hodgkin Lymphoma, or Acute Lymphoblastic Leukemia

    ClinicalTrials.gov

    2016-08-16

    Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Chronic Lymphocytic Leukemia; Recurrent Diffuse Large B-Cell Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Non-Hodgkin Lymphoma; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Diffuse Large B-Cell Lymphoma; Refractory Mantle Cell Lymphoma; Refractory Non-Hodgkin Lymphoma; Refractory Small Lymphocytic Lymphoma

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

    PubMed Central

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

    2013-01-01

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

  4. Recurrent Arterial Thrombosis as a Presenting Feature of a Variant M3-Acute Promyelocytic Leukemia

    PubMed Central

    Chotai, Pranit N.; Kasangana, Kalenda; Chandra, Abhinav B.; Rao, Atul S.

    2016-01-01

    Acute limb ischemia (ALI) is a common vascular emergency. Hematologic malignancies are commonly associated with derangement of normal hemostasis and thrombo-hemorrhagic symptoms during the course of the disease are common. However, ALI as an initial presenting feature of acute leukemia is rare. Due to the rarity of this presentation, there is a scarcity of prospective randomized data to optimally guide the management of these patients. Current knowledge is mainly based on isolated cases. We report our experience managing a patient who presented with ALI and was found to have occult leukemia. A review of all cases with ALI as a presenting feature of acute leukemia is also presented. PMID:27386455

  5. Hemophagocytosis by Leukemic Blasts in T Cell Acute Lymphoblastic Leukemia: An Unusual Finding.

    PubMed

    Harrison, Aradhana; Chandra, Dinesh; Kakkar, Naveen; Das, Sheila; John, M Joseph

    2016-06-01

    Hemophagocytosis shows engulfment of hematopoietic cells by histiocytes and is a property generally associated with cells of the histiocytic lineage. It can be familial or is seen in a wide spectrum of acquired disorders. Hemophagocytosis by leukemic blasts is an uncommon phenomenon and has been reported mainly in acute myeloid leukemia. Its association with acute lymphoblastic leukemia is rare. We present a case of hemophagocytosis by blasts in the bone marrow in a 11 year old boy with T cell-acute lymphoblastic leukemia. PMID:27408348

  6. Recurrent Arterial Thrombosis as a Presenting Feature of a Variant M3-Acute Promyelocytic Leukemia.

    PubMed

    Chotai, Pranit N; Kasangana, Kalenda; Chandra, Abhinav B; Rao, Atul S

    2016-06-01

    Acute limb ischemia (ALI) is a common vascular emergency. Hematologic malignancies are commonly associated with derangement of normal hemostasis and thrombo-hemorrhagic symptoms during the course of the disease are common. However, ALI as an initial presenting feature of acute leukemia is rare. Due to the rarity of this presentation, there is a scarcity of prospective randomized data to optimally guide the management of these patients. Current knowledge is mainly based on isolated cases. We report our experience managing a patient who presented with ALI and was found to have occult leukemia. A review of all cases with ALI as a presenting feature of acute leukemia is also presented. PMID:27386455

  7. Hemophagocytosis by Leukemic Blasts in T Cell Acute Lymphoblastic Leukemia: An Unusual Finding.

    PubMed

    Harrison, Aradhana; Chandra, Dinesh; Kakkar, Naveen; Das, Sheila; John, M Joseph

    2016-06-01

    Hemophagocytosis shows engulfment of hematopoietic cells by histiocytes and is a property generally associated with cells of the histiocytic lineage. It can be familial or is seen in a wide spectrum of acquired disorders. Hemophagocytosis by leukemic blasts is an uncommon phenomenon and has been reported mainly in acute myeloid leukemia. Its association with acute lymphoblastic leukemia is rare. We present a case of hemophagocytosis by blasts in the bone marrow in a 11 year old boy with T cell-acute lymphoblastic leukemia.

  8. Wilms tumor 1 mutations in the pathogenesis of acute myeloid leukemia

    PubMed Central

    Rampal, Raajit; Figueroa, Maria E.

    2016-01-01

    Wilms tumor 1 (WT1) has long been implicated in acute myeloid leukemia. It has been described to be both overexpressed and mutated in different forms of acute myeloid leukemia, and overexpression has been reported to play a prognostic role in this disease. However, the precise mechanism through which WT1 may play a role in leukemogenesis has remained elusive. In recent years, new evidence has emerged that points towards a novel role of WT1 mutations in the deregulation of epigenetic programs in leukemic cells through its interaction with TET proteins. Herein we review the current status of the field and its therapeutic and prognostic implications in acute myeloid leukemia. PMID:27252512

  9. Recurrent Arterial Thrombosis as a Presenting Feature of a Variant M3-Acute Promyelocytic Leukemia.

    PubMed

    Chotai, Pranit N; Kasangana, Kalenda; Chandra, Abhinav B; Rao, Atul S

    2016-06-01

    Acute limb ischemia (ALI) is a common vascular emergency. Hematologic malignancies are commonly associated with derangement of normal hemostasis and thrombo-hemorrhagic symptoms during the course of the disease are common. However, ALI as an initial presenting feature of acute leukemia is rare. Due to the rarity of this presentation, there is a scarcity of prospective randomized data to optimally guide the management of these patients. Current knowledge is mainly based on isolated cases. We report our experience managing a patient who presented with ALI and was found to have occult leukemia. A review of all cases with ALI as a presenting feature of acute leukemia is also presented.

  10. Serotonin storage pools in basophil leukemia and mast cells: characterization of two types of serotonin binding protein and radioautographic analysis of the intracellular distribution of (/sup 3/H)serotonin

    SciTech Connect

    Tamir, H.; Theoharides, T.C.; Gershon, M.D.; Askenase, P.W.

    1982-06-01

    The binding of serotonin to protein(s) derived from rat basophil leukemia (RBL) cells and mast cells was studied. Two types of serotonin binding protein in RBL cells was found. These proteins differed from one another in molecular weight and eluted in separate peaks from sephadex G-200 columns. Peak I protein (KD = 1.9 x 10/sup -6/ M) was a glycoprotein that bound to concanavalin A (Con A); Peak II protein (KD/sub 1/ = 4.5 x 10/sup -/8 M; KD/sub 2/ = 3.9 x 10/sup -6/ M) did not bind to Con A. Moreover, binding of (/sup 3/H)serotonin to protein of Peak I was sensitive to inhibition by reserpine, while binding of (/sup 3/H)serotonin to protein of Peak II resisted inhibition by that drug. Other differences between the two types of binding protein were found, the most significant of which was the far more vigorous conditions of homogenization required to extract Peak I than Peak II protein. Electron microscope radioautographic analysis of the intracellular distribution of (/sup 3/H) serotonin taken up in vitro by RBL cells or in vivo by murine mast cells indicated that essentially all of the labeled amine was located in cytoplasmic granules.No evidence for a pool in the cytosol was found and all granules were capable of becoming labeled. The presence of two types of intracellular serotonin binding proteins in these cells may indicate that there are two intracellular storage compartments for the amine. Both may be intragranular, but Peak I protein may be associated with the granular membrane while Peak II protein may be more free within the granular core. Different storage proteins may help to explain the differential release of amines from mast cell granules.

  11. Activation of protein tyrosine kinase p72syk by Fc epsilon RI aggregation in rat basophilic leukemia cells. p72syk is a minor component but the major protein tyrosine kinase of pp72.

    PubMed

    Minoguchi, K; Benhamou, M; Swaim, W D; Kawakami, Y; Kawakami, T; Siraganian, R P

    1994-06-17

    Aggregation of the high affinity IgE receptors (Fc epsilon RI) on rat basophilic leukemia RBL-2H3 cells results in protein tyrosine phosphorylations. Previously we reported that there is prominent tyrosine phosphorylation of approximately 72-kDa proteins (pp72) and that the tyrosine kinase p72syk is one component of pp72. Here we studied further the relationship of p72syk to pp72. The aggregation of Fc epsilon RI induced the activation of p72syk which was parallel to its tyrosine phosphorylation. By in vitro kinase assay of immune complexes purified with anti-phosphotyrosine antibodies, p72syk was the major pp72 tyrosine kinase. However, by immunoblotting with anti-phosphotyrosine antibodies, p72syk was a minor component of pp72. The heterogeneous nature of pp72 was indicated by different studies. Under optimum conditions of one-dimensional sodium dodecyl sulfate-polyacrylamide gel electrophoresis, pp72 consisted of a heterogeneous group of 69-, 71-, and 72-kDa tyrosine-phosphorylated proteins. There were differences in the tyrosine phosphorylation of these proteins in cells activated in the absence of extracellular calcium or when stimulation was with the calcium ionophore A23187 or with phorbol myristate acetate. One of the proteins migrating at 69 kDa was p72syk. By two-dimensional gel electrophoresis pp72 was found to consist of multiple tyrosine-phosphorylated protens including 71-80-kDa proteins that associate with p53/56lyn. A 75-kDa tyrosine-phosphorylated protein, different from pp72, was identified as p75HS1 (SPY75). These results demonstrate the heterogeneous nature of the pp72 and that p72syk is activated after Fc epsilon RI aggregation. PMID:7515887

  12. Diagnosis of chronic myeloid and acute lymphocytic leukemias by detection of leukemia-specific mRNA sequences amplified in vitro.

    PubMed Central

    Kawasaki, E S; Clark, S S; Coyne, M Y; Smith, S D; Champlin, R; Witte, O N; McCormick, F P

    1988-01-01

    The Philadelphia chromosome is present in more than 95% of chronic myeloid leukemia patients and 13% of acute lymphocytic leukemia patients. The Philadelphia translocation, t(9;22), fuses the BCR and ABL genes resulting in the expression of leukemia-specific, chimeric BCR-ABL messenger RNAs. To facilitate diagnosis of these leukemias, we have developed a method of amplifying and detecting only the unique mRNA sequences, using an extension of the polymerase chain reaction technique. Diagnosis of chronic myeloid and acute lymphocytic leukemias by this procedure is rapid, much more sensitive than existing protocols, and independent of the presence or absence of an identifiable Philadelphia chromosome. Images PMID:3165197

  13. Acute myelogenous leukemia following radiation therapy and chemotherapy for osteogenic sarcoma

    SciTech Connect

    Jacobs, A.D.; Gale, R.P.

    1984-06-01

    Patients receiving ionizing radiation therapy or cytotoxic chemotherapy are at increased risk of developing acute myelogenous leukemia. Ten cases of therapy-linked myelogenous leukemia have been reported in patients with sarcoma, and the authors report here the first case in a patient who received combined-modality therapy for treatment of an osteogenic sarcoma. As treatment for this disease becomes more intensive and survival improves, the incidence of leukemia following therapy for osteogenic sarcoma may increase.

  14. Transplant Outcomes for Children with Hypodiploid Acute Lymphoblastic Leukemia

    PubMed Central

    Mehta, Parinda A.; Zhang, Mei-Jie; Eapen, Mary; He, Wensheng; Seber, Adriana; Gibson, Brenda; Camitta, Bruce M.; Kitko, Carrie L.; Dvorak, Christopher C.; Nemecek, Eneida R.; Frangoul, Haydar A.; Abdel-Azim, Hisham; Kasow, Kimberly A.; Lehmann, Leslie; Vicent, Marta Gonzalez; Diaz Pérez, Miguel A.; Ayas, Mouhab; Qayed, Muna; Carpenter, Paul A.; Jodele, Sonata; Lund, Troy C.; Leung, Wing H.; Davies, Stella M.

    2015-01-01

    Children with hypodiploid acute lymphoblastic leukemia (ALL) have inferior outcomes despite intensive risk adapted chemotherapy regimens. We describe 78 children with hypodiploid ALL who underwent hematopoietic stem cell transplant (HSCT) between 1990 and 2010. Thirty nine (50%) patients had ≤ 43 chromosomes, 12 (15%) had 44 chromosomes and 27 (35%) had 45 chromosomes. Forty three (55%) patients were transplanted in first remission (CR1) while 35 (45%) were transplanted in ≥CR2. Twenty nine patients (37%) received a graft from a related donor and 49 (63%) from an unrelated donor. All patients received a myeloablative conditioning regimen. The 5-year probabilities of leukemia-free survival (LFS), overall survival (OS), relapse, and treatment related mortality (TRM) for the entire cohort were 51%, 56%, 27% and 22% respectively. Multivariate analysis confirmed that mortality risks were higher for patients transplanted in CR2 (HR 2.16, p=0.05), with chromosome number ≤43 (HR 2.15, p=0.05) and for those transplanted in the first decade of the study period (HR 2.60, p=0.01). Similarly, treatment failure risks were higher with chromosome number ≤43 (HR 2.28, p=0.04) and the earlier transplant period (HR 2.51, p=0.01). Although survival is better with advances in donor selection and supportive care, disease-related risk factors significantly influence transplantation outcomes. PMID:25865650

  15. Small molecule activation of NOTCH signaling inhibits acute myeloid leukemia.

    PubMed

    Ye, Qi; Jiang, Jue; Zhan, Guanqun; Yan, Wanyao; Huang, Liang; Hu, Yufeng; Su, Hexiu; Tong, Qingyi; Yue, Ming; Li, Hua; Yao, Guangmin; Zhang, Yonghui; Liu, Hudan

    2016-01-01

    Aberrant activation of the NOTCH signaling pathway is crucial for the onset and progression of T cell leukemia. Yet recent studies also suggest a tumor suppressive role of NOTCH signaling in acute myeloid leukemia (AML) and reactivation of this pathway offers an attractive opportunity for anti-AML therapies. N-methylhemeanthidine chloride (NMHC) is a novel Amaryllidaceae alkaloid that we previously isolated from Zephyranthes candida, exhibiting inhibitory activities in a variety of cancer cells, particularly those from AML. Here, we report NMHC not only selectively inhibits AML cell proliferation in vitro but also hampers tumor development in a human AML xenograft model. Genome-wide gene expression profiling reveals that NMHC activates the NOTCH signaling. Combination of NMHC and recombinant human NOTCH ligand DLL4 achieves a remarkable synergistic effect on NOTCH activation. Moreover, pre-inhibition of NOTCH by overexpression of dominant negative MAML alleviates NMHC-mediated cytotoxicity in AML. Further mechanistic analysis using structure-based molecular modeling as well as biochemical assays demonstrates that NMHC docks in the hydrophobic cavity within the NOTCH1 negative regulatory region (NRR), thus promoting NOTCH1 proteolytic cleavage. Our findings thus establish NMHC as a potential NOTCH agonist that holds great promises for future development as a novel agent beneficial to patients with AML. PMID:27211848

  16. Karyotype complexity and prognosis in acute myeloid leukemia

    PubMed Central

    Stölzel, F; Mohr, B; Kramer, M; Oelschlägel, U; Bochtler, T; Berdel, W E; Kaufmann, M; Baldus, C D; Schäfer-Eckart, K; Stuhlmann, R; Einsele, H; Krause, S W; Serve, H; Hänel, M; Herbst, R; Neubauer, A; Sohlbach, K; Mayer, J; Middeke, J M; Platzbecker, U; Schaich, M; Krämer, A; Röllig, C; Schetelig, J; Bornhäuser, M; Ehninger, G

    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 in AML with regard to adverse prognosis. Our study demonstrated that (1) patients with a pure hyperdiploid karyotype have an adverse risk irrespective of the number of chromosomal gains, (2) patients with translocation t(9;11)(p21∼22;q23) have an intermediate risk independent of the number of additional aberrations, (3) patients with ⩾4 abnormalities have an adverse risk per se and (4) patients with three aberrations in the absence of abnormalities of strong influence (hyperdiploid karyotype, t(9;11)(p21∼22;q23), CBF-AML, unique adverse-risk aberrations) have borderline intermediate/adverse risk with a reduced overall survival compared with patients with a normal karyotype. PMID:26771812

  17. Stem Cell Hierarchy and Clonal Evolution in Acute Lymphoblastic Leukemia

    PubMed Central

    Lang, Fabian; Wojcik, Bartosch; Rieger, Michael A.

    2015-01-01

    Cancer is characterized by a remarkable intertumoral, intratumoral, and cellular heterogeneity that might be explained by the cancer stem cell (CSC) and/or the clonal evolution models. CSCs have the ability to generate all different cells of a tumor and to reinitiate the disease after remission. In the clonal evolution model, a consecutive accumulation of mutations starting in a single cell results in competitive growth of subclones with divergent fitness in either a linear or a branching succession. Acute lymphoblastic leukemia (ALL) is a highly malignant cancer of the lymphoid system in the bone marrow with a dismal prognosis after relapse. However, stabile phenotypes and functional data of CSCs in ALL, the so-called leukemia-initiating cells (LICs), are highly controversial and the question remains whether there is evidence for their existence. This review discusses the concepts of CSCs and clonal evolution in respect to LICs mainly in B-ALL and sheds light onto the technical controversies in LIC isolation and evaluation. These aspects are important for the development of strategies to eradicate cells with LIC capacity. Common properties of LICs within different subclones need to be defined for future ALL diagnostics, treatment, and disease monitoring to improve the patients' outcome in ALL. PMID:26236346

  18. Small molecule activation of NOTCH signaling inhibits acute myeloid leukemia

    PubMed Central

    Ye, Qi; Jiang, Jue; Zhan, Guanqun; Yan, Wanyao; Huang, Liang; Hu, Yufeng; Su, Hexiu; Tong, Qingyi; Yue, Ming; Li, Hua; Yao, Guangmin; Zhang, Yonghui; Liu, Hudan

    2016-01-01

    Aberrant activation of the NOTCH signaling pathway is crucial for the onset and progression of T cell leukemia. Yet recent studies also suggest a tumor suppressive role of NOTCH signaling in acute myeloid leukemia (AML) and reactivation of this pathway offers an attractive opportunity for anti-AML therapies. N-methylhemeanthidine chloride (NMHC) is a novel Amaryllidaceae alkaloid that we previously isolated from Zephyranthes candida, exhibiting inhibitory activities in a variety of cancer cells, particularly those from AML. Here, we report NMHC not only selectively inhibits AML cell proliferation in vitro but also hampers tumor development in a human AML xenograft model. Genome-wide gene expression profiling reveals that NMHC activates the NOTCH signaling. Combination of NMHC and recombinant human NOTCH ligand DLL4 achieves a remarkable synergistic effect on NOTCH activation. Moreover, pre-inhibition of NOTCH by overexpression of dominant negative MAML alleviates NMHC-mediated cytotoxicity in AML. Further mechanistic analysis using structure-based molecular modeling as well as biochemical assays demonstrates that NMHC docks in the hydrophobic cavity within the NOTCH1 negative regulatory region (NRR), thus promoting NOTCH1 proteolytic cleavage. Our findings thus establish NMHC as a potential NOTCH agonist that holds great promises for future development as a novel agent beneficial to patients with AML. PMID:27211848

  19. Acute myeloid leukemia risk by industry and occupation

    PubMed Central

    Tsai, Rebecca J.; Luckhaupt, Sara E.; Schumacher, Pam; Cress, Rosemary D.; Deapen, Dennis M.; Calvert, Geoffrey M.

    2015-01-01

    Acute myeloid leukemia (AML) is the most common type of leukemia found in adults. Identifying jobs that pose a risk for AML may be useful for identifying new risk factors. A matched case–control analysis was conducted using California Cancer Registry data from 1988 to 2007. This study included 8999 cases of AML and 24 822 controls. Industries with a statistically significant increased AML risk were construction (matched odds ratio [mOR] = 1.13); crop production (mOR = 1.41); support activities for agriculture and forestry (mOR = 2.05); and animal slaughtering and processing (mOR = 2.09). Among occupations with a statistically significant increased AML risk were miscellaneous agricultural workers (mOR = 1.76); fishers and related fishing workers (mOR = 2.02); nursing, psychiatric and home health aides (mOR = 1.65); and janitors and building cleaners (mOR = 1.54). Further investigation is needed to confirm study findings and to identify specific exposures responsible for the increased risks. PMID:24547710

  20. Current management of newly diagnosed acute promyelocytic leukemia.

    PubMed

    Cicconi, L; Lo-Coco, F

    2016-08-01

    The management of acute promyelocytic leukemia (APL) has considerably evolved during the past two decades. The advent of all-trans retinoic acid (ATRA) and its inclusion in combinatorial regimens with anthracycline chemotherapy has provided cure rates exceeding 80%; however, this widely adopted approach also conveys significant toxicity including severe myelosuppression and rare occurrence of secondary leukemias. More recently, the advent of arsenic trioxide (ATO) and its use in association with ATRA with or without chemotherapy has further improved patient outcome by allowing to minimize the intensity of chemotherapy, thus reducing serious toxicity while maintaining high anti-leukemic efficacy. The advantage of ATRA-ATO over ATRA chemotherapy has been recently demonstrated in two large randomized trials and this option has now become the new standard of care in low-risk (i.e. non-hyperleukocytic) patients. In light of its rarity, abrupt onset and high risk of early death and due to specific treatment requirements, APL remains a challenging condition that needs to be managed in highly experienced centers. We review here the results of large clinical studies conducted in newly diagnosed APL as well as the recommendations for appropriate diagnosis, prevention and management of the main complications associated with modern treatment of the disease. PMID:27084953

  1. Retinoid receptor signaling and autophagy in acute promyelocytic leukemia

    SciTech Connect

    Orfali, Nina; McKenna, Sharon L.; Cahill, Mary R.; Gudas, Lorraine J.; Mongan, Nigel P.

    2014-05-15

    Retinoids are a family of signaling molecules derived from vitamin A with well established roles in cellular differentiation. Physiologically active retinoids mediate transcriptional effects on cells through interactions with retinoic acid (RARs) and retinoid-X (RXR) receptors. Chromosomal translocations involving the RARα gene, which lead to impaired retinoid signaling, are implicated in acute promyelocytic leukemia (APL). All-trans-retinoic acid (ATRA), alone and in combination with arsenic trioxide (ATO), restores differentiation in APL cells and promotes degradation of the abnormal oncogenic fusion protein through several proteolytic mechanisms. RARα fusion-protein elimination is emerging as critical to obtaining sustained remission and long-term cure in APL. Autophagy is a degradative cellular pathway involved in protein turnover. Both ATRA and ATO also induce autophagy in APL cells. Enhancing autophagy may therefore be of therapeutic benefit in resistant APL and could broaden the application of differentiation therapy to other cancers. Here we discuss retinoid signaling in hematopoiesis, leukemogenesis, and APL treatment. We highlight autophagy as a potential important regulator in anti-leukemic strategies. - Highlights: • Normal and aberrant retinoid signaling in hematopoiesis and leukemia is reviewed. • We suggest a novel role for RARα in the development of X-RARα gene fusions in APL. • ATRA therapy in APL activates transcription and promotes onco-protein degradation. • Autophagy may be involved in both onco-protein degradation and differentiation. • Pharmacologic autophagy induction may potentiate ATRA's therapeutic effects.

  2. Acute myeloid leukemia risk by industry and occupation.

    PubMed

    Tsai, Rebecca J; Luckhaupt, Sara E; Schumacher, Pam; Cress, Rosemary D; Deapen, Dennis M; Calvert, Geoffrey M

    2014-11-01

    Acute myeloid leukemia (AML) is the most common type of leukemia found in adults. Identifying jobs that pose a risk for AML may be useful for identifying new risk factors. A matched case-control analysis was conducted using California Cancer Registry data from 1988 to 2007. This study included 8999 cases of AML and 24 822 controls. Industries with a statistically significant increased AML risk were construction (matched odds ratio [mOR] = 1.13); crop production (mOR = 1.41); support activities for agriculture and forestry (mOR = 2.05); and animal slaughtering and processing (mOR = 2.09). Among occupations with a statistically significant increased AML risk were miscellaneous agricultural workers (mOR = 1.76); fishers and related fishing workers (mOR = 2.02); nursing, psychiatric and home health aides (mOR = 1.65); and janitors and building cleaners (mOR = 1.54). Further investigation is needed to confirm study findings and to identify specific exposures responsible for the increased risks.

  3. Nucleophosmin mutations in childhood acute myelogenous leukemia with normal karyotype.

    PubMed

    Cazzaniga, Giovanni; Dell'Oro, Maria Grazia; Mecucci, Cristina; Giarin, Emanuela; Masetti, Riccardo; Rossi, Vincenzo; Locatelli, Franco; Martelli, Massimo F; Basso, Giuseppe; Pession, Andrea; Biondi, Andrea; Falini, Brunangelo

    2005-08-15

    Nucleophosmin (NPM) is a nucleocytoplasmic shuttling protein involved in leukemia-associated chromosomal translocations, and it regulates the alternate reading frame (ARF)-p53 tumor-suppressor pathway. Recently, it has been demonstrated that mutations of the NPM1 gene alter the protein at its C-terminal, causing its cytoplasmic localization. Cytoplasmic NPM was detected in 35% of adult patients with primary non-French-American-British (FAB) classification M3 acute myeloid leukemia (AML), associated mainly with normal karyotype. We evaluated the prevalence of the NPM1 gene mutation in non-M3 childhood AML patients enrolled in the ongoing Associazione Italiana di Ematologia e Oncologia Pediatrica (AIEOP-AML02) protocol in Italy. NPM1 mutations were found in 7 (6.5%) of 107 successfully analyzed patients. NPM1-mutated patients carried a normal karyotype (7/26, 27.1%) and were older in age. Thus, the NPM1 mutation is a frequent abnormality in AML patients without known genetic marker; the mutation may represent a new target to monitor minimal residual disease in AML and a potential candidate for alternative and targeted treatments.

  4. Erythema nodosum and granulomatous lesions preceding acute myelomonocytic leukemia.

    PubMed

    Anan, Takashi; Imamura, Tomoyuki; Yokoyama, Shigeo; Fujiwara, Sakuhei

    2004-09-01

    A 65-year-old female with a one-month history of painful eruptions on her lower extremities was admitted to our hospital. Histological examination revealed erythema nodosum (EN), and the patient was treated with oral prednisolone (PSL; 20 mg daily). The eruptions subsided in two weeks. One month later, painful reddish eruptions recurred on her upper limbs and abdomen in addition to her lower extremities. A skin biopsy from an abdominal erythematous plaque revealed a non-caseating granuloma without microorganisms or foreign-body materials. These eruptions also disappeared with treatment with oral PSL (20 mg daily). No underlying disease, including sarcoidosis, diabetes mellitus, or rheumatoid arthritis, was found. However, five months later, the patient developed conspicuous leukocytosis. She was diagnosed with acute myelomonocytic leukemia (M4) and treated with chemotherapy. After complete remission had been achieved, the EN reappeared, in association with an increase in blastic cells in the bone marrow. Serum levels of tumor necrosis factor-alpha and interleukin-1 beta, which are thought to be essential for granuloma formation and induction of EN, were markedly elevated. Physicians must remember that recurrent EN and granulomatous lesions can be a prodromal sign of leukemia.

  5. Targeting leukemia stem cells in vivo with antagomiR-126 nanoparticles in acute myeloid leukemia.

    PubMed

    Dorrance, A M; Neviani, P; Ferenchak, G J; Huang, X; Nicolet, D; Maharry, K S; Ozer, H G; Hoellarbauer, P; Khalife, J; Hill, E B; Yadav, M; Bolon, B N; Lee, R J; Lee, L J; Croce, C M; Garzon, R; Caligiuri, M A; Bloomfield, C D; Marcucci, G

    2015-11-01

    Current treatments for acute myeloid leukemia (AML) are designed to target rapidly dividing blast populations with limited success in eradicating the functionally distinct leukemia stem cell (LSC) population, which is postulated to be responsible for disease resistance and relapse. We have previously reported high miR-126 expression levels to be associated with a LSC-gene expression profile. Therefore, we hypothesized that miR-126 contributes to 'stemness' and is a viable target for eliminating the LSC in AML. Here we first validate the clinical relevance of miR-126 expression in AML by showing that higher expression of this microRNA (miR) is associated with worse outcome in a large cohort of older (⩾60 years) cytogenetically normal AML patients treated with conventional chemotherapy. We then show that miR-126 overexpression characterizes AML LSC-enriched cell subpopulations and contributes to LSC long-term maintenance and self-renewal. Finally, we demonstrate the feasibility of therapeutic targeting of miR-126 in LSCs with novel targeting nanoparticles containing antagomiR-126 resulting in in vivo reduction of LSCs likely by depletion of the quiescent cell subpopulation. Our findings suggest that by targeting a single miR, that is, miR-126, it is possible to interfere with LSC activity, thereby opening potentially novel therapeutic approaches to treat AML patients.

  6. Childhood Acute Lymphoblastic Leukemia and Indicators of Early Immune Stimulation: A Childhood Leukemia International Consortium Study

    PubMed Central

    Rudant, Jérémie; Lightfoot, Tracy; Urayama, Kevin Y.; Petridou, Eleni; Dockerty, John D.; Magnani, Corrado; Milne, Elizabeth; Spector, Logan G.; Ashton, Lesley J.; Dessypris, Nikolaos; Kang, Alice Y.; Miller, Margaret; Rondelli, Roberto; Simpson, Jill; Stiakaki, Eftichia; Orsi, Laurent; Roman, Eve; Metayer, Catherine; Infante-Rivard, Claire; Clavel, Jacqueline

    2015-01-01

    The associations between childhood acute lymphoblastic leukemia (ALL) and several proxies of early stimulation of the immune system, that is, day-care center attendance, birth order, maternally reported common infections in infancy, and breastfeeding, were investigated by using data from 11 case-control studies participating in the Childhood Leukemia International Consortium (enrollment period: 1980–2010). The sample included 7,399 ALL cases and 11,181 controls aged 2–14 years. The data were collected by questionnaires administered to the parents. Pooled odds ratios and 95% confidence intervals were estimated by unconditional logistic regression adjusted for age, sex, study, maternal education, and maternal age. Day-care center attendance in the first year of life was associated with a reduced risk of ALL (odds ratio = 0.77, 95% confidence interval: 0.71, 0.84), with a marked inverse trend with earlier age at start (P < 0.0001). An inverse association was also observed with breastfeeding duration of 6 months or more (odds ratio = 0.86, 95% confidence interval: 0.79, 0.94). No significant relationship with a history of common infections in infancy was observed even though the odds ratio was less than 1 for more than 3 infections. The findings of this large pooled analysis reinforce the hypothesis that day-care center attendance in infancy and prolonged breastfeeding are associated with a decreased risk of ALL. PMID:25731888

  7. Parental Tobacco Smoking and Acute Myeloid Leukemia: The Childhood Leukemia International Consortium.

    PubMed

    Metayer, Catherine; Petridou, Eleni; Aranguré, Juan Manuel Mejía; Roman, Eve; Schüz, Joachim; Magnani, Corrado; Mora, Ana Maria; Mueller, Beth A; de Oliveira, Maria S Pombo; Dockerty, John D; McCauley, Kathryn; Lightfoot, Tracy; Hatzipantelis, Emmanouel; Rudant, Jérémie; Flores-Lujano, Janet; Kaatsch, Peter; Miligi, Lucia; Wesseling, Catharina; Doody, David R; Moschovi, Maria; Orsi, Laurent; Mattioli, Stefano; Selvin, Steve; Kang, Alice Y; Clavel, Jacqueline

    2016-08-15

    The association between tobacco smoke and acute myeloid leukemia (AML) is well established in adults but not in children. Individual-level data on parental cigarette smoking were obtained from 12 case-control studies from the Childhood Leukemia International Consortium (CLIC, 1974-2012), including 1,330 AML cases diagnosed at age <15 years and 13,169 controls. We conducted pooled analyses of CLIC studies, as well as meta-analyses of CLIC and non-CLIC studies. Overall, maternal smoking before, during, or after pregnancy was not associated with childhood AML; there was a suggestion, however, that smoking during pregnancy was associated with an increased risk in Hispanics (odds ratio = 2.08, 95% confidence interval (CI): 1.20, 3.61) but not in other ethnic groups. By contrast, the odds ratios for paternal lifetime smoking were 1.34 (95% CI: 1.11, 1.62) and 1.18 (95% CI: 0.92, 1.51) in pooled and meta-analyses, respectively. Overall, increased risks from 1.2- to 1.3-fold were observed for pre- and postnatal smoking (P < 0.05), with higher risks reported for heavy smokers. Associations with paternal smoking varied by histological type. Our analyses suggest an association between paternal smoking and childhood AML. The association with maternal smoking appears limited to Hispanic children, raising questions about ethnic differences in tobacco-related exposures and biological mechanisms, as well as study-specific biases.

  8. Leukemia Associated Antigens: Their Dual Role as Biomarkers and Immunotherapeutic Targets for Acute Myeloid Leukemia

    PubMed Central

    Guinn, Barbara-ann; Mohamedali, Azim; Mills, Ken I.; Czepulkowski, Barbara; Schmitt, Michael; Greiner, Jochen

    2007-01-01

    Leukemia associated antigens (LAAs) are being increasingly identified by methods such as cytotoxic T-lymphocyte (CTL) cloning, serological analysis of recombinant cDNA expression libraries (SEREX) and mass spectrometry (MS). In additional, large scale screening techniques such as microarray, single nucleotide polymorphisms (SNPs), serial analysis of gene expression (SAGE) and 2-dimensional gel electrophoresis (2-DE) have expanded our understanding of the role that tumor antigens play in the biological processes which are perturbed in acute myeloid leukemia (AML). It has become increasingly apparent that these antigens play a dual role, not only as targets for immunotherapy, but also as biomarkers of disease state, stage, response to treatment and survival. We need biomarkers to enable the identification of the patients who are most likely to benefit from specific treatments (conventional and/or novel) and to help clinicians and scientists improve clinical end points and treatment design. Here we describe the LAAs identified in AML, to date, which have already been shown to play a dual role as biomarkers of AML disease. PMID:19662193

  9. Parental Tobacco Smoking and Acute Myeloid Leukemia: The Childhood Leukemia International Consortium.

    PubMed

    Metayer, Catherine; Petridou, Eleni; Aranguré, Juan Manuel Mejía; Roman, Eve; Schüz, Joachim; Magnani, Corrado; Mora, Ana Maria; Mueller, Beth A; de Oliveira, Maria S Pombo; Dockerty, John D; McCauley, Kathryn; Lightfoot, Tracy; Hatzipantelis, Emmanouel; Rudant, Jérémie; Flores-Lujano, Janet; Kaatsch, Peter; Miligi, Lucia; Wesseling, Catharina; Doody, David R; Moschovi, Maria; Orsi, Laurent; Mattioli, Stefano; Selvin, Steve; Kang, Alice Y; Clavel, Jacqueline

    2016-08-15

    The association between tobacco smoke and acute myeloid leukemia (AML) is well established in adults but not in children. Individual-level data on parental cigarette smoking were obtained from 12 case-control studies from the Childhood Leukemia International Consortium (CLIC, 1974-2012), including 1,330 AML cases diagnosed at age <15 years and 13,169 controls. We conducted pooled analyses of CLIC studies, as well as meta-analyses of CLIC and non-CLIC studies. Overall, maternal smoking before, during, or after pregnancy was not associated with childhood AML; there was a suggestion, however, that smoking during pregnancy was associated with an increased risk in Hispanics (odds ratio = 2.08, 95% confidence interval (CI): 1.20, 3.61) but not in other ethnic groups. By contrast, the odds ratios for paternal lifetime smoking were 1.34 (95% CI: 1.11, 1.62) and 1.18 (95% CI: 0.92, 1.51) in pooled and meta-analyses, respectively. Overall, increased risks from 1.2- to 1.3-fold were observed for pre- and postnatal smoking (P < 0.05), with higher risks reported for heavy smokers. Associations with paternal smoking varied by histological type. Our analyses suggest an association between paternal smoking and childhood AML. The association with maternal smoking appears limited to Hispanic children, raising questions about ethnic differences in tobacco-related exposures and biological mechanisms, as well as study-specific biases. PMID:27492895

  10. Flow cytometric analysis of cell-surface and intracellular antigens in the diagnosis of acute leukemia.

    PubMed

    Paredes-Aguilera, R; Romero-Guzman, L; Lopez-Santiago, N; Burbano-Ceron, L; Camacho-Del Monte, O; Nieto-Martinez, S

    2001-10-01

    To evaluate the usefulness of flow cytometric detection of intracellular antigens (Ags) in establishing proper lineage affiliation and its contribution to the diagnosis of acute leukemia, we studied 100 consecutive patients in whom acute leukemia was diagnosed between January 1997 and July 1998. Immunological classification was assessed using a three-line panel of monoclonal antibodies for phenotypic characterization of leukemic blast cells as proposed at the First Latin American Consensus Conference for Flow Cytometric Immunophenotyping of Leukemia. We found 74 cases of B-cell lineage acute lymphoblastic leukemia (ALL), seven cases of T-cell ALL, and 19 cases of acute myeloid leukemia (AML). In this study cytoplasmic (cy) CD79a, cyCD22, cyCD3, and cyMPO were highly sensitive, specific B, T, and myeloid markers that were expressed in virtually all cases of B and T cell ALL and in all subtypes of AML. Applied in combination with immunophenotyping this knowledge led to improvement in diagnostic precision and refinement of immunological classification, ensuring the selection of the most appropriate therapy for the patients studied. In conclusion, intracellular Ags detection was of utmost importance in establishing correct lineage affiliation in cases lacking expression of B, T, or myeloid surface Ags or disclosing equivocal or ambiguous immunophenotypic features and in identifying biphenotypic acute leukemia. In combination with FAB morphology and immunophenotyping, we were able to reliably classify all patients with acute leukemia in this study.

  11. Novel immunotherapeutic approaches for the treatment of acute leukemia (myeloid and lymphoblastic)

    PubMed Central

    Ishii, Kazusa; Barrett, Austin J.

    2016-01-01

    There have been major advances in our understanding of the multiple interactions between malignant cells and the innate and adaptive immune system. While the attention of immunologists has hitherto focused on solid tumors, the specific immunobiology of acute leukemias is now becoming defined. These discoveries have pointed the way to immune interventions building on the established graft-versus-leukemia (GVL) effect from hematopoietic stem-cell transplant (HSCT) and extending immunotherapy beyond HSCT to individuals with acute leukemia with a diversity of immune manipulations early in the course of the leukemia. At present, clinical results are in their infancy. In the coming years larger studies will better define the place of immunotherapy in the management of acute leukemias and lead to treatment approaches that combine conventional chemotherapy, immunotherapy and HSCT to achieve durable cures. PMID:26834952

  12. Undiagnosed, untreated acute lymphoblastic leukemia presenting as suspected child abuse.

    PubMed

    McClain, J L; Clark, M A; Sandusky, G E

    1990-05-01

    Natural disease being mistaken for child abuse is rare. A two-year-old child was found unresponsive at home and transported to a local hospital, where she expired in the emergency room. Several cutaneous contusions were observed. Prior to the autopsy it was learned that an anonymous report of "child abuse" had been previously filed concerning this child. At autopsy there were multiple metasynchronous cutaneous contusions, but no radiologic or gross evidence of other injuries. A pericardial effusion, massive hepatosplenomegaly and generalized lymphadenopathy were apparent. The bone marrow, liver, spleen, lymph nodes, kidneys, pancreas, heart, stomach, and dura mater showed a monotonous lymphocytic infiltrate. Immunocytochemical studies confirmed the diagnosis of acute lymphoblastic leukemia of childhood. This case reaffirms the need for an objective examination of all cases by a forensic pathologist. PMID:2189946

  13. Inherited genetic variants associated with childhood acute lymphoblastic leukemia risk.

    PubMed

    Takagi, Masatoshi; Urayama, Kevin

    2016-07-01

    Numerous efforts have been made to elucidate the roles of individual genetic background factors in the risk of childhood acute lymphoblastic leukemia. Most have taken the form of case-control studies focusing on specific candidate gene polymorphisms. Recently, a more rigorous and comprehensive approach referred to as a genome-wide association study (GWAS) has been widely utilized and has achieved success. Case-control studies evaluating candidate gene associations have shown cumulative evidence of a role for folate metabolism and xenobiotic metabolism/transport pathway genetic variants. In addition, single nucleotide polymorphism (SNP)s identified by GWAS appear to indicate a strong role for genes encoding transcription factors involved in cellular differentiation. Further studies are needed to clarify the accumulating evidence obtained from both candidate gene and genome-wide investigations. PMID:27498736

  14. Current findings for recurring mutations in acute myeloid leukemia

    PubMed Central

    2011-01-01

    The development of acute myeloid leukemia (AML) is a multistep process that requires at least two genetic abnormalities for the development of the disease. The identification of genetic mutations in AML has greatly advanced our understanding of leukemogenesis. Recently, the use of novel technologies, such as massively parallel DNA sequencing or high-resolution single-nucleotide polymorphism arrays, has allowed the identification of several novel recurrent gene mutations in AML. The aim of this review is to summarize the current findings for the identification of these gene mutations (Dnmt, TET2, IDH1/2, NPM1, ASXL1, etc.), most of which are frequently found in cytogenetically normal AML. The cooperative interactions of these molecular aberrations and their interactions with class I/II mutations are presented. The prognostic and predictive significances of these aberrations are also reviewed. PMID:21917154

  15. [Acute lymphoblastic leukemia of T progenitors: from biology to clinics].

    PubMed

    Genescà, Eulàlia; Ribera, Jordi; Ribera, Josep-Maria

    2015-03-01

    Acute lymphoblastic leukemia (ALL) is the most common cancer in children and the main cause of morbidity among childhood blood disorders. There are 2 subtypes according to the affected lymphoid progenitor: B-ALL and T-ALL. The T-ALL is the less common and, although historically was associated with poor prognosis in both adults and children, at present, treatment outcomes do not differ significantly between the 2 types of ALL. The T-ALL subtype is the most complex and heterogeneous at the genetic level and currently the one with less new therapeutic alternatives available. This trend is changing thanks to the remarkable progress upon understanding its biology. This review summarizes the most recent and important biological findings in T-ALL and their possible therapeutic implications.

  16. Management of older or unfit patients with acute myeloid leukemia.

    PubMed

    Walter, R B; Estey, E H

    2015-04-01

    Acute myeloid leukemia (AML) is primarily a disease of older adults, for whom optimal treatment strategies remain controversial. Because of the concern for therapeutic resistance and, in particular, excessive toxicity or even treatment-related mortality, many older or medically unfit patients do not receive AML-directed therapy. Yet, evidence suggests that outcomes are improved if essentially all of these patients are offered AML therapy, ideally at a specialized cancer center. Medical fitness for tolerating intensive chemotherapy can be estimated relatively accurately with multiparameter assessment tools; this information should serve as basis for the assignment to intensive or non-intensive therapy. Until our accuracy in predicting the success of individual therapies improves, all patients should be considered for participation in a randomized controlled trial. Comparisons between individual trials will be facilitated once standardized, improved response criteria are developed, and standard treatment approaches have been defined against which novel therapies can be tested.

  17. How to manage asparaginase hypersensitivity in acute lymphoblastic leukemia.

    PubMed

    Burke, Michael J

    2014-12-01

    Outcomes for children with acute lymphoblastic leukemia (ALL) have improved significantly in recent decades, primarily due to dose-intensified, multi-agent chemotherapy regimens, of which asparaginase has played a prominent role. Despite this success, hypersensitivity remains a significant problem, often requiring the termination of asparaginase. Failure to complete the entire asparaginase therapy course due to clinical hypersensitivity, subclinical hypersensitivity (i.e., silent inactivation), or other treatment-related toxicity is associated with poor ALL outcomes. Thus, it is critical to rapidly identify patients who develop clinical/subclinical hypersensitivity and switch these patients to an alternate asparaginase formulation. This article provides an overview of asparaginase hypersensitivity, identification and management of hypersensitivity and subclinical hypersensitivity, and issues related to switching patients to asparaginase Erwinia chrysanthemi following hypersensitivity reaction.

  18. Biology and treatment of adult acute lymphoblastic leukemia.

    PubMed Central

    Levitt, L; Lin, R

    1996-01-01

    The molecular analysis of acute lymphoblastic leukemia (ALL) has provided exciting insights into the pathogenesis of this disease. This disease is heterogenous and can be subtyped based on chromosomal, immunophenotypic, and structural criteria. The varying prognostic implications of different ALL subtypes markedly influence the treatment decisions in adults. Many patients with T-cell ALL can be cured with chemotherapy alone. In contrast, patients with early B-lineage ALL with certain chromosomal abnormalities, especially the Philadelphia chromosome, do not have durable responses to chemotherapy and should receive a bone marrow transplantation if an HLA-matched donor is available. Recent reports have shown improved results for adults with B-cell ALL (Burkitt's) after intensive alternating cycles of chemotherapy containing high doses of methotrexate and cyclophosphamide. Future clinical and laboratory investigation should lead to the development of novel and possibly more effective treatments specifically tailored for different subsets of ALL. PMID:8775728

  19. Novel Prognostic and Therapeutic Mutations in Acute Myeloid Leukemia.

    PubMed

    Medinger, Michael; Lengerke, Claudia; Passweg, Jakob

    Acute myeloid leukemia (AML) is a biologically complex and molecularly and clinically heterogeneous disease, and its incidence increases with age. Cytogenetics and mutation testing remain important prognostic tools for treatment after induction therapy. The post-induction treatment is dependent on risk stratification. Despite rapid advances in determination of gene mutations involved in the pathophysiology and biology of AML, and the rapid development of new drugs, treatment improvements changed slowly over the past 30 years, with the majority of patients eventually experiencing relapse and dying of their disease. Allogenic hematopoietic stem cell transplantation remains the best chance of cure for patients with intermediate- or high-risk disease. This review gives an overview about advances in prognostic markers and novel treatment options for AML, focusing on new prognostic and probably therapeutic mutations, and novel drug therapies such as tyrosine kinase inhibitors. PMID:27566651

  20. The increasing genomic complexity of acute myeloid leukemia.

    PubMed

    Rowe, Jacob M

    2014-01-01

    Therapy of acute myeloid leukemia (AML) is impacted by the increasing genomic complexity of the disease. Multiple targets as expressed by genetics and mutations and the relationships between them add another layer of intricacy to the prognosis and treatment of the disease. It is becoming increasingly apparent that the interactions between mutations are of utmost importance, particularly from a prognostic standpoint. For example, inv(16) or 6(16; 16) AML frequently involves a second genetic lesion that significantly impacts prognosis. In addition, epigenetic changes, including DNA methylation, are becoming increasingly integrated into the genetic landscape and may also have prognostic impact. Despite increased understanding of the genetic and epigenetic aspects of AML, the outcome for AML patients has not changed significantly. Until it does, further inquiry into the genomic complexity of the disease and advances in drug development are needed.

  1. Recent advancements of bortezomib in acute lymphocytic leukemia treatment.

    PubMed

    Du, Xiao-Li; Chen, Qi

    2013-01-01

    Although survival rates for acute lymphocytic leukemia (ALL), especially in children, have shown dramatic improvement over time, poor outcomes are still observed in patients who have refractory or relapsed disease after conventional chemotherapy. New therapeutic options are urgently needed. Bortezomib (Velcade, formerly PS-341) is the first proteasome inhibitor approved by the US FDA for the treatment of newly diagnosed multiple myeloma and relapsed/refractory multiple myeloma and mantle cell lymphoma. Although the mechanisms of bortezomib anticancer activity are still not completely understood, it is a new treatment option for patients with refractory or relapsed ALL, particularly when used in combination with conventional chemotherapy or targeted agents. This review summarizes recent advancements in the understanding of the bortezomib molecular mechanism of action in ALL. Understanding of the molecular approaches might help customize cancer chemotherapy for each individual patient, directing the field towards rational therapeutics.

  2. Acute Lymphocytic Leukemia in Adults. Pathologic Features and Prognosis.

    PubMed

    Marinescu, Cristina; Vlădăreanu, Ana-Maria; Mihai, Felicia

    2015-01-01

    Acute lymphoblastic leukemia (ALL) is a malignant neoplasm of the lymphocyte precursor cells. Among adults it is a relatively rare neoplasm with a curability rate around 30% at 5 years. Currently, the diagnosis and classification of ALL is a multistep procedure that relies on the simultaneous application of multiple techniques that include: cytomorphology, immunophenotype and cytogenetic assays. Some of them have important clinical implications for both diagnosis and predicting response to specific treatment regimens, while the role of others is still to be defined. Over the years, several prognostic factors have been identified and today a risk stratification at diagnosis and during the follow-up is based on the characteristics of the leukemic cells.

  3. L-asparaginase and venous thromboembolism in acute lymphocytic leukemia.

    PubMed

    Goyal, Gaurav; Bhatt, Vijaya Raj

    2015-01-01

    The occurrence of venous thromboembolism (VTE) in acute lymphocytic leukemia patients receiving L-asparaginase therapy may cause significant morbidity, neurological sequela and possibly worse outcomes. The prophylactic use of antithrombin infusion (to keep antithrombin activity >60%) or low molecular weight heparin (LMWH) may reduce the risk of VTE. The decision to continue L-asparaginase therapy after the development of VTE should be based on anticipated benefits, severity of VTE and the ability to continue therapeutic anticoagulation. In patients receiving asparaginase rechallenge, the use of therapeutic LMWH, monitoring of anti-Xa level and antithrombin level are important. Novel oral anticoagulants are not dependent on antithrombin level, hence offer theoretical advantages over LMWH for the prevention and therapy of asparaginase-related VTE.

  4. Childhood Acute Lymphoblastic Leukemia: Integrating Genomics into Therapy

    PubMed Central

    Tasian, Sarah K; Loh, Mignon L; Hunger, Stephen P

    2015-01-01

    Acute lymphoblastic leukemia (ALL), the most common malignancy of childhood, is a genetically complex entity that remains a major cause of childhood cancer-related mortality. Major advances in genomic and epigenomic profiling during the past decade have appreciably enhanced knowledge of the biology of de novo and relapsed ALL and have facilitated more precise risk stratification of patients. These achievements have also provided critical insights regarding potentially targetable lesions for development of new therapeutic approaches in the era of precision medicine. This review delineates the current genetic landscape of childhood ALL with emphasis upon patient outcomes with contemporary treatment regimens, as well as therapeutic implications of newly identified genomic alterations in specific subsets of ALL. PMID:26194091

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

    PubMed

    Zeidner, Joshua F; Karp, Judith E

    2015-12-01

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

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

    PubMed

    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

  7. Sapacitabine in the treatment of acute myeloid leukemia.

    PubMed

    Norkin, Maxim; Richards, Ashley I

    2015-01-01

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

  8. Acute leukemia diagnosis aid using multicriteria fuzzy assignment methodology.

    PubMed

    Belacel, N; Vincke, P; Scheiff, J M; Boulassel, M R

    2001-02-01

    We recently developed a new multicriteria classification method called PROAFTN to help medical diagnosis. The aim of this paper is to present the application of the proposed method for the diagnosis of acute leukemia (AL). The implementation of PROAFTN was carried out on cytological data of 108 cases of AL, using the classification rules of French, American and British hematologists, and was then applied on an independent test set of 83 cases of AL. Forty-seven features, obtained by examining patients' bone-marrow smears with light microscope, defined each case. In order to determine the percentage of correct classifications for each subtype of AL, we compared our results with the clinical diagnosis given previously by the hematologist. 96.4% of the cases were correctly classified by the program, suggesting that the method yields good results in terms of discrimination between AL subtypes.

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

    PubMed

    Zeidner, Joshua F; Karp, Judith E

    2015-12-01

    There have been minimal therapeutic advancements in acute myeloid leukemia (AML) over the past 4 decades and outcomes remain unsatisfactory. Alvocidib (formerly flavopiridol) is a multi-serine threonine cyclin-dependent kinase inhibitor with demonstrable in vitro and clinical activity in AML when combined in a timed sequential chemotherapy regimen, FLAM (alvocidib followed by cytarabine continuous infusion and mitoxantrone). FLAM has been evaluated in sequential phase 1 and phase 2 studies in 149 and 256 relapsed/refractory and newly diagnosed non-favorable risk AML patients, respectively, with encouraging findings in both patient populations warranting further investigation. This review highlights the mechanism of action of alvocidib, pre-clinical studies of alvocidib in AML, and the clinical trials evaluating alvocidib alone and in combination with cytotoxic agents (FLAM) in AML. PMID:26521988

  10. Cranial radiation in childhood acute lymphocytic leukemia. Neuropsychologic sequelae

    SciTech Connect

    Whitt, J.K.; Wells, R.J.; Lauria, M.M.; Wilhelm, C.L.; McMillan, C.W.

    1984-08-01

    A battery of neuropsychologic tests was administered ''blindly'' to 18 children with acute lymphocytic leukemia (ALL) who had been randomly assigned to treatment regimens with or without cranial radiation. These children were all in complete continuous remission for more than 3 1/2 years and were no longer receiving therapy. The results indicated no substantial differences between groups as a function of radiation therapy. However, decreased neuropsychologic performance was found when the entire sample was compared with population norms. These data do not support the hypothesis that cranial radiation therapy is responsible for the neuropsychologic sequelae seen in these survivors of ALL. Post hoc multiple regression analysis indicated that parental education levels accounted for more of the neuropsychologic variability seen in these children than other factors such as age at diagnosis, type of therapy, or sex of child.

  11. Acute Myeloid Leukemia in Infants: Biology and Treatment

    PubMed Central

    Masetti, Riccardo; Vendemini, Francesca; Zama, Daniele; Biagi, Carlotta; Pession, Andrea; Locatelli, Franco

    2015-01-01

    Children aged 0–2 years (i.e., infants) with acute myeloid leukemia (AML) are a peculiar subgroup of patients in the childhood AML scenario. They present with distinctive biological and clinical characteristics, including a high prevalence of prognostically unfavorable risk factors and an increased susceptibility to therapy-related toxicity. Remarkable improvements have been achieved over the last two decades in the treatment of these patients and their outcome is becoming superimposable to that of the older age groups. In this review, we will focus on peculiarities of this young subgroup of children with AML, describing their clinical presentation, the biology of disease, and factors influencing outcome. Treatment results and toxicity data reported by major collaborative groups are also summarized and compared. PMID:25973412

  12. Intestinal permeability in patients with acute myeloid leukemia.

    PubMed

    Sundström, G M; Wahlin, A; Nordin-Andersson, I; Suhr, O B

    1998-10-01

    Intestinal permeability was studied in patients with acute myeloid leukemia (AML) before, during and after chemotherapy. Intestinal permeability was determined by the lactulose (La)/mannitol (Ma) absorption test in 16 adult patients with de novo AML. The hydrogen breath test was used to disclose bacterial fermentation of the test substances in the small intestine. The permeability was found significantly increased (p<0.02) in the patients before induction chemotherapy treatment. During induction treatment and throughout the cytopenic period the intestinal permeability was constantly and significantly increased, compared with controls. In patients with abnormally increased permeability, no increase in hydrogen breath test result was noted. From our results it can be concluded that increased intestinal permeability is present in AML patients before commencing chemotherapy. Factors other than chemotherapy would seem to be more important regarding the occurrence of intestinal disturbances in these patients.

  13. Isolated central nervous system relapse of acute lymphoblastic leukemia.

    PubMed

    Sung, Sang-Hyun; Jang, In-Seok

    2014-10-01

    Acute lymphoblastic leukemia (ALL) is the most common form of childhood cancer and may exhibit central nervous system (CNS) involvement. Advances in chemotherapy and effective CNS prophylaxis have significantly decreased the incidence of CNS relapse of ALL to 5-10%. Here, we report the case of a patient with isolated CNS relapse of standard risk group pre-B-cell type ALL in an 11-year-old girl, relapsed 3 years after successful completion of chemotherapy. An 11-year-old girl visited our hospital complaining of headache, dizziness, vomiting, and visual field defects. Neurological examination revealed left-side homonymous hemianopsia. Brain magnetic resonance imaging showed a large irregular dural-based sulcal hematoma in the right parietal and occipital lobes. Surgery to remove the hematoma revealed the existence of hematopoietic malignancy after pathologic evaluation. Bone marrow biopsy was subsequently performed but showed no evidence of malignancy. PMID:25408936

  14. Acquired pericentric inversion of chromosome 9 in acute myeloid leukemia.

    PubMed

    Udayakumar, A M; Pathare, A V; Dennison, D; Raeburn, J A

    2009-01-01

    Pericentric inversion of chromosome 9 involving the qh region is relatively common as a constitutional genetic aberration without any apparent phenotypic consequences. However, it has not been established as an acquired abnormality in cancer. Among the three patients reported so far in the literature with acquired inv(9), only one had acute myeloid leukemia (AML). Here we describe an unique case where both chromosomes 9 presented with an acquired pericentric inversion with breakpoints at 9p13 and 9q12 respectively, in a AML patient with aberrant CD7 and CD9 positivity. Additionally, one der(9) also showed short arm deletion at 9p21 to the centromeric region and including the p16 gene. The constitutional karyotype was normal. This is probably the first report describing an acquired inv(9) involving both chromosomes 9 in AML. The possible significance of this inversion is discussed.

  15. [Acute lymphoblastic leukemia of T progenitors: from biology to clinics].

    PubMed

    Genescà, Eulàlia; Ribera, Jordi; Ribera, Josep-Maria

    2015-03-01

    Acute lymphoblastic leukemia (ALL) is the most common cancer in children and the main cause of morbidity among childhood blood disorders. There are 2 subtypes according to the affected lymphoid progenitor: B-ALL and T-ALL. The T-ALL is the less common and, although historically was associated with poor prognosis in both adults and children, at present, treatment outcomes do not differ significantly between the 2 types of ALL. The T-ALL subtype is the most complex and heterogeneous at the genetic level and currently the one with less new therapeutic alternatives available. This trend is changing thanks to the remarkable progress upon understanding its biology. This review summarizes the most recent and important biological findings in T-ALL and their possible therapeutic implications. PMID:24667111

  16. Monoclonal Antibody Therapy in Treating Patients With Ovarian Epithelial Cancer, Melanoma, Acute Myeloid Leukemia, Myelodysplastic Syndrome, or Non-Small Cell Lung Cancer

    ClinicalTrials.gov

    2013-01-09

    Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Atypical Chronic Myeloid Leukemia, BCR-ABL1 Negative; Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Myeloid Leukemia; Recurrent Melanoma; Recurrent Non-small Cell Lung Cancer; Recurrent Ovarian Epithelial Cancer; Stage IV Melanoma; Stage IV Non-small Cell Lung Cancer

  17. Acute respiratory distress syndrome associated with tumor lysis syndrome in a child with acute lymphoblastic leukemia.

    PubMed

    Macaluso, Alessandra; Genova, Selene; Maringhini, Silvio; Coffaro, Giancarlo; Ziino, Ottavio; D'Angelo, Paolo

    2015-02-24

    Tumor lysis syndrome is a serious and dangerous complication usually associated with antiblastic treatment in some malignancies characterized by high cell turn-over. Mild or severe electrolyte abnormalities including high serum levels of uric acid, potassium, phosphorus, creatinine, bun and reduction of calcium can be responsible for multi-organ failure, involving mostly kidneys, heart and central nervous system. Renal damage can be followed by acute renal failure, weight gain, progressive liver impairment, overproduction of cytokines, and subsequent maintenance of multi-organ damage. Life-threatening acute respiratory failure associated with tumor lysis syndrome is rare. We describe a child with T-cell acute lymphoblastic leukemia, who developed an unusually dramatic tumor lysis syndrome, after administration of the first low doses of steroid, that was rapidly associated with severe acute respiratory distress syndrome. Subsequent clinical course and treatment modalities that resulted in the gradual and full recovery of the child are also described. PMID:25918625

  18. Acute Respiratory Distress Syndrome Associated with Tumor Lysis Syndrome in a Child with Acute Lymphoblastic Leukemia

    PubMed Central

    Macaluso, Alessandra; Genova, Selene; Maringhini, Silvio; Coffaro, Giancarlo; Ziino, Ottavio; D’Angelo, Paolo

    2015-01-01

    Tumor lysis syndrome is a serious and dangerous complication usually associated with antiblastic treatment in some malignancies characterized by high cell turn-over. Mild or severe electrolyte abnormalities including high serum levels of uric acid, potassium, phosphorus, creatinine, bun and reduction of calcium can be responsible for multi-organ failure, involving mostly kidneys, heart and central nervous system. Renal damage can be followed by acute renal failure, weight gain, progressive liver impairment, overproduction of cytokines, and subsequent maintenance of multi-organ damage. Life-threatening acute respiratory failure associated with tumor lysis syndrome is rare. We describe a child with T-cell acute lymphoblastic leukemia, who developed an unusually dramatic tumor lysis syndrome, after administration of the first low doses of steroid, that was rapidly associated with severe acute respiratory distress syndrome. Subsequent clinical course and treatment modalities that resulted in the gradual and full recovery of the child are also described. PMID:25918625

  19. A Revised Definition for Cure of Childhood Acute Lymphoblastic Leukemia

    PubMed Central

    Pui, CH; Pei, D; Campana, D; Cheng, C; Sandlund, JT; Bowman, WP; Hudson, MM; Ribeiro, RC; Raimondi, SC; Jeha, S; Howard, SC; Bhojwani, D; Inaba, H; Rubnitz, JE; Metzger, ML; Gruber, TA; Coustan-Smith, E; Downing, JR; Leung, WH; Relling, MV; Evans, WE

    2014-01-01

    With improved contemporary therapy, we re-assess long-term outcome in patients completing treatment for childhood acute lymphoblastic leukemia to determine when cure can be declared with a high degree of confidence. In 6 successive clinical trials between 1984 and 2007, 1291(84.5%) patients completed all therapy in continuous complete remission. The post-therapy cumulative risk of relapse or development of a second neoplasm and the event-free survival rate and overall survival were analyzed according to the presenting features and the three treatment periods defined by relative outcome. Over the three treatment periods, there has been progressive increase in the rate of event-free survival (65.2% vs. 74.8% vs. 85.1% [P<0.001]) and overall survival (76.5% vs. 81.1% vs. 91.7% [P<0.001]) at 10 years. The most important predictor of outcome after completion of therapy was the type of treatment. In the most recent treatment period, which omitted the use of prophylactic cranial irradiation, the post-treatment cumulative risk of relapse was 6.4%, death in remission 1.5%, and development of a second neoplasm 2.3% at 10 years, with all relapses except one occurring within 4 years off therapy. None of the 106 patients with the t(9;22)/BCR-ABL1, t(1;19)/TCF3-PBX1 or t(4;11)/MLL-AFF1 had relapsed after 2 years from completion of therapy. These findings demonstrate that with contemporary effective therapy that excludes cranial irradiation, approximately 6% of children with acute lymphoblastic leukemia may relapse after completion of treatment, and those who remain in remission at 4 years post-treatment may be considered cured (i.e., less than 1 % chance of relapse). PMID:24781017

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

    PubMed

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

    2015-06-01

    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 successes in characterizing the genetic landscape of AML have highlighted that, despite its heterogeneity, many cases of AML carry recurrent mutations in genes encoding epigenetic regulators. Transcriptional dysregulation and altered epigenetic function have therefore emerged as exciting areas in AML research and it is becoming increasingly clear that epigenetic dysfunction is central to leukemogenesis in AML. This has subsequently paved the way for the development of epigenetically targeted therapies. In this review, we will discuss the most recent advances in our understanding of the role of epigenetic dysregulation in AML pathobiology. We will particularly focus on those altered epigenetic programs that have been shown to be central to the development and maintenance of AML in preclinical models. We will discuss the recent development of therapeutics specifically targeting these key epigenetic programs in AML, describe their mechanism of action and present their current clinical development. Finally, we will discuss the opportunities presented by epigenetically targeted therapy in AML and will highlight future challenges ahead for the AML community, to ensure that these novel therapeutics are optimally translated into clinical practice and result in clinical improvement for AML patients.

  1. Delayed Neurotoxicity Associated with Therapy for Children with Acute Lymphoblastic Leukemia

    ERIC Educational Resources Information Center

    Cole, Peter D.; Kamen, Barton A.

    2006-01-01

    Most children diagnosed today with acute lymphoblastic leukemia (ALL) will be cured. However, treatment entails risk of neurotoxicity, causing deficits in neurocognitive function that can persist in the years after treatment is completed. Many of the components of leukemia therapy can contribute to adverse neurologic sequelae, including…

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

    PubMed Central

    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 (P<0.001) and more frequently carried cytogenetic abnormalities (P=0.009) compared with de novo AML patients. The overall survival time was observed to be significantly poorer among individuals with t-AML (P<0.001). However, in younger patients (age, <50 years) there was no difference between the overall survival time of patients with t-AML 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. PMID:27347135

  3. [Quantitative morphology of periferal erythrocytes and bone marrow erythrokaryocytes in acute leukemia and hemopoietic depressions].

    PubMed

    Sokolinskiĭ, B Z; Piatnitskiĭ, A M; Betrozova, M V; Diagileva, O A; Pogorelov, V M; Kozinets, G I

    1999-02-01

    Morphology of peripheral blood erythrocytes was studied in patients with acute leukemia and aplastic anemia by a Russian cytoanalyzer Mekos-C. Twenty-eight patients with acute myeloblastic leukemia, 15 with acute lymphoblastic leukemia, and 11 with aplastic anemia were examined. Erythrocytes (n = 500) were examined in fixed non-stained blood smears. Hemoglobin content and morphometric parameters of each cell were studied and automatic classification of cells was carried out. The data of computer morphodensitometry are compatible with the data of cytochemical studies of the bone marrow erythroid cells (PAS reaction after McManus). The results indicate circulation of erythrocyte subpopulations differing by shape and other signs (hemoglobin content, section area, shape factor) in the blood of patients with acute leukemia and aplastic anemia. The share of pathological erythrocytes in the peripheral blood reflects failure of erythropoiesis. PMID:10876688

  4. General Information about Childhood Acute Myeloid Leukemia and Other Myeloid Malignancies

    MedlinePlus

    ... Other Myeloid Malignancies Treatment (PDQ®)–Patient Version General Information About Childhood Acute Myeloid Leukemia and Other Myeloid ... the PDQ Pediatric Treatment Editorial Board . Clinical Trial Information A clinical trial is a study to answer ...

  5. Carfilzomib and Hyper-CVAD in Treating Patients With Newly Diagnosed Acute Lymphoblastic Leukemia or Lymphoma

    ClinicalTrials.gov

    2016-08-09

    Contiguous Stage II Adult Lymphoblastic Lymphoma; Noncontiguous Stage II Adult Lymphoblastic Lymphoma; Stage I Adult Lymphoblastic Lymphoma; Stage III Adult Lymphoblastic Lymphoma; Stage IV Adult Lymphoblastic Lymphoma; Untreated Adult Acute Lymphoblastic Leukemia

  6. Scientific Achievements May Not Reach Everyone: Understanding Disparities in Acute Leukemia.

    PubMed

    Patel, Manali I

    2016-08-01

    Over the past decade, scientific advancements have resulted in improved survival from acute leukemia. Continued advancements are expected given the attention to precision medicine and the resulting growth in development and adoption of risk-stratified, personalized therapies. While precision medicine has great potential to improve acute leukemia outcomes, there remain significant barriers to ensuring equitable access to these technologies and receipt of these prescribed targeted, personalized therapies. Over the past 3 years, studies report persistent outcome disparities among patients from specific racial and ethnic backgrounds, insurance and socioeconomic status, and other socio-demographic factors after a diagnosis of acute leukemia. A few recent studies examine etiologies for acute leukemia disparities and highlight the importance of ensuring access and equitable delivery of scientific advancements. In the context of continued scientific progress, future strategies require thoughtfully considered improvements in the delivery of care that can overcome the current challenges our patients face.

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

    ClinicalTrials.gov

    2016-08-30

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

  8. B Cell Acute Lymphocytic Leukemia Presenting as a Bile Duct Stricture Diagnosed With Cholangioscopy

    PubMed Central

    Bartel, Michael J.; Jiang, Liuyan; Lukens, Frank

    2016-01-01

    Indeterminate biliary strictures represent a diagnostic challenge requiring further work-up, which encompasses a variety of diagnostic modalities. We report a very rare case of B-cell acute lymphocytic leukemia presenting as a biliary stricture following remission of acute myeloid leukemia, which was initially treated with allogenic stem cell transplant. After multiple diagnostic modalities were implemented with no success, the use of cholangioscopy-guided biopsies was the key for the final diagnosis.

  9. [Research Progress on the Role of Chromatin Remodeling Factor BRG1 in Acute Myeloid Leukemia].

    PubMed

    Gao, Shuo; Xu, Xue-Jing; Zhang, Kui

    2016-06-01

    BRG1 (Brahma-related gene 1, BRG1) is the ATPase subunit of SWI/SNF chromatin remodeling complexes, which plays an important role in cell cycle regulation, DNA repair and tumor development. Unlike the evidence as tumor suppressor genes in the past reports, latest researches show that BRG1 plays an important role in sustaining the growth of leukemia cells in acute myeloid leukemia, and these effects on normal hematopoietic stem cells are dispensable. Further studies of the role and mechanism of BRG1 in acute myeloid leukemia will contribute to the development of a new and promising targeted therapy strategy. This article reviews the role of BRG1 on leukemia cells and leukemia stem cells in AML and discusses the related mechanism, which providing some reference for the targeted treatment strategy of AML. PMID:27342536

  10. The evolution of clinical trials for infant acute lymphoblastic leukemia

    PubMed Central

    Kotecha, R S; Gottardo, N G; Kees, U R; Cole, C H

    2014-01-01

    Acute lymphoblastic leukemia (ALL) in infants has a significantly inferior outcome in comparison with older children. Despite initial improvements in survival of infants with ALL since establishment of the first pediatric cooperative group ALL trials, the poor outcome has plateaued in recent years. Historically, infants were treated on risk-adapted childhood ALL protocols. These studies were pivotal in identifying the need for infant-specific protocols, delineating prognostic categories and the requirement for a more unified approach between study groups to overcome limitations in accrual because of low incidence. This subsequently led to the development of collaborative infant-specific studies. Landmark outcomes have included the elimination of cranial radiotherapy following the discovery of intrathecal and high-dose systemic therapy as a superior and effective treatment strategy for central nervous system disease prophylaxis, with improved neurodevelopmental outcome. Universal prospective identification of independent adverse prognostic factors, including presence of a mixed lineage leukemia rearrangement and young age, has established the basis for risk stratification within current trials. The infant-specific trials have defined limits to which conventional chemotherapeutic agents can be intensified to optimize the balance between treatment efficacy and toxicity. Despite variations in therapeutic intensity, there has been no recent improvement in survival due to the equilibrium between relapse and toxicity. Ultimately, to improve the outcome for infants with ALL, key areas still to be addressed include identification and adaptation of novel prognostic markers and innovative therapies, establishing the role of hematopoietic stem cell transplantation in first complete remission, treatment strategies for relapsed/refractory disease and monitoring and timely intervention of late effects in survivors. This would be best achieved through a single unified

  11. Pathogenesis and treatment of thrombohemorrhagic diathesis in acute promyelocytic leukemia.

    PubMed

    Falanga, Anna; Russo, Laura; Tartari, Carmen J

    2011-01-01

    Acute promyelocytic leukemia (APL) is a distinct subtype of myeloid leukemia characterized by t(15;17) chromosomal translocation, which involves the retinoic acid receptor-alpha (RAR-alpha). APL typically presents with a life-threatening hemorrhagic diathesis. Before the introduction of all-trans retinoic acid (ATRA) for the cure of APL, fatal hemorrhages due, at least in part, to the APL-associated coagulopathy, were a major cause of induction remission failure. The laboratory abnormalities of blood coagulation found in these patients indicate the occurrence of a hypercoagulable state. Major determinants of the coagulopathy of APL are endogenous factors expressed by the leukemic cells, including procoagulant factors, fibrinolytic proteins, and non-specific proteolytic enzymes. In addition, these cells have an increased capacity to adhere to the vascular endothelium, and to secrete inflammatory cytokines [i.e. interleukin-1beta (IL-1beta) and tumor necrosis factor (TNF-alpha)], which in turn stimulate the expression of prothrombotic activities by endothelial cells and leukocytes. ATRA can interfere with each of the principal hemostatic properties of the leukemic cell, thus reducing the APL cell procoagulant potential, in parallel to the induction of cellular differentiation. This effect occurs in vivo, in the bone marrow of APL patients receiving ATRA, and is associated with the improvement of the bleeding symptoms. Therapy with arsenic trioxide (ATO) also beneficially affects coagulation in APL. However, early deaths from bleeding still remain a major problem in APL and further research is required in this field. In this review, we will summarize our current knowledge of the pathogenesis of the APL-associated coagulopathy and will overview the therapeutic approaches for the management of this complication. PMID:22220265

  12. Pathogenesis and Treatment of Thrombohemorrhagic Diathesis in Acute Promyelocytic Leukemia

    PubMed Central

    Falanga, Anna; Russo, Laura; Tartari, Carmen J

    2011-01-01

    Acute promyelocytic leukemia (APL) is a distinct subtype of myeloid leukemia characterized by t(15;17) chromosomal translocation, which involves the retinoic acid receptor-alpha (RAR-alpha). APL typically presents with a life-threatening hemorrhagic diathesis. Before the introduction of all-trans retinoic acid (ATRA) for the cure of APL, fatal hemorrhages due, at least in part, to the APL-associated coagulopathy, were a major cause of induction remission failure. The laboratory abnormalities of blood coagulation found in these patients indicate the occurrence of a hypercoagulable state. Major determinants of the coagulopathy of APL are endogenous factors expressed by the leukemic cells, including procoagulant factors, fibrinolytic proteins, and non-specific proteolytic enzymes. In addition, these cells have an increased capacity to adhere to the vascular endothelium, and to secrete inflammatory cytokines [i.e. interleukin-1beta (IL-1beta) and tumor necrosis factor (TNF-alpha)], which in turn stimulate the expression of prothrombotic activities by endothelial cells and leukocytes. ATRA can interfere with each of the principal hemostatic properties of the leukemic cell, thus reducing the APL cell procoagulant potential, in parallel to the induction of cellular differentiation. This effect occurs in vivo, in the bone marrow of APL patients receiving ATRA, and is associated with the improvement of the bleeding symptoms. Therapy with arsenic trioxide (ATO) also beneficially affects coagulation in APL. However, early deaths from bleeding still remain a major problem in APL and further research is required in this field. In this review, we will summarize our current knowledge of the pathogenesis of the APL-associated coagulopathy and will overview the therapeutic approaches for the management of this complication. PMID:22220265

  13. Phase I/II study of the hypoxia-activated prodrug PR104 in refractory/relapsed acute myeloid leukemia and acute lymphoblastic leukemia

    PubMed Central

    Konopleva, Marina; Thall, Peter F.; Yi, Cecilia Arana; Borthakur, Gautam; Coveler, Andrew; Bueso-Ramos, Carlos; Benito, Juliana; Konoplev, Sergej; Gu, Yongchuan; Ravandi, Farhad; Jabbour, Elias; Faderl, Stefan; Thomas, Deborah; Cortes, Jorge; Kadia, Tapan; Kornblau, Steven; Daver, Naval; Pemmaraju, Naveen; Nguyen, Hoang Q.; Feliu, Jennie; Lu, Hongbo; Wei, Caimiao; Wilson, William R.; Melink, Teresa J.; Gutheil, John C.; Andreeff, Michael; Estey, Elihu H.; Kantarjian, Hagop

    2015-01-01

    We previously demonstrated vast expansion of hypoxic areas in the leukemic microenvironment and provided a rationale for using hypoxia-activated prodrugs. PR104 is a phosphate ester that is rapidly hydrolyzed in vivo to the corresponding alcohol PR-104A and further reduced to the amine and hydroxyl-amine nitrogen mustards that induce DNA cross-linking in hypoxic cells under low oxygen concentrations. In this phase I/II study, patients with relapsed/refractory acute myeloid leukemia (n=40) after 1 or 2 prior treatments or acute lymphoblastic leukemia (n=10) after any number of prior treatments received PR104; dose ranged from 1.1 to 4 g/m2. The most common treatment-related grade 3/4 adverse events were myelosuppression (anemia 62%, neutropenia 50%, thrombocytopenia 46%), febrile neutropenia (40%), infection (24%), and enterocolitis (14%). Ten of 31 patients with acute myeloid leukemia (32%) and 2 of 10 patients with acute lymphoblastic leukemia (20%) who received 3 g/m2 or 4 g/m2 had a response (complete response, n=1; complete response without platelet recovery, n=5; morphological leukemia-free state, n=6). The extent of hypoxia was evaluated by the hypoxia tracer pimonidazole administered prior to a bone marrow biopsy and by immunohistochemical assessments of hypoxia-inducible factor alpha and carbonic anhydrase IX. A high fraction of leukemic cells expressed these markers, and PR104 administration resulted in measurable decrease of the proportions of hypoxic cells. These findings indicate that hypoxia is a prevalent feature of the leukemic microenvironment and that targeting hypoxia with hypoxia-activated prodrugs warrants further evaluation in acute leukemia. The trial is registered at clinicaltrials.gov identifier: 01037556. PMID:25682597

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

    PubMed

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

    2016-01-01

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

  15. [Ocular infiltration in the anterior chamber in a female infant with acute non-lymphoblastic leukemia].

    PubMed

    Garrido Colino, C; Mateos González, M; Torres Valdivieso, M; López Pérez, J; Melero Moreno, C; Vivanco Martínez, J

    2001-07-01

    Unlike myeloid sarcoma, ocular involvement is unusual in acute non-lymphoblastic leukemia.A 9-month-old female infant with acute non-lymphoblastic leukemia M5 and evidence of active central nervous system (CNS) disease showed infiltration of the anterior chamber during therapy. At that time, the CNS disease was in completed remission. She was treated with topical corticosteroids, chemotherapy and bilateral ocular radiotherapy (total dose 1,000 cGy). The ocular manifestations responded well to treatment but hematologic response was poor. The patient died a few months later. Any ophthalmic manifestation in children with leukemia should be detected and treated early. Radiotherapy is warranted in infiltration of the anterior chamber of the eye. The presence of ocular, central CNS or bone marrow involvement indicates poor prognosis in acute childhood leukemia.

  16. Minimal residual disease analysis by eight-color flow cytometry in relapsed childhood acute lymphoblastic leukemia.

    PubMed

    Karawajew, Leonid; Dworzak, Michael; Ratei, Richard; Rhein, Peter; Gaipa, Giuseppe; Buldini, Barbara; Basso, Giuseppe; Hrusak, Ondrej; Ludwig, Wolf-Dieter; Henze, Günter; Seeger, Karl; von Stackelberg, Arend; Mejstrikova, Ester; Eckert, Cornelia

    2015-07-01

    Multiparametric flow cytometry is an alternative approach to the polymerase chain reaction method for evaluating minimal residual disease in treatment protocols for primary acute lymphoblastic leukemia. Given considerable differences between primary and relapsed acute lymphoblastic leukemia treatment regimens, flow cytometric assessment of minimal residual disease in relapsed leukemia requires an independent comprehensive investigation. In the present study we addressed evaluation of minimal residual disease by flow cytometry in the clinical trial for childhood relapsed acute lymphoblastic leukemia using eight-color flow cytometry. The major challenge of the study was to reliably identify low amounts of residual leukemic cells against the complex background of regeneration, characteristic of follow-up samples during relapse treatment. In a prospective study of 263 follow-up bone marrow samples from 122 patients with B-cell precursor acute lymphoblastic leukemia, we tested various B-cell markers, adapted the antibody panel to the treatment protocol, and evaluated its performance by a blinded parallel comparison with the polymerase chain reaction data. The resulting eight-color single-tube panel showed a consistently high overall concordance (P<0.001) and, under optimal conditions, sensitivity similar to that of the reference polymerase chain reaction method. Overall, evaluation of minimal residual disease by flow cytometry can be successfully integrated into the clinical management of relapsed childhood acute lymphoblastic leukemia either as complementary to the polymerase chain reaction or as an independent risk stratification tool. ALL-REZ BFM 2002 clinical trial information: NCT00114348.

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

    PubMed Central

    Schmiegelow, Kjeld; Levinsen, Mette Frandsen; Attarbaschi, Andishe; Baruchel, Andre; Devidas, Meenakshi; Escherich, Gabriele; Gibson, Brenda; Heydrich, Christiane; Horibe, Keizo; Ishida, Yasushi; Liang, Der-Cherng; Locatelli, Franco; Michel, Gérard; Pieters, Rob; Piette, Caroline; Pui, Ching-Hon; Raimondi, Susana; Silverman, Lewis; Stanulla, Martin; Stark, Batia; Winick, Naomi; Valsecchi, Maria Grazia

    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 and 2007. Results Acute myeloid leukemia (AML; n = 186), myelodysplastic syndrome (MDS; n = 69), and nonmeningioma brain tumor (n = 116) were the most common types of SMNs and had the poorest outcome (5-year survival rate, 18.1% ± 2.9%, 31.1% ± 6.2%, and 18.3% ± 3.8%, respectively). Five-year survival estimates for AML were 11.2% ± 2.9% for 125 patients diagnosed before 2000 and 34.1% ± 6.3% for 61 patients diagnosed after 2000 (P < .001); 5-year survival estimates for MDS were 17.1% ± 6.4% (n = 36) and 48.2% ± 10.6% (n = 33; P = .005). Allogeneic stem-cell transplantation failed to improve outcome of secondary myeloid malignancies after adjusting for waiting time to transplantation. Five-year survival rates were above 90% for patients with meningioma, Hodgkin lymphoma, thyroid carcinoma, basal cell carcinoma, and parotid gland tumor, and 68.5% ± 6.4% for those with non-Hodgkin lymphoma. Eighty-nine percent of patients with brain tumors had received cranial irradiation. Solid tumors were associated with cyclophosphamide exposure, and myeloid malignancy was associated with topoisomerase II inhibitors and starting doses of methotrexate of at least 25 mg/m2 per week and mercaptopurine of at least 75 mg/m2 per day. Myeloid malignancies with monosomy 7/5q− were associated with high hyperdiploid ALL karyotypes, whereas 11q23/MLL-rearranged AML or MDS was associated with ALL harboring translocations of t(9;22), t(4;11), t(1;19), and t(12;21) (P = .03). Conclusion SMNs, except for brain tumors, AML, and MDS, have outcomes similar to their primary counterparts. PMID:23690411

  18. Targeting acute myeloid leukemia stem cells: a review and principles for the development of clinical trials.

    PubMed

    Pollyea, Daniel A; Gutman, Jonathan A; Gore, Lia; Smith, Clayton A; Jordan, Craig T

    2014-08-01

    Despite an increasingly rich understanding of its pathogenesis, acute myeloid leukemia remains a disease with poor outcomes, overwhelmingly due to disease relapse. In recent years, work to characterize the leukemia stem cell population, the disease compartment most difficult to eliminate with conventional therapy and most responsible for relapse, has been undertaken. This, in conjunction with advances in drug development that have allowed for increasingly targeted therapies to be engineered, raises the hope that we are entering an era in which the leukemia stem cell population can be eliminated, resulting in therapeutic cures for acute myeloid leukemia patients. For these therapies to become available, they must be tested in the setting of clinical trials. A long-established clinical trials infrastructure has been employed to shepherd new therapies from proof-of-concept to approval. However, due to the unique features of leukemia stem cells, drugs that are designed to specifically eliminate this population may not be adequately tested when applied to this model. Therefore, in this review article, we seek to identify the relevant features of acute myeloid leukemia stem cells for clinical trialists, discuss potential strategies to target leukemia stem cells, and propose a set of guidelines outlining the necessary elements of clinical trials to allow for the successful testing of stem cell-directed therapies.

  19. Molecular and epidemiologic findings of childhood acute leukemia in Costa Rica.

    PubMed

    Santamaría-Quesada, Carlos; Vargas, Mario; Venegas, Patricia; Calvo, Melvin; Obando, Catalina; Valverde, Berta; Cartín, Walter; Carrillo, Juan Manuel; Jimenez, Rafael; González, Marcos

    2009-02-01

    In Central America, nearly 70% of pediatric cancer is related to hemato-oncologic disorders, especially acute lymphoblastic leukemia (ALL). Preliminary studies have described a high incidence of childhood leukemia in these countries; however, no molecular analyses of these malignancies have yet been carried out. We studied diagnostic samples from 84 patients from the National Children's Hospital in San Jose, Costa Rica (65 precursor B-ALL, 5 T-cell ALL, and 14 acute myeloblastic leukemia). Our methodology included cytogenetic, fluorescent in situ hybridization, and polymerase chain reaction approaches. The observed rate of leukemia was 52.2 cases per million children per year. Twelve out of 65 (18.4%) precursor B-ALL tested positive for TEL-AML1 and 3 cases for BCR-ABL (4.6%). In addition, we detected 2 patients carrying an E2A-PBX1 transcript (3.1%) and 1 patient with an MLL-AF4 fusion gene (1.5%). None of the T-cell ALL cases were positive for either SIL-TAL1 or HOX11L2. Within 14 acute myeloblastic leukemia patients, we confirmed 2 cases with FLT3-internal tandem duplication+, 1 patient with AML1-ETO, and only 1 case carrying a PML-RARalpha rearrangement. The present study confirms the relatively high incidence of pediatric leukemia in Costa Rica and constitutes the first report regarding the incidence of the main molecular alterations of childhood leukemia in our region.

  20. Combination Chemotherapy in Treating Young Patients With Newly Diagnosed T-Cell Acute Lymphoblastic Leukemia or T-cell Lymphoblastic Lymphoma

    ClinicalTrials.gov

    2016-11-02

    Adult T Acute Lymphoblastic Leukemia; Childhood T Acute Lymphoblastic Leukemia; Stage II Adult T-Cell Leukemia/Lymphoma; Stage II Childhood Lymphoblastic Lymphoma; Stage II Contiguous Adult Lymphoblastic Lymphoma; Stage II Non-Contiguous Adult Lymphoblastic Lymphoma; Stage III Adult Lymphoblastic Lymphoma; Stage III Adult T-Cell Leukemia/Lymphoma; Stage III Childhood Lymphoblastic Lymphoma; Stage IV Adult Lymphoblastic Lymphoma; Stage IV Adult T-Cell Leukemia/Lymphoma; Stage IV Childhood Lymphoblastic Lymphoma; Untreated Adult Acute Lymphoblastic Leukemia; Untreated Childhood Acute Lymphoblastic Leukemia

  1. The Notch driven long non-coding RNA repertoire in T-cell acute lymphoblastic leukemia.

    PubMed

    Durinck, Kaat; Wallaert, Annelynn; Van de Walle, Inge; Van Loocke, Wouter; Volders, Pieter-Jan; Vanhauwaert, Suzanne; Geerdens, Ellen; Benoit, Yves; Van Roy, Nadine; Poppe, Bruce; Soulier, Jean; Cools, Jan; Mestdagh, Pieter; Vandesompele, Jo; Rondou, Pieter; Van Vlierberghe, Pieter; Taghon, Tom; Speleman, Frank

    2014-12-01

    Genetic studies in T-cell acute lymphoblastic leukemia have uncovered a remarkable complexity of oncogenic and loss-of-function mutations. Amongst this plethora of genetic changes, NOTCH1 activating mutations stand out as the most frequently occurring genetic defect, identified in more than 50% of T-cell acute lymphoblastic leukemias, supporting a role as an essential driver for this gene in T-cell acute lymphoblastic leukemia oncogenesis. In this study, we aimed to establish a comprehensive compendium of the long non-coding RNA transcriptome under control of Notch signaling. For this purpose, we measured the transcriptional response of all protein coding genes and long non-coding RNAs upon pharmacological Notch inhibition in the human T-cell acute lymphoblastic leukemia cell line CUTLL1 using RNA-sequencing. Similar Notch dependent profiles were established for normal human CD34(+) thymic T-cell progenitors exposed to Notch signaling activity in vivo. In addition, we generated long non-coding RNA expression profiles (array data) from ex vivo isolated Notch active CD34(+) and Notch inactive CD4(+)CD8(+) thymocytes and from a primary cohort of 15 T-cell acute lymphoblastic leukemia patients with known NOTCH1 mutation status. Integration of these expression datasets with publicly available Notch1 ChIP-sequencing data resulted in the identification of long non-coding RNAs directly regulated by Notch activity in normal and malignant T cells. Given the central role of Notch in T-cell acute lymphoblastic leukemia oncogenesis, these data pave the way for the development of novel therapeutic strategies that target hyperactive Notch signaling in human T-cell acute lymphoblastic leukemia.

  2. High-risk acute myelogenous leukemia: treatment today ... and tomorrow.

    PubMed

    Schiller, Gary J

    2013-01-01

    High-risk acute myelogenous leukemia (AML) constitutes a distinct subset of disease based on clinical and biological characteristics and comprises a significant percentage of all cases of adult AML. Biologic features such as distinct clonal cytogenetic and molecular abnormalities identify a subgroup of AML patients characterized by poor response to induction chemotherapy and poor long-term survival after treatment with consolidation chemotherapy. Clinical variables that predict for poor response include AML relapsed after less than 1 year of remission and AML characterized by resistance to conventional agents. We review here our understanding of the defining biologic subtypes of AML and discuss how adequate initial evaluation can be used to inform the choice of treatment. By defining high-risk biologic and clinical variables, a strong case can be made for treating patients with investigational agents, with treatment directed at distinct cytogenetic or molecular abnormalities. Allogeneic transplantation is the only form of therapy available outside of the setting of a clinical trial that may offer a chance for long-term survival for patients with high-risk AML.

  3. Acute promyelocytic leukemia during pregnancy: a systematic analysis of outcome.

    PubMed

    Verma, Vivek; Giri, Smith; Manandhar, Samyak; Pathak, Ranjan; Bhatt, Vijaya Raj

    2016-01-01

    The outcomes of acute promyelocytic leukemia (APL) in pregnancy are largely unknown. The MEDLINE database was systematically searched to obtain 43 articles with 71 patients with new-onset APL during pregnancy. Induction therapy included various regimens of all-trans retinoic acid (ATRA), cytarabine, and anthracycline and resulted in a complete remission rate of 93%. Obstetric and fetal complications included pre-term deliveries (46%), spontaneous/therapeutic abortion/intrauterine death (33.3%) and other neonatal complications (25.9%). Mothers diagnosed in the first trimester were more likely to experience obstetric (p < 0.01) and fetal (p < 0.01) complications. To our knowledge, this is the largest systematic review of APL in pregnancy. The vast majority of APL patients in pregnancy may achieve remission with initial induction therapy. APL or its therapy in pregnancy, however, is associated with a high risk of fetal and obstetrical complications. The results of our study may help in patient counseling and informed decision-making. PMID:26110880

  4. Definition of Cure in Childhood Acute Myeloid Leukemia

    PubMed Central

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

    2014-01-01

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

  5. A 50-Year Journey to Cure Childhood Acute Lymphoblastic Leukemia

    PubMed Central

    Pui, Ching-Hon; Evans, William E.

    2013-01-01

    The 50th anniversary of Seminars in Hematology coincides with the 50th of St. Jude Children’s Research Hospital, and both milestones are inexorably linked to studies contributing to the cure of childhood acute lymphoblastic leukemia (ALL). We thought it fitting, therefore, to mark these events by traveling back in time to point out some of the achievements, institutions, study groups and individuals that have made cure of childhood ALL a reality. In many instances, progress was driven by new ideas, while in others it was driven by new experimental tools that allowed more precise assessment of the biology of leukemic blasts and their utility in selecting therapy. We also discuss a number of contemporary advances that point the way to exciting future directions. Whatever pathways are taken, a clear challenge will be to use emerging genome-based or immunologic-based treatment options in ways that will enhance, rather than duplicate or compromise, recent gains in outcome with classic cytotoxic chemotherapy. The theme of this journey serves as a reminder of the chief ingredient of any research directed to a catastrophic disease such as ALL. It is the audacity of a small group of investigators who confronted a childhood cancer with the goal of cure, not palliation, as their mindset. PMID:23953334

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

    PubMed

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

    2006-09-15

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

  7. The molecular genetic makeup of acute lymphoblastic leukemia.

    PubMed

    Mullighan, Charles G

    2012-01-01

    Genomic profiling has transformed our understanding of the genetic basis of acute lymphoblastic leukemia (ALL). Recent years have seen a shift from microarray analysis and candidate gene sequencing to next-generation sequencing. Together, these approaches have shown that many ALL subtypes are characterized by constellations of structural rearrangements, submicroscopic DNA copy number alterations, and sequence mutations, several of which have clear implications for risk stratification and targeted therapeutic intervention. Mutations in genes regulating lymphoid development are a hallmark of ALL, and alterations of the lymphoid transcription factor gene IKZF1 (IKAROS) are associated with a high risk of treatment failure in B-ALL. Approximately 20% of B-ALL cases harbor genetic alterations that activate kinase signaling that may be amenable to treatment with tyrosine kinase inhibitors, including rearrangements of the cytokine receptor gene CRLF2; rearrangements of ABL1, JAK2, and PDGFRB; and mutations of JAK1 and JAK2. Whole-genome sequencing has also identified novel targets of mutation in aggressive T-lineage ALL, including hematopoietic regulators (ETV6 and RUNX1), tyrosine kinases, and epigenetic regulators. Challenges for the future are to comprehensively identify and experimentally validate all genetic alterations driving leukemogenesis and treatment failure in childhood and adult ALL and to implement genomic profiling into the clinical setting to guide risk stratification and targeted therapy.

  8. Antitumoral effect of Ocoxin on acute myeloid leukemia

    PubMed Central

    Díaz-Rodríguez, Elena; Hernández-García, Susana; Sanz, Eduardo; Pandiella, Atanasio

    2016-01-01

    Acute myeloid leukemia (AML) is a heterogeneous hematological malignancy whose incidence is growing in developed countries. In the relapse setting, very limited therapeutic options are available and in most cases only palliative care can be offered to patients. The effect of a composite formulation that contains several antioxidants, Ocoxin Oral solution (OOS), was tested in this condition. When analyzed in vitro, OOS exhibited anti-AML action that was both time and dose dependent. In vivo OOS induced a ralentization of tumor growth that was due to a decrease in cell proliferation. Such effect could, at least partially, be due to an increase in the cell cycle inhibitor p27, although other cell cycle proteins seemed to be altered. Besides, OOS induced an immunomodulatory effect through the induction of IL6. When tested in combination with other therapeutic agents normally used in the treatment of AML patients, OOS demonstrated a higher antiproliferative action, suggesting that it may be used in combination with those standard of care treatments to potentiate their antiproliferative action in the AML clinic. PMID:26756220

  9. Inhibition of pentose phosphate pathway suppresses acute myelogenous leukemia.

    PubMed

    Chen, Yan; Xu, Qian; Ji, Dexiang; Wei, Yanlin; Chen, Huamei; Li, Tingting; Wan, Bolin; Yuan, Liya; Huang, Ruibin; Chen, Guoan

    2016-05-01

    Pentose phosphate pathway (PPP) is a metabolic pathway that generates NADPH and pentose. PPP genes have been reported to be primarily or secondarily upregulated in many cancers. We aimed to study the general alteration of PPP in acute myelogenous leukemia (AML). We performed data mining and analysis of the Cancer Genome Atlas (TCGA) AML dataset for genetic alteration of the PPP gene set. In vitro studies including proliferation, migration, and invasion assays, together with metabolite consumption and oxidation assays, were performed. PPP genes were upregulated in 61 % of patients with AML. The majority of altered cases were expression changes measured by RNA sequencing. Expressions of critical PPP genes such as G6PD, PFKL, PFKP, and PGLS were consistently upregulated in all altered cases. Altered PPP is not associated with survival or disease relapse. PPP inhibition using 6-aminonicotinamide (6AN) increases glucose oxidative metabolism in AML. 6AN decreased the glucose oxidation and increased fatty acid oxidation. Here, we showed that PPP inhibition increased glucose oxidative metabolism in AML. PPP inhibition suppressed growth, migration, and invasion of AML, but not colony formation. PPP plays an important role in AML. Our results could contribute to the development of novel targeted treatment.

  10. Recent discoveries in molecular characterization of acute myeloid leukemia.

    PubMed

    Khasawneh, Mohamad K; Abdel-Wahab, Omar

    2014-06-01

    Acute myeloid leukemia (AML) is a clinically heterogeneous disease, yet it is one of the most molecularly well-characterized cancers. Risk stratification of patients currently involves determination of the presence of cytogenetic abnormalities in combination with molecular genetic testing in a few genes. Several new recurrent genetic molecular abnormalities have recently been identified, including TET2, ASXL1, IDH1, IDH2, DNMT3A, and PHF6. Mutational analyses have identified that patients with DNMT3A or NPM1 mutations or MLL translocation have improved overall survival with high-dose chemotherapy. Mutational profiling can refine prognostication, particularly for patients in the intermediate-risk group or with a normal karyotype. CD25 expression status improves prognostic risk classification in AML independent of established biomarkers. Biomarkers such as 2- hydroxyglutarate in IDH1/2-mutant AML patients predict patient responses and minimal residual disease. These recent discoveries are being incorporated into our existing molecular risk stratification as well as the exploration of new therapeutics directed to these molecular targets.

  11. Recent advances and novel treatment paradigms in acute lymphocytic leukemia

    PubMed Central

    Papadantonakis, Nikolaos; Advani, Anjali S.

    2016-01-01

    This is an exciting time in the treatment of acute lymphoblastic leukemia (ALL) given the advances in the relapsed/refractory setting. The development of antibody treatments (including antibody drug conjugates with toxins) offers a different treatment approach compared with conventional chemotherapy regimens. Moreover, the use of bispecific T-cell-engager antibodies (BiTEs) such as blinatumomab harness the cytotoxic activity of T cells against CD19-positive lymphoblasts. Another strategy involves the use of chimeric antigen receptor (CAR) T cells. CAR T cells have demonstrated promising results in the relapsed/refractory setting. However, the use of BiTEs and CAR T cells is also associated with a distinct set of adverse reactions that must be taken into account by the treating physician. Apart from the above strategies, the use of other targeted therapies has attracted interest. Namely, the discovery of the Philadelphia (Ph)-like signature in children and young adults with ALL has led to the use of tyrosine kinase inhibitors (TKI) in these patients. The different drugs and strategies that are being tested in the relapsed/refractory ALL setting pose a unique challenge in identifying the optimum sequence of treatment and determining which approaches should be considered for frontline treatment.

  12. Poor survival of treatment-related acute nonlymphocytic leukemia

    SciTech Connect

    Neugut, A.I. Nieves, J.; Murray, T.; Tsai, Weiyann ); Robinson, E. )

    1990-08-29

    Population-based data on more than 1 million patients registered in the Surveillance, Epidemiology, and End-Results Program of the National Cancer Institute, 1973-1984, were analyzed to determine the survival of patients with de novo acute nonlymphocytic leukemia (ANLL) and following a first primary tumor treated (with chemotherapy and/or radiation therapy) or untreated. Cases that occurred within 12 months of the first malignant neoplasm were excluded. Survival was estimated using Cox proportional-hazards modeling, with age, sex, and specific type of ANLL as covariates. The 6,271 patients with de novo ANLL had an estimated 12-month survival of 30%, while the 107 patients with treatment-related ANLL had an estimated 12-month survival of 10%. The authors conclude that ANLL that occurs after chemotherapy or radiation therapy is biologically more aggressive and/or resistant to therapy than spontaneous ANLL. This provides a rationale for current studies on treatment-induced cellular changes and on more aggressive therapy for these patients.

  13. Molecular analysis of childhood acute lymphoblastic leukemia in Israel.

    PubMed

    Blau, O; Avigad, S; Frisch, A; Kilim, Y; Stark, B; Kodman, Y; Luria, D; Cohen, I J; Zaizov, R

    1998-06-01

    Ninety-two Israeli children with acute lymphoblastic leukemia (ALL) (67 B-lineage and 25 T-lineage) were analyzed for the immunological antigen receptor gene configuration. Thirty-nine of the patients (27 B-lineage and 12 T-lineage) relapsed. The incidence of the identified rearrangements within the immunoglobulin heavy chain (IgH) and T-cell receptor (TCR)beta, gamma and delta genes, at diagnosis, was in accordance with previous studies from other countries. Furthermore, the clinical relevance of bi/oligoclonal status, at diagnosis, and clonal selection was determined in this long-term follow-up study (median 112 months). A similar relapse rate was observed among the B-lineage patients with bi/oligoclonal and monoclonal patterns indicated by IgH gene rearrangement. Based on our results, we suggest that bi/oligoclonality has no prognostic significance (P=0.8533). Clonal variations between diagnosis and subsequent relapses were detected in 60% (12/20) of the patients; 64% (7/11) B-lineage and 55% (5/9) T-lineage. Clonal selection significantly correlated with shorter duration of remission and earlier recurrence (P=0.0025).

  14. Biology and Clinical Relevance of Acute Myeloid Leukemia Stem Cells.

    PubMed

    Reinisch, Andreas; Chan, Steven M; Thomas, Daniel; Majeti, Ravindra

    2015-07-01

    Evidence for the cancer stem cell model was first demonstrated in xenotransplanted blood and bone marrow samples from patients with acute myeloid leukemia (AML) almost two decades ago, supporting the concept that a rare clonal and mutated leukemic stem cell (LSC) population is sufficient to drive leukemic growth. The inability to eliminate LSCs with conventional therapies is thought to be the primary cause of disease relapse in AML patients, and as such, novel therapies with the ability to target this population are required to improve patient outcomes. An important step towards this goal is the identification of common immunophenotypic surface markers and biological properties that distinguish LSCs from normal hematopoietic stem and progenitor cells (HSPCs) across AML patients. This work has resulted in the development of a large number of potential LSC-selective therapies that target cell surface molecules, intracellular signaling pathways, and the bone marrow microenvironment. Here, we will review the basic biology, immunophenotypic detection, and clinical relevance of LSCs, as well as emerging biological and small-molecule strategies that either directly target LSCs or indirectly target these cells through modulation of their microenvironment.

  15. BCL6 modulation of acute lymphoblastic leukemia response to chemotherapy

    PubMed Central

    Slone, William L.; Moses, Blake S.; Hare, Ian; Evans, Rebecca; Piktel, Debbie; Gibson, Laura F.

    2016-01-01

    The bone marrow niche has a significant impact on acute lymphoblastic leukemia (ALL) cell phenotype. Of clinical relevance is the frequency with which quiescent leukemic cells, in this niche, survive treatment and contribute to relapse. This study suggests that marrow microenvironment regulation of BCL6 in ALL is one factor that may be involved in the transition between proliferative and quiescent states of ALL cells. Utilizing ALL cell lines, and primary patient tumor cells we observed that tumor cell BCL6 protein abundance is decreased in the presence of primary human bone marrow stromal cells (BMSC) and osteoblasts (HOB). Chemical inhibition, or shRNA knockdown, of BCL6 in ALL cells resulted in diminished ALL proliferation. As many chemotherapy regimens require tumor cell proliferation for optimal efficacy, we investigated the consequences of constitutive BCL6 expression in leukemic cells during co-culture with BMSC or HOB. Forced chronic expression of BCL6 during co-culture with BMSC or HOB sensitized the tumor to chemotherapy induced cell death. Combination treatment of caffeine, which increases BCL6 expression in ALL cells, with chemotherapy extended the event free survival of mice. These data suggest that BCL6 is one factor, modulated by microenvironment derived cues that may contribute to regulation of ALL therapeutic response. PMID:27015556

  16. A mathematical model of phosphorylation AKT in Acute Myeloid Leukemia

    NASA Astrophysics Data System (ADS)

    Adi, Y. A.; Kusumo, F. A.; Aryati, L.; Hardianti, M. S.

    2016-04-01

    In this paper we consider a mathematical model of PI3K/AKT signaling pathways in phosphorylation AKT. PI3K/AKT pathway is an important mediator of cytokine signaling implicated in regulation of hematopoiesis. Constitutive activation of PI3K/AKT signaling pathway has been observed in Acute Meyloid Leukemia (AML) it caused by the mutation of Fms-like Tyrosine Kinase 3 in internal tandem duplication (FLT3-ITD), the most common molecular abnormality associated with AML. Depending upon its phosphorylation status, protein interaction, substrate availability, and localization, AKT can phosphorylate or inhibite numerous substrates in its downstream pathways that promote protein synthesis, survival, proliferation, and metabolism. Firstly, we present a mass action ordinary differential equation model describing AKT double phosphorylation (AKTpp) in a system with 11 equations. Finally, under the asumtion enzyme catalyst constant and steady state equilibrium, we reduce the system in 4 equation included Michaelis Menten constant. Simulation result suggested that a high concentration of PI3K and/or a low concentration of phospatase increased AKTpp activation. This result also indicates that PI3K is a potential target theraphy in AML.

  17. Premature adiposity rebound in children treated for acute lymphoblastic leukemia.

    PubMed

    Reilly, J J; Kelly, A; Ness, P; Dorosty, A R; Wallace, W H; Gibson, B E; Emmett, P M

    2001-06-01

    The adiposity rebound (AR), when body mass index begins to increase after its nadir in childhood, is a critical period for the regulation of energy balance and adult obesity risk. The aim of the present study was to test whether children treated for acute lymphoblastic leukemia (ALL) experience premature AR. This might, in part, explain their tendency to develop obesity. Timing of AR was assessed by visual inspection of body mass index plots in 68 patients treated for ALL in first remission. This sample comprised all eligible patients treated in Scotland between 1991 and 1998, age 30 months or less at the time of diagnosis. Timing of AR in patients was compared against a cohort of 889 healthy British children studied during the 1990s using the same method. AR occurred significantly earlier in the patients treated for ALL (chi(2) test, P < 0.001). The AR had occurred in 43% (29 of 68) of the patients and 4% (40 of 889) of the comparison group by age 37 months. At 49 months AR had occurred in 81% (55 of 68) of the patients and 21% (190 of 889) of the comparison group. Treatment of ALL is associated with a significantly advanced AR. This might, in part, explain the extremely high prevalence of obesity in long-term survivors. Clinical management should focus on minimizing excess weight gain during therapy to reduce long-term obesity risk.

  18. The clinically relevant pharmacogenomic changes in acute myelogenous leukemia.

    PubMed

    Emadi, Ashkan; Karp, Judith E

    2012-08-01

    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 myelodysplastic syndromes or myeloproliferative neoplasms, treatment-related AML, relapsed or refractory AML, and AML that occurs in older populations remains grim. Taken into account the heterogeneity of AML, one size does not and should not be tried to fit all. In this article, the authors review currently understood, applicable and relevant findings related to cytarabine and anthracycline drug-metabolizing enzymes and drug transporters in adult patients with AML. To provide a prime-time example of clinical applicability of pharmacogenomics in distinguishing a subset of patients with AML who might be better responders to farnesyltransferase inhibitors, the authors also reviewed findings related to a two-gene transcript signature consisting of high RASGRP1 and low APTX, the ratio of which appears to positively predict clinical response in AML patients treated with farnesyltransferase inhibitors.

  19. Management of adult Ph-positive acute lymphoblastic leukemia.

    PubMed

    Chiaretti, Sabina; Foà, Robin

    2015-01-01

    Philadelphia-positive acute lymphoblastic leukemia (Ph+ ALL) has been regarded for decades as the ALL subgroup with the worse outcome. It represents the most frequent genetic subtype of adult ALL, and increases progressively with age. The introduction of tyrosine kinase inhibitors (TKIs) has enabled to obtain complete hematologic remissions (CHRs) in virtually all patients, including the elderly, to improve disease-free survival and overall survival, as well as to increase the percentage of patients who can undergo an allogeneic stem cell transplant (allo-SCT).The current management of adult Ph+ ALL patients relies on the use of a TKI with or without chemotherapy followed by an allo-SCT, which still remains the only curative option. Minimal residual disease screening is permitting not only a better stratification of patients, but has also allowed to reconsider the role of autologous stem cell transplant for a set of patients who do not have a donor or are not eligible for an allo-SCT. At present, clinical challenges are represented by the emergence of resistant mutations, particularly the gatekeeper T315I, for which alternative approaches, comprising novel TKIs or therapies based on the combination of TKI with immunotherapeutic strategies, are being considered in order to overcome resistance.

  20. Genetic and epigenetic characterization of hypodiploid acute lymphoblastic leukemia

    PubMed Central

    Safavi, Setareh; Olsson, Linda; Biloglav, Andrea; Veerla, Srinivas; Blendberg, Molly; Tayebwa, Johnbosco; Behrendtz, Mikael; Castor, Anders; Hansson, Markus; Johansson, Bertil; Paulsson, Kajsa

    2015-01-01

    Purpose To investigate the genetic and epigenetic landscape of hypodiploid (<45 chromosomes) acute lymphoblastic leukemia (ALL). Methods Single nucleotide polymorphism array, whole exome sequencing, RNA sequencing, and methylation array analyses were performed on eleven hypodiploid ALL cases. Results In line with previous studies, mutations in IKZF3 and FLT3 were detected in near-haploid (25–30 chromosomes) cases. Low hypodiploidy (31–39 chromosomes) was associated with somatic TP53 mutations. Notably, mutations of this gene were also found in 3/3 high hypodiploid (40–44 chromosomes) cases, suggesting that the mutational patterns are similar in low hypodiploid and high hypodiploid ALL. The high hypodiploid ALLs frequently displayed substantial cell-to-cell variability in chromosomal content, indicative of chromosomal instability; a rare phenomenon in ALL. Gene expression analysis showed that genes on heterodisomic chromosomes were more highly expressed in hypodiploid cases. Cases clustered according to hypodiploid subtype in the unsupervised methylation analyses, but there was no association between chromosomal copy number and methylation levels. A comparison between samples obtained at diagnosis and relapse showed that the relapse did not arise from the major diagnostic clone in 3/4 cases. Conclusion Taken together, our data support the conclusion that near-haploid and low hypodiploid ALL are different with regard to mutational profiles and also suggest that ALL cases with high hypodiploidy may harbor chromosomal instability. PMID:26544893

  1. [Cytarabine and skin reactions in acute myeloid leukemia].

    PubMed

    Grille, Sofía; Guadagna, Regina; Boada, Matilde; Irigoin, Victoria; Stevenazzi, Mariana; Guillermo, Cecilia; Díaz, Lilián

    2013-01-01

    Cytarabine is an antimetabolite used in the treatment of acute myeloid leukemia (AML). It has many adverse effects as: myelosuppression, toxic reactions involving central nervous system, liver, gastrointestinal tract, eyes or skin. Dermatologic toxicity is often described as rare; nevertheless there are differences in the reported frequency. We performed a retrospective study including all AML treated with chemotherapy that involved cytarabine between 1st July of 2006 and 1st July of 2012; 46 patients were included with a median age of 55 years. The overall incidence of skin reactions was 39% (n = 18). Sex, age, history of atopy, history of drug reactions, or dose of cytarabine used, were not associated with them. Skin reactions were observed from 2 to 8 days after treatment started. Considering injury degree: 27.8% had grade 1, 38.9% grade 2 and 33.3% grade 3. We did not find any injury grade 4 or death associated with skin toxicity. As for the type of injury: 55.6% presented macules, 22.2% papules and 22.2% erythema. Lesions distribution was diffuse in 52% of patients, acral in 39.3%, and at flexural level in 8.7%. Adverse cutaneous reactions secondary to the administration of cytarabine are frequent in our service and include some cases with severe involvement. Although these reactions usually resolve spontaneously, they determine an increased risk of infection and a compromise of the patient quality of life.

  2. Epigenetics in T-cell acute lymphoblastic leukemia.

    PubMed

    Peirs, Sofie; Van der Meulen, Joni; Van de Walle, Inge; Taghon, Tom; Speleman, Frank; Poppe, Bruce; Van Vlierberghe, Pieter

    2015-01-01

    Normal T-cell development is a strictly regulated process in which hematopoietic progenitor cells migrate from the bone marrow to the thymus and differentiate from early T-cell progenitors toward mature and functional T cells. During this maturation process, cooperation between a variety of oncogenes and tumor suppressors can drive immature thymocytes into uncontrolled clonal expansion and cause T-cell acute lymphoblastic leukemia (T-ALL). Despite improved insights in T-ALL disease biology and comprehensive characterization of its genetic landscape, clinical care remained largely similar over the past decades and still consists of high-dose multi-agent chemotherapy potentially followed by hematopoietic stem cell transplantation. Even with such aggressive treatment regimens, which are often associated with considerable side effects, clinical outcome is still extremely poor in a significant subset of T-ALL patients as a result of therapy resistance or hematological relapses. Recent genetic studies have identified recurrent somatic alterations in genes involved in DNA methylation and post-translational histone modifications in T-ALL, suggesting that epigenetic homeostasis is critically required in restraining tumor development in the T-cell lineage. In this review, we provide an overview of the epigenetic regulators that could be implicated in T-ALL disease biology and speculate how the epigenetic landscape of T-ALL could trigger the development of epigenetic-based therapies to further improve the treatment of human T-ALL. PMID:25510271

  3. Acute myeloid leukemia ontogeny is defined by distinct somatic mutations.

    PubMed

    Lindsley, R Coleman; Mar, Brenton G; Mazzola, Emanuele; Grauman, Peter V; Shareef, Sarah; Allen, Steven L; Pigneux, Arnaud; Wetzler, Meir; Stuart, Robert K; Erba, Harry P; Damon, Lloyd E; Powell, Bayard L; Lindeman, Neal; Steensma, David P; Wadleigh, Martha; DeAngelo, Daniel J; Neuberg, Donna; Stone, Richard M; Ebert, Benjamin L

    2015-02-26

    Acute myeloid leukemia (AML) can develop after an antecedent myeloid malignancy (secondary AML [s-AML]), after leukemogenic therapy (therapy-related AML [t-AML]), or without an identifiable prodrome or known exposure (de novo AML). The genetic basis of these distinct pathways of AML development has not been determined. We performed targeted mutational analysis of 194 patients with rigorously defined s-AML or t-AML and 105 unselected AML patients. The presence of a mutation in SRSF2, SF3B1, U2AF1, ZRSR2, ASXL1, EZH2, BCOR, or STAG2 was >95% specific for the diagnosis of s-AML. Analysis of serial samples from individual patients revealed that these mutations occur early in leukemogenesis and often persist in clonal remissions. In t-AML and elderly de novo AML populations, these alterations define a distinct genetic subtype that shares clinicopathologic properties with clinically confirmed s-AML and highlights a subset of patients with worse clinical outcomes, including a lower complete remission rate, more frequent reinduction, and decreased event-free survival. This trial was registered at www.clinicaltrials.gov as #NCT00715637. PMID:25550361

  4. Evaluation of artemisinins for the treatment of acute myeloid leukemia

    PubMed Central

    Drenberg, Christina D.; Buaboonnam, Jassada; Orwick, Shelley J.; Hu, Shuiying; Li, Lie; Fan, Yiping; Shelat, Anang A.; Guy, R. Kiplin; Rubnitz, Jeffrey

    2016-01-01

    Purpose Investigate antileukemic activity of artemisinins, artesunate (ART), and dihydroartemisinin (DHA), in combination with cytarabine, a key component of acute myeloid leukemia (AML) chemotherapy using in vitro and in vivo models. Methods Using ten human AML cell lines, we conducted a high-throughput screen to identify antimalarial agents with antileukemic activity. We evaluated effects of ART and DHA on cell viability, cytotoxicity, apoptosis, lysosomal integrity, and combination effects with cytarabine in cell lines and primary patient blasts. In vivo pharmacokinetic studies and efficacy of single-agent ART or combination with cytarabine were evaluated in three xenograft models. Results ART and DHA had the most potent activity in a panel of AML cell lines, with selectivity toward samples harboring MLL rearrangements and FLT3-ITD mutations. Combination of ART or DHA was synergistic with cytarabine. Single-dose ART (120 mg/kg) produced human equivalent exposures, but multiple dose daily administration required for in vivo efficacy was not tolerated. Combination treatment produced initial regression, but did not prolong survival in vivo. Conclusions The pharmacology of artemisinins is problematic and should be considered in designing AML treatment strategies with currently available agents. Artemisinins with improved pharmacokinetic properties may offer therapeutic benefit in combination with conventional therapeutic strategies in AML. PMID:27125973

  5. MINIMAL RESIDUAL DISEASE QUANTITATION IN ACUTE MYELOID LEUKEMIA

    PubMed Central

    Shook, David; Coustan-Smith, Elaine; Ribeiro, Raul C.; Rubnitz, Jeffrey E.; Campana, Dario

    2009-01-01

    The prognosis for patients with acute myeloid leukemia (AML) is heterogeneous. A minority of patients has clinical and biologic features that are associated with a very high risk of relapse. For the remaining patients no clear prognostic factors can be identified at diagnosis. The degree of treatment response is likely to be an informative predictor of outcome for these patients. Modern assays to detect AML cells that are undetectable by conventional morphologic techniques, i.e. minimal residual disease (MRD), can potentially improve measurements of treatment response. It is plausible that modifications to treatment based on the results of these assays will improve clinical management and ultimately increase cure rates. Established MRD assays for AML are based on either polymerase chain reaction (PCR) amplification of genetic abnormalities or flow cytometric detection of abnormal immunophenotypes. Residual disease and treatment response can be measured by these assays in a manner that is much more sensitive and objective than that afforded by conventional morphologic examination. The expanding use of MRD testing is beginning to change the definition of treatment response and of remission. Other clinically informative uses of MRD testing include the detection of early relapse and the evaluation of the efficacy of new antileukemic agents. PMID:19778853

  6. Pediatric Acute Lymphoblastic Leukemia and Exposure to Pesticides

    PubMed Central

    Soldin, Offie P.; Nsouly-Maktabi, Hala; Genkinger, Jeanine M.; Loffredo, Christopher A.; Ortega-Garcia, Juan Antonio; Colantino, Drew; Barr, Dana B.; Luban, Naomi L.; Shad, Aziza T.; Nelson, David

    2013-01-01

    Organophosphates are pesticides ubiquitous in the environment and have been hypothesized as one of the risk factors for acute lymphoblastic leukemia (ALL). In this study, we evaluated the associations of pesticide exposure in a residential environment with the risk for pediatric ALL. This is a case–control study of children newly diagnosed with ALL, and their mothers (n = 41 child–mother pairs) were recruited from Georgetown University Medical Center and Children's National Medical Center in Washington, DC, between January 2005 and January 2008. Cases and controls were matched for age, sex, and county of residence. Environmental exposures were determined by questionnaire and by urinalysis of pesticide metabolites using isotope dilution gas chromatography–high-resolution mass spectrometry. We found that more case mothers (33%) than controls (14%) reported using insecticides in the home (P < 0.02). Other environmental exposures to toxic substances were not significantly associated with the risk of ALL. Pesticide levels were higher in cases than in controls (P < 0.05). Statistically significant differences were found between children with ALL and controls for the organophosphate metabolites diethylthiophosphate (P < 0.03) and diethyldithiophosphate (P < 0.05). The association of ALL risk with pesticide exposure merits further studies to confirm the association. PMID:19571777

  7. Acute myeloid leukemia ontogeny is defined by distinct somatic mutations

    PubMed Central

    Lindsley, R. Coleman; Mar, Brenton G.; Mazzola, Emanuele; Grauman, Peter V.; Shareef, Sarah; Allen, Steven L.; Pigneux, Arnaud; Wetzler, Meir; Stuart, Robert K.; Erba, Harry P.; Damon, Lloyd E.; Powell, Bayard L.; Lindeman, Neal; Steensma, David P.; Wadleigh, Martha; DeAngelo, Daniel J.; Neuberg, Donna

    2015-01-01

    Acute myeloid leukemia (AML) can develop after an antecedent myeloid malignancy (secondary AML [s-AML]), after leukemogenic therapy (therapy-related AML [t-AML]), or without an identifiable prodrome or known exposure (de novo AML). The genetic basis of these distinct pathways of AML development has not been determined. We performed targeted mutational analysis of 194 patients with rigorously defined s-AML or t-AML and 105 unselected AML patients. The presence of a mutation in SRSF2, SF3B1, U2AF1, ZRSR2, ASXL1, EZH2, BCOR, or STAG2 was >95% specific for the diagnosis of s-AML. Analysis of serial samples from individual patients revealed that these mutations occur early in leukemogenesis and often persist in clonal remissions. In t-AML and elderly de novo AML populations, these alterations define a distinct genetic subtype that shares clinicopathologic properties with clinically confirmed s-AML and highlights a subset of patients with worse clinical outcomes, including a lower complete remission rate, more frequent reinduction, and decreased event-free survival. This trial was registered at www.clinicaltrials.gov as #NCT00715637. PMID:25550361

  8. Mechanism of relapse in pediatric acute lymphoblastic leukemia.

    PubMed

    Henderson, Michelle J; Choi, Seoyeon; Beesley, Alex H; Sutton, Rosemary; Venn, Nicola C; Marshall, Glenn M; Kees, Ursula R; Haber, Michelle; Norris, Murray D

    2008-05-15

    Relapse following initial chemotherapy remains a barrier to survival in approximately 20% of children suffering from acute lymphoblastic leukemia (ALL). Recently, to investigate the mechanism of relapse, we analysed clonal populations in 27 pairs of matched diagnosis and relapse ALL samples using PCR-based detection of multiple antigen receptor gene rearrangements. These clonal markers revealed the emergence of apparently new populations at relapse in 13 patients. In those cases where the new 'relapse clone' could be detected in the diagnosis population, there was a close correlation between length of first remission and quantity of the relapse clone in the diagnosis sample. A shorter length of time to first relapse correlated with a higher quantity of the relapsing clone at diagnosis. This observation, together with demonstrated differential chemosensitivity between sub-clones at diagnosis, indicates that relapse in ALL patients may commonly involve selection of a minor intrinsically resistant sub-clone that is undetectable by routine PCR-based methods. From a clinical perspective, relapse prediction may be improved with strategies to detect minor potentially resistant sub-clones early during treatment, hence allowing intensification of therapy. Together with the availability of relevant in vivo experimental models and powerful technology for detailed analysis of patient specimens, this new information will help shape future experimentation towards targeted therapy for high-risk ALL.

  9. Imaging of acute invasive fungal rhinosinusitis in a patient with gorlin syndrome and acute lymphocytic leukemia.

    PubMed

    Donovan, S T; Thompson, J W; Sandlund, J T; Adderson, E E; Pivnick, E K; Harreld, J H

    2013-01-01

    Gorlin Syndrome (GS), also known as nevoid basal cell carcinoma syndrome, is a rare autosomal dominant condition characterized by developmental abnormalities and predisposition to certain neoplasms. Acute invasive fungal rhinosinusitis (AIFRS) is an uncommon clinical entity characterized by high morbidity and mortality. In immunocompromised patients, computed tomography plays a critical role in screening for suspected AIFRS. However, due to the association between exposure to ionizing radiation and subsequent development of malignancies in patients with GS, patients with GS and suspected AIFRS present a unique and challenging clinical scenario. We present a case of a pediatric patient with GS and acute lymphocytic leukemia (ALL) diagnosed with AIFRS; to the best of our knowledge, it is the only case described in the literature.

  10. Acute myocardial/cerebral infarction as first/relapse manifestation in one acute promyelocytic leukemia patient

    PubMed Central

    Li, Ying; Suo, Shanshan; Mao, Liping; Wang, Lei; Yang, Chunmei; Xu, Weilai; Lou, Yinjun; Mai, Wenyuan

    2015-01-01

    In the clinical setting, bleeding is a common manifestation of acute promyelocytic leukemia (APL), whereas thrombosis is relatively rare, especially as an initial symptom. Here, we report an unusual case of APL with acute myocardial infarction as the first manifestation and cerebral infarction as the relapse manifestation in a healthy young woman. This unique case emphasizes that a thrombotic event could be the first manifestation of an underlying hematological disorder such as APL and could also be a sign of relapse. Rapid detection of the underlying disorder and the timely use of anticoagulation therapy and ATRA are crucial for preventing further deterioration of the disease and saving the patient’s life. PMID:26550398

  11. Incremental value of the bone marrow trephine biopsy in detecting residual leukemia following treatment for Acute Myeloid Leukemia.

    PubMed

    Saini, Lalit; Brandwein, Joseph; Turner, Robert; Larratt, Loree; Hamilton, Marlene; Peters, Anthea; Wu, Cynthia; Zhu, Nancy; Taparia, Minakshi; Patterson, Jeffery M; Bolster, Lauren; Mant, Michael; Ritchie, Bruce; Liew, Elena; Mirza, Imran; Quest, Graeme; Nahirniak, Susan; Ghosh, Sunita; Sandhu, Irwindeep

    2016-06-01

    Most guidelines suggest that only the bone marrow aspirate (BMA) is necessary to assess residual disease following intensive chemotherapy for Acute Myeloid Leukemia (AML) with the bone marrow trephine biopsy (BMTB) recommended in cases of a poor quality BMA. We performed a retrospective study evaluating this in a cohort of patients receiving intensive chemotherapy for AML. Residual disease was assessed by morphological examination of the BMA and BMTB±immunohistochemistry. Of the 647 marrows 32.6% were interim marrows performed prior to peripheral count recovery, 41.7% were end of induction (EOI) marrows and the remaining were 'other marrows'. The BMA and BMTB findings were concordant in 92.8% of cases. The BMTB led to a change in diagnosis from 'no leukemia' to 'residual leukemia' in 5.2% of interim, 3.7% of EOI and 2.4% of 'other' marrows. The BMA alone had a sensitivity of 86.8% in detecting residual leukemia and of 82.3%, 82.5% and 94.2% for interim, EOI and 'other marrows', respectively. Despite the high concordance between the BMA and the BMTB the poor sensitivity of the BMA in detecting residual leukemia, particularly at EOI, may lead to an overestimation of the complete remission rates which may have therapeutic and clinical trial implications.

  12. Acute myelogenous leukemia cells with the MLL-ELL translocation convert morphologically and functionally into adherent myofibroblasts

    SciTech Connect

    Tashiro, Haruko; Mizutani-Noguchi, Mitsuho; Shirasaki, Ryosuke

    2010-01-01

    Bone marrow-myofibroblasts, a major component of bone marrow-stroma, are reported to originate from hematopoietic stem cells. We show in this paper that non-adherent leukemia blasts can change into myofibroblasts. When myeloblasts from two cases of acute myelogenous leukemia with a fusion product comprising mixed lineage leukemia and RNA polymerase II elongation factor, were cultured long term, their morphology changed to that of myofibroblasts with similar molecular characteristics to the parental myeloblasts. The original leukemia blasts, when cultured on the leukemia blast-derived myofibroblasts, grew extensively. Leukemia blasts can create their own microenvironment for proliferation.

  13. Thrombosis in children with acute lymphoblastic leukemia: part I. Epidemiology of thrombosis in children with acute lymphoblastic leukemia.

    PubMed

    Athale, Uma H; Chan, Anthony K C

    2003-01-01

    Acute lymphoblastic leukemia (ALL) is the most common childhood malignancy. With the advent of aggressive multimodality therapy, ALL has become a curable disease for majority of pediatric patients. Thromboembolism (TE) is a well-recognized serious complication in association with ALL leading to significant morbidity. It can be potentially fatal in over 50% of the affected patients. Development of TE does interfere with the scheduled treatment plan for ALL and, thus, ultimate outcome from ALL. Recent evidence indicates that concomitant administration of asparaginase and steroids is likely to be associated with higher incidence of TE, especially in children with at least one prothrombotic risk factor. In addition, older children and patients with high risk ALL may be at higher risk for developing TE. However, the epidemiology and the exact pathogenesis of this entity have not yet been clearly defined. To reduce the incidence of TE and its impact on overall outcome as well as on the quality of life in children undergoing treatment for ALL, further studies to define the epidemiology of TE in relation to the biology of ALL and chemotherapy protocols are urgently needed. The purpose of this review is to evaluate the current knowledge of TE in association with ALL in children, especially in relation with the treatment protocols and genetic background. This review will be published in three parts. The first part will review the available information regarding epidemiology of TE in children with ALL. PMID:14678808

  14. Recognition of adult and pediatric acute lymphoblastic leukemia blasts by natural killer cells.

    PubMed

    Torelli, Giovanni F; Peragine, Nadia; Raponi, Sara; Pagliara, Daria; De Propris, Maria S; Vitale, Antonella; Bertaina, Alice; Barberi, Walter; Moretta, Lorenzo; Basso, Giuseppe; Santoni, Angela; Guarini, Anna; Locatelli, Franco; Foà, Robin

    2014-07-01

    In this study, we aimed to investigate the pathways of recognition of acute lymphoblastic leukemia blasts by natural killer cells and to verify whether differences in natural killer cell activating receptor ligand expression among groups defined by age of patients, or presence of cytogenetic/molecular aberrations correlate with the susceptibility to recognition and killing. We analyzed 103 newly diagnosed acute lymphoblastic leukemia patients: 46 adults and 57 children. Pediatric blasts showed a significantly higher expression of Nec-2 (P=0.03), ULBP-1 (P=0.01) and ULBP-3 (P=0.04) compared to adult cells. The differential expression of these ligands between adults and children was confined to B-lineage acute lymphoblastic leukemia with no known molecular alterations. Within molecularly defined subgroups of patients, a high surface expression of NKG2D and DNAM1 ligands was found on BCR-ABL(+) blasts, regardless of patient age. Accordingly, BCR-ABL(+) blasts proved to be significantly more susceptible to natural killer-dependent lysis than B-lineage blasts without molecular aberrations (P=0.03). Cytotoxic tests performed in the presence of neutralizing antibodies indicated a pathway of acute lymphoblastic leukemia cell recognition in the setting of the Nec-2/DNAM-1 interaction. These data provide a biological explanation of the different roles played by alloreactive natural killer cells in pediatric versus adult acute lymphoblastic leukemia and suggest that new natural killer-based strategies targeting specific subgroups of patients, particularly those BCR-ABL(+), are worth pursuing further.

  15. Leukemia

    MedlinePlus

    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, the bone marrow produces abnormal white blood cells. ...

  16. New Strategies in Acute Myeloid Leukemia: Redefining prognostic markers to guide therapy

    PubMed Central

    Khan, Irum; Altman, Jessica K.; Licht, Jonathan D.

    2012-01-01

    While the standard therapy of AML has been relatively constant over the past two decades, this may be changing with enhanced technologies allowing for the classification of acute myeloid leukemia (AML) into molecularly distinct subsets. Some specific subsets of AML have an excellent prognosis in response to standard therapy while the poor prognosis of AML associated with specific sets of mutations or chromosomal anomalies require the development of new therapies. Elucidation of the molecular pathogenesis of AML has led to the development and of therapies that affect signaling, apoptosis, protein and intermediate metabolism, the surface of the leukemia cell, leukemia cell/stromal interaction and epigenetic regulation of gene expression. PMID:22893630

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

    PubMed Central

    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 selection for these high-risk patients. PMID:26525596

  18. Morphologic, immunologic, and cytogenetic characteristics of secondary acute unclassifiable leukemia in Hodgkin's disease.

    PubMed

    Orazi, A; Cattoretti, G; Sozzi, G; Miozzo, M; Polli, N; Delia, D; Viviani, S; Negretti, E; Della Porta, G; Rilke, F

    1988-08-31

    Blast cells from five cases of secondary unclassifiable leukemia following therapy for Hodgkin's disease were studied by cytochemical, immunological and cytogenetic analyses. Cytochemical and immunological reactivity were in accordance with poorly differentiated, myeloid blasts. The four cases in which karyotype analysis was performed showed specific chromosomal abnormalities. No evidence of multiple lineage involvement was found. Problems in classifying these cases of secondary ANLL were due to the high grade of undifferentiation of the blast cells. Their low cytochemical reactivity with markers of myeloid differentiation was similar to what may be observed in patients with acute undifferentiated leukemia or with chronic myeloid leukemia in blast crisis.

  19. Identification of TP53 as an acute lymphocytic leukemia susceptibility gene through exome sequencing.

    PubMed

    Powell, Bradford C; Jiang, Lichun; Muzny, Donna M; Treviño, Lisa R; Dreyer, Zoann E; Strong, Louise C; Wheeler, David A; Gibbs, Richard A; Plon, Sharon E

    2013-06-01

    Although acute lymphocytic leukemia (ALL) is the most common childhood cancer, genetic predisposition to ALL remains poorly understood. Whole-exome sequencing was performed in an extended kindred in which five individuals had been diagnosed with leukemia. Analysis revealed a nonsense variant of TP53 which has been previously reported in families with sarcomas and other typical Li Fraumeni syndrome-associated cancers but never in a familial leukemia kindred. This unexpected finding enabled identification of an appropriate sibling bone marrow donor and illustrates that exome sequencing will reveal atypical clinical presentations of even well-studied genes.

  20. Hyperostosis - an unusual radiographic presentation of Myelodysplastic Syndrome transformed to Acute Myeloid Leukemia

    PubMed Central

    Franco, Arie; Lewis, Kristopher N.; Blackmon, Joshua M.; Manaloor, Elizabeth J.

    2010-01-01

    Acute myeloid leukemia (AML) is also referred to non-lymphocytic leukemia in the literature. It comprises about 15% of the childhood leukemia. There are multiple subtypes of AML from M0-M7 with approximately 45% of the cases being M0–M2 and the remaining subtypes being rare. The definitive diagnosis relies on bone marrow biopsy showing bone marrow infiltration with leukemic cells. We describe a rare radiographic presentation of myelodysplastic syndrome (MDS) transformed to AML in an 8 month old boy who presented with a orbital wall fracture, periosteal reaction, and mixed lytic and sclerotic lesions. PMID:22470698

  1. Congenital abnormalities and acute leukemia among children with Down syndrome: a Children's Oncology Group study.

    PubMed

    Linabery, Amy M; Blair, Cindy K; Gamis, Alan S; Olshan, Andrew F; Heerema, Nyla A; Ross, Julie A

    2008-10-01

    Children with Down syndrome, due to their heightened risk of leukemia and increased prevalence of congenital abnormalities, comprise a valuable population in which to study etiology. A Children's Oncology Group study investigated the causes of childhood leukemia in children with Down syndrome diagnosed at ages 0 to 19 years during the period 1997-2002. Telephone interviews were completed with mothers of 158 cases [n=97 acute lymphoblastic leukemia (ALL) and n=61 acute myeloid leukemia (AML)] and 173 controls. Odds ratios (OR) and 95% confidence intervals (95% CI) were computed via unconditional logistic regression to evaluate the association between congenital abnormalities and acute leukemia overall, and ALL and AML analyzed separately. The results do not provide evidence for an association among the index children (OR(Combined), 0.74; 95% CI, 0.45-1.23; OR(ALL), 0.67; 95% CI, 0.38-1.20; OR(AML),1.03; 95% CI, 0.49-2.16) or their siblings (OR(Combined), 1.23; 95% CI, 0.71-2.13; OR(ALL), 1.12; 95% CI, 0.60-2.09; OR(AML), 1.60; 95% CI, 0.66-3.86), suggesting congenital malformations do not confer additional risk of leukemia beyond the risk attributable to trisomy 21 in this population.

  2. Acute Lymphoblastic Leukemia in a Young Adult Presenting as Hepatitis and Acute Kidney Injury

    PubMed Central

    Heincelman, Marc; Karakala, Nithin; Rockey, Don C.

    2016-01-01

    Acute lymphoblastic leukemia (ALL) in adults is a relatively rare malignancy. The typical presentation includes signs and symptoms associated with bone marrow failure, including fevers, infections, fatigue, and excessive bruising. In this article, we report an unusual systemic presentation of ALL in a previously healthy 18-year-old man. He initially presented with several-day history of nausea and vomiting, 10-pound weight loss, and right upper quadrant abdominal pain with evidence of acute hepatocellular liver injury (elevations in aspartate aminotransferase/alanine aminotransferase) and elevation in serum creatinine. Further history revealed that he just joined the Marine Corp; in preparation, he had been lifting weights and taking protein and creatine supplements. A complete serological evaluation for liver disease was negative and creatine phosphokinase was normal. His aspartate aminotransferase and alanine aminotransferase declined, and he was discharged with expected improvement. However, he returned one week later with continued symptoms and greater elevation of aminotransferases. Liver biopsy was nondiagnostic, revealing scattered portal and lobular inflammatory cells (primarily lymphocytes) felt to be consistent with drug-induced liver injury or viral hepatitis. Given his elevated creatinine, unresponsive to aggressive volume expansion, a kidney biopsy was performed, revealing normal histology. He subsequently developed an extensive left lower extremity deep venous thrombosis. Given his deep venous thrombosis, his peripheral blood was sent for flow cytometry, which revealed lymphoblasts. Bone marrow biopsy revealed 78% blasts with markers consistent with acute B-cell lymphoblastic leukemia. This report emphasizes that right upper quadrant abdominal pain with liver test abnormalities may be the initial presentation of a systemic illness such as ALL. PMID:27722178

  3. Cholinergic Machinery as Relevant Target in Acute Lymphoblastic T Leukemia

    PubMed Central

    Dobrovinskaya, Oxana; Valencia-Cruz, Georgina; Castro-Sánchez, Luis; Bonales-Alatorre, Edgar O.; Liñan-Rico, Liliana; Pottosin, Igor

    2016-01-01

    Various types of non-neuronal cells, including tumors, are able to produce acetylcholine (ACh), which acts as an autocrine/paracrine growth factor. T lymphocytes represent a key component of the non-neuronal cholinergic system. T cells-derived ACh is involved in a stimulation of their activation and proliferation, and acts as a regulator of immune response. The aim of the present work was to summarize the data about components of cholinergic machinery in T lymphocytes, with an emphasis on the comparison of healthy and leukemic T cells. Cell lines derived from acute lymphoblastic leukemias of T lineage (T-ALL) were found to produce a considerably higher amount of ACh than healthy T lymphocytes. Additionally, ACh produced by T-ALL is not efficiently hydrolyzed, because acetylcholinesterase (AChE) activity is drastically decreased in these cells. Up-regulation of muscarinic ACh receptors was also demonstrated at expression and functional level, whereas nicotinic ACh receptors seem to play a less important role and not form functional channels in cells derived from T-ALL. We hypothesized that ACh over-produced in T-ALL may act as an autocrine growth factor and play an important role in leukemic clonal expansion through shaping of intracellular Ca2+ signals. We suggest that cholinergic machinery may be attractive targets for new drugs against T-ALL. Specifically, testing of high affinity antagonists of muscarinic ACh receptors as well as antagomiRs, which interfere with miRNAs involved in the suppression of AChE expression, may be the first choice options. PMID:27630569

  4. Cholinergic Machinery as Relevant Target in Acute Lymphoblastic T Leukemia

    PubMed Central

    Dobrovinskaya, Oxana; Valencia-Cruz, Georgina; Castro-Sánchez, Luis; Bonales-Alatorre, Edgar O.; Liñan-Rico, Liliana; Pottosin, Igor

    2016-01-01

    Various types of non-neuronal cells, including tumors, are able to produce acetylcholine (ACh), which acts as an autocrine/paracrine growth factor. T lymphocytes represent a key component of the non-neuronal cholinergic system. T cells-derived ACh is involved in a stimulation of their activation and proliferation, and acts as a regulator of immune response. The aim of the present work was to summarize the data about components of cholinergic machinery in T lymphocytes, with an emphasis on the comparison of healthy and leukemic T cells. Cell lines derived from acute lymphoblastic leukemias of T lineage (T-ALL) were found to produce a considerably higher amount of ACh than healthy T lymphocytes. Additionally, ACh produced by T-ALL is not efficiently hydrolyzed, because acetylcholinesterase (AChE) activity is drastically decreased in these cells. Up-regulation of muscarinic ACh receptors was also demonstrated at expression and functional level, whereas nicotinic ACh receptors seem to play a less important role and not form functional channels in cells derived from T-ALL. We hypothesized that ACh over-produced in T-ALL may act as an autocrine growth factor and play an important role in leukemic clonal expansion through shaping of intracellular Ca2+ signals. We suggest that cholinergic machinery may be attractive targets for new drugs against T-ALL. Specifically, testing of high affinity antagonists of muscarinic ACh receptors as well as antagomiRs, which interfere with miRNAs involved in the suppression of AChE expression, may be the first choice options.

  5. Improved Prognosis for Older Adolescents With Acute Lymphoblastic Leukemia

    PubMed Central

    Pui, Ching-Hon; Pei, Deqing; Campana, Dario; Bowman, W. Paul; Sandlund, John T.; Kaste, Sue C.; Ribeiro, Raul C.; Rubnitz, Jeffrey E.; Coustan-Smith, Elaine; Jeha, Sima; Cheng, Cheng; Metzger, Monika L.; Bhojwani, Deepa; Inaba, Hiroto; Raimondi, Susana C.; Onciu, Mihaela; Howard, Scott C.; Leung, Wing; Downing, James R.; Evans, William E.; Relling, Mary V.

    2011-01-01

    Purpose The prognosis for older adolescents and young adults with acute lymphoblastic leukemia (ALL) has been historically much worse than that for younger patients. We reviewed the outcome of older adolescents (age 15 to 18 years) treated in four consecutive Total Therapy studies to determine if recent improved treatment extended to this high-risk group. Patients and Methods Between 1991 and 2007, 963 pediatric patients, including 89 older adolescents, were enrolled on Total Therapy studies XIIIA, XIIIB, XIV, and XV. In the first three studies, treatment selection was based on presenting clinical features and leukemic cell genetics. In study XV, the level of residual disease was used to guide treatment, which featured intensive methotrexate, glucocorticoid, vincristine, and asparaginase, as well as early triple intrathecal therapy for higher-risk ALL. Results The 89 older adolescents were significantly more likely to have T-cell ALL, the t(4;11)(MLL-AF4), and detectable minimal residual disease during or at the end of remission induction; they were less likely to have the t(12;21)(ETV6-RUNX1) compared with younger patients. In the first three studies, the 44 older adolescents had significantly poorer event-free survival and overall survival than the 403 younger patients. This gap in prognosis was abolished in study XV: event-free survival rates at 5 years were 86.4% ± 5.2% (standard error) for the 45 older adolescents and 87.4% ± 1.7% for the 453 younger patients; overall survival rates were 87.9% ± 5.1% versus 94.1% ± 1.2%, respectively. Conclusion Most older adolescents with ALL can be cured with risk-adjusted intensive chemotherapy without stem-cell transplantation. PMID:21172890

  6. PML, a growth suppressor disrupted in acute promyelocytic leukemia.

    PubMed Central

    Mu, Z M; Chin, K V; Liu, J H; Lozano, G; Chang, K S

    1994-01-01

    The nonrandom chromosomal translocation t(15;17)(q22;q21) in acute promyelocytic leukemia (APL) juxtaposes the genes for retinoic acid receptor alpha (RAR alpha) and the putative zinc finger transcription factor PML. The breakpoint site encodes fusion protein PML-RAR alpha, which is able to form a heterodimer with PML. It was hypothesized that PML-RAR alpha is a dominant negative inhibitor of PML. Inactivation of PML function in APL may play a critical role in APL pathogenesis. Our results demonstrated that PML, but not PML-RAR alpha, is a growth suppressor. This is supported by the following findings: (i) PML suppressed anchorage-independent growth of APL-derived NB4 cells on soft agar and tumorigenicity in nude mice, (ii) PML suppressed the oncogenic transformation of rat embryo fibroblasts by cooperative oncogenes, and (iii) PML suppressed transformation of NIH 3T3 cells by the activated neu oncogene. Cotransfection of PML with PML-RAR alpha resulted in a significant reduction in PML's transformation suppressor function in vivo, indicating that the fusion protein can be a dominant negative inhibitor of PML function in APL cells. This observation was further supported by the finding that cotransfection of PML and PML-RAR alpha resulted in altered normal cellular localization of PML. Our results also demonstrated that PML, but not PML-RAR alpha, is a promoter-specific transcription suppressor. Therefore, we hypothesized that disruption of the PML gene, a growth or transformation suppressor, by the t(15;17) translocation in APL is one of the critical events in leukemogenesis. Images PMID:7935403

  7. Predictors of Antiemetic Alteration in Pediatric Acute Myeloid Leukemia

    PubMed Central

    Freedman, Jason L.; Faerber, Jennifer; Kang, Tammy I.; Dai, Dingwei; Fisher, Brian T.; Huang, Yuan-Shung; Li, Yimei; Aplenc, Richard; Feudtner, Chris

    2014-01-01

    Background Better knowledge of patient and cancer treatment factors associated with nausea/vomiting (NV) in pediatric oncology patients could enhance prophylaxis. We aimed to describe such factors in children receiving treatment for acute myeloid leukemia (AML). Methods Retrospective longitudinal cohort study of 1668 hospitalized children undergoing treatment for AML from the Pediatric Health Information System database (39 hospitals, 1999–2010). Antiemetic alteration, which included switch (a change in prescribed 5-HT3 receptor antagonists) and rescue (receipt of an adjunct antiemetic), were first validated and then used as surrogates of problematic NV. Logistic and negative binomial regression modeling were used to test whether patient characteristics were associated with problematic NV. Results Increasing age is associated with greater odds of experiencing antiemetic switch and higher relative rate of antiemetic rescue. Within a treatment cycle, each consecutive inpatient chemotherapy-day decreased the likelihood of requiring antiemetic alteration. Each consecutive inpatient day post-chemotherapy was associated with decreased need for switch, but increased need for rescue. Subsequent cycles of AML therapy were associated with lower odds of antiemetic switch on both chemotherapy and non-chemotherapy days, a lower rate of antiemetic rescue on chemotherapy days, and an increased rate of rescue on non-chemotherapy days. Conclusion In pediatric patients with AML, increasing age is strongly associated with greater antiemetic alteration. Antiemetic alteration occurs early in treatment overall, and early within each admission. While additional cycles of therapy are associated with less alteration overall, there is persistent rescue in the days after chemotherapy, suggesting additional etiologies of NV in pediatric cancer patients. PMID:24939039

  8. Targeted alpha-particle immunotherapy for acute myeloid leukemia.

    PubMed

    Jurcic, Joseph G; Rosenblat, Todd L

    2014-01-01

    Because alpha-particles have a shorter range and a higher linear energy transfer (LET) compared with beta-particles, targeted alpha-particle immunotherapy offers the potential for more efficient tumor cell killing while sparing surrounding normal cells. To date, clinical studies of alpha-particle immunotherapy for acute myeloid leukemia (AML) have focused on the myeloid cell surface antigen CD33 as a target using the humanized monoclonal antibody lintuzumab. An initial phase I study demonstrated the safety, feasibility, and antileukemic effects of bismuth-213 ((213)Bi)-labeled lintuzumab. In a subsequent study, (213)Bi-lintuzumab produced remissions in some patients with AML after partial cytoreduction with cytarabine, suggesting the utility of targeted alpha-particle therapy for small-volume disease. The widespread use of (213)Bi, however, is limited by its short half-life. Therefore, a second-generation construct containing actinium-225 ((225)Ac), a radiometal that generates four alpha-particle emissions, was developed. A phase I trial demonstrated that (225)Ac-lintuzumab is safe at doses of 3 μCi/kg or less and has antileukemic activity across all dose levels studied. Fractionated-dose (225)Ac-lintuzumab in combination with low-dose cytarabine (LDAC) is now under investigation for the management of older patients with untreated AML in a multicenter trial. Preclinical studies using (213)Bi- and astatine-211 ((211)At)-labeled anti-CD45 antibodies have shown that alpha-particle immunotherapy may be useful as part conditioning before hematopoietic cell transplantation. The use of novel pretargeting strategies may further improve target-to-normal organ dose ratios. PMID:24857092

  9. Molecular allelokaryotyping of relapsed pediatric acute lymphoblastic leukemia.

    PubMed

    Kawamata, Norihiko; Ogawa, Seishi; Seeger, Karl; Kirschner-Schwabe, Renate; Huynh, Thien; Chen, John; Megrabian, Nairi; Harbott, Jochen; Zimmermann, Martin; Henze, Günter; Schrappe, Martin; Bartram, Claus R; Koeffler, H Phillip

    2009-06-01

    Acute lymphoblastic leukemia (ALL) cells at relapse are frequently more resistant to treatment than primary clones and this may be caused by further genetic changes in the ALL cells at relapse. These acquired genomic abnormalities have not been fully characterized. To examine the additional genomic alterations of ALL at relapse, we performed single nucleotide polymorphism genomic microarry (SNP-chip) analysis on 14 ALL bone marrow samples at initial diagnosis, remission and relapse. Only two cases at initial diagnosis had a normal appearing genome by SNP-chip. All 14 cases had genomic alterations at relapse; and 10 of these had additional genomic abnormalities not present at diagnosis. Deletion of either the INK4A/ARF gene (2 cases) or the NF2 gene (2 cases) at 22q12.2 was an acquired genomic change at relapse. Loss of heterozygosity with normal copy number [uniparental disomy (UPD)] was detected in 3 cases as an additional genomic change at relapse. Interestingly, several genomic alterations, especially deletions, detected at initial diagnosis, disappeared at relapse, suggesting the ALL cells at relapse were minor clones at initial diagnosis and emerged at relapse. For several cases, trisomy at initial diagnosis changed to either UPD (2 cases) or normal appearing genome (2 cases). Further, we found disruption of PTPRD gene occurring at intron 23 as an additional genomic abnormality in one case. In summary, additional genomic changes are very common events in ALL at relapse; whether these abnormalities are associated with resistance to treatment remains to clarified in further studies.

  10. Rituximab in B-Lineage Adult Acute Lymphoblastic Leukemia.

    PubMed

    Maury, Sébastien; Chevret, Sylvie; Thomas, Xavier; Heim, Dominik; Leguay, Thibaut; Huguet, Françoise; Chevallier, Patrice; Hunault, Mathilde; Boissel, Nicolas; Escoffre-Barbe, Martine; Hess, Urs; Vey, Norbert; Pignon, Jean-Michel; Braun, Thorsten; Marolleau, Jean-Pierre; Cahn, Jean-Yves; Chalandon, Yves; Lhéritier, Véronique; Beldjord, Kheira; Béné, Marie C; Ifrah, Norbert; Dombret, Hervé

    2016-09-15

    Background Treatment with rituximab has improved the outcome for patients with non-Hodgkin's lymphoma. Patients with B-lineage acute lymphoblastic leukemia (ALL) may also have the CD20 antigen, which is targeted by rituximab. Although single-group studies suggest that adding rituximab to chemotherapy could improve the outcome in such patients, this hypothesis has not been tested in a randomized trial. Methods We randomly assigned adults (18 to 59 years of age) with CD20-positive, Philadelphia chromosome (Ph)-negative ALL to receive chemotherapy with or without rituximab, with event-free survival as the primary end point. Rituximab was given during all treatment phases, for a total of 16 to 18 infusions. Results From May 2006 through April 2014, a total of 209 patients were enrolled: 105 in the rituximab group and 104 in the control group. After a median follow-up of 30 months, event-free survival was longer in the rituximab group than in the control group (hazard ratio, 0.66; 95% confidence interval [CI], 0.45 to 0.98; P=0.04); the estimated 2-year event-free survival rates were 65% (95% CI, 56 to 75) and 52% (95% CI, 43 to 63), respectively. Treatment with rituximab remained associated with longer event-free survival in a multivariate analysis. The overall incidence rate of severe adverse events did not differ significantly between the two groups, but fewer allergic reactions to asparaginase were observed in the rituximab group. Conclusions Adding rituximab to the ALL chemotherapy protocol improved the outcome for younger adults with CD20-positive, Ph-negative ALL. (Funded by the Regional Clinical Research Office, Paris, and others; ClinicalTrials.gov number, NCT00327678 .). PMID:27626518

  11. Advances in the Genetics and Therapy of Acute Lymphoblastic Leukemia.

    PubMed

    Chiaretti, Sabina; Gianfelici, Valentina; O'Brien, Susan M; Mullighan, Charles G

    2016-01-01

    Acute lymphoblastic leukemia (ALL) remains an important cause of morbidity in children and adults. In this article, we highlight advances in the genetics and therapy of three key subtypes of ALL: T-cell ALL, BCR-ABL1 (Philadelphia [Ph] chromosone-positive), and Ph-like ALL. T-ALL is an aggressive disease that accounts for about 15% and 25% of ALL among pediatric and adult cohorts, respectively, and exhibits a multistep nature of cancer initiation and progression. The integration of cytogenetics, molecular biology, and immunophenotype analyses has led to the identification of defined T-ALL subgroups, such as early T-cell precursor ALL and novel lesions with a prognostic role, for which specific inhibitors are being developed. Ph-positive ALL was historically regarded as a subtype of ALL with a poor prognosis, and allogeneic stem cell transplant was recommended for all patients who could undergo this procedure. The deep complete responses seen with combination tyrosine kinase inhibitors (TKIs) and chemotherapy in Ph-positive ALL, and the reports of long-term survival among some patients not undergoing allogeneic stem cell transplant, has raised the question of whether there is a subset of patients who could be cured without this intervention. Ph-like ALL is a subtype of B-progenitor ALL common among older children and adults and associated with a diverse range of genetic alterations that activate kinase signaling. Ph-like ALL is also associated with poor outcome, for which precision medicine trials identifying kinase alterations and testing TKI therapy are being developed. PMID:27249738

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

    PubMed

    Brendel, Cornelia; Teichler, Sabine; Millahn, Axel; Stiewe, Thorsten; Krause, Michael; Stabla, Kathleen; Ross, Petra; Huynh, Minh; Illmer, Thomas; Mernberger, Marco; Barckhausen, Christina; Neubauer, Andreas

    2015-01-01

    RAS mutations are frequently found among acute myeloid leukemia patients (AML), generating a constitutively active signaling protein changing cellular proliferation, differentiation and apoptosis. We have previously shown that treatment of AML patients with high-dose cytarabine is preferentially beneficial for those harboring oncogenic RAS. On the basis of a murine AML cell culture model, we ascribed this effect to a RAS-driven, p53-dependent induction of differentiation. Hence, in this study we sought to confirm the correlation between RAS status and differentiation of primary blasts obtained from AML patients. The gene expression signature of AML blasts with oncogenic NRAS indeed corresponded to a more mature profile compared to blasts with wildtype RAS, as demonstrated by gene set enrichment analysis (GSEA) and real-time PCR analysis of myeloid ecotropic viral integration site 1 homolog (MEIS1) in a unique cohort of AML patients. In addition, in vitro cell culture experiments with established cell lines and a second set of primary AML cells showed that oncogenic NRAS mutations predisposed cells to cytarabine (AraC) driven differentiation. Taken together, our findings show that AML with inv(16) and NRAS mutation have a differentiation gene signature, supporting the notion that NRAS mutation may predispose leukemic cells to AraC induced differentiation. We therefore suggest that promotion of differentiation pathways by specific genetic alterations could explain the superior treatment outcome after therapy in some AML patient subgroups. Whether a differentiation gene expression status may generally predict for a superior treatment outcome in AML needs to be addressed in future studies. PMID:25901794

  13. Metabolism of arsenic trioxide in acute promyelocytic leukemia cells.

    PubMed

    Khaleghian, Ali; Ghaffari, Seyed H; Ahmadian, Shahin; Alimoghaddam, Kamran; Ghavamzadeh, Ardeshir

    2014-10-01

    Arsenic trioxide (As2O3) effectively induces complete clinical and molecular remissions in acute promyelocytic leukemia (APL) patients and triggers apoptosis in APL cells. The effect induced by As2O3 is also associated with extensive genomic-wide epigenetic changes with large-scale alterations in DNA methylation. We investigated the As2O3 metabolism in association with factors involved in the production of its methylated metabolites in APL-derived cell line, NB4. We used high performance liquid chromatography (HPLC) technique to detect As2O3 metabolites in NB4 cells. The effects of As2O3 on glutathione level, S-Adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH) levels were investigated. Also, we studied the expression levels of arsenic methyltransferase (AS3MT) and DNA methyltransferases (DNMT1, DNMT3a, and DNMT3b) by real-time PCR. Our results show that after As2O3 entry into the cell, it was converted into methylated metabolites, mono-methylarsenic (MMA) and dimethylarsenic (DMA). The glutathione (GSH) production was increased in parallel with the methylated metabolites formations. As2O3 treatment inhibited DNMTs (DNMT1, DNMT3a, and DNMT3b) in dose- and time-dependent manners. The SAH levels in As2O3-treated cells were increased; however, the SAM level was not affected. The present study shows that APL cell is capable of metabolizing As2O3. The continuous formation of intracellular methylated metabolites, the inhibition of DNMTs expression levels and the increase of SAH level by As2O3 biotransformation would probably affect the DNMTs-methylated DNA methylation in a manner related to the extent of DNA hypomethylation. Production of intracellular methylated metabolites and epigenetic changes of DNA methylation during As2O3 metabolism may contribute to the therapeutic effect of As2O3 in APL. PMID:24819152

  14. Cholinergic Machinery as Relevant Target in Acute Lymphoblastic T Leukemia.

    PubMed

    Dobrovinskaya, Oxana; Valencia-Cruz, Georgina; Castro-Sánchez, Luis; Bonales-Alatorre, Edgar O; Liñan-Rico, Liliana; Pottosin, Igor

    2016-01-01

    Various types of non-neuronal cells, including tumors, are able to produce acetylcholine (ACh), which acts as an autocrine/paracrine growth factor. T lymphocytes represent a key component of the non-neuronal cholinergic system. T cells-derived ACh is involved in a stimulation of their activation and proliferation, and acts as a regulator of immune response. The aim of the present work was to summarize the data about components of cholinergic machinery in T lymphocytes, with an emphasis on the comparison of healthy and leukemic T cells. Cell lines derived from acute lymphoblastic leukemias of T lineage (T-ALL) were found to produce a considerably higher amount of ACh than healthy T lymphocytes. Additionally, ACh produced by T-ALL is not efficiently hydrolyzed, because acetylcholinesterase (AChE) activity is drastically decreased in these cells. Up-regulation of muscarinic ACh receptors was also demonstrated at expression and functional level, whereas nicotinic ACh receptors seem to play a less important role and not form functional channels in cells derived from T-ALL. We hypothesized that ACh over-produced in T-ALL may act as an autocrine growth factor and play an important role in leukemic clonal expansion through shaping of intracellular Ca(2+) signals. We suggest that cholinergic machinery may be attractive targets for new drugs against T-ALL. Specifically, testing of high affinity antagonists of muscarinic ACh receptors as well as antagomiRs, which interfere with miRNAs involved in the suppression of AChE expression, may be the first choice options. PMID:27630569

  15. Heterogeneity of clonogenic cells in acute myeloblastic leukemia.

    PubMed

    Sabbath, K D; Ball, E D; Larcom, P; Davis, R B; Griffin, J D

    1985-02-01

    The expression of differentiation-associated surface antigens by the clonogenic leukemic cells from 20 patients with acute myeloblastic leukemia (AML) was studied with a panel of seven cytotoxic monoclonal antibodies (anti-Ia, -MY9, -PM-81, -AML-2-23, -Mol, -Mo2, and -MY3). The surface antigen phenotypes of the clonogenic cells were compared with the phenotypes of the whole leukemic cell population, and with the phenotypes of normal hematopoietic progenitor cells. In each case the clonogenic leukemic cells were found within a distinct subpopulation that was less "differentiated" than the total cell population. Clonogenic leukemic cells from different patients could be divided into three phenotype groups. In the first group (7 of 20 cases), the clonogenic cells expressed surface antigens characteristic of the normal multipotent colony-forming cell (Ia, MY9). These cases tended to have "undifferentiated" (FAB M1) morphology, and the total cell population generally lacked expression of "late" monocyte antigens such as MY3 and Mo2. A second group (seven cases) of clonogenic cells expressed surface antigens characteristic of an "early" (day 14) colony-forming unit granulocyte-monocyte (CFU-GM), and a third group (six cases) was characteristic of a "late" (day 7) CFU-GM. The cases in these latter two groups tended to have myelomonocytic (FAB M4) morphology and to express monocyte surface antigens. These results suggest that the clonogenic cells are a distinct subpopulation in all cases of AML, and may be derived from normal hematopoietic progenitor cells at multiple points in the differentiation pathway. The results further support the possibility that selected monoclonal antibodies have the potential to purge leukemic clonogenic cells from bone marrow in some AML patients without eliminating critical normal progenitor cells.

  16. Circulating endothelial cells and their progenitors in acute myeloid leukemia

    PubMed Central

    Zahran, Asmaa Mohammed; Aly, Sanaa Shaker; Altayeb, Hanan Ahmed; Ali, Arwa Mohammed

    2016-01-01

    Acute myeloid leukemia (AML) is an aggressive hematological malignancy characterized by the accumulation of immature myeloid progenitor cells in the bone marrow. Studies are required to investigate the prognostic and predictive value of surrogate biomarkers. Given the importance of angiogenesis in oncology in terms of pathogenesis as well as being a target for treatment, circulating endothelial cells (CECs) and endothelial progenitor cells (EPCs) are promising candidates to serve as such markers. The aim of the present study was to quantify CECs and EPCs in patients with AML at initial diagnosis and following induction chemotherapy, and to correlate these findings with the response to treatment in AML patients. The present study included 40 patients with de novo AML and 20 age- and gender-matched healthy controls. CECs and EPCs were evaluated by flow cytometry at initial diagnosis and after induction chemotherapy (3+7 protocol for AML other than M3 and all-trans-retinoic acid plus anthracycline for M3 disease). CECs and EPCs were significantly higher in AML patients at diagnosis and after induction chemotherapy than in controls. After induction chemotherapy, CECs and EPCs were significantly decreased compared with the levels at initial diagnosis. Patients who achieved complete response (n=28) had lower initial CEC and EPC levels compared with patients who did not respond to treatment. These results suggest that CEC levels are higher in AML patients and may correlate with disease status and treatment response. Further investigations are required to better determine the predictive value and implication of these cells in AML management. PMID:27602121

  17. Midostaurin: an emerging treatment for acute myeloid leukemia patients

    PubMed Central

    Gallogly, Molly Megan; Lazarus, Hillard M

    2016-01-01

    Acute myeloid leukemia (AML) is a hematologic malignancy that carries a poor prognosis and has garnered few treatment advances in the last few decades. Mutation of the internal tandem duplication (ITD) region of fms-like tyrosine kinase (FLT3) is considered high risk for decreased response and overall survival. Midostaurin is a Type III receptor tyrosine kinase inhibitor found to inhibit FLT3 and other receptor tyrosine kinases, including platelet-derived growth factor receptors, cyclin-dependent kinase 1, src, c-kit, and vascular endothelial growth factor receptor. In preclinical studies, midostaurin exhibited broad-spectrum antitumor activity toward a wide range of tumor xenografts, as well as an FLT3-ITD-driven mouse model of myelodysplastic syndrome (MDS). Midostaurin is orally administered and generally well tolerated as a single agent; hematologic toxicity increases substantially when administered in combination with standard induction chemotherapy. Clinical trials primarily have focused on relapsed/refractory AML and MDS and included single- and combination-agent studies. Administration of midostaurin to relapsed/refractory MDS and AML patients confers a robust anti-blast response sufficient to bridge a minority of patients to transplant. In combination with histone deacetylase inhibitors, responses appear comparable to historic controls, while the addition of midostaurin to standard induction chemotherapy may prolong survival in FLT3-ITD mutant patients. The response of some wild-type (WT)-FLT3 patients to midostaurin therapy is consistent with midostaurin’s ability to inhibit WT-FLT3 in vitro, and also may reflect overexpression of WT-FLT3 in those patients and/or off-target effects such as inhibition of kinases other than FLT3. Midostaurin represents a well-tolerated, easily administered oral agent with the potential to bridge mutant and WT-FLT3 AML patients to transplant and possibly deepen response to induction chemotherapy. Ongoing studies are

  18. Campylobacter jejuni Bacteremia in a Patient With Acute Lymphocytic Leukemia

    PubMed Central

    Anvarinejad, Mojtaba; Amin Shahidi, Maneli; Pouladfar, Gholam Reza; Dehyadegari, Mohammad Ali; Mardaneh, Jalal

    2016-01-01

    Introduction Campylobacter jejuni is a slender, motile, non-spore-forming, helical-shaped, gram-negative bacterium. It is one of the most common causes of human gastroenteritis in the world. The aim of this study was to present a patient with acute lymphocytic leukemia (ALL), who was infected with Campylobacter jejuni. Case Presentation We describe the medical records of a pediatric ALL patient with bacteremia caused by C. jejuni, who was diagnosed at Amir hospital, Shiraz, Iran. This 14-year-old male visited the emergency department of Amir hospital with night sweats, severe polar high-grade fever, reduced appetite, and nausea in August 2013. Given the suspected presence of an anaerobic or microaerophilic microorganism, aerobic and anaerobic blood cultures were performed using an automated blood cultivator, the BACTEC 9240 system. In order to characterize the isolate, diagnostic biochemical tests were used. Antibiotic susceptibility testing was done with the disk diffusion method. The primary culture was found to be positive for Campylobacter, and the subculture of the solid plate yielded a confluent growth of colonies typical for Campylobacter, which was identified as C. jejuni by morphological and biochemical tests. The isolate was resistant to ciprofloxacin, cefotaxime, cephalexin, piperacillin/tazobactam, nalidixic acid, aztreonam, cefuroxime, cefixime, ceftazidime, and tobramycin. Conclusions C. jejuni should be considered in the differential diagnosis as a potential cause of bacteremia in immunosuppressed patients. In cases where the BACTEC result is positive in aerobic conditions but the organism cannot be isolated, an anaerobic culture medium is suggested, especially in immunocompromised patients. PMID:27621914

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

    Cancer.gov

    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. |

  20. Acute leukemia in children: A review of the current Indian data

    PubMed Central

    Arora, Ramandeep Singh; Arora, Brijesh

    2016-01-01

    Acute leukemias are the most common diagnostic group of childhood cancer. This review summarizes the published literature on reported current outcomes of childhood acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) from India. Overall survival in ALL ranged from 45% to 81% (commonly >60%) and event-free survival ranged from 41% to 70% (commonly >50%). Outcome data for AML was patchy with varying duration of follow-up, but it can be inferred that 50–80% of treated patients had experienced an event (toxic death, refractory disease or relapse). It is imperative that going forward focus should be on collaborative efforts, which promote treatment of patients on risk-stratified adapted protocols based on local infrastructure, improvement in supportive care and encourage prospective multi-center clinical trials.

  1. Risk factors for relapse after allogeneic transplantation in acute myeloid leukemia

    PubMed Central

    Ossenkoppele, Gert J.; Janssen, Jeroen J.W.M.; van de Loosdrecht, Arjan A.

    2016-01-01

    Acute myeloid leukemia is a clonal neoplasm derived from myeloid progenitor cells with a varying outcome. The initial goal of treatment is the achievement of complete remission, defined for over 40 years by morphology. However, without additional post-remission treatment the majority of patients relapse. In many cases of acute myeloid leukemia, allogeneic stem cell transplantation offers the best prospects of cure. In 2013, 5608 stem cell transplantations in acute myeloid leukemia were performed in Europe (5228 allogeneic and 380 autologous stem cell transplantations). Most stem cell transplantations are performed in first complete remission. However, despite a considerable reduction in the chance of relapse, in most studies, overall survival benefit of allogeneic stem cell transplantation is modest due to substantial non-relapse mortality. Here we discuss the many factors related to the risk of relapse after allogeneic stem cell transplantation. PMID:26721801

  2. Duplication and loss of chromosome 21 in two children with Down syndrome and acute leukemia

    SciTech Connect

    Rogan, P.K.; Close, P.; Gannutz, L.

    1995-11-06

    Acute leukemia in Down syndrome (DS) is often associated with additional changes in the number of structure of chromosome 21. We present two DS patients whose leukemic karyotypes were associated with changes in chromosome 21 ploidy. Patient 1 developed acute lymphocytic leukemia (type L1); disomy for chromosome 21 was evident in all blast cells examined. Loss of the paternal chromosome in the leukemic clone produced maternal uniparental disomy with isodisomy over a 25-cM interval. The second patient had acute monoblastic leukemia (type M5) with tetrasomy 21 in all leukemic cells. DNA polymorphism analysis showed duplicate paternal chromosomes in the constitutional genotype. The maternal chromosome was subsequently duplicated in the leukemic clone. The distinct inheritance patterns of chromosome 21 in the blast cells of these patients would appear to indicate that leukemogenesis occurred by different genetic mechanisms in each individual. 57 refs., 2 figs., 3 tabs.

  3. Acute leukemia in children: A review of the current Indian data.

    PubMed

    Arora, Ramandeep Singh; Arora, Brijesh

    2016-01-01

    Acute leukemias are the most common diagnostic group of childhood cancer. This review summarizes the published literature on reported current outcomes of childhood acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) from India. Overall survival in ALL ranged from 45% to 81% (commonly >60%) and event-free survival ranged from 41% to 70% (commonly >50%). Outcome data for AML was patchy with varying duration of follow-up, but it can be inferred that 50-80% of treated patients had experienced an event (toxic death, refractory disease or relapse). It is imperative that going forward focus should be on collaborative efforts, which promote treatment of patients on risk-stratified adapted protocols based on local infrastructure, improvement in supportive care and encourage prospective multi-center clinical trials. PMID:27606304

  4. Acute leukemia in children: A review of the current Indian data

    PubMed Central

    Arora, Ramandeep Singh; Arora, Brijesh

    2016-01-01

    Acute leukemias are the most common diagnostic group of childhood cancer. This review summarizes the published literature on reported current outcomes of childhood acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) from India. Overall survival in ALL ranged from 45% to 81% (commonly >60%) and event-free survival ranged from 41% to 70% (commonly >50%). Outcome data for AML was patchy with varying duration of follow-up, but it can be inferred that 50–80% of treated patients had experienced an event (toxic death, refractory disease or relapse). It is imperative that going forward focus should be on collaborative efforts, which promote treatment of patients on risk-stratified adapted protocols based on local infrastructure, improvement in supportive care and encourage prospective multi-center clinical trials. PMID:27606304

  5. 17-N-Allylamino-17-Demethoxygeldanamycin in Treating Young Patients With Relapsed or Refractory Solid Tumors or Leukemia

    ClinicalTrials.gov

    2013-06-03

    Acute Undifferentiated Leukemia; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia; Unspecified Childhood Solid Tumor, Protocol Specific

  6. Acute promyelocytic leukemia after renal transplant and filgrastim treatment for neutropenia

    PubMed Central

    Krause, John R.

    2016-01-01

    Prolonged immunosuppression in solid organ transplant recipients has been considered a risk for developing opportunistic infections and malignancies. Acute leukemia is a rare complication. We report a case of acute promyelocytic leukemia (APL) (FAB M3) after cadaveric renal transplant for focal segmental glomerulosclerosis in a 24-year-old woman. Her immunosuppressive therapy included tacrolimus, mycophenolate mofetil, and prednisone. Approximately 2 years after transplant, she became pancytopenic, prompting administration of filgrastim. A few doses caused a markedly increased blast count, resulting in a diagnosis of APL. She was successfully treated with all-trans-retinoic acid and arsenic trioxide. Myeloproliferative neoplasms after organ transplant or due to filgrastim are rare. PMID:27695174

  7. Acute promyelocytic leukemia after renal transplant and filgrastim treatment for neutropenia

    PubMed Central

    Krause, John R.

    2016-01-01

    Prolonged immunosuppression in solid organ transplant recipients has been considered a risk for developing opportunistic infections and malignancies. Acute leukemia is a rare complication. We report a case of acute promyelocytic leukemia (APL) (FAB M3) after cadaveric renal transplant for focal segmental glomerulosclerosis in a 24-year-old woman. Her immunosuppressive therapy included tacrolimus, mycophenolate mofetil, and prednisone. Approximately 2 years after transplant, she became pancytopenic, prompting administration of filgrastim. A few doses caused a markedly increased blast count, resulting in a diagnosis of APL. She was successfully treated with all-trans-retinoic acid and arsenic trioxide. Myeloproliferative neoplasms after organ transplant or due to filgrastim are rare.

  8. Hemiparesis in an Adolescent With Acute Lymphoblastic Leukemia: Everything Is Not Always What it Seems.

    PubMed

    Andina, David; Lassaletta, Alvaro; Sevilla, Julian; Gutierrez, Silvia; Madero, Luis

    2016-01-01

    Acute lymphoblastic leukemia is a common malignancy in childhood. Managing adverse events during treatment can result in very complex situations. A previously healthy adolescent diagnosed with T-cell acute lymphoblastic leukemia developed on day +55 of induction chemotherapy hemiparesis, dysesthesia, and facial palsy. Blood tests and brain imaging techniques were unremarkable. The patient was diagnosed with a conversion disorder, which completely resolved. Although rare in clinical practice, children and adolescents with cancer do not always have organic pathology explaining their symptoms. Psychiatric disorders such as those of the somatoform spectrum must be considered, particularly in patients with anxiety or depression.

  9. [Successful pregnancy after 6 years complete remission in patient with acute myeloblastic leukemia].

    PubMed

    Shimazaki, C; Oku, N; Gotoh, H; Inaba, T; Murakami, S; Oku, N; Itoh, K; Nakanishi, S; Nakagawa, M; Fujita, N

    1991-01-01

    A 25-year-old woman was diagnosed as acute myeloblastic leukemia (M1 in FAB classification) in May 1983, and treated with DCMP regimen, which led to the complete remission. Intensification therapies and maintenance therapy with OK-432 were continued until August 1988, and 10 months later she conceived. She delivered a healthy 2,680 g male baby at 36th week of pregnancy by Cesarean section because of abruptio placentae. This case suggests that normal pregnancy is possible in patients with acute leukemia who received anti-cancer drugs.

  10. Drugs under preclinical and clinical study for treatment of acute and chronic lymphoblastic leukemia

    PubMed Central

    Jacob, Joe Antony; Salmani, Jumah Masoud Mohammad; Chen, Baoan

    2016-01-01

    Targeted therapy has modernized the treatment of both chronic and acute lymphoblastic leukemia. The introduction of monoclonal antibodies and combinational drugs has increased the survival rate of patients. Preclinical studies with various agents have resulted in positive outputs with Phase III trial drugs and monoclonal antibodies entering clinical trials. Most of the monoclonal antibodies target the CD20 and CD22 receptors. This has led to the approval of a few of these drugs by the US Food and Drug Administration. This review focuses on the drugs under preclinical and clinical study in the ongoing efforts for treatment of acute and chronic lymphoblastic leukemia. PMID:27382259

  11. Acute isolated appendicitis due to Aspergillus carneus in a neutropenic child with acute myeloid leukemia.

    PubMed

    Decembrino, Nunzia; Zecca, Marco; Tortorano, Anna Maria; Mangione, Francesca; Lallitto, Fabiola; Introzzi, Francesca; Bergami, Elena; Marone, Piero; Tamarozzi, Francesca; Cavanna, Caterina

    2016-01-01

    We describe a case of isolated acute appendicitis due to Aspergillus carneus in a neutropenic child with acute myeloid leukemia (AML) treated according to the AIEOP AML 2002/01 protocol. Despite prophylaxis with acyclovir, ciprofloxacin and fluconazole administered during the neutropenic phase, 16 days after the end of chemotherapy the child developed fever without identified infective foci, which prompted a therapy shift to meropenem and liposomial amphotericin B. After five days of persisting fever he developed ingravescent abdominal lower right quadrant pain. Abdominal ultrasound was consistent with acute appendicitis and he underwent appendectomy with prompt defervescence. PAS+ fungal elements were found at histopathology examination of the resected vermiform appendix, and galactomannan was low positive. A. carneus, a rare species of Aspergillus formerly placed in section Flavipedes and recently considered a member of section Terrei, was identified in the specimen. Treatment with voriconazole was promptly started with success. No other site of Aspergillus localization was detected. Appendicitis is rarely caused by fungal organisms and isolated intestinal aspergillosis without pulmonary infection is unusual. To our knowledge, this is the first report of infection due to A. carneus in a child and in a primary gastrointestinal infection.

  12. Acute Activation of Metabolic Syndrome Components in Pediatric Acute Lymphoblastic Leukemia Patients Treated with Dexamethasone

    PubMed Central

    Warris, Lidewij T.; van den Akker, Erica L. T.; Bierings, Marc B.; van den Bos, Cor; Zwaan, Christian M.; Sassen, Sebastiaan D. T.; Tissing, Wim J. E.; Veening, Margreet A.; Pieters, Rob; van den Heuvel-Eibrink, Marry M.

    2016-01-01

    Although dexamethasone is highly effective in the treatment of pediatric acute lymphoblastic leukemia (ALL), it can cause serious metabolic side effects. Because studies regarding the effects of dexamethasone are limited by their small scale, we prospectively studied the direct effects of treating pediatric ALL with dexamethasone administration with respect to activation of components of metabolic syndrome (MetS); in addition, we investigated whether these side effects were correlated with the level of dexamethasone. Fifty pediatric patients (3–16 years of age) with ALL were studied during a 5-day dexamethasone course during the maintenance phase of the Dutch Childhood Oncology Group ALL-10 and ALL-11 protocols. Fasting insulin, glucose, total cholesterol, HDL, LDL, and triglycerides levels were measured at baseline (before the start of dexamethasone; T1) and on the fifth day of treatment (T2). Dexamethasone trough levels were measured at T2. We found that dexamethasone treatment significantly increased the following fasting serum levels (P<0.05): HDL, LDL, total cholesterol, triglycerides, glucose, and insulin. In addition, dexamethasone increased insulin resistance (HOMA-IR>3.4) from 8% to 85% (P<0.01). Dexamethasone treatment also significantly increased the diastolic and systolic blood pressure. Lastly, dexamethasone trough levels (N = 24) were directly correlated with high glucose levels at T2, but not with other parameters. These results indicate that dexamethasone treatment acutely induces three components of the MetS. Together with the weight gain typically associated with dexamethasone treatment, these factors may contribute to the higher prevalence of MetS and cardiovascular risk among survivors of childhood leukemia who received dexamethasone treatment. PMID:27362350

  13. Role of CXCR4-mediated bone marrow colonization in CNS infiltration by T cell acute lymphoblastic leukemia.

    PubMed

    Jost, Tanja Rezzonico; Borga, Chiara; Radaelli, Enrico; Romagnani, Andrea; Perruzza, Lisa; Omodho, Lorna; Cazzaniga, Giovanni; Biondi, Andrea; Indraccolo, Stefano; Thelen, Marcus; Te Kronnie, Geertruy; Grassi, Fabio

    2016-06-01

    Infiltration of the central nervous system is a severe trait of T cell acute lymphoblastic leukemia. Inhibition of CXC chemokine receptor 4 significantly ameliorates T cell acute lymphoblastic leukemia in murine models of the disease; however, signaling by CXC chemokine receptor 4 is important in limiting the divagation of peripheral blood mononuclear cells out of the perivascular space into the central nervous system parenchyma. Therefore, Inhibition of CXC chemokine receptor 4 potentially may untangle T cell acute lymphoblastic leukemia cells from retention outside the brain. Here, we show that leukemic lymphoblasts massively infiltrate cranial bone marrow, with diffusion to the meninges without invasion of the brain parenchyma, in mice that underwent xenotransplantation with human T cell acute lymphoblastic leukemia cells or that developed leukemia from transformed hematopoietic progenitors. We tested the hypothesis that T cell acute lymphoblastic leukemia neuropathology results from meningeal infiltration through CXC chemokine receptor 4-mediated bone marrow colonization. Inhibition of leukemia engraftment in the bone marrow by pharmacologic CXC chemokine receptor 4 antagonism significantly ameliorated neuropathologic aspects of the disease. Genetic deletion of CXCR4 in murine hematopoietic progenitors abrogated leukemogenesis induced by constitutively active Notch1, whereas lack of CCR6 and CCR7, which have been shown to be involved in T cell and leukemia extravasation into the central nervous system, respectively, did not influence T cell acute lymphoblastic leukemia development. We hypothesize that lymphoblastic meningeal infiltration as a result of bone marrow colonization is responsible for the degenerative alterations of the neuroparenchyma as well as the alteration of cerebrospinal fluid drainage in T cell acute lymphoblastic leukemia xenografts. Therefore, CXC chemokine receptor 4 may constitute a pharmacologic target for T cell acute lymphoblastic

  14. Acute leukemia of adults. Ultrastructural, cytochemical and histologic observations in 100 cases.

    PubMed

    Glick, A D; Paniker, K; Flexner, J M; Graber, S E; Collins, R D

    1980-04-01

    In order to establish guidelines for categorization of acute leukemia, marrow histology, special stains, and electron microscopy were performed in 100 adult leukemia cases. Differential counts for each stain were performed, and the results were combined with those obtained by electron microscopy for final classification. Myeloid (non-lymphoid) leukemia was most common (83 cases), and there were 13 lymphoid cases, two cases of erythroleukemia, and two undifferentiated leukemias. Histologic studies of marrow particles revealed significant admixtures of lymphocytes, plasma cells, and abnormal erythroid elements, particularly in acute myelomonocytic leukemia. Interpretations of cytochemical results were confirmed by ultrastructural studies in 90% of the cases. Clinically significant discrepancies between cytochemical and ultrastructural interpretations were rarely found. Only two myeloid and five lymphoid cases did not mark typically with any cytochemical stain. The single most reliable special stain was the periodic acid-Schiff stain, whereas the stain most difficult to interpret was the alpha-naphthyl acetate esterase stain. Sudan black stain was particularly helpful in demonstrating Auer rods. Five of six cases unclassified by cytochemistry were categorized by electron microscopy. Although patterns of cytochemical staining were delineated for each type of leukemia, significant intragroup variation in cytochemical reactions was recognized. This study indicates that ultrastructural examination should be routinely used for categorization of cases with equivocal cytochemical findings and for analysis of unclassified cases.

  15. The effects of aspartame on mast cells and basophils.

    PubMed

    Szucs, E F; Barrett, K E; Metcalfe, D D

    1986-02-01

    The artificial sweetener aspartame was studied to determine whether it had any direct effects on mast cells and basophils. Aspartame was not shown to be a direct mast cell or basophil secretagogue in vitro, or in vivo as assessed by skin testing. During an acute incubation, aspartame did not affect IgE-mediated histamine release from mast cells. However, mast cells cultured in aspartame for periods of up to 9 days showed enhanced rates of proliferation and decreased responsiveness to releasing stimuli. The effect of aspartame on proliferation of cells in culture could be ascribed to a non-specific enhancing effect of its constituent amino acids.

  16. Numbers and cytotoxicities of CD3+CD56+ T lymphocytes in peripheral blood of patients with acute myeloid leukemia and acute lymphocytic leukemia.

    PubMed

    Guo, Wenjian; Xing, Chao; Dong, Aishu; Lin, Xiaoji; Lin, Ying; Zhu, Baoling; He, Muqing; Yao, Rongxing

    2013-10-01

    Recent reports have highlighted the role of cellular immunity in anti-tumor defenses. T lymphocytes are known to play important part in anti-cancer immunity. The number and function of T lymphocytes are altered in chronic leukemia patients. CD3(+)CD56(+) T lymphocytes have also been found to be abnormal in cancer patients. We therefore investigated changes in the number and cytotoxicity of CD3(+)CD56(+) T lymphocytes in the peripheral blood of acute leukemia (AL) patients (excluding acute promyelocytic leukemia), to improve our understanding of the role of this T lymphocyte subset. We analyzed CD3(+)CD56(+) T lymphocyte numbers and cytotoxicities in healthy controls, AL patients, and AL patients with complete remission. Lymphocyte counts were performed in peripheral blood and flow cytometry was used to determine cell numbers and cytotoxicities. The absolute number of CD3(+)CD56(+) T lymphocytes was increased in AL patients (including acute myeloid [AML] and acute lymphocytic leukemia [ALL]) compared with healthy controls (P<0.05), but their functioning was significantly reduced (P<0.05). The number of CD3(+)CD56(+) T lymphocytes in AML and ALL patients who achieved remission following chemotherapy was close to healthy controls (P>0.05), but their functioning was still significantly reduced (P<0.05). In addition, the number of CD3(+)CD56(+) T lymphocytes increased significantly in AML patients with increased peripheral blood white blood cell (WBC) counts, and in ALL patients without increased WBCs. These results suggest that cellular immunity may respond to AML and ALL, but that lymphocyte cytotoxicity remains impaired. Dysfunction of CD3(+)CD56(+) T lymphocytes in AML and ALL patients may contribute to the failure of the host immune response against leukemic blasts.

  17. Dasatinib in high-risk core binding factor acute myeloid leukemia in first complete remission: a French Acute Myeloid Leukemia Intergroup trial.

    PubMed

    Boissel, Nicolas; Renneville, Aline; Leguay, Thibaut; Lefebvre, Pascale Cornillet; Recher, Christian; Lecerf, Thibaud; Delabesse, Eric; Berthon, Céline; Blanchet, Odile; Prebet, Thomas; Pautas, Cécile; Chevallier, Patrice; Leprêtre, Stéphane; Girault, Stéphane; Bonmati, Caroline; Guièze, Romain; Himberlin, Chantal; Randriamalala, Edouard; Preudhomme, Claude; Jourdan, Eric; Dombret, Hervé; Ifrah, Norbert

    2015-06-01

    Core-binding factor acute myeloid leukemia is a favorable acute myeloid leukemia subset cytogenetically defined by t(8;21) or inv(16)/t(16;16) rearrangements, disrupting RUNX1 (previously CBFA/AML1) or CBFB transcription factor functions. The receptor tyrosine kinase KIT is expressed in the vast majority of these acute myeloid leukemias and frequent activating KIT gene mutations have been associated with a higher risk of relapse. This phase II study aimed to evaluate dasatinib as maintenance therapy in patients with core-binding factor acute myeloid leukemia in first hematologic complete remission, but at higher risk of relapse due to molecular disease persistence or recurrence. A total of 26 patients aged 18-60 years old previously included in the CBF-2006 trial were eligible to receive dasatinib 140 mg daily if they had a poor initial molecular response (n=18) or a molecular recurrence (n=8). The tolerance of dasatinib as maintenance therapy was satisfactory. The 2-year disease-free survival in this high-risk population of patients was 25.7%. All but one patient with molecular recurrence presented subsequent hematologic relapse. Patients with slow initial molecular response had a similar disease-free survival when treated with dasatinib (40.2% at 2 years) or without any maintenance (50.0% at 2 years). The disappearance of KIT gene mutations at relapse suggests that clonal devolution may in part explain the absence of efficacy observed with single-agent dasatinib in these patients (n. EudraCT: 2006-006555-12).

  18. Relative osteopenia after treatment for acute lymphoblastic leukemia.

    PubMed

    Warner, J T; Evans, W D; Webb, D K; Bell, W; Gregory, J W

    1999-04-01

    Osteoporosis in adult life is associated with a significant morbidity and may be predisposed to by osteopenia and failure to reach peak bone mass in childhood. Children treated for acute lymphoblastic leukemia (ALL) may be at risk of osteopenia as a result of previous therapy or as a consequence of the disease process itself. Dual energy x-ray absorptiometry measurements of bone mineral content (BMC) for the whole body and at the lumbar spine and hip were taken in 35 (14 male) long-term survivors of ALL and compared with results in 20 (10 male) survivors of other malignancies and 31 (17 male) healthy sibling controls. The measured BMC was expressed as a percentage of a predicted value derived from the control group and based on the variables that had influence upon it. BMC (%) was reduced at the spine in the ALL group compared with controls [92.4 (8.0)% versus 100.4 (9.7)%, respectively; p < 0.005] and at the hip compared with both other malignancies and controls [89.0 (11.5)% versus 96.1 (11.7)% and 100.4 (9.2)%, respectively; p < 0.0005]. Increasing length of time off therapy was associated with a significant increase in %BMC at both the spine and the hip. For the spine, this association was significantly different between the ALL group and other malignancies, suggesting that any gain in %BMC after therapy was slower in children treated for ALL. Both exercise capacity and levels of physical activity were correlated with %BMC at the hip (r = 0.44, p < 0.001 and r = 0.29, p < 0.01, respectively). Previous exposure to methotrexate, ifosfamide, and bleomycin was associated with a reduction in %BMC at the spine. Exposure to 6-mercaptopurine and cisplatin was associated with a reduction at the hip. In conclusion, children treated for ALL are osteopenic. The mechanism is probably multifactorial but is partially related to previous chemotherapy, limited exercise capacity, and relative physical inactivity.

  19. Biology, Risk Stratification, and Therapy of Pediatric Acute Leukemias: An Update

    PubMed Central

    Pui, Ching-Hon; Carroll, William L.; Meshinchi, Soheil; Arceci, Robert J.

    2011-01-01

    Purpose We review recent advances in the biologic understanding and treatment of childhood acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML), identify therapeutically challenging subgroups, and suggest future directions of research. Methods A review of English literature on childhood acute leukemias from the past 5 years was performed. Results Contemporary treatments have resulted in 5-year event-free survival rates of approximately 80% for childhood ALL and almost 60% for pediatric AML. The advent of high-resolution genome-wide analyses has provided new insights into leukemogenesis and identified many novel subtypes of leukemia. Virtually all ALL and the vast majority of AML cases can be classified according to specific genetic abnormalities. Cooperative mutations involved in cell differentiation, cell cycle regulation, tumor suppression, drug responsiveness, and apoptosis have also been identified in many cases. The development of new formulations of existing drugs, molecularly targeted therapy, and immunotherapies promises to further advance the cure rates and improve quality of life of patients. Conclusion The application of new high-throughput sequencing techniques to define the complete DNA sequence of leukemia and host normal cells and the development of new agents targeted to leukemogenic pathways promise to further improve outcome in the coming decade. PMID:21220611

  20. ZFX controls propagation and prevents differentiation of acute T-lymphoblastic and myeloid leukemia

    PubMed Central

    Weisberg, Stuart P.; Smith-Raska, Matthew R.; Esquilin, Jose M.; Zhang, Ji; Arenzana, Teresita L.; Lau, Colleen M.; Churchill, Michael; Pan, Haiyan; Klinakis, Apostolos; Dixon, Jack E.; Mirny, Leonid A.; Mukherjee, Siddhartha; Reizis, Boris

    2014-01-01

    Summary Tumor-propagating cells in acute leukemia maintain a stem/progenitor-like immature phenotype and proliferative capacity. Acute myeloid leukemia (AML) and acute T-lymphoblastic leukemia (T-ALL) originate from different lineages through distinct oncogenic events such as MLL fusions and Notch signaling, respectively. We found that Zfx, a transcription factor that controls hematopoietic stem cell self-renewal, controls the initiation and maintenance of AML caused by MLL-AF9 fusion and of T-ALL caused by Notch1 activation. In both leukemia types, Zfx prevents differentiation and activates gene sets characteristic of immature cells of the respective lineages. In addition, endogenous Zfx contributes to gene induction and transformation by Myc overexpression in myeloid progenitors. Key Zfx target genes include the mitochondrial enzymes Ptpmt1 and Idh2, whose overexpression partially rescues the propagation of Zfx-deficient AML. These results show that distinct leukemia types maintain their undifferentiated phenotype and self-renewal by exploiting a common stem cell-related genetic regulator. PMID:24485662