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Sample records for acute leukemia patients

  1. Thrombosis in adult patients with acute leukemia.

    Science.gov (United States)

    Del Principe, Maria Ilaria; Del Principe, Domenico; Venditti, Adriano

    2017-11-01

    Recent studies indicate that the risk of thrombosis in hematologic patients may be similar or even higher than that found in patients with solid tumors. However, available information about pathogenesis and incidence of thrombosis in acute leukemia is limited. This review focuses on mechanisms underlying thrombosis in acute leukemia and discusses recent literature data. In the last few years, proofs have been provided that leukemic cells release free prothrombotic products, such as micro-vesicles, tissue factors, circulating free DNA and RNA. Furthermore, leukemic blasts can activate the procoagulant population of platelets, which initiate and amplify coagulation, causing thrombosis. In addition to factors produced by acute leukemia itself, others concur to trigger thrombosis. Some drugs, infections and insertion of central venous catheter have been described to increase risk of thrombosis in patients with acute leukemia. Thrombosis represents a serious complication in patients affected by myeloid and lymphoid acute leukemia. A proper knowledge of its pathophysiology and of the predisposing risk factors may allow to implement strategies of prevention. Improving prevention of thrombosis appears a major goal in patients whose frequent conditions of thrombocytopenia impede an adequate delivery of anticoagulant therapy.

  2. CYTOGENETIC ANALYSIS IN SLOVENIAN ACUTE LEUKEMIA PATIENTS

    Directory of Open Access Journals (Sweden)

    Helena Podgornik

    2008-04-01

    Using molecular cytogenetic and genetic methods a possibility that some of chromosomalchanges were overlooked was considerably minimized. On the basis of the analyzed datawe can be confident that the cytogenetic diagnostic approach in our acute leukemia patients is in accordance with international guidelines

  3. Fatal Candidemia in a Patient with Acute Lymphoblastic Leukemia

    Science.gov (United States)

    2018-02-16

    NOTES 14. ABSTRACT Fatal Candidcn1ia in a Patient \\\\ith Acute Lympboblastic Leukemia Brittany Lenz. MD. Arturo Dominguez.. MD. Adnan J’vlir. MD, PhD...Profoosionaf 7 ,0 Fatal Candidemia in a Patient with Acute Lymphoblastic Leukemia Brittany Lenz, MD, Arturo Dominguez, MD, Adnan Mir, MD, PhD Objectives...with pre-B cell acute lymphoblastic leukemia was admitted for presumed septic shock secondary to an unknown infectious etiology. The patient was

  4. Vorinostat in Treating Patients With Acute Myeloid Leukemia

    Science.gov (United States)

    2014-04-30

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

  5. Pneumonia during Remission Induction Chemotherapy in Patients with Acute Leukemia

    Science.gov (United States)

    Garcia, Javier Barreda; Lei, Xiudong; Wierda, William; Cortes, Jorge E.; Dickey, Burton F.; Evans, Scott E.

    2013-01-01

    Background: Pneumonia is a major cause of death during induction chemotherapy for acute leukemia. The purpose of this study was to quantify the incidence, risk factors, and outcomes of pneumonia in patients with acute leukemia. Methods: We conducted a retrospective cohort study of 801 patients with acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), or acute lymphocytic leukemia (ALL) who underwent induction chemotherapy. Measurements and Main Results: Pneumonia was present at induction start in 85 patients (11%). Of the 716 remaining patients, 148 (21%) developed pneumonia. The incidence rate of pneumonia was higher in MDS and AML than in ALL (0.013 vs. 0.008 vs. 0.003 pneumonias per day, respectively; P risk factors. The case fatality rate of pneumonia was 17% (40 of 233). Competing risk analysis demonstrated that in the absence of pneumonia, death was rare: 28-day mortality was 6.2% for all patients but only 1.26% in those without pneumonia. Compared with patients without pneumonia, patients with pneumonia had more intensive care unit days, longer hospital stays, and 49% higher costs (P Pneumonia after induction chemotherapy for acute leukemia continues to be common, and it is the most important determinant of early mortality after induction chemotherapy. Given the high incidence, morbidity, mortality, and cost of pneumonia, interventions aimed at prevention are warranted in patients with acute leukemia. PMID:23987587

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

    Science.gov (United States)

    2018-02-22

    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

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

    Science.gov (United States)

    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

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

    Science.gov (United States)

    2018-02-28

    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 Acute Myeloid Leukemia; Refractory Adult Acute Lymphoblastic Leukemia; Refractory Childhood Acute Lymphoblastic Leukemia

  9. Pneumatosis Intestinalis in a Patient with Acute Promyelocytic Leukemia

    Directory of Open Access Journals (Sweden)

    Abhishek Mangaonkar

    2015-01-01

    Full Text Available Pneumatosis Intestinalis is a rare condition characterized by the presence of gas within the intestinal wall. We describe a case of a 33-year-old woman with acute promyelocytic leukemia who developed nausea and nonbloody diarrhea. CT showed intramural air in transverse and descending colon. Patient clinically improved with conservative management.

  10. Acute Myeloid Leukemia in Childhood

    OpenAIRE

    Yöntem, Ahmet; Bayram, İbrahim

    2018-01-01

    Acute leukemia is basically divided intoacute lymphoblastic leukemia and acute myeloid leukemia. About 15-20% ofchildhood leukemia is caused by acute myeloid leukemia.AML is classified according to morphological, cytochemical and immunophenotypiccharacteristics. AML patients may present with various clinical signsand symptoms due to leukemic cell infiltration. Age, gender, race, structuralfeatures of the patient and cytogenetic abnormalities are important factorsaffecting prognosis in AML. Th...

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

    Science.gov (United States)

    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. Published by Elsevier Ltd.

  12. Comorbidity and performance status in acute myeloid leukemia patients

    DEFF Research Database (Denmark)

    Østgård, Lene Sofie Granfeldt; Nørgaard, J M; Sengeløv, H

    2015-01-01

    As the world population ages, the comorbidity burden in acute myeloid leukemia (AML) patients increases. Evidence on how to integrate comorbidity measures into clinical decision-making is sparse. We determined the prognostic impact of comorbidity and World Health Organization Performance Status (...... with an increased short- and long-term mortality (adjusted 90 day MR, PS⩾2=3.43 (95%CI=2.30-5.13); adjusted 91 day-3 year MR=1.35 (95%CI=1.06-1.74)). We propose that more patients with comorbidity may benefit from intensive chemotherapy....

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

    Science.gov (United States)

    2017-03-27

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

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

    Science.gov (United States)

    2018-01-24

    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. Acute Myeloid Leukemia: Clinical Spectrum of 125 Patients.

    Science.gov (United States)

    Sultan, Sadia; Zaheer, Hasan Abbas; Irfan, Syed Mohammed; Ashar, Sana

    2016-01-01

    Acute myeloid leukemia is an acquired clonal heterogeneous stem cell disorder. Hence, various parameters are sought out to categorize this disease into subtypes, so that as a consequence specific treatment modalities can be offered. Conventionally, the practically used method for classification utilizes French American British (FAB) criteria based on morphology and cytochemistry. The aim of present study was to determine the current spectrum of AML sub types in patients in Karachi. This single centre cross sectional study was conducted at Liaquat National Hospital, Karachi, extending from January 2010 to December 2014. Data were retrieved from archives were analyzed with SPSS version 22. A total of 125 patients were diagnosed at our institution with de novo AML during five years period, 76 males and 49 females. Median age was 34.5 years. AML-M1 was the predominant FAB subtype (23.2%) followed by M2 (18.4%), M3 and M4 (16% each), M0 (14.4%), M5 (7.2%), M6 (3.2%) and M7 (1.6%). AML in Pakistani patients is seen in a relatively young population. The most common FAB subtype observed in our study was acute myeloblastic leukemia, without maturation (M1).

  16. Coagulation Profile at Diagnosis in Patients with Acute Lymphoblastic Leukemia.

    Science.gov (United States)

    Sehgal, Shivali; Sharma, Sunita; Chandra, Jagdish; Nangia, Anita

    2016-10-01

    To evaluate the coagulation parameters at the time of diagnosis in pediatric acute lymphoblastic leukemia (ALL) patients. A total of 65 newly diagnosed ALL patients upto 18 y of age along with 30 age and sex matched controls were included in the study. Coagulation tests including Prothrombin Time (PT), Activated Partial Thromboplastin Time (APTT), Fibrinogen (FBG) assay, D-dimer (D-DI) assay, Coagulation inhibitor levels and tests for fibrinolysis were performed. At baseline, APTT of the patients was significantly prolonged (p 0.033), but PT and fibrinogen were comparable in the two groups. Protein C (PC) and Protein S (PS) were both significantly reduced in the cases, while antithrombin was comparable to control values (p DI levels were significantly high (p < 0.001). The onset of leukemia is associated with hemostatic derangement favouring hypercoagulability. The coagulopathy is due to thrombin activation (as evidenced by raised d-dimer). The decreased fibrinolysis (due to reduced tPA and raised PAI-1) and low levels of PC and PS contribute to the hypercoagulable state at the time of diagnosis.

  17. Daunorubicin Hydrochloride, Cytarabine and Oblimersen Sodium in Treating Patients With Previously Untreated Acute Myeloid Leukemia

    Science.gov (United States)

    2013-06-04

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

  18. 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

    Science.gov (United States)

    2018-03-05

    Acute Biphenotypic Leukemia; Acute Erythroid Leukemia; Acute Lymphoblastic Leukemia in Remission; Acute Megakaryoblastic Leukemia; Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome; Acute Myeloid Leukemia in Remission; Blasts Under 10 Percent of Bone Marrow Nucleated Cells; Blasts Under 5 Percent of Bone Marrow Nucleated Cells; Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Mixed Phenotype Acute Leukemia; Myelodysplastic Syndrome; Myelodysplastic Syndrome With Excess Blasts; Pancytopenia; Refractory Anemia; Secondary Acute Myeloid Leukemia

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

    Science.gov (United States)

    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

  20. Acute interstitial nephritis in T-cell leukemia in a pediatric patient.

    Science.gov (United States)

    Biro, Erika; Szikszay, Edit; Pethő-Orosz, Petronella; Bigida, László; Balla, György; Szabó, Tamás

    2016-09-01

    Acute lymphoid leukemia is the most frequently occurring malignancy in childhood, but acute tubulointerstitial nephritis with associated acute renal failure as the leading manifestation of leukemia is extremely rare. Only a few pediatric cases have been described in the literature. We present a surprising case in which physical examination and initial investigation were not typical for leukemia. Ultrasound showed only modest kidney enlargement while laboratory results indicated acute renal failure. Renal biopsy indicated tubulointerstitial nephritis, and subsequent steroid treatment led to sudden clinical improvement. One month later, however, the patient returned with typical clinical features of leukemia. Re-evaluation of the original kidney biopsy block indicated T-cell acute lymphoid leukemia. The present case highlights the importance of renal biopsy. © 2016 Japan Pediatric Society.

  1. Development of acute myeloid leukemia in patients with untreated chronic lymphocytic leukemia.

    Science.gov (United States)

    Ito, Shoko; Fujiwara, Shin-Ichiro; Mashima, Kiyomi; Umino, Kento; Minakata, Daisuke; Nakano, Hirofumi; Yamasaki, Ryoko; Kawasaki, Yasufumi; Sugimoto, Miyuki; Ashizawa, Masahiro; Yamamoto, Chihiro; Hatano, Kaoru; Okazuka, Kiyoshi; Sato, Kazuya; Oh, Iekuni; Ohmine, Ken; Suzuki, Takahiro; Muroi, Kazuo; Kanda, Yoshinobu

    2017-05-01

    The development of acute myeloid leukemia (AML) in patients with untreated chronic lymphocytic leukemia (CLL) is rare. We experienced a 65-year-old man who developed AML with aberrant CD7 expression and monoallelic CEBPA mutation during watchful waiting for CLL. He failed to achieve complete response (CR) by standard induction therapy for AML. We retrospectively reviewed 27 patients who developed AML with untreated CLL published between 1973 and 2016. The median age at diagnosis of AML was 68 years, and the median duration between the diagnoses of AML and CLL was 4.2 years. Diagnosis of AML and CLL was made simultaneously in 16 patients. The CR rate of AML was 42.9%, and the median survival was only 1.5 months after the diagnosis of AML. Patients who achieved CR tended to survive longer than those who did not. Our results demonstrated that the development of AML in patients with untreated CLL was associated with a poor response to chemotherapy and an extremely poor prognosis.

  2. Translational Studies in Elderly Patients with Acute Myeloid Leukemia

    NARCIS (Netherlands)

    B. van der Holt (Bronno)

    2007-01-01

    textabstractThe production of blood cells (hematopoiesis) takes place in the bone marrow. Acute myeloid leukemia (AML) is a clonal disease, which is characterized by an increase in the number of myeloid cells in the bone marrow and an arrest in their maturation. This frequently results in a severe

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

    International Nuclear Information System (INIS)

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

    1988-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Guldane Cengiz Seval

    2015-03-01

    Full Text Available The objectives of this review were to discuss standard and investigational treatment strategies for adolescent and young adult with acute myeloid leukemia, excluding acute promyelocytic leukemia. Acute myeloid leukemia (AML in adolescent and young adult patients (AYAs may need a different type of therapy than those currently used in children and older patients. As soon as AML is diagnosed, AYA patient should be offered to participate in well-designed clinical trials. The standard treatment approach for AYAs with AML is remission induction chemotherapy with an anthracycline/cytarabine combination, followed by either consolidation chemotherapy or stem cell transplantation, depending on the ability of the patient to tolerate intensive treatment and cytogenetic features. Presently, continuing progress of novel drugs targeting specific pathways in acute leukemia may bring AML treatment into a new era.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1988-01-01

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

  6. Detection of anti-Toxoplasma gondii antibodies in chronic myeloid leukemia and acute myeloid leukemia patients

    Directory of Open Access Journals (Sweden)

    Mohammad Javad Gharavi

    2017-09-01

    Full Text Available Background and Aim: Infection of Toxoplasma gondii is a worldwide distribution. Toxoplasmosis in patients who are immunocompromised by virtue of underlying leukemia disease has received relatively little attention. This study was aimed to evaluate IgG and IgM antibodies of T. gondii and to minimize the role of T. gondii and opportunistic infection complication at the early stage of infection in leukemia patients. Materials and Methods: The purpose of this assay was to measure anti-T. gondii IgG and IgM antibodies by enzyme-linked immunosorbent assay (ELISA technique in leukemia patients. Results: IgG antibodies against T. gondii were detected by ELISA in 96 (56.4% leukemia patients and 72 (42.4% control group. IgM antibodies were found in 10 patients (5.9% with leukemia and 3 (1.8% in the corresponding. Conclusion: Our finding indicated that leukemia patients under immunosuppressive condition should not be neglected. Toxoplasmosis in leukemia patients as a main risk factor is considered, meanwhile in some patients, due to possibility of the presence of secondary infection that leads to severe toxoplasmosis.

  7. Hypercalcemia and acute pancreatitis in a male patient with acute promyelocytic leukemia and pulmonary tuberculosis.

    Science.gov (United States)

    Abdullah, Ali S; Adel, Ahmad M; Hussein, Radwa M; Abdullah, Mohammed Aj; Yousaf, Anil; Mudawi, Deena; Mohamed, Shehab F; Nashwan, Abdulqadir J; Soliman, Dina; Ibrahim, Feryal; Yassin, Mohamed A

    2018-04-03

    We report a rare case of hypercalcemia and acute pancreatitis in a subject with acute promyelocytic leukemia (APL) and pulmonary tuberculosis, during all-trans-retinoic acid (ATRA) treatment. Both associated complications were potentially due to several causes. A careful monitoring and exclusion of all causative factors must be addressed. Further research is necessary to improve our understanding of risk factors for these complications in patients with (APL). Studying these patterns may help us to improve outcomes for all children and young adults with hematologic malignancies.

  8. Acute myelomonocytic leukemia following splenectomy in a patient with long-standing Hodgkin disease

    International Nuclear Information System (INIS)

    Rosenbloom, B.E.; Klein, E.J.; Uszler, J.M.; Ellis, R.; Block, J.B.; Tanaka, K.R.

    1978-01-01

    The association of acute nonlymphocytic leukemia with Hodgkin disease has been recorded in more than 100 instances. In most of these cases the patient has had long-standing Hodgkin disease and radiotherapy has been carried out. The combination of previous radiotherapy and chemotherapy appears to further increase the risk of leukemia developing. In a patient under our care with Hodgkin disease acute myelomonocytic leukemia developed following splenectomy for hypersplenism. The onset of acute leukemia immediately following splenectomy in a patient with Hodgkin disease has not previously been noted. In addition, because the patient's usual bone marrow sampling sites were hypoplastic, we utilized an 111 In-chloride bone marrow scan to find a site that was accessible for aspiration

  9. Outcome of pediatric acute myeloid leukemia patients receiving intensive care in the United States.

    Science.gov (United States)

    Maude, Shannon L; Fitzgerald, Julie C; Fisher, Brian T; Li, Yimei; Huang, Yuan-Shung; Torp, Kari; Seif, Alix E; Kavcic, Marko; Walker, Dana M; Leckerman, Kateri H; Kilbaugh, Todd J; Rheingold, Susan R; Sung, Lillian; Zaoutis, Theoklis E; Berg, Robert A; Nadkarni, Vinay M; Thomas, Neal J; Aplenc, Richard

    2014-02-01

    Children with acute myeloid leukemia are at risk for sepsis and organ failure. Outcomes associated with intensive care support have not been studied in a large pediatric acute myeloid leukemia population. Our objective was to determine hospital mortality of pediatric acute myeloid leukemia patients requiring intensive care. Retrospective cohort study of children hospitalized between 1999 and 2010. Use of intensive care was defined by utilization of specific procedures and resources. The primary endpoint was hospital mortality. Forty-three children's hospitals contributing data to the Pediatric Health Information System database. Patients who are newly diagnosed with acute myeloid leukemia and who are 28 days through 18 years old (n = 1,673) hospitalized any time from initial diagnosis through 9 months following diagnosis or until stem cell transplant. A reference cohort of all nononcology pediatric admissions using the same intensive care resources in the same time period (n = 242,192 admissions) was also studied. None. One-third of pediatric patients with acute myeloid leukemia (553 of 1,673) required intensive care during a hospitalization within 9 months of diagnosis. Among intensive care admissions, mortality was higher in the acute myeloid leukemia cohort compared with the nononcology cohort (18.6% vs 6.5%; odds ratio, 3.23; 95% CI, 2.64-3.94). However, when sepsis was present, mortality was not significantly different between cohorts (21.9% vs 19.5%; odds ratio, 1.17; 95% CI, 0.89-1.53). Mortality was consistently higher for each type of organ failure in the acute myeloid leukemia cohort versus the nononcology cohort; however, mortality did not exceed 40% unless there were four or more organ failures in the admission. Mortality for admissions requiring intensive care decreased over time for both cohorts (23.7% in 1999-2003 vs 16.4% in 2004-2010 in the acute myeloid leukemia cohort, p = 0.0367; and 7.5% in 1999-2003 vs 6.5% in 2004-2010 in the nononcology

  10. Vorinostat and Decitabine in Treating Patients With Advanced Solid Tumors or Relapsed or Refractory Non-Hodgkin's Lymphoma, Acute Myeloid Leukemia, Acute Lymphocytic Leukemia, or Chronic Myelogenous Leukemia

    Science.gov (United States)

    2014-08-26

    Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Blastic Phase Chronic Myelogenous Leukemia; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Nodal Marginal Zone B-cell Lymphoma; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Small Lymphocytic Lymphoma; Secondary Acute Myeloid Leukemia; Splenic Marginal Zone Lymphoma; Stage III Adult Burkitt Lymphoma; Stage III Adult Diffuse Large Cell Lymphoma; Stage III Adult Diffuse Mixed Cell Lymphoma; Stage III Adult Diffuse Small Cleaved Cell Lymphoma; Stage III Adult Immunoblastic Large Cell Lymphoma; Stage III Adult Lymphoblastic Lymphoma; Stage III Grade 1 Follicular Lymphoma; Stage III Grade 2 Follicular Lymphoma; Stage III Grade 3 Follicular Lymphoma; Stage III Mantle Cell Lymphoma; Stage III Marginal Zone Lymphoma; Stage III Small Lymphocytic Lymphoma; Stage IV Adult Burkitt Lymphoma; Stage IV Adult Diffuse Large Cell Lymphoma; Stage IV Adult Diffuse Mixed Cell Lymphoma; Stage IV Adult Diffuse Small Cleaved Cell Lymphoma; Stage IV Adult Immunoblastic Large Cell Lymphoma; Stage IV Adult Lymphoblastic Lymphoma; Stage IV Grade 1 Follicular Lymphoma; Stage IV Grade 2 Follicular Lymphoma; Stage IV Grade 3 Follicular Lymphoma; Stage IV Mantle Cell Lymphoma; Stage IV Marginal Zone Lymphoma

  11. Campylobacter jejuni Bacteremia in a Patient With Acute Lymphocytic Leukemia

    Science.gov (United States)

    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

  12. MicroRNA profiling can classify acute leukemias of ambiguous lineage as either acute myeloid leukemia or acute lymphoid leukemia.

    Science.gov (United States)

    de Leeuw, David C; van den Ancker, Willemijn; Denkers, Fedor; de Menezes, Renée X; Westers, Theresia M; Ossenkoppele, Gert J; van de Loosdrecht, Arjan A; Smit, Linda

    2013-04-15

    Classification of acute leukemia is based on the commitment of leukemic cells to the myeloid or the lymphoid lineage. However, a small percentage of acute leukemia cases lack straightforward immunophenotypical lineage commitment. These leukemias of ambiguous lineage represent a heterogeneous category of acute leukemia that cannot be classified as either acute myeloid leukemia (AML) or acute lymphoid leukemia (ALL). The lack of clear classification of acute leukemias of ambiguous lineage as either AML or ALL is a hurdle in treatment choice for these patients. Here, we compared the microRNA (miRNA) expression profiles of 17 cases with acute leukemia of ambiguous lineage and 16 cases of AML, B-cell acute lymphoid leukemia (B-ALL), and T-cell acute lymphoid leukemia (T-ALL). We show that leukemias of ambiguous lineage do not segregate as a separate entity but exhibit miRNA expression profiles similar to AML, B-ALL, or T-ALL. We show that by using only 5 of the most lineage-discriminative miRNAs, we are able to define acute leukemia of ambiguous lineage as either AML or ALL. Our results indicate the presence of a myeloid or lymphoid lineage-specific genotype, as reflected by miRNA expression, in these acute leukemias despite their ambiguous immunophenotype. miRNA-based classification of acute leukemia of ambiguous lineage might be of additional value in therapeutic decision making.

  13. Patient-derived xenotransplants can recapitulate the genetic driver landscape of acute leukemias.

    Science.gov (United States)

    Wang, K; Sanchez-Martin, M; Wang, X; Knapp, K M; Koche, R; Vu, L; Nahas, M K; He, J; Hadler, M; Stein, E M; Tallman, M S; Donahue, A L; Frampton, G M; Lipson, D; Roels, S; Stephens, P J; Sanford, E M; Brennan, T; Otto, G A; Yelensky, R; Miller, V A; Kharas, M G; Levine, R L; Ferrando, A; Armstrong, S A; Krivtsov, A V

    2017-01-01

    Genomic studies have identified recurrent somatic mutations in acute leukemias. However, current murine models do not sufficiently encompass the genomic complexity of human leukemias. To develop preclinical models, we transplanted 160 samples from patients with acute leukemia (acute myeloid leukemia, mixed lineage leukemia, B-cell acute lymphoblastic leukemia, T-cell ALL) into immunodeficient mice. Of these, 119 engrafted with expected immunophenotype. Targeted sequencing of 374 genes and 265 frequently rearranged RNAs detected recurrent and novel genetic lesions in 48 paired primary tumor (PT) and patient-derived xenotransplant (PDX) samples. Overall, the frequencies of 274 somatic variant alleles correlated between PT and PDX samples, although the data were highly variable for variant alleles present at 0-10%. Seventeen percent of variant alleles were detected in either PT or PDX samples only. Based on variant allele frequency changes, 24 PT-PDX pairs were classified as concordant while the other 24 pairs showed various degree of clonal discordance. There was no correlation of clonal concordance with clinical parameters of diseases. Significantly more bone marrow samples than peripheral blood samples engrafted discordantly. These data demonstrate the utility of developing PDX banks for modeling human leukemia, and emphasize the importance of genomic profiling of PDX and patient samples to ensure concordance before performing mechanistic or therapeutic studies.

  14. Successful hematopoietic cell transplantation in a patient with X-linked agammaglobulinemia and acute myeloid leukemia.

    Science.gov (United States)

    Abu-Arja, Rolla F; Chernin, Leah R; Abusin, Ghada; Auletta, Jeffery; Cabral, Linda; Egler, Rachel; Ochs, Hans D; Torgerson, Troy R; Lopez-Guisa, Jesus; Hostoffer, Robert W; Tcheurekdjian, Haig; Cooke, Kenneth R

    2015-09-01

    X-linked agammaglobulinemia (XLA) is a primary immunodeficiency characterized by marked reduction in all classes of serum immunoglobulins and the near absence of mature CD19(+) B-cells. Although malignancy has been observed in patients with XLA, we present the first reported case of acute myeloid leukemia (AML) in a patient with XLA. We also demonstrate the complete correction of the XLA phenotype following allogeneic hematopoietic cell transplantation for treatment of the patient's leukemia. © 2015 Wiley Periodicals, Inc.

  15. Genetically Modified T-cell Immunotherapy in Treating Patients With Relapsed/Refractory Acute Myeloid Leukemia and Persistent/Recurrent Blastic Plasmacytoid Dendritic Cell Neoplasm

    Science.gov (United States)

    2018-03-02

    Adult Acute Myeloid Leukemia in Remission; Acute Biphenotypic Leukemia; Early Relapse of Acute Myeloid Leukemia; Late Relapse of Acute Myeloid Leukemia; Recurrent Adult Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia; Blastic Plasmacytoid Dendritic Cell Neoplasm; Acute Myeloid Leukemia; Adult Acute Lymphoblastic Leukemia; Interleukin-3 Receptor Subunit Alpha Positive; Minimal Residual Disease; Refractory Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

  16. Increased regulatory T cells in acute lymphoblastic leukemia patients.

    Science.gov (United States)

    Idris, Siti-Zuleha; Hassan, Norfarazieda; Lee, Le-Jie; Md Noor, Sabariah; Osman, Raudhawati; Abdul-Jalil, Marsitah; Nordin, Abdul-Jalil; Abdullah, Maha

    2015-10-01

    Regulation in adaptive immune response balances a fine line that prevents instigation of self-damage or fall into unresponsiveness permitting abnormal cell growth. Mechanisms that keep this balance in check include regulatory T cells (Tregs). Tregs consist of a small but heterogeneous population which may be identified by the phenotype, CD3+CD4+CD25+CD127-. Role of Tregs in pathogenesis of cancers is thus far supported by evidence of increased Tregs in various cancers and may contribute to poorer prognosis. Tregs may also be important in acute leukemias. A review of the literature on Tregs in acute leukemias was conducted and Tregs were determined in B-cell acute lymphoblastic leukemias (ALLs). Studies on Tregs in B-cell ALL are few and controversial. We observed a significantly increased percentage of Tregs (mean ± SD, 9.72 ± 3.79% vs. 7.05 ± 1.74%; P = 0.047) in the bone marrow/peripheral blood of ALL (n = 17) compared to peripheral blood of normal controls (n = 35). A positive trend between Tregs and age (R = 0.474, P = 0.055, n = 17) implicates this factor of poor prognosis in B-cell ALL. Tregs in cancer are particularly significant in immunotherapy. The manipulation of the immune system to treat cancer has for a long time ignored regulatory mechanisms inducible or in place. In lymphoma studies tumor-specific mechanisms that are unlike conventional methods in the induction of Tregs have been hypothesized. In addition, tumor-infiltrating Tregs may present different profiles from peripheral blood pictures. Tregs will continue to be dissected to reveal their mysteries and their impact on clinical significance.

  17. Rhabdomyolysis Following Initiation of Posaconazole Use for Antifungal Prophylaxis in a Patient With Relapsed Acute Myeloid Leukemia

    Directory of Open Access Journals (Sweden)

    Mayur D. Mody MD

    2017-02-01

    Full Text Available Posaconazole is a commonly used medication for antifungal prophylaxis in patients with high-risk acute leukemia, such as acute myeloid leukemia. Despite clinical data that show that posaconazole is superior to other antifungal prophylaxis medications, posaconazole is known to have many side effects and drug-drug interactions. We present a patient who developed rhabdomyolysis after being started on posaconazole for prophylaxis in the setting of relapsed acute myeloid leukemia.

  18. Rhabdomyolysis Following Initiation of Posaconazole Use for Antifungal Prophylaxis in a Patient With Relapsed Acute Myeloid Leukemia

    Science.gov (United States)

    Mody, Mayur D.; Ravindranathan, Deepak; Gill, Harpaul S.; Kota, Vamsi K.

    2017-01-01

    Posaconazole is a commonly used medication for antifungal prophylaxis in patients with high-risk acute leukemia, such as acute myeloid leukemia. Despite clinical data that show that posaconazole is superior to other antifungal prophylaxis medications, posaconazole is known to have many side effects and drug-drug interactions. We present a patient who developed rhabdomyolysis after being started on posaconazole for prophylaxis in the setting of relapsed acute myeloid leukemia. PMID:28203579

  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

    Science.gov (United States)

    2018-03-19

    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. The Effect of Aromatherapy on Insomnia and Other Common Symptoms Among Patients With Acute Leukemia

    Science.gov (United States)

    Blackburn, Lisa; Achor, Sara; Allen, Betty; Bauchmire, Nicole; Dunnington, Danielle; Klisovic, Rebecca; Naber, Steven; Roblee, Kirsten; Samczak, Angela; Tomlinson-Pinkham, Kelly; Chipps, Esther

    2017-07-01

    To determine if the use of aromatherapy improves insomnia and other common symptoms in hospitalized patients with newly diagnosed acute leukemia. A randomized, crossover, washout trial. An inpatient acute leukemia unit at the Arthur G. James Cancer Hospital and Richard L. Solove Research Institute of the Wexner Medical Center at Ohio State University in Columbus. 50 patients who were newly diagnosed with acute leukemia and hospitalized to receive their initial four weeks of intensive induction chemotherapy. Patients were offered a choice of three scents to be used during the trial: lavender, peppermint, or chamomile. Each patient was randomized to receive either the chosen aromatherapy intervention or a placebo intervention during alternate weeks, with a washout period in between. Sleep quality and other common symptoms were measured. Aromatherapy, sleep, insomnia, pain, tiredness, drowsiness, nausea, lack of appetite, shortness of breath, depression, anxiety, and well-being. Most patients reported poor quality sleep at baseline, but aromatherapy had a statistically significant positive impact. Improvements were noted in tiredness, drowsiness, lack of appetite, depression, anxiety, and well-being because of aromatherapy. Aromatherapy is a viable intervention for improving insomnia and other symptoms commonly experienced by patients with acute leukemia. Oncology nurses can employ aromatherapy safely and inexpensively, and with minimal training, as an effective tool in decreasing many symptoms that plague patients with leukemia. Patients can exercise a greater sense of control over their treatment environments through the use of aromatherapy.

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

    Directory of Open Access Journals (Sweden)

    Chien-Yuan Chen

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

  2. [Study on cytogenetic changes with relation to FAB classification in 397 patients with acute leukemias].

    Science.gov (United States)

    Huo, Fei-Fei; Liu, Xin; Sun, Zi-Min; Zhu, Wei-Bo; Zheng, Chang-Cheng; Wang, Jian; Wu, Zhi-Wei

    2011-02-01

    The purpose of study was to investigate the cytogenetic abnormality of acute leukemias (AL), to analyze the relationship in the chromosomal abnormality and the AL FAB types, and to explore the impact of the chromosomal abnormalities on the prognostic factors of AL. The chromosome karyotypes of 397 patients with AL were analyzed by means of bone marrow short-term culture and G banding technique. The results showed that in 319 out of 397 patients, the chromosome karyotypes could be analyzed, and the chromosomal abnormality occurred in 175 patients (54.9%). In the patients with acute lymphocytic leukemia (ALL), acute myelogenous leukemia (AML) and acute mixed-lineage leukemia (AMLL), the chromosomal abnormality occurred respectively in 33 of 120 patients (27.5%), 129 of 252 patients (51.2%) and 13 of 25 patients (52.0%). Hyper-diploids, hypo-diploids and diploids occurred in 41 of 175 patients (23.4%), 22 of 175 patients (12.5%), and 112 of 175 patients (64.0%) respectively. In patients with AML the FAB type-associated chromosomal abnormality occurred in 69 of 129 patients (53.5%). It is concluded that chromosomal abnormalities exist in about 55% AL patients. Some special chromosomal abnormalities are cytogenetic characteristics of AL, and obviously correlated with AL FAB types, the combination of chromosomal detection with cytogenetics is useful for the diagnosis of AL, and the evaluation of therapeutic effects and prognosis.

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

    International Nuclear Information System (INIS)

    Eriksson, A; Österroos, A; Hassan, S; Gullbo, J; Rickardson, L; Jarvius, M; Nygren, P; Fryknäs, M; Höglund, M; Larsson, R

    2015-01-01

    To find drugs suitable for repositioning for use against leukemia, samples from patients with chronic lymphocytic, acute myeloid and lymphocytic leukemias as well as peripheral blood mononuclear cells (PBMC) were tested in response to 1266 compounds from the LOPAC 1280 library (Sigma). Twenty-five compounds were defined as hits with activity in all leukemia subgroups (<50% cell survival compared with control) at 10 μM drug concentration. Only one of these compounds, quinacrine, showed low activity in normal PBMCs and was therefore selected for further preclinical evaluation. Mining the NCI-60 and the NextBio databases demonstrated leukemia sensitivity and the ability of quinacrine to reverse myeloid leukemia gene expression. Mechanistic exploration was performed using the NextBio bioinformatic software using gene expression analysis of drug exposed acute myeloid leukemia cultures (HL-60) in the database. Analysis of gene enrichment and drug correlations revealed strong connections to ribosomal biogenesis nucleoli and translation initiation. The highest drug–drug correlation was to ellipticine, a known RNA polymerase I inhibitor. These results were validated by additional gene expression analysis performed in-house. Quinacrine induced early inhibition of protein synthesis supporting these predictions. The results suggest that quinacrine have repositioning potential for treatment of acute myeloid leukemia by targeting of ribosomal biogenesis

  4. HA-1 T TCR T Cell Immunotherapy for the Treating of Patients With Relapsed or Refractory Acute Leukemia After Donor Stem Cell Transplant

    Science.gov (United States)

    2018-03-26

    HLA-A*0201 HA-1 Positive Cells Present; Minimal Residual Disease; Recurrent Acute Biphenotypic Leukemia; Recurrent Acute Undifferentiated Leukemia; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Refractory Acute Myeloid Leukemia; Refractory Adult Acute Lymphoblastic Leukemia; Refractory Childhood Acute Lymphoblastic Leukemia

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

    International Nuclear Information System (INIS)

    Kim, Min Sung; Jee, Won Hee; Kim, Sun Ki; Lee, So Yeon; Lim, Gye Yeon; Park, Gyeong Sin; Lee, Seok

    2010-01-01

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

  6. Acute Lymphoblastic Leukemia in Two Patients with β-Thalassemia Major

    OpenAIRE

    Majid Naderi; Ebrahim Miri-Moghaddam; Shaban Alizadeh; Akbar Dorgalaleh; Shadi Tabibian

    2014-01-01

    Occurrence of leukemia in thalassemia major is a rare presentation. Here we report two cases of thalassemic patients, developing acute lymphoblastic leukemia. The genetic analysis revealed that, female and male patients were homozygous for IVSI-6 and IVSI-5, respectively. Two years ago the female patient presented by a high leukocyte count (154,000 µL) and male one also presented by 80,000 WBC/µL count 1 year ago. Microscopic examination of both patients revealed lymphoblasts that morphologic...

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

    Science.gov (United States)

    2017-07-18

    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

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

    Science.gov (United States)

    2017-06-27

    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 Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Recurrent Adult Acute Myeloid Leukemia

  9. MEK Inhibitor MEK162, Idarubicin, and Cytarabine in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia

    Science.gov (United States)

    2017-12-04

    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 Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Recurrent Adult Acute Myeloid Leukemia

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

    Directory of Open Access Journals (Sweden)

    Vali A Mehrzad

    2012-01-01

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

  11. Bloodstream infections in pediatric patients with acute leukemia: Emphasis on gram-negative bacteria infections.

    Science.gov (United States)

    Kuo, Fu-Chun; Wang, Shih-Min; Shen, Ching-Fen; Ma, Yun-Ju; Ho, Tzong-Shiann; Chen, Jiann-Shiuh; Cheng, Chao-Neng; Liu, Ching-Chuan

    2017-08-01

    Acute leukemia is the most common pediatric hematological malignancy. Bloodstream infections (BSIs) are severe complications in these patients during chemotherapy. This study aims to explore clinical features, laboratory, and microbiological characteristics of BSIs in acute leukemic children. Patients aged leukemia or acute lymphocytic leukemia with BSIs from January 2004 to December 2013 were enrolled. BSIs was defined as positive isolate(s) of blood culture and associated with clinical findings. Clinical presentations, demographic features, and microbiological findings were retrospectively reviewed. In total, 126 isolates of 115 episodes of BSIs were identified from 69 patients (acute lymphocytic leukemia 56; acute myeloid leukemia 13). Gram-negative bacteria (GNB), gram-positive cocci, and fungi constituted 56.3%, 42.3%, and 2.4% of the pathogens, respectively. Eighty-three and a half percent of BSIs occurred along with neutropenia, and 73% had severe neutropenia. GNB was the leading pathogen of BSIs. The major GNBs were Escherichia coli, Klebsiella pneumonia, and Pseudomonas aeruginosa. White blood cell counts, absolute neutrophil counts, and platelet counts were significantly lower in patients of BSIs caused by GNB than gram-positive cocci. Plasma level of C-reactive protein was significant high in patients of GNB BSIs (179.8 mg/L vs. 127.2 mg/L; p = 0.005). Eighty-two percent of patients of E. coli, K. pneumonia, and P. aeruginosa BSIs had sepsis related organ failure or organ dysfunction. P. aeruginosa BSIs had the highest case-mortality (40%). Neutropenia was the major risk factor of BSIs in pediatric leukemic patients. BSIs of GNB were associated with severe neutropenia, systemic inflammatory responses, and high mortality. Copyright © 2015. Published by Elsevier B.V.

  12. Cytomegalovirus induced hemophagocytic lymphocytic histiocytosis in two pediatric patients with acute lymphoblastic leukemia

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    Benjamin Waddell

    2017-01-01

    Full Text Available Hemophagocytic lymphohistiocytosis (HLH is a rare inflammatory condition with tissue destruction due to abnormal immune activation. We present a series of 2 cases of cytomegalovirus-induced HLH in children during maintenance chemotherapy for acute lymphoblastic leukemia. These cases emphasize the importance of considering secondary HLH in this high-risk subset of pediatric patients.

  13. Cytomegalovirus induced hemophagocytic lymphocytic histiocytosis in two pediatric patients with acute lymphoblastic leukemia.

    Science.gov (United States)

    Waddell, Benjamin; Belcher, Chris; Willey, Emily

    2017-01-01

    Hemophagocytic lymphohistiocytosis (HLH) is a rare inflammatory condition with tissue destruction due to abnormal immune activation. We present a series of 2 cases of cytomegalovirus-induced HLH in children during maintenance chemotherapy for acute lymphoblastic leukemia. These cases emphasize the importance of considering secondary HLH in this high-risk subset of pediatric patients.

  14. Aspergillus vegetative endocarditis and complete heart block in a patient with acute leukemia.

    Science.gov (United States)

    Mikulski, S M; Love, L J; Bergquist, E J; Hargadon, M T; Applefeld, M M; Mergner, W

    1979-10-01

    Aspergillus flavus vegetative endocarditis together with myocardial abscesses and pneumonitis developed in a patient with acute lymphocytic leukemia. The initial diagnosis was not suspected until 67gallium imaging revealed a radiographically undetectable thoracic abnormality. Despite apparently "early" diagnosis, antifungal therapy was inadequate to prevent disruption of the bundle of His, complete heart block and death.

  15. One hundred patients with acute leukemia treated by chemotherapy, total body irradiation, and allogeneic marrow transplantation

    International Nuclear Information System (INIS)

    Thomas, E.D.; Buckner, C.D.; Banaji, M.

    1977-01-01

    One hundred patients, 54 with acute myelogenous leukemia (AML) and 46 with acute lymphoblastic leukemia (ALL), considered to be in the end stages of their disease, after combination chemotherapy were treated by marrow transplantation. All patients were given a marrow graft from an HLA-identical sibling after receiving 1000-rad total body irradiation (TBI). One group of 43 patients was given cyclophosphamide (CY), 60 mg/kg on each of 2 days, 5 and 4 days before TBI. In a second group of 31 patients, additional chemotherapy was given before CY and TBI. In a third group of 19 patients, BCNU was given before CY and TBI. A fourth group of 7 patients received other chemotherapy regimens before TBI. Six patients died 3 to 17 days after marrow infusion without evidence of engraftment. Ninety-four patients were engrafted rejected and only one patient rejected the graft. Thirteen patients are alive with a marrow graft, on no maintenance antileukemic therapy, and without recurrent leukemia 1--4 1 / 2 yr after transplantation. Three have chronic graft-versus-host disease (GVHD). The relapse rate appeared to be relatively constant over the first 2 yr and was extremely low after that time. Neither survival nor leukemic relapse appeared to be influenced by the type of leukemia nor by the preparative chemotherapy regimen given before TBI. Patients in fair clinical condition at the time of transplantation showed significantly longer survival times than patients in poor condition (p = 0.001). This observation, coupled with the observation that some patients may be cured of their disease, indicates that marrow transplantation should now be undertaken earlier in the management of patients with acute leukemia who have an HLA-matched sibling marrow donor

  16. Relationship between the general condition of acute lymphoblastic leukemia patients with remission rate and convulsion as an adverse effect chemotherapy

    Directory of Open Access Journals (Sweden)

    Rusdi Andid

    2017-02-01

    Full Text Available A retrospective study on the relationship between the general condition of acute lymphoblastic leukemia patients with remission rale and convulsion as an adverse effect of chemotherapy was conducted in leukemia patients of the hematology-oncology subdivision, Departmenl of Child Health, Medical School, University of North Sumatra, Medan. Of 114 children with acute lymphoblastic leukemia, 81 (71.05% received chemotherapy, 31 patients among them was in good general condition. Remission rate of the 31 patients was 80.6% (25 children. Whereas in the remaining 50 patients, the remission rate among them was 84% (42 patients. There was no significant relationship between their general condition to the recurrence rate of acute lymphoblastic leukemia patients who had been administered chemotherapy during induction phase. Convulsion was found In 2 cases, due to CNS leukemia.

  17. Impact of ABO incompatibility on patients' outcome after haploidentical hematopoietic stem cell transplantation for acute myeloid leukemia - a report from the Acute Leukemia Working Party of the EBMT.

    Science.gov (United States)

    Canaani, Jonathan; Savani, Bipin N; Labopin, Myriam; Huang, Xiao-Jun; Ciceri, Fabio; Arcese, William; Tischer, Johanna; Koc, Yener; Bruno, Benedetto; Gülbas, Zafer; Blaise, Didier; Maertens, Johan; Ehninger, Gerhard; Mohty, Mohamad; Nagler, Arnon

    2017-06-01

    A significant proportion of hematopoietic stem cell transplants are performed with ABO-mismatched donors. The impact of ABO mismatch on outcome following transplantation remains controversial and there are no published data regarding the impact of ABO mismatch in acute myeloid leukemia patients receiving haploidentical transplants. Using the European Blood and Marrow Transplant Acute Leukemia Working Group registry we identified 837 patients who underwent haploidentical transplantation. Comparative analysis was performed between patients who received ABO-matched versus ABO-mismatched haploidentical transplants for common clinical outcome variables. Our cohort consisted of 522 ABO-matched patients and 315 ABO-mismatched patients including 150 with minor, 127 with major, and 38 with bi-directional ABO mismatching. There were no significant differences between ABO matched and mismatched patients in terms of baseline disease and clinical characteristics. Major ABO mismatching was associated with inferior day 100 engraftment rate whereas multivariate analysis showed that bi-directional mismatching was associated with increased risk of grade II-IV acute graft- versus -host disease [hazard ratio (HR) 2.387; 95% confidence interval (CI): 1.22-4.66; P =0.01). Non-relapse mortality, relapse incidence, leukemia-free survival, overall survival, and chronic graft- versus -host disease rates were comparable between ABO-matched and -mismatched patients. Focused analysis on stem cell source showed that patients with minor mismatching transplanted with bone marrow grafts experienced increased grade II-IV acute graft- versus -host disease rates (HR 2.03; 95% CI: 1.00-4.10; P =0.04). Patients with major ABO mismatching and bone marrow grafts had decreased survival (HR=1.82; CI 95%: 1.048 - 3.18; P =0.033). In conclusion, ABO incompatibility has a marginal but significant clinical effect in acute myeloid leukemia patients undergoing haploidentical transplantation. Copyright© Ferrata

  18. [Abnormality of blood coagulation indexes in patients with de novo acute leukemia and its clinical significance].

    Science.gov (United States)

    Xiao, Fang-Fang; Hu, Kai-Xun; Guo, Mei; Qiao, Jian-Hui; Sun, Qi-Yun; Ai, Hui-Sheng; Yu, Chang-Lin

    2013-04-01

    To explore hemorrhage risk and the clinical significance of abnormal change of prothrombin time (PT), activated partial thromboplastin time (APTT), plasma fibrinogen (FIB), plasma thrombin time (TT) and d-dimer (D-D) in de novo acute leukemia (except for APL), the different bleeding manifestations of 114 cases of de novo acute leukemia with different coagulation indexes were analyzed retrospectively. The correlation between these blood coagulation indexes and the possible correlative clinical characteristics were analysed, including age, sex, type of acute leukemia, initial white blood cell(WBC) and platelet(Plt) count, the proportion of blast cells in bone marrow and cytogenetic abnormality of patients at diagnosis. The results indicated that the incidence of abnormal blood coagulation was as high as 78.1% for de novo AL patients. These patients with 5 normal blood coagulation indexes may have mild bleeding manifestation, but the more abnormal indexes, the more severe bleeding. Both PT and D-D were sensitive indexes for diagnosis of level II bleeding. Incidence of abnormal blood coagulation significantly correlates with the proportion of blast cells in bone marrow (χ(2) = 4.184, OR = 1.021, P coagulation. It is concluded that the coagulation and fibrinolysis are abnormal in most patients with de novo acute leukemia. More abnormal indexes indicate more severe bleeding, and both PT and D-D are sensitive indexes for diagnosis of level II bleeding. Higher proportion of blast cells in bone marrow predicts higher incidence of abnormal blood clotting. Acute leukemia with elderly age, high white blood cell count and adverse cytogenetics do not predict severer abnormal blood clotting. Detection of PT, APTT, TT, FIB, and D-D may help to judge whether the patients are in a state of hypercoagulability or disseminated intravenous coagulation, which will provide experiment evidences for early intervention and medication.

  19. Genetics Home Reference: acute promyelocytic leukemia

    Science.gov (United States)

    ... Home Health Conditions Acute promyelocytic leukemia Acute promyelocytic leukemia Printable PDF Open All Close All Enable Javascript ... view the expand/collapse boxes. Description Acute promyelocytic leukemia is a form of acute myeloid leukemia, a ...

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

    Directory of Open Access Journals (Sweden)

    Škiljević Dušan

    2008-01-01

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

  1. Acute Activation of Metabolic Syndrome Components in Pediatric Acute Lymphoblastic Leukemia Patients Treated with Dexamethasone

    NARCIS (Netherlands)

    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

  2. [Clinical and biological prognostic factors in relapsed acute myeloid leukemia patients].

    Science.gov (United States)

    Yébenes-Ramírez, Manuel; Serrano, Josefina; Martínez-Losada, Carmen; Sánchez-García, Joaquín

    2016-09-02

    Acute myeloid leukemia (AML) is the most frequent type of acute leukemia in adults. Despite recent advances in the characterization of pathogenesis of AML, the cure rates are under 40%, being leukemia relapse the most common cause of treatment failure. Leukaemia relapse occurs due to clonal evolution or clonal escape. In this study, we aimed to analyze the clinical and biological factors influencing outcomes in patients with AML relapse. We included a total of 75 AML patients who experienced leukaemia relapse after achieving complete remission. We performed complete immunophenotyping and conventional karyotyping in bone marrow aspirates obtained at diagnosis and at leukemia relapse. Overall survival (OS) of the series was 3.7%±2.3, leukaemia progression being the most common cause of death. Patients relapsing before 12 months and those with adverse cytogenetic-molecular risk had statistically significant worse outcomes. A percentage of 52.5 of patients showed phenotypic changes and 50% cytogenetic changes at relapse. We did not find significant clinical factors predicting clonal evolution. The presence of clonal evolution at relapse did not have a significant impact on outcome. Patients with relapsed AML have a dismal prognosis, especially those with early relapse and adverse cytogenetic-molecular risk. Clonal evolution with phenotypic and cytogenetic changes occurred in half of the patients without predictive clinical factors or impact on outcome. Copyright © 2016 Elsevier España, S.L.U. All rights reserved.

  3. The Danish National Acute Leukemia Registry

    DEFF Research Database (Denmark)

    Østgård, Lene Sofie Granfeldt; Nørgaard, Jan Maxwell; Raaschou-Jensen, Klas Kræsten

    2016-01-01

    AIM OF DATABASE: The main aim of the Danish National Acute Leukemia Registry (DNLR) was to obtain information about the epidemiology of the hematologic cancers acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), and myelodysplastic syndrome (MDS). STUDY POPULATION: The registry...... was established in January 2000 by the Danish Acute Leukemia Group and has been expanded over the years. It includes adult AML patients diagnosed in Denmark since 2000, ALL patients diagnosed since 2005, and MDS patients diagnosed since 2010. The coverage of leukemia patients exceeds 99%, and the coverage of MDS...... years. To ensure this high coverage, completeness, and quality of data, linkage to the Danish Civil Registration System and the Danish National Registry of Patients, and several programmed data entry checks are used. CONCLUSION: The completeness and positive predictive values of the leukemia data have...

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

    DEFF Research Database (Denmark)

    Jarden, Mary; Møller, Tom; Kjeldsen, Lars

    2013-01-01

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

  5. CRUSTED SCABIES IN A PATIENT WITH ACUTE LYMPHOCYTIC LEUKEMIA

    Directory of Open Access Journals (Sweden)

    Mamatha

    2015-06-01

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

  6. Phase 2 study of the JAK kinase inhibitor ruxolitinib in patients with refractory leukemias, including postmyeloproliferative neoplasm acute myeloid leukemia.

    Science.gov (United States)

    Eghtedar, Alireza; Verstovsek, Srdan; Estrov, Zeev; Burger, Jan; Cortes, Jorge; Bivins, Carol; Faderl, Stefan; Ferrajoli, Alessandra; Borthakur, Gautam; George, Solly; Scherle, Peggy A; Newton, Robert C; Kantarjian, Hagop M; Ravandi, Farhad

    2012-05-17

    We conducted a phase 2 study of ruxolitinib in patients with relapsed/refractory leukemias. Patients with acceptable performance status (0-2), adequate organ function, and no active infection, received ruxolitinib 25 mg orally twice a day for 4 weeks (1 cycle). Response was assessed after every 2 cycles of treatment, and patients who completed 2 cycles were allowed to continue treatment until disease progression. Dose escalation to 50 mg twice daily was permitted in patients demonstrating a benefit. Thirty-eight patients, with a median age of 69 years (range, 45-88), were treated. The median number of prior therapies was 2 (range, 1-6). Twelve patients had JAK2V617F mutation. Patients received a median of 2 cycles of therapy (range, 1-22). Three of 18 patients with postmyeloproliferative neoplasm (MPN) acute myeloid leukemia (AML) showed a significant response; 2 achieved complete remission (CR) and one achieved a CR with insufficient recovery of blood counts (CRi). The responding patients with palpable spleens also had significant reductions in spleen size. Overall, ruxolitinib was very well tolerated with only 4 patients having grade 3 or higher toxicity. Ruxolitinib has modest antileukemic activity as a single agent, particularly in patients with post-MPN AML. The study was registered at www.clinicaltrials.gov as NCT00674479.

  7. Cytarabine and daunorubicin or idarubicin in induction therapy of Acute Myeloid Leukemia patients

    International Nuclear Information System (INIS)

    Eivazi-Ziaei, J.; Kermani, I.A.; Nikanfar, A.; Maljaie, H.; Mahmoudpour, A.; Dolatkhah, R.

    2010-01-01

    Objectives: Acute myeloid leukemia (AML), the most common form of acute leukemia, is treated by remission induction and post-remission therapy. Remission induction is usually achieved by administration of cytarabine along with an anthracycline such as Daunorubicin (DAU) or Idarubicin (IDA). Our objective was see the benefits if any of IDA over DAU in AML therapy. Methodology: Eighty adult AML patients were enrolled in this study, where 40 received DAU and 40 were treated with IDA. Remission status in each subject was studied and response to therapy was subsequently analyzed using SPSS. Results: Complete remission, partial remission and no responsive status were 15, 19, and 14 respectively for patients on DAU and 14, 18, and 11 for patients on IDA protocol. No significant benefit was detected for IDA compared to DAU in response to therapy. Conclusion: We found no benefit in using IDA over DAU in induction therapy for AML patients treated in northwest of Iran. (author)

  8. Frequency of fab subtypes in acute myeloid leukemia patients at Aga Khan University Hospital Karachi.

    Science.gov (United States)

    Harani, Mahadev S; Adil, Salman Naseem; Shaikh, Mohammad Usman; Kakepoto, Ghulam Nabi; Khurshid, Mohammmad

    2005-01-01

    Acute myeloid leukemia (AML) is a heterogeneous disease. Therefore, various parameters are needed to classify this disease into subtypes, so that specific treatment approaches can be utilized effectively. The commonly used method for diagnosis and classification is based on FAB criteria using morphology and cytochemical stains. For some of the categories, immunophenotyping is necessary. The aim of present study is to determine the frequency of various sub types in acute myeloid leukemia using FAB criteria in our population. This will aid in the correct diagnosis of acute leukemia and hence proper management of the patients. This is descriptive case control study conducted at Aga Khan University Hospital from January 1999 to December 2000. The total number of subjects was 116 that included both adults and children. The patients were diagnosed on the basis of bone marrow morphology using FAB classification. Cytochemistry was done in all cases, while immunophenotyping was considered only in those cases that were found to be problematic. Among 116 patients, 70 were males and 46 were females with male to female ratio 1.5:1. The age ranged between 6 months to 85 years with a mean age of 32 years. AML-M4 was the predominant French-American-British (FAB) subtype (36.2%) followed by M2 (30.25%), M3 (10.4%), M1 (8.7%), M0 (7.7%), M5a (3.5%), M5b (2.5%) and M6 (0.8%). The most common FAB subtype observed in our study was Acute myelomonocytic leukemia (M4) which is in accordance with studies reported from Saudia Arabia and a previous study reported from our institution. However,other national and international studies have reported Myeloblastic Leukemia with maturation (M2) as the predominant subtype of AML.

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

    OpenAIRE

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

    2015-01-01

    Abstract To assess the self-esteem of pediatric patients on chemotherapy for acute lymphoblastic leukemia (ALL) and psychological status of their parents. The psychological status of 178 children receiving chemotherapy for ALL and their parents was assessed using parenting stress index (PSI) to determine the degree of stress the parents are exposed to using parent's and child's domains. Self-esteem Scale was used to determine the psychological status of patients. The study revealed significan...

  10. acute leukemias immunophenotypes at agakhan university hospital ...

    African Journals Online (AJOL)

    2013-02-01

    Feb 1, 2013 ... specimens from patients suspected to have acute leukemia were analysed for cytomorphological characteristics ... Conclusion: Immunophenotyping of acute leukemia is beneficial in accurate diagnosis of patients with these ..... AML-M2 in both pediatric and adult population in. India(15). The proportion of ...

  11. Clinical Characteristics of Bloodstream Infections in Pediatric Acute Leukemia: A Single-center Experience with 231 Patients

    Directory of Open Access Journals (Sweden)

    Jia-Feng Yao

    2017-01-01

    Conclusions: Gram-negative bacteria were the main pathogenic bacteria in patients with acute leukemia in our center. NR primary illness, agranulocytosis, and drug-resistant pathogenic bacteria were all risk factors for poor prognosis.

  12. Targeted Therapies in Hematology and Their Impact on Patient Care: Chronic and Acute Myeloid Leukemia

    Science.gov (United States)

    Cortes, Elias Jabbour Jorge; Ravandi, Farhad; O’Brien, Susan; Kantarjian, Hagop

    2014-01-01

    Advances in the genetic and molecular characterizations of leukemias have enhanced our capabilities to develop targeted therapies. The most dramatic examples of targeted therapy in cancer to date are the use of targeted BCR-ABL protein tyrosine kinase inhibitors (TKI) which has revolutionized the treatment of chronic myeloid leukemia (CML). Inhibition of the signaling activity of this kinase has proved to be a highly successful treatment target, transforming the prognosis of patients with CML. In contrast, acute myeloid leukemia (AML) is an extremely heterogeneous disease with outcomes that vary widely according to subtype of the disease. Targeted therapy with monoclonal antibodies and small molecule kinase inhibitors are promising strategies to help improve the cure rates in AML. In this review, we will highlight the results of recent clinical trials in which outcomes of CML and AML have been influenced significantly. Also, novel approaches to sequencing and combining available therapies will be covered. PMID:24246694

  13. MEK inhibition is a promising therapeutic strategy for MLL-rearranged infant acute lymphoblastic leukemia patients carrying RAS mutations

    NARCIS (Netherlands)

    Kerstjens, M. (Mark); E.M.C. Driessen; M. Willekes (Merel); Pinhanços, S.S. (Sandra S.); P. Schneider (Pauline); R. Pieters (Rob); R.W. Stam (Ronald)

    2017-01-01

    textabstractAcute lymphoblastic leukemia (ALL) in infants is an aggressive malignancy with a poor clinical outcome, and is characterized by translocations of the Mixed Lineage Leukemia (MLL) gene. Previously, we identified RAS mutations in 14-24% of infant ALL patients, and showed that the presence

  14. Managing acute promyelocytic leukemia in patients belonging to the Jehovah’s Witness congregation

    Directory of Open Access Journals (Sweden)

    Anand P. Jillella

    2017-09-01

    Full Text Available Acute promyelocytic leukemia (APL is a hyper-acute leukemia and presents with cytopenias and disseminated intravascular coagulation. Jehovah’s Witnesses with APL offer a unique challenge during induction by refusing transfusion and pose a difficult challenge in this curable disease. Our focus over the last 8 years has been decreasing early deaths in APL in both academic and community centers. As a result we have extensive experience in APL induction with a proven improvement in early deaths. Three patients with APL belonging to the Jehovah’s Witness congregation were treated in our practice and published literature in treating Witnesses with APL was reviewed. It is highly imperative to prevent induction mortality in this patient population. The goal of treatment among the Witnesses is to prevent death during induction and subsequently cure them. We discuss the management and proactive measures to prevent induction mortality in this most curable blood cancer.

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

    International Nuclear Information System (INIS)

    Vizcaino Valderrama, Martha; Suarez Mattos, Amaranto; Hernandez Kunzel, Jorge Alberto; Restrepo, Alexandra

    2002-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Kakucs Enikő

    2013-04-01

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

  17. An analysis of 1690 patients from the acute leukemia working party of EBMT

    OpenAIRE

    Canaani, Jonathan; Beohou, Eric; Labopin, Myriam; Socie, Gerard; Huynh, Anne; Volin, Liisa; Cornelissen, Jan; Milpied, Noel; Gedde-Dahl, Tobias; Deconinck, Eric; Fegueux, Nathalie; Blaise, Didier; Mohty, Mohamad; Nagler, Arnon

    2017-01-01

    The French, American, and British (FAB) classification system for acute myeloid leukemia (AML) is extensively used and is incorporated into the AML, not otherwise specified (NOS) category in the 2016 WHO edition of myeloid neoplasm classification. While recent data proposes that FAB classification does not provide additional prognostic information for patients for whom NPM1 status is available, it is unknown whether FAB still retains a current prognostic role in predicting outcome of AML pati...

  18. [Acute myeloid Leukemia].

    Science.gov (United States)

    Braess, Jan

    2016-11-01

    Acute myeloid leukemia (AML) has been genetically characterized extensively and can now be subdivided into 9 to 11 pathogenetically different subtypes according to their profile of driver mutations. In clinical practice karyotyping and molecular analysis of NPM1, cEBPa and FLT3-ITD are required for treatment stratification and potentially genotype specific treatment. Some markers such as NPM1 not only offer prognostic information but can also serve as markers of minimal residual disease and thus have the potential to guide therapy in the future.The basis of curative treatment is intensive combination chemotherapy comprizing cytarabine and an anthracycline ("7 + 3" regimen). The prolonged duration of aplasia can be reduced significantly by accelerated therapy ("S-HAM" regimen). Following achievement of a complete remission patients with a low risk of relapse - based on genetic and clinical features - receive chemotherapy based consolidation therapy whereas high risk patients - and potentially also those with an intermediate risk - receive an allogeneic stem cell transplantation. Whereas adding the rather unspecific tyrosinekinase inhibitor sorafenib to standard treatment in unselected AML patients has not improved overall survival (OS), the addition of midostaurin to standard therapy in the selected group FLT3 mutated patients has resulted in a moderate but significant OS benefit.Real world data show that in patients below 50 years a cure rate of ca. 50 % can be achieved. However less than 10 % of patients above the age of 70 will be alive after five years even after intensive treatment. Therefore when curative and intensive treatment is deemed impossible the therapeutic standard in elderly and unfit patients used to be low-dose cytarabine with an average OS of 4 months. This has now been replaced by a new standard of care of hypomethylating agents - azacytidine and decitabine - which both achieve higher remission rates and show strong trends towards a prolonged OS

  19. Prognostic Value of a CYP2B6 Gene Polymorphism in Patients with Acute Myeloid Leukemia.

    Science.gov (United States)

    Alazhary, Nevin M; Shafik, Roxan E; Shafik, Hanan E; Kamel, Mahmoud M

    2015-01-01

    The objectives of this study aimed to detect a CYP2B6 polymorphism in de novo cases of acute myeloid leukemia patients and identify any role in disease progression and outcome. DNA was isolated from peripheral blood of 82 newly diagnosed acute myeloid leukemia cases and the CYP2B6 G15631T gene polymorphism was assayed by PCR restriction fragment length polymorphism (PCR-RFLP). The frequency of the GG genotype (wild type) was 48 (58.5%) and that of the mutant type T allele was 34 (41.9%). GT genotype heterozygous variants were found in 28 (34%), and TT genotype homozygous variants in 6 (7.3%) cases. We found no significant association between the CYP2B6 G15631T polymorphism and complete response (CR) (p-value=0.768), FAB classification (p-value=0.51), cytogenetic analysis (p-value=0.673), and overall survival (p-value=0.325). Also, there were no significant links with early toxic death (p-value=0.92) or progression- free survival (PFS) (p-value=0.245). Our results suggest that the CYP2B6 polymorphism has no role in disease progression, therapeutic outcome, patient free survival, early toxic death and overall survival in acute myeloid leukemia patients.

  20. [Role of Dynamic Monitoring Chromosome Karyotypes for Evaluation of Chemotherapy Efficacy in Patients with Acute Leukemia].

    Science.gov (United States)

    Liu, Yan-Chun; Li, Wei; Wang, Huan; Chen, Xi; Li, Jun; Chai, Tie

    2015-06-01

    To explore the role of dynamic monitoring the karyotype changes for evaluation of chemotherapy efficacy in patients with acute leukemia. A total of 80 patients with acute leukemia were collected and according to FAB classification standards they were divided into 65 cases of acute myeloid leukemia (AML) and 15 cases of acute lymphoblastic leukemia (ALL); R banding technique was used taken to detect their chromosome and to analyze the relationship between chromosome and efficacy of chemotherapy. Out of 65 cases of AML, 31 cases showed abnormal karyotypes and their aberration rate was 47.7%; among 31 cases of AML with chromosome abnormalities, the t (15; 17) was found in 9 cases and they accounted for 29%; t (8; 21) was found in 7 cases and they accounted for 22.6%; other karyotype and complex karyotypes were found in 15 cases and they accounted for 48.4%; the remission rate of t (15; 17) group was 88.9%, remission rate of t (8; 21) group was 71.4%, remission rate of other karyotype group was 66.7%. The comparison of between different groups showed that remission rate of t (15; 17) group was significantly higher than that in T (8; 21) group, other karyotype group and normal karyotype group (χ2=9.625,14.267,7.768, P0.05). In 15 cases of ALL, 8 cases with normal karyotype accounted for 53.3%, 7 cases with abnormal karyotype accounted for 46.7% of ALL; as compared with AML, no significant difference was shown (χ2=0.020, P>0.05); the remission rates of patients with normal karyotype and abnormal karyotype were 87.5% and 42.9% respectively, the difference between the two groups had statistical significance (χ2=43.834, Pleukemia.

  1. Impact of Aberrant Antigens in the Outcome of Patients with Acute Leukemia at a Referral Institution in Mexico City.

    Science.gov (United States)

    Rodríguez-Rodríguez, Sergio; Pomerantz, Alan; Demichelis-Gómez, Roberta; Barrera-Lumbreras, Georgina; Barrales-Benítez, Olga V; Lopez-Karpovitch, Xavier; Aguayo, Álvaro

    2016-01-01

    Patients with acute leukemia can express aberrant markers, defined as antigens that are normally restricted to a different lineage. The reported significance and frequency of these markers is inconclusive. We assessed the frequency and impact of aberrant markers in patients with acute leukemia in a referral institution in Mexico City. We included 433 patients, diagnosed and treated between 2005 and 2015 in our institution. Aberrant markers were expressed in 128 patients (29.6%); CD13 and CD33 were the most frequent aberrant markers in patients with acute lymphoblastic leukemia, while CD7 and CD19 were the most frequent in patients with acute myeloid leukemia. In the univariate analysis, the group with aberrant markers had a lower disease-free survival when compared with the aberrant-free group (8 vs. 13 months) (p = 0.03). Aberrant expression of CD10, CD20, and CD33 correlated with a worse outcome in a statistically significant manner. In the multivariate analysis, male gender, lymphoid lineage, secondary leukemia, high risk at diagnosis, and the presence of aberrant markers had a significantly negative impact on disease-free survival. The use of more aggressive treatment strategies could be considered in patients with acute leukemia and an aberrant expression of CD10, CD20, and CD33.

  2. Acute leukemia in early childhood

    Directory of Open Access Journals (Sweden)

    M. Emerenciano

    2007-06-01

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

  3. Extramedullary leukemia in children with acute myeloid leukemia

    DEFF Research Database (Denmark)

    Støve, Heidi Kristine; Sandahl, Julie Damgaard; Abrahamsson, Jonas

    2017-01-01

    BACKGROUND: The prognostic significance of extramedullary leukemia (EML) in childhood acute myeloid leukemia is not clarified. PROCEDURE: This population-based study included 315 children from the NOPHO-AML 2004 trial. RESULTS: At diagnosis, 73 (23%) patients had EML: 39 (12%) had myeloid sarcoma...

  4. Acute acalculous cholecystitis complicating chemotherapy for acute myeloblastic leukemia

    Directory of Open Access Journals (Sweden)

    Olfa Kassar

    2015-01-01

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

  5. Intensive induction is effective in selected octogenarian acute myeloid leukemia patients: prognostic significance of karyotype and selected molecular markers used in the European LeukemiaNet classification.

    Science.gov (United States)

    Wetzler, Meir; Mrózek, Krzysztof; Kohlschmidt, Jessica; Dombret, Hervé; Döhner, Hartmut; Pilorge, Sylvain; Krug, Utz; Carroll, Andrew J; Larson, Richard A; Marcucci, Guido; Hiddemann, Wolfgang; Büchner, Thomas; Bloomfield, Clara D

    2014-02-01

    We investigated whether octogenarian patients with acute myeloid leukemia enrolled onto Cooperative Group clinical trials and treated with intensive induction therapy could be cured, and whether karyotype and selected molecular markers had any prognostic significance in these patients. Among 138 patients with cytogenetic information, normal karyotype was the most common (47.1%) followed by complex karyotype (14.5%) and sole +8 (9.4%). Among these patients, the relapse-free survival rate at 1 year was 37% and 13% at 3 years, and the respective overall survival rates were 24% and 8%. Whereas the 90 patients who survived beyond 30 days had the same relapse-free survival rates, their 1-year and 3-year overall survival rates were 36% and 11%, respectively. Of the 66 patients surviving beyond 30 days who could be classified into European LeukemiaNet genetic groups, those in the intermediate-I group had better overall survival than patients in the adverse group (P=0.01). Among patients with cytogenetically normal acute myeloid leukemia who were tested for the European LeukemiaNet-associated molecular alterations, FLT3-internal tandem duplication and NPM1 mutations, it was found that FLT3-internal tandem duplication (detected in 29% of patients) did not associate with overall survival (P=0.31), whereas NPM1 mutations (30%) were associated with a significantly longer overall survival (P=0.002). We conclude that intensive induction is effective and indicated in selected octogenarians with acute myeloid leukemia, that their overall survival varies among the European LeukemiaNet genetic groups and that NPM1 mutations may be of prognostic significance among octogenarian patients with cytogenetically normal acute myeloid leukemia.

  6. Red cells with paroxysmal nocturnal hemoglobinuria-phenotype in patients with acute leukemia.

    Science.gov (United States)

    Meletis, John; Terpos, Evangelos; Samarkos, Michalis; Meletis, Christos; Apostolidou, Effie; Komninaka, Veroniki; Anargyrou, Konstantinos; Korovesis, Konstantinos; Mavrogianni, Despina; Variami, Eleni; Viniou, Nora; Konstantopoulos, Konstantinos

    2002-04-01

    CD55 and CD59 are complement regulatory proteins that are linked to the cell membrane via a glycosyl-phosphatidylinositol anchor. They are reduced mainly in paroxysmal nocturnal hemoglobinuria (PNH) and in other hematological disorders. However, there are very few reports in the literature concerning their expression in patients with acute leukemias (AL). We studied the CD55 and CD59 expression in 88 newly diagnosed patients with AL [65 with acute non-lymphoblastic leukemia (ANLL) and 23 with acute lymphoblastic leukemia (ALL)] using the sephacryl gel test, the Ham and sucrose lysis tests and we compared the results with patients' clinical data and disease course. Eight patients with PNH were also studied as controls. Red cell populations deficient in both CD55 and CD59 were detected in 23% of ANLL patients (especially of M(0), M(2) and M(6) FAB subtypes), 13% of ALL and in all PNH patients. CD55-deficient erythrocytes were found in 6 ANLL patients while the expression of CD59 was decreased in only 3 patients with ANLL. No ALL patient had an isolated deficiency of these antigens. There was no correlation between the existence of CD55 and/or CD59 deficiency and the percentage of bone marrow infiltration, karyotype or response to treatment. However no patient with M(3), M(5), M(7) subtype of ANLL and mature B- or T-cell ALL showed a reduced expression of both antigens. The deficient populations showed no alteration after chemotherapy treatment or during disease course. This study provides evidence about the lower expression of CD55 and CD59 in some AL patients and the correlation with their clinical data. The possible mechanisms and the significance of this phenotype are discussed.

  7. An unusual case of acute leukemia.

    Science.gov (United States)

    Fleury, Carole; Passet, Marie; Settegrana, Catherine; Simon, Laurence; Chapiro, Elise; Trinquand, Amélie; Safra Zaghouani, Ines; Uzunov, Madalina; Le Garff-Tavernier, Magali; Armand, Marine; Costopoulos, Myrto

    2017-06-01

    We report the case of a 31 year-old man diagnosed with an atypical acute leukemia difficult to characterize cytologically. The immunophenotyping identified a blastic population co-expressing myeloid, lymphoid B and lymphoid T markers suggesting the diagnosis of either a mixed phenotype acute leukemia (MPAL) or an early T-cell precursor acute lymphoblastic leukemia (ETP-ALL). Because of the poor prognosis linked to these leukemias, the patient benefited from chemotherapy targeting both myeloid and lymphoid components, followed by allogeneic hematopoietic stem cell transplantation. DNA-based techniques analyzing B and T-cell clonality identified partial rearrangements in immunoglobulin and TCR genes, allowing the monitoring of minimal residual disease. This observation highlights the difficulty to classify some atypical cases of acute leukemias. It emphasizes on the complementarity of cytomorphology, immunophenotyping by flow cytometry and molecular techniques in order to promptly characterize and treat these leukemias.

  8. The mutational oncoprint of recurrent cytogenetic abnormalities in adult patients with de novo acute myeloid leukemia.

    Science.gov (United States)

    Eisfeld, A-K; Mrózek, K; Kohlschmidt, J; Nicolet, D; Orwick, S; Walker, C J; Kroll, K W; Blachly, J S; Carroll, A J; Kolitz, J E; Powell, B L; Wang, E S; Stone, R M; de la Chapelle, A; Byrd, J C; Bloomfield, C D

    2017-10-01

    Recurrent chromosomal abnormalities and gene mutations detected at the time of diagnosis of acute myeloid leukemia (AML) are associated with particular disease features, treatment response and survival of AML patients, and are used to denote specific disease entities in the World Health Organization classification of myeloid neoplasms and acute leukemia. However, large studies that integrate cytogenetic and comprehensive mutational information are scarce. We created a comprehensive oncoprint of mutations associated with recurrent cytogenetic findings by combining the information on mutational patterns of 80 cancer- and leukemia-associated genes with cytogenetic findings in 1603 adult patients with de novo AML. We show unique differences in the mutational profiles among major cytogenetic subsets, identify novel associations between recurrent cytogenetic abnormalities and both specific gene mutations and gene functional groups, and reveal differences in cytogenetic and mutational features between patients younger than 60 years and those aged 60 years or older. The identified associations between cytogenetic and molecular genetic data may help guide mutation testing in AML, and result in more focused application of targeted therapy in patients with de novo AML.

  9. Cerebrospinal fluid beta-2-microglobulin in adult patients with acute leukemia or lymphoma

    DEFF Research Database (Denmark)

    Hansen, P B; Kjeldsen, L; Dalhoff, K

    1992-01-01

    Beta-2-microglobulin (B2m) was measured in the cerebrospinal fluid (CSF) and serum from 18 adults with acute lymphoblastic leukemia, acute myeloblastic leukemia or lymphoma in order to detect early central nervous system (CNS) involvement or relapse. Six had CNS-involvement documented by neurologic...

  10. A comprehensive cytogenetic classification of 1466 Chinese patients with de novo acute lymphoblastic leukemia.

    Science.gov (United States)

    Li, Xin; Li, Juan; Hu, Yanjie; Xie, Wei; Du, Wen; Liu, Wei; Li, Xiaoqing; Chen, Xiangjun; Li, Hongrui; Wang, Junfeng; Zhang, Lannan; Huang, Shiang

    2012-06-01

    Cytogenetics and molecular cytogenetics of 1466 Chinese patients with de novo acute lymphoblastic leukemia (ALL) were studied. Cytogenetic results were available in 1175 patients. Cross-correlations of 23 subclasses of cytogenetic abnormalities were described. Childhood cases had higher incidences of normal karyotype, t(1;19), +8, 12q-, +21, +22 and high hyperdiploidy with 51-65 chromosomes, and lower incidences of t(9;22) and -5/5q- than adult ones (all pcytogenetic subclasses with immunophenotyping subgroups of ALL were studied. Our study presents the cytogenetic characteristics of a large series of Chinese ALL patients. Copyright © 2011 Elsevier Ltd. All rights reserved.

  11. Tumor suppressors BTG1 and IKZF1 cooperate during mouse leukemia development and increase relapse risk in B-cell precursor acute lymphoblastic leukemia patients.

    Science.gov (United States)

    Scheijen, Blanca; Boer, Judith M; Marke, René; Tijchon, Esther; van Ingen Schenau, Dorette; Waanders, Esmé; van Emst, Liesbeth; van der Meer, Laurens T; Pieters, Rob; Escherich, Gabriele; Horstmann, Martin A; Sonneveld, Edwin; Venn, Nicola; Sutton, Rosemary; Dalla-Pozza, Luciano; Kuiper, Roland P; Hoogerbrugge, Peter M; den Boer, Monique L; van Leeuwen, Frank N

    2017-03-01

    Deletions and mutations affecting lymphoid transcription factor IKZF1 (IKAROS) are associated with an increased relapse risk and poor outcome in B-cell precursor acute lymphoblastic leukemia. However, additional genetic events may either enhance or negate the effects of IKZF1 deletions on prognosis. In a large discovery cohort of 533 childhood B-cell precursor acute lymphoblastic leukemia patients, we observed that single-copy losses of BTG1 were significantly enriched in IKZF1 -deleted B-cell precursor acute lymphoblastic leukemia ( P =0.007). While BTG1 deletions alone had no impact on prognosis, the combined presence of BTG1 and IKZF1 deletions was associated with a significantly lower 5-year event-free survival ( P =0.0003) and a higher 5-year cumulative incidence of relapse ( P =0.005), when compared with IKZF1 -deleted cases without BTG1 aberrations. In contrast, other copy number losses commonly observed in B-cell precursor acute lymphoblastic leukemia, such as CDKN2A/B, PAX5, EBF1 or RB1 , did not affect the outcome of IKZF1 -deleted acute lymphoblastic leukemia patients. To establish whether the combined loss of IKZF1 and BTG1 function cooperate in leukemogenesis, Btg1 -deficient mice were crossed onto an Ikzf1 heterozygous background. We observed that loss of Btg1 increased the tumor incidence of Ikzf1 +/- mice in a dose-dependent manner. Moreover, murine B cells deficient for Btg1 and Ikzf1 +/- displayed increased resistance to glucocorticoids, but not to other chemotherapeutic drugs. Together, our results identify BTG1 as a tumor suppressor in leukemia that, when deleted, strongly enhances the risk of relapse in IKZF1 -deleted B-cell precursor acute lymphoblastic leukemia, and augments the glucocorticoid resistance phenotype mediated by the loss of IKZF1 function. Copyright© Ferrata Storti Foundation.

  12. Germline activating TYK2 mutations in pediatric patients with two primary acute lymphoblastic leukemia occurrences.

    Science.gov (United States)

    Waanders, E; Scheijen, B; Jongmans, M C J; Venselaar, H; van Reijmersdal, S V; van Dijk, A H A; Pastorczak, A; Weren, R D A; van der Schoot, C E; van de Vorst, M; Sonneveld, E; Hoogerbrugge, N; van der Velden, V H J; Gruhn, B; Hoogerbrugge, P M; van Dongen, J J M; Geurts van Kessel, A; van Leeuwen, F N; Kuiper, R P

    2017-04-01

    The contribution of genetic predisposing factors to the development of pediatric acute lymphoblastic leukemia (ALL), the most frequently diagnosed cancer in childhood, has not been fully elucidated. Children presenting with multiple de novo leukemias are more likely to suffer from genetic predisposition. Here, we selected five of these patients and analyzed the mutational spectrum of normal and malignant tissues. In two patients, we identified germline mutations in TYK2, a member of the JAK tyrosine kinase family. These mutations were located in two adjacent codons of the pseudokinase domain (p.Pro760Leu and p.Gly761Val). In silico modeling revealed that both mutations affect the conformation of this autoregulatory domain. Consistent with this notion, both germline mutations promote TYK2 autophosphorylation and activate downstream STAT family members, which could be blocked with the JAK kinase inhibitor I. These data indicate that germline activating TYK2 mutations predispose to the development of ALL.

  13. Hyperglycemia increases the complicated infection and mortality rates during induction therapy in adult acute leukemia patients

    Directory of Open Access Journals (Sweden)

    Carolina do Nascimento Matias

    2013-01-01

    Full Text Available OBJECTIVE: To determine the prevalence of hyperglycemia during induction therapy in adult patients with acute leukemia and its effect on complicated infections and mortality during the first 30 days of treatment. METHODS: An analysis was performed in a retrospective cohort of 280 adult patients aged 18 to 60 years with previously untreated acute leukemia who received induction chemotherapy from January 2000 to December 2009 at the Hemocentro de Pernambuco (HEMOPE, Brazil. Hyperglycemia was defined as the finding of at least one fasting glucose measurement > 100 mg/dL observed one week prior to induction therapy until 30 days after. The association between hyperglycemia and complicated infections, mortality and complete remission was evaluated using the Chi-square or Fisher's exact tests by the Statistical Package for Social Sciences (SPSS in the R software package version 2.9.0. RESULTS: One hundred and eighty-eight patients (67.1% presented hyperglycemia at some moment during induction therapy. Eighty-two patients (29.3% developed complicated infections. Infection-related mortality during the neutropenia period was 20.7% (58 patients. Mortality from other causes during the first 30 days after induction was 2.8%. Hyperglycemia increased the risk of complicated infections (OR 3.97; 95% confidence interval: 2.08 - 7.57; p-value < 0.001 and death (OR 3.55; 95% confidence interval: 1.77-7.12; p-value < 0.001 but did not increase the risk of fungal infections or decrease the probability of achieving complete remission. CONCLUSION: This study demonstrates an association between the presence of hyperglycemia and the development of complicated infections and death in adult patients during induction therapy for acute leukemia.

  14. [Clinical study of 572 adult acute leukemia patients in Shanghai according to WHO classification].

    Science.gov (United States)

    2007-07-01

    To evaluate WHO classification of acute leukemia (AL) in Shanghai and compare the difference between WHO and FAB classification. Successive and unselected leukemia patients were referred to Sino-US Leukemia Cooperative Group of Shanghai from 2003 to 2006. A total of 572 adult AL cases were diagnosed and classified according to WHO and FAB classification. Of the 572 AL patients, 436 (76.2%) were diagnosed as acute myeloid leukemia (AML), 119 (20.8%) acute lymphoblastic leukemia (ALL). The AML and ALL percentage ratio was 3.66: 1. AML with recurrent cytogenetic abnormalities accounted for 35.3%, and with multilineage dysplasia for 13.1%, therapy-related AML accounted for 0.9%, and AML not otherwise categorized for 50.7%. The percentage of therapy-related AML in Shanghai was lower than that in the Western. B-ALL was the majority (84.9%) in ALL. According to FAB classification, AML-M4 was the most (38.5%) common subtype. The percentage of AML-M3 and M4 in Shanghai were higher than that in the Western, but that of AML-M, was lower. The incidence of karyotypic abnormalities in AML was 60.8%. The incidence of AML with t (15;17) was higher than that in the Western. Favorable cytogenetic risk group accounted for 30.6%, intermediate group for 51.5%, unfavorable group for 17.9% of AML. B-ALL with t (9;22) was 33.7%. The percentages of AML with t (15;17) and AML-M4 in Shanghai and the incidence of cytogenetic favorable group were higher than that in the Western. It was different in WHO classification and karyotypic abnormalities of AML between Shanghai and the Western. Comparing to the AL data of Shanghai Leukemia Group between 1984 and 1994, the percentage of AML-M4 was increased, but that of AML-M1 and M5 were decreased.

  15. The Basel experience with total body irradiation for conditioning patients with acute leukemia for allogenic bone marrow transplantation

    International Nuclear Information System (INIS)

    Speck, B.; Cornu, P.; Nissen, C.; Gratwohl, A.; Sartorius, J.

    1979-01-01

    We are reporting our experience with 13 patients suffering from end stage acute leukemia that were prepared for allogeneic bone marrow transplantation by combined chemotherapy followed by high dose cyclophosphamide (Cy) and total body irradiation (TBI). Only one patient became a long term survivor. Of the evaluable 12 patients, 6 died of interstitial pneumonia, 4 of GvH and 1 of recurrent leukemia. We conclude that adding combined chemotherapy to the standard conditioning program with Cy and TBI probably increases the risk of developing fatal interstitial pneumonia without eliminating the risk of recurrent leukemia. We suggest that allogenic marrow grafts should be performed earlier in the course of refractory acute leukemias, because in patients with end stage disease its chances of being curative are small

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

    International Nuclear Information System (INIS)

    Derwich, K.; Andrzejewska, M.; Wachowiak, J.; Mankowski, P.

    2009-01-01

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

  17. Profile of Infections in Newly Diagnosed Patients with Acute Leukemia During the Induction Phase of Treatment

    International Nuclear Information System (INIS)

    Sayed, H.A.; Talaat, S.M.; El-Mahallawy, H.A.; Kaddah, A.M.; Ismael, H.T.

    2009-01-01

    Acute leukemia is the most common pediatric malignancy. Despite the significant progress in the treatment of infectious complications, infection-related morbidity and mortality continue to be of great importance. Prompt initiation of the appropriate empiric antibiotic treatment has improved infection outcome. The aim of the present study is to assess the type, frequency, and severity of infectious complications in a cohort of pediatric cancer patients treated at a single medical institution. We also aim to identify factors affecting bloodstream infections in newly diagnosed ALL and AML pediatric patients during the induction phase of treatment. Patients and Methods: This study was carried out at the Department of Pediatric Oncology, National Cancer Institute, Cairo University, during the time period from January 1st to June 30th 2007. Inclusion criteria were pediatric age group (from 0-16 years), newly diagnosed acute leukemia, positive blood culture and documented site of infection. Data were analyzed using the SPSS package version 15. A p-value £0.05 was considered significant. Results: This is a retrospective study including 100 newly diagnosed cases of acute leukemia. Fifty-four patients had ALL, and 46 patients had AML. 348 infectious episodes were recorded. Blood stream infections (BSI) occurred once or twice in 32%, 3-4 episodes in 58%, and five or more episodes in 10% of the cases. Gram-positive cocci were the most frequently observed cause of BSI, accounting for 77.9% of the total isolates followed by Gram negative organisms seen in 18.9% and mixed infections in 8%. The majority of the episodes (n= 208, 58.4%) responded to first-line empirical antibiotic therapy. Conclusion: Clinical and laboratory risk factors could be identified and can help prediction of serious BSI.

  18. Childhood Acute Lymphoblastic Leukemia

    DEFF Research Database (Denmark)

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

    2015-01-01

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

  19. A phase II study of the EGFR inhibitor gefitinib in patients with acute myeloid leukemia.

    Science.gov (United States)

    Deangelo, Daniel J; Neuberg, Donna; Amrein, Philip C; Berchuck, Jacob; Wadleigh, Martha; Sirulnik, L Andres; Galinsky, Ilene; Golub, Todd; Stegmaier, Kimberly; Stone, Richard M

    2014-04-01

    Novel therapies for the treatment of acute myeloid leukemia are required to overcome disease resistance and to provide potentially less toxic therapies for older adults. Prior clinical trials involving patients with non-small cell lung cancer have demonstrated the safety and biologic activity of the administration of EGFR inhibitors in carefully selected patients. The potential efficacy of this approach in patients with acute myeloid leukemia is unknown. The effects of gefitinib on differentiation induction and cell viability in AML cell lines and primary patient AML cells were previously reported and cell viability was inhibited in a clinically achievable range. To determine if EGFR inhibitors would be therapeutically efficacious in advanced AML, we performed a phase II trial in which 18 patients with a median age of 72 (range, 57-84 years) were treated with gefitinib (750mg orally daily). While there were no unexpected toxicities, no patients experienced an objective response, though one had stable disease lasting 16 months. We conclude that in spite of pre-clinical activity and anecdotal cases of response to EGFR inhibitors, routine use of the EGFR inhibitor gefitinib as a single agent for advanced AML is not appropriate. Copyright © 2013 Elsevier Ltd. All rights reserved.

  20. Early invasive pulmonary aspergillosis with fatal outcome in a patient with acute lymphoblastic leukemia

    International Nuclear Information System (INIS)

    Gaspar, M.; Poczova, M.; Sladekova, M.; Drgona, L.

    2015-01-01

    Purpose: The main objective of this publication is to highlight the complexity of the issue of care for patients with hemato-oncological disease, with a focus on infectious complication - invasive pulmonary aspergillosis. Case: We present a case report of a 49-year-old patient treated for acute lymphoblastic leukemia. In the early post-transplant period, in spite of combined antimicrobial treatment, an onset of fever and dyspnoea occurred. Because of the clinical condition of our immunosuppressed patient, as well as radiological finding of suspected inflammatory changes in the lung, antibiotic and antifungal therapy was changed. Respiratory symptoms progressed and the state extorted artificial ventilation. Realized bronchoscopy showed structural changes in bronchial mucosa. The results of laboratory analyses of bronchoalveolar lavage testified to fungal infection - pulmonary aspergillosis, with the cultures of Aspergillus flavus. Despite intensive complex treatment, the patient's condition led to multiple organ failure and on the Day D +27 after transplantation physicians stated exitus letalis. Autopsy confirmed invasive pulmonary aspergillosis. Conclusion: Acute leukemia and its treatment is an increased risk of systemic fungal infections in those patients - especially invasive aspergillosis. The fatality rate for invasive aspergillosis in this risk group represents on average 50 %. With this in mind, it is necessary for life-saving to diagnose the infection in time and treat it appropriately. (author)

  1. Bacillus Cereus catheter related bloodstream infection in a patient in a patient with acute lymphblastic leukemia

    Directory of Open Access Journals (Sweden)

    Lütfiye Öksüz

    2012-01-01

    Full Text Available Bacillus cereus infection is rarely associated with actual infection and for this reason single positive blood culture is usually regarded as contamination . However it may cause a number of infections, such catheter-related blood stream infections. Significant catheter-related bloodstream infections (CRBSI caused by Bacillus spp. are mainly due to B.cereus and have been predominantly reported in immunocompromised hosts1 . Catheter removal is generally advised for management of infection. In this report, catheter-related bacteremia caused by B.cereus in a patient with acute lymphoblastıc leukemia (ALL in Istanbul Medical Faculty was presented.A 44-year old man presented with fatigue, weight loss, epistaxis and high fever. A double-lumen Hickman–catheter (Bard 12.0 Fr, Round Dual Lumen was inserted by surgical cut-down to access the right subclavian vein which would be necessary for allogeneic stem cell transplantation. Three weeks later the patient presented with high fever and headache. Bacillus spp. was isolated from the cathether while blood culture obtained from the peripheral vein remained negative. The bacterial identification was confirmed as B.cereus using VITEK identification system It has been reported Bacillus cereus septicemia may be fatal in immunocompromised hosts despite broad-spectrum appropriate treatment10. Catheter removal is essential for prevention of recurrent bacteremia. Long-term cathater salvage should be reserved for appropriate patient group.

  2. DNMT3A GENE POINT MUTATIONS DETECTION IN ACUTE MYELOID LEUKEMIA PATIENTS USING SEQUENCING TECHNIQUE

    OpenAIRE

    A. V. Vinogradov; A. V. Rezaykin; A. G. Sergeev

    2015-01-01

    Aim: to estimate the frequency of DNMT3A gene exons 18–26 point mutations in acute myeloid leukemia (AML) patients (pts) using target automatic sequencing technique.Material and Methods. Bone marrow and peripheral blood samples were obtained from 34 AML pts aged 21 to 64, who were treated in Sverdlovsk Regional Hematological Centre (Ekaterinburg) during the period 2012–2014. Distribution of the pts according to FAB-classification was as follows: AML M0 – 3, M1 – 1, M2 – 12, M3 – 3, M4 – 10, M...

  3. Rhabdomyolysis Caused by Candida parapsilosis in a Patient with Acute Myeloid Leukemia after Bone Marrow Transplantation.

    Science.gov (United States)

    Kakiuchi, Seiji; Yakushijin, Kimikazu; Yamamoto, Katsuya; Tomioka, Hideo; Inui, Yumiko; Okamura, Atsuo; Kawamoto, Shinichiro; Minami, Yosuke; Murayama, Tohru; Ito, Mitsuhiro; Matsuoka, Hiroshi; Minami, Hironobu

    2015-01-01

    Rhabdomyolysis is characterized by a marked elevation of the creatine kinase (CK) levels and myoglobinuria, thus leading to renal dysfunction. Various viruses or bacteria can be etiologic agents, but mycosis has only rarely been reported to be a cause of rhabdomyolysis. In this report, we describe an adolescent male with acute myeloid leukemia who underwent allogeneic bone marrow transplantation and thereafter developed rhabdomyolysis and Candida parapsilosis fungemia almost at the same time. Following treatment for C. parapsilosis, the transaminase and CK levels both satisfactorily decreased. This case illustrates that C. parapsilosis infection may be a causative agent of rhabdomyolysis in immunocompromised patients.

  4. TIGAR cooperated with glycolysis to inhibit the apoptosis of leukemia cells and associated with poor prognosis in patients with cytogenetically normal acute myeloid leukemia.

    Science.gov (United States)

    Qian, Sixuan; Li, Jianyong; Hong, Ming; Zhu, Yu; Zhao, Huihui; Xie, Yue; Huang, Jiayu; Lian, Yun; Li, Yanru; Wang, Shuai; Mao, Jianping; Chen, Yaoyu

    2016-11-25

    Cancer cells show increased glycolysis and take advantage of this metabolic pathway to generate ATP. The TP53-induced glycolysis and apoptosis regulator (TIGAR) inhibits aerobic glycolysis and protects tumor cells from intracellular reactive oxygen species (ROS)-associated apoptosis. However, the function of TIGAR in glycolysis and survival of acute myeloid leukemia cells remains unclear. We analyzed TIGAR expression in cytogenetically normal (CN-) AML patients and the correlations with clinical and biological parameters. In vivo and in vitro, we tested whether glycolysis may induce TIGAR expression and evaluated the combination effect of glycolysis inhibitor and TIGAR knockdown on human leukemia cell proliferation. High TIGAR expression was an independent predictor of poor survival and high incidence of relapse in adult patients with CN-AML. TIGAR also showed high expression in multiple human leukemia cell lines and knockdown of TIGAR activated glycolysis through PFKFB3 upregulation in human leukemia cells. Knockdown of TIGAR inhibited the proliferation of human leukemia cells and sensitized leukemia cells to glycolysis inhibitor both in vitro and in vivo. Furthermore, TIGAR knockdown in combination with glycolysis inhibitor 2-DG led leukemia cells to apoptosis. In addition, the p53 activator Nutlin-3α showed a significant combinational effect with TIGAR knockdown in leukemia cells. However, TIGAR expression and its anti-apoptotic effects were uncoupled from overexpression of exogenous p53 in leukemia cells. TIGAR might be a predictor of poor survival and high incidence of relapse in AML patients, and the combination of TIGAR inhibitors with anti-glycolytic agents may be novel therapies for the future clinical use in AML patients.

  5. [A clinical study of chronic disseminated candidiasis in patients with acute leukemia].

    Science.gov (United States)

    Xu, Bing; Guo, Xu-Tao; Wei, Yong-Qiang; Meng, Fan-Yi; Liu, Qi-Fa; Zhou, Shu-Yun

    2008-06-01

    To deepen the understanding of chronic disseminated candidiasis (CDC) in patients with acute leukemia (AL). CDC was investigated in 119 AL patients who received induction chemotherapy from August 2004 to May 2005. Clinical manifestations, laboratory tests, imaging modalities, diagnosis and treatment were investigated retrospectively. Three patients (2.5%) were identified to be suffering from CDC. All the three patients had an absolute neutrophil count (ANC) nodular patchy shadows in lungs. Nuclear magnetic resonance imaging showed multiple abnormal signal in liver, spleen and kidneys in one of the patients. Two patients had positive bleed fungal cultures and histologic examination in one of the patients were positive for Candida tropicalis. Two patients received amphotericin B therapy empirically, but it was replaced by amphotericin B colloid dispersion (ABCD) later in one and combined with voriconazole in another because of unresponsiveness to the drug. One patient took a favorable turn after receiving ABCD therapy for 45 d, which was replaced by voriconazole because of the emergence of fever after discontinuation of ABCD. All the three patients received further chemotherapy smoothly after the diagnosis of CDC. The diagnosis of CDC remains difficult. Fungal blood cultures and histologic examination have been considered in many studies as the golden standard for the diagnosis of CDC. Amphotericin B is the cornerstone of treatment in patients with CDC and lipid formulations of amphotericin B can be used in CDC patients who are intolerant of or refractory to conventional amphotericin B. Voriconazole has a favorable response for refractory/relapse patients and could be used for second line treatment. The development of CDC in patients with acute leukemia does not preclude further chemotherapy.

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

    Directory of Open Access Journals (Sweden)

    Gil Cunha De Santis

    2014-07-01

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

  7. Genomic Characterization of Acute Leukemias

    Science.gov (United States)

    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. PMID:24968698

  8. Relapsed acute promyelocytic leukemia in a hemodialysis-dependent patient treated with arsenic trioxide: a case report

    Directory of Open Access Journals (Sweden)

    Emmons Gregory S

    2012-10-01

    Full Text Available Abstract Introduction In the relapsed setting, arsenic trioxide remains the backbone of treatment. Scant literature exists regarding treatment of relapsed acute promyelocytic leukemia in patients with renal failure. To the best of our knowledge we are the first to report a safe and effective means of treatment for relapsed acute promyelocytic leukemia in the setting of advanced renal failure, employing titration of arsenic trioxide based on clinical parameters rather than arsenic trioxide levels. Case presentation A 33-year-old Caucasian man with a history of acute promyelocytic leukemia in remission for 3 years, as well as dialysis-dependent chronic renal failure secondary to a solitary kidney and focal segmental glomerulosclerosis and human immunodeficiency virus infection, receiving highly active antiretroviral therapy presented to our hospital with bone marrow biopsy-confirmed relapsed acute promyelocytic leukemia. Arsenic trioxide was begun at a low dose with dose escalation based only on side effect profile monitoring and not laboratory testing for induction as well as maintenance without undue toxicity. Our patient achieved and remains in complete hematologic and molecular remission as of this writing. Conclusion Arsenic trioxide can be used safely and effectively to treat acute promyelocytic leukemia in patients with advanced renal failure using careful monitoring of side effects rather than blood levels of arsenic to guide therapeutic dosing.

  9. Acute Myelogenous Leukemia Mimicking Fulminant Periorbital Cellulitis

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    Abbas Bagheri

    2013-01-01

    Full Text Available Purpose: To report a patient who was referred for orbital cellulitis but was finally diagnosed with acute leukemia. Case Report: A 17-year-old boy presented with fever, periorbital erythema and swelling mimicking periorbital cellulitis. He underwent empiric antibiotic therapy. Complete blood counts revealed leukocytosis with a predominance of immature blast cells. Bone marrow aspiration confirmed the diagnosis of acute myelogenous leukemia. Chemotherapy was initiated resulting in resolution of signs and symptoms. Conclusion: Acute leukemia may mimic periorbital cellulitis and must be considered in the differential diagnosis.

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

    Science.gov (United States)

    2018-03-01

    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

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

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    Nadia El Menshawy

    2014-06-01

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

  12. Central nervous system leukemia in a patient with concurrent nasopharyngeal carcinoma and acute myeloid leukaemia: A case report.

    Science.gov (United States)

    Liu, Jun-Qing; Mai, Wen-Yuan; Wang, Si-Ben; Lou, Yin-Jun; Yan, Sen-Xiang; Jin, Jie; Xu, Wei-Lai

    2017-12-01

    Concurrent case of nasopharyngeal carcinoma (NPC) and acute myeloid leukemia (AML) has not been reported. Here, we report a case of NPC, who was concurrently suffered from AML one mother after the NPC diagnosis. The patient was a 45-year-old male who presented with a mass on his right side neck. The patient was diagnosed with Epstein-Barr virus negative type-2 non-keratinizing carcinoma with clivus involvement and unilateral metastasis to the cervical lymph node. He was treated with one cycle of cisplatin and 69.76 Gy of concurrent external-beam radiation. Three months after completion of chemo-radiotherapy, the patient was diagnosed as acute myeloid leukemia, which achieved complete remission after one course induction chemotherapy. Two months later, however, the patient was diagnosed as central nervous system leukemia. He ultimately died of relapsed leukemia. The overall survival of the patient was 10 months. The co-occurrence of NPC and AML is rare and prognosis is poor. Radiotherapy in NPC can disrupt the blood-brain barrier, which may contribute to the pathogenesis of central nervous system leukemia. Early alert and prevention of central nervous system leukemia following radiotherapy in NPC patient is recommended. Copyright © 2017 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.

  13. Recombinant EphB4-HSA Fusion Protein and Azacitidine or Decitabine for Relapsed or Refractory Myelodysplastic Syndrome, Chronic Myelomonocytic Leukemia, or Acute Myeloid Leukemia Patients Previously Treated With a Hypomethylating Agent

    Science.gov (United States)

    2017-08-18

    Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome; Chronic Myelomonocytic Leukemia; Previously Treated Myelodysplastic Syndrome; Recurrent Acute Myeloid Leukemia With Myelodysplasia-Related Changes; Recurrent Adult Acute Myeloid Leukemia

  14. Distinct protein signatures of acute myeloid leukemia bone marrow-derived stromal cells are prognostic for patient survival.

    Science.gov (United States)

    Kornblau, Steven M; Ruvolo, Peter P; Wang, Rui-Yu; Battula, V Lokesh; Shpall, Elisabeth J; Ruvolo, Vivian R; McQueen, Teresa; Qui, YiHua; Zeng, Zhihong; Pierce, Sherry; Jacamo, Rodrigo; Yoo, Suk-Young; Le, Phuong M; Sun, Jeffery; Hail, Numsen; Konopleva, Marina; Andreeff, Michael

    2018-03-15

    Mesenchymal stromal cells support acute myeloid leukemia cell survival in the bone marrow microenvironment. Protein expression profiles of acute myeloid leukemia-derived mesenchymal stromal cells are unknown. Reverse phase protein array analysis was performed to compare expression of 151 proteins from acute myeloid leukemia mesenchymal stromal cells (n = 106) with mesenchymal stromal cells from healthy donors (n = 71). Protein expression differed significantly between the two groups with nineteen proteins overexpressed in leukemia stromal cells and nine overexpressed in normal stromal cells. Unbiased hierarchical clustering analysis of the samples using these twenty-eight proteins revealed three protein constellations whose variation in expression defined four mesenchymal stromal cells protein expression signatures: Class 1, Class 2, Class 3, and Class 4. These cells populations appear to have clinical relevance. Specifically, patients with Class 3 cells have longer survival and remission duration compared to other groups. Comparison of leukemia mesenchymal stromal cells at first diagnosis with those obtained at salvage (i.e., relapse/refractory) showed differential expression of nine proteins reflecting a shift toward osteogenic differentiation. Leukemia mesenchymal stromal cells are more senescent compared to their normal counterparts, possibly due to the over expressed p53/p21 axis as confirmed by high β-galactosidase staining. In addition, over expression of BCL-XL in leukemia mesenchymal stromal cells might accord survival advantage under conditions of senescence or stress and over-expressed galectin-3 exerts profound immunosuppression. Together, our findings suggest that the identification of specific populations of mesenchymal stromal cells in acute myeloid leukemia patients may be an important determinant of therapeutic response. Copyright © 2018, Ferrata Storti Foundation.

  15. Successful treatment of Pseudomembranous necrotizing Aspergillus tracheobronchitis in a patient with acute myeloid leukemia

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    Stanić Jelena

    2014-01-01

    Full Text Available Introduction. Pseudomembranous necrotizing Aspergillus tracheobronchitis is a rare form of pulmonary aspergillosis which occurs in immunocompromised patients. Case Outline. A female patient aged 71, suffering from acute myeloid leukemia, developed the symptoms of progressive shortness of breath and inspiratory stridor. The diagnosis in our case was made on the histological findings from tissues obtained by bronchoscopy. A chest CT scan suggested the state of the compromised trachea and left principal bronchus lumen. The long-term regimen with itraconazole in the dose of 400 mg/24 hours proved efficient in our patient. Conclusion. Progressive shortness of breath and inspiratory stridor in immunocompromised patients along with radiological and CT changes should be also considered as pulmonary aspergillosis in differential diagnosis. [Projekat Ministarstva nauke Republike Srbije, br. 175056

  16. Nilotinib-Induced Acute Pancreatitis in a Patient with Chronic Myeloid Leukemia

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    Vihang Patel

    2017-05-01

    Full Text Available Nilotinib, a second-generation tyrosine kinase inhibitor, is used for treatment of chronic myeloid leukemia (CML; it has been widely used especially for imatinib-resistant CML. Despite being a novel drug in this therapeutic class, it has the potential to be harmful. We present the case of an elderly woman who developed life-threatening acute pancreatitis as an adverse event after having started the drug. There is only one reported case in the literature of nilotinib-induced acute pancreatitis. The purpose of this case report is to educate physicians who prescribe this medication to be aware of potential life-threatening adverse events. As more and more therapies are available, physicians should be aware of potential effects of cancer treatment that could be life-threatening to patients.

  17. Acute Myeloid Leukemia in a Patient With X-linked Severe Combined Immunodeficiency.

    Science.gov (United States)

    Shigemura, Tomonari; Motobayashi, Mitsuo; Matsuda, Kazuyuki; Shimodaira, Takahiro; Kurata, Takashi; Kobayashi, Norimoto; Agematsu, Kazunaga; Nakazawa, Yozo

    2017-11-01

    Severe combined immunodeficiency (SCID) is a defect in the differentiation and function of T cells. An increased malignancy risk, mainly lymphatic malignancy, has been described in patients with SCID. We report a patient with X-linked SCID who developed acute myeloid leukemia, derived from the recipient with somatic NRAS mutation 4 months after cord blood transplantation (CBT). Loss of heterozygosity phenomenon of the recipient at 6q14 locus was observed at 2 months post-CBT and progressed to 6q deletion (6q-) chromosome abnormality. Somatic NRAS mutation was detected at 3 months post-CBT. Thus, 6q- and NRAS mutation were strongly associated with the leukemic transformation in our patient.

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

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    Ye Zhang

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

  19. ReCAP: Gaps in Insurance Coverage for Pediatric Patients With Acute Lymphoblastic Leukemia.

    Science.gov (United States)

    Smits-Seemann, Rochelle R; Kaul, Sapna; Hersh, Aimee O; Fluchel, Mark N; Boucher, Kenneth M; Kirchhoff, Anne C; Smits-Seemann, Rochelle R; Kaul, Sapna; Hersh, Aimee O; Fluchel, Mark N; Boucher, Kenneth M; Kirchhoff, Anne C

    2016-02-01

    Continuous insurance coverage is an important component of effective health care. Evaluation of insurance gaps in pediatric cancer care is an understudied area. We conducted a retrospective analysis of payer data from outpatient oncology encounters at Primary Children's Hospital (Salt Lake City, UT) over the first 2 years of therapy for pediatric patients with acute lymphoblastic leukemia diagnosed from 1998 to 2010 (N = 380). Using logistic regression, we evaluated demographic and clinical predictors (age at diagnosis, sex, ethnicity, high/standard acute lymphoblastic leukemia risk, and rural/urban county of residence at diagnosis) of a gap in health insurance. The median age at diagnosis was 4 years (interquartile range, 3 to 8 years), and 172 patients (45%) were girls. In the first 2 years of treatment, 45 patients (12%) experienced a gap in health insurance. The odds of having a gap in insurance coverage decreased by 16% each year from 1998 to 2010 (odds ratio, 0.84; 95% CI, 0.76 to 0.93; test for trend, P = .001). Public insurance at diagnosis was associated with a four-fold increased likelihood of experiencing an insurance gap (odds ratio, 4.09; 95% CI, 1.98 to 8.44; P insurance at diagnosis. Gaps in insurance coverage during pediatric cancer treatment are not uncommon, which highlights the importance of discussing insurance status at diagnosis and throughout a patient's treatment course to help patients and their families prepare for any changes and avoid unnecessary financial burden. Future research should focus on examining the effect of insurance gaps on patient outcomes and evaluating likelihood of gaps in insurance after health care reform. Copyright © 2015 by American Society of Clinical Oncology.

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

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    Zohreh Sanaat

    2012-07-01

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

  1. High Risk of Hepatitis B Reactivation among Patients with Acute Myeloid Leukemia.

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    Chien-Yuan Chen

    Full Text Available Hepatitis B virus (HBV infections are common and associated with significant morbidity and mortality in cancer patients. However, the incidence and risk factors of HBV reactivation in patients with acute myeloid leukemia (AML are rarely investigated.AML patients followed-up at the National Taiwan University Hospital between 2006 and 2012 were analyzed. The clinical characteristics and laboratory data were retrospectively reviewed.Four hundred and ninety patients comprising 265 men and 225 women were studied. The median age was 52 years (range, 18 - 94. Chronic HBV carriage was documented at the time of leukemia diagnosis in 57 (11.6% patients. Forty-six (80.7% of the 57 HBV carriers received prophylaxis with anti-HBV agents. Sixteen HBV carriers (28.1% developed hepatitis B reactivation during or after chemotherapy, including 7 patients who had discontinued antiviral therapy. The incidence of hepatitis B reactivation among AML patients with HBV carriage was 9.5 per 100 person-years. Prophylaxis with anti-HBV agents significantly decreased the risk of hepatitis B reactivation among HBV carriers (13% vs. 61%, p<0.001. Four (2.8% of 142 patients with initial positive anti-HBsAb and anti-HBcAb experienced hepatitis B reactivation and lost their protective anti-HBsAb. Multivariate analysis revealed that diabetes mellitus (p=0.008, odds ratio (OR = 2.841, 95% confident interval (CI: 0.985-8.193 and carriage of HBsAg (p<0.001, OR=36.878, 95% CI: 11.770-115.547 were independent risk factors for hepatitis B reactivation in AML patients.Hepatitis B reactivation is not uncommon in the HBsAg positive AML patients. Prophylaxis with anti-HBV agent significantly decreased the risk of hepatitis B reactivation.

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

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    Vicari Perla

    2003-01-01

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

  3. High Risk of Hepatitis B Reactivation among Patients with Acute Myeloid Leukemia

    Science.gov (United States)

    Chen, Chien-Yuan; Huang, Sheng-Yi; Cheng, Aristine; Chou, Wen-Chien; Yao, Ming; Tang, Jih-Luh; Tsay, Woei; Sheng, Wang-Huei; Tien, Hwei-Fang

    2015-01-01

    Background Hepatitis B virus (HBV) infections are common and associated with significant morbidity and mortality in cancer patients. However, the incidence and risk factors of HBV reactivation in patients with acute myeloid leukemia (AML) are rarely investigated. Methods AML patients followed-up at the National Taiwan University Hospital between 2006 and 2012 were analyzed. The clinical characteristics and laboratory data were retrospectively reviewed. Results Four hundred and ninety patients comprising 265 men and 225 women were studied. The median age was 52 years (range, 18 - 94). Chronic HBV carriage was documented at the time of leukemia diagnosis in 57 (11.6%) patients. Forty-six (80.7%) of the 57 HBV carriers received prophylaxis with anti-HBV agents. Sixteen HBV carriers (28.1%) developed hepatitis B reactivation during or after chemotherapy, including 7 patients who had discontinued antiviral therapy. The incidence of hepatitis B reactivation among AML patients with HBV carriage was 9.5 per 100 person-years. Prophylaxis with anti-HBV agents significantly decreased the risk of hepatitis B reactivation among HBV carriers (13% vs. 61%, pHBcAb experienced hepatitis B reactivation and lost their protective anti-HBsAb. Multivariate analysis revealed that diabetes mellitus (p=0.008, odds ratio (OR) = 2.841, 95% confident interval (CI): 0.985-8.193) and carriage of HBsAg (p<0.001, OR=36.878, 95% CI: 11.770-115.547) were independent risk factors for hepatitis B reactivation in AML patients. Conclusions Hepatitis B reactivation is not uncommon in the HBsAg positive AML patients. Prophylaxis with anti-HBV agent significantly decreased the risk of hepatitis B reactivation. PMID:25973905

  4. A novel 6-mercaptopurine oral liquid formulation for pediatric acute lymphoblastic leukemia patients - results of a randomized clinical trial

    NARCIS (Netherlands)

    Hanff, Lidwien M.; Mathot, Ron A. A.; Smeets, Oscar; Postma, Doerine J.; Ramnarain, Satianand; Vermes, Andras; Pieters, Rob; Zwaan, C. Michel

    2014-01-01

    Pediatric patients with acute lymphoblastic leukemia (ALL) are treated with oral 6-mercaptopurine (6MP) for nearly 2 years, but no pediatric formulation has been available. In this study, an oral 6MP liquid suitable for pediatric use was developed and tested in the target population. A randomized

  5. Clinical efficacy and safety of imatinib in the management of Ph+ chronic myeloid or acute lymphoblastic leukemia in Chinese patients

    Science.gov (United States)

    Zhu, Yu; Qian, Si-Xuan

    2014-01-01

    Imatinib mesylate is considered the standard first-line systemic treatment for patients with chronic myeloid leukemia (CML) and functions by targeting BCR-ABL tyrosine kinases. Imatinib has substantially changed the clinical management and improved the prognosis of CML and Philadelphia chromosome-positive acute lymphocytic leukemia (Ph+ ALL). Here, we review the pharmacology, mode of action, and pharmacokinetics of imatinib; Chinese efficacy studies in CML and Ph+ ALL; safety and tolerability; patient-focused perspectives, such as quality of life, patient satisfaction, acceptability, and adherence; and uptake of imatinib. PMID:24623982

  6. Phase 1 dose-finding study of rebastinib (DCC-2036) in patients with relapsed chronic myeloid leukemia and acute myeloid leukemia.

    Science.gov (United States)

    Cortes, Jorge; Talpaz, Moshe; Smith, Hedy P; Snyder, David S; Khoury, Jean; Bhalla, Kapil N; Pinilla-Ibarz, Javier; Larson, Richard; Mitchell, David; Wise, Scott C; Rutkoski, Thomas J; Smith, Bryan D; Flynn, Daniel L; Kantarjian, Hagop M; Rosen, Oliver; Van Etten, Richard A

    2017-03-01

    A vailable tyrosine kinase inhibitors for chronic myeloid leukemia bind in an adenosine 5'-triphosphate-binding pocket and are affected by evolving mutations that confer resistance. Rebastinib was identified as a switch control inhibitor of BCR-ABL1 and FLT3 and may be active against resistant mutations. A Phase 1, first-in-human, single-agent study investigated rebastinib in relapsed or refractory chronic or acute myeloid leukemia. The primary objectives were to investigate the safety of rebastinib and establish the maximum tolerated dose and recommended Phase 2 dose. Fifty-seven patients received treatment with rebastinib. Sixteen patients were treated using powder-in-capsule preparations at doses from 57 mg to 1200 mg daily, and 41 received tablet preparations at doses of 100 mg to 400 mg daily. Dose-limiting toxicities were dysarthria, muscle weakness, and peripheral neuropathy. The maximum tolerated dose was 150 mg tablets administered twice daily. Rebastinib was rapidly absorbed. Bioavailability was 3- to 4-fold greater with formulated tablets compared to unformulated capsules. Eight complete hematologic responses were achieved in 40 evaluable chronic myeloid leukemia patients, 4 of which had a T315I mutation. None of the 5 patients with acute myeloid leukemia responded. Pharmacodynamic analysis showed inhibition of phosphorylation of substrates of BCR-ABL1 or FLT3 by rebastinib. Although clinical activity was observed, clinical benefit was insufficient to justify continued development in chronic or acute myeloid leukemia. Pharmacodynamic analyses suggest that other kinases inhibited by rebastinib, such as TIE2, may be more relevant targets for the clinical development of rebastinib ( clinicaltrials.gov Identifier:00827138 ). Copyright© Ferrata Storti Foundation.

  7. [Favorable Outcome of Hepatosplenic Candidiasis in a Patient with Acute Leukemia].

    Science.gov (United States)

    Čolović, Nataša; Arsenijević, Valentina Arsić; Suvajdžić, Nada; Djunić, Irena; Tomin, Dragica

    2015-01-01

    Acute leukemias treatment requires strong chemotherapy. Patients that develop bone marrow aplasia become immunocompromised, thus becoming liable to bacterial and fungal infections. Fungal infections caused by Candida are frequent. Hepatosplenic candidiasis (HSC) is a frequent consequence of invasive candidiasis which is clinically presented with prolonged febrility unresponsive to antibiotics. A 53-year-old patient with acute myeloid leukemia was submitted to standard chemotherapy "3+7" regimen (daunoblastine 80 mg i.v. on days 1 to 3, cytarabine 2 x 170 mg i.v. during 7 days) and achieved complete remission. However, during remission he developed febrility unresponsive to antibiotics. Computerised tomography (CT) of the abdomen showed multiple hypodense lesions within the liver and spleen. Haemocultures on fungi were negative. However, seroconversion of biomarkers for invasive fungal infection (FI) (Candida and Aspergillus antigen/Ag and antibody/Ab) indicated possible HSC. Only high positivity of anti-Candida IgG antibodies, positivity of mannan and CT finding we regarded sufficient for the diagnosis and antimycotic therapy.Three months of treatment with different antimycotics were necessary for complete disappearance of both clinical symptoms and CT findings. In patients with prolonged febrile neutropenia IFI has to be strongly suspected. If imaging techniques show multiple hypodense lesions within liver and spleen, HSC has to be taken seriously into consideration. We believe that, along with CT finding, positive laboratory Candida biomarkers (mannan and IgG antibodies) should be considered sufficient for"probable HSC" and commencement of antifungal therapy, which must be long enough, i.e. until complete disappearance of clinical symptoms and CT findings are achieved.

  8. Outcome disparities by insurance type for patients with acute myeloblastic leukemia.

    Science.gov (United States)

    Pulte, Dianne; Castro, Felipe A; Brenner, Hermann; Jansen, Lina

    2017-05-01

    Survival for patients with acute myeloblastic leukemia (AML) has increased during the past two decades. However, socioeconomic disparities may affect survival for some patient populations. We examine survival by insurance type for patients with AML. Using data from the Surveillance, Epidemiology, and End Results database we estimated survival according to insurance status (no insurance, Medicaid, and other insurance) for patients diagnosed with AML in the United States in 2007-2013. One, 3-, and 5-year survival was lower for patients with no insurance and Medicaid than for patients with other insurance. Five-year survival estimates were 24.7%, 25.6%, and 35.7%, respectively, for patients with Medicaid, no insurance, and other insurance. After adjustment, hazard ratios of 1.46 for uninsured and 1.35 for Medicaid compared to other insurance for overall survival and 1.50 for uninsured and 1.30 for Medicaid compared to other insurance for AML-specific survival were observed. Similar results were seen in all ages and both genders. Patients with no insurance or Medicaid have lower survival expectations after diagnosis with AML than patients with other insurance. Further research into reasons for the poor outcomes for Medicaid patients and continued reduction of number of uninsured people are urgently needed to improve population-level outcomes for AML. Published by Elsevier Ltd.

  9. The prognostic implication of SRSF2 mutations in Chinese patients with acute myeloid leukemia.

    Science.gov (United States)

    Yang, Jing; Yao, Dong-Ming; Ma, Ji-Chun; Yang, Lei; Guo, Hong; Wen, Xiang-Mei; Xiao, Gao-Fei; Qian, Zhen; Lin, Jiang; Qian, Jun

    2016-08-01

    Recently, somatic mutations in SRSF2 gene have been discovered in a proportion of hematologic malignancies including acute myeloid leukemia (AML). This study was aimed to investigate SRSF2 mutations in Chinese AML patients. High-resolution melting analysis (HRMA) was developed to screen SRSF2 mutations in 249 cases with AML, and then direct DNA sequencing was used to verify the results of HRMA. In this study, 3.6 % (9/249) of Chinese AML patients were found with heterozygous SRSF2 mutations. Patients with SRSF2 mutations were older than those with wild-type SRSF2 (P = 0.014). No differences in the sex, blood parameters, French-American-British classification (FAB) subtypes, and karyotypes were observed between AML patients with and without SRSF2 mutations. Although the overall survival (OS) of SRSF2-mutated patients was inferior to those without mutations in both whole AML patients (median 4 vs. 11 months, respectively; P = 0.006) and cytogenetically normal patients (median 2 vs. 12 months, respectively; P = 0.008), multiple analysis disclosed that SRSF2 mutation was not an independent prognostic factor in AML patients. These results suggest that SRSF2 mutation occurs at a low frequency in aged AML patients and might not be associated with adverse prognosis in Chinese AML patients.

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

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    Khalid Safoorah

    2010-10-01

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

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

    Science.gov (United States)

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

    2014-01-01

    Objective: This study aimed to assess the prognostic impact of Wilms tumor 1 (WT1) mutations in cytogenetically normal acute myeloid leukemia (CN-AML) among Egyptian patients. Materials and Methods: Exons 1, 2, 3, 7, 8, and 9 of WT1 were screened for mutations in samples from 82 CN-AML patients out of 203 newly diagnosed AML patients, of age ranging from 21 to 74 years, using high-resolution capillary electrophoresis. Results: Eleven patients out of 82 (13.41%) harbored WT1 mutations. Mutations were detected in exon 7 (n=7), exon 9 (n=2), exon 8 (n=1), and exon 3 (n=1), but not in exons 1 or 2. There was no statistically significant difference between the WT1 mutants and wild types as regards age, sex, French-American-British subtypes, and the prevalence of success of induction remission therapy (p=0.966; 28.6% vs. 29.3%). Patients with WT1 mutations had overall survival lower than patients with the wild type (HR=1.38; 95% CI 4.79-6.86; p=0.004). Conclusion: CN-AML patients with WT1 mutations have poor clinical outcome. We recommend molecular testing for WT1 mutations in patients with CN-AML at diagnosis in order to improve risk stratification of those patients. PMID:25035671

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

    Directory of Open Access Journals (Sweden)

    Salah Aref

    2014-03-01

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

  13. Oral manifestations in pediatric patients receiving chemotherapy for acute lymphoblastic leukemia.

    Science.gov (United States)

    Ponce-Torres, Elena; Ruíz-Rodríguez, Ma del Socorro; Alejo-González, Francisco; Hernández-Sierra, Juan Francisco; Pozos-Guillén, Amaury de J

    2010-01-01

    The purpose of this study was to determine the prevalence of oral manifestations in pediatric patients with acute lymphoblastic leukemia (ALL) receiving chemotherapy, and to evaluate the significance of independent risk factors (oral health, gender, age, time and type of treatment, and phase of chemotherapy). A cross-sectional study was made in 49 children with ALL between 2 and 14 years of age. To describe oral manifestations, a clinical diagnosis was made and the following criteria were applied: the OHI-S index to describe oral health and the IMPA index to describe periodontal conditions and to differentiate gingivitis from periodontitis. The prevalence of oral manifestations was: gingivitis, 91.84%; caries, 81.63%; mucositis, 38.77%; periodontitis, 16.32%; cheilitis, 18.36%; recurrent herpes, 12.24%; and primary herpetic gingivostomatitis, 2.04%. Other oral manifestations were: dry lips, mucosal pallor, mucosal petechiae, ecchymoses, and induced ulcers. The prevalence of oral candidiasis was 6.12%. It was observed that high risk ALL and poor oral hygiene were important risk factors for the development of candidiasis and gingivitis. The type of leukemia, gender and phase of chemotherapy were apparently associated with the presence of candidiasis, gingivitis, and periodontitis, and they could be considered risk factors for the development of oral manifestations.

  14. Bone Density in Pediatric Patients with Acute Lymphoblastic Leukemia (ALL: A Literature Review

    Directory of Open Access Journals (Sweden)

    Ali Ghassemi

    2015-02-01

    Full Text Available Introduction:  Acute Lymphoblastic Leukemia (ALL is the most common malignancy in children and the main form of childhood leukemia (75%. ALL different treatment options have a great impact on children weight and appetite. The improving prognosis for children with cancer refocuses attention to long-term outcomes with an emphasis on quality of life. More survival rate allows researchers to evaluate long term complication of ALL and its different treatment options such as endocrine abnormalities for example decreased bone mineral density. METHODS:  a systematic web base search was conducted in MEDLINE up to December 2014. We included articles with available abstract in English language, and participants younger than 18 years. Manual searching was done within the reference list of articles.  Two reviewers independently reviewed and assessed eligibility criteria, assessed quality, and extracted data. RESULTS:  Trace elements concentration decline due to malabsorption or inadequate intake in children with ALL. Osteopenia occurs more frequent in younger children and those who treated with higher doses of corticosteroids. CONCLUSION:  The dietary history of ALL patients who are at more risk for fractures and osteopenia should be screened by paying more attention to calcium and vitamin D intake.

  15. Trisomy 19 and T(9;22 In a Patient with Acute Basophilic Leukemia

    Directory of Open Access Journals (Sweden)

    Alicia Rojas-Atencio

    2011-01-01

    Full Text Available We report a case of acute basophilic leukemia with two coexisting clonal abnormalities, t(9;22 and trisomy 19. The blast showed positive reaction with myeloperoxidase but negative reaction with chloroacetate esterase and acid phosphatase. Metachromatic features of the blast were observed with toluidine blue stain. Ultrastructure study showed the presence of azurophilic granules in basophils and blast mast cells. Conventional and molecular cytogenetic studies revealed, t(9;22 with BCR/ABL positive and trisomy 19 in all metaphase cells. To our knowledge, this paper here is the first to present acute basophilic leukemia with trisomy 19 and t(9;22.

  16. Acute Lymphocytic Leukemia

    Science.gov (United States)

    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. Acute Myeloid Leukemia

    Science.gov (United States)

    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 ...

  18. Nosocomial infections among acute leukemia patients in China: An economic burden analysis.

    Science.gov (United States)

    Wu, Xiaohui; Yan, Tianyuan; Liu, Yunhong; Wang, Jingna; Li, Yingxia; Wang, Shuhui

    2016-10-01

    The economic burden associated nosocomial infections (NIs) in patients with acute leukemia (AL) in China was unclear. A prospective study was conducted to quantify the medical cost burden of NIs among AL patients. Nine hundred ninety-four patients diagnosed with AL between January 2011 and December 2013 were included. Relevant necessary information was extracted from the hospital information system and hospital infection surveillance system. The primary outcome was incidence of NIs and the secondary was economic burden results, including extra medical costs and prolonged length of stay (LOS). We estimated the total incremental cost of NIs by comparing all-cause health care costs in patients with versus without infections. Prolonged duration of stay was compared in patients with different infections. Of 994 patients with AL, 277 (27.9%) experienced NIs. NI was associated with a total incremental cost of $3,092 per patient ($5,227 vs $2,135; P economic burden on patients with AL. The study highlights the influence of NIs on LOS and health care costs and appeal to the establishment of prophylactic measures for NIs to reduce the unnecessary waste of medical resources in the long run. Copyright © 2016 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.

  19. Clinical value of blood lipid, serum β2-microglolulin and tumor necrosis factor-α level in patients with acute leukemia

    International Nuclear Information System (INIS)

    Shen Xiaohua; Huang Zhairong; Yang Yongqing

    2010-01-01

    Objective: To study on diagnosis value of blood lipid, serum β 2 -microglolulin (β 2 -MG) and tumor necrosis factor-α (TNF-α) in acute leukemia. Methods: The serum β 2 -MG and TNF-α (with radioimmunoassay) blood lipid (with biochemistry) levels were determined in 123 patients with acute leukemia as well as 36 controls, then conducted the correlative tests. Results: Serum β 2 -MG, TNF-α and triglyceride levels in 123 patients including 46 patients with acute monocytic leukemia, 32 patients with acute lymphocytic leukemia and 45 patients with acute nonlymphocytic leukemia were significantly higher than those in 36 controls (t=4.123-6.815, P 0.05); The serum cholesterol, high density lipoprotein-cholesterol, low density lipoprotein-cholesterol, apolipoprotein A levels in 123 patients with acute leukemia were significantly lower than those in 36 controls (t=2.110-2.574, P 0.05). Conclusion: The determination of blood lipid, serum β 2 -MG and TNF-α level might be useful for diagnosing acute leukemia and reflecting the prognostic value. (authors)

  20. Membranoproliferative glomerulonephritis and acute renal failure in a patient with chronic lymphocytic leukemia: Response to obinutuzumab.

    Science.gov (United States)

    Jain, Punit; Kanagal-Shamanna, Rashmi; Wierda, William; Ferrajoli, Alessandra; Keating, Michael; Jain, Nitin

    2017-09-01

    Membranoproliferative glomerulonephritis (MPGN) is a common extramedullary renal presentation in chronic lymphocytic leukemia (CLL) and can present with either a frank renal failure or proteinuria. One of its etiologies has been attributed to a paraneoplastic, immune complex phenomenon occurring in CLL. Although there is no standard of care in such patients, use of anti-CD20 monoclonal antibodies like rituximab have been used before in such patients with variable responses. Obinutuzumab is a novel, type II, immunoglobulin-G1 monoclonal antibody with a higher efficacy than rituximab and has an established safely profile in patients with comorbidities and poor renal functions. There are no such reported cases of MPGN in CLL being treated with obinutuzumab. We used the standard doses of obinutuzumab in our elderly patient (78-year-old woman) with high-risk CLL due to an underlying TP53 mutation, along with a MPGN-related acute renal failure. The patient achieved complete remission after six cycles of obinutuzumab; however, she remained positive for minimal residual disease on flow cytometry. Her renal function improved completely, suggesting a complete response of her underlying MPGN. Obinutuzumab has an established safety profile in patients with CLL, but our case is the first reported case of a paraneoplastic, immune complex-mediated MPGN in CLL being treated with obinutuzumab. Obinutuzumab should be explored as a potential option in patients with CLL and MPGN. Copyright © 2016 King Faisal Specialist Hospital & Research Centre. Published by Elsevier B.V. All rights reserved.

  1. Induction chemotherapy versus palliative treatment for acute myeloid leukemia in a consecutive cohort of elderly patients.

    Science.gov (United States)

    Colovic, Milica; Colovic, Natasa; Radojkovic, Milica; Stanisavljevic, Dejana; Kraguljac, Nada; Jankovic, Gradimir; Tomin, Dragica; Suvajdzic, Nada; Vidovic, Ana; Atkinson, Henry Dushan

    2012-09-01

    A retrospective survey of 210 consecutive patients aged ≥ 65 years (median age 69 years, range 65-88 years) with acute myeloid leukemia (AML) diagnosed at a single center over a 6-year period (January 2001 to December 2006) is presented. De novo AML was diagnosed in 179 (85.2 %) patients and 31 (14.7 %) patients had a secondary AML. Twenty-three patients had M0 (11 %), 36 M1 (17.15 %), 57 M2 (27.1 %), eight M3 (3.8 %), 45 M4 (21.4 %), 31 M5 (14.8 %), one M6 (0.5 %), one M7 (0.5 %), and eight patients had unclassified myeloid leukemia (3.8 %) according to French-American-British (FAB) Study Group Classification. Eight patients with M3 (acute promyelocytic leukemia) were excluded from the study. Cytogenetic analysis was performed in 172/202 (85 %) patients. The normal karyotype was found in 81/172 (47 %), high risk aberrations in 32/172 (18.6 %), and favorable karyotype in 13/172 (7.5 %) patients. Supportive and palliative therapies were applied in 115 (56.9 %) patients, a no induction chemotherapy (NIC) group, and 87 (43.1 %) patients received induction chemotherapy (IC group). Complete remission (CR) was achieved in 45/87 (51.7 %) in the IC group and in 5/115 (4.3 %) in the NIC group of patients. After a median follow up of 4 years, 194 (96 %) patients died. The variables significantly associated with a longer overall survival (OS) by univariate analysis were an age of <75 years, a better ECOG performance status (PS) (p = 0.000, CI 95.0 %, 1.358-2.049), a serum LDH activity <600 U/l (p = 0.000, CI 95.0 %, 1.465-2.946), lower white blood cell (WBC) count at diagnosis (p = 0.011, CI 95.0 %, 1.102-2.100), lower comorbidity HCT-CI index (p = 0.000, CI 95 % 2.209-3.458), absence of splenomegaly (p = 0.015, CI 95.0 %, 1.082-2.102) and hepatomegaly (p = 0.008, CI 95.0 %, 1.125-2.171), and no preceding nonhematological malignancy. Multivariate analysis showed that significant factors affecting OS in the IC group were achievement of CR (p = 0.000), the ECOG PS (p = 0

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

    International Nuclear Information System (INIS)

    Naeem, S.; Bukhari, M. H.

    2015-01-01

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

  3. Patients with Acute Myeloid Leukemia Admitted to Intensive Care Units: Outcome Analysis and Risk Prediction.

    Science.gov (United States)

    Pohlen, Michele; Thoennissen, Nils H; Braess, Jan; Thudium, Johannes; Schmid, Christoph; Kochanek, Matthias; Kreuzer, Karl-Anton; Lebiedz, Pia; Görlich, Dennis; Gerth, Hans U; Rohde, Christian; Kessler, Torsten; Müller-Tidow, Carsten; Stelljes, Matthias; Hullermann, Carsten; Büchner, Thomas; Schlimok, Günter; Hallek, Michael; Waltenberger, Johannes; Hiddemann, Wolfgang; Berdel, Wolfgang E; Heilmeier, Bernhard; Krug, Utz

    2016-01-01

    This retrospective, multicenter study aimed to reveal risk predictors for mortality in the intensive care unit (ICU) as well as survival after ICU discharge in patients with acute myeloid leukemia (AML) requiring treatment in the ICU. Multivariate analysis of data for 187 adults with AML treated in the ICU in one institution revealed the following as independent prognostic factors for death in the ICU: arterial oxygen partial pressure below 72 mmHg, active AML and systemic inflammatory response syndrome upon ICU admission, and need for hemodialysis and mechanical ventilation in the ICU. Based on these variables, we developed an ICU mortality score and validated the score in an independent cohort of 264 patients treated in the ICU in three additional tertiary hospitals. Compared with the Simplified Acute Physiology Score (SAPS) II, the Logistic Organ Dysfunction (LOD) score, and the Sequential Organ Failure Assessment (SOFA) score, our score yielded a better prediction of ICU mortality in the receiver operator characteristics (ROC) analysis (AUC = 0.913 vs. AUC = 0.710 [SAPS II], AUC = 0.708 [LOD], and 0.770 [SOFA] in the training cohort; AUC = 0.841 for the developed score vs. AUC = 0.730 [SAPSII], AUC = 0.773 [LOD], and 0.783 [SOFA] in the validation cohort). Factors predicting decreased survival after ICU discharge were as follows: relapse or refractory disease, previous allogeneic stem cell transplantation, time between hospital admission and ICU admission, time spent in ICU, impaired diuresis, Glasgow Coma Scale intensive care.

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

    NARCIS (Netherlands)

    Dubois, V.; Sloan-Bena, F.; Cesbron, A.; Hepkema, B. G.; Gagne, K.; Gimelli, S.; Heim, D.; Tichelli, A.; Delaunay, J.; Drouet, M.; Jendly, S.; Villard, J.; Tiercy, J-M

    Although acquired uniparental disomy (aUPD) has been reported in relapse acute myeloid leukemia (AML), pretransplant aUPD involving chromosome 6 is poorly documented. Such events could be of interest because loss of heterozygosity (LOH) resulting from aUPD in leukemic cells may lead to erroneous

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

    Czech Academy of Sciences Publication Activity Database

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

    2014-01-01

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

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

    Science.gov (United States)

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

    2015-12-01

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

  7. Acute encephalomyelitis complicated with severe neurological sequelae after intrathecal administration of methotrexate in a patient with acute lymphoblastic leukemia.

    Science.gov (United States)

    Nishikawa, Takuro; Okamoto, Yasuhiro; Maruyama, Shinsuke; Tanabe, Takayuki; Kurauchi, Koichiro; Kodama, Yuichi; Nakagawa, Shunsuke; Shinkoda, Yuichi; Kawano, Yoshifumi

    2014-11-01

    A four-year-old girl on maintenance therapy for acute lymphoblastic leukemia (ALL) complained of a headache and low back pain on the day she received her 21st intrathecal methotrexate (it-MTX) administration, and the next day experienced numbness and pain in her foot. This numbness gradually spread to her hand. She thereafter developed a fever and was hospitalized on day 8. After antibiotic therapy, the fever disappeared. However, her lower limbs became paralyzed, and she also developed urinary retention. On day 12, her paralysis progressed upwards, and she also developed paralysis of the upper limbs. Finally, she experienced convulsions with an impairment of consciousness. A magnetic resonance imaging study of the brain and spinal cord showed abnormal signals in the brain cortex and anterior horn. Accordingly, we diagnosed acute encephalomyelitis associated with it-MTX. High-dose intravenous immunoglobulin, steroid pulse therapy, plasma exchange, and dextromethorphan administration were initiated, while she received mechanical ventilation. Despite this intensive treatment, she suffered severe neurological damage and had to be maintained on mechanical ventilation due to persistent flaccid quadriplegia one year after the onset. When patients have symptoms of ascending paralysis during it-MTX treatment, clinicians should carefully consider the possibility of acute encephalomyelitis due to it-MTX.

  8. The relationship between clinical feature, complex immunophenotype, chromosome karyotype, and outcome of patients with acute myeloid leukemia in China.

    Science.gov (United States)

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

    2015-01-01

    Mixed phenotype acute leukemia (MPAL) is a complex entity expressing both lymphoid and myeloid immunophenotyping. In the present study, 47 MPAL, 60 lymphoid antigen-positive acute myeloid leukemia (Ly(+)AML), and 90 acute myeloid leukemia with common myeloid immunophenotype (Ly(-)AML) patients were investigated. We found that, in MPAL patients, there were high proportions of blast cells in bone marrow and incidence of hepatosplenomegaly, lymphadenopathy, and Philadelphia chromosome. The overall survival (OS) and relapse-free survival (RFS) in MPAL patients were significantly shorter than those in Ly(+)AML and Ly(-)AML. With regard to the patients with normal karyotype only, the OS and RFS of MPAL were significantly lower than those of the Ly(+)AML and Ly(-)AML; but there were no significant differences in OS and RFS among the patients with complex karyotype. The OS rates of 3 groups with complex karyotype were lower than those of patients with normal karyotype. In Cox multivariate analysis, complex karyotype was an independent pejorative factor for both OS and RFS. Therefore, MPAL is confirmed to be a poor-risk disease while Ly(+)AML does not impact prognosis. Complex karyotype is an unfavorable prognosis factor in AML patients with different immunophenotype. Mixed immunophenotype and complex karyotype increase the adverse risk when they coexist.

  9. Upregulation of microRNA-100 predicts poor prognosis in patients with pediatric acute myeloid leukemia

    Directory of Open Access Journals (Sweden)

    Kuai W

    2012-09-01

    Full Text Available Jin Bai,1 Aiping Guo,2 Ze Hong,3 Wenxia Kuai31Department of Pediatrics, Huai'an Hospital to Xuzhou Medical College and Huai'an Second People's Hospital, Huai'an, China; 2Department of Pediatrics, Chuzhou Hospital, Huai'an, China; 3Department of Pediatrics, Huai'an First People's Hospital, Huai'an, ChinaObjective: MicroRNA-100 (miR-100, a small noncoding RNA molecule, acts as a tumor suppressor or an oncogene in different cancers. The aberrant expression of this microRNA has been demonstrated as a frequent event in adult patients with acute myeloid leukemia (AML, but little is known for pediatric AML. The aim of this study was to investigate the expression and clinical significance of miR-100 in pediatric AML.Methods: The expression levels of miR-100 in bone marrow mononuclear cells were detected by real-time quantitative polymerase chain reaction in a cohort of 106 patients with de novo pediatric AML. The prognostic values of miR-100 in pediatric AML were also analyzed.Results: Compared with normal controls, upregulation of miR-100 in the bone marrow of pediatric AML patients with statistically significant differences (P < 0.001 was found. The expression levels of miR-100 were found to be significantly higher in pediatric AML patients with extramedullary disease, with the French–American–British classification subtype M7, and with unfavorable day 7 response to induction chemotherapy (P = 0.008, 0.001 and 0.01, respectively. Moreover, both univariate and multivariate analyses revealed that miR-100 upregulation was associated with poorer relapse-free and overall survival in pediatric AML patients.Conclusion: This is the first report demonstrating the upregulation of miR-100 in pediatric AML, and its association with poor relapse-free and overall survival. These results suggest that miR-100 upregulation may be used as an unfavorable prognostic marker in pediatric AML.Keywords: pediatric acute myeloid leukemia, microRNA-100, real

  10. When should patients receive consolidation chemotherapy before allogeneic hematopoietic cell transplantation for acute myeloid leukemia in first complete remission?

    Science.gov (United States)

    Yeshurun, Moshe; Wolach, Ofir

    2018-03-01

    Allogeneic hematopoietic cell transplantation (alloHCT) is a potentially curative therapy for patients with acute myeloid leukemia. Despite the associated graft-versus-leukemia effect, leukemia relapse remains the most common cause of treatment failure after alloHCT. Here, we review the available data on whether there is an advantage in providing pretransplant consolidation chemotherapy prior to alloHCT. Randomized controlled studies are lacking. Data derive largely from four large retrospective registry studies. These analyses are consistent in demonstrating the lack of any survival benefit for pretransplant consolidation chemotherapy once a patient achieves a complete remission and a donor is readily available. These results are valid across conditioning regimen intensities, donor sources, and doses of cytarabine administered during consolidation. Available evidence suggests that patients with acute myeloid leukemia in first complete remission for whom a suitable donor is readily available should not be given pretransplant consolidation before proceeding to alloHCT, regardless of conditioning regimen intensity and that transplantation should be offered promptly at the time remission is achieved without undue delay. Nevertheless, patients for whom a suitable donor is not readily available after achieving first remission, should probably receive 'bridging' consolidation chemotherapy while waiting for a donor to be identified in an attempt to decrease the risk of early disease recurrence before transplantation. The role of minimal residual disease and genetic markers in directing consolidation choices are unclear to date.

  11. Analyzing transformation of myelodysplastic syndrome to secondary acute myeloid leukemia using a large patient database.

    Science.gov (United States)

    Shukron, Ofir; Vainstein, Vladimir; Kündgen, Andrea; Germing, Ulrich; Agur, Zvia

    2012-09-01

    One-third of patients with myelodysplastic syndrome (MDS) progress to secondary acute myeloid leukemia (sAML), with its concomitant poor prognosis. Recently, multiple mutations have been identified in association with MDS-to-sAMLtransition, but it is still unclear whether all these mutations are necessary for transformation. If multiple independent mutations are required for the transformation, sAML risk should increase with time from MDS diagnosis. In contrast, if a single critical biological event determines sAML transformation; its risk should be constant in time elapsing from MDS diagnosis. To elucidate this question, we studied a database of 1079 patients with MDS. We classified patients according to the International Prognostic Scoring System (IPSS), using either the French-American-British (FAB) or the World Health Organization (WHO) criteria, and statistically analyzed the resulting transformation risk curves of each group. The risk of transformation after MDS diagnosis remained constant in time within three out of four risk groups, and in all four risk groups, when patients were classified according to FAB or to the WHO-determined criteria, respectively. Further subdivision by blast percentage or cytogenetics had no influence on this result. Our analysis suggests that a single random biological event leads to transformation to sAML, thus calling for the exclusion of time since MDS diagnosis from the clinical decision-making process. Copyright © 2012 Wiley Periodicals, Inc.

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

    Science.gov (United States)

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

    2016-01-19

    Hypocellular acute myeloid leukemia (Hypo-AML) is a rare disease entity. Studies investigating the biological characteristics of hypo-AML have been largely lacking. We examined the clinical and biological characteristics, as well as treatment outcomes of hypo-AML in our institutes over a seven years period. We retrospectively analyzed data on 631 adult AML patients diagnosed according to the French-American-British (FAB) classification and WHO classification of tumors of haematopoietic and lymphoid tissue, including 43 patients with hypo-AML. Biological variables, treatment outcomes and follow-up data on hypo-AML patients were analyzed. Out of 631 AML patients, 47 (7.4%) were diagnosed as hypo-AML, out of which 43 patients were evaluable. Compared with non-hypocellular AML, hypo-AML patients tended to be older (P = 0.05), more likely to present with leukocytopenia (P < 0.01) and anterior hematological diseases (P = 0.02). The overall complete remission (CR) rate, disease free survival (DFS), and overall survival (OS) in hypo-AML patients were comparable to those in non-hypo AML patients. Twenty-seven (62.8%) patients with hypocellular AML were treated with the standard regimen of anthracyclines and cytarabine (XA) (associated CR rate: 51.9%; median OS: 7 months; median DFS: 6.5 months). Sixteen (37.2%) patients were treated with a priming regimen containing homoharringtonine, cytarabine and G-CSF (HAG) (associated CR rate: 81.25%; median OS: 16 months; median DFS: 16 months). The overall prognosis of hypo-AML was not inferior to that of non-hypo AML. HAG regimen might increase response rates and improve survival in hypo-AML patients.

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

    Science.gov (United States)

    ... Videos for Educators Search English Español Acute Lymphoblastic Leukemia (ALL) KidsHealth / For Parents / Acute Lymphoblastic Leukemia (ALL) ... Coping Print en español Leucemia linfoblástica aguda About Leukemia Leukemia is a type of cancer that affects ...

  14. Severe malnutrition evaluated by patient-generated subjective global assessment results in poor outcome among adult patients with acute leukemia

    Science.gov (United States)

    Li, Ji; Wang, Chang; Liu, Xiaoliang; Liu, Qiuju; Lin, Hai; Liu, Chunshui; Jin, Fengyan; Yang, Yan; Bai, Ou; Tan, Yehui; Gao, Sujun; Li, Wei

    2018-01-01

    Abstract To evaluate nutritional status in adult patients with acute leukemia (AL) using patient-generated subjective global assessment (PG-SGA) and to investigate the influence of nutritional status on prognosis. We observationally investigated 68 adult patients with newly diagnosed AL who received PG-SGA at the First Hospital of Jilin University between May 2013 and July 2015. Clinical features, chemotherapy regimens, biochemical indexes, body composition, complete remission (CR) rate, minimal residual disease (MRD), survival time, and side-effects of chemotherapy were compared between patients with and without severe malnutrition. Mean PG-SGA scores of the total patients were 6.1 ± 4.0, and 19 of 68 (27.9%) patients had severe malnutrition (PG-SGA score ≥9). Patients with acute myeloid leukemia (AML) had higher scores than those with acute lymphocytic leukemia (ALL; P = .011) and high-risk patients had higher scores regardless of whether they had AML or ALL (AML, P = .012; ALL, P = .043). Univariate analysis showed that severe malnutrition was correlated with age (P = .041), transferrin (P = .042), Karnofsky Performance Status score (P = .006), and C-reactive protein (CRP) (P = .018). Multivariate analysis demonstrated that severe malnutrition was associated with CRP (hazard ratio [HR] = 1.020, 95% confidence interval [CI]: 1.002–1.039, P = .026). No difference was found in CR rate (P = .831) between patients with and without malnutrition, but those who were severely malnourished had higher MRD (P = .048 in AML patients, P = .036 in ALL patients) and more gastrointestinal side-effects (P = .014). Severe malnutrition was also associated with inferior overall survival (HR = 0.243, 95% CI: 0.063–0.945, P = .041) but not with event-free survival (HR = 0.808, 95% CI: 0.338–1.934, P = .663). Severe malnutrition defined by PG-SGA in adult patients with de novo AL may result in poor outcome

  15. Independent prognostic impact of CD15 on complete remission achievement in patients with acute myeloid leukemia.

    Science.gov (United States)

    Chisini, Marta; Stefanizzi, Caterina; Ceglie, Teresa; Raponi, Sara; Vozella, Federico; Colafigli, Gioia; Salaroli, Adriano; D'Angiò, Mariella; Mancini, Marco; Diverio, Daniela; Breccia, Massimo; Mancini, Francesca; Minotti, Clara; Trisolini, Silvia; Capria, Saveria; Testi, Anna Maria; Guarini, Anna; Latagliata, Roberto; De Propris, Maria Stefania; Foà, Robin

    2017-12-01

    The prognostic role of CD15 in acute myeloid leukemia (AML) has been tested in different studies with conflicting results. To address this issue, we retrospectively evaluated a cohort of 460 AML patients of all ages with the exclusion of acute promyelocytic leukemia (M/F 243/217, median age 50.6 years [range 0.9-81.2]) intensively treated at our institute between January 1999 and December 2010. CD15 positivity was found in 171 of 406 evaluable patients (42.1%). Complete remission (CR) was achieved by 334 patients (72.6%), while 82 (17.8%) were resistant and 44 (9.6%) died during induction: the median CR duration was 15.5 months (range 0.6-176.0), with 2-year disease-free survival rate of 45.1% (95% confidence interval 39.6-50.6). The median overall survival was 14.4 months (range 0.3-177.0), with 2-year overall survival rate of 42.2% (95% confidence interval 37.5-46.9). At univariate analysis for CR achievement, age classification (P = .045), low-risk karyotype (P  8 g/dL (P = .020), and white blood cell < 50 × 10 9 /L (P = .034) had a favorable impact. At a multivariate logistic regression model, CD15 positivity (P = .002), age < 60 years (P = .008), white blood cell < 50 × 10 9 /L (P = .017), and low-risk/no high-risk karyotype (P = .026/P = .025) retained an independent prognostic role on CR achievement. The baseline assessment of CD15 positivity appears to have a role in the risk evaluation for CR achievement in AML patients undergoing intensive chemotherapy and should be assessed in prospective studies together with other clinical and biologic features already reported. Copyright © 2016 John Wiley & Sons, Ltd.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2002-07-01

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

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

    International Nuclear Information System (INIS)

    Matsuyama, Takaharu; Kato, Koji

    2002-01-01

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

  18. Mutations in the gene for the granulocyte colony-stimulating-factor receptor in patients with acute myeloid leukemia preceded by severe congenital neutropenia

    NARCIS (Netherlands)

    F. Dong (Fan); R.K. Brynes; N. Tidow; K. Welte (Karl); B. Löwenberg (Bob); I.P. Touw (Ivo)

    1995-01-01

    textabstractBACKGROUND. In severe congenital neutropenia the maturation of myeloid progenitor cells is arrested. The myelodysplastic syndrome and acute myeloid leukemia develop in some patients with severe congenital neutropenia. Abnormalities in the signal-transduction

  19. Iron chelation therapy with deferasirox induced complete remission in a patient with chemotherapy-resistant acute monocytic leukemia.

    Science.gov (United States)

    Fukushima, Toshihiro; Kawabata, Hiroshi; Nakamura, Takuji; Iwao, Haruka; Nakajima, Akio; Miki, Miyuki; Sakai, Tomoyuki; Sawaki, Toshioki; Fujita, Yoshimasa; Tanaka, Masao; Masaki, Yasufumi; Hirose, Yuko; Umehara, Hisanori

    2011-05-01

    A patient with chemotherapy-resistant acute monocytic leukemia who achieved complete remission (CR) after iron chelation therapy (ICT) with deferasirox is reported for the first time. A 73-year-old Japanese man with acute monocytic leukemia who was refractory to conventional remission induction chemotherapies achieved a partial response, with some improvement of his hemoglobin level and white blood cell count after gemtuzumab ozogamicin (GO) treatment. Seven months after GO treatment, the disease relapsed and the patient developed pancytopenia. He declined further chemotherapy, and started receiving 1,200-1,800 ml of packed red blood cell transfusion per month together with ICT with deferasirox (baseline serum ferritin level was 1,412 ng/ml). Twelve months after the initiation of deferasirox, the patient's serum ferritin level decreased to below 1,000 ng/ml and deferasirox was discontinued. Four months after discontinuation of deferasirox, the blood cell count normalized and the patient became transfusion-independent. Bone marrow aspiration and biopsy revealed hematological and cytogenetic CR. CR was achieved after ICT with deferasirox in a patient with acute myelogenous leukemia, suggesting that deferasirox may have an antileukemic effect in the clinical setting.

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

    Directory of Open Access Journals (Sweden)

    Geetaram Sahu

    2011-11-01

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

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

    Science.gov (United States)

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

    2014-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Grazia Locafaro

    2014-01-01

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

  3. The Past, Present and Future Subclassification of Patients with Acute Myeloid Leukemia.

    Science.gov (United States)

    Forthun, Rakel B; Hinrichs, Carina; Dowling, Tara H; Bruserud, Øystein; Selheim, Frode

    2016-01-01

    Acute myeloid leukemia (AML) is characterized as a heterogeneous disease where the patients are sub grouped according to several classification systems and mutational analyses. Diagnosis of AML is based on identification of the specific myeloid cell initiating the disease, quantification of immature blasts in bone marrow and peripheral blood, as well as detection of mutations and translocations. The heterogeneity of AML is caused by a block in differentiation that may occur in any of the different myeloid cell populations. These undifferentiated cells also harbor an increased proliferation potential that leads to accumulation of immature leukemic cells. The current development of more sensitive and less labor intensive analysis methods has led classification of patients from being a system based on morphology of the leukemic cells to being more sophisticated, detecting translocations and small mutations found in the whole leukemic clone or in a minor subclone. This review aims to describe the most common classification systems of AML, including frequently occurring translocations, mutations and epigenetic alterations, as well as describe traditional and novel methods for diagnosis and analysis of these patients.

  4. [Copy number alterations in adult patients with mature B acute lymphoblastic leukemia treated with specific immunochemotherapy].

    Science.gov (United States)

    Ribera, Jordi; Zamora, Lurdes; García, Olga; Hernández-Rivas, Jesús-María; Genescà, Eulàlia; Ribera, Josep-Maria

    2016-12-02

    Unlike Burkitt lymphoma, molecular abnormalities other than C-MYC rearrangements have scarcely been studied in patients with mature B acute lymphoblastic leukemia (B-ALL). The aim of this study was to analyze the frequency and prognostic significance of copy number alterations (CNA) in genes involved in lymphoid differentiation, cell cycle and tumor suppression in adult patients with B-ALL. We have analyzed by multiplex ligation-dependent probe amplification the genetic material from bone marrow at diagnosis from 25 adult B-ALL patients treated with rituximab and specific chemotherapy. The most frequent CNA were alterations in the 14q32.33 region (11 cases, 44%) followed by alterations in the cell cycle regulator genes CDKN2A/B and RB1 (16%). No correlation between the presence of specific CNA and the clinical-biologic features or the response to therapy was found. The high frequency of CNA in the 14q32.33 region, CDKN2A/B and RB1 found in our study could contribute to the aggressiveness and invasiveness of mature B-ALL. Copyright © 2016 Elsevier España, S.L.U. All rights reserved.

  5. Role of regulatory T cells in acute myeloid leukemia patients undergoing relapse-preventive immunotherapy.

    Science.gov (United States)

    Sander, Frida Ewald; Nilsson, Malin; Rydström, Anna; Aurelius, Johan; Riise, Rebecca E; Movitz, Charlotta; Bernson, Elin; Kiffin, Roberta; Ståhlberg, Anders; Brune, Mats; Foà, Robin; Hellstrand, Kristoffer; Thorén, Fredrik B; Martner, Anna

    2017-11-01

    Regulatory T cells (T regs ) have been proposed to dampen functions of anti-neoplastic immune cells and thus promote cancer progression. In a phase IV trial (Re:Mission Trial, NCT01347996, http://www.clinicaltrials.gov ) 84 patients (age 18-79) with acute myeloid leukemia (AML) in first complete remission (CR) received ten consecutive 3-week cycles of immunotherapy with histamine dihydrochloride (HDC) and low-dose interleukin-2 (IL-2) to prevent relapse of leukemia in the post-consolidation phase. This study aimed at defining the features, function and dynamics of Foxp3 + CD25 high CD4 + T regs during immunotherapy and to determine the potential impact of T regs on relapse risk and survival. We observed a pronounced increase in T reg counts in peripheral blood during initial cycles of HDC/IL-2. The accumulating T regs resembled thymic-derived natural T regs (nT regs ), showed augmented expression of CTLA-4 and suppressed the cell cycle proliferation of conventional T cells ex vivo. Relapse of AML was not prognosticated by T reg counts at onset of treatment or after the first cycle of immunotherapy. However, the magnitude of T reg induction was diminished in subsequent treatment cycles. Exploratory analyses implied that a reduced expansion of T regs in later treatment cycles and a short T reg telomere length were significantly associated with a favorable clinical outcome. Our results suggest that immunotherapy with HDC/IL-2 in AML entails induction of immunosuppressive T regs that may be targeted for improved anti-leukemic efficiency.

  6. Acute leukemias of ambiguous origin.

    Science.gov (United States)

    Porwit, Anna; Béné, Marie C

    2015-09-01

    This session of the Society for Hematopathology/European Association for Haematopathology Workshop focused on acute leukemias of ambiguous origin. We provide an overview of mixed-phenotype acute leukemia (MPAL) as recognized in the current World Health Organization classification and summarize diagnostic criteria for major categories of MPAL: B/myeloid, T/myeloid, B/T, and B/T/myeloid. Most MPAL cases submitted were B/myeloid and T/myeloid MPAL, the most frequent types, but three cases of B/T MPAL were also submitted, and examples of all categories are illustrated. We emphasize that a comprehensive approach to immunophenotyping is required to accurately establish the diagnosis of MPAL. Flow cytometry immunophenotyping using a large panel of antibodies is needed as well as confirmatory immunohistochemical analysis and cytochemistry studies for myeloperoxidase and nonspecific esterase. We discuss technical issues in determining blast lineage and possible pitfalls in MPAL diagnosis. In particular, rare cases of B-acute lymphoblastic leukemia (B-ALL) can express myeloperoxidase but are otherwise consistent with B-ALL and should be treated as such. Last, we review the differential diagnosis between acute undifferentiated leukemia and acute myeloid leukemia with minimal differentiation. There was an agreement that diagnosis of MPAL can be challenging, especially if applied flow cytometry panels are not comprehensive enough. Copyright© by the American Society for Clinical Pathology.

  7. Frank hematuria as the presentation feature of acute leukemia

    Directory of Open Access Journals (Sweden)

    Suriya Owais

    2010-01-01

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

  8. Detection of cytokine expression patterns in the peripheral blood of patients with acute leukemia by antibody microarray analysis.

    Science.gov (United States)

    Li, Qing; Li, Mei; Wu, Yao-hui; Zhu, Xiao-jian; Zeng, Chen; Zou, Ping; Chen, Zhi-chao

    2014-04-01

    The cytokines of acute leukemia (AL) patients have certain expression patterns, forming a complex network involved in diagnosis, progression, and prognosis. We collected the serum of different AL patients before and after complete remission (CR) for detection of cytokines by using an antibody chip. The expression patterns of cytokines were determined by using bioinformatics computational analysis. The results showed that there were significant differences in the cytokine expression patterns between AL patients and normal controls, as well as between acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL). In confirmatory test, ELISA revealed the expression of uPAR in AL. Moreover, the bioinformatic analysis showed that the differentially expressed cytokines among the AL groups were involved in different biological behaviors and were closely related with the development of the disease. It was concluded that the cytokine expression pattern of AL patients is significantly different from that of healthy volunteers. Also, differences of cytokine expression patterns exist between AML and ALL, and between before and after CR in the same subtype of AL, which holds important clinical significance for revealing disease progression.

  9. A Modified Integrated Genetic Model for Risk Prediction in Younger Patients with Acute Myeloid Leukemia.

    Science.gov (United States)

    Sloan, Caroline E; Luskin, Marlise R; Boccuti, Anne M; Sehgal, Alison R; Zhao, Jianhua; Daber, Robert D; Morrissette, Jennifer J D; Luger, Selina M; Bagg, Adam; Gimotty, Phyllis A; Carroll, Martin

    2016-01-01

    Although cytogenetics-based prognostication systems are well described in acute myeloid leukemia (AML), overall survival (OS) remains highly variable within risk groups. An integrated genetic prognostic (IGP) model using cytogenetics plus mutations in nine genes was recently proposed for patients ≤60 years to improve classification. This model has not been validated in clinical practice. We retrospectively studied 197 patients with newly diagnosed de novo AML. We compared OS curves among the mutational profiles defined by the IGP model. The IGP model assigned patients with intermediate cytogenetics as having favorable, intermediate or unfavorable mutational profiles. The IGP model reassigned 50 of 137 patients with intermediate cytogenetics to favorable or unfavorable mutational profiles. Median OS was 2.8 years among 14 patients with intermediate cytogenetics and favorable mutational profiles (mutant NPM1 and mutant IDH1 or IDH2) and 1.3 years among patients with intermediate mutational profiles. Among patients with intermediate cytogenetics labeled as having unfavorable mutational profiles, median OS was 0.8 years among 24 patients with FLT3-ITD positive AML and high-risk genetic changes (trisomy 8, TET2 and/or DNMT3A) and 1.7 years among 12 patients with FLT3-ITD negative AML and high-risk mutations (TET2, ASXL1 and/or PHF6). OS for patients with intermediate cytogenetics and favorable mutational profiles was similar to OS for patients with favorable cytogenetics (p = 0.697) and different from patients with intermediate cytogenetics and intermediate mutational profiles (p = 0.028). OS among patients with FLT3-ITD positive AML and high-risk genetic changes was similar to patients with unfavorable cytogenetics (p = 0.793) and different from patients with intermediate IGP profile (p = 0.022). Patients with FLT3-ITD negative AML and high-risk mutations, defined as 'unfavorable' in the IGP model, had OS similar to patients with intermediate IGP profile (p = 0

  10. A Modified Integrated Genetic Model for Risk Prediction in Younger Patients with Acute Myeloid Leukemia.

    Directory of Open Access Journals (Sweden)

    Caroline E Sloan

    Full Text Available Although cytogenetics-based prognostication systems are well described in acute myeloid leukemia (AML, overall survival (OS remains highly variable within risk groups. An integrated genetic prognostic (IGP model using cytogenetics plus mutations in nine genes was recently proposed for patients ≤60 years to improve classification. This model has not been validated in clinical practice.We retrospectively studied 197 patients with newly diagnosed de novo AML. We compared OS curves among the mutational profiles defined by the IGP model. The IGP model assigned patients with intermediate cytogenetics as having favorable, intermediate or unfavorable mutational profiles. The IGP model reassigned 50 of 137 patients with intermediate cytogenetics to favorable or unfavorable mutational profiles. Median OS was 2.8 years among 14 patients with intermediate cytogenetics and favorable mutational profiles (mutant NPM1 and mutant IDH1 or IDH2 and 1.3 years among patients with intermediate mutational profiles. Among patients with intermediate cytogenetics labeled as having unfavorable mutational profiles, median OS was 0.8 years among 24 patients with FLT3-ITD positive AML and high-risk genetic changes (trisomy 8, TET2 and/or DNMT3A and 1.7 years among 12 patients with FLT3-ITD negative AML and high-risk mutations (TET2, ASXL1 and/or PHF6. OS for patients with intermediate cytogenetics and favorable mutational profiles was similar to OS for patients with favorable cytogenetics (p = 0.697 and different from patients with intermediate cytogenetics and intermediate mutational profiles (p = 0.028. OS among patients with FLT3-ITD positive AML and high-risk genetic changes was similar to patients with unfavorable cytogenetics (p = 0.793 and different from patients with intermediate IGP profile (p = 0.022. Patients with FLT3-ITD negative AML and high-risk mutations, defined as 'unfavorable' in the IGP model, had OS similar to patients with intermediate IGP profile (p

  11. CNS relapse in a low risk acute promyelocytic leukemia patient treated with ATRA-based regimen: is there a role for prophylactic CNS therapy in acute promyelocytic leukemia?

    OpenAIRE

    Gangadharan, K. V.; Prabhu, Raghuveer; Mampilly, Neena

    2009-01-01

    Though the incidence of CNS relapse in acute promyelocytic leukemia (AML-M3 FAB classification) has increased following the advent of all-trans retinoic acid (ATRA), still CNS relapse accounts for only 2–3% of all relapses in AML-M3 trated with standard ATRA plus chemotherapy regimen. We report a case of low risk AML-M3 treated with standard therapy, developing CNS relapse while on maintenance therapy with ATRA + 6-mercaptopurine (6-MP) + methotrexate (MTX).

  12. Association of the methylenetetrahydrofolate reductase polymorphism in Korean patients with childhood acute lymphoblastic leukemia.

    Science.gov (United States)

    Kim, Nam Keun; Chong, So Young; Jang, Moon Ju; Hong, Seung Ho; Kim, Heung Sik; Cho, Eun Kyung; Lee, Jung Ae; Ahn, Myung Ju; Kim, Chul Soo; Oh, Doyeun

    2006-01-01

    Methylenetetrahydrofolate reductase plays a central role in converting folate to methyl donor for DNA methylation. Recently, methylenetetrahydrofolate reductase (MTHFR C677T and A1298C) mutations were discovered to be associated with childhood acute lymphoblastic leukemia (ALL), as well as colon cancer, lymphoma, esophageal and stomach cancer. Therefore, it was hypothesized that the MTHFR polymorphisms are associated with the risk of childhood ALL in the Korean population. DNA samples taken from 66 patients with ALL and 100 age-matched controls were analyzed using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay for detection of MTHFR C677T and A1298C mutations. The frequency of the AC genotype for MTHFR A1298C polymorphism was significantly different between the controls and the cases (OR, 2.22; CI, 95% 1.09-4.51, p=0.03). The 1298AC+CC genotype was also significantly different (OR, 2.11; 95% CI, 1.06-4.22; p=0.049). There was, however, no significant difference for MTHFR C677T polymorphism and combined genotype frequencies between the two groups. Although no consistent results on associations between MTHFR A 1298C polymorphism and ALL in the populations studied were obtained, the A1298C polymorphism, at least in Koreans, may be a genetic determinant among childhood ALL patients.

  13. Significance of BAFF/APRIL Expression and Their Receptors in Pediatric Patients With Acute Lymphoblastic Leukemia.

    Science.gov (United States)

    Sun, Baolan; Li, Lin; Xu, Meiyu; Wang, Xudong; Wang, Feng; Ni, Hongbing

    2016-04-01

    In this study, we investigated the mRNA expression and protein levels of B-cell activating factor (BAFF)/a proliferation-inducing ligand (APRIL) and their receptors in acute lymphoblastic leukemia (ALL) cell lines and pediatric patients with ALL using real-time polymerase chain reaction, enzyme-linked immunosorbent assay, and Western blotting. The location and level of the BAFF/APRIL proteins in ALL cell lines were also detected by immunofluorescence cytochemistry and flow cytometry. Correlations between plasma protein levels of BAFF/APRIL and primary clinical parameters were analyzed. We found that BAFF/APRIL was highly expressed in pediatric ALL patients and ALL cell lines. The BAFF/APRIL proteins were located on the cell membrane, and the proportion of positive cells and mean fluorescence intensity were significantly higher than in the healthy control group (PBAFF/APRIL and their receptors in untreated ALL children were significantly higher than in healthy controls (PBAFF/APRIL were positively correlated with the white blood cell count, lactate dehydrogenase, and serum ferritin. Abnormal levels of BAFF/APRIL in pediatric ALL suggest that BAFF/APRIL are associated with the development and progression of ALL in children and may provide information for the development of BAFF-based and APRIL-based targeted therapies.

  14. Autoantibodies Against Carbonic Anhydrase I and II in Patients with Acute Myeloid Leukemia

    Directory of Open Access Journals (Sweden)

    Ahmet Menteşe

    2017-12-01

    Full Text Available Objective: Cancer, one of the principal causes of death, is a global social health problem. Autoantibodies developed against the organism’s self-antigens are detected in the sera of subjects with cancer. In recent years carbonic anhydrase (CA I and II autoantibodies have been shown in some autoimmune diseases and carcinomas, but the mechanisms underlying this immune response have not yet been explained. The aim of this study was to evaluate CA I and II autoantibodies in patients with acute myeloid leukemia (AML and to provide a novel perspective regarding the autoimmune basis of the disease. Materials and Methods: Anti-CA I and II antibody levels were investigated using ELISA in serum samples from 30 patients with AML and 30 healthy peers. Results: Anti-CA I and II antibody titers in the AML group were significantly higher compared with the control group (p=0.0001 and 0.018, respectively. A strong positive correlation was also determined between titers of anti-CA I and II antibodies (r=0.613, p=0.0001. Conclusion: Our results suggest that these autoantibodies may be involved in the pathogenesis of AML. More extensive studies are now needed to reveal the entire mechanism.

  15. An improved pre-clinical patient-derived liquid xenograft mouse model for acute myeloid leukemia

    Directory of Open Access Journals (Sweden)

    Zhisheng Her

    2017-10-01

    Full Text Available Abstract Background Xenotransplantation of patient-derived AML (acute myeloid leukemia cells in NOD-scid Il2rγ null (NSG mice is the method of choice for evaluating this human hematologic malignancy. However, existing models constructed using intravenous injection in adult or newborn NSG mice have inferior engraftment efficiency, poor peripheral blood engraftment, or are difficult to construct. Methods Here, we describe an improved AML xenograft model where primary human AML cells were injected into NSG newborn pups intrahepatically. Results Introduction of primary cells from AML patients resulted in high levels of engraftment in peripheral blood, spleen, and bone marrow (BM of recipient mice. The phenotype of engrafted AML cells remained unaltered during serial transplantation. The mice developed features that are consistent with human AML including spleen enlargement and infiltration of AML cells into multiple organs. Importantly, we demonstrated that although leukemic stem cell activity is enriched and mediated by CD34+CD117+ subpopulation, CD34+CD117− subpopulation can acquire CD34+CD117+ phenotype through de-differentiation. Lastly, we evaluated the therapeutic potential of Sorafenib and Regorafenib in this AML model and found that periphery and spleen AML cells are sensitive to these treatments, whereas BM provides a protective environment to AML. Conclusions Collectively, our improved model is robust, easy-to-construct, and reliable for pre-clinical AML studies.

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

    Science.gov (United States)

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

    2016-08-01

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

  17. Health care utilization and end-of-life care for older patients with acute myeloid leukemia.

    Science.gov (United States)

    El-Jawahri, Areej R; Abel, Gregory A; Steensma, David P; LeBlanc, Thomas W; Fathi, Amir T; Graubert, Timothy A; DeAngelo, Daniel J; Wadleigh, Martha; Ballen, Karen K; Foster, Julia E; Attar, Eyal C; Amrein, Philip C; Brunner, Andrew M; Stone, Richard M; Temel, Jennifer S

    2015-08-15

    Health care utilization in older adults (age ≥60 years) with acute myeloid leukemia (AML) has not been well studied. We conducted a retrospective analysis of 330 consecutive older patients who were diagnosed with AML between May 1, 2005 and December 23, 2011, at 2 hospitals in Boston to examine their health care utilization and end-of-life care. Using multivariable logistic and linear regression models adjusting for covariates, we also compared health care utilization between patients who received intensive induction chemotherapy (n = 197; cytarabine/ anthracycline combination) versus nonintensive chemotherapy (n = 133; single-agent therapy). The median number of hospitalizations for the entire cohort was 4.2 (range, 1-18 hospitalizations). Patients who died spent a mean of 28.3% of their life after diagnosis in the hospital and 13.8% of their life attending outpatient clinic appointments. Although the majority of patients (87.9%) died during the 2-year follow-up period, a minority received palliative care (16.2%) or hospice (23.1%) services. Within 30 days of death, 84.5% of patients were hospitalized, and 61% died in the hospital. Among the patients who died, those who received intensive induction therapy (vs nonintensive therapy) spent 30% more of their life after diagnosis in the hospital (P < .0001) and were less likely to receive hospice services (odds ratio, 0.45; P = .05). The current findings highlight the intensity of health care utilization among older patients with AML, regardless of treatment modality. Despite the poor prognosis, palliative care and hospice services are rarely used. Future work should study novel health care delivery models to optimize care throughout the course of illness and at the end of life. © 2015 American Cancer Society.

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

    Science.gov (United States)

    Samra, Mohamed A; Mahmoud, Hossam K; Abdelhamid, Thoraya M; El Sharkawy, Nahla M; Elnahass, Yasser H; Elgammal, Mossaad; Abdelfattah, Rafaat M; Eid, Salem; Ghaleb, Fayek M; Kamel, Azza M

    2013-09-01

    Minimal residual disease (MRD) studies in adult acute lymphoblastic leukemia (ALL) give highly significant prognostic information superior to other standard criteria as age, gender and total leucocytic count (TLC) in distinguishing patients at high and low risk of relapse. We aimed to determine the value of MRD monitoring by flowcytometry (FCM) in predicting outcome in adult Precursor ALL patients. Bone marrow (BM) samples were analyzed by 4-color FCM collected at diagnosis and after induction therapy (MRD1) to correlate MRD positivity with disease free survival (DFS) and overall survival (OS). Study included 57 adult ALL patients (44 males and 13 females) with a median age of 22 years (18-49). DFS showed no significant difference with age, gender and initial TLC (p=0.838, 0.888 and 0.743, respectively). Cumulative DFS at 2 years was 34% for B-lineage ALL (n: 35) and 57% for T-lineage ALL (n: 18) (p = 0.057). Cumulative DFS at 2 years was 7% for MRD1 positive (high risk, HR) versus 57% for MRD1 negative patients (Low risk, LR) (p MRD1, OS at 2 years was 18% for MRD1 HR (n: 17) versus 65% for MRD1 LR (n: 38) (p < 0.001). OS was 35% for high-risk patients (n: 30) and 62% for low-risk patients (n: 27) classified according to GMALL risk stratification (p = 0.017). MRD by FCM is a strong independent predictor of outcome in terms of DFS and OS and is a powerful informative parameter in guiding individual treatment in ALL patients. Copyright © 2013. Production and hosting by Elsevier B.V.

  19. Liver and spleen MRI findings in virus-associated hemophagocytic syndrome in a patient with acute lymphocytic leukemia

    International Nuclear Information System (INIS)

    Zilkha, A.; Madan, V.; Leonidas, J.C.; Valderrama, E.

    1998-01-01

    Virus-associated hemophagocytic syndrome is characterized by the phagocytosis of erthythrocytes and other blood elements in multiple organ systems, especially the liver and spleen. Magnetic resonance imaging (MRI) can suggest this diagnosis in the proper clinical setting by demonstrating multiple, rounded signal voids in the spleen corresponding to hemosiderin deposition. We report a patient with virus-associated hemophagocytic syndrome during the course of acute lymphocytic leukemia and MRI findings that suggested the preoperative diagnosis. (orig.)

  20. Liver and spleen MRI findings in virus-associated hemophagocytic syndrome in a patient with acute lymphocytic leukemia

    Energy Technology Data Exchange (ETDEWEB)

    Zilkha, A.; Madan, V.; Leonidas, J.C. [Division of Pediatric Radiology, Island Jewish Medical Center, New Hyde Park, NY (United States); Valderrama, E. [Department of Pathology, Long Island Jewish Medical Center, New Hyde Park, NY (United States)

    1998-12-01

    Virus-associated hemophagocytic syndrome is characterized by the phagocytosis of erthythrocytes and other blood elements in multiple organ systems, especially the liver and spleen. Magnetic resonance imaging (MRI) can suggest this diagnosis in the proper clinical setting by demonstrating multiple, rounded signal voids in the spleen corresponding to hemosiderin deposition. We report a patient with virus-associated hemophagocytic syndrome during the course of acute lymphocytic leukemia and MRI findings that suggested the preoperative diagnosis. (orig.) With 1 fig., 4 refs.

  1. [Chronic hepatic damage in acute promyelocytic leukemia patients treated with tetra-arsenic tetra-sulfide].

    Science.gov (United States)

    Qin, Xiao-ying; Jiang, Bin; Li, Guo-xuan; Lu, Dao-pei

    2006-04-01

    To investigate the chronic hepatic damage in acute promyelocytic leukemia (APL) patients long-term treated with tetra-arsonic tetra-sulfide (As(4)S(4)). The periodical liver biochemical examinations and ultrasonography results and hepatic fibrosis indicators (P III NP and type IV collagen) of patients were analysed. 106 APL patients treated with As(4)S(4), the median follow-up time was 36 months (6 - 72). The HCV(-) group includes 84 APL patients. During the first course the abnormal rate of the alanine aminotransferase (ALT) and aspartate aminotransferase (AST) was 16.7% and 14.5% (higher than the two times of the normal value), the ALT, AST, gamma-glyoxylate aminotransferase (GGT) levels during the first course were statistically higher than As4S4 treatment before (P 0.05). Other biochemical indicators such as ALP, LDH, TBIL, DBIL, TP, ALB, A/G, BUN, CRE, there were no significantly differences before and after As(4)S(4) treatment (P > 0.05). The HCV(+) group includes 22 APL patients, during the first course, the abnormal rate of the ALT, AST were 63.6% and 59.1%, but at the 2 year, more than 3 years there were no significantly differences compared with As(4)S(4) treatment before (P > 0.05). 42 APL patients were treated with As(4)S(4) more than 3 years, in 33 HCV(-) APL patients, two APL patients had splenomegaly, one APL patient's breadth of the portal vein was wider than 1.4 cm, 21 APL patients had fatty liver (63.6%). The hepatic fibrosis indicators of the 16 APL patients were all normal. In 9 HCV(+) APL patients, 4 APL patients had splenomegaly, 2 APL patients, breadth of portal vein were wider than 1.4 cm, 6 APL patients had fatty liver (66.7%). 6 patients were examined with the hepatic fibrosis indicators, 2 patients, were higher than the normal value. Long term As(4)S(4) treatment for APL patients had no obvious effects on hepatic function, no obvious hepatic fibrosis and portal hypertension signs at more than 3 years, excepting for the rate of fatty liver

  2. Acute Lymphoblastic Leukemia Presented as Multiple Breast Masses

    International Nuclear Information System (INIS)

    Bayrak, Ilkay Koray; Yalin, Turkay; Ozmen, Zafer; Aksoz, Tolga; Doughanji, Roula

    2009-01-01

    Breast metastases in cases leukemia are very rare and occur primarily in patients with acute myeloid leukemia. We report the involvement of breast metastases in a 30-year-old woman with acute T cell lymphoblastic leukemia. The patient's mammograms revealed an extremely dense pattern with ill-defined, denser mass-like lesions in both breasts. A bilateral breast ultrasonographic evaluation revealed lobular-shaped and partly ill-defined hypoechoic masses with a multi-septated nodular (mottled) appearance

  3. PRAME overexpression predicted good outcome in pediatric B-cell acute lymphoblastic leukemia patients receiving chemotherapy.

    Science.gov (United States)

    Zhang, Yan-Huan; Lu, Ai-Dong; Yang, Lu; Li, Ling-Di; Chen, Wen-Min; Long, Ling-Yu; Zhang, Le-Ping; Qin, Ya-Zhen

    2017-01-01

    To investigate the prognostic value of PRAME expression in pediatric acute lymphoblastic leukemia(ALL), we measured PRAME transcript levels at diagnosis in 191 patients(146 B-ALL; 45T-ALL)receiving chemotherapy only. PRAME overexpression was defined as transcript levels higher than 0.30%, which is the upper limit of normal bone marrow and the optimal cutoff value derived from ROC curve analysis. PRAME overexpression was identified in 45.5% of patients. In B-ALL, PRAME overexpression was significantly associated with lower CIR(cumulative incidence of relapse), higher DFS (disease-freesurvival), and OS(overall survival) rates at 3 years, respectively (5.8% vs. 14.9%, P=0.014; 94.2% vs. 85.1%, P=0.014; 96.0% vs. 87.4%, P=0.039). PRAME overexpression had no impact on outcome in T-ALL patients. Among B-ALL patients with non-poor cytogenetic risk, those with PRAME overexpression showed significantly lower CIR, higher DFS and OS rates at 3 years, respectively (8.47% vs. 14.5%, P=0.009; 96.5% vs. 85.5%, P=0.009; 98.4% vs. 88.0%, P=0.023). Furthermore, PRAME overexpression was an independent good prognostic factor for relapse in all B-ALL patients and B-ALL patients with non-poor cytogenetic risk. Therefore, the prognostic significance of PRAME overexpression differed by ALL subtype; It predicted good outcome in pediatric B-ALL receiving chemotherapy. Copyright © 2016 Elsevier Ltd. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    Osman Yokuş

    2013-06-01

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

  5. Patterns of DNMT1 Promoter Methylation in Patients with Acute Lymphoblastic Leukemia.

    Science.gov (United States)

    Rahmani, Tirdad; Azad, Mehdi; Chahardouli, Bahram; Nasiri, Hajar; Vatanmakanian, Mousa; Kaviani, Saeid

    2017-07-01

    Background: Acute lymphoblastic leukemia (ALL) is a clonal malignant disorder characterized by an uncontrolled proliferation of immature T or B lymphocytes. Extensive studies have shown that the epigenetic changes, especially modified DNA methylation patterns in the regulatory regions through the DNA methyltransferase (DNMTs), play an important role in the development of genetic disorders and abnormal growth and maturation capacity of leukemic stem cells (LSCs).The aim of this study was to evaluate the changes in DNMT1 promoter methylation and its expression pattern in patients with ALL. Materials and Methods: In this experimental study, methylation specific PCR (MSP) was used to assess the methylation status of DNMT1 promoter regions in samples collected from ALL patients (n=45) and healthy control subjects. According to this method, un-methylated cytosine nucleotides are converted to uracil by sodium bisulfite and the proliferation of methylated and un-methylated regions are performed using specific primers for target sequences. Results: None of the patients with B and T-ALL showed methylated promoter regions of the DNMT1 gene, while the methylation pattern of both pre-B ALL patients and the control group showed a relative promoter methylation. Conclusion: Analysis of promoter methylation patterns in various subgroups of ALL has revealed the importance of DNMT1 in the regulation of gene expression. Likewise, extensive data have also highlighted the methylation-based mechanisms exerted by DNAM1 as one of the main participants regulating gene expression in B-ALL and T-ALL patients. Investigation of the overall DNA methylation pattern offers significant improvements in the prediction of disease prognosis and treatment response.

  6. Neonatal acute megakaryoblastic leukemia mimicking congenital neuroblastoma

    OpenAIRE

    Kawasaki, Yukako; Makimoto, Masami; Nomura, Keiko; Hoshino, Akihiro; Hamashima, Takeru; Hiwatari, Mitsuteru; Nakazawa, Atsuko; Takita, Junko; Yoshida, Taketoshi; Kanegane, Hirokazu

    2014-01-01

    Key Clinical Message We describe a neonate with abdominal distension, massive hepatomegaly, and high serum neuron-specific enolase level suggestive of congenital neuroblastoma. The patient died of pulmonary hemorrhage after therapy. Autopsy revealed that the tumor cells in the liver indicated acute megakaryocytic leukemia with the RBM15-MKL1 fusion gene.

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

    International Nuclear Information System (INIS)

    Yamamoto, Akira; Miki, Yukio; Adachi, Souichi

    2006-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2006-03-15

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

  9. Results of NOPHO ALL2008 treatment for patients aged 1-45 years with acute lymphoblastic leukemia

    DEFF Research Database (Denmark)

    Toft, N; Birgens, H; Abrahamsson, J

    2018-01-01

    Adults with acute lymphoblastic leukemia (ALL) do worse than children. From 7/2008 to 12/2014, Nordic and Baltic centers treated 1509 consecutive patients aged 1-45 years with Philadelphia chromosome-negative ALL according to the NOPHO ALL2008 without cranial irradiation. Overall, 1022 patients w...... 10 years. In conclusion, a pediatric-based protocol is tolerable and effective for young adults, despite their increased frequency of higher risk features.Leukemia advance online publication, 22 September 2017; doi:10.1038/leu.2017.265.......Adults with acute lymphoblastic leukemia (ALL) do worse than children. From 7/2008 to 12/2014, Nordic and Baltic centers treated 1509 consecutive patients aged 1-45 years with Philadelphia chromosome-negative ALL according to the NOPHO ALL2008 without cranial irradiation. Overall, 1022 patients...... time to relapse of 1.6 years and 13 (no adult) developed a second malignancy. Median follow-up time was 4.6 years. Among the three age groups, older patients more often had higher risk ALL due to T-ALL (32%/25%/9%, Pleukemia...

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

    DEFF Research Database (Denmark)

    Møller, Tom; Adamsen, Lis; Appel, Charlotte

    2012-01-01

    a longitudinal HRQOL evaluation (European Organisation for Research and Treatment of Cancer core 30-item questionnaire; EORTC-QLQ C-30) and the impact of infectious comorbidity among 60 patients with leukemia (median age 47) treated in an outpatient management program at Copenhagen University Hospital......Although survival has improved among patients with acute leukemia, there is still a considerable risk of severe complications throughout the course of treatment. This contrast increases the interest in monitoring health related quality of life (HRQOL) in these patients. This study presents....... Significant improvement was seen on several HRQOL scores during follow-up. Explorative general linear models (GLMs) suggest that high cumulative severity of infectious comorbidity significantly reduces physical functioning and overall quality of life at treatment completion....

  11. The MLL recombinome of acute leukemias in 2017

    DEFF Research Database (Denmark)

    Meyer, C; Burmeister, T; Gröger, D

    2018-01-01

    Chromosomal rearrangements of the human MLL/KMT2A gene are associated with infant, pediatric, adult and therapy-induced acute leukemias. Here we present the data obtained from 2345 acute leukemia patients. Genomic breakpoints within the MLL gene and the involved translocation partner genes (TPGs)...

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

    Directory of Open Access Journals (Sweden)

    Yuan Zhou

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

  13. Geographic Heterogeneity of the AML1-ETO Fusion Gene in Iranian Patients with Acute Myeloid Leukemia

    Directory of Open Access Journals (Sweden)

    Saeedeh Ghazaey Zidanloo

    2014-10-01

    Full Text Available Background: The human AML1 gene, located on chromosome 21, can be fused to the AML1- eight-twenty-one (ETO oncoprotein on chromosome eight, resulting in a t(8;21(q22;q22 translocation. Acute myeloid leukemia (AML associated with this translocation is considered a distinct AML with a favorable prognosis. Due to the various incidences of the translocation, which is associated with geographic diversities, investigation of molecular epidemiology is important to increase the awareness of physicians and hematologists regarding the frequency this chromosomal aberration. Methods: The patients were classified according to the French–American–British classification into eight groups: M0–M7. Determination of the prevalence of the AML1-ETO fusion gene was accomplished by TaqMan real-time PCR. Bone marrow samples from 113 patients with newly-diagnosed, untreated AML -M1, -M2, and -M4, and 20 healthy controls admitted to the Ghaem Hospital in Mashhad, Iran were studied. Results: The AML1-ETO fusion gene was detected up 50% of the M2 subgroup and absent in the M1 and M4 subtypes and healthy controls. Comparison of the prevalence of the t(8;21 translocation with results of previous studies showed that it varies between countries. This result may be due to geographic or ethnic differences, or both. Conclusions: The relatively high prevalence of the t(8;21 translocation in Iran was similar to that found in other Asian countries. It was closely associated with female gender, relatively young age, and FAB-M2 subtype. Its distribution varied considerably with geographic area. Therefore, further studies are needed to provide epidemiological data important for the establishment of optimal therapeutic strategies applicable to patients of each region.

  14. Prognostic impact of Wilms tumor gene mutations in Egyptian patients with acute myeloid leukemia with normal karyotype.

    Science.gov (United States)

    Zidan, Magda Abdel Aziz; Kamal Shaaban, Howyda M; Elghannam, Doaa M

    2014-07-01

    The Wilms' tumor (WT1) gene mutations were detected in patients with most forms of acute leukemia. However, the biological significance and the prognostic impact of WT1 mutation in Egyptian patients with acute myeloid leukemia with normal karyotype (AML-NK) are still uncertain. We aimed to evaluate the incidence and clinical relevance of WT1 gene mutations in acute myeloid leukemia with normal karyotype (AML-NK). Exons 7 and 9 of WT1 were screened in samples from 216 adult NK-AML using polymerase chain reaction single-strand conformation polymorphism techniques. Twenty-three patients (10.6%) harbored WT1 mutations. Younger ages and higher marrow blasts were significantly associated with WT1 mutations (P = 0.006 and 0.003 respectively). Complete remission rates were significantly lower in patients with WT1 mutations than those with WT1 wild-type (P = 0.015). Resistance, relapse, and mortality rates were significantly higher in patients with WT1 mutations than those without (P = 0.041, 0.016, and 0.008 respectively). WT1 mutations were inversely associated with NPM1 mutations (P = 0.007). Patients with WT1 mutations had worse disease-free survival (P < 0.001) and overall survival (P < 0.001) than patients with WT1 wild-type. In multivariable analyses, WT1 mutations independently predicted worse DFS (P < 0.001; hazard ratio [HR] 0.036) and overall survival (P = 0.001; HR = 0.376) when controlling for age, total leukocytic count (TLC), and NPM1 mutational status. In conclusion, WT1 mutations are a negative prognostic indicator in intensively treated patients with AML-NK, may be a part of molecularly based risk assessment and risk-adapted treatment stratification of patients with AML-NK.

  15. Potent anti-leukemia activities of humanized CD19-targeted CAR-T cells in patients with relapsed/refractory acute lymphoblastic leukemia.

    Science.gov (United States)

    Cao, Jiang; Wang, Gang; Cheng, Hai; Wei, Chen; Qi, Kunming; Sang, Wei; Zhenyu, Li; Shi, Ming; Li, Huizhong; Qiao, Jianlin; Pan, Bin; Zhao, Jing; Wu, Qingyun; Zeng, Lingyu; Niu, Mingshan; Jing, Guangjun; Zheng, Junnian; Xu, Kailin

    2018-04-10

    Chimeric antigen receptor T (CAR-T) cell therapy has shown promising results for relapsed/refractory (R/R) acute lymphoblastic leukemia (ALL). The immune response induced by murine single-chain variable fragment (scFv) of the CAR may limit CAR-T cell persistence and thus increases the risk of leukemia relapse. In this study, we developed a novel humanized scFv from the murine FMC63 antibody. A total of 18 R/R ALL patients with or without prior murine CD19 CAR-T therapy were treated with humanized CD19-targeted CAR-T cells (hCART19s). After lymphodepletion chemotherapy with cyclophosphamide and fludarabine, the patients received a single dose (1 × 10 6 /kg) of autologous hCART19s infusion. Among the 14 patients without previous CAR-T therapy, 13 (92.9%) achieved complete remission (CR) or CR with incomplete count recovery (CRi) on day 30, whereas 1 of the 3 patients who failed a second murine CAR-T infusion achieved CR after hCART19s infusion. At day 180, the overall and leukemia-free survival rates were 65.8% and 71.4%, respectively. The cumulative incidence of relapse was 22.6%, and the non-relapse mortality rate was 7.1%. During treatment, 13 patients developed grade 1-2 cytokine release syndrome (CRS), 4 patients developed grade 3-5 CRS, and 1 patient experienced reversible neurotoxicity. These results indicated that hCART19s could induce remission in patients with R/R B-ALL, especially in patients who received a reinfusion of murine CAR-T. This article is protected by copyright. All rights reserved. © 2018 Wiley Periodicals, Inc.

  16. Central nervous system involvement at first relapse in patients with acute promyelocytic leukemia treated with all-trans retinoic acid and anthracycline monochemotherapy without intrathecal prophylaxis

    NARCIS (Netherlands)

    P. Montesinos (Pau); J. Díaz-Mediavilla (Joaquín); G. Debén (Guillermo); V. Prates (Virginia); M. Tormo (Mar); V. Rybio (Vicente); I. Pérez (Inmaculada); I. Fernández (Isolda); M. Viguria (Maricruz); C. Rayón (Chelo); J. de Serna (Javier); J. Esteve (Jordi); J.M. Bergua (Juan Miguel); C. Rivas (Concha); J.D. González (José David); M. González (Marcos); S. Negri (Silvia); S. Brunet (Salut); B. Löwenberg (Bob); M.A. Sanz (Miguel Angel)

    2009-01-01

    textabstractBackground: The prevalence of and risk factors for central nervous system recurrence in patients with acute promyelocytic leukemia are not well established and remain a controversial matter. Design and Methods: Between 1996 and 2005, 739 patients with newly diagnosed acute promyelocytic

  17. Healing Touch as a Supportive Intervention for Adult Acute Leukemia Patients: A Pilot Investigation of Effects on Distress and Symptoms

    Science.gov (United States)

    Danhauer, Suzanne C.; Tooze, Janet A.; Holder, Paige; Miller, Christina; Jesse, Michelle T.

    2013-01-01

    Background Goals were to determine the feasibility of conducting a study of Healing Touch (HT) for acute leukemia patients and to obtain preliminary data on its effectiveness. Methods Forty hospitalized leukemia patients completed a brief survey of HT knowledge/experience. A prospective cohort (N=12) was invited to participate in an HT intervention (9 30-minute sessions over 3 weeks); they completed measures of distress, symptoms, and sleep (at weeks 1 and 5), and completed single item ratings of fatigue, nausea, distress, and pain immediately pre-post selected HT sessions. The Wilcoxon signed rank test was used to analyze change in pre-post session ratings and distress, symptom, and sleep measures. Results Among survey respondents, 8% had used HT in the past, and 71% were interested in using HT. In the prospective cohort, there were significant pre-post session improvements in fatigue and nausea (but not in distress and pain). There were no significant changes between weeks 1 and 5 in distress, symptoms, or sleep. Ratings and qualitative feedback on HT were positive, focused mainly on feeling relaxed following HT sessions. Conclusions It is feasible to recruit patients hospitalized for acute leukemia to a study of HT. Preliminary data on short-term improvements in symptoms indicate these are promising outcomes for future study. PMID:19087765

  18. [A patient with acute Philadelphia-chromosome-positive mixed phenotype leukemia developing ecthyma gangrenosum while undergoing combined imatinib mesylate chemotherapy].

    Science.gov (United States)

    Suzuki, Kei; Sekine, Takao

    2014-05-01

    A 67-year-old woman with acute Philadelphia-chromosome-positive mixed phenotype leukemia developed bilateral periorbital ecthyma gangrenousum (EG) subsequent to periorbital edema while undergoing combined imatinib mesylate (imatinib) chemotherapy. Although initial periorbital edema was considered an imatinib side effect, the lesion deteriorated rapidly with high fever in the neutropenic phase, and the woman died of septic shock. Cultures from blood and exudative fluid grew Pseudomonas aeruginosa, after which EG was diagnosed. EG is a well-recognized emergent cutaneous infection most commonly associated with Pseudomonas aeruginosa bactremia. Because some patients present with EG a few days prior to developing life-threatening septicemia, it is important that EG be diagnosed correctly. Imatinib side effects such as edema are usually tolerable, and imatinib is widely used to treat Philadelphia-chromosome-positive leukemia, particularly in those with acute lymphoblastic leukemia, and neutropenic patients undergoing imatinib therapy are expected to increase in number. Delay in initiating appropriate therapy is correlated with poor outcome, so drug side effects and EG must be carefully differentiated when skin edema with surrounding erythema is noted in neutropenic patients undergoing imatinib therapy.

  19. Acute myeloid leukemia: advances in diagnosis and classification.

    Science.gov (United States)

    Hasserjian, R P

    2013-06-01

    Acute myeloid leukemia is an aggressive myeloid neoplasm characterized by ≥20% myeloblasts in the blood or bone marrow. Current treatment strategies for acute myeloid leukemia are based on both patient-related parameters such as age and performance status as well as the intrinsic characteristics of particular disease subtypes. Subtyping of acute myeloid leukemia requires an integration of information from the patient's clinical history (such as any prior preleukemic myeloid neoplasm or cytotoxic potentially leukemogenic therapy), the leukemia morphology, cytogenetic findings, and the mutation status of particular genes (NPM1, FLT3, and CEBPA). In recent years, a barrage of information has become available regarding gene mutations that occur in acute myeloid leukemia and their influence on prognosis. Future therapies for acute myeloid leukemia will increasingly rely on the genetic signatures of individual leukemias and will adjust therapy to the predicted disease aggressiveness as well as employ therapies targeted against particular deregulated genetic pathways. This article reviews current standards for diagnosing and classifying acute myeloid leukemia according to the 2008 WHO Classification. Data that have subsequently accumulated regarding newly characterized gene mutations are also presented. It is anticipated that future leukemia classifications will employ a combination of karyotypic features and the gene mutation pattern to stratify patients to increasingly tailored treatment plans. © 2013 Blackwell Publishing Ltd.

  20. Leukemia-associated aberrant immunophenotype in patients with acute myeloid leukemia: changes at refractory disease or first relapse and clinicopathological findings.

    Science.gov (United States)

    Cui, W; Zhang, D; Cunningham, M T; Tilzer, L

    2014-12-01

    Multiparameter flow cytometry (MFC) is commonly used to detect minimal residual disease (MRD) during the course of chemotherapy or relapse. Only one study addressed the immunophenotypic changes in refractory disease. We studied changes in leukemia-associated aberrant immunophenotype (LAIP) in patients with refractory and relapsed acute myeloid leukemia (AML). We analyzed 47 patients (refractory = 22; relapsed = 25) by MFC, morphology, and cytogenetic studies. Thirty-five patients (74%) showed variably changed LAIPs. The frequently altered LAIPs were lack of lineage-specific antigen and lineage infidelity. The most frequently changed marker was CD13, followed by CD33, CD56, CD7, CD4, and CD11b. Cytogenetic clonal evolution at persistence/relapse was observed in 15 patients (32%). Morphologically, three patients (6%) showed significant changes at relapse. Patients with refractory AML had a higher association with poor cytogenetic risk and classification of AML with myelodysplasia-related changes. Positive MRD at postinduction was of prognostic significance. Allogeneic stem cell transplant improved overall survival. LAIP alterations in refractory/relapsed AMLs are common findings. Presence of persistent disease indicates a poor prognosis, regardless of cytogenetic risk or expression of CD7 or CD56. Discordance between cytogenetic and LAIP changes suggests that gross cytogenetic clonal evolution during disease progression only partly contributes to immunophenotypic instability. © 2014 John Wiley & Sons Ltd.

  1. The need for evidence based nutritional guidelines for pediatric acute lymphoblastic leukemia patients: acute and long-term following treatment.

    Science.gov (United States)

    Owens, Joyce L; Hanson, Sheila J; McArthur, Jennifer A; Mikhailov, Theresa A

    2013-10-31

    High survival rates for pediatric leukemia are very promising. With regard to treatment, children tend to be able to withstand a more aggressive treatment protocol than adults. The differences in both treatment modalities and outcomes between children and adults make extrapolation of adult studies to children inappropriate. The higher success is associated with a significant number of children experiencing nutrition-related adverse effects both in the short and long term after treatment. Specific treatment protocols have been shown to deplete nutrient levels, in particular antioxidants. The optimal nutrition prescription during, after and long-term following cancer treatment is unknown. This review article will provide an overview of the known physiologic processes of pediatric leukemia and how they contribute to the complexity of performing nutritional assessment in this population. It will also discuss known nutrition-related consequences, both short and long term in pediatric leukemia patients. Since specific antioxidants have been shown to be depleted as a consequence of therapy, the role of oxidative stress in the pediatric leukemia population will also be explored. More pediatric studies are needed to develop evidence based therapeutic interventions for nutritional complications of leukemia and its treatment.

  2. Molecular detection of BCR/ABL fusion gene in Saudi acute lymphoblastic leukemia patients.

    Science.gov (United States)

    El-Sissy, Azza; El-Mashari, May; Bassuni, Wafaa; El-Swaayed, Aziza

    2006-06-01

    Molecular cytogenetics is becoming one of the most useful tools targeting some genes which are generally considered to lead to leukemic transformation (as well as for numerical abnormalities). A fraction of acute lymphoblastic leukemia (ALL) cases carry the translocation t(9;22) (q34;q11.2) which juxtaposes the ABL proto-oncogene to the BCR gene generating a chimeric gene, BCR/ABL. This aberration is more frequent in adult ALL (20%-40%) than in pediatric ALL (<5%), and predicts poor clinical outcome. AIM OF OUR WORK: Is to study BCR/ABL fusion gene in ALL cases using fluorescent in situ hybridization. Twenty newly diagnosed ALL patients, 16 adult and 4 paediatric cases, were included in the study, 11 cases (55%) were of precursor B phenotype, 8 cases (40%) belonged to T lineage, while one case was biphenotypic expressing mainly precursor B cell markers tether with CD13, CD33, CD117, Detection of BCR/ABL fusion gene was done using interphase FISH technique and was confirmed molecularly using the RT-PCR technique. BCR/ABL fusion gene was negative in all the examined cases, yet abnormality involving 9q34, ABL gene, either by addition or deletion was detected in three cases (15%). Two of these cases were associated with BCR gene extra copies (three and four copies, respectively). This may reflect the frequency of association of ABL gene and BCR gene abnormality in our cases, and that absence of fusion gene BCR/ABL does not exclude their role in the leukomogenic process, yet a larger study is required to confirm and detect the prevalence of these gene disturbances in ALL and their association.

  3. DNMT3A GENE POINT MUTATIONS DETECTION IN ACUTE MYELOID LEUKEMIA PATIENTS USING SEQUENCING TECHNIQUE

    Directory of Open Access Journals (Sweden)

    A. V. Vinogradov

    2015-01-01

    Full Text Available Aim: to estimate the frequency of DNMT3A gene exons 18–26 point mutations in acute myeloid leukemia (AML patients (pts using target automatic sequencing technique.Material and Methods. Bone marrow and peripheral blood samples were obtained from 34 AML pts aged 21 to 64, who were treated in Sverdlovsk Regional Hematological Centre (Ekaterinburg during the period 2012–2014. Distribution of the pts according to FAB-classification was as follows: AML M0 – 3, M1 – 1, M2 – 12, M3 – 3, M4 – 10, M5 – 2, M6 – 1, M7 – 1, blastic plasmacytoid dendritic cell neoplasm – 1. Total RNA was extracted from leukemic cells and subjected to reverse transcription. DNMT3A gene exons 18–26 were amplified by PCR. Detection of mutations in DNMT3A gene was performed by direct sequencing. Sequencing was realized using an automatic genetic analyzer ABI Prism 310.Results. The average frequency of functionally significant point mutations in DNMT3A gene exons 18– 26 among the treated AML pts was 5.9%. They were detected in morphological subgroups M2 and M4(according to WHO classification. The average frequency of DNMT3A gene exons 18–26 point mutations among the AML M2 and M4 pts without chromosomal aberrations and TP53 gene point mutations was 14.3%. In both cases there were samples in which DNMT3A gene mutations were accompanied by molecular lesions of NPM1, KRAS and WT1 genes. AML pts with DNMT3A gene exons 18–26 point mutations characterized by poor response to standard chemotherapeutic regimens and unfavorable prognosis.

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

    DEFF Research Database (Denmark)

    Jarden, Mary; Adamsen, Lis; Kjeldsen, Lars

    2013-01-01

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

  5. Expression of CD133 in acute leukemia.

    Science.gov (United States)

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

    2013-06-01

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

  6. The Experiences of Parents of Pediatric Patients With Acute Lymphoblastic Leukemia, 2 Months After Completion of Treatment.

    Science.gov (United States)

    Muskat, Barbara; Jones, Heather; Lucchetta, Sonia; Shama, Wendy; Zupanec, Sue; Greenblatt, Andrea

    Diagnosis and treatment of childhood acute lymphoblastic leukemia (ALL) can be a highly stressful time for the entire family. While completion of treatment may bring relief to some families, it may also bring about additional anxieties and fear. The primary objective of this article is to present an analysis of the experiences, emotional states, and support needs of parents of pediatric cancer patients 2 months after treatment completion for ALL. Using a qualitative interpretive description approach, transcripts from interviews with 17 parents from the leukemia/lymphoma program of a large urban pediatric cancer center were analyzed using N-Vivo 10 data analysis software. Parents reported simultaneous feelings of relief and apprehension, changing relationships with their health care team and the experience of returning to a life following treatment. Results highlight the need for support for parents on completion of treatment.

  7. [Leukemia research in Germany: the Competence Network Acute and Chronic Leukemias].

    Science.gov (United States)

    Kossak-Roth, Ute; Saußele, Susanne; Aul, Carlo; Büchner, Thomas; Döhner, Hartmut; Dugas, Martin; Ehninger, Gerhard; Ganser, Arnold; Giagounidis, Aristoteles; Gökbuget, Nicola; Griesshammer, Martin; Hasford, Jörg; Heuser, Michael; Hiddemann, Wolfgang; Hochhaus, Andreas; Hoelzer, Dieter; Niederwieser, Dietger; Reiter, Andreas; Röllig, Christoph; Hehlmann, Rüdiger

    2016-04-01

    The Competence Network "Acute and Chronic Leukemias" was founded in 1997 by the consolidation of the leading leukemia study groups in Germany. Key results are the development of new trials and cooperative studies, the setup of patient registries and biobanking facilities, as well as the improvement of study infrastructure. In 2003, the concept of the competence network contributed to the foundation of the European LeukemiaNet (ELN). Synergy with the ELN resulted in cooperation on a European and international level, standardization of diagnostics and treatment, and recommendations for each leukemia and interdisciplinary specialty. The ultimate goal of the network is the cure of leukemia through cooperative research.

  8. Mesenchymal stromal cells from patients with acute myeloid leukemia have altered capacity to expand differentiated hematopoietic progenitors.

    Science.gov (United States)

    Chandran, Priya; Le, Yevgeniya; Li, Yuhua; Sabloff, Mitchell; Mehic, Jelica; Rosu-Myles, Michael; Allan, David S

    2015-04-01

    The bone marrow microenvironment may be permissive to the emergence and progression of acute myeloid leukemia (AML). Studying interactions between the microenvironment and leukemia cells should provide new insight for therapeutic advances. Mesenchymal stromal cells (MSCs) are central to the maintenance of the hematopoietic niche. Here we compared the functions and gene expression patterns of MSCs derived from bone marrow aspirates of healthy donors and patients with AML. MSCs expanded from AML patients had heterogeneous morphology and displayed a wide range of proliferation capacity compared to MSCs from healthy controls. The ability of AML-MSCs to support the expansion of committed hematopoietic progenitors from umbilical cord blood-derived CD34+ cells may be impaired while the expression of genes associated with maintaining hematopoietic quiescence appeared to be increased in AML-MSCs compared to healthy donors. These results highlight important potential differences in the biologic profile of MSCs from AML patients compared to healthy donors that may contribute to the emergence or progression of leukemia. Copyright © 2015 Elsevier Ltd. All rights reserved.

  9. Glycogen phosphorylase BB as a potential marker of cardiac toxicity in patients treated with anthracyclines for acute leukemia.

    Science.gov (United States)

    Horacek, J M; Jebavy, L; Vasatova, M; Pudil, R; Tichy, M; Jakl, M; Maly, J

    2013-01-01

    The aim of the presented study was to assess plasma glycogen phosphorylase BB (GPBB) concentrations in acute leukemia patients treated with anthracycline containing chemotherapy. Anthracyclines represent the highest risk for development of cardiotoxicity. GPBB belongs to proposed biomarkers of cardiac injury with a very limited experience in this context. Totally, 24 adult patients with acute leukemia were enrolled. Plasma GPBB concentrations were measured by ELISA at diagnosis (before chemotherapy), after first chemotherapy with anthracyclines and 6 months after the completion of treatment. The cut-off value for GPBB positivity was 10.00 µg/L as recommended by the manufacturer. Before chemotherapy, the mean plasma GPBB concentration was 5.25±3.81 µg/L, increased above the cut-off in 1 patient (4.2 %). After the first chemotherapy, the mean GPBB was 6.61±5.54 µg/L, positive in 7 (29.2 %) patients. Six months after treatment, the mean GPBB was 10.06±11.41 µg/L, positive in 8 (33.3 %) patients. Six months after treatment, we found a significant correlation between elevation in GPBB and diastolic left ventricular dysfunction on echocardiography (r=0.621; pfuture is not clear and will be evaluated during the follow-up. Further studies are needed to define the potential role of GPBB and other biomarkers in the assessment of chemotherapy-induced cardiotoxicity (Ref. 21). Text in PDF www.elis.sk.

  10. [Characteristics and treatment outcomes in 822 adult patients with acute myeloid leukemia:a single center experience].

    Science.gov (United States)

    Lin, Dong; Zhou, Chunlin; Wei, Hui; Liu, Bingcheng; Wang, Ying; Liu, Kaiqi; Li, Wei; Gong, Benfa; Wang, Jinyu; Wei, Shuning; Zhang, Guangji; Zhao, Xingli; Li, Yan; Liu, Yuntao; Gong, Xiaoyuan; Sun, Mingyuan; Lu, Yuan; Mi, Yingchang; Wang, Jianxiang

    2014-12-01

    To investigate the characteristics and the short- or long-term treatment outcomes of the adult patients with acute myeloid leukemia (AML) in China. From 1999 to 2010, 822 adult cases with AML were enrolled, diagnosed and classified by the FAB and WHO criteria, respectively. The treatment outcomes and prognostic factors were analyzed retrospectively. In all patients with a median age of 38.5(15-83) years, acute monoblastic and monocytic leukemia (M5), AML with t(15;17)/PML-RARα (APL) and AML with t(8;21)/AML1-ETO(M2b) were the most common subtypes, accounting for 29.7%, 20.9% and 14.6% respectively. In APL patients, CR was achieved in 95.2%, with an early death (ED) rate of 4.8%. And the estimated overall survival (OS) and disease-free survival (DFS) at 5 year was 87.5% and 88.8%, respectively. Patients with other AML subtype (Non-APL) revealed a CR rate of 82.0%, ED of 4.3%, and estimated 5-year OS and DFS both of 48.8%. The OS rate of Non-APL patients at 3-year varied significantly (Pleukemia centers. Chemotherapy by risk stratification, after diagnosis and classification according to the WHO criteria, is a key point to improve the outcomes in AML.

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

    International Nuclear Information System (INIS)

    Elsayed, Gh.M.; Zaher, A.; Elnoshokaty, E.H.; Nassar, H.R.; Moneer, M.M.

    2014-01-01

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

  12. Effects of Slow-Stroke Back Massage on Symptom Cluster in Adult Patients With Acute Leukemia: Supportive Care in Cancer Nursing.

    Science.gov (United States)

    Miladinia, Mojtaba; Baraz, Shahram; Shariati, Abdolali; Malehi, Amal Saki

    Patients with acute leukemia usually experience pain, fatigue, and sleep disorders, which affect their quality of life. Massage therapy, as a nondrug approach, can be useful in controlling such problems. However, very few studies have been conducted on the effects of massage therapy on the complications of leukemia. The aim of this study was to examine the effects of slow-stroke back massage (SSBM) on the symptom cluster in acute leukemia adult patients undergoing chemotherapy. In this randomized controlled trial, 60 patients with acute leukemia were allocated randomly to either the intervention or control group. The intervention group received SSBM 3 times a week (every other day for 10 minutes) for 4 weeks. The pain, fatigue, and sleep disorder intensities were measured using the numeric rating scale. The sleep quality was measured using the Pittsburgh Sleep Quality Index. Statistical tests of χ, t test, and the repeated-measure analysis of variance were used for data analysis. Results showed that the SSBM intervention significantly reduced the progressive sleep disorder, pain, fatigue, and improved sleep quality over time. Slow-stroke back massage, as a simple, noninvasive, and cost-effective approach, along with routine nursing care, can be used to improve the symptom cluster of pain, fatigue, and sleep disorders in leukemia patients. Oncology nurses can increase their knowledge regarding this symptom cluster and work to diminish the cluster components by using SSBM in adult leukemia patients.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2015-11-15

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

  14. Immunophenotype and increased presence of CD4+CD25+ regulatory T cells in patients with acute lymphoblastic leukemia

    OpenAIRE

    WU, CUI-PING; QING, XI; WU, CUI-YUN; ZHU, HONG; ZHOU, HAI-YAN

    2011-01-01

    Acute lymphoblastic leukemia (ALL), cancer of the white blood cells, is a heterogeneous disease that mainly occurs due to the malignant cloning of original and naive lymphocytes. The aim of this study was to explore the immunophenotype, the percentage of CD4+CD25+ regulatory T cells (Tregs) and the expression of cytokines interleukin (IL)-2, IL-10 and TGF-β in patients with ALL. The immunophenotype and levels of CD4+CD25+ Tregs were detected using flow cytometry in the peripheral blood of 35 ...

  15. Targeting MTHFD2 in acute myeloid leukemia.

    Science.gov (United States)

    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. © 2016 Pikman et al.

  16. Genetics Home Reference: cytogenetically normal acute myeloid leukemia

    Science.gov (United States)

    ... normal acute myeloid leukemia Cytogenetically normal acute myeloid leukemia Printable PDF Open All Close All Enable Javascript ... expand/collapse boxes. Description Cytogenetically normal acute myeloid leukemia (CN-AML) is one form of a cancer ...

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

    Science.gov (United States)

    ... acute myeloid leukemia Core binding factor acute myeloid leukemia Printable PDF Open All Close All Enable Javascript ... collapse boxes. Description Core binding factor acute myeloid leukemia (CBF-AML) is one form of a cancer ...

  18. Impact of FAB classification on predicting outcome in acute myeloid leukemia, not otherwise specified, patients undergoing allogeneic stem cell transplantation in CR1: An analysis of 1690 patients from the acute leukemia working party of EBMT.

    Science.gov (United States)

    Canaani, Jonathan; Beohou, Eric; Labopin, Myriam; Socié, Gerard; Huynh, Anne; Volin, Liisa; Cornelissen, Jan; Milpied, Noel; Gedde-Dahl, Tobias; Deconinck, Eric; Fegueux, Nathalie; Blaise, Didier; Mohty, Mohamad; Nagler, Arnon

    2017-04-01

    The French, American, and British (FAB) classification system for acute myeloid leukemia (AML) is extensively used and is incorporated into the AML, not otherwise specified (NOS) category in the 2016 WHO edition of myeloid neoplasm classification. While recent data proposes that FAB classification does not provide additional prognostic information for patients for whom NPM1 status is available, it is unknown whether FAB still retains a current prognostic role in predicting outcome of AML patients undergoing allogeneic stem cell transplantation. Using the European Society of Blood and Bone Marrow Transplantation registry we analyzed outcome of 1690 patients transplanted in CR1 to determine if FAB classification provides additional prognostic value. Multivariate analysis revealed that M6/M7 patients had decreased leukemia free survival (hazard ratio (HR) of 1.41, 95% confidence interval (CI), 1.01-1.99; P = .046) in addition to increased nonrelapse mortality (NRM) rates (HR, 1.79; 95% CI, 1.06-3.01; P = .028) compared with other FAB types. In the NPM1 wt AML, NOS cohort, FAB M6/M7 was also associated with increased NRM (HR, 2.17; 95% CI, 1.14-4.16; P = .019). Finally, in FLT3-ITD + patients, multivariate analyses revealed that specific FAB types were tightly associated with adverse outcome. In conclusion, FAB classification may predict outcome following transplantation in AML, NOS patients. © 2017 Wiley Periodicals, Inc.

  19. Identification of an MLC suppressor cell population in acute leukemia

    International Nuclear Information System (INIS)

    Bryan, C.F.; Broxmeyer, H.E.; Hansen, J.; Pollack, M.; Dupont, B.

    1978-01-01

    The MLC data from the 20 nonsuppressing patients and the 10 suppressing leukemia patients were analyzed with regard to HLA-A, -B, and -C antigens in the leukemia patients and compared with the presence or absence of suppression. These results demonstrate a significant increase (p < 0.02, Mann-Whitney U test) of HLA antigens Al, A3, and A11 in the leukemia suppressor group. Seven of the 10 leukemia patients showing suppression were A1, A3, or A11, while only 4 of the 20 nonsuppressing leukemia patients carried any of these three HLA-A antigens. The studies demonstrate that a nonspecific suppression of MLC responses is observed in 33% of the patients with acute leukemia

  20. An operational definition of primary refractory acute myeloid leukemia allowing early identification of patients who may benefit from allogeneic stem cell transplantation

    DEFF Research Database (Denmark)

    Ferguson, Paul; Hills, Robert K; Grech, Angela

    2016-01-01

    Up to 30% of adults with acute myeloid leukemia fail to achieve a complete remission after induction chemotherapy - termed primary refractory acute myeloid leukemia. There is no universally agreed definition of primary refractory disease, nor have the optimal treatment modalities been defined. We...... studied 8907 patients with newly diagnosed acute myeloid leukemia, and examined outcomes in patients with refractory disease defined using differing criteria which have previously been proposed. These included failure to achieve complete remission after one cycle of induction chemotherapy (RES), less than...... a 50% reduction in blast numbers with >15% residual blasts after one cycle of induction chemotherapy (REF1) and failure to achieve complete remission after two courses of induction chemotherapy (REF2). 5-year overall survival was decreased in patients fulfilling any criteria for refractory disease...

  1. Clinical application of determination of changes of serum Hcy, IL-8 and VEGF levels after treatment in patients with acute leukemia

    International Nuclear Information System (INIS)

    Liu Huijie

    2011-01-01

    Objective: To investigate the changes of serum Hcy, IL-8 and VEGF levels after treatment in patients with acute leukemia. Methods: Serum IL-8 (with RIA), Hcy and VEGF (with ELISA) levels were detected in 33 patients with acute leukemia both before and after treatment as well as in 35 normal controls. Results: Before treatment,the serum Hcy, IL-8 and VEGF levels in patients were significantly higher than those in controls (P<0.01), after six months of treatment, the serum Hcy, IL-8 and VEGF levels were still remained notably higher than those in controls (P<0.05). Conclusion: The development and clinical occurrence of acute leukemia were closely related to the serum Hcy, IL-8 and VEGF levels. (authors)

  2. Combination of broad molecular screening and cytogenetic analysis for genetic risk assignment and diagnosis in patients with acute leukemia.

    Science.gov (United States)

    Meyer-Monard, S; Parlier, V; Passweg, J; Mühlematter, D; Hess, U; Bargetzi, M; Kühne, T; Cabrol, C; Gratwohl, A; Jotterand, M; Tichelli, A

    2006-02-01

    We evaluated the impact of genetic analysis combining cytogenetics and broad molecular screening on leukemia diagnosis according to World Health Organization (WHO) and on genetic risk assignment. A two-step nested multiplex RT-PCR assay was used that allowed the detection of 29 fusion transcripts. A total of 186 patients (104 males (56%), 174 adults (94%), 12 children (6%), 155 AML (83%), 31 ALL (17%)) characterized by morphology and immunophenotyping were included. Of these 186 patients, 120 (65%) had a genetic abnormality. Molecular typing revealed a fusion transcript in 49 (26%) patients and cytogenetic analysis revealed an abnormal karyotype in 119 (64%). A total of 27 (14%) cases were genetically classified as favorable, 107 (58%) intermediate and 52 (28%) unfavorable. For 38 (20%) patients, there was a discrepancy in the genetic risk assignments obtained from broad molecular screening and cytogenetics. Cryptic fusion transcripts in nine (5%) patients changed the genetic risk assignment in four and the WHO classification in four patients. In 34 patients (18%), cytogenetics defined the risk assignment by revealing structural and numerical chromosomal abnormalities not detected by molecular screening. Broad molecular screening and cytogenetics are complementary in the diagnosis and genetic risk assignment of acute leukemia.

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

    Science.gov (United States)

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

    2011-06-01

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

  4. Epidemiology of acute lymphoblastic leukemia

    International Nuclear Information System (INIS)

    Pendergrass, T.W.

    1985-01-01

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

  5. Acute myeloid leukemia (AML) - children

    Science.gov (United States)

    Having a child with cancer can make you feel very alone. In a cancer support group, you can find people who are going ... Updated July 28, 2016. National Cancer Institute. www.cancer.gov/types/leukemia/patient/child-aml-treatment-pdq . Accessed August 3, 2016. Wei ...

  6. Recombinant interleukin-2 in patients aged younger than 60 years with acute myeloid leukemia in first complete remission: results from Cancer and Leukemia Group B 19808.

    Science.gov (United States)

    Kolitz, Jonathan E; George, Stephen L; Benson, Don M; Maharry, Kati; Marcucci, Guido; Vij, Ravi; Powell, Bayard L; Allen, Steven L; Deangelo, Daniel J; Shea, Thomas C; Stock, Wendy; Bakan, Courtney E; Hars, Vera; Hoke, Eva; Bloomfield, Clara D; Caligiuri, Michael A; Larson, Richard A

    2014-04-01

    Recombinant interleukin-2 (rIL-2) induces cellular cytotoxicity against leukemia blasts. Patients with acute myeloid leukemia (AML) in first complete remission (CR) may harbor minimal residual disease that is susceptible to rIL-2-activated effector cells. In the Cancer and Leukemia Group B (CALGB) 19808 study, patients with AML in first CR were randomly assigned after all planned chemotherapy to receive a 90-day course of subcutaneously administered rIL-2 or no further therapy. The primary objective was to compare disease-free survival (DFS) between the 2 treatment arms. A total of 534 patients achieved a CR, 214 of whom were randomized. Six courses of low-dose daily rIL-2 were given for the expansion of cytotoxic effector cells, each followed by 3-day high-dose boluses given to trigger cytotoxicity against minimal residual disease. On the protocol-specified intention-to-treat analysis, the hazards ratio for DFS was 0.75 (95% confidence interval, 0.52-1.09; P = .13); the 5-year DFS rate was 42% in the observation arm and 53% in the rIL-2 treatment arm. The hazards ratio for overall survival (OS) was 0.88 (95% confidence interval, 0.54-1.23; P = .34); the 5-year OS rate was 58% for the observation arm and 63% for the rIL-2 treatment arm. Twenty-five of the 107 patients randomized to treatment with rIL-2 either refused or were unable to initiate therapy and 30 patients did not complete their assigned therapy. However, significant toxicities were not commonly observed. The trial design did not anticipate the difficulties patients would encounter with protocol compliance. The efficacy of immunotherapy with rIL-2 administered after intensive postremission treatment was not assessed as planned because of unexpected refusals by patients and/or their physicians to comply with protocol-directed therapy. Neither DFS nor OS was found to be significantly improved. © 2013 American Cancer Society.

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

    Science.gov (United States)

    Yan, Ying; Wieman, Eric A; Guan, Xiuqin; Jakubowski, Ann A; Steinherz, Peter G; O'Reilly, Richard J

    2009-12-29

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

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

    Directory of Open Access Journals (Sweden)

    Jakubowski Ann A

    2009-12-01

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

  9. Long-term outcome of older patients with newly diagnosed de novo acute promyelocytic leukemia treated with ATRA plus anthracycline-based therapy

    NARCIS (Netherlands)

    Martinez-Cuadron, D.; Montesinos, P.; Vellenga, E.; Bernal, T.; Salamero, O.; Holowiecka, A.; Brunet, S.; Gil, C.; Benavente, C.; Ribera, J. M.; Perez-Encinas, M.; De la Serna, J.; Esteve, J.; Rubio, V.; Gonzalez-Campos, J.; Escoda, L.; Amutio, M. E.; Arnan, M.; Arias, J.; Negri, S.; Lowenberg, B.; Sanz, M. A.

    Treatment outcome in older patients with acute promyelocytic leukemia (APL) is lower compared with younger patients, mainly because of a higher induction death rate and postremission non-relapse mortality (NRM). This prompted us to design a risk-and age-adapted protocol (Programa Espanol de

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2013-01-01

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

  11. MEK inhibition is a promising therapeutic strategy for MLL-rearranged infant acute lymphoblastic leukemia patients carrying RAS mutations.

    Science.gov (United States)

    Kerstjens, Mark; Driessen, Emma M C; Willekes, Merel; Pinhanços, Sandra S; Schneider, Pauline; Pieters, Rob; Stam, Ronald W

    2017-02-28

    Acute lymphoblastic leukemia (ALL) in infants is an aggressive malignancy with a poor clinical outcome, and is characterized by translocations of the Mixed Lineage Leukemia (MLL) gene. Previously, we identified RAS mutations in 14-24% of infant ALL patients, and showed that the presence of a RAS mutation decreased the survival chances even further. We hypothesized that targeting the RAS signaling pathway could be a therapeutic strategy for RAS-mutant infant ALL patients. Here we show that the MEK inhibitors Trametinib, Selumetinib and MEK162 severely impair primary RAS-mutant MLL-rearranged infant ALL cells in vitro. While all RAS-mutant samples were sensitive to MEK inhibitors, we found both sensitive and resistant samples among RAS-wildtype cases. We confirmed enhanced RAS pathway signaling in RAS-mutant samples, but found no apparent downstream over-activation in the wildtype samples. However, we did confirm that MEK inhibitors reduced p-ERK levels, and induced apoptosis in the RAS-mutant MLL-rearranged ALL cells. Finally, we show that MEK inhibition synergistically enhances prednisolone sensitivity, both in RAS-mutant and RAS-wildtype cells. In conclusion, MEK inhibition represents a promising therapeutic strategy for MLL-rearranged ALL patients harboring RAS mutations, while patients without RAS mutations may benefit through prednisolone sensitization.

  12. Epigenetic Regulation of Hematopoiesis and Acute Leukemia

    NARCIS (Netherlands)

    D.G. Valerio (Daria)

    2017-01-01

    markdownabstractIn this thesis we have explored chromatin regulation in acute leukemia and normal hematopoiesis. In doing so, we have focused on the H3K4 methyltransferase MLL1 and the H4K16 acetyltransferase MOF. MLL- and NUP98-translocations are quite common in acute leukemia and even more

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

    Directory of Open Access Journals (Sweden)

    Motohiro Shindo

    2012-01-01

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

  14. Tumor suppressors BTG1 and IKZF1 cooperate during mouse leukemia development and increase relapse risk in B-cell precursor acute lymphoblastic leukemia patients

    NARCIS (Netherlands)

    Scheijen, B.; Boer, J.M.A.; Marke, R.; Tijchon, E.J.; Ingen Schenau, D.S. van; Waanders, E.; Emst, L. van; Meer, L.T. van der; Pieters, R.; Escherich, G.; Horstmann, M.A.; Sonneveld, E.; Venn, N.; Sutton, R.; Dalla-Pozza, L.; Kuiper, R.P.; Hoogerbrugge, P.M.; Boer, M.L. Den; Leeuwen, F.N. van

    2017-01-01

    Deletions and mutations affecting lymphoid transcription factor IKZF1 (IKAROS) are associated with an increased relapse risk and poor outcome in B-cell precursor acute lymphoblastic leukemia. However, additional genetic events may either enhance or negate the effects of IKZF1 deletions on prognosis.

  15. Hematopoietic stem cells can be separated from leukemic cells in a subgroup of adult acute lymphoblastic leukemia patients.

    Science.gov (United States)

    Wang, Wenwen; Foerner, Elena; Buss, Eike; Jauch, Anna; Eckstein, Volker; Wuchter, Patrick; Ho, Anthony D; Lutz, Christoph

    2017-06-01

    In B-cell acute lymphoblastic leukemia (B-ALL) separation of normal hematopoietic stem cells (HSC) has so far been limited to a subgroup of patients. As aldehyde dehydrogenase (ALDH)-activity is enriched in various stem cells we investigated its value for HSC isolation in adult B-ALL. Based on ALDH-activity patients could be stratified in ALDH-numerous (≥1.9% ALDH +  cells) and ALDH-rare (cells) cases. In ALDH-rare B-ALL clonal-marker negative HSC could be separated by the CD34 + CD38 - ALDH +  phenotype, whereas this separation was not possible in ALDH-numerous B-ALL. Functional analysis confirmed the HSC-potential of isolated cells, which were uniformly CD19-negative. However, addition of ALDH-activity further improved HSC-purity. In summary, we provide a method to separate functionally normal HSC from leukemic cells in a subgroup of B-ALL patients that can be identified prospectively. This protocol thereby facilitates comparative analyses of matched HSC and leukemic cells in order to improve our understanding of leukemia evolution.

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

    Science.gov (United States)

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

    2010-02-11

    Despite improvements in the prognosis of childhood acute lymphoblastic leukemia (ALL), subgroups of patients would benefit from alternative treatment approaches. Our aim was to identify genes with DNA methylation profiles that could identify such groups. We determined the methylation levels of 1320 CpG sites in regulatory regions of 416 genes in cells from 401 children diagnosed with ALL. Hierarchical clustering of 300 CpG sites distinguished between T-lineage ALL and B-cell precursor (BCP) ALL and between the main cytogenetic subtypes of BCP ALL. It also stratified patients with high hyperdiploidy and t(12;21) ALL into 2 subgroups with different probability of relapse. By using supervised learning, we constructed multivariate classifiers by external cross-validation procedures. We identified 40 genes that consistently contributed to accurate discrimination between the main subtypes of BCP ALL and gene sets that discriminated between subtypes of ALL and between ALL and controls in pairwise classification analyses. We also identified 20 individual genes with DNA methylation levels that predicted relapse of leukemia. Thus, methylation analysis should be explored as a method to improve stratification of ALL patients. The genes highlighted in our study are not enriched to specific pathways, but the gene expression levels are inversely correlated to the methylation levels.

  17. Myeloid Sarcoma after Allogenic Stem Cell Transplantation for Acute Myeloid Leukemia: Successful Consolidation Treatment Approaches in Two Patients

    Directory of Open Access Journals (Sweden)

    Silje Johansen

    2018-01-01

    Full Text Available Myeloid sarcoma is an extramedullary (EM manifestation (i.e., manifestation outside the bone marrow of acute myeloid leukemia (AML; it is assumed to be relatively uncommon and can be the only manifestation of leukemia relapse after allogenic stem cell transplantation (allo-SCT. An EM sarcoma can manifest in any part of the body, although preferentially manifesting in immunological sanctuary sites as a single or multiple tumors. The development of myeloid sarcoma after allo-SCT is associated with certain cytogenetic abnormalities, developing of graft versus host disease (GVHD, and treatment with donor lymphocytes infusion (DLI. It is believed that posttransplant myeloid sarcomas develop because the EM sites evade immune surveillance. We present two patients with EM myeloid sarcoma in the breast and epipharynx, respectively, as the only manifestation of leukemia relapse. Both patients were treated with a combination of local and systemic therapy, with successfully longtime disease-free survival. Based on these two case reports, we give an updated review of the literature and discuss the pathogenesis, diagnosis, and treatment of EM sarcoma as the only manifestation of AML relapse after allo-SCT. There are no standard guidelines for the treatment of myeloid sarcomas in allotransplant recipients. In our opinion, the treatment of these patients needs to be individualized and should include local treatment (i.e., radiotherapy combined with systemic therapy (i.e., chemotherapy, immunotherapy, DLI, or retransplantation. The treatment has to consider both the need for sufficient antileukemic efficiency versus the risk of severe complications due to cumulative toxicity.

  18. Identification and validation of potential prognostic gene biomarkers for predicting survival in patients with acute myeloid leukemia

    Directory of Open Access Journals (Sweden)

    Huang R

    2017-11-01

    Full Text Available Rui Huang,1,* Xiwen Liao,2,* Qiaochuan Li1 1Department of Hematology, 2Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, People’s Republic of China *These authors contributed equally to this work Background: Molecular analysis is a promising source of clinically useful prognostic biomarkers. The aim of this investigation was to identify prognostic biomarkers for patients with acute myeloid leukemia (AML by using the gene expression profile dataset from public database. Methods: The gene expression profile dataset and corresponding overall survival (OS information of three cohorts of AML patients from GSE12417 and The Cancer Genome Atlas AML project (TCGA-LAML were included in the present study. Prognostic gene screening was performed by using a survival package, whereas time-dependent receiver operating characteristic (ROC curve analysis was performed using the survivalROC package. Results: In the three cohorts, 11 genes were identified that were significantly associated with AML OS. A linear prognostic model of the 11 genes was constructed and weighted by regression coefficient (β from the multivariate Cox regression analyses of GSE12417 HG-U133A cohort to divide patients into high- and low-risk groups. GSE12417 HG-U133 plus 2.0 and TCGA-LAML were validation cohorts. Patients assigned to the high-risk group exhibited poor OS compared to patients in the low-risk group. The 11-gene signature is a prognostic marker of AML and demonstrates good performance for predicting 1-, 3-, and 5-year OS as evaluated by survivalROC in the three cohorts. Conclusion: Our study has identified an mRNA signature including 11 genes, which may serve as a potential prognostic marker of AML. Keywords: acute myeloid leukemia, prognosis, biomarker, GEO, TCGA

  19. mRNA overexpression of BAALC: A novel prognostic factor for pediatric acute lymphoblastic leukemia

    OpenAIRE

    AZIZI, ZAHRA; RAHGOZAR, SOHEILA; MOAFI, ALIREZA; DABAGHI, MOHAMMAD; NADIMI, MOTAHAREH

    2015-01-01

    BAALC is a novel molecular marker in leukemia that is highly expressed in patients with acute leukemia. Increased expression levels of BAALC are known as poor prognostic factors in adult acute myeloid and lymphoid leukemia. The purpose of the present study was to evaluate the prognostic significance of the BAALC gene expression levels in pediatric acute lymphoblastic leukemia (ALL) and its association with MDR1. Using reverse transcription-quantitative polymerase chain reaction (RT-qPCR), the...

  20. A phase 1 trial of vadastuximab talirine as monotherapy in patients with CD33-positive acute myeloid leukemia.

    Science.gov (United States)

    Stein, Eytan M; Walter, Roland B; Erba, Harry P; Fathi, Amir T; Advani, Anjali S; Lancet, Jeffrey E; Ravandi, Farhad; Kovacsovics, Tibor; DeAngelo, Daniel J; Bixby, Dale; Faderl, Stefan; Jillella, Anand P; Ho, Phoenix A; O'Meara, Megan M; Zhao, Baiteng; Biddle-Snead, Charles; Stein, Anthony S

    2018-01-25

    Vadastuximab talirine (SGN-CD33A, 33A) is an antibody-drug conjugate consisting of pyrrolobenzodiazepine dimers linked to a monoclonal antibody targeting CD33, which is expressed in the majority of acute myeloid leukemia (AML) patients. This phase 1 study evaluated the safety, pharmacokinetics, and preliminary activity of vadastuximab talirine and determined the recommended monotherapy dose in patients with relapsed or refractory AML. Additional expansion cohorts tested vadastuximab talirine in specific subpopulations of relapsed AML, and in a cohort of older, treatment-naive patients. Patients received vadastuximab talirine IV on day 1 (5-60 µg/kg) or on days 1 and 4 (20 µg/kg) of 21-day cycles. A total of 131 patients (median age, 73 years [range, 26-89 years]) had intermediate I-II (48%) or adverse (34%) risk by European LeukemiaNet classification; 50% of patients had underlying myelodysplasia. Two dose-limiting toxicities (grade 2 pulmonary embolism and grade 4 hypocellular marrow) occurred during dose finding. Most adverse events (AEs) were consistent with myelosuppression; nonhematologic AEs included fatigue, nausea, and diarrhea. The 30-day mortality was 8%. At the recommended monotherapy dose of 40 µg/kg, the complete remission + CRi rate was 28% (5 of 18 patients); 50% of patients who responded achieved minimal residual disease negativity. In patients across dose levels who achieved CR or CRi, the median time to full count recovery was 6.4 weeks for neutrophils (≥1000/µL) and 10.6 weeks for platelets (≥100 × 10 9 /L). Vadastuximab talirine demonstrates activity and a tolerable safety profile as a single agent in patients with AML. The recommended monotherapy dose of vadastuximab talirine is 40 µg/kg. This trial was registered at www.clinicaltrials.gov as # NCT01902329. © 2018 by The American Society of Hematology.

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

    DEFF Research Database (Denmark)

    Milani, Lili; Lundmark, Anders; Kiialainen, Anna

    2010-01-01

    CpG sites in regulatory regions of 416 genes in cells from 401 children diagnosed with ALL. Hierarchical clustering of 300 CpG sites distinguished between T-lineage ALL and B-cell precursor (BCP) ALL and between the main cytogenetic subtypes of BCP ALL. It also stratified patients with high......Despite improvements in the prognosis of childhood acute lymphoblastic leukemia (ALL), subgroups of patients would benefit from alternative treatment approaches. Our aim was to identify genes with DNA methylation profiles that could identify such groups. We determined the methylation levels of 1320...... hyperdiploidy and t(12;21) ALL into 2 subgroups with different probability of relapse. By using supervised learning, we constructed multivariate classifiers by external cross-validation procedures. We identified 40 genes that consistently contributed to accurate discrimination between the main subtypes of BCP...

  2. Herpes simplex type 1 pneumonitis and acute respiratory distress syndrome in a patient with chronic lymphatic leukemia: a case report.

    Science.gov (United States)

    Luginbuehl, Miriam; Imhof, Alexander; Klarer, Alexander

    2017-11-23

    Pulmonary pathogenicity of herpes simplex virus type 1 in patients in intensive care without classic immunosuppression as well as the necessity of antiviral treatment in the case of herpes simplex virus detection in respiratory specimens in these patients is controversial. We present a case of acute respiratory distress syndrome in a patient with stable chronic lymphatic leukemia not requiring treatment, in whom we diagnosed herpes simplex virus type 1 bronchopneumonitis based on herpes simplex virus type 1 detection in bronchoalveolar lavage fluid and clinical response to antiviral treatment. A 72-year-old white man presented with symptoms of lower respiratory tract infection. His medical history was significant for chronic lymphatic leukemia, which had been stable without treatment, arterial hypertension, multiple squamous cell carcinomas of the scalp, and alcohol overuse. Community-acquired pneumonia was suspected and appropriate broad-spectrum antibacterial treatment was initiated. Within a few hours, rapid respiratory deterioration led to cardiac arrest. He was successfully resuscitated, but developed acute respiratory distress syndrome. Furthermore, he remained febrile and inflammation markers remained elevated despite antibacterial treatment. Polymerase chain reaction from bronchoalveolar lavage fluid and viral culture from tracheobronchial secretions tested positive for herpes simplex virus type 1. We initiated antiviral treatment with acyclovir. Concomitantly we further escalated the antibacterial treatment, although no bacterial pathogen had been isolated at any point. Defervescence occurred rapidly and his C-reactive protein and leukocyte levels decreased. He was successfully weaned from mechanical ventilation, transferred to the ward, and eventually discharged to home. Herpes simplex virus should be considered a cause for lower respiratory tract infection in critically ill patients, especially in the setting of an underlying disease.

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

    NARCIS (Netherlands)

    L. Slobbe (Lennert); S. Polinder (Suzanne); J.K. Doorduijn (Jeanette); P.J. Lugtenburg (Pieternella); A. el Barzouhi (Abdelilah); E.W. Steyerberg (Ewout); B.J.A. Rijnders (Bart)

    2008-01-01

    textabstractBackground. Invasive aspergillosis (IA) is a leading cause of mortality in patients with acute leukemia. Management of IA is expensive, which makes prevention desirable. Because hospital resources are limited, prevention costs have to be compared with treatment costs and outcome.

  4. Prognostic value of FLT3 mutations in patients with acute promyelocytic leukemia treated with all-trans retinoic acid and anthracycline monochemotherapy

    NARCIS (Netherlands)

    Barragan, Eva; Montesinos, Pau; Camos, Mireia; Gonzalez, Marcos; Calasanz, Maria J.; Roman-Gomez, Jose; Gomez-Casares, Maria T.; Ayala, Rosa; Lopez, Javier; Fuster, Oscar; Colomer, Dolors; Chillon, Carmen; Larrayoz, Maria J.; Sanchez-Godoy, Pedro; Gonzalez-Campos, Jose; Manso, Felix; Amador, Maria L.; Vellenga, Edo; Lowenberg, Bob; Sanz, Miguel A.

    2011-01-01

    Background Fms-like tyrosine kinase-3 (FLT3) gene mutations are frequent in acute promyelocytic leukemia but their prognostic value is not well established. Design and Methods We evaluated FLT3-internal tandem duplication and FLT3-D835 mutations in patients treated with all-trans retinoic acid and

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

    NARCIS (Netherlands)

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

    2009-01-01

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

  6. Phase 1/2 study to assess the safety, efficacy, and pharmacokinetics of barasertib (AZD1152) in patients with advanced acute myeloid leukemia

    NARCIS (Netherlands)

    B. Löwenberg (Bob); P. Muus (P.); G.J. Ossenkoppele (Gert); P. Rousselot (Philippe); J.-Y. Cahn (Jean-Yves); N. Ifrah (Norbert); G. Martinelli (Giovanni); S. Amadori (Sergio); E. Berman (Ellin); P. Sonneveld (Pieter); M. Jongen-Lavrencic (Mojca); S. Rigaudeau (Sophie); P. Stockman (Paul); D. Goudie (David); S. Faderl (Stefan); J. Jabbour (Jason); H. Kantarjian (Hagop)

    2011-01-01

    textabstractThe primary objective of this 2-part phase 1/2 study was to determine the maximum-tolerated dose (MTD) of the potent and selective Aurora B kinase inhibitor barasertib (AZD1152) in patients with newly diagnosed or relapsed acute myeloid leukemia (AML). Part A determined the MTD of

  7. Integrating a prospective pilot trial and patient-derived xenografts to trace metabolic changes associated with acute myeloid leukemia

    Directory of Open Access Journals (Sweden)

    Matteo G. Carrabba

    2016-10-01

    Full Text Available Abstract Despite the considerable progress in understanding the molecular bases of acute myeloid leukemia (AML, new tools to link disease biology to the unpredictable patient clinical course are still needed. Herein, high-throughput metabolomics, combined with the other “-omics” disciplines, holds promise in identifying disease-specific and clinically relevant features. In this study, we took advantage of nuclear magnetic resonance (NMR to trace AML-associated metabolic trajectory employing two complementary strategies. On the one hand, we performed a prospective observational clinical trial to identify metabolic changes associated with blast clearance during the first two cycles of intensive chemotherapy in nine adult patients. On the other hand, to reduce the intrinsic variability associated with human samples and AML genetic heterogeneity, we analyzed the metabolic changes in the plasma of immunocompromised mice upon engraftment of primary human AML blasts. Combining the two longitudinal approaches, we narrowed our screen to seven common metabolites, for which we observed a mirror-like trajectory in mice and humans, tracing AML progression and remission, respectively. We interpreted this set of metabolites as a dynamic fingerprint of AML evolution. Overall, these NMR-based metabolomic data, to be consolidated in larger cohorts and integrated in more comprehensive system biology approaches, hold promise for providing valuable and non-redundant information on the systemic effects of leukemia.

  8. DIAGNOSIS AND SUBCLASSIFICATION OF ACUTE LYMPHOBLASTIC LEUKEMIA

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    Sabina Chiaretti

    2014-10-01

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

  9. [Our experiences in the treatment of acute leukemias].

    Science.gov (United States)

    Jelić, S; Dragović, M; Vidaković, B; Plecas, V

    1976-01-01

    This paper deals with observations concerning treatment of acute leukemia in the Department of haematology of The Clinical hospital of Belgrade during the period from 1970 to 1975, and with results of the treatment itself. During the last five years, 27 patients with different types of acute leukemia were treated. The type of acute leukemia was determined using cytological criteria of Levy and Lortholary and cytochemical criteria as described by Hayhoe. One thrid of the patients died during the first days of hospitalisation, before any effect of cytostatic treatment could be evaluated. The cause of death in those patients was septic shock, intracranial haemorrhage or cardiovascular colapsus; initial signs of those complications of acute leukemia were allready present before diagnosis. Those data point to the fact that diagnosis of acute leukemia is often made too late, when irreversible ocmplications of the disease are allready established. Patients over sixty, often "fragile" to aggresive cytostatic therapy, may enter complete and relatively long lasting remission with induction therapy cosisting of 6-mercaptopurine and methotrexate only. Allthough the number of cases was rather limited, the authors had rather disappointing results with the 06-LA-66 protocole in adult lymphoblastic leukemia. The first with COAP treatment protocole seem encouraging. Adequate cytostatic therapy was in several cases impossible, duo to the lack of adequate substitution therapy; such inadequate cytostatic therapy resulted in partial remissions with a rather poor quality survival. A beeter cooperation is needed between hospital centers and institutions which provide matherial for the substitution theapy.

  10. The Role of Azacitidine in the Treatment of Elderly Patients with Acute Myeloid Leukemia: Results of a Retrospective Multicenter Study

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    Anıl Tombak

    2016-12-01

    Full Text Available Objective: In this study, we aimed to investigate the efficacy and safety of azacitidine (AZA in elderly patients with acute myeloid leukemia (AML, including patients with >30% bone marrow (BM blasts. Materials and Methods: In this retrospective multicenter study, 130 patients of ≥60 years old who were ineligible for intensive chemotherapy or had progressed despite conventional treatment were included. Results: The median age was 73 years and 61.5% of patients had >30% BM blasts. Patients received AZA for a median of four cycles (range: 1-21. Initial overall response [including complete remission (CR/CR with incomplete recovery/partial remission] was 36.2%. Hematologic improvement (HI of any kind was documented in 37.7% of all patients. HI was also documented in 27.1% of patients who were unresponsive to treatment.nMedian overall survival (OS was 18 months for responders and 12 months for nonresponders (p=0.005. In the unresponsive patient group, any HI improved OS compared to patients without any HI (median OS was 14 months versus 10 months, p=0.068. Eastern Cooperative Oncology Group performance status of <2, increasing number of AZA cycles (≥5 courses, and any HI predicted better OS. Age, AML type, and BM blast percentage had no impact. Conclusion: We conclude that AZA is effective and well tolerated in elderly comorbid AML patients, irrespective of BM blast count, and HI should be considered a sufficient response to continue treatment with AZA.

  11. Temozolomide and cisplatin in relapsed/refractory acute leukemia

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    Rasul Muhammad

    2009-05-01

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

  12. Outpatient management of intensively treated acute leukemia patients-the patients' perspective

    DEFF Research Database (Denmark)

    Jepsen, Lene Østergaard; Høybye, Mette Terp; Hansen, Dorte Gilså

    2016-01-01

    the possibility of maintaining everyday life, which was essential to the patients. The privacy ensured by the home was important to patients, and they accepted the necessary responsibility that came with it. However, time spent together with fellow patients and their relatives was an important and highly valued......, responsibility and the home were performed. Twenty-two patients were interviewed the first time, and 15 of these were interviewed the second time. The data were analyzed in an everyday life relational perspective. RESULTS: Outpatient management facilitates time to be administrated by the patients and thereby...... part of their social life. CONCLUSIONS: Approached from the patient perspective, outpatient management provided a motivation for patients as it ensured their presence at home and provided the possibility of taking part in everyday life of the family, despite severe illness and intensive treatment...

  13. Elevated Th22 Cells Correlated with Th17 Cells in Peripheral Blood of Patients with Acute Myeloid Leukemia

    Science.gov (United States)

    Yu, Shuang; Liu, Chuanfang; Zhang, Lei; Shan, Baozhong; Tian, Tian; Hu, Yu; Shao, Linlin; Sun, Yuanxin; Ji, Chunyan; Ma, Daoxin

    2014-01-01

    Acute myeloid leukemia (AML) is a hematological tumor in which progress T helper (Th) subsets including Th22, Th17, and Th1 cells play a pivotal role. However, the role of T helper (Th) subsets in the immune pathogenesis of AML remains unclear. Here, we investigated frequencies of Th22, Th17, pure Th17, and Th1 cells in the peripheral blood (PB) of AML patients. We demonstrated that Th22, Th17, and pure Th17 in newly-diagnosed (ND) and non-complete remission (Non-CR) AML patients and plasma IL-22 in ND AML patients were significantly increased. Retinoid-related orphan receptor C (RORC) expression was significantly elevated in CR and Non-CR AML patients. However, Th1 in ND AML patients and IL-17 in ND, Non-CR or CR AML patients was significantly decreased compared with controls. Moreover, Th22 and IL-22 showed positive correlation with pure Th17, but Th22 showed negative correlation with Th1 in ND AML patients. RORC showed positive correlation with Th22 and approximately positive correlation with pure Th17 in Non-CR patients. PB blast cell showed positive correlation with Th22 and negative correlation with Th1 in ND AML patients. Our results indicate that Th22 and pure Th17 cells conjointly contribute to the pathogenesis of AML and might be promising novel clinical index for AML. PMID:24473142

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

    International Nuclear Information System (INIS)

    Saburi, Yoshio; Shuto, Ryusuke; Mizutani, Ryoko; Hosokawa, Takafumi; Itoga, Takashi

    1983-01-01

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

  15. Safety, efficacy, and clinical utility of asparaginase in the treatment of adult patients with acute lymphoblastic leukemia

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    Koprivnikar J

    2017-03-01

    Full Text Available Jamie Koprivnikar, James McCloskey, Stefan Faderl Division of Leukemia, John Theurer Cancer Center at Hackensack University Medical Center, Hackensack, NJ, USA Abstract: Adults with acute lymphoblastic leukemia (ALL are known to have inferior outcomes compared to the pediatric population. Although the reasons for this are likely manyfold, the agents utilized and the increased intensity of pediatric treatments compared to adult treatments are likely significant contributing factors. Asparaginase, an enzyme that converts asparagine to aspartic acid, forms the backbone of almost all pediatric regimens and works by depleting extracellular asparagine, which ALL cells are unable to synthesize. Asparaginase toxicities, which include hypersensitivity reactions, pancreatitis, liver dysfunction, and thrombosis, have hindered its widespread use in the adult population. Here, we review the toxicity and efficacy of asparaginase in adult patients with ALL. With the proper precautions, it is a safe and effective agent in the treatment of younger adults with ALL with response rates in the frontline setting ranging from 78% to 96%, compared to most trials showing a 4-year overall survival of 50% or better. The age cutoff for consideration of treatment with pediatric-inspired regimens is not clear, but recent studies show promise particularly in the adolescent and young adult population. New formulations of asparaginase are actively in development, including erythrocyte-encapsulated asparaginase, which is designed to minimize the toxicity and improve the delivery of the drug. Keywords: PEG-asparaginase, ALL, chemotherapy, pegaspargase, AYA, pediatric 

  16. Evaluation of Serum Leptin Level in Children With Acute Leukemia

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    Iraj Shahramian

    2016-01-01

    Full Text Available Background Leptin is a multifunctional hormone plays an important role in regulating lipid, energy, homeostasis, angiogenesis, inflammation, hematopoiesis and cell cycle. This polypeptide is effective in growth and differentiation of leukemic cells through an Ob-R receptor expressed by them. Objectives The purpose of this study was to evaluate serum leptin levels in patients with acute leukemia and compare it in lymphoid and myeloid groups. Patients and Methods This analytical case-control study, conducted on 60 children in age ranged from 6 months to 16 years in two case and control groups in Ali ibn Abi Talib hospital, Zahedan. They matched based on age and gender and examined after their parent’s satisfaction according to the parental consent forms. None of patients had heart disease, digestive, glandular and metabolic problems, iron deficiency anemia and chronic kidney disease. After collecting the samples, leptin levels of both groups were measured with ELISA kit. Then, the gathered data were analyzed in SPSS-20 software, using independent t-test in considering of 95% confidence interval. Results Leptin serum levels in patients with acute leukemia and controls showed significant difference (P < 0.05. Leptin serum levels in patients with acute lymphoblastic leukemia and acute myeloblastic leukemia showed significant difference (P < 0.05. Leptin serum level in relation to age and gender groups was not statistically significant. Conclusions The findings of this study showed that in patients with acute leukemia, leptin serum levels increase independently of age and gender. In addition, leptin serum levels in acute lymphoid leukemia were higher than acute myeloid leukemia in this study.

  17. Low platelet count is potentially the most important contributor to severe bleeding in patients newly diagnosed with acute promyelocytic leukemia

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    Song Y

    2017-10-01

    Full Text Available Yu-hua Song,1,2 Peng Peng,3 Chun Qiao,1 Run Zhang,1 Jian-yong Li,1 Hua Lu1 1Department of Hematology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, 2Department of Hematology, 3Department of Oncology, The Second Hospital of Nanjing, Nanjing, People’s Republic of China Abstract: The objective of the current study was to provide more appropriate therapeutic strategies for reducing severe hemorrhaging by assessing the recovery of abnormal coagulation indexes in patients with acute promyelocytic leukemia (APL during induction therapy. Retrospective analyses of 112 patients newly diagnosed with APL were performed during initial treatment. In our study, the early death rate was 5.36%. Hemorrhage was the leading cause of death during the induction period (4/6. The values of white blood cell count, lactate dehydrogenase, prothrombin time (PT, fibrinogen (Fbg, hemoglobin, and bone marrow leukemic promyelocytes were significantly different in the high-risk group compared to the low/intermediate-risk groups. There were significant differences in the white blood cell count, bone marrow leukemic promyelocytes, platelet (PLT count, and the levels of lactate dehydrogenase, d-dimer, PT, and Fbg, as well as in FLT3-ITD mutations between patients with major bleeding and those with minor bleeding. Hemostatic variables significantly improved over time during induction therapy. The recovery times of the PLT, PT, and Fbg values were significantly slower in patients with major bleeding than in those with minor bleeding. Specifically, the PLT level in patients with major bleeding was not similar to that in the minor bleeding group until after 4 weeks of treatment. Hemorrhages were the most common cause of induction death in this study. High-risk patients were more prone to serious clinical bleeding symptoms. Patients with major bleeding had more rapid proliferation characteristics and an increased incidence of FLT3-ITD

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

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    Ahmad EI

    2011-07-01

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

  19. [Minor phenotypic variants in patients with acute lymphoblastic leukemia from west Mexico].

    Science.gov (United States)

    Estrada-Padilla, S A; Corona-Rivera, J R; Sánchez-Zubieta, F; Bobadilla-Morales, L; Corona-Rivera, A

    2015-02-01

    Acute lymphoblastic leukemia (ALL) has been associated with an excess of minor phenotypic variants (MPV), including common variants and minor anomalies, indicative of an altered phenogenesis. The objective of the study was to determine the association between MPV and ALL. In a hospital based case-control study, we studied 120 children with ALL (including standard and high risk) and 120 healthy children as a control group, matched for age and sex, seen in the Hospital Civil de Guadalajara Dr. Juan I. Menchaca (Guadalajara, Mexico). In both groups, 28 anthropometric measurements were made, as well as a systematic search for 405 MPV, through a physical examination. Adjusted odds ratio was estimated (aOR) with its intervening variables by logistic regression. The confidence interval was 95% (95%CI). Anthropometric signs associated with ALL were: long upper segment (aOR= 2.19, 95%CI: 1.01-4.76), broad jaw (aOR= 2.62, 95%CI: 1.29-5.30), narrow ears (aOR= 6.22, 95%CI: 2.60-14.85), and increase in internipple distance (aOR= 2.53, 95%CI: 1.07-5.98). The hypoplasia mesofacial, broad forehead, small nose, short columella, narrow ears, telethelia, Sydney crease (SC), Greek type feet and café-au-lait spots (CALS), had a 3 to 17 times higher frequency in children with ALL. By number, an association was found from ≥4 MPV (aOR= 2.14, 95%CI: 1.25-3.66, P=.004). From ≥4 MPV, an association was found with ALL, suggesting prenatal factors in phenogenesis and leukemogenesis. CALS and SC were confirmed as MPV in children with ALL. Copyright © 2013 Asociación Española de Pediatría. Published by Elsevier España, S.L.U. All rights reserved.

  20. Reproducibility and prognostic significance of morphologic dysplasia in de novo acute myeloid leukemia.

    Science.gov (United States)

    Weinberg, Olga K; Pozdnyakova, Olga; Campigotto, Federico; DeAngelo, Daniel J; Stone, Richard M; Neuberg, Donna; Hasserjian, Robert P

    2015-07-01

    The 2008 WHO classification of acute myeloid leukemia includes a category of acute myeloid leukemia with myelodysplasia-related changes; however, the significance of multilineage dysplasia alone is controversial and its reproducibility has not been evaluated in acute myeloid leukemia. We performed an in-depth analysis of morphologic dysplasia in 159 de novo acute myeloid leukemia cases lacking myelodysplasia-related cytogenetic abnormalities. Using the 2008 WHO criteria, there were 89 acute myeloid leukemia-not otherwise specified (56%) and 43 acute myeloid leukemia with myelodysplasia-related changes (27%), while 27 cases were ambiguous as to myelodysplasia-related changes status due to limited maturing cells (acute myeloid leukemia-not evaluable, 17%). On multivariable analysis, neither acute myeloid leukemia with myelodysplasia-related changes nor acute myeloid leukemia-not evaluable showed significantly different event-free survival compared with acute myeloid leukemia-not otherwise specified in the 137 patients treated with induction chemotherapy. When individual dysplastic features were analyzed, only micromegakaryocytes and hypogranulated myeloid cells emerged as factors significantly associated with shorter event-free survival in a multivariable analysis that included the other significant covariates of age, white blood count, platelet count, abnormal karyotype and stem-cell transplantation. Our findings indicate that the current 2008 WHO definition of multilineage dysplasia in acute myeloid leukemia in its current form is not optimal, and that the use of a more restricted definition of morphologic dysplasia results in more relevant risk stratification that is independent of other conventional prognostic factors.

  1. An mRNA expression signature for prognostication in de novo acute myeloid leukemia patients with normal karyotype

    Science.gov (United States)

    Chou, Wen-Chien; Hou, Hsin-An; Tseng, Mei-Hsuan; Kuo, Yi-Yi; Chen, Yidong; Chuang, Eric Y.; Tien, Hwei-Fang

    2015-01-01

    Although clinical features, cytogenetics, and mutations are widely used to predict prognosis in patients with acute myeloid leukemia (AML), further refinement of risk stratification is necessary for optimal treatment, especially in cytogenetically normal (CN) patients. We sought to generate a simple gene expression signature as a predictor of clinical outcome through analyzing the mRNA arrays of 158 de novo CN AML patients. We compared the gene expression profiles of patients with poor response to induction chemotherapy with those who responded well. Forty-six genes expressed differentially between the two groups. Among them, expression of 11 genes was significantly associated with overall survival (OS) in univariate Cox regression analysis in 104 patients who received standard intensive chemotherapy. We integrated the z-transformed expression levels of these 11 genes to generate a risk scoring system. Higher risk scores were significantly associated with shorter OS (median 17.0 months vs. not reached, P signature for prognostication in CN-AML patients. This prognostic biomarker will help refine the treatment strategies for this group of patients. PMID:26517675

  2. Deferasirox and vitamin D improves overall survival in elderly patients with acute myeloid leukemia after demethylating agents failure.

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    Etienne Paubelle

    Full Text Available The prognosis of acute myeloid leukemia (AML in elderly (≥65 years patients is poor and treatment remains non-consensual especially for those who are not eligible for intensive therapies. Our group has shown that in vitro the iron chelator deferasirox (DFX synergizes with vitamin D (VD to promote monocyte differentiation in primary AML cells. Herein, we present results from a retrospective case-control study in which the association of DFX (1-2 g/d and 25-hydroxycholecalciferol (100,000 IU/week (DFX/VD was proposed to patients following demethylating agents failure. Median survival of patients treated with DFX/VD combination (n = 17 was significantly increased in comparison with matched patients receiving best supportive care (BSC alone (n = 13 (10.4 versus 4 months respectively. In addition, the only factor associated to an increased overall survival in DFX/VD-treated patients was serum VD levels. We conclude that DFX/VD treatment correlated with increased overall survival of AML patients in this retrospective cohort of elderly patients.

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

    Science.gov (United States)

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

    2016-08-01

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

  4. Phase 2 study of intensified chemotherapy and allogeneic hematopoietic stem cell transplantation for older patients with acute lymphoblastic leukemia.

    Science.gov (United States)

    Fathi, Amir T; DeAngelo, Daniel J; Stevenson, Kristen E; Kolitz, Jonathan E; Asch, Julie D; Amrein, Philip C; Attar, Eyal C; Steensma, David P; Wadleigh, Martha; Foster, Julia; Connolly, Christine; Galinsky, Ilene; Devoe, Craig E; Stone, Richard M; Neuberg, Donna S; Ballen, Karen K

    2016-08-01

    Outcomes among older patients with acute lymphoblastic leukemia remain poor. This study sought to determine the efficacy of an intensified, multi-agent approach derived from a Dana-Farber consortium trial in younger adults for patients older than 50 years (trial identifier NCT00973752). The primary endpoint was overall survival (OS) at 1 year. Patients received induction chemotherapy with vincristine, prednisone, doxorubicin, and pegylated asparaginase. Imatinib was incorporated for Philadelphia chromosome-positive disease. After induction, the first consolidation incorporated clofarabine. Patients in remission could proceed to allogeneic hematopoietic cell transplantation (HCT) after induction and consolidation I. Those not receiving HCT went on to receive central nervous system, consolidation II, and continuation phases of treatment. Thirty patients were enrolled: 19 achieved a complete remission (CR) after induction and 1 achieved CR after consolidation I for a CR rate of 67%. Sixteen patients underwent HCT. The proportion surviving at 1 year was 63%, and this met the primary endpoint. The 2-year OS rate was 52% (n = 30), and the 2-year disease-free survival rate was 52% for patients achieving CR (n = 20). There was no survival advantage among those undergoing HCT. Therapy-related hyperbilirubinemia prompted adjustments and limitations to asparaginase dosing. Intensified chemotherapy can result in improved outcomes in comparison with historical data. Additional studies of similarly intensive regimens are warranted in this population. Cancer 2016;122:2379-2388. © 2016 American Cancer Society. © 2016 American Cancer Society.

  5. Measurement and clinical significance of serum TPO and LDH levels in patients with myelodysplastic syndrome and acute leukemia.

    Science.gov (United States)

    Wu, Yong-Xia; Wang, Hai-Yan; Wang, Wei

    2010-06-01

    The aim of this study was to explore the measurement and clinical significance of serum thrombopoietin (TPO) and lactate dehydrogenase (LDH) levels in patients with myelodysplastic syndrome (MDS) and acute leukemia (AL). The levels of serum TPO and lactate dehydrogenase in 25 patients with MDS and 40 patients with AL were measured by using sandwich ELISA and velocity methods before chemotherapy, at the stages of bone marrow depression and bone marrow recovery, respectively. The levels of serum TPO and LDH in 15 healthy controls were also measured. The results indicated that the serum TPO and LDH levels in ALL, AML and MDS patients before chemotherapy were significantly higher than those in healthy controls, the differences were statistically significant (q = 7.2943 - 27.4149, p TPO and LDH levels in the patients at the stages of bone marrow depression or bone marrow recovery were significantly lower than those in patients before treatment (q = 7.2943 - 25.9396, p 0.05). It is concluded that there is a strong correlation between serum TPO, LDH levels and the status of patients with hematologic malignancies, suggesting that TPO and LDH levels can be used for evaluation of therapeutic effect in hematologic malignancies.

  6. [The First Switched Time of PML/RARα Fusion Gene in Patients with Acute Promyelocytic Leukemia and Its Clinical Significance].

    Science.gov (United States)

    Pu, Lian-Fang; Tao, Qian-Shan; Wang, Hui-Ping; Zhai, Zhi-Min; Xiong, Shu-Dao

    2015-12-01

    To investigate the first switched time of PML/RARα fusion gene in patients with acute promyelocytic leukemia (APL) and its clinical significance. sixty cases of newly diagnosed APL were enrolled in this study. They received standard remission induction, consolidation and maintenance treatments according to the clinical pathway for APL, and were followed up. During the same time the PML/RARα fusion gene mRNA expression of all cases was detected by multi-nested PCR. except for 3 death cases and 1 case failed to follow-up, the PML/RARα fusion genes in the remaining 56 cases were firstly found to be negative from 24 to 381 days respectively, the mean value of the first switched time was 131 ± 90 days. There was no statistically significant difference in age, sex and risk stratification between different groups. However, the cases with L-type PML/RARα gene had shorter time compared with the patients with S-type PML/RARα gene (P = 0.032); then, for the above-mentimed 56 cases, the follow-up duration ranged from 25-1979 days (median 946 days), long-term molecular remissions had been observed in most cases, but 1 case with the first switched time of 133 days unfortunately recurred to be positive and followed by clinical relapse. The PML/RARα fusion gene in newly diagnosed APL patients was first switched to be negative in about 4 months after treatment. The first switched time of PML/RARα fusion gene can objectively reflect the reduction of leukemia cells, and the differences among different subtypes of PML/RARα fusion gene may have some suggestions for the treatment, but without important significance for the evaluation of prognosis and recurrence for APL patients. In addition, minimal residual disease (MRD) can be dynamically monitored by detecting PML/RARα fusion gene, thus having an important clinical significance for analysis of APL recurrence.

  7. Population pharmacokinetics and pharmacokinetics/pharmacodynamics of bendamustine in pediatric patients with relapsed/refractory acute leukemia.

    Science.gov (United States)

    Darwish, Mona; Megason, Gail; Bond, Mary; Hellriegel, Edward; Robertson, Philmore; Grasela, Thaddeus; Phillips, Luann

    2014-11-01

    The pharmacokinetic (PK) profile of bendamustine has been characterized in adults with indolent non-Hodgkin lymphoma (NHL), but remains to be elucidated in pediatric patients with hematologic malignancies. This analysis used data from a nonrandomized pediatric study in patients with relapsed/refractory acute lymphocytic leukemia or acute myeloid leukemia. Bendamustine 90 or 120 mg/m(2) (60-minute infusion) was administered on days 1 and 2 of 21 day cycles. The population PK base model was adjusted for body surface area (BSA), and the appropriateness of the final model was evaluated by visual predictive check. A covariate analysis explored PK variability. Bayesian PK parameter estimates and concentration-time profiles for each patient were generated. Bendamustine PK in pediatric patients was compared with that of adults with indolent NHL. PK/pharmacodynamic analyses were conducted for fatigue, nausea, vomiting, and infection. Thirty-eight patients (median age: 7 years; range: 1-19 years) receiving bendamustine 120 mg/m(2) and an additional five patients receiving bendamustine 90 mg/m(2) (median age: 12 years; range: 8-14 years) were included in the population PK analysis. Peak plasma concentrations of bendamustine (Cmax) occurred at the end of infusion (about 1 h). Decline from peak showed a rapid distribution phase (t½α = 0.308 h) and a slower elimination phase (t½β = 1.47 h). Model-predicted mean Cmax and area under the curve values from time 0-24 h were 6806 ng/mL and 8240 ng*h/mL, respectively. When dosed based upon BSA, it appeared that age, body weight, race, mild renal (n = 3) or hepatic (n = 2) dysfunction, cancer type, and cytochrome P450 1A2 inhibitors (n = 17) or inducers (n = 3) did not affect systemic exposure, which was comparable between pediatric and adult patients. Infection was the only adverse event associated with bendamustine Cmax. However, due to the small sample size for some subgroups, the

  8. Marked response to imatinib mesylate in a patient with platelet-derived growth factor receptor beta-associated acute myeloid leukemia.

    Science.gov (United States)

    Shimomura, Yoshimitsu; Maruoka, Hayato; Ishikawa, Takayuki

    2017-05-01

    Abnormal platelet-derived growth factor receptor (PDGFR)-mediated signaling may cause hematologic neoplasm. The PDGFR beta (PDGFRB) gene, located at chromosome band 5q31-33, forms a fusion gene as a result of chromosome translocation. Although patients with PDGFRB rearrangement mostly present with myeloproliferative neoplasm and eosinophilia, acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) have also been reported in this population. Treatment with imatinib mesylate alone has been shown to have excellent long-term efficacy against myeloproliferative neoplasms; however, its long-term effects on ALL and AML have not been elucidated. A 75-year-old man was diagnosed with acute myeloid leukemia having the PDGFRB and cGMP-dependent protein kinase 2 fusion gene with additional genetic abnormalities. Continuous therapy with single-agent imatinib mesylate resulted in cytogenetic remission and decreased molecular burden for 9 months; however, the leukemia subsequently recurred, and the patient died 1 year after initiation of treatment. This case report supports the importance of cytogenetic analysis during patient screening.

  9. Acute lymphoblastic leukemia in a patient with chronic granulomatous disease and a novel mutation in CYBB: First report

    NARCIS (Netherlands)

    Wolach, Baruch; Ash, Shifra; Gavrieli, Ronit; Stark, Batia; Yaniv, Isaac; Roos, Dirk

    2005-01-01

    We report for the first time a child with chronic granulomatous disease (CGD) who developed acute lymphoblastic leukemia (ALL). The diagnosis of CGD was made at the age of 4 months, by studies of his neutrophil functions. The superoxide production of the cells was negligible, as was the bactericidal

  10. [Bone scintigraphy with 99mTc-MDP in a patient with acute lymphoblastic leukemia initially diagnosed of Still's disease].

    Science.gov (United States)

    Benítez Velazco, A; González García, F M; Albalá González, M D; Pacheco Capote, C; Latre Romero, J M

    2005-01-01

    We present a 43-year-old male, who was admitted with the diagnosis of Adult-onset Still's disease, after several months of arthralgias, febricula and loss of weight. Chest x-ray, abdominal ultrasonography, chest, abdomen and pelvic CT scan and bone scintigraphy were performed. Scintigraphic findings oriented to the performance of a bone marrow biopsy with diagnosis of acute lymphoblastic leukemia.

  11. Blimp-1 impairs T cell function via upregulation of TIGIT and PD-1 in patients with acute myeloid leukemia.

    Science.gov (United States)

    Zhu, Liuluan; Kong, Yaxian; Zhang, Jianhong; Claxton, David F; Ehmann, W Christopher; Rybka, Witold B; Palmisiano, Neil D; Wang, Ming; Jia, Bei; Bayerl, Michael; Schell, Todd D; Hohl, Raymond J; Zeng, Hui; Zheng, Hong

    2017-06-19

    T cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif (ITIM) domain (TIGIT) and programmed cell death protein 1 (PD-1) are important inhibitory receptors that associate with T cell exhaustion in acute myeloid leukemia (AML). In this study, we aimed to determine the underlying transcriptional mechanisms regulating these inhibitory pathways. Specifically, we investigated the role of transcription factor B lymphocyte-induced maturation protein 1 (Blimp-1) in T cell response and transcriptional regulation of TIGIT and PD-1 in AML. Peripheral blood samples collected from patients with AML were used in this study. Blimp-1 expression was examined by flow cytometry. The correlation of Blimp-1 expression to clinical characteristics of AML patients was analyzed. Phenotypic and functional studies of Blimp-1-expressing T cells were performed using flow cytometry-based assays. Luciferase reporter assays and ChIP assays were applied to assess direct binding and transcription activity of Blimp-1. Using siRNA to silence Blimp-1, we further elucidated the regulatory role of Blimp-1 in the TIGIT and PD-1 expression and T cell immune response. Blimp-1 expression is elevated in T cells from AML patients. Consistent with exhaustion, Blimp-1 + T cells upregulate multiple inhibitory receptors including PD-1 and TIGIT. In addition, they are functionally impaired manifested by low cytokine production and decreased cytotoxicity capacity. Importantly, the functional defect is reversed by inhibition of Blimp-1 via siRNA knockdown. Furthermore, Blimp-1 binds to the promoters of PD-1 and TIGIT and positively regulates their expression. Our study demonstrates an important inhibitory effect of Blimp-1 on T cell response in AML; thus, targeting Blimp-1 and its regulated molecules to improve the immune response may provide effective leukemia therapeutics.

  12. Blimp-1 impairs T cell function via upregulation of TIGIT and PD-1 in patients with acute myeloid leukemia

    Directory of Open Access Journals (Sweden)

    Liuluan Zhu

    2017-06-01

    Full Text Available Abstract Background T cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif (ITIM domain (TIGIT and programmed cell death protein 1 (PD-1 are important inhibitory receptors that associate with T cell exhaustion in acute myeloid leukemia (AML. In this study, we aimed to determine the underlying transcriptional mechanisms regulating these inhibitory pathways. Specifically, we investigated the role of transcription factor B lymphocyte-induced maturation protein 1 (Blimp-1 in T cell response and transcriptional regulation of TIGIT and PD-1 in AML. Methods Peripheral blood samples collected from patients with AML were used in this study. Blimp-1 expression was examined by flow cytometry. The correlation of Blimp-1 expression to clinical characteristics of AML patients was analyzed. Phenotypic and functional studies of Blimp-1-expressing T cells were performed using flow cytometry-based assays. Luciferase reporter assays and ChIP assays were applied to assess direct binding and transcription activity of Blimp-1. Using siRNA to silence Blimp-1, we further elucidated the regulatory role of Blimp-1 in the TIGIT and PD-1 expression and T cell immune response. Results Blimp-1 expression is elevated in T cells from AML patients. Consistent with exhaustion, Blimp-1+ T cells upregulate multiple inhibitory receptors including PD-1 and TIGIT. In addition, they are functionally impaired manifested by low cytokine production and decreased cytotoxicity capacity. Importantly, the functional defect is reversed by inhibition of Blimp-1 via siRNA knockdown. Furthermore, Blimp-1 binds to the promoters of PD-1 and TIGIT and positively regulates their expression. Conclusions Our study demonstrates an important inhibitory effect of Blimp-1 on T cell response in AML; thus, targeting Blimp-1 and its regulated molecules to improve the immune response may provide effective leukemia therapeutics.

  13. Esophageal strictures during treatment for acute lymphoblastic leukemia.

    LENUS (Irish Health Repository)

    Kelly, Kevin

    2012-02-01

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

  14. Prevention of bacterial and fungal infections in acute leukemia patients: a new and potent combination of oral norfloxacin and amphotericin B.

    Science.gov (United States)

    Yamada, T; Dan, K; Nomura, T

    1993-09-01

    The effect of a combination regimen using norfloxacin (NFLX) and amphotericin B (AMPH-B) for prevention of infections in patients with acute leukemia being treated by remission-induction chemotherapy in a randomized, controlled trial was studied. One hundred and six consecutive, evaluable patients were randomly assigned to receive orally 200 mg of norfloxacin two or four times daily and 200 mg of amphotericin B four times daily, or amphotericin B only. A smaller percentage of patients with bacteriologically-documented infections was observed in the study group compared with the control group (34.6% vs 56.9%; P combination antimicrobial regimen is safe and effective for prevention of gram-negative bacterial as well as fungal infections in patients with acute leukemia being treated with cytotoxic remission-induction chemotherapy.

  15. A case report of acute myeloid leukemia and neurofibromatosis 1

    Directory of Open Access Journals (Sweden)

    Chiara Sartor

    2013-07-01

    Full Text Available We report a case of a 65-year old patient affected by neurofibromatosis 1, documented by the presence of germ-line mutation on the NF1 gene, who developed various hyperproliferative malignant and benign diseases. He was brought to our attention for the diagnosis of acute myeloid leukemia revealed by major fatigue and dyspnea. The disease characteristics at diagnosis were hyperleukocytosis and complex karyotype with the inversion of the chromosome 16, classifying as a high-risk leukemia. The association between leukemia and neurofibromatosis 1 is controversial and needs to be further investigated. Nevertheless, such patients present a wide number of comorbidities that make therapeutic strategies most difficult.

  16. DNMT3A R882 mutations in patients with cytogenetically normal acute myeloid leukemia and myelodysplastic syndrome.

    Science.gov (United States)

    El Ghannam, Doaa; Taalab, Mona M; Ghazy, Hayam F; Eneen, Asmaa F

    2014-01-01

    Several molecular markers have been described that help to classify patients with acute myeloid leukemia (AML), a heterogeneous hematopoietic tissue neoplasm, into risk groups. We determined the frequency of DNMT3A mutations, their associations with clinical and molecular characteristics and outcome, in primary, cytogenetically-normal AML (CN-AML) and CN-myelodysplastic syndrome (MDS). A total of 63 CN-AML and 16 CN-MDS patients were analyzed for mutations in DNMT3A, codon R822 by direct sequencing and mutation of NPM1 and FLT3/ITD. DNMT3A mutations were found in 17/63 (27%) of CN-AML and in 1/16 (6.3%) of CN-MDS patients. Patients with DNMT3A mutations were older (p=0.047), had higher white blood cell (WBC) counts (p=0.046), more often belonged to FAB groups M4 and M5 (p=0.017), and were more associated with NPM1 mutations (p=0.017), than those with wild-type DNMT3A. DNMT3A-mutated patients had shorter overall disease survival (pclassification of CN-AML. Crown Copyright © 2014. Published by Elsevier Inc. All rights reserved.

  17. CT findings of brain atrophy after chemotherapy in acute leukemia

    Energy Technology Data Exchange (ETDEWEB)

    Lim, Jun; Park, Seog Hee; Kim, Choon Yul; Bahk, Yong Whee [Catholic University Medicine College, Seoul (Korea, Republic of)

    1988-10-15

    A study was performed to evaluate the atrophic changes of the central nerve system after chemotherapy in the patients with acute leukemia. The computed tomographic findings and medical records of 20 proven acute leukemia patients under 35 years-old who developed various CNS symptoms and signs during and/or after 2 courses of chemotherapy were reviewed. The results were as follows: 1. Age distribution was from 14 to 5 years (mean was 26 years). Male was 15. 2. Presenting clinical symptoms and signs were headache (16/20), nausea and vomiting (11/20) and loss of consciousness (5/20). 3. Brain atrophy was noted in 16 patients including cortical and subcortical atrophy 15 cases and subcortical atrophy 1 case. 4. Two cases of hemorrhage, one each of intracranial hematoma and chronic subdural hematoma were found in addition to brain atrophy. This showed that chemotherapeutic agents cause brain atrophy in a considerable number of the patients with symptomatic acute leukemia.

  18. Improved treatment results in high-risk pediatric acute myeloid leukemia patients after intensification with high-dose cytarabine and mitoxantrone: results of Study Acute Myeloid Leukemia-Berlin-Frankfurt-Münster 93.

    Science.gov (United States)

    Creutzig, U; Ritter, J; Zimmermann, M; Reinhardt, D; Hermann, J; Berthold, F; Henze, G; Jürgens, H; Kabisch, H; Havers, W; Reiter, A; Kluba, U; Niggli, F; Gadner, H

    2001-05-15

    To improve outcome in high-risk patients, high-dose cytarabine and mitoxantrone (HAM) was introduced into the treatment of children with acute myelogenous leukemia (AML) in study AML-BFM 93. Patients were randomized to HAM as either the second or third therapy block, for the purpose of evaluation of efficacy and toxicity. A total of 471 children with de novo AML were entered onto the trial; 161 were at standard risk and 310 were at high risk. After the randomized induction (daunorubicin v idarubicin), further therapy, with the exception of HAM, was identical in the two risk groups and also comparable to that in study Acute Myeloid Leukemia-Berlin-Frankfurt-Münster (AML-BFM) 87. Overall, 387 (82%) of 471 patients achieved complete remission, and 5-year survival, event-free survival (EFS), and disease-free survival rates were 60%, 51%, and 62%, respectively. Idarubicin induction resulted in a significantly better blast cell reduction in the bone marrow on day 15. Estimated survival and probability of EFS were superior in study AML-BFM 93 compared with study AML-BFM 87 (P =.01, log-rank test). This improvement, however, was restricted to the 310 high-risk patients (remission rate and probability of 5-year EFS in study AML-BFM 93 v study AML-BFM 87: 78% v 68%, P =.007; and 44% v 31%, P =.01, log-rank test). Probability of 5-year EFS among standard-risk patients in study AML-BFM 93 was similar to that in study AML-BFM 87 (65% v 63%, P = not significant). Whether HAM was placed as the second or third therapy block was of minor importance. However, patients who received the less intensive daunorubicin treatment during induction benefited from early HAM. Improved treatment results in children with high-risk AML in study AML-BFM 93 must be attributed mainly to the introduction of HAM.

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

    Directory of Open Access Journals (Sweden)

    Chiara Sartor

    2013-07-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2014-06-01

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

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

    Science.gov (United States)

    Hernandez-Valladares, Maria; Aasebø, Elise; Selheim, Frode; Berven, Frode S; Bruserud, Øystein

    2016-08-22

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

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

    Directory of Open Access Journals (Sweden)

    Maria Hernandez-Valladares

    2016-08-01

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

  3. Significance of FAB subclassification of "acute myeloid leukemia, NOS" in the 2008 WHO classification: analysis of 5848 newly diagnosed patients.

    Science.gov (United States)

    Walter, Roland B; Othus, Megan; Burnett, Alan K; Löwenberg, Bob; Kantarjian, Hagop M; Ossenkoppele, Gert J; Hills, Robert K; van Montfort, Kees G M; Ravandi, Farhad; Evans, Anna; Pierce, Sherry R; Appelbaum, Frederick R; Estey, Elihu H

    2013-03-28

    The World Health Organization (WHO) classifies acute myeloid leukemia (AML) via genetic, immunophenotypic, biological, and clinical features. Still, "AML, not otherwise specified (NOS)" is further subdivided based on morphologic criteria similar to those of the French-American-British (FAB) classification. We analyzed the relevance of this practice in patients with newly diagnosed "AML, NOS" with available FAB information undergoing curative-intent therapy in trials of 3 cooperative study groups (Dutch-Belgian Cooperative Trial Group for Hematology/Oncology [HOVON], UK Medical Research Council/National Cancer Research Institute [MRC/NCRI], and the US cooperative group Southwest Oncology Group [SWOG]) or at MD Anderson Cancer Center. Ignoring information on NPM1 and CEBPA, 5848 patients met criteria for "AML, NOS." After multivariate adjustment, FAB M0 was independently associated with significantly lower likelihood of achieving complete remission and inferior relapse-free and overall survival as compared with FAB M1, M2, M4, M5, and M6, with inconclusive data regarding M7. However, restricting attention to known NPM1(neg) patients, FAB M0 was no longer associated with worse outcomes; restricting attention to patients known to be NPM1(neg)/CEPBA(neg) (ie, honoring the provisional entities of "AML with mutated NPM1" and "AML with mutated CEBPA") did not affect this result. In conclusion, in the 2008 WHO classification scheme, FAB subclassification does not provide prognostic information for "AML, NOS" cases if data on NPM1 and CEBPA mutations are available.

  4. Molecular Genetic Markers in Acute Myeloid Leukemia

    Directory of Open Access Journals (Sweden)

    Sophia Yohe

    2015-03-01

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

  5. Expression of CD71 by flow cytometry in acute leukemias: More often seen in acute myeloid leukemia

    Directory of Open Access Journals (Sweden)

    Amit Pande

    2016-01-01

    Full Text Available Background: CD71 is a marker that has been usually used for identifying dysplasia in the erythroid series. We have tried to evaluate the expression of CD71 in various types of acute leukemias. Materials and Methods: We studied 48 patients of acute leukemia, of which 25 were acute myeloid leukemia (AML, 13 were precursor B-acute lymphoblastic leukemia (B-ALL, 8 were T-ALL, and 2 were mixed phenotype acute leukemia (T/myeloid as per the WHO classification. Results: We found that the expression of CD71 was most prevalent in AMLs (84%, followed by T-ALL (50% and least in B-ALL (30%. Conclusion: This finding clearly shows the higher expression of CD71 in AMLs compared to other common type of leukemias, such as B- and T-ALL. We suggest that the high expression of CD71 in AMLs could be used as a diagnostic marker and may also be used for minimal residual disease analysis after further studies in posttreatment scenario. This study is the first of its kind in the South Asian population.

  6. Expression of CD71 by flow cytometry in acute leukemias: More often seen in acute myeloid leukemia.

    Science.gov (United States)

    Pande, Amit; Dorwal, Pranav; Jain, Dharmendra; Tyagi, Neetu; Mehra, Simmi; Sachdev, Ritesh; Raina, Vimarsh

    2016-01-01

    CD71 is a marker that has been usually used for identifying dysplasia in the erythroid series. We have tried to evaluate the expression of CD71 in various types of acute leukemias. We studied 48 patients of acute leukemia, of which 25 were acute myeloid leukemia (AML), 13 were precursor B-acute lymphoblastic leukemia (B-ALL), 8 were T-ALL, and 2 were mixed phenotype acute leukemia (T/myeloid) as per the WHO classification. We found that the expression of CD71 was most prevalent in AMLs (84%), followed by T-ALL (50%) and least in B-ALL (30%). This finding clearly shows the higher expression of CD71 in AMLs compared to other common type of leukemias, such as B- and T-ALL. We suggest that the high expression of CD71 in AMLs could be used as a diagnostic marker and may also be used for minimal residual disease analysis after further studies in posttreatment scenario. This study is the first of its kind in the South Asian population.

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

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    Ilana de França Azevedo

    2014-10-01

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

  8. Leukemia-Initiating Cells in T-Cell Acute Lymphoblastic Leukemia.

    Science.gov (United States)

    Tan, Shi Hao; Bertulfo, Fatima Carla; Sanda, Takaomi

    2017-01-01

    T-cell acute lymphoblastic leukemia (T-ALL) is a hematological malignancy characterized by the clonal proliferation of immature T-cell precursors. T-ALL has many similar pathophysiological features to acute myeloid leukemia, which has been extensively studied in the establishment of the cancer stem cell (CSC) theory, but the CSC concept in T-ALL is still debatable. Although leukemia-initiating cells (LICs), which can generate leukemia in a xenograft setting, have been found in both human T-ALL patients and animal models, the nature and origin of LICs are largely unknown. In this review, we discuss recent studies on LICs in T-ALL and the potential mechanisms of LIC emergence in this disease. We focus on the oncogenic transcription factors TAL1, LMO2 , and NOTCH1 and highlight the significance of the transcriptional regulatory programs in normal hematopoietic stem cells and T-ALL.

  9. Leukemia-Initiating Cells in T-Cell Acute Lymphoblastic Leukemia

    Directory of Open Access Journals (Sweden)

    Shi Hao Tan

    2017-09-01

    Full Text Available T-cell acute lymphoblastic leukemia (T-ALL is a hematological malignancy characterized by the clonal proliferation of immature T-cell precursors. T-ALL has many similar pathophysiological features to acute myeloid leukemia, which has been extensively studied in the establishment of the cancer stem cell (CSC theory, but the CSC concept in T-ALL is still debatable. Although leukemia-initiating cells (LICs, which can generate leukemia in a xenograft setting, have been found in both human T-ALL patients and animal models, the nature and origin of LICs are largely unknown. In this review, we discuss recent studies on LICs in T-ALL and the potential mechanisms of LIC emergence in this disease. We focus on the oncogenic transcription factors TAL1, LMO2, and NOTCH1 and highlight the significance of the transcriptional regulatory programs in normal hematopoietic stem cells and T-ALL.

  10. Prophylaxis of invasive aspergillosis with caspofungin during construction works in patient with acute lymphoblasic leukemia treated with vincristin

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    Mojca Modic

    2012-12-01

    Case presentation: A 59-year old woman with common ALL relapsed after 22 years (normal cytogenetics. She was treated according to the UKALL XII regimen and achieved complete second remission. She received four cycles of vincristine 2 mg i.v. In a retrospective cohort study, prolonged neutropenia, use of steroids, nursing unit without laminar air flow during a period of construction works were associated with an increased incidence of invasive aspergillosis in patients who did not receive primary antifungal prophylaxis. Intravenous caspofungin was administered to the patient as primary aspergillosis prophylaxis on the first day of chemotherapy. Galactomannan antigen tests were negative during the period of neutropenia. There was no infection in the period of prolonged neutropenia. Conclusions: The author discusses primary prophylaxis of invasive aspergillosis with caspofungin during construction works in patients with acute lymphoblastic leukemia treated with vincristine. Because of non-conventional unit without laminar air flow during induction chemotherapy treatment, which leads to an increased risk of invasive fungal infection with Aspergillus, caspofungin prophylaxis is recommended at least until upgrade to laminar flow or cessation of construction works.

  11. Upregulation of microRNA-21 is a poor prognostic marker in patients with childhood B cell acute lymphoblastic leukemia.

    Science.gov (United States)

    Labib, Hany Abedelmalik; Elantouny, Neveen G; Ibrahim, Nevin F; Alnagar, Ahmed A

    2017-08-01

    Many studies have demonstrated that microRNA-21 (miR-21) is an oncogene and is upregulated in tumor tissue. However, its association with B-cell acute lymphoblastic leukemia (B-ALL) remains poorly understood. The expression of miR-21 was detected by real-time quantitative PCR in 75 children with de novo B-ALL as well as in 50 healthy controls. This study was conducted to evaluate the miR-21 as a biomarker for risk assessment, diagnosis and prognosis. Compared with normal controls, miR-21 expression was significantly upregulated in childhood B-ALL patients. Using the receiver operating characteristic curve 3.23 was selected as the cut-off value of miR-21 expression in distinguishing patients from controls. Patients group with High miR-21 expression was significantly associated with those aged 10 years, lower platelets count, more incidence of CNS infiltration and poorer treatment outcome also, they showed a significantly poorer disease-free survival (DFS) and overall survival (OS) compared to those with low miR-21 expression group. Its expression was an independent prognostic marker according to multivariate analysis. This is the first report demonstrating the upregulation of miR-21 in childhood B-ALL, and its association with poor response to induction therapy, shorter DFS and OS. These results suggest that miR-21 upregulation represent an unfavorable prognostic marker in Childhood B-ALL.

  12. Prognostically significant fusion oncogenes in Pakistani patients with adult acute lymphoblastic leukemia and their association with disease biology and outcome.

    Science.gov (United States)

    Sabir, Noreen; Iqbal, Zafar; Aleem, Aamer; Awan, Tashfeen; Naeem, Tahir; Asad, Sultan; Tahir, Ammara H; Absar, Muhammad; Hasanato, Rana M W; Basit, Sulman; Chishti, Muhammad Azhar; Faiyaz Ul-Haque, Muhammad; Khalid, Ahmad Muktar; Sabar, Muhammad Farooq; Rasool, Mahmood; Karim, Sajjad; Khan, Mahwish; Samreen, Baila; Akram, Afia M; Siddiqi, Muhammad Hassan; Shahzadi, Saba; Shahbaz, Sana; Ali, Agha Shabbir; Mahmood, Amer; Akram, Muhammad; Saeed, Tariq; Saleem, Arsalan; Mohsin, Danish; Shah, Ijaz Hussain; Khalid, Muhammad; Asif, Muhammad; Iqbal, Mudassar; Akhtar, Tanveer

    2012-01-01

    Chromosomal abnormalities play an important role in genesis of acute lymphoblastic leukemia (ALL) and have prognostic implications. Five major risk stratifying fusion genes in ALL are BCR-ABL, MLL-AF4, ETV6-RUNX11, E2A-PBX1 and SIL-TAL1. This work aimed to detect common chromosomal translocations and associated fusion oncogenes in adult ALL patients and study their relationship with clinical features and treatment outcome. We studied fusion oncogenes in 104 adult ALL patients using RT-PCR and interphase-FISH at diagnosis and their association with clinical characteristics and treatment outcome. Five most common fusion genes i.e. BCR-ABL (t 9; 22), TCF3-PBX1 (t 1; 19), ETV6-RUNX1 (t 12; 21), MLL-AF4 (t 4; 11) and SIL-TAL1 (Del 1p32) were found in 82/104 (79%) patients. TCF3-PBX1 fusion gene was associated with lymphadenopathy, SIL-TAL positive patients had frequent organomegaly and usually presented with a platelets count of less than 50 x10(9)/l. Survival of patients with fusion gene ETV6-RUNX1 was better when compared to patients harboring other genes. MLL-AF4 and BCR-ABL positivity characterized a subset of adult ALL patients with aggressive clinical behaviour and a poor outcome. This is the first study from Pakistan which investigated the frequency of 5 fusion oncogenes in adult ALL patients, and their association with clinical features, treatment response and outcome. Frequencies of some of the oncogenes were different from those reported elsewhere and they appear to be associated with distinct clinical characteristics and treatment outcome. This information will help in the prognostic stratification and risk adapted management of adult ALL patients.

  13. Effect of all-trans retinoic acid on newly diagnosed acute promyelocytic leukemia patients: results of a Brazilian center

    Directory of Open Access Journals (Sweden)

    B.C. de-Medeiros

    1998-12-01

    Full Text Available Thirty-seven patients with acute promyelocytic leukemia (APL were treated with all-trans retinoic acid (ATRA. Patients received 45 mg m-2 day-1 po of ATRA until complete remission (CR was achieved, defined as: a presence of less than 5% blasts in the bone marrow, with b white blood cells >103/mm3, c platelets >105/mm3 and d hemoglobin concentration >8 g/dl, with no blood or platelet transfusions. Thirty-one (83.7% patients achieved CR by day 50, and 75% of these before day 30. Correction of the coagulopathy, achieved between days 2 and 10 (mean, 3 days, was the first evidence of response to treatment. Only one patient had been previously treated with chemotherapy and three had the microgranular variant M3 form. Dryness of skin and mucosae was the most common side effect observed in 82% of the patients. Thrombosis, hepatotoxicity and retinoid acid syndrome (RAS were observed in 7 (19%, 6 (16% and 4 (11% patients, respectively. Thirteen (35% patients had to be submitted to chemotherapy due to hyperleukocytosis (above 40 x 103/mm3 and six of these presented with new signs of coagulopathy after chemotherapy. Four (11% patients died secondarily to intracerebral hemorrhage (IH and two (5.4% dropped out of the protocol due to severe ATRA side effects (one RAS and one hepatotoxicity. RAS and IH were related strictly to hyperleukocytosis. The reduced use of platelets and fresh frozen plasma probably lowered the total cost of treatment. We conclude that ATRA is an effective agent for inducing complete remission in APL patients.

  14. Immunophenotype and increased presence of CD4(+)CD25(+) regulatory T cells in patients with acute lymphoblastic leukemia.

    Science.gov (United States)

    Wu, Cui-Ping; Qing, Xi; Wu, Cui-Yun; Zhu, Hong; Zhou, Hai-Yan

    2012-02-01

    Acute lymphoblastic leukemia (ALL), cancer of the white blood cells, is a heterogeneous disease that mainly occurs due to the malignant cloning of original and naive lymphocytes. The aim of this study was to explore the immunophenotype, the percentage of CD4(+)CD25(+) regulatory T cells (Tregs) and the expression of cytokines interleukin (IL)-2, IL-10 and TGF-β in patients with ALL. The immunophenotype and levels of CD4(+)CD25(+) Tregs were detected using flow cytometry in the peripheral blood of 35 ALL patients, with 18 healthy individuals being selected as controls. The results suggested that 22 patients had B cell ALL (B-ALL) and 13 had T cell ALL (T-ALL) among the 35 ALL patients. In B-ALL patients, the surface antigen CD19 was most commonly expressed; in T-ALL patients, CD7 was most common. Furthermore, the percentage of CD4(+)CD25(+) Treg cells in the peripheral blood of B-ALL and T-ALL patients was higher compared to that of healthy individuals (Pcell culture supernatants from B-ALL and T-ALL patients were higher compared to those in the controls (Pcells, IL-2, IL-10 or TGF-β in B-ALL versus T-ALL patients. The authors concluded that CD19 and CD7 may serve as diagnostic markers of B-ALL and T-ALL, respectively. The increased presence of CD4(+)CD25(+) Treg cells and the altered levels of secreted cytokines are indicative of an immunosuppressive mechanism in the pathogenesis of ALL.

  15. Importance of pharmacogenetic markers in the methylenetetrahydrofolate reductase gene during methotrexate treatment in pediatric patients with acute lymphoblastic leukemia

    Directory of Open Access Journals (Sweden)

    Lazić Jelena

    2017-01-01

    Full Text Available Despite remarkable progress in survival of children with acute lymphoblastic leukemia (ALL which has reached about 85%, early toxicity and relapse rate remain issues that need to to be resolved. Genetic variants are important factors influencing the metabolism of cytotoxic drugs in ALL treatment. Variants in genes coding for methotrexate (MTX-metabolizing enzymes are under constant scientific interest due to their potential impact on drug toxicity and relapse rate. We investigated methylenetetrahydrofolate reductase (MTHFR c.677C>T and MTHFR c.1298A>C variants as pharmacogenetic markers of MTX toxicity and predictors of relapse. The study enrolled 161 children with ALL, treated according to the current International Berlin-Frankfurt-Munster group (BFM for diagnostics and treatment of leukemia and lymphoma protocols. Genotyping was performed using PCRRFLP and allele-specific PCR assays. Our results revealed similar distributions of MTHFR c.677C>T and MTHFR c.1298A>C genotypes among 104 healthy individuals as compared to pediatric ALL patients. A lower incidence of early MTX toxicity was noted in the MTHFR c.677TT genotype (p=0.017, while MTHFR c.1298A>C genotypes were not associated with MTX toxicity. Carriers of any MTHFR c.677C>T and MTHFR c.1298A>C genotypes did not experience decreased overall survival (OAS or higher relapse rates. Genetic variants in the MTHFR gene are not involved in leukemogenesis in pediatric ALL. The presence of the MTHFR c.677TT genotype was recognized as a predictive factor for decreased MTX toxicity during the intensification phase of therapy. Neither MTHFR c.677C>T nor MTHFR c.1298A>C genotypes correlated with an increased number of toxic deaths or relapse rate. Our study emphasizes the importance of implementing pharmacogenetic markers in order to optimize pediatric ALL therapy. [Project of the Serbian Ministry of Education, Science and Technological Development, Grant no. III 41004

  16. Allogeneic compared with autologous stem cell transplantation in the treatment of patients younger than 46 years with acute myeloid leukemia (AML) in first complete remission (CR1): an intention-to-treat analysis of the EORTC/GIMEMAAML-10 trial.

    NARCIS (Netherlands)

    Suciu, S.; Mandelli, F.; Witte, T.J.M. de; Zittoun, R.; Gallo, E.; Labar, B.; Rosa, G. De; Belhabri, A.; Giustolisi, R.; Delarue, R.; Liso, V.; Mirto, S.; Leone, G.; Bourhis, J.; Fioritoni, G.; Jehn, U.; Amadori, S.; Fazi, P.; Hagemeijer, A.; Willemze, R.

    2003-01-01

    In the European Organization for Research and Treatment of Cancer Leukemia Group and Gruppo Italiano Malattie Ematologiche dell' Adulto (EORTC-LG/GIMEMA) acute myeloid leukemia (AML)-10 trial, patients in first complete remission (CR1) received a single intensive consolidation (IC) course.

  17. Length of stay variations between rural and urban patients with acute myeloid leukemia: a case-matched study.

    Science.gov (United States)

    Heinz, Sean J; Milliken, Sam

    2013-06-01

    Keeping patients in hospital longer than medically necessary is costly and occupies resources that could be better utilised. If patients from regional areas remain in hospital longer because of logistical issues such as transport and accommodation, then there is an argument for establishing or expanding appropriate medical services for rural areas. However, if the length of stay (LOS) for rural and urban patients is similar, it could be surmised that current logistic services appropriately meet demand. This study reviews the cases of 40 patients with acute myeloid leukemia. This disease was selected as patients are generally required to travel to a metropolitan hospital for treatment, regardless of location. Twenty patients resided within the Sydney metropolitan area and 20 lived in rural New South Wales. Each of the 20 metropolitan patients were case-matched (1:1) with 20 rural patients with reference to sex, specific acute myeloid leukemia subtype (by World Health Organisation ICD-10 classification), and age. Following statistical non-parametric (t-test) analysis, rural and urban medians were found to be very similar with a high t-value and small mean (urban median=29, rural median=29.5, t-value=0.722, m=-0.95, s.d.=15.236, two-tailed P=0.789, 95% CI=-7.89, 5.99). This demonstrates that there was no statistically significant difference between mean LOS for rural or urban patients after case-matching, a conclusion supported by qualitative analysis of the data. Logistical issues are therefore unlikely to keep rural patients with AML in hospital beyond their immediate medical treatment. What is known about this topic? A United States-based study found that LOS in hospital for rural patients with human immunodeficiency virus was one-third longer than for urban patients across each of the 6 years analysed (from 1998 to 2003). However it was noted that after adjusting for covariates such as age and sex, differences between LOS for rural and urban residents were not of

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

    Directory of Open Access Journals (Sweden)

    Ola Khorshid

    2011-12-01

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

  19. A reevaluation of erythroid predominance in Acute Myeloid Leukemia using the updated WHO 2016 Criteria.

    Science.gov (United States)

    Margolskee, Elizabeth; Mikita, Geoff; Rea, Bryan; Bagg, Adam; Zuo, Zhuang; Sun, Yi; Goswami, Maitrayee; Wang, Sa A; Oak, Jean; Arber, Daniel A; Allen, M Brandon; George, Tracy I; Rogers, Heesun J; Hsi, Eric; Hasserjian, Robert P; Orazi, Attilio

    2018-02-05

    The 2016 WHO update changed the diagnostic criteria for myeloid neoplasms with erythroid predominance, limiting the diagnosis of acute myeloid leukemia to cases with ≥20% blasts in the bone marrow or peripheral blood. Although acute myeloid leukemia with ≥50% erythroid cells has historically been presumed to represent acute myeloid leukemia with myelodysplasia-related changes, this hypothesis has never been systematically examined. We sought to investigate the clinicopathologic, cytogenetic, and molecular features of acute myeloid leukemia with erythroid predominance to subclassify cases as defined by the 2016 WHO. We retrospectively identified patients with ≥50% erythroid precursors and either ≥20% bone marrow blasts or ≥20% peripheral blood blasts at the time of initial diagnosis at seven major academic centers. Laboratory and clinical data were obtained. Patients were then reclassified according to 2016 WHO guidelines. A matched control group was also obtained. We identified 146 patients with acute myeloid leukemia with erythroid predominance (62% M, average age: 62 y, range: 5-93 y). Of these, 91 were acute myeloid leukemia with myelodysplasia-related changes, 20 (14%) were therapy-related myeloid neoplasm, 23 (16%) acute myeloid leukemia, not otherwise specified, and ten acute myeloid leukemia with recurrent cytogenetic/molecular abnormalities. The bone marrow blast count ranged from 9-41%. There was no difference in survival for patients with erythroid predominance compared to patients with acute myeloid leukemia without erythroid proliferations. In a multivariable analysis, cytogenetic risk was the only significant predictor of survival. We find a significantly lower rate of FLT3 and RAS pathway alterations in acute myeloid leukemia with erythroid predominance compared to controls. Our study is one of the first to apply the 2016 WHO guidelines for classification of acute myeloid leukemia. We find acute myeloid leukemia with erythroid

  20. Severe malnutrition evaluated by patient-generated subjective global assessment results in poor outcome among adult patients with acute leukemia: A retrospective cohort study.

    Science.gov (United States)

    Li, Ji; Wang, Chang; Liu, Xiaoliang; Liu, Qiuju; Lin, Hai; Liu, Chunshui; Jin, Fengyan; Yang, Yan; Bai, Ou; Tan, Yehui; Gao, Sujun; Li, Wei

    2018-01-01

    To evaluate nutritional status in adult patients with acute leukemia (AL) using patient-generated subjective global assessment (PG-SGA) and to investigate the influence of nutritional status on prognosis.We observationally investigated 68 adult patients with newly diagnosed AL who received PG-SGA at the First Hospital of Jilin University between May 2013 and July 2015. Clinical features, chemotherapy regimens, biochemical indexes, body composition, complete remission (CR) rate, minimal residual disease (MRD), survival time, and side-effects of chemotherapy were compared between patients with and without severe malnutrition.Mean PG-SGA scores of the total patients were 6.1 ± 4.0, and 19 of 68 (27.9%) patients had severe malnutrition (PG-SGA score ≥9). Patients with acute myeloid leukemia (AML) had higher scores than those with acute lymphocytic leukemia (ALL; P = .011) and high-risk patients had higher scores regardless of whether they had AML or ALL (AML, P = .012; ALL, P = .043). Univariate analysis showed that severe malnutrition was correlated with age (P = .041), transferrin (P = .042), Karnofsky Performance Status score (P = .006), and C-reactive protein (CRP) (P = .018). Multivariate analysis demonstrated that severe malnutrition was associated with CRP (hazard ratio [HR] = 1.020, 95% confidence interval [CI]: 1.002-1.039, P = .026). No difference was found in CR rate (P = .831) between patients with and without malnutrition, but those who were severely malnourished had higher MRD (P = .048 in AML patients, P = .036 in ALL patients) and more gastrointestinal side-effects (P = .014). Severe malnutrition was also associated with inferior overall survival (HR = 0.243, 95% CI: 0.063-0.945, P = .041) but not with event-free survival (HR = 0.808, 95% CI: 0.338-1.934, P = .663).Severe malnutrition defined by PG-SGA in adult patients with de novo AL may result in poor outcome. Copyright

  1. Cellulitis with Leukocytopenia as an Initial Sign of Acute Promyelocytic Leukemia

    Directory of Open Access Journals (Sweden)

    Sachiko Sakamoto

    2012-03-01

    Full Text Available Patients with hematologic malignancies are immunosuppressive and may develop cutaneous or invasive infections as a primary sign of immune suppression. Acute promyelocytic leukemia (acute myeloid leukemia M3 is caused by translocation of reciprocal chromosomal rearrangement t(15;17, which produces an oncogenic protein. We herein describe a 71-year-old man having cellulitis with leukocytopenia as a first sign of acute promyelocytic leukemia. Dermatologists and hematologists should keep in mind that patients with a hematologic malignancy, such as acute promyelocytic leukemia, can develop cellulitis with leukocytopenia.

  2. Reduction in WT1 gene expression during early treatment predicts the outcome in patients with acute myeloid leukemia.

    Science.gov (United States)

    Andersson, Charlotta; Li, Xingru; Lorenz, Fryderyk; Golovleva, Irina; Wahlin, Anders; Li, Aihong

    2012-12-01

    Wilms tumor gene 1 (WT1) expression has been suggested as an applicable minimal residual disease marker in acute myeloid leukemia (AML). We evaluated the use of this marker in 43 adult AML patients. Quantitative assessment of WT1 gene transcripts was performed using real-time quantitative-polymerase chain reaction assay. Samples from both the peripheral blood and the bone marrow were analyzed at diagnosis and during follow-up. A strong correlation was observed between WT1 normalized with 2 different control genes (β-actin and ABL1, P0.05). A≥1-log reduction in WT1 expression in bone marrow samples taken freedom from relapse (P=0.010) when β-actin was used as control gene. Furthermore, a reduction in WT1 expression by ≥2 logs in peripheral blood samples taken at a later time point significantly correlated with a better outcome for overall survival (P=0.004) and freedom from relapse (P=0.012). This result was achieved when normalizing against both β-actin and ABL1. These results therefore suggest that WT1 gene expression can provide useful information for minimal residual disease detection in adult AML patients and that combined use of control genes can give more informative results.

  3. Efficacy and tolerability of treatment with azacitidine for 5 days in elderly patients with acute myeloid leukemia

    International Nuclear Information System (INIS)

    Sadashiv, Santhosh K; Hilton, Christie; Khan, Cyrus; Rossetti, James M; Benjamin, Heather L; Fazal, Salman; Sahovic, Entezam; Shadduck, Richard K; Lister, John

    2014-01-01

    Acute myeloid leukemia (AML) patients aged ≥60 years tolerate standard induction chemotherapy poorly. Therapy with azacitidine at a dose of 75 mg/m 2 /day for 7 days appears to be better tolerated, and is approved by the Food and Drug Administration (FDA) for the treatment of elderly AML patients with bone marrow (BM) blast counts of 20–30%. Here, we report the results of a prospective, phase 2, open-label study that evaluated the tolerability and efficacy of a 5-day regimen of single-agent subcutaneous azacitidine 100 mg/m 2 /day administered every 28 days in 15 elderly patients with newly diagnosed AML, 14 of whom had BM blast counts >30%. The overall response rate was 47%. Complete remission, partial remission, and hematologic improvement were achieved by 20, 13, and 13% of patients, respectively. Median overall survival was 355 days for the entire cohort, and 532 days for responders. Median time to best response was 95 days, and median treatment duration was 198 days (range = 13–724 days). Grade 3–4 hematologic toxicities comprised predominantly febrile neutropenia (40%) and thrombocytopenia (20%). Febrile neutropenia was the most common cause of hospitalization. Nonhematologic toxicities, consisting of injection-site skin reactions and fatigue (Grades 1–2), occurred in 73% (n = 11) of patients. No treatment-related deaths occurred during the study. The dose and schedule of therapy remained constant in all but four patients. The findings of this study suggest that administration of subcutaneous azacitidine 100 mg/m 2 /day for 5 days every 28 days is a feasible, well-tolerated, and effective alternative to standard induction chemotherapy in elderly patients with AML

  4. Epidemiologic Investigation of a Cluster of Neuroinvasive Bacillus cereus Infections in 5 Patients With Acute Myelogenous Leukemia.

    Science.gov (United States)

    Rhee, Chanu; Klompas, Michael; Tamburini, Fiona B; Fremin, Brayon J; Chea, Nora; Epstein, Lauren; Halpin, Alison Laufer; Guh, Alice; Gallen, Rachel; Coulliette, Angela; Gee, Jay; Hsieh, Candace; Desjardins, Christopher A; Pedamullu, Chandra Sekhar; DeAngelo, Daniel J; Manzo, Veronica E; Folkerth, Rebecca Dunn; Milner, Danny A; Pecora, Nicole; Osborne, Matthew; Chalifoux-Judge, Diane; Bhatt, Ami S; Yokoe, Deborah S

    2015-09-01

    Background.  Five neuroinvasive Bacillus cereus infections (4 fatal) occurred in hospitalized patients with acute myelogenous leukemia (AML) during a 9-month period, prompting an investigation by infection control and public health officials. Methods.  Medical records of case-patients were reviewed and a matched case-control study was performed. Infection control practices were observed. Multiple environmental, food, and medication samples common to AML patients were cultured. Multilocus sequence typing was performed for case and environmental B cereus isolates. Results.  All 5 case-patients received chemotherapy and had early-onset neutropenic fevers that resolved with empiric antibiotics. Fever recurred at a median of 17 days (range, 9-20) with headaches and abrupt neurological deterioration. Case-patients had B cereus identified in central nervous system (CNS) samples by (1) polymerase chain reaction or culture or (2) bacilli seen on CNS pathology stains with high-grade B cereus bacteremia. Two case-patients also had colonic ulcers with abundant bacilli on autopsy. No infection control breaches were observed. On case-control analysis, bananas were the only significant exposure shared by all 5 case-patients (odds ratio, 9.3; P = .04). Five environmental or food isolates tested positive for B cereus, including a homogenized banana peel isolate and the shelf of a kitchen cart where bananas were stored. Multilocus sequence typing confirmed that all case and environmental strains were genetically distinct. Multilocus sequence typing-based phylogenetic analysis revealed that the organisms clustered in 2 separate clades. Conclusions.  The investigation of this neuroinvasive B cereus cluster did not identify a single point source but was suggestive of a possible dietary exposure. Our experience underscores the potential virulence of B cereus in immunocompromised hosts.

  5. Clinical case of acute myeloblastic leukemia with t(8;21)(q22;q22) in a patient with Klinefelter’s syndrome

    OpenAIRE

    Vanya Slavcheva; T. Lukanov; G. Balatsenko; S. Angelova; А. Antonov; L. Bogdanov; N. Tsvetkov

    2010-01-01

    Klinefelter’s syndrome is characterized by abnormal karyotype 47, XXY and a phenotype associated with hypogonadism and gynecomastia. Often the disease can be diagnosed accidentally, when carrying out cytogenetic analysis in cases of a malignant blood disease. We present the clinical case of a patient diagnosed with acute myelomonoblastic leukemia- M4 Eo (AML- M4), where by means of classic cytogenetics a karyotype was found corre-sponding to Klinefelter’s syndrome. Three induction courses of ...

  6. Serum hepcidin level and disease course of acute leukemia in ...

    African Journals Online (AJOL)

    Acute leukemia (AL) is a heterogeneous group of hematopoietic neoplasms and it is the most common childhood malignancy. Many patients with AL develop severe anemia that requires multiple blood transfusions. Hepcidin expression may play a role in anemia which is often seen in these patients. The aim of this study is ...

  7. Acute lymphoblastic leukemia in children with Down syndrome

    DEFF Research Database (Denmark)

    Buitenkamp, Trudy D; Izraeli, Shai; Zimmermann, Martin

    2014-01-01

    Children with Down syndrome (DS) have an increased risk of B-cell precursor (BCP) acute lymphoblastic leukemia (ALL). The prognostic factors and outcome of DS-ALL patients treated in contemporary protocols are uncertain. We studied 653 DS-ALL patients enrolled in 16 international trials from 1995...

  8. Clinical features and early treatment response of central nervous system involvement in childhood acute lymphoblastic leukemia

    DEFF Research Database (Denmark)

    Levinsen, Mette; Taskinen, Mervi; Abrahamsson, Jonas

    2014-01-01

    BACKGROUND: Central nervous system (CNS) involvement in childhood acute lymphoblastic leukemia (ALL) remains a therapeutic challenge. PROCEDURE: To explore leukemia characteristics of patients with CNS involvement at ALL diagnosis, we analyzed clinical features and early treatment response of 744...... leukemia and patients without such characteristics (0.50 vs. 0.61; P = 0.2). CONCLUSION: CNS involvement at diagnosis is associated with adverse prognostic features but does not indicate a less chemosensitive leukemia....

  9. Factor V Leiden 1691G/A and prothrombin gene 20210G/A polymorphisms as prothrombotic markers in adult Egyptian acute leukemia patients.

    Science.gov (United States)

    El Sissy, Azza Hamdy; El Sissy, Maha H; Elmoamly, Shereef

    2014-11-01

    Factor V Leiden 1691G/A and prothrombin gene 20210G/A mutations are the most common genetic defects leading to thrombosis. This work aimed to study the FV Leiden and the prothrombin gene polymorphism in adult Egyptian patients with acute leukemia and their importance in thrombophilia screening. The study included 76 patients with acute leukemia and 100 healthy controls. Genotyping was done by real-time polymerase chain reaction technique. For factor V Leiden, the frequency of G/A mutation conferred more than 2.5-fold of increased risk of (OR 2.639 95 % CI 1.045-6.669). The frequency of factor V Leiden combined (G/A + A/A) genotypes conferred 2.83-fold of increased risk (OR 2.828, CI 1.13-7.075), The A allele conferred almost threefold increased risk (OR 2.824, 95 % CI 1.175-6.785). Despite higher frequency in patients compared to controls, there was no risk of association between prothrombin gene mutation and acute leukemia in adult Egyptians nor was there between combined genotypes of prothrombin gene mutation and factor V Leiden.

  10. Impact of physician assistants on the outcomes of patients with acute myelogenous leukemia receiving chemotherapy in an academic medical center.

    Science.gov (United States)

    Glotzbecker, Brett E; Yolin-Raley, Deborah S; DeAngelo, Daniel J; Stone, Richard M; Soiffer, Robert J; Alyea, Edwin P

    2013-09-01

    Inpatient academic medical center care historically has been delivered by faculty physicians in conjunction with physicians in training (house officers [HOs]). Alternative staffing models have emerged secondary to American Counsel for Graduate Medical Education work-hour restrictions. The purpose of this study was to assess the quality of acute myelogenous leukemia (AML) care provided by a physician assistant (PA) service compared with a traditional model. Data were retrospectively collected on patients admitted with AML for reinduction chemotherapy from 2008 to 2012. Primary outcome measures were inpatient mortality and length of stay (LOS). Secondary measures included readmissions, intensive care unit (ICU) transfers, consults requested, and radiologic studies ordered. Ninety-five patients with AML were reviewed. Forty-seven patients (49.5%) were admitted to the HO service, and 48 patients (50.5%) were admitted to the PA service. Demographic data were similar between services. LOS was significantly different between the services, with a mean of 36.8 days with the HO model compared with 30.9 days with the PA service (P=.03). The 14-day readmission rate also differed significantly; it was 10.6% (five of 47 patients) and zero for the HO and PA models, respectively (P=.03). The mean number of consults with the HO model was 2.11 (range, zero to five) versus 1.47 (range, zero to four) with the PA service (P=.03). Mortality and ICU transfers were not significantly different. The data demonstrate equivalent mortality and ICU transfers, with a decrease in LOS, readmission rates, and consults for patients cared for in the PA service. This suggests that the PA service is associated with increased operational efficiency and decreased health service use without compromising health care outcomes.

  11. [Acute myeloid leukemia originating from the same leukemia clone after the complete remission of acute lymphoid leukemia].

    Science.gov (United States)

    Matsuda, Isao; Nakamaki, Tsuyoshi; Amaya, Hiroshi; Kiyosaki, Masanobu; Kawakami, Keiichiro; Yamada, Kazunari; Yokoyama, Akihiro; Hino, Ken-ichiro; Tomoyasu, Shigeru

    2003-09-01

    A 22-year-old female was diagnosed as having acute lymphoid leukemia (ALL) in February 1995, from the findings of peroxidase negative, CD10+, CD19+, TdT+ and rearrangement of IgH and TCR beta. AdVP (doxorubicin, vincristine and prednisolone) therapy achieved a complete remission (CR). Bone marrow transplantation had to be abandoned because of the lack of an HLA-identical donor. Intensification therapy was thus carried out repeatedly. In June 1998, myeloblast with Auer rods, peroxidase positive, CD13+, CD33+ and HLA-DR+, appeared. The patient was diagnosed as having lineage switch acute myeloid leukemia (AML) from ALL. Though A-DMP (cytosine arabinoside, daunorubicin, 6-mercaptopurine) therapy was resistant, AdVP therapy led to a CR. The patient died of cardiotoxicity from anthracyclines in February 1999. From the results of the Ramasamy method using the clonal rearrangements of the Ig heavy chain gene locus, the origin of the pathological cells of ALL and AML was indicated to be the same leukemia clone.

  12. Benzene and childhood acute leukemia in Oklahoma.

    Science.gov (United States)

    Janitz, Amanda E; Campbell, Janis E; Magzamen, Sheryl; Pate, Anne; Stoner, Julie A; Peck, Jennifer D

    2017-10-01

    Although childhood cancer is a leading cause of childhood mortality in the US, evidence regarding the etiology is lacking. The goal of this study was to evaluate the association between benzene, a known carcinogen, and childhood acute leukemia. We conducted a case-control study including cases diagnosed with acute leukemia between 1997 and 2012 (n = 307) from the Oklahoma Central Cancer Registry and controls matched on week of birth from birth certificates (n = 1013). We used conditional logistic regression to evaluate the association between benzene, measured with the 2005 National-Scale Air Toxics Assessment (NATA) at census tract of the birth residence, and childhood acute leukemia. We observed no differences in benzene exposure overall between cases and controls. However, when stratified by year of birth, cases born from 2005 to 2010 had a three-fold increased unadjusted odds of elevated exposure compared to controls born in this same time period (4th Quartile OR: 3.53, 95% CI: 1.35, 9.27). Furthermore, the estimates for children with acute myeloid leukemia (AML) were stronger than those with acute lymphoid leukemia, though not statistically significant. While we did not observe an association between benzene and childhood leukemia overall, our results suggest that acute leukemia is associated with increased benzene exposure among more recent births, and children with AML may have increased benzene exposure at birth. Using the NATA estimates allowed us to assess a specific pollutant at the census tract level, providing an advantage over monitor or point source data. Our study, however, cannot rule out the possibility that benzene may be a marker of other traffic-related exposures and temporal misclassification may explain the lack of an association among earlier births. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Nucleophosmin 1 expression in acute myeloid leukemia

    Directory of Open Access Journals (Sweden)

    Mohammad Davoudi

    2015-09-01

    Full Text Available Nucleophosmin1 is a multifunctional protein that shuttles between nucleus and cytoplasm in some subtypes of acute myeloid leukemias. Mutated Nucleophosmin1 expresses aberrantly in the cytoplasm of the cell and transports from nucleolus to the cytoplasm. It is diagnosed by immunohistochemical techniques, flow cytometry assay and mutational analysis.The aim of this study is to evaluate the effects of Nucleophosmin1 mutation on the clinical presentations, prognosis, diagnosis and the treatment of acute myeloid leukemia. Thirteen articles were extracted from PubMed, Google scholar and Scopus in which the Nucleophosmin1 mutation correlated with gingival hyperplasia, high white blood cell count, lymphadenopathy, high platelet count and other signs and symptoms of myelomonocytic and monocytic acute myeloid leukemias. This mutation is a provisional entity in the classification of acute myeloid leukemia, which influences on the prognosis, clinical course and the treatment of some subtypes of acute myeloid leukemias. Nucleophosmin1 mutation has favorable prognostic value in the absence of other concomitant mutations.

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

    Science.gov (United States)

    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.

  15. Azacitidine augments expansion of regulatory T cells after allogeneic stem cell transplantation in patients with acute myeloid leukemia (AML).

    Science.gov (United States)

    Goodyear, Oliver C; Dennis, Mike; Jilani, Nadira Y; Loke, Justin; Siddique, Shamyla; Ryan, Gordon; Nunnick, Jane; Khanum, Rahela; Raghavan, Manoj; Cook, Mark; Snowden, John A; Griffiths, Mike; Russell, Nigel; Yin, John; Crawley, Charles; Cook, Gordon; Vyas, Paresh; Moss, Paul; Malladi, Ram; Craddock, Charles F

    2012-04-05

    Strategies that augment a GVL effect without increasing the risk of GVHD are required to improve the outcome after allogeneic stem cell transplantation (SCT). Azacitidine (AZA) up-regulates the expression of tumor Ags on leukemic blasts in vitro and expands the numbers of immunomodulatory T regulatory cells (Tregs) in animal models. Reasoning that AZA might selectively augment a GVL effect, we studied the immunologic sequelae of AZA administration after allogeneic SCT. Twenty-seven patients who had undergone a reduced intensity allogeneic transplantation for acute myeloid leukemia were treated with monthly courses of AZA, and CD8(+) T-cell responses to candidate tumor Ags and circulating Tregs were measured. AZA after transplantation was well tolerated, and its administration was associated with a low incidence of GVHD. Administration of AZA increased the number of Tregs within the first 3 months after transplantation compared with a control population (P = .0127). AZA administration also induced a cytotoxic CD8(+) T-cell response to several tumor Ags, including melanoma-associated Ag 1, B melanoma antigen 1, and Wilm tumor Ag 1. These data support the further examination of AZA after transplantation as a mechanism of augmenting a GVL effect without a concomitant increase in GVHD.

  16. [Infections in the child with acute leukemia].

    Science.gov (United States)

    Carrillo, J M; Jiménez, E; Jiménez, R

    1981-01-01

    One hundred and twenty-five febrile episodes in 82 children with acute leukemia were studied; 46% of the patients were from urban and 54% from rural areas. The origin of the fever was identified in 91% of the episodes, prevailing pneumonia, septicemia, chickenpox and herpes zoster. The etiological agent was identified in 46% of the cases. A viral predominance was evident, and among them varicela-zoster, following in importance gram-negative bacteria. Histoplasma capsulatum and Pneumocystis carinii were isolated in two occassions each. Sepsis was found more frequently in children with active leukemia than in those in remission (p less than 0.001). Forty-four febrile episodes occurred in patients with less than 1,000 neutrophils/ul. The daily-risk rate of infection was higher in children fom rural than in those from urban areas (p less than 0.001). After clinical and laboratory studies, methicillin and gentamicin were used, in addition to carbenicillin or trimethoprim-sulfamethoxazole is selected cases. This treatment was effective in 86% of the cases. Twelve (15%) children died, 6 of whom were in remission at that moment.

  17. The MLL recombinome of acute leukemias in 2013.

    Science.gov (United States)

    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

    2013-11-01

    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.

  18. [Influence of Leukodeplated Blood Transfusion on Cellular Immunity of Acute Leukemia Patients].

    Science.gov (United States)

    Lu, Ya-Lan; Zhang, Xin; Wang, Yu-Fang; Ke, Shan-Dong; Ke, Jin-Yong; Liu, Geng-Fu; Chen, Shi-Ming

    2016-08-01

    To study the influence of leukodeplated blood transfusion on cellular immunity of patients with acute leuemia, so as to provide support for application of leuko-deplated blood transfusion in clinic. A total of 100 AL patients from January 2012 to December 2015 were chosen, and were divided into 2 groups: leukodeplated blood transfusion group(50 cases) and routine blood transfusion group(RBT) as control (50 cases). The effective rate, side effects, peripheral blood T cells and expression level of TLR2 and TLR4 were compared between 2 groups. The expression levels CD3(+), CD4(+), CD8(+), CD4(+)/CD8(+) of TLR2 and TLR4 in control group were (52.18±2.14)%, (27.28±1.19)%,(24.21±1.65)%,1.22±0.18,0.62±0.04 and 0.57±0.05, respectively, after treatment; while these indicators in LdBT group were (52.18±2.14)%,(30.97±2.01)%,(27.08±1.55)%,1.39±0.24,0.91±0.06 and 0.87±0.07, respectively, and above-mentioned indicators in LdBT group were significantly higher than those in control group(P0.05). The rate of side effects in study group was 6% (3/50), 18% (9/50) in control group, with statistically significance difference (Pblood transfusion can improve the cellular immunity of AL patients, and reduce the rate of side effects.

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

    DEFF Research Database (Denmark)

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

    2013-01-01

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

  20. Relapsed childhood acute lymphoblastic leukemia in the Nordic countries

    DEFF Research Database (Denmark)

    Oskarsson, Trausti; Söderhäll, Stefan; Arvidson, Johan

    2016-01-01

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

  1. Comparison of biochemical and immunological profile of pediatric patients with acute myeloid leukemia in relation to healthy individuals

    Directory of Open Access Journals (Sweden)

    Fabiane L.F.Z. Sanches

    2015-10-01

    Full Text Available ABSTRACT OBJECTIVE: To compare the biochemical and immunological profiles of pediatric patients with acute myeloid leukemia (AML with healthy children and adolescents. METHODS: This was a cross-sectional study in which 21 therapy-naïve patients with AML were compared with a group of 24 healthy individuals. The following data were analyzed: serum proteins, leucocytes and subgroups, erythrocytes, hematocrit, hemoglobin, platelets, cytokines in peripheral blood mononuclear cells cultures under spontaneous and BCG- or PHA-stimulated conditions, immunoglobulin A, and erythrocytic glutathione. Statistical analysis was performed using SPSS software, considering as significant p-values < 0.05. RESULTS: Serum albumin levels were higher (p < 0.0001 in the control group, as well as all the parameters related to red blood cells (p < 0.0001. For leucocytes and subgroups, no statistical difference was found between the AML and the control groups. For cytokines, the concentrations were significantly higher under spontaneous and BCG-stimulated conditions for TNF-a, IL-6, IL-10, and IFN-? in the control group. Under PHA-stimulated conditions, the concentration was higher (p = 0.002 only for IL-6. No difference was found between the two groups for the other cytokines and for IgA in the saliva. Erythrocytic glutathione was higher (p < 0.0001 in AML patients. CONCLUSIONS: It was possible to characterize the biochemical and immunological profile of pediatric patients with AML, as well as highlight some significant differences in these parameters when comparing with healthy children and adolescents.

  2. Comparison of biochemical and immunological profile of pediatric patients with acute myeloid leukemia in relation to healthy individuals.

    Science.gov (United States)

    Sanches, Fabiane L F Z; Nitsch, Taís M; Vilela, Maria Marluce S; Sgarbieri, Valdemiro C

    2015-01-01

    To compare the biochemical and immunological profiles of pediatric patients with acute myeloid leukemia (AML) with healthy children and adolescents. This was a cross-sectional study in which 21 therapy-naïve patients with AML were compared with a group of 24 healthy individuals. The following data were analyzed: serum proteins, leucocytes and subgroups, erythrocytes, hematocrit, hemoglobin, platelets, cytokines in peripheral blood mononuclear cells cultures under spontaneous and BCG- or PHA-stimulated conditions, immunoglobulin A, and erythrocytic glutathione. Statistical analysis was performed using SPSS software, considering as significant p-values<0.05. Serum albumin levels were higher (p<0.0001) in the control group, as well as all the parameters related to red blood cells (p<0.0001). For leucocytes and subgroups, no statistical difference was found between the AML and the control groups. For cytokines, the concentrations were significantly higher under spontaneous and BCG-stimulated conditions for TNF-α, IL-6, IL-10, and IFN-γ in the control group. Under PHA-stimulated conditions, the concentration was higher (p=0.002) only for IL-6. No difference was found between the two groups for the other cytokines and for IgA in the saliva. Erythrocytic glutathione was higher (p<0.0001) in AML patients. It was possible to characterize the biochemical and immunological profile of pediatric patients with AML, as well as highlight some significant differences in these parameters when comparing with healthy children and adolescents. Copyright © 2015 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

  3. Leukemia

    International Nuclear Information System (INIS)

    Kamada, Nanao

    1992-01-01

    This chapter deals with clinical features associated with chromosomal aberration in A-bomb survivors with leukemia. Clinical features are presented by dividing them into three categories: (1) those from preleukemic stage up to the development of overt leukemia, (2) those specific to A-bomb survivors, and (3) changes in chromosomes. Many of the A-bomb survivors had normocytic anemia and leukopenia for a long time preceding the development of overt leukemia. A woman exposed to 483 rad (estimated by the T65D) 800 m from the hypocenter who finally developed erythroleukemia is presented; and in 6 other A-bomb survivors, abnormal hematological findings up to the development of overt acute leukemia are mentioned. Hematological findings in chronic myeloid leukemia (CML) are discussed by presenting two cases: one was exposed at 800 m from the hypocenter and developed CML 35 years later and the other was exposed at 1800 m and developed it 22 years later. In A-bomb survivors, acute leukemia tended to be associated with smaller number of leukemic cells in both peripheral blood and bone marrow, and non-leukemic leukemia was observed. Chromosomal analysis has been made in 75 A-bomb survivors with acute leukemia and 55 CML A-bomb survivors. In acute leukemic patients exposed to one Gy or more, bone marrow stem cells with chromosomal aberrations occurring at the time of exposure were considered to be proliferated by various factors. A-bomb survivors with CML are found to be characterized by having Philadelphia chromosome, t(9;22)(q34;q11). (N.K.)

  4. The MLL recombinome of acute leukemias in 2017

    Science.gov (United States)

    Meyer, C; Burmeister, T; Gröger, D; Tsaur, G; Fechina, L; Renneville, A; Sutton, R; Venn, N C; Emerenciano, M; Pombo-de-Oliveira, M S; Barbieri Blunck, C; Almeida Lopes, B; Zuna, J; Trka, J; Ballerini, P; Lapillonne, H; De Braekeleer, M; Cazzaniga, G; Corral Abascal, L; van der Velden, V H J; Delabesse, E; Park, T S; Oh, S H; Silva, M L M; Lund-Aho, T; Juvonen, V; Moore, A S; Heidenreich, O; Vormoor, J; Zerkalenkova, E; Olshanskaya, Y; Bueno, C; Menendez, P; Teigler-Schlegel, A; zur Stadt, U; Lentes, J; Göhring, G; Kustanovich, A; Aleinikova, O; Schäfer, B W; Kubetzko, S; Madsen, H O; Gruhn, B; Duarte, X; Gameiro, P; Lippert, E; Bidet, A; Cayuela, J M; Clappier, E; Alonso, C N; Zwaan, C M; van den Heuvel-Eibrink, M M; Izraeli, S; Trakhtenbrot, L; Archer, P; Hancock, J; Möricke, A; Alten, J; Schrappe, M; Stanulla, M; Strehl, S; Attarbaschi, A; Dworzak, M; Haas, O A; Panzer-Grümayer, R; Sedék, L; Szczepański, T; Caye, A; Suarez, L; Cavé, H; Marschalek, R

    2018-01-01

    Chromosomal rearrangements of the human MLL/KMT2A gene are associated with infant, pediatric, adult and therapy-induced acute leukemias. Here we present the data obtained from 2345 acute leukemia patients. Genomic breakpoints within the MLL gene and the involved translocation partner genes (TPGs) were determined and 11 novel TPGs were identified. Thus, a total of 135 different MLL rearrangements have been identified so far, of which 94 TPGs are now characterized at the molecular level. In all, 35 out of these 94 TPGs occur recurrently, but only 9 specific gene fusions account for more than 90% of all illegitimate recombinations of the MLL gene. We observed an age-dependent breakpoint shift with breakpoints localizing within MLL intron 11 associated with acute lymphoblastic leukemia and younger patients, while breakpoints in MLL intron 9 predominate in AML or older patients. The molecular characterization of MLL breakpoints suggests different etiologies in the different age groups and allows the correlation of functional domains of the MLL gene with clinical outcome. This study provides a comprehensive analysis of the MLL recombinome in acute leukemia and demonstrates that the establishment of patient-specific chromosomal fusion sites allows the design of specific PCR primers for minimal residual disease analyses for all patients. PMID:28701730

  5. Expression of HER2/Neu in B-Cell Acute Lymphoblastic Leukemia.

    Science.gov (United States)

    Rodriguez-Rodriguez, Sergio; Pomerantz, Alan; Demichelis-Gomez, Roberta; Barrera-Lumbreras, Georgina; Barrales-Benitez, Olga; Aguayo-Gonzalez, Alvaro

    2016-01-01

    The expression of HER2/neu in B-cell acute lymphoblastic leukemia has been reported in previous studies. The objective of this research was to study the expression of HER2/neu on the blasts of patients with acute leukemia from the Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran. From June 2015 to February 2016, a HER2/neu monoclonal antibody was added to the panel of antibodies that we routinely use in patients with acute leukemia. An expression of ≥ 30% was considered positive. We studied 33 patients: 19 had de novo leukemia (57.6%), three (9.1%) were in relapse, and in 11 (33.3%) their status could not be specified. Seventeen patients (51.5%) were classified as B-cell acute lymphoblastic leukemia with a median expression of HER2/neu of 0.3% (range 0-90.2). Three patients with B-cell acute lymphoblastic leukemia were positive for HER2/neu: 89.4%, 90.9%, and 62.4%. The first and third patient had de novo B-cell acute lymphoblastic leukemia. The second patient was in second relapse after allogeneic stem cell transplant. All three patients were categorized as high-risk at the time of diagnosis. In the studied Mexican population, we found a positive expression of HER2/neu in 17% of the B-cell acute lymphoblastic leukemia patients, similar to previous studies in which the expression was found in 15-50%.

  6. Computed tomographic findings of intracranial acute leukemia

    Energy Technology Data Exchange (ETDEWEB)

    Park, Dong Woo; Ryu, Weon Don; Kim, Jong Sung; Koh, Byung Hee; Jeon, Seok Chol; Lee, Seung Ro; Hahm, Chang Kok [Hanyang University College of Medicine, Seoul (Korea, Republic of)

    1990-07-15

    Computed tomographic (CT) abnormalities in the brain were retrospectively analyzed in 16 of 103 patients with acute leukemia confirmed by CSF cytology or combined surgery at Hanyang University Hospital, from August 1980 to August 1989. The results were as follows : 1. With FAB classification, the most frequent pathologic type was L1 : 8 cases (50%) 2. The range of age distribution showed typical pattern that ALL occurred below the 15 years old, and AML, over 15 years old. 3. Abnormal CT findings were ; Meningitis(2 cases), Mass(3), Thrombosis(1), Infarction(2), Edema(1), Hemorrhage(7), Hydrocephalus(2), Atrophy(2). 4. Most of infracranial hemorrhage were seen in M{sub 2} and M{sub 3} type.

  7. FLT3 Mutation as a Significant Prognostic Marker in de novo Acute Myeloid Leukemia Patients: Incidence, Distribution and Association with Cytogenetic Findings in a Study from South India

    Directory of Open Access Journals (Sweden)

    Santhi Sarojam

    2014-10-01

    Full Text Available Background: Fms-like tyrosine kinase 3 is a tyrosine kinase receptor that plays an important role in proliferation and differentiation of hematopoietic stem cells. Internal tandem duplication and tyrosine kinase domain mutation are the two most common types of fms-like tyrosine kinase 3 mutations frequently reported in acute myeloid leukemia associated with pathogenesis of this disease. The present study investigates the prevalence and distribution pattern in different acute myeloid leukemia sub- and cytogenetic groups, the association with clinical parameters and the prognostic importance of these mutations in acute myeloid leukemia patients from South India. Methods:Mutation analysis was performed in 276 de novo acute myeloid leukemia patients by polymerase chain reaction restriction fragment length polymorphism using specific restriction enzymes followed by sequencing to confirm the mutations. Kaplan-Meier survival analysis was performed to detect the prognosis. Results: Fms-like tyrosine kinase 3 internal tandem duplication mutations were observed in 20%, tyrosine kinase domain mutation in 4% and dual mutations in 0.3% of the analyzed cases. The internal tandem duplication mutations ranged from 15-107 nucleotides with the majority at the juxta membrane domain of the receptor. Three types of tyrosine kinase domain point mutations were identified: D835Y, D835H and D835V. We observed a significant association between fms-like tyrosine kinase 3 mutations and increased WBC and LDH counts (P<0.001 and blast percentage but not with age, gender and FAB subtypes. A significant association with normal karyotype was observed for the mutants (P=0.002. Survival analysis revealed that the fms-like tyrosine kinase 3 gene mutation was a negative prognostic marker for acute myeloid leukemia patients. The risk stratified analysis showed the mutation to be a risk factor for the intermediate karyotype group, especially for those with normal cytogenetics

  8. Minimal Residual Disease Monitoring of Acute Myeloid Leukemia by Massively Multiplex Digital PCR in Patients with NPM1 Mutations.

    Science.gov (United States)

    Mencia-Trinchant, Nuria; Hu, Yang; Alas, Maria Antonina; Ali, Fatima; Wouters, Bas J; Lee, Sangmin; Ritchie, Ellen K; Desai, Pinkal; Guzman, Monica L; Roboz, Gail J; Hassane, Duane C

    2017-07-01

    The presence of minimal residual disease (MRD) is widely recognized as a powerful predictor of therapeutic outcome in acute myeloid leukemia (AML), but methods of measurement and quantification of MRD in AML are not yet standardized in clinical practice. There is an urgent, unmet need for robust and sensitive assays that can be readily adopted as real-time tools for disease monitoring. NPM1 frameshift mutations are an established MRD marker present in half of patients with cytogenetically normal AML. However, detection is complicated by the existence of hundreds of potential frameshift insertions, clonal heterogeneity, and absence of sequence information when the NPM1 mutation is identified using capillary electrophoresis. Thus, some patients are ineligible for NPM1 MRD monitoring. Furthermore, a subset of patients with NPM1-mutated AML will have false-negative MRD results because of clonal evolution. To simplify and improve MRD testing for NPM1, we present a novel digital PCR technique composed of massively multiplex pools of insertion-specific primers that selectively detect mutated but not wild-type NPM1. By measuring reaction end points using digital PCR technology, the resulting single assay enables sensitive and specific quantification of most NPM1 exon 12 mutations in a manner that is robust to clonal heterogeneity, does not require NPM1 sequence information, and obviates the need for maintenance of hundreds of type-specific assays and associated plasmid standards. Copyright © 2017 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. All rights reserved.

  9. Prevalence and Clinical Significance of FLT3 Mutation Status in Acute Myeloid Leukemia Patients: A Multicenter Study.

    Science.gov (United States)

    Cuervo-Sierra, Jorge; Jaime-Pérez, José Carlos; Martínez-Hernández, Ramón A; García-Sepúlveda, Ricardo D; Sánchez-Cárdenas, Mónica; Gómez-Almaguer, David; Ortíz-López, Rocío; Villarreal-Villarreal, César D; Ruiz-Arguelles, Guillermo J; Ruiz-Delgado, Guillermo; Lutz-Presno, Julia; Garcés-Eisele, Javier; Ignacio-Ibarra, Gregorio; Muciño-Hernández, Gabriel; Arana-Trejo, Rosa M; Jiménez-Mejia, Angélica M; Vásquez-Palacio, Gonzalo

    2016-04-01

    FLT3-ITD mutations in acute myeloid leukemia (AML) are associated with a poor prognosis. In Latin America, little epidemiological data exist about these mutations and their influence on clinical evolution and prognosis. Standardization and well-established clinical correlation make FLT3 mutational analysis by molecular methods an invaluable tool to decide among treatment options and to determine AML prognosis. We assessed the prevalence of FLT3-ITD mutations in 138 patients with AML at four hematology referral centers from Mexico and Colombia. Molecular methods based on polymerase chain reaction (PCR) were employed for determining FLT3-ITD status. Mutations were present in 28 patients indicating a prevalence of 20.28%. Median age was 47 years (5-96). The FLT3 mutation positive group was older, had higher WBC and hemoglobin values and lower platelet counts but without statistical significance. A not previously described mutation in the FLT3 gene was found in one patient involving a nucleotide exchange of timine for cytosine at the 66608 position. A high mortality was found in the FLT3-mutated group, 67.8 vs. 42.72% in the non-mutated group and median survival was 4.9 months vs. 20.4 months, p = 0.009. A mutated FLT3 did not confer poor prognosis to those with M3 AML. The mutated FLT3 population had poor overall survival (OS) despite hematoprogenitor stem cell transplantation (HSCT). Prevalence of FLT3-ITD mutation in AML was present in a proportion comparable to other populations and, when present, was associated with a very poor prognosis. Copyright © 2016 IMSS. Published by Elsevier Inc. All rights reserved.

  10. Detection of acute lymphoblastic leukemia involvement in pleural fluid in an adult patient with ataxia telangiectasia by flow cytometry method.

    Science.gov (United States)

    Keklik, Muzaffer; Koker, M Yavuz; Sivgin, Serdar; Camlica, Demet; Pala, Cigdem; Cetin, Mustafa; Kaynar, Leylagul; Unal, Ali; Eser, Bulent

    2014-09-01

    Ataxia-telangiectasia (AT) is a rare multisystem, neurodegenerative genetic disorder. Patients should be closely monitored due to risk of malignancy development. Due to its wide clinical heterogeneity, it often leads physicians to an inaccurate or missed diagnosis, and insight into this rare disease is important. Pediatric patients may develop lymphomas and acute lymphoblastic leukemia (ALL). However, in adults, there are limited numbers of reports regarding association of AT and ALL. Rarely, ALL cases may present with pleural fluid involvement. In our study, we presented an adult case with AT, in which ALL involvement was detected in pleural fluid by flow cytometry (FC). A 20-years old male presented to emergency department with fever, shortness of breath and cough, as he had been followed with a diagnosis of AT. The following findings were detected in laboratory tests: Hb, 11.5 g/L; WBC, 36 × 10(9)/L; Plt: 140 × 10(9)/L. Blastic cells were observed in peripheral blood smear. On chest radiography, pleural fluid appearance was observed. On thorax CT, pleural fluid was detected in both hemithorax. Cytoplasmic CD3(+) and superficial CD3 (+), CD45 (+), CD5 (+), CD7 (+) and CD38 (+) was found in the flow cytometric evaluation of peripheral blood. Superficial CD3 (+), CD2 (+), CD5 (+) and CD7 (+) were found in flow cytometric evaluation of pleural fluid. These findings were considered as consistent with pleural involvement of T-ALL. FC is a potentially useful diagnostic tool for clinical practice and it is a convenience method which has an important role in detection of ALL in patients with pleural fluid.

  11. ERYTHEMA NODOSUM REVEALING ACUTE MYELOID LEUKEMIA

    Directory of Open Access Journals (Sweden)

    Chebbi Wafa

    2013-07-01

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

  12. Cutis verticis gyrata secondary to acute monoblastic leukemia.

    Science.gov (United States)

    Passarini, B; Neri, I; Patrizi, A; Masina, M

    1993-04-01

    A 64-year-old man affected by acute monoblastic leukemia developed a cutis verticis gyrata during the terminal phase of hemopathy. The association between these two diseases is rare. The classification of cutis verticis gyrata in primary essential, primary non-essential and secondary forms is reviewed. Performing a skin biopsy is necessary in the diagnostic approach to patients with cutis verticis gyrata.

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

    International Nuclear Information System (INIS)

    Izumi, Mayuko; Hosoya, Ryouta; Oohira, Mutsuro; Kaneko, Takashi; Matsushita, Taketsugu

    2000-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2000-10-01

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

  15. Human leukocyte antigen-E mismatch is associated with better hematopoietic stem cell transplantation outcome in acute leukemia patients.

    Science.gov (United States)

    Tsamadou, Chrysanthi; Fürst, Daniel; Vucinic, Vladan; Bunjes, Donald; Neuchel, Christine; Mytilineos, Daphne; Gramatzki, Martin; Arnold, Renate; Wagner, Eva Maria; Einsele, Hermann; Müller, Carlheinz; Schrezenmeier, Hubert; Mytilineos, Joannis

    2017-11-01

    The immunomodulatory role of human leukocyte antigen (HLA)-E in hematopoietic stem cell transplantation (HSCT) has not been extensively investigated. To this end, we genotyped 509 10/10 HLA unrelated transplant pairs for HLA-E , in order to study the effect of HLA-E as a natural killer (NK)-alloreactivity mediator on HSCT outcome in an acute leukemia (AL) setting. Overall survival (OS), disease free survival (DFS), relapse incidence (RI) and non-relapse mortality (NRM) were set as endpoints. Analysis of our data revealed a significant correlation between HLA-E mismatch and improved HSCT outcome, as shown by both univariate (53% vs 38%, P =0.002, 5-year OS) and multivariate (hazard ratio (HR)=0.63, confidence interval (CI) 95%=0.48-0.83, P =0.001) analyses. Further subgroup analysis demonstrated that the positive effect of HLA-E mismatch was significant and pronounced in advanced disease patients (n=120) (5-year OS: 50% vs 18%, P =0.005; HR=0.40, CI 95%=0.22-0.72, P =0.002; results from univariate and multivariate analyses, respectively). The study herein is the first to report an association between HLA-E incompatibility and improved post-transplant prognosis in AL patients who have undergone matched unrelated HSCT. Combined NK and T cell HLA-E-mediated mechanisms may account for the better outcomes observed. Notwithstanding the necessity for in vitro and confirmational studies, our findings highlight the clinical relevance of HLA-E matching and strongly support prospective HLA-E screening upon donor selection for matched AL unrelated HSCTs. Copyright© Ferrata Storti Foundation.

  16. Intermediate-dose cytarabine plus mitoxantrone versus standard-dose cytarabine plus daunorubicine for acute myeloid leukemia in elderly patients.

    Science.gov (United States)

    Röllig, C; Kramer, M; Gabrecht, M; Hänel, M; Herbst, R; Kaiser, U; Schmitz, N; Kullmer, J; Fetscher, S; Link, H; Mantovani-Löffler, L; Krümpelmann, U; Neuhaus, T; Heits, F; Einsele, H; Ritter, B; Bornhäuser, M; Schetelig, J; Thiede, C; Mohr, B; Schaich, M; Platzbecker, U; Schäfer-Eckart, K; Krämer, A; Berdel, W E; Serve, H; Ehninger, G; Schuler, U

    2018-01-30

    The combination of intermediate-dose cytarabine plus mitoxantrone (IMA) can induce high complete remission rates with acceptable toxicity in elderly patients with acute myeloid leukemia (AML). We present the final results of a randomized-controlled trial comparing IMA with the standard 7 + 3 induction regimen consisting of continuous infusion daunorubicin plus cytarabine (DA). Patients with newly diagnosed AML >60 years were randomized to receive either intermediate-dose cytarabine (1000 mg/m2 BID days 1,3,5,7) plus mitoxantrone (10 mg/m2 days 1-3) (IMA) or standard induction therapy with cytarabine (100 mg/m2 continuously days 1-7) plus daunorubicin (45 mg/m2 days 3-5) (DA). Patients in complete remission after DA received intermediate-dose cytarabine plus amsacrine as consolidation treatment, whereas patients after IMA were consolidated with standard-dose cytarabine plus mitoxantrone. Between February 2005 and October 2009, 485 patients were randomized; 241 for treatment arm DA and 244 for IMA; 76% of patients were >65 years. The CR rate after DA was 39% (95%-CI; 33-45) versus 55% (95%-CI; 49-61) after IMA (OR 1.89, p=0.001). The six-week early-death rate was 14% in both arms. Relapse-free survival (RFS) curves were superimposable in the first year, but separated afterwards, resulting in 3-year RFS rates of 29% versus 14% in the DA versus IMA arms, respectively (p=0.042). The median OS was 10 months in both arms (p=0.513). The dose escalation of cytarabine in induction therapy lead to improved remission rates in the elderly AML patients. This did not translate into a survival advantage, most likely due to differences in consolidation treatment. Thus, effective consolidation strategies need to be further explored. In combination with an effective consolidation strategy, the use of intermediate dose cytarabine in induction may improve curative treatment for elderly AML patients. © The Author 2018. Published by Oxford University Press on behalf of the

  17. Philadelphia-positive acute lymphoblastic leukemia patients already harbor BCR-ABL kinase domain mutations at low levels at the time of diagnosis

    Science.gov (United States)

    Soverini, Simona; Vitale, Antonella; Poerio, Angela; Gnani, Alessandra; Colarossi, Sabrina; Iacobucci, Ilaria; Cimino, Giuseppe; Elia, Loredana; Lonetti, Annalisa; Vignetti, Marco; Paolini, Stefania; Meloni, Giovanna; di Maio, Valeria; Papayannidis, Cristina; Amabile, Marilina; Guarini, Anna; Baccarani, Michele; Martinelli, Giovanni; Foà, Robin

    2011-01-01

    Background In patients with Philadelphia-positive acute lymphoblastic leukemia, resistance to treatment with tyrosine kinase inhibitors is frequent and most often associated with the development of point mutations in the BCR-ABL kinase domain. We aimed to assess: (i) in how many patients BCR-ABL kinase domain mutations are already detectable at relatively low levels at the time of diagnosis, and (ii) whether mutation detection correlates with subsequent response to therapy. Design and Methods We retrospectively analyzed samples collected at diagnosis from 15 patients with Philadelphia-positive acute lymphoblastic leukemia who subsequently received tyrosine kinase inhibitor therapy (dasatinib) by cloning the BCR-ABL kinase domain in a bacterial vector and sequencing 200 independent clones per sample. Results Mutations at relatively low levels (2–4 clones out of 200) could be detected in all patients – eight who relapsed and seven who achieved persistent remission. Each patient had evidence of two to eight different mutations, the majority of which have never been reported in association with resistance to tyrosine kinase inhibitors. In two patients out of six who relapsed because of a mutation, the mutation (a T315I) was already detectable in a few clones at the time of diagnosis. On the other hand, a patient who was found to harbor an F317L mutation is in persistent remission on dasatinib. Conclusions Our results suggest that the BCR-ABL kinase domain is prone to randomly accumulate point mutations in Philadelphia-positive acute lymphoblastic leukemia, although the presence of these mutations in a relatively small leukemic subclone does not always preclude a primary response to tyrosine kinase inhibitors. PMID:21193419

  18. New vessel formation and aberrant VEGF/VEGFR signaling in acute leukemia : Does it matter?

    NARCIS (Netherlands)

    De Bont, ESJM; Neefjes, VME; Rosati, S; Vellenga, E; Kamps, WA

    2002-01-01

    Although many patients with acute leukemia achieve a hematological complete remission with aggressive intensive therapy protocols, a large proportion shows reoccurrence of disease. Novel strategies are warranted. In acute leukemia new vessel formation is observed. New vessel formation is the result

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

    International Nuclear Information System (INIS)

    Wong, Jeffrey Y.C.; Rosenthal, Joseph; Liu An; Schultheiss, Timothy; Forman, Stephen; Somlo, George

    2009-01-01

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

  20. Optimization of chemotherapy for younger patients with acute myeloid leukemia: results of the medical research council AML15 trial.

    Science.gov (United States)

    Burnett, Alan K; Russell, Nigel H; Hills, Robert K; Hunter, Ann E; Kjeldsen, Lars; Yin, John; Gibson, Brenda E S; Wheatley, Keith; Milligan, Donald

    2013-09-20

    Treatment outcomes in younger patients with acute myeloid leukemia (AML) have improved, but optimization and new combinations are needed. We assess three combinations in induction and consolidation. Younger untreated patients with AML (median age, 49 years; range, 0 to 73 years) were randomly allocated to two induction courses of daunorubicin and cytarabine (DA) with or without etoposide (ADE; n = 1983) or ADE versus fludarabine, cytarabine, granulocyte colony-stimulating factor, and idarubicin (FLAG-Ida; n = 1268), and to amsacrine, cytarabine, etoposide, and then mitoxantrone/cytarabine (MACE-MidAC) or high-dose cytarabine (n = 1,445) 3 g/m(2) or 1.5 g/m(2) (n = 657) in consolidation, and finally to a fifth course (cytarabine) or not (n = 227). Overall remission rates were similar for DA versus ADE (84% v 86%; P = .14) and ADE versus FLAG-Ida (86% v 85%; P = .7), with more course 1 remissions after FLAG-Ida (77%) reducing relapse (38% v 55%; P < .001) and improving relapse-free survival (45% v 34%; P = .01), overall and in subgroups, but with increased myelosuppression, reducing participation in the consolidation randomization. Overall outcomes were similar between MACE/MidAc and high-dose cytarabine (1.5/3.0 g/m(2)), but cytarabine required less supportive care. MACE/MidAc was superior for high-risk patients. A fifth course provided no benefit. The outcome for recipients of only two FLAG-Ida courses were not different from that with DA/ADE with consolidation. FLAG-Ida is an effective remission induction treatment, with a high complete remission rate after course 1 and reduced relapse. Consolidation with MACE/MidAc is similar overall to high-dose cytarabine, but superior in high-risk patients. Cytarabine at 1.5 g/m(2) is equivalent to a 3 g/m(2) dose. A fifth course is unnecessary. In patients receiving FLAG-Ida (two courses) and cytarabine (two courses), 8-year survival was 63% for patients with intermediate-risk and 95% for those with favorable-risk disease.

  1. Treatment strategies in acute myeloid leukemia

    NARCIS (Netherlands)

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

    2011-01-01

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

  2. Expression of Th17 and CD4+ CD25+ T regulatory cells in peripheral blood of acute leukemia patients and their prognostic significance.

    Science.gov (United States)

    Xiang, Mingli; Guo, Li; Ma, Yan; Li, Yi

    2016-11-01

    To discuss the expression of T helper cell 17 (Th17) cells and CD4+ CD25+ Foxp3+ regulatory T cells (Treg) in peripheral blood (PB) of patients with acute leukemia (AL), and to explore the relationship between them and disease prognosis. 40 patients diagnosed with acute leukemia in The First Affiliated Hospital of Zhengzhou University from July 2012 to August 2014 were selected as the observation group. Meanwhile, 40 healthy people were taken as the control group. Flow Cytometry Method (FCM) was used to detect the level of Th17 cells and CD4 + CD25 + Foxp3 + cells in peripheral blood of the two groups, and enzyme-linked immuno sorbent assay (ELISA) method was used to test the level of IL17 and TGF-β in peripheral blood of two groups; reverse transcription-polymerase chain reaction (RT-PCR) was adopted to analyze the mRNA levels of RORγT and Foxp3 in peripheral blood. In addition, we examined the levels of Th17 and CD4 + CD25 + Foxp3 + cells and associated factor levels in patients with remission after AL chemotherapy. the Th17 cells (CD3 + CD4 + IL-17 + ) in acute leukemia patients accounted for (1.51±0.27)%, which was significantly higher than that of control group (0.36±0.23)%, with statistical significance (t=20.51, Pcells in AL patients was (3.37±0.48)%, which was significantly higher than that of control group of (1.26±0.27)%, with statistical significance (t=24.23, Pt=7.83, Pt=7.83, Pt=12.27, Pt=7.89, Pcells and CD4 + CD25 + Foxp3 + cells, and the serum levels of IL-17 and TGF-β in acute leukemia patients all decreased significantly after 6 months of chemotherapy, and the difference was statistically significant (Pcells, CD4+ CD25+ Foxp3 + cells and their secretory proteins IL-17, TGF-β and transcription factors were significantly increased in AL patients. Therefore, regular detection of peripheral blood Th17 and Treg cells, as well as their secretory proteins are useful for monitoring the immune status and prognosis of patients.

  3. Phase 1/2 study to assess the safety, efficacy, and pharmacokinetics of barasertib (AZD1152) in patients with advanced acute myeloid leukemia

    OpenAIRE

    Löwenberg, Bob; Muus, P.; Ossenkoppele, Gert; Rousselot, Philippe; Cahn, Jean-Yves; Ifrah, Norbert; Martinelli, Giovanni; Amadori, Sergio; Berman, Ellin; Sonneveld, Pieter; Jongen-Lavrencic, Mojca; Rigaudeau, Sophie; Stockman, Paul; Goudie, David; Faderl, Stefan

    2011-01-01

    textabstractThe primary objective of this 2-part phase 1/2 study was to determine the maximum-tolerated dose (MTD) of the potent and selective Aurora B kinase inhibitor barasertib (AZD1152) in patients with newly diagnosed or relapsed acute myeloid leukemia (AML). Part A determined the MTD of barasertib administered as a continuous 7-day infusion every 21 days. In part B, the efficacy of barasertib was evaluated at the MTD. In part A, 32 patients were treated with barasertib 50 mg (n = 3), 10...

  4. Phase 1/2 study to assess the safety, efficacy, and pharmacokinetics of barasertib (AZD1152) in patients with advanced acute myeloid leukemia

    OpenAIRE

    Löwenberg, Bob; Muus, Petra; Ossenkoppele, Gert; Rousselot, Philippe; Cahn, Jean-Yves; Ifrah, Norbert; Martinelli, Giovanni; Amadori, Sergio; Berman, Ellin; Sonneveld, Pieter; Jongen-Lavrencic, Mojca; Rigaudeau, Sophie; Stockman, Paul; Goudie, Alison; Faderl, Stefan

    2011-01-01

    The primary objective of this 2-part phase 1/2 study was to determine the maximum-tolerated dose (MTD) of the potent and selective Aurora B kinase inhibitor barasertib (AZD1152) in patients with newly diagnosed or relapsed acute myeloid leukemia (AML). Part A determined the MTD of barasertib administered as a continuous 7-day infusion every 21 days. In part B, the efficacy of barasertib was evaluated at the MTD. In part A, 32 patients were treated with barasertib 50 mg (n = 3), 100 mg (n = 3)...

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

    Directory of Open Access Journals (Sweden)

    Yahui Ding

    2016-09-01

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

  6. Is there a role for B lymphocyte chimerism in the monitoring of B-acute lymphoblastic leukemia patients receiving allogeneic stem cell transplantation?

    Directory of Open Access Journals (Sweden)

    Yi-Ning Yang

    2015-03-01

    Full Text Available Objective: To determine the sensitivity and significance of B-cell chimerism for the detection of early engraftment, transplant rejection, and disease relapse. Methods: The dynamic monitoring of lineage-specific cell subtypes (B, T, and NK cells was made in 20 B-cell acute lymphoblastic leukemia (B-ALL patients following allogeneic hematopoietic stem cell transplantation (allo-HSCT. In the early period after allo-HSCT, the latest establishment of B-cell complete chimerism (CC was observed in a majority of patients. Results: The percentage of donor cells of B-cell lineage was lower than the percent of T-cell lineage in most of the mixed chimerism (MC patients. During graft rejection, the frequency of patients with decreasing MC of B-, T- and NK-cell lineage were 5/5, 2/5, and 2/5. When disease relapsed, five patients showed a faster decrease of the donor percent of B-cells than of T- or NK-cells. Only one patient displayed a more rapid decrease in NK-cells than in T- or B-cells. Conclusion: Monitoring of B-cell chimerism after HSCT seems to be valuable for insuring complete engraftment, anticipating graft rejection, and relapse in B-ALL patients. Keywords: B cell acute lymphoblastic leukemia (B-ALL, B-cell, T-cell, Chimerism, Allogeneic hematopoietic stem cell transplantation (allo-HSCT

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

    Directory of Open Access Journals (Sweden)

    Mike Fischer

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

  8. Unfavorable-risk acute myeloid leukemia dissected.

    Science.gov (United States)

    Strickland, Stephen A; Mohan, Sanjay R; Savona, Michael R

    2016-03-01

    Acute myeloid leukemia (AML) is an immensely heterogeneous disease based on the presence of varying combinations of morphologic, immunophenotypic, genetic, and molecular characteristics identified among those diagnosed with this disease. Although current therapeutic strategies provide a reasonable likelihood of achieving a complete remission for the majority of patients, relapse rates and subsequent disease-related mortality remain unacceptably high. Improved methods of risk stratification are needed to better identify patients at considerable risk of relapse in hopes of allowing for early therapeutic intervention and/or intensification that may lead to a higher likelihood of cure. The current status of risk stratification of AML and emerging technologies with potential to improve prognostic classification and outcomes are summarized in this review. Refinement of our understanding of the impact of current pretreatment AML cytogenetic, immunophenotypic, and molecular aberrations to predict outcomes and guide therapeutic decision-making is ongoing. Emerging data suggest that incorporation of the degree of posttreatment response and/or the detection of minimal residual disease can improve the accuracy of risk stratification for individual patients. Although pretreatment disease characteristics remain the hallmark of prognostication for AML patients, posttreatment parameters such as minimal residual disease assessment and degree of response to therapy possess the ability to further refine our identification of patients with unfavorable disease and thereby influence decisions regarding therapeutic planning.

  9. Translational Phase I Trial of Vorinostat (Suberoylanilide Hydroxamic Acid) Combined with Cytarabine and Etoposide in Patients with Relapsed, Refractory, or High-Risk Acute Myeloid Leukemia

    Science.gov (United States)

    Gojo, Ivana; Tan, Ming; Fang, Hong-Bin; Sadowska, Mariola; Lapidus, Rena; Baer, Maria R.; Carrier, France; Beumer, Jan H.; Anyang, Bean N.; Srivastava, Rakesh K.; Espinoza-Delgado, Igor; Ross, Douglas D.

    2015-01-01

    Purpose To determine the maximum-tolerated dose (MTD) of the histone deacetylase inhibitor vorinostat combined with fixed doses of cytarabine (ara-C or cytosine arabinoside) and etoposide in patients with poor-risk or advanced acute leukemia, to obtain preliminary efficacy data, describe pharmacokinetics, and in vivo pharmacodynamic effects of vorinostat in leukemia blasts. Experimental Design In this open-label phase I study, vorinostat was given orally on days one to seven at three escalating dose levels: 200 mg twice a day, 200 mg three times a day, and 300 mg twice a day. On days 11 to 14, etoposide (100 mg/m2) and cytarabine (1 or 2 g/m2 twice a day if ≥65 or vorinostat 200 mg twice a day. Of 21 patients enrolled, seven attained a complete remission (CR) or CR with incomplete platelet recovery, including six of 13 patients treated at the MTD. The median remission duration was seven months. No differences in percentage S-phase cells or multidrug resistance transporter (MDR1 or BCRP) expression or function were observed in vivo in leukemia blasts upon vorinostat treatment. Conclusions Vorinostat 200 mg twice a day can be given safely for seven days before treatment with cytarabine and etoposide. The relatively high CR rate seen at the MTD in this poor-risk group of patients with AML warrants further studies to confirm these findings. PMID:23403629

  10. Allogeneic stem cell transplantation in acute myeloid leukemia

    Directory of Open Access Journals (Sweden)

    Natasha Ali

    2012-11-01

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

  11. The MLL recombinome of acute leukemias in 2013

    DEFF Research Database (Denmark)

    Meyer, C; Hofmann, Julian; Burmeister, T

    2013-01-01

    Chromosomal rearrangements of the human MLL (mixed lineage leukemia) gene are associated with high-risk infant, pediatric, adult and therapy-induced acute leukemias. We used long-distance inverse-polymerase chain reaction to characterize the chromosomal rearrangement of individual acute leukemia ...

  12. A Review of DNA Methylation and microRNA Expression in Recurrent Pediatric Acute Leukemia.

    Science.gov (United States)

    Hale, Victoria; Hale, Gregory A; Brown, Patrick A; Amankwah, Ernest K

    2017-01-01

    Acute leukemia is the most common childhood cancer diagnosis and leading cause of cancer-related death among children and adolescents. Despite substantial improvements in the survival rate of childhood acute leukemia, approximately 20-40% of the patients who undergo treatment develop relapse, with a dismal one third of these patients surviving in the long term. Epigenetics plays an important role in the progression of cancer, and existing evidence suggests a role in childhood acute leukemia relapse. A better understanding of the epigenetic mechanisms in recurrent acute leukemia could potentially lead to novel therapeutic regimens to prevent or treat disease recurrences. In this review, we summarize existing evidence on two of the most studied epigenetic mechanisms, DNA methylation and microRNA expression, in recurrent pediatric acute leukemia. © 2016 S. Karger AG, Basel.

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

    International Nuclear Information System (INIS)

    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, the authors 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

  14. Early presentation of osteonecrosis in acute lymphoblastic leukemia

    DEFF Research Database (Denmark)

    Mogensen, Signe Sloth; Harila-Saari, Arja; Frandsen, Thomas Leth

    2017-01-01

    Osteonecrosis (ON) is usually considered treatment related in patients with acute lymphoblastic leukemia (ALL). We report two patients with presentation of ON at the time of ALL diagnosis. Both were females and diagnosed with ALL at age 8 and 14 years. In the latter, some symptoms and radiologica......Osteonecrosis (ON) is usually considered treatment related in patients with acute lymphoblastic leukemia (ALL). We report two patients with presentation of ON at the time of ALL diagnosis. Both were females and diagnosed with ALL at age 8 and 14 years. In the latter, some symptoms...... and radiologically verified ON in both knees were still present after the end of ALL therapy. No pediatric patients have previously been reported with ON presenting before initiation of ALL therapy....

  15. [Acute lymphoblastic leukemia: a genomic perspective].

    Science.gov (United States)

    Jiménez-Morales, Silvia; Hidalgo-Miranda, Alfredo; Ramírez-Bello, Julián

    In parallel to the human genome sequencing project, several technological platforms have been developed that let us gain insight into the genome structure of human entities, as well as evaluate their usefulness in the clinical approach of the patient. Thus, in acute lymphoblastic leukemia (ALL), the most common pediatric malignancy, genomic tools promise to be useful to detect patients at high risk of relapse, either at diagnosis or during treatment (minimal residual disease), and they also increase the possibility to identify cases at risk of adverse reactions to chemotherapy. Therefore, the physician could offer patient-tailored therapeutic schemes. A clear example of the useful genomic tools is the identification of single nucleotide polymorphisms (SNPs) in the thiopurine methyl transferase (TPMT) gene, where the presence of two null alleles (homozygous or compound heterozygous) indicates the need to reduce the dose of mercaptopurine by up to 90% to avoid toxic effects which could lead to the death of the patient. In this review, we provide an overview of the genomic perspective of ALL, describing some strategies that contribute to the identification of biomarkers with potential clinical application. Copyright © 2017 Hospital Infantil de México Federico Gómez. Publicado por Masson Doyma México S.A. All rights reserved.

  16. [Clinical Efficacy of Sorafenib Combined with Low Dose Cytarabine for Treating Patients with FLT3+ Relapsed and Refractory Acute Myeloid Leukemia].

    Science.gov (United States)

    Liu, Xiao-Shu; Long, Hui; Huang, Yu-Xian; Xu, Jian-Hui; Zhu, Jun-Yu; DU, Qing-Feng; Wu, Bing-Yi

    2016-04-01

    To study the efficacy and safety of sorafenib combined with low dose cytarabine for treating patients with FLT3(+) relapsed and refractory acute myeloid leukemia (FLT3(+) RR-AML). Seven patients with FLT3(+) RR-AML were treated with sorafenib and low dose cytarabine. The curative rate and adverse effects were observed in these patients. Out of 7 RR-AML patients after treatment, 5 patients achieved complete remission (CR), 2 patients achieved partial remission (PR), and the overall response rate (ORR) after one course of therapy was 100%. No severe bleeding, nausea, vomiting and other side effects were found in these patients. Sorafenib combined with low dose cytarabine can effectively induce the remission of FLT3(+) RR-AML patients, and is worth for further clinical trails to verify its safty and efficiency.

  17. Molecular evaluation of CEBPA gene mutation in normal karyotype acute myeloid leukemia: a comparison of two methods and report of novel CEBPA mutations from Indian acute myeloid leukemia patients.

    Science.gov (United States)

    Ahmad, Firoz; Rajput, Saket; Mandava, Swarna; Das, Bibhu Ranjan

    2012-07-01

    Mutation in the CAAT/enhancer binding protein-α (CEBPA) gene has been reported as being one of the common genetic abnormalities in acute myeloid leukemia (AML) and is associated with a good clinical outcome. We intend to explore the prevalence of CEBPA mutations and evaluate the efficacy of fragment and sequencing analysis methods for CEBPA mutation detection in Indian AML patients. The coding region of the CEBPA gene was screened in 36 normal karyotype AML patients by fragment analysis and direct sequencing. We identified five CEBPA sequence variations in three patient samples (8.3%) by direct sequencing analysis, of which three were novel mutations. These mutations were clustered mostly in the TAD1 and basic region leucine zipper region of the CEBPA protein. Six cases demonstrated a previously reported polymorphism. Two of the three positive cases showed double mutations, and one case had a single mutation. All five mutations were also detected by fragment analysis, indicating a sensitivity of 100% (5/5). No correlation with clinical parameters including age, sex, white blood cell count, hemoglobin, and platelet count between patients with and without mutation was observed. Interestingly, CEBPA mutations were significantly higher in patients with WT1 mutation, while no correlation with FLT3 and NPM1 was observed. We report for the first time the frequency of CEBPA mutation from an Indian patients (8.3%). The identification of novel CEBPA mutations added new insights into the genetic heterogeneity of AML. Our result suggests that the optimal approach for detecting CEBPA mutations in AML can be a combination of fragment analysis and direct sequencing.

  18. huJCAR014 CAR-T Cells in Treating Adult Patients With Relapsed or Refractory B-Cell Non-Hodgkin Lymphoma or Acute Lymphoblastic Leukemia

    Science.gov (United States)

    2018-03-26

    Adult B Acute Lymphoblastic Leukemia; BCL2 Gene Rearrangement; BCL6 Gene Rearrangement; CD19 Positive; Diffuse Large B-Cell Lymphoma, Not Otherwise Specified; MYC Gene Rearrangement; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent B-Cell Non-Hodgkin Lymphoma; Recurrent Diffuse Large B-Cell Lymphoma; Recurrent Mediastinal (Thymic) Large B-Cell Cell Lymphoma; Refractory Adult Acute Lymphoblastic Leukemia; Refractory B-Cell Non-Hodgkin Lymphoma; Refractory Diffuse Large B-Cell Lymphoma; Refractory Mediastinal (Thymic) Large B-Cell Cell Lymphoma; Transformed Recurrent Non-Hodgkin Lymphoma

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

    Directory of Open Access Journals (Sweden)

    Chung-Jen Teng

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

  20. The Association of Viral Infection and Acute Leukemia in Childhood: Two Case Reports

    Directory of Open Access Journals (Sweden)

    Murat Söker

    2005-01-01

    Full Text Available Hepatitis A and Measles are the most common viral infection in pediatric patients. Viral infections causes to serious problem in immunocompromised patients such as acute leukemias. It is known that some viral infection agent causes hematologic malignancies. We report here two patient with acute leukemias who admitted to our clinic with similar to viral infection. The first case is a patient with acute lymphoblastic leukemia (ALL presented with ascites and pleural effusion. In this patient, the major clinical problem is hepatitis A. The second case is a patient with ALL who admitted with symptoms of measles. We discussed here, some viral infections may cause to leukemia and those may be associated with leukemias.

  1. Effective chemotherapy of acute myelocytic leukemia occurring after alkylating agent or radiation therapy for prior malignancy

    International Nuclear Information System (INIS)

    Vaughan, W.P.; Karp, J.E.; Burke, P.J.

    1983-01-01

    Eleven consecutive patients with acute myelocytic leukemia occurring as a second malignancy were treated with high-dose, timed, sequential chemotherapy. Eight of the patients were felt to have ''secondary'' acute leukemia because they had received an alkylating agent or radiation therapy. The other three patients were considered controls. Despite a median age of 65, four of the eight secondary leukemia patients achieved complete remission with this regimen. One of the three control patients also achieved complete remission. This remission rate and duration are comparable to what was achieved with this treatment of ''primary'' acute myelocytic leukemia during the same period of time. These results suggest that patients with leukemia occurring after an alkylating agent or radiation therapy are not at especially high risk if treated aggressively

  2. Oral health of children with acute lymphoblastic leukemia: A review

    Directory of Open Access Journals (Sweden)

    Kadalagere Lakshmana Girish Babu

    2016-01-01

    Full Text Available Leukemia is a malignancy of the bone marrow and blood. It is the most common childhood cancer in India. Advances in the treatment regimens have greatly increased the chances of survival. Both the disease and its treatment change the oral environment. In some cases, oral manifestations are the presenting feature of the disease and it will be the dentist′s responsibility to identify the underlying disorder and guide the diagnosis of the patient. Hence, the aim of present article is to review the literature concerning the oral health of children with acute lymphoblastic leukemia (ALL.

  3. Negative effect of DNA hypermethylation on the outcome of intensive chemotherapy in older patients with high-risk myelodysplastic syndromes and acute myeloid leukemia following myelodysplastic syndrome

    DEFF Research Database (Denmark)

    Grövdal, Michael; Khan, Rasheed; Aggerholm, Anni

    2007-01-01

    was designed to assess the effect of methylation status on the outcome of conventional induction chemotherapy. EXPERIMENTAL DESIGN: Sixty patients with high-risk MDS or acute myeloid leukemia following MDS were treated with standard doses of daunorubicin and 1-beta-d-arabinofuranosylcytosine. Standard.......008), and CDH methylation retained its prognostic value also in the multivariate analysis. Hypermethylation was associated with increased CD34 expression, but not with other known predictive factors for response, such as cytogenetic profile. CONCLUSIONS: We show for the first time a significant effect...

  4. Clinical case of acute myeloblastic leukemia with t(8;21(q22;q22 in a patient with Klinefelter’s syndrome

    Directory of Open Access Journals (Sweden)

    Vanya Slavcheva

    2010-12-01

    Full Text Available Klinefelter’s syndrome is characterized by abnormal karyotype 47, XXY and a phenotype associated with hypogonadism and gynecomastia. Often the disease can be diagnosed accidentally, when carrying out cytogenetic analysis in cases of a malignant blood disease. We present the clinical case of a patient diagnosed with acute myelomonoblastic leukemia- M4 Eo (AML- M4, where by means of classic cytogenetics a karyotype was found corre-sponding to Klinefelter’s syndrome. Three induction courses of polychemotherapy wermade, which led to remission of the disease, documented both flowcytometrically and cytogenetically.

  5. [Detecting HB-1 Expression Level in Bone Marrow of Acute Leukemia Patients by Real-Time Fluorescence Quantitative RT-PCR].

    Science.gov (United States)

    Wang, Qing-Yun; Li, Yuan; Ji, Li; Liang, Ze-Yin; Liu, Wei; Ren, Han-Yun; Qiu, Zhi-Xiang

    2018-02-01

    To investigate the expression level of HB-1 gene in patients with acute lymphoblastic leukemia (ALL) and the significance of HB-1 gene in monitoring of minimal residual disease (MRD). The method of real-time fluorescence quantitative RT-PCR (Taqman probe) was established to detect the expression levels of HB-1 gene; then the sensitivity, specificity and repeatability of this assay were evaluated and verified. The HB-1 gene expression levels in bone marrow of 183 cases of ALL, 70 cases of acute myeloid leukemias (AML), 52 cases of non-malignant hematologic diseases and 24 healthy hematopoietic stem cell donors were detected. The correlation of HB-1 level with diagnosis and relapse was analyzed by detecting bone marrow samples of 33 B-ALL. The sensitivity of this assay reached the 10 -4 level. The coefficient of variation for inter-batch and inter-tube of HB-1 were 6.79% and 4.80%, respectively. It was found that HB-1 gene specifically expressed in acute B lymphoblastic leukemia. The median expression levels of HB-1 gene in newly diagnosed and relapsed B-ALL patients were statistically significantly higher than those in ALL in complete remission(CR), newly diagnosed T-ALL, newly diagnosed AML, non-malignant hematologic diseases, and healthy hematopoietic stem cell donors(33.0% vs 0.68%, 0.07%, 0.02%, 0.58% and 0, respectively) (P0.05). The expression level of HB-1 gene declined sharply when B-ALL patients reached complete remission (0-7.99%, with median level 0.68%), but increased when relapsed (7.69%, 8.08% and 484.0% in 3 relapsed samples), which was in accordance with results of flow cytometry. HB-1 gene specifically expressed in acute B lymphoblastic leukemia cells. The established real-time fluorescence quantitative RT-PCR assay shows good sensitivity, specificity and repeatability, thus, can be used as a biological marker in the clinical detection, monitoring MRD and predicting of early relapse for B-ALL patients.

  6. Acute Lymphoblastic Leukemia, Version 2.2015.

    Science.gov (United States)

    Alvarnas, Joseph C; Brown, Patrick A; Aoun, Patricia; Ballen, Karen Kuhn; Barta, Stefan K; Borate, Uma; Boyer, Michael W; Burke, Patrick W; Cassaday, Ryan; Castro, Januario E; Coccia, Peter F; Coutre, Steven E; Damon, Lloyd E; DeAngelo, Daniel J; Douer, Dan; Frankfurt, Olga; Greer, John P; Johnson, Robert A; Kantarjian, Hagop M; Klisovic, Rebecca B; Kupfer, Gary; Litzow, Mark; Liu, Arthur; Rao, Arati V; Shah, Bijal; Uy, Geoffrey L; Wang, Eunice S; Zelenetz, Andrew D; Gregory, Kristina; Smith, Courtney

    2015-10-01

    Treatment of acute lymphoblastic leukemia (ALL) continues to advance, as evidenced by the improved risk stratification of patients and development of newer treatment options. Identification of ALL subtypes based on immunophenotyping and cytogenetic and molecular markers has resulted in the inclusion of Philadelphia-like ALL and early T-cell precursor ALL as subtypes that affect prognosis. Identification of Ikaros mutations has also emerged as a prognostic factor. In addition to improved prognostication, treatment options for patients with ALL have expanded, particularly with regard to relapsed/refractory ALL. Continued development of second-generation tyrosine kinase inhibitors and the emergence of immunotherapy, including blinatumomab and chimeric antigen receptor T-cell therapy, have improved survival. Furthermore, incorporation of minimal residual disease (MRD) monitoring has shown insight into patient outcomes and may lead to treatment modification or alternative treatment strategies in select populations. This excerpt focuses on the sections of the ALL guidelines specific to clinical presentation and diagnosis, treatment of relapsed/refractory ALL, and incorporation of MRD monitoring. To view the most recent complete version of these guidelines, visit NCCN.org. Copyright © 2015 by the National Comprehensive Cancer Network.

  7. Alternative Donor Transplantation for Acute Myeloid Leukemia

    Directory of Open Access Journals (Sweden)

    Nelli Bejanyan

    2015-06-01

    Full Text Available Allogeneic hematopoietic cell transplantation (allo-HCT is a potentially curative therapy for adult patients with acute myeloid leukemia (AML, but its use for consolidation therapy after first remission with induction chemotherapy used to be limited to younger patients and those with suitable donors. The median age of AML diagnosis is in the late 60s. With the introduction of reduced-intensity conditioning (RIC, many older adults are now eligible to receive allo-HCT, including those who are medically less fit to receive myeloablative conditioning. Furthermore, AML patients commonly have no human leukocyte antigen (HLA-identical or medically suitable sibling donor available to proceed with allo-HCT. Technical advances in donor matching, suppression of alloreactivity, and supportive care have made it possible to use alternative donors, such as unrelated umbilical cord blood (UCB and partially HLA-matched related (haploidentical donors. Outcomes after alternative donor allo-HCT are now approaching the outcomes observed for conventional allo-HCT with matched related and unrelated donors. Thus, with both UCB and haploidentical donors available, lack of donor should rarely be a limiting factor in offering an allo-HCT to adults with AML.

  8. CDX2 gene expression in acute lymphoblastic leukemia

    International Nuclear Information System (INIS)

    Arnaoaut, H.H.; Mokhtar, D.A.; Samy, R.M.; Omar, Sh.A.; Khames, S.A.

    2014-01-01

    CDX genes are classically known as regulators of axial elongation during early embryogenesis. An unsuspected role for CDX genes has been revealed during hematopoietic development. The CDX gene family member CDX2 belongs to the most frequent aberrantly expressed proto-oncogenes in human acute leukemias and is highly leukemogenic in experimental models. We used reversed transcriptase polymerase chain reaction (RT-PCR) to determine the expression level of CDX2 gene in 30 pediatric patients with acute lymphoblastic leukemia (ALL) at diagnosis and 30 healthy volunteers. ALL patients were followed up to detect minimal residual disease (MRD) on days 15 and 42 of induction. We found that CDX2 gene was expressed in 50% of patients and not expressed in controls. Associations between gene expression and different clinical and laboratory data of patients revealed no impact on different findings. With follow up, we could not confirm that CDX2 expression had a prognostic significance.

  9. Phase I trial of sodium salicylate in patients with myelodysplastic syndromes and acute myelogenous leukemia.

    Science.gov (United States)

    Klimek, Virginia M; Dolezal, Emily K; Smith, Larry; Soff, Gerald; Nimer, Stephen D

    2012-05-01

    Sodium salicylate is an inexpensive, readily available anti-inflammatory agent which inhibits NF-κB in in vitro models. We examined whether it was possible to safely achieve and maintain salicylate levels known to inhibit NF-κB in vitro in 11 patients with MDS or AML taking sodium salicylate. Most patients achieved the target blood salicylate level (20-30mg/dL) with acceptable toxicity, including reversible grade 1/2 elevations of hepatic transaminases (n=4) and ototoxicity (n=4). One patient had grade 3/4 elevations in AST/ALT. This study suggests that sodium salicylate may be safely combined with conventional chemotherapy regimens which are not associated with significant ototoxicity or hepatotoxicity. Copyright © 2011 Elsevier Ltd. All rights reserved.

  10. Targeted immunotherapy in acute myeloblastic leukemia: from animals to humans.

    Science.gov (United States)

    Robin, Marie; Schlageter, Marie-Hélène; Chomienne, Christine; Padua, Rose-Ann

    2005-10-01

    Immunity against acute myeloid leukemia (AML) is demonstrated in humans by the graft-versus-leukemia effect in allogeneic hematopoietic stem cell transplantation. Specific leukemic antigens have progressively been discovered and circulating specific T lymphocytes against Wilms tumor antigen, proteinase peptide or fusion-proteins produced from aberrant oncogenic chromosomal translocations have been detected in leukemic patients. However, due to the fact that leukemic blasts develop various escape mechanisms, antileukemic specific immunity is not able to control leukemic cell proliferation. The aim of immunotherapy is to overcome tolerance and boost immunity to elicit an efficient immune response against leukemia. We review different immunotherapy strategies tested in preclinical animal models of AML and the human trials that spurred from encouraging results obtained in animal models, demonstrate the feasibility of immunotherapy in AML patients.

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

    DEFF Research Database (Denmark)

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

    and methods in the everyday clinical setting: technical expertise may not be available and inter-study variations have hampered direct comparison of results between centers. As a consequence the practical implications of analyzing single patient samples have to some extent been overlooked. We hypothesized...

  12. Intracranial CNS Manifestations of Myeloid Sarcoma in Patients with Acute Myeloid Leukemia: Review of the Literature and Three Case Reports from the Author’s Institution

    Directory of Open Access Journals (Sweden)

    Gustavo M. Cervantes

    2015-05-01

    Full Text Available Myeloid sarcoma (MS of the central nervous system (CNS is a rare presentation of leukemic mass infiltration outside of the bone marrow. It may involve the subperiosteum and dura mater and, on rare occasions, can also invade the brain parenchyma. The disease is most commonly seen in children or young adults; however, it has been described in multiple age groups. MS can be seen in patients with acute myeloid leukemia (AML, chronic myeloid leukemia and other myeloproliferative disorders. This entity has the potential to be underdiagnosed if the MS appearance precedes the first diagnosis of leukemia. The main reason is that their appearance on CT and MRI has a broad differential diagnosis, and proper diagnosis of MS can only be made if the imaging findings are correlated with the clinical history and laboratory findings. Herein, we describe the intracranial CNS manifestations of MS in patients with AML on CT and MRI involving the brain and/or meninges. This study is based on a systematic review of the literature. In addition, three case reports from the author’s institution with AML and intracranial involvement of MS are included. Our aim is to enhance the awareness of this entity among both clinicians and radiologists.

  13. Sequential Combination of Gemtuzumab Ozogamicin and Standard Chemotherapy in Older Patients With Newly Diagnosed Acute Myeloid Leukemia: Results of a Randomized Phase III Trial by the EORTC and GIMEMA Consortium (AML-17).

    NARCIS (Netherlands)

    Amadori, S.; Suciu, S.; Stasi, R.; Salih, H.R.; Selleslag, D.; Muus, P.; Fabritiis, P. De; Venditti, A.; Ho, A.D.; Lubbert, M.; Thomas, X.; Latagliata, R.; Halkes, C.J.; Falzetti, F.; Magro, D.; Guimaraes, J.E.; Berneman, Z.; Specchia, G.; Karrasch, M.; Fazi, P.; Vignetti, M.; Willemze, R.; Witte, T.J. de; Marie, J.P.

    2013-01-01

    PURPOSE: This randomized trial evaluated the efficacy and toxicity of sequential gemtuzumab ozogamicin (GO) and standard chemotherapy in older patients with newly diagnosed acute myeloid leukemia (AML). PATIENTS AND METHODS: Patients (n = 472) age 61 to 75 years were randomly assigned to induction

  14. Optic nerve infiltration by acute lymphoblastic leukemia: MRI contribution

    Energy Technology Data Exchange (ETDEWEB)

    Soares, Maria de Fatima; Braga, Flavio Tulio [Federal University of Sao Paulo, Department of Diagnostic Imaging, Paulista School of Medicine, Sao Paulo (Brazil); Rocha, Antonio Jose da [Santa Casa de Misericordia de Sao Paulo, Servico de Diagnostico por Imagem, Sao Paulo (Brazil); Lederman, Henrique Manoel [Federal University of Sao Paulo, Division of Diagnostic Imaging in Pediatrics, Department of Diagnostic Imaging, Sao Paulo (Brazil)

    2005-08-01

    We describe the clinical presentation and imaging features of a patient with acute lymphoblastic leukemia (ALL) that was complicated by optic nerve infiltration. The clinical and diagnostic characteristics of this complication must be recognized so that optimal therapy can be started to prevent blindness. MR imaging is useful in early detection and should be performed in any leukemic patient with ocular complaints, even during remission. (orig.)

  15. Optic nerve infiltration by acute lymphoblastic leukemia: MRI contribution

    International Nuclear Information System (INIS)

    Soares, Maria de Fatima; Braga, Flavio Tulio; Rocha, Antonio Jose da; Lederman, Henrique Manoel

    2005-01-01

    We describe the clinical presentation and imaging features of a patient with acute lymphoblastic leukemia (ALL) that was complicated by optic nerve infiltration. The clinical and diagnostic characteristics of this complication must be recognized so that optimal therapy can be started to prevent blindness. MR imaging is useful in early detection and should be performed in any leukemic patient with ocular complaints, even during remission. (orig.)

  16. [Comparison of chromosome karyotype between myelodysplastic syndrome and acute leukemia patients confirmed at the same period].

    Science.gov (United States)

    Jiang, Ming; Wen, Bing-Zhao; Li, Ling; Chen, Shuang; Cheng, Hong; Hao, Jian-Ping; Chen, Rong; Wang, Lei; Zhao, Fang

    2014-04-01

    This study was purposed to compare and analyze the relationship between the abnormality of chromosome karyotypes and diagnosis, prognosis of MDS and AML patients, as well as to explore the characteristics of chromosome prognostic stratification in MDS and AML patients of different ages. The cytogenetic karyotype analysis was performed in 134 cases of MDS and 123 cases of AML by using bone marrow short-term culture and R-banding technique. The results indicated that the detected rates of chromosome abnormal karyotypes in MDS and AML patients were 41% and 61% respectively. The abnormal karyotype analysis of MDS and AML group showed that the abnormal karyotype in MDS group displayed number abnormality as the dominate (mainly the +8), while the abnormal karyotype in AML group displayed structure abnormality as the dominant [mainly, t(15;17) and t(8;21)]. The detected abnormal karyotype are mainly for the +8 which has ambiguous correlation with FAB subtype; the detection rates of complex karyotype abnormalities, favourable prognosis karyotype as well as poor prognosis karyotype in the MDS group obviously higher than that of AML group. Among patients with MDS transformed into AML, 12 cases had chromosome abnormal karyotype. There were 3 cases of chromosome abnormal karyotype in AML group which were transformed by MDS. The analysis of age stratification between two groups showed that the detected rate of abnormal karyotype was enhanced with the increase of age in MDS group, and detected rate in ≥ 60 years old group was obviously higher than that in patients with ≤ 30 age group.The detected rate of complex karyotype abnormalities in three age groups of MDS did not show statistical difference; the detected rate of abnormal karyotype in AML group decreased with the increase of age, the detected rate in ≤ 30 years old group was obviously higher than that in ≥ 60 age group,while the detection rate of complex karyotype abnormalities showed that the detected rate in

  17. Acute Leukemia in Down Syndrome Children in Hong Kong: Retrospective Review.

    Science.gov (United States)

    Lam, Grace Kee See; Leung, Alex Wing Kwan; Ha, Shau Yin; Luk, Chung Wing; Li, Chak Ho; Ling, Siu Cheung; Chiang, Alan Kwok Shing; Li, Chi Kong

    2016-03-01

    Children with Down syndrome (DS) are at higher risk of developing acute leukemia. Treatment continues to evolve as we accumulate better understanding of the distinctive clinical and biological features of acute leukemia in DS patients. A retrospective review of the clinical features, treatment outcomes, and survival of DS children with acute leukemia in Hong Kong from 1993 to 2013 was conducted. Patients were identified from the registry of the Hong Kong Pediatric Hematology and Oncology study group. This cohort included a total of 29 patients with DS. Ten were diagnosed with acute lymphoblastic leukemia and 19 had acute myeloid leukemia (AML). The mean follow-up duration was 8.3 years (range, 0.6 mo to 18.1 y). The 5-year overall survival and event-free survival for DS-acute lymphoblastic leukemia and DS-AML were 65.6%, 54.9%, 89.5%, and 89.5%, respectively. The clinical characteristics and treatment outcomes of DS patients with acute leukemia in Hong Kong were comparable with results from other international study groups. Patients with DS-AML had a better prognosis.

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

    Directory of Open Access Journals (Sweden)

    Michael Schmitt

    2007-01-01

    Full Text Available Leukemia associated antigens (LAAs are being increasingly identified by methods such as cytotoxic T-lymphocyte (CTL cloning, serological analysis of recombinant cDNA expression libraries (SEREX and mass spectrometry (MS. In additional, large scale screening techniques such as microarray, single nucleotide polymorphisms (SNPs, serial analysis of gene expression (SAGE and 2-dimensional gel electrophoresis (2-DE have expanded our understanding of the role that tumor antigens play in the biological processes which are perturbed in acute myeloid leukemia (AML. It has become increasingly apparent that these antigens play a dual role, not only as targets for immunotherapy, but also as biomarkers of disease state, stage, response to treatment and survival. We need biomarkers to enable the identification of the patients who are most likely to benefit from specific treatments (conventional and/or novel and to help clinicians and scientists improve clinical end points and treatment design. Here we describe the LAAs identified in AML, to date, which have already been shown to play a dual role as biomarkers of AML disease.Abbreviations: AML: acute myeloid leukemia; APL: acute promyelocytic leukemia; ATRA: all-trans-retinoic acid; B-CLL: B-cell chronic lymphocytic leukemia; CT: cancer-testis; CTL: cytotoxic T-lymphocyte; FAB: French-American-British; HI: hypusination inhibitors; HSP: heat shock protein; ITD: internal tandem duplication; LAA: leukemia associated antigen; MDS: myelodysplastic syndrome; MGEA6: meningioma antigen 6; MPD: myeloproliferative disease; MS: mass spectrometry; NK: natural killer; PRAME: preferentially expressed antigen of melanoma; PRTN3: proteinase 3; RAGE-1: renal antigen 1; RHAMM: receptor for hyaluronic acid-mediated motility; RQ-PCR: real-time PCR; SAGE: serial analysis of gene expression; SCT: stem cell transplant; SEREX: serological analysis of recombinant cDNA expression libraries; SNPs: single nucleotide polymorphisms; UPD

  19. Genetic association with B-cell acute lymphoblastic leukemia in allogeneic transplant patients differs by age and sex.

    Science.gov (United States)

    Clay-Gilmour, Alyssa I; Hahn, Theresa; Preus, Leah M; Onel, Kenan; Skol, Andrew; Hungate, Eric; Zhu, Qianqian; Haiman, Christopher A; Stram, Daniel O; Pooler, Loreall; Sheng, Xin; Yan, Li; Liu, Qian; Hu, Qiang; Liu, Song; Battaglia, Sebastiano; Zhu, Xiaochun; Block, AnneMarie W; Sait, Sheila N J; Karaesmen, Ezgi; Rizvi, Abbas; Weisdorf, Daniel J; Ambrosone, Christine B; Tritchler, David; Ellinghaus, Eva; Ellinghaus, David; Stanulla, Martin; Clavel, Jacqueline; Orsi, Laurent; Spellman, Stephen; Pasquini, Marcelo C; McCarthy, Philip L; Sucheston-Campbell, Lara E

    2017-09-12

    The incidence and mortality rates of B-cell acute lymphoblastic leukemia (B-ALL) differ by age and sex. To determine if inherited genetic susceptibility contributes to these differences we performed 2 genome-wide association studies (GWAS) by age, sex, and subtype and subsequent meta-analyses. The GWAS included 446 B-ALL cases, and 3027 healthy unrelated blood and marrow transplant (BMT) donors as controls from the Determining the Influence of Susceptibility Conveying Variants Related to One-Year Mortality after BMT (DISCOVeRY-BMT) study. We identified 1 novel variant, rs189434316, significantly associated with odds of normal cytogenetic B-ALL (odds ratio from meta-analysis [OR meta ] = 3.7; 95% confidence interval [CI], 2.5, 6.2; P value from meta-analysis [ P meta ] = 6.0 × 10 -9 ). The previously reported pediatric B-ALL GWAS variant, rs11980379 ( IKZF1 ), replicated in B-ALL pediatric patients (OR meta = 2.3; 95% CI, 1.5, 3.7; P meta = 1.0 × 10 -9 ), with evidence of heterogeneity ( P = .02) between males and females. Sex differences in single-nucleotide polymorphism effect were seen in those >15 years (OR = 1.7; 95% CI, 1.4, 2.2, P Males = 6.38 × 10 -6 /OR = 1.1; 95% CI, 0.8, 1.5; P Females = .6) but not ≤15 years (OR = 2.3; 95% CI, 1.4, 3.8; P Males = .0007/OR = 1.9; 95% CI, 1.2, 3.2; P Females = .007). The latter association replicated in independent pediatric B-ALL cohorts. A previously identified adolescent and young-adult onset ALL-associated variant in GATA3 is associated with B-ALL risk in those >40 years. Our findings provide more evidence of the influence of genetics on B-ALL age of onset and we have shown the first evidence that IKZF1 associations with B-ALL may be sex and age specific.

  20. [PCR detection of relevant translocations in pediatric acute lymphoblastic leukemia].

    Science.gov (United States)

    Guerra-Castillo, Francisco Xavier; Ramos-Cervantes, María Teresa; Rosel-Pech, Cecilia; Jiménez-Hernández, Elva; Bekker-Méndez, Vilma Carolina

    2016-01-01

    In Mexico, leukemia represents the most common type of cancer in the population under 15 years old with a high incidence rate when compared with developed countries. The etiology of leukemia may be unknown, however different factors are involve such as chromosomal translocations. The aim of this work is to detect the molecular alterations: TEL-AML1, MLL-AF4, BCR-ABL minor and E2A-PBX1 in pediatric patients with acute lymphoblastic leukemia. 91 bone marrow samples were collected from pediatric patients with acute lymphoblastic leukemia from january 2012 to march 2013 at the Pediatric Hematology Service, Hospital General "Gaudencio González Garza". Translocations detected (TEL-AML1, MLL-AF4, BCR-ABL minor and E2A-PBX1) using real time PCR, SYBR Green (Qiagen, Alameda, CA). 91 samples were processed, the detected frequencies for each translocation were: TEL-AML1 (7.21%), E2A-PBX1 (5.15%). The MLL-AF4 and the BCR-ABL minor translocations were not detected in this study. The frequencies shown in this study are consistent with the data shown in the literature, where TEL-AML1 is the most common translocation found in pediatric patients. It is of relevance to mention that E2A-PBX1 is found in a high frequency in developing countries when compared with developed countries.

  1. High-resolution Antibody Array Analysis of Childhood Acute Leukemia Cells*

    Science.gov (United States)

    Kanderova, Veronika; Kuzilkova, Daniela; Stuchly, Jan; Vaskova, Martina; Brdicka, Tomas; Fiser, Karel; Hrusak, Ondrej; Lund-Johansen, Fridtjof

    2016-01-01

    Acute leukemia is a disease pathologically manifested at both genomic and proteomic levels. Molecular genetic technologies are currently widely used in clinical research. In contrast, sensitive and high-throughput proteomic techniques for performing protein analyses in patient samples are still lacking. Here, we used a technology based on size exclusion chromatography followed by immunoprecipitation of target proteins with an antibody bead array (Size Exclusion Chromatography-Microsphere-based Affinity Proteomics, SEC-MAP) to detect hundreds of proteins from a single sample. In addition, we developed semi-automatic bioinformatics tools to adapt this technology for high-content proteomic screening of pediatric acute leukemia patients. To confirm the utility of SEC-MAP in leukemia immunophenotyping, we tested 31 leukemia diagnostic markers in parallel by SEC-MAP and flow cytometry. We identified 28 antibodies suitable for both techniques. Eighteen of them provided excellent quantitative correlation between SEC-MAP and flow cytometry (p leukemia. In this assay, we used 632 different antibodies and detected 501 targets. Of those, 47 targets were differentially expressed between at least two of the three acute leukemia subgroups. The CD markers correlated with immunophenotypic categories as expected. From non-CD markers, we found DBN1, PAX5, or PTK2 overexpressed in B-cell precursor acute lymphoblastic leukemias, LAT, SH2D1A, or STAT5A overexpressed in T-cell acute lymphoblastic leukemias, and HCK, GLUD1, or SYK overexpressed in acute myeloid leukemias. In addition, OPAL1 overexpression corresponded to ETV6-RUNX1 chromosomal translocation. In summary, we demonstrated that SEC-MAP technology is a powerful tool for detecting hundreds of proteins in clinical samples obtained from pediatric acute leukemia patients. It provides information about protein size and reveals differences in protein expression between particular leukemia subgroups. Forty-seven of SEC-MAP identified

  2. Acute leukemias of ambiguous lineage in adults: molecular and clinical characterization.

    Science.gov (United States)

    Heesch, Sandra; Neumann, Martin; Schwartz, Stefan; Bartram, Isabelle; Schlee, Cornelia; Burmeister, Thomas; Hänel, Matthias; Ganser, Arnold; Heuser, Michael; Wendtner, Clemens-Martin; Berdel, Wolfgang E; Gökbuget, Nicola; Hoelzer, Dieter; Hofmann, Wolf-Karsten; Thiel, Eckhard; Baldus, Claudia D

    2013-06-01

    Acute leukemias of ambiguous lineage represent a heterogeneous group of rare, poorly characterized leukemias with adverse outcome. No larger studies have yet performed a combined approach of molecular and clinical characterization of acute undifferentiated leukemia (AUL) and biphenotypic acute leukemia (BAL) in adults. Here we describe 16 adults with AUL and 26 with BAL and performed mutational as well as expression studies of genes with prognostic impact in acute leukemia (BAALC, ERG, MN1, WT1, and IGFBP7). AUL showed overexpression of these genes compared to T-lymphoblastic leukemia (T-ALL), B-precursor ALL, and to acute myeloid leukemia (AML). Genotype alterations were not detectable in AUL. BAL samples were characterized by frequent WT1 mutations (18 %) and BCR-ABL translocations (30 %). ALL-based treatment protocols induced complete remissions in 40 % and AML-like therapies in 22 % of AUL/BAL patients. The outcome in both groups was very poor; a long-term survival was only observed in patients undergoing allogeneic stem cell transplantation (SCT). Our findings indicate that AUL and BAL share important molecular and high-risk features of both myeloid and lymphoid leukemias. BAL patients exhibited genetic alterations, which can be targeted therapeutically. Importantly, ALL therapy might be more effective than AML protocols and AUL/BAL patients should be considered for allogeneic SCT.

  3. Association of the 5,10-methylenetetrahydrofolate reductase (MTHFR C677T and A1298C) polymorphisms in Korean patients with adult acute lymphoblastic leukemia.

    Science.gov (United States)

    Oh, Doyeun; Kim, Nam Keun; Jang, Moon Ju; Kim, Hugh Chul; Lee, Jae Hoon; Lee, Jung Ae; Ahn, Myung Ju; Kim, Chul Soo; Kim, Heung Sik; Park, Seonyang; Chio, Hyun Sook; Min, Yoo Hong

    2007-01-01

    Methylenetetrahydrofolate reductase (MTHFR) plays a central role in converting folate to methyl donor for DNA methylation. Because MTHFR is a key enzyme in folate metabolism, changes in its activity resulting from polymorphisms in the MTHFR gene could modify the susceptibility to cancer. Recently, the C677T and A1298C mutations of MTHFR were discovered to be associated with susceptibility in acute lymphoblastic leukemia (ALL). The association between MTHFR polymorphisms and susceptibility and clinical outcome in ALL was studied in 118 adult ALL patients and matched healthy controls (n =427). DNA samples taken from patients with ALL and controls were analyzed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assays to detect the MTHFR C677T and A1298C mutations. No significant difference was found in the development of adult ALL among those with different MTHFR genotypes of the C677T or A1298C polymorphisms. However, the MTHFR 677CT+TT genotype showed a tendency to be associated with adult ALL [crude odds ratio (OR), 0.67; 95% confidence interval (CI), 0.44-1.02; adjusted OR, 0.74 95% CI, 0.47-1.14]. The MTHFR C677T and A1298C polymorphisms are not significant risk factors in adult acute leukemia in the Korean population.

  4. Acute Lymphoblastic Leukemia in a Man Treated With Fingolimod for Relapsing Multiple Sclerosis

    Directory of Open Access Journals (Sweden)

    Stanley Cohan MD, PhD

    2015-03-01

    Full Text Available A man with relapsing multiple sclerosis, treated with fingolimod 0.5 mg/d for 15 months, developed acute lymphoblastic leukemia and died 4 months after immune ablation and bone marrow allograft, from graft versus host disease. To our knowledge, this is the first case of acute lymphoblastic leukemia reported in a patient treated with fingolimod. Although no causal relationship can be established between fingolimod use and acute lymphoblastic leukemia risk in this single case, future surveillance for lymphatic cell malignancies in patients treated with fingolimod appears justified.

  5. The Epigenetic Landscape of Acute Myeloid Leukemia

    Directory of Open Access Journals (Sweden)

    Emma Conway O’Brien

    2014-01-01

    Full Text Available Acute myeloid leukemia (AML is a genetically heterogeneous disease. Certain cytogenetic and molecular genetic mutations are recognized to have an impact on prognosis, leading to their inclusion in some prognostic stratification systems. Recently, the advent of high-throughput whole genome or exome sequencing has led to the identification of several novel recurrent mutations in AML, a number of which have been found to involve genes concerned with epigenetic regulation. These genes include in particular DNMT3A, TET2, and IDH1/2, involved with regulation of DNA methylation, and EZH2 and ASXL-1, which are implicated in regulation of histones. However, the precise mechanisms linking these genes to AML pathogenesis have yet to be fully elucidated as has their respective prognostic relevance. As massively parallel DNA sequencing becomes increasingly accessible for patients, there is a need for clarification of the clinical implications of these mutations. This review examines the literature surrounding the biology of these epigenetic modifying genes with regard to leukemogenesis and their clinical and prognostic relevance in AML when mutated.

  6. Novel therapeutic options in Acute Myeloid Leukemia

    Directory of Open Access Journals (Sweden)

    Michael Medinger

    2016-01-01

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

  7. 3 Tesla proton MRI for the diagnosis of pneumonia/lung infiltrates in neutropenic patients with acute myeloid leukemia: initial results in comparison to HRCT.

    Science.gov (United States)

    Attenberger, U I; Morelli, J N; Henzler, T; Buchheidt, D; Fink, C; Schoenberg, S O; Reichert, M

    2014-01-01

    To evaluate the diagnostic accuracy of 3 Tesla proton MRI for the assessment of pneumonia/lung infiltrates in neutropenic patients with acute myeloid leukemia. In a prospective study, 3 Tesla MRI was performed in 19 febrile neutropenic patients (5 women, 14 men; mean age 61 years ± 14.2; range 23-77 years). All patients underwent high-resolution CT less than 24h prior to MRI. The MRI protocol (Magnetom Tim Trio, Siemens) included a T2-weighted HASTE sequence (TE/TR: 49 ms/∞, slice thickness 6mm) and a high-resolution 3D VIBE sequence with an ultra-short TETesla MRI with a sensitivity of 82.3% and a specificity of 78.6%, resulting in an overall accuracy of 88% (NPV/PPV 66.7%/89.5%). In 51 lobes (19 of 19 patients), pulmonary abnormalities visualized by MR were judged to be concordant in their location and in the lesion type identified by both readers. In 22 lobes (11 of 19 patients), no abnormalities were present on either MR or HRCT (true negative). In 6 lobes (5 of 19 patients), ground glass opacity areas were detected on MRI but were not visible on HRCT (false positives). In 11 lobes (7 of 19 patients), MRI failed to detect ground glass opacity areas identified by HRCT. However, since the abnormalities were disseminated in these patients, accurate treatment decisions were possible in every case based on MRI. In one case MRI showed a central area of cavitation, which was not visualized by HRCT. Infectious nodules and consolidations can be detected in neutropenic patients with acute myeloid leukemia with a sufficient diagnostic accuracy by 3 Tesla MRI. Detection of ground glass opacity areas is the main limitation of 3-Tesla MRI when compared to HRCT. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  8. CD8+T cells expressing both PD-1 and TIGIT but not CD226 are dysfunctional in acute myeloid leukemia (AML) patients.

    Science.gov (United States)

    Wang, Mengjie; Bu, Jin; Zhou, Maohua; Sido, Jessica; Lin, Yu; Liu, Guanfang; Lin, Qiwen; Xu, Xiuzhang; Leavenworth, Jianmei W; Shen, Erxia

    2018-05-01

    Acute myeloid leukemia (AML) is one of the most common types of leukemia among adults with an overall poor prognosis and very limited treatment management. Immune checkpoint blockade of PD-1 alone or combined with other immune checkpoint blockade has gained impressive results in murine AML models by improving anti-leukemia CD8 + T cell function, which has greatly promoted the strategy to utilize combined immune checkpoint inhibitors to treat AML patients. However, the expression profiles of these immune checkpoint receptors, such as co-inhibitory receptors PD-1 and TIGIT and co-stimulatory receptor CD226, in T cells from AML patients have not been clearly defined. Here we have defined subsets of CD8 + and CD4 + T cells in the peripheral blood (PB) from newly diagnosed AML patients and healthy controls (HCs). We have observed increased frequencies of PD-1- and TIGIT- expressing CD8 + T cells but decreased occurrence of CD226-expressing CD8 + T cells in AML patients. Further analysis of these CD8 + T cells revealed a unique CD8 + T cell subset that expressed PD-1 and TIGIT but displayed lower levels of CD226 was associated with failure to achieve remission after induction chemotherapy and FLT3-ITD mutations which predict poor clinical prognosis in AML patients. Importantly, these PD-1 + TIGIT + CD226 - CD8 + T cells are dysfunctional with lower expression of intracellular IFN-γ and TNF-α than their counterparts in HCs. Therefore, our studies revealed that an increased frequency of a unique CD8 + T cell subset, PD-1 + TIGIT + CD226 - CD8 + T cells, is associated with CD8 + T cell dysfunction and poor clinical prognosis of AML patients, which may reveal critical diagnostic or prognostic biomarkers and direct more efficient therapeutic strategies. Copyright © 2017. Published by Elsevier Inc.

  9. Potential of ponatinib to treat chronic myeloid leukemia and acute lymphoblastic leukemia

    Directory of Open Access Journals (Sweden)

    Price KE

    2013-08-01

    Full Text Available Kimberly E Price, Najma Saleem, Georgina Lee, Michael SteinbergMassachusetts College of Pharmacy and Health Sciences University, Worcester, MA, USAAbstract: Development of BCR-ABL tyrosine kinase inhibitors (TKIs have improved outcomes for patients diagnosed with chronic myeloid leukemia and Philadelphia chromosome positive acute lymphoblastic leukemia. However, resistance or intolerance to these TKIs still leaves some patients without many treatment options. One point mutation in particular, the T315I mutation, has been shown to be resistant to first and second generation TKIs. The third generation TKI, ponatinib, may provide an option for these patients. Ponatinib (Iclusig®, an orally available, pan-tyrosine kinase inhibitor has a unique binding mechanism allowing inhibition of BCR-ABL kinases, including those with the T315I point mutation. A Phase II study evaluated ponatinib in patients who were resistant or intolerant to nilotinib or dasatinib or patients who had the T315I mutation. In the Phase II study, ponatinib produced a major cytogenetic response in 54% of chronic phase chronic myeloid leukemia patients. It further achieved major hematologic response in 52% of patients in the accelerated phase, 31% of patients in the blast phase, and 41% of Philadelphia chromosome positive acute lymphoblastic leukemia patients. Ponatinib also showed efficacy in patients with the T315I mutation. Serious adverse events included arterial thrombosis, hepatotoxicity, cardiovascular risks, pancreatitis, hemorrhage, fluid retention, myelosuppression, rash, abdominal pain, and embryo–fetal toxicity. Due to the risk of these adverse events and potential drug interactions, the use of ponatinib must be carefully weighed against the benefits in treating patients who have limited treatment options.Keywords: BCR-ABL, tyrosine kinase inhibitor, TKI, T315I, Philadelphia chromosome

  10. Diagnosis of a case of relapse of acute lymphoblastic leukemia based on oral manifestation of leukemic gingival enlargement and acute necrotizing gingivitis: A case report

    Directory of Open Access Journals (Sweden)

    Gopikrishna Kolli

    2014-01-01

    Full Text Available Acute leukemias are the most common malignancy in childhood. They represent approximately 30% of malignant diseases in patients under the age of 15 years. Acute lymphoblastic leukemia (ALL is the most frequent type of leukemia in children. Despite high cure rates, approximately 20% of patients with ALL have disease relapse. Oral manifestations are common in leukemia, particularly in acute leukemias. One of the oral manifestations of leukemia is diffuse gingival enlargement thought to be, at least partly, the result of gross infiltration of the gingiva by blast cells. The occurrence of acute necrotizing gingivitis, although a rare occurrence, is seen in such immunocompromised individuals. This is a case report of a 19-year-old patient who was under remission after treatment for ALL in whom a recurrence of leukemia was detected based on the oral findings and highlights the importance of its early detection by the dentist in preventing further complications and for instituting therapy swiftly.

  11. Brief Report: Human Acute Myeloid Leukemia Reprogramming to Pluripotency Is a Rare Event and Selects for Patient Hematopoietic Cells Devoid of Leukemic Mutations.

    Science.gov (United States)

    Lee, Jong-Hee; Salci, Kyle R; Reid, Jennifer C; Orlando, Luca; Tanasijevic, Borko; Shapovalova, Zoya; Bhatia, Mickie

    2017-09-01

    Induced pluripotent stem cell reprogramming has provided critical insights into disease processes by modeling the genetics and related clinical pathophysiology. Human cancer represents highly diverse genetics, as well as inter- and intra-patient heterogeneity, where cellular model systems capable of capturing this disease complexity would be invaluable. Acute myeloid leukemia (AML) represents one of most heterogeneous cancers and has been divided into genetic subtypes correlated with unique risk stratification over the decades. Here, we report our efforts to induce pluripotency from the heterogeneous population of human patients that represents this disease in the clinic. Using robust optimized reprogramming methods, we demonstrate that reprogramming of AML cells harboring leukemic genomic aberrations is a rare event with the exception of those with de novo mixed-lineage leukemia (MLL) mutations that can be reprogrammed and model drug responses in vitro. Our findings indicate that unlike hematopoietic cells devoid of genomic aberrations, AML cells harboring driver mutations are refractory to reprogramming. Expression of MLL fusion proteins in AML cells did not contribute to induced reprogramming success, which continued to select for patient derived cells devoid of AML patient-specific aberrations. Our study reveals that unanticipated blockades to achieving pluripotency reside within the majority of transformed AML patient cells. Stem Cells 2017;35:2095-2102. © 2017 AlphaMed Press.

  12. FLAG-induced remission in a patient with acute mast cell leukemia (MCL exhibiting t(7;10(q22;q26 and KIT D816H

    Directory of Open Access Journals (Sweden)

    Peter Valent

    2014-01-01

    Full Text Available Mast cell leukemia (MCL is a life-threatening disease associated with high mortality and drug-resistance. Only few patients survive more than 12 months. We report on a 55-year-old female patient with acute MCL diagnosed in May 2012. The disease was characterized by a rapid increase in white blood cells and mast cells (MC in the peripheral blood, and a rapid increase of serum tryptase levels. The KIT D816H mutation was detected in the blood and bone marrow (BM. Induction chemotherapy with high-dose ARA-C and fludarabine (FLAG was administered. Unexpectedly, the patient entered a hematologic remission with almost complete disappearance of neoplastic MC and a decrease of serum tryptase levels to normal range after 2 cycles of FLAG. Consecutively, the patient was prepared for allogeneic stem cell transplantation. However, shortly after the third cycle of FLAG, tryptase levels increased again, immature MC appeared in the blood, and the patient died from cerebral bleeding. Together, this case shows that intensive chemotherapy regimens, like FLAG, may induce remission in acute MCL. However, treatment responses are short-lived and the overall outcome remains dismal in these patients. We propose to separate this acute type of MCL from more subacute or chronic variants of MCL.

  13. CD20 positivity and white blood cell count predict treatment outcomes in Philadelphia chromosome-negative acute lymphoblastic leukemia patients ineligible for pediatric-inspired chemotherapy.

    Science.gov (United States)

    Isshiki, Yusuke; Ohwada, Chikako; Sakaida, Emiko; Onoda, Masahiro; Aotsuka, Nobuyuki; Tanaka, Hiroaki; Fukazawa, Motoharu; Cho, Ryuko; Sugawara, Takeaki; Kawaguchi, Takeharu; Hara, Satoru; Yokota, Akira

    2017-11-01

    The efficacy of conventional chemotherapy and allogeneic hematopoietic stem cell transplantation (allo-HSCT) has been controversial as post-remission therapies for adult Philadelphia chromosome-negative acute lymphoblastic leukemia patients. We retrospectively analyzed 96 adolescent and adult cases of Philadelphia chromosome-negative acute lymphoblastic leukemia to evaluate whether allo-HSCT should be performed after first complete remission (1CR). In total, 34 patients received chemotherapy followed by allo-HSCT (HSCT group) and 62 received chemotherapy alone (chemotherapy group). No significant differences in the event-free survival (EFS) or overall survival were observed between the two groups. In the chemotherapy group, use of pediatric regimens was significantly associated with favorable EFS, while high white blood cell (WBC) count and CD20 positivity were associated with poor outcome. In patients who received pediatric regimens, subsequent allo-HSCT did not influence EFS. In patients who received conventional chemotherapy (adult regimen), subsequent allo-HSCT did not improve EFS. High WBC count and CD20 positivity were also significantly associated with poor EFS in patients who received adult regimens. Patients with low WBC count and absence of CD20 who received adult regimens did not benefit from allo-HSCT. Allo-HSCT may not be required in the pediatric regimen-eligible patients; however, pediatric regimen-ineligible patients with either CD20 positivity or high WBC count should receive allo-HSCT after achieving 1CR. This study was registered at http://www.umin.ac.jp/ctr/ as #C000016287. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

  14. Flowcytometric Immunophenotypic Profile of Acute Leukemia: Mansoura Experience

    OpenAIRE

    Salem, Dalia A.; Abd El-Aziz, Sherin M.

    2011-01-01

    Acute leukemia (AL) displays characteristic patterns of antigen expression, which facilitate their identification and proper classification. The purpose of this study is to evaluate the diagnostic usefulness of commonly used immune-markers for immunophenotyping of AL and to define the best immune-markers to be used for proper diagnosis and classification of AL. Besides, to recognize the frequency of different AL subtypes and the antigen expression profile in our Egyptian patients. We retrospe...

  15. Acute Central Nervous System Complications in Pediatric Acute Lymphoblastic Leukemia.

    Science.gov (United States)

    Baytan, Birol; Evim, Melike Sezgin; Güler, Salih; Güneş, Adalet Meral; Okan, Mehmet

    2015-10-01

    The outcome of childhood acute lymphoblastic leukemia has improved because of intensive chemotherapy and supportive care. The frequency of adverse events has also increased, but the data related to acute central nervous system complications during acute lymphoblastic leukemia treatment are sparse. The purpose of this study is to evaluate these complications and to determine their long term outcome. We retrospectively analyzed the hospital reports of 323 children with de novo acute lymphoblastic leukemia from a 13-year period for acute neurological complications. The central nervous system complications of leukemic involvement, peripheral neuropathy, and post-treatment late-onset encephalopathy, and neurocognitive defects were excluded. Twenty-three of 323 children (7.1%) suffered from central nervous system complications during acute lymphoblastic leukemia treatment. The majority of these complications (n = 13/23; 56.5%) developed during the induction period. The complications included posterior reversible encephalopathy (n = 6), fungal abscess (n = 5), cerebrovascular lesions (n = 5), syndrome of inappropriate secretion of antidiuretic hormone (n = 4), and methotrexate encephalopathy (n = 3). Three of these 23 children (13%) died of central nervous system complications, one from an intracranial fungal abscess and the others from intracranial thrombosis. Seven of the survivors (n = 7/20; 35%) became epileptic and three of them had also developed mental and motor retardation. Acute central neurological complications are varied and require an urgent approach for proper diagnosis and treatment. Collaboration among the hematologist, radiologist, neurologist, microbiologist, and neurosurgeon is essential to prevent fatal outcome and serious morbidity. Copyright © 2015 Elsevier Inc. All rights reserved.

  16. Reduced folate carrier mutations are not the mechanism underlying methotrexate resistance in childhood acute lymphoblastic leukemia.

    NARCIS (Netherlands)

    Kaufman, Y; Drori, S.; Cole, PD; Kamen, BA; Sirota, J; Ifergan, I; Arush, MW; Elhasid, R; Sahar, D; Kaspers, G.J.L.; Jansen, G.; Matherly, LH; Rechavi, G; Toren, A; Assaraf, Y.G.

    2004-01-01

    BACKGROUND: Although the majority of children with acute lymphoblastic leukemia (ALL) are cured with combination chemotherapy containing methotrexate (MTX), drug resistance contributes to treatment failure for a substantial fraction of patients. The primary transporter for folates and MTX is the

  17. Construction of protein profile classification model and screening of proteomic signature of acute leukemia.

    Science.gov (United States)

    Xu, Yun; Zhuo, Jiacai; Duan, Yonggang; Shi, Benhang; Chen, Xuhong; Zhang, Xiaoli; Xiao, Liang; Lou, Jin; Huang, Ruihong; Zhang, Qiongli; Du, Xin; Li, Ming; Wang, Daping; Shi, Dunyun

    2014-01-01

    The French-American-British (FAB) and WHO classifications provide important guidelines for the diagnosis, treatment, and prognostic prediction of acute leukemia, but are incapable of accurately differentiating all subtypes, and not well correlated with the clinical outcomes. In this study, we performed the protein profiling of the bone marrow mononuclear cells from the patients with acute leukemia and the health volunteers (control) by surface enhanced laser desorption/ionization-time of flight mass spectrometry (SELDI_TOF_MS). The patients with acute leukemia were analyzed as unitary by the profiling that were grouped into acute promyelocytic leukemia (APL), acute myeloid leukemia-granulocytic (AML-Gran), acute myeloid leukemia-monocytic (AML-Mon) acute lymphocytic leukemia (ALL), and control. Based on 109 proteomic signatures, the classification models of acute leukemia were constructed to screen the predictors by the improvement of the proteomic signatures and to detect their expression characteristics. According to the improvement and the expression characteristics of the predictors, the proteomic signatures (M3829, M1593, M2121, M2536, M1016) characterized successively each group (CON, APL, AML-Gra, AML-Mon, ALL) were screened as target molecules for identification. Meanwhile, the proteomic-based class of determinant samples could be made by the classification models. The credibility of the proteomic-based classification passed the evaluation of Biomarker Patterns Software 5.0 (BPS 5.0) scoring and validated application in clinical practice. The results suggested that the proteomic signatures characterized by different blasts were potential for developing new treatment and monitoring approaches of leukemia blasts. Moreover, the classification model was potential in serving as new diagnose approach of leukemia.

  18. Choreito, a formula from Japanese traditional medicine (Kampo medicine), for massive hemorrhagic cystitis and clot retention in a pediatric patient with refractory acute lymphoblastic leukemia.

    Science.gov (United States)

    Kawashima, Nozomu; Deveaux, Teykia E; Yoshida, Nao; Matsumoto, Kimikazu; Kato, Koji

    2012-09-15

    Hemorrhagic cystitis is critical in patients with hemato-oncological disorders. Unlike adult patients, there are limited modalities and invasive procedures are often not well tolerated in children with poor general conditions. We report a pediatric patient with refractory acute lymphoblastic leukemia who developed life-threatening massive gross hematuria. Along with platelet infusion every other day due to suppressed hematopoiesis, his gross hematuria and clot retention in the bladder were successfully treated with choreito, a formula from Japanese traditional medicine (Kampo medicine). He survived free from hematuria for more than four months. Choreito was well tolerated, and no adverse effects were observed throughout the course. Copyright © 2012 Elsevier GmbH. All rights reserved.

  19. Estimation of the prevalence of Fanconi anemia among patients with de novo acute myelogenous leukemia who have poor recovery from chemotherapy.

    Science.gov (United States)

    Rochowski, Andrzej; Rosenberg, Philip S; Alonzo, Todd A; Gerbing, Robert B; Lange, Beverly J; Alter, Blanche P

    2012-01-01

    We speculated that some individuals with de novo acute myelogenous leukemia (AML) may have undiagnosed Fanconi Anemia (FA). Data from patients enrolled on AML protocol CCG-2961, published FA cohort studies, SEER, and Bayes rule were used to estimate the probability of FA among all newly diagnosed AML cases, and among those who had no or delayed recovery of the absolute neutrophil count following initial chemotherapy. We determined that the probability of undiagnosed FA in patients in a treatment trial for newly diagnosed patients was around 0.18%, and around 0.83% in the subset who had poor marrow recovery. We suggest that FA or other inherited bone marrow failure syndromes be considered prior to treatment, or certainly among those with poor recovery. Published by Elsevier Ltd.

  20. Diagnosis of disseminated candidiasis by fine needle aspiration of lymph node and by splenic imprint in a patient with acute promyelocytic leukemia.

    Science.gov (United States)

    Chao, T Y; Chang, J Y; Yu, C Y; Tsao, T Y

    1995-01-01

    Cytologic studies were done on fine needle aspirates of the lymph node and imprints of splenic biopsies from a patient with acute promyelocytic leukemia who was febrile while being treated with chemotherapy. Examination of the lymph node aspirates revealed pus and numerous pseudohyphae which were later identified as Candida tropicalis. When multiple nodular lesions were detected in the spleen by abdominal sonography and CT scan, needle biopsy of the spleen was done. Cytologic examination of touch imprints of the biopsy disclosed intracellular fungal blastospores. The patient was treated with and responded well to amphotericin B and 5-fluorocytosine. As a result of our experience with this patient we emphasize the importance of close incorporation of clinical information and diagnostic cytology. With such a cooperation, cytologic studies become a most useful method for diagnosis.

  1. Effects of Education and Income on Treatment and Outcome in Patients With Acute Myeloid Leukemia in a Tax-Supported Health Care System

    DEFF Research Database (Denmark)

    Ostgard, Lene Sofie Granfeldt; Norgaard, Mette; Medeiros, Bruno C.

    2017-01-01

    level using logistic regression (odds ratios). We used Cox regression (hazard ratios [HRs]) to compare survival, adjusting for age, sex, SES, and clinical prognostic markers. Results Of 2,992 patients, 1,588 (53.1%) received intensive chemotherapy. Compared with low-education patients, highly educated......Purpose Previous US studies have shown that socioeconomic status (SES) affects survival in acute myeloid leukemia (AML). However, no large study has investigated the association between education or income and clinical characteristics, treatment, and outcome in AML. Methods To investigate...... the effects of education and income in a tax-supported health care system, we conducted a population-based study using individual-level SES and clinical data on all Danish patients with AML (2000 to 2014). We compared treatment intensity, allogeneic transplantation, and response rates by education and income...

  2. [Treatment of acute myeloid leukemia -- a single center experience (2007-2013)].

    Science.gov (United States)

    Selmeczi, Anna; Udvardy, Miklós; Illés, Arpád; Telek, Béla; Kiss, Attila; Batár, Péter; Reményi, Gyula; Szász, Róbert; Ujj, Zsófia; Márton, Adrienn; Ujfalusi, Anikó; Hevessy, Zsuzsanna; Pinczés, László; Bedekovics, Judit; Rejtő, László

    2014-04-27

    Mortality of acute myeloid leukemia is still 60-70% in young (myeloid leukemia. From 2007 to 2013, 173 patients with acute myeloid leukemia were treated. Patients were classified according to the European LeukemiaNet prognostic guideline. Association between mortality and the type of acute myeloid leukemia (secondary or primary), dose of daunoblastin at induction of treatment, and the rate of minimal residual disease were investigated. The 5-year survival probability was 25% in young adults and 2% in the elderly. The survival was significantly influenced by these prognostic factors. The 5-year survival rate was 50% in the young, favorable prognostic group. The 90 mg/m2 daunoblastin dose was found to be beneficial. Addition of bortezomib to the standard induction protocol had an additional beneficial effect. The speed and depth of the response to induction therapy, and the initial white blood cell count had an apparent effect on survival.

  3. An integrative scoring system for survival prediction following umbilical cord blood transplantation in acute leukemia

    NARCIS (Netherlands)

    Shouval, Roni; Ruggeri, Annalisa; Labopin, Myriam; Mohty, Mohamad; Sanz, Guillermo; Michel, Gerard; Kuball, Jürgen; Chevallier, Patrice; Al-Seraihy, Amal; Milpied, Noel Jean; De Heredia, Cristina Diaz; Arcese, William; Blaise, Didier; Rocha, Vanderson; Fein, Joshua; Unger, Ron; Baron, Frederic; Bader, Peter; Gluckman, Eliane; Nagler, Arnon

    2017-01-01

    Purpose: Survival of acute leukemia (AL) patients following umbilical cord blood transplantation (UCBT) is dependent on an array of individual features. Integrative models for risk assessment are lacking. We sought to develop a scoring system for prediction of overall survival (OS) and leukemia-free

  4. A comparison of surface marker analysis and FAB classification in acute myeloid leukemia

    NARCIS (Netherlands)

    van der Reijden, H. J.; van Rhenen, D. J.; Lansdorp, P. M.; van't Veer, M. B.; Langenhuijsen, M. M.; Engelfriet, C. P.; von dem Borne, A. E.

    1983-01-01

    Surface marker analysis with rosette tests and a large panel of xenoantisera and monoclonal antibodies was done on the malignant cells of 55 patients with acute myeloid leukemia (AML). The diagnosis was made on morphological and cytochemical grounds, and the leukemias were classified according to

  5. An analysis of 97 previously diagnosed de novo adult acute erythroid leukemia patients following the 2016 revision to World Health Organization classification.

    Science.gov (United States)

    Qiu, Shaowei; Jiang, Erlie; Wei, Hui; Lin, Dong; Zhang, Guangji; Wei, Shuning; Zhou, Chunlin; Liu, Kaiqi; Wang, Ying; Liu, Bingcheng; Liu, Yuntao; Gong, Benfa; Gong, Xiaoyuan; Feng, Sizhou; Mi, Yingchang; Han, Mingzhe; Wang, Jianxiang

    2017-08-09

    The incidence of acute erythroid leukemia subtype (AEL) is rare, accounting for 5% of cases of acute myeloid leukemia (AML), and the outcome is dismal. However, in 2016 revision to the WHO classification, the subcategory of AEL has been removed. Myeloblasts are redefined as the percentage of total marrow cells, not non-erythroid cells. Therefore, the previously diagnosed AEL cases are currently diagnosed as AML or myelodyspalstic syndrome (MDS) according to new criteria. We respectively reviewed cases of 97 de novo previously diagnosed AEL and all the patients were diagnosed as AML or MDS according to the new classification scheme, and then the clinical characteristics of these two subtypes were compared. Statistical analyses were performed by SPSS software version 18.0. The median age was 37 years-old, the two-thirds of previous AEL cases were diagnosed as MDS, and there was no obvious difference between two subtypes except for male/female ratio and age. Cytogenetic, rather than MDS/AML subtypes, can better represent the prognostic factor of previously diagnosed AEL patients. When the cytogenetic risk of patients belonged to MRC intermediate category and age were below 40 years-old in previous AEL cases, the patients who received induction chemotherapy without transplantation had a similar survival compared with the patients who underwent transplantation (3-year OS: 67.2% vs 68.5%). Cytogenetic, rather than MDS/AML subtypes, can better represent the prognostic factor of previously diagnosed AEL patients. Transplantation was a better choice for those whose cytogenetic category was unfavorable.

  6. Acute erythroid leukemia: autopsy report of a rare disease

    Directory of Open Access Journals (Sweden)

    Cristiane Rúbia Ferreira

    2011-12-01

    Full Text Available Acute erythroid leukemia (AEL is a rare subtype of acute myeloid leukemia(AML, characterized by predominant erythroid proliferation. The 2008 WorldHealth Organization (WHO classification of AML defined two AEL subtypes:erythroleukaemia (EL, in which erythroid precursors account for 50% or moreof all nucleated bone marrow cells and myeloblasts account for 20% or more ofthe nonerythroid cell population; and pure erythroid leukemia (PEL, in whicherythroid precursors account for 80% or more of all nucleated bone marrowcells. We report the case of an elderly female patient with wasting syndromeand pancytopenia without evidence of blasts in peripheral blood. A diagnosisof PEL was established on the basis of bone marrow biopsy findings. Thepatient died on postadmission day 20, and an autopsy was performed. Wereclassified the disease as EL on the basis of the autopsy findings, whichincluded myeloblasts accounting for more than 20% of the nonerythroid cellsin the bone marrow, as well as leukemic infiltration and myeloid metaplasia insolid organs, such as the liver, spleen, kidneys, adrenal glands, and abdominallymph nodes. A rare disease, AEL accounts for less than 5% of all AMLs and ispractically a diagnosis of exclusion. Autopsy reports of AEL are extremely rarein the literature. We demonstrate that in the case reported here, leukemia cellstended to infiltrate solid organs with myeloid metaplasia. Our findings alsoshow that a larger neoplastic bone marrow sample is crucial to the correctdiagnosis of EL, which is based on morphological and quantitative criteria.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2014-07-01

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

  8. Diagnostic work-up of acute myeloid leukemia.

    Science.gov (United States)

    Weinberg, Olga K; Sohani, Aliyah R; Bhargava, Parul; Nardi, Valentina

    2017-03-01

    Acute myeloid leukemia (AML) is characterized by a clonal expansion of undifferentiated myeloid precursors resulting in impaired hematopoiesis and bone marrow failure. In 2016, the World Health Organization (WHO) published revisions to the classification of myeloid neoplasms and acute leukemias. Similar to the 2008 classification, the updated classification incorporates clinical features, morphology, immunophenotyping, and cytogenetics, with greater emphasis on molecular genetics, to define disease entities. This brief review addresses the various components of pathologic assessment to establish a diagnosis of AML and to help risk stratify patients, with an emphasis on newer techniques used in the detection of mutations with prognostic significance, as well as assays employed in the evaluation of minimal residual disease following treatment. © 2017 Wiley Periodicals, Inc.

  9. The role of ZAP70 kinase in acute lymphoblastic leukemia infiltration into the central nervous system.

    Science.gov (United States)

    Alsadeq, Ameera; Fedders, Henning; Vokuhl, Christian; Belau, Nele M; Zimmermann, Martin; Wirbelauer, Tim; Spielberg, Steffi; Vossen-Gajcy, Michaela; Cario, Gunnar; Schrappe, Martin; Schewe, Denis M

    2017-02-01

    Central nervous system infiltration and relapse are poorly understood in childhood acute lymphoblastic leukemia. We examined the role of zeta-chain-associated protein kinase 70 in preclinical models of central nervous system leukemia and performed correlative studies in patients. Zeta-chain-associated protein kinase 70 expression in acute lymphoblastic leukemia cells was modulated using short hairpin ribonucleic acid-mediated knockdown or ectopic expression. We show that zeta-chain-associated protein kinase 70 regulates CCR7/CXCR4 via activation of extracellular signal-regulated kinases. High expression of zeta-chain-associated protein kinase 70 in acute lymphoblastic leukemia cells resulted in a higher proportion of central nervous system leukemia in xenografts as compared to zeta-chain-associated protein kinase 70 low expressing counterparts. High zeta-chain-associated protein kinase 70 also enhanced the migration potential towards CCL19/CXCL12 gradients in vitro CCR7 blockade almost abrogated homing of acute lymphoblastic leukemia cells to the central nervous system in xenografts. In 130 B-cell precursor acute lymphoblastic leukemia and 117 T-cell acute lymphoblastic leukemia patients, zeta-chain-associated protein kinase 70 and CCR7/CXCR4 expression levels were significantly correlated. Zeta-chain-associated protein kinase 70 expression correlated with central nervous system disease in B-cell precursor acute lymphoblastic leukemia, and CCR7/CXCR4 correlated with central nervous system involvement in T-cell acute lymphoblastic leukemia patients. In multivariate analysis, zeta-chain-associated protein kinase 70 expression levels in the upper third and fourth quartiles were associated with central nervous system involvement in B-cell precursor acute lymphoblastic leukemia (odds ratio=7.48, 95% confidence interval, 2.06-27.17; odds ratio=6.86, 95% confidence interval, 1.86-25.26, respectively). CCR7 expression in the upper fourth quartile correlated with central

  10. Textural characteristics of bone marrow blast nucleus images with different variants of acute lymphoblastic leukemia

    Science.gov (United States)

    Nikitaev, V. G.; Pronichev, A. N.; Polyakov, E. V.; Mozhenkova, A. V.; Tupitsin, N. N.; Frenkel, M. A.

    2018-01-01

    The paper describes the method of recognition of T - and B - variants of acute lymphoblastic leukemia in microscopic images of blood cells. The method is based on the use of texture characteristics of images. Experimental recognition accuracy evaluation is obtained from the sample of 38 patients (17 with T-ALL and 21 with B-ALL variants of acute lymphoblastic leukemia). The obtained results show the possibility of applying of the proposed approach to the differential diagnosis of T- and B- variants of acute lymphoblastic leukemia.

  11. Influence of Methylenetetrahydrofolate Reductase C677T, A1298C, and G80A Polymorphisms on the Survival of Pediatric Patients with Acute Lymphoblastic Leukemia

    Directory of Open Access Journals (Sweden)

    Dayse Maria Vasconcelos de Deus

    2012-01-01

    Full Text Available The influence of genic polymorphisms involved in metabolism of chemotherapeutic agents as the methotrexate (MTX has been studied mainly in acute lymphoblastic leukemia (ALL of childhood. Advances in treatment may be attributed to identification of prognostic factors added to chemotherapy protocol. The aim of this study was to analyze the association of the C677T, A1298C, and G80A polymorphisms on MTHFR gene and on the overall survival of pediatric patients (n=126 with lymphoblastic leukemia treated with MTX according to the Brazilian protocol in 187 months. The C677T and G80A polymorphisms were genotyped by PCR-RFLP and A1298C polymorphism by allele-specific PCR. We observed that ALL patients presented rate (dead/alive of 0.36 for the 677CC genotype, corresponding also to lower overall survival (P=0.0013; on the other hand, the 677TT genotype showed a better survival (98%. Thus, we believe that patients with 80AA genotype presented a small reduction in MTX plasma level, suggesting that ALL children, carrying the 80AA genotype, showed a high toxicity to MTX (P<0.0001.

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

    Directory of Open Access Journals (Sweden)

    Mina Islambulchilar

    2015-03-01

    Full Text Available Purpose: The purpose of our study was to evaluate the effect of oral taurine on the incidence of febrile episodes during chemotherapy in young adults with acute lymphoblastic leukemia. Methods: Forty young adults with acute lymphoblastic leukemia, at the beginning of maintenance course of their chemotherapy, were eligible for this study. The study population was randomized in a double blind manner to receive either taurine or placebo (2 gram per day orally. Life quality and side effects including febrile episodes were assessed using questionnaire. Data were analyzed using Pearson’s Chi square test. Results: Of total forty participants, 43.8% were female and 56.3 % were male. The mean age was 19.16±1.95 years (ranges: 16-23 years. The results indicated that the levels of white blood cells are significantly (P<0.05 increased in taurine treated group. There was no elevation in blasts count. A total of 70 febrile episodes were observed during study, febrile episodes were significantly (P<0.05 lower in taurine patients in comparison to the control ones. Conclusion: The overall incidence of febrile episodes and infectious complications in acute lymphoblastic leukemia patients receiving taurine was lower than placebo group. Taurine’s ability to increase leukocyte count may result in lower febrile episodes.

  13. Leucemia congénita aguda Acute congenital leukemia

    Directory of Open Access Journals (Sweden)

    Nilvia Esther González García

    2011-06-01

    Full Text Available La leucemia aguda durante el período neonatal es poco frecuente de evolución rápida y pronóstico sombrío. Sus características clínicas y biológicas difieren de las encontradas en niños de mayor edad, y su inicio se caracteriza por afectación cutánea, hepatoesplenomegalia, hiperleucocitosis e infiltración del sistema nervioso central. Se han observado pacientes con formas tanto mieloides como linfoides, pero la leucemia mieloide aguda parece predominar en esta etapa de la vida. Se presenta el caso de un paciente con leucemia congénita clasificada morfológicamente, con aparición de manifestaciones clínicas de enfermedad hematológica desde el nacimiento y diagnóstico de leucemia linfoblástica aguda congénita.Acute leukemia during neonatal period is not frequent, of a fast course and gloomy prognosis. Its clinical and biological features differ of that present in older children and it onset is characterized by cutaneous affection, hepatosplenomegaly, hyperleukocytosis and infiltration of central nervous system (CNS. There are patients presenting with myeloid and lymphoid types, but the acute leukemia seems to predominate in this stage of life. This is the case of a patient with acute leukemia morphologically classified, with appearance of clinical manifestations of hematologic disease from birth and a diagnosis of congenital acute lymphoblastic leukemia.

  14. [Local involvement of the optic nerve by acute lymphoblastic leukemia].

    Science.gov (United States)

    Bernardczyk-Meller, Jadwiga; Stefańska, Katarzyna

    2005-01-01

    The leucemias quite commonly involve the eyes and adnexa. In some cases it causes visual complants. Both, the anterior chamber of the eye and the posterior portion of the globe may sites of acute or chronic leukemia and leucemic relapse. We report an unique case of a 14 years old leucemic patient who suffered visual loss and papilloedema, due to a unilateral local involvement within optic nerve, during second relapse of acute lymphocytic leuemia. In spite of typical treatment of main disease, the boy had died. The authors present typical ophthalmic features of the leucemia, too.

  15. ACUTE MYELOGENOUS LEUKEMIA PRESENTING WITH ABRUPT ONSET LEUKEMIA CUTIS IN A YOUNG BOY: A RARE CASE REPORT

    Directory of Open Access Journals (Sweden)

    Lohit Kumar

    2015-05-01

    Full Text Available We report an 25 - year - old young male patient who presented with sudden onset multiple generalized skin lesions of dusky erythematous plaques of various size and shape all over the body which tends to bleed on rubbing. Histological evaluation revealed leukemia cutis wit h underlying atypical infiltrate contained atypical myeloid forms consistent with acute myelogenous leukemia (AML. His skin biopsy provided the first evidence of progression to AML. AML presenting with sudden onset leukemia cutis in a young boy is an extr emely rare entity

  16. Method of automating of the separation of blasts and lymphocytes in the diagnosis of acute myeloid leukemia

    Science.gov (United States)

    Blindar, V. N.; Nikitaev, V. G.; Polyakov, E. V.; Matveeva, I. I.

    2017-01-01

    The work deals with the separation of the lymphocytes of healthy patients from blasts of patients with acute myeloblastic leukemia (different variants of the disease). In this study the evaluation of textural characteristics has been done for nuclei of blood cells for cells classification and for the determination of a variant of acute myeloblastic leukemia.

  17. Overexpression of Rac1 in leukemia patients and its role in leukemia cell migration and growth

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Jiying [State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 288 Nanjing Road, Tianjin 300020 (China); Rao, Qing, E-mail: raoqing@gmail.com [State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 288 Nanjing Road, Tianjin 300020 (China); Wang, Min; Wei, Hui; Xing, Haiyan; Liu, Hang; Wang, Yanzhong; Tang, Kejing; Peng, Leiwen; Tian, Zheng; Wang, Jianxiang [State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 288 Nanjing Road, Tianjin 300020 (China)

    2009-09-04

    Rac1 belongs to the Rho family that act as critical mediators of signaling pathways controlling cell migration and proliferation and contributes to the interactions of hematopoietic stem cells with their microenvironment. Alteration of Rac1 might result in unbalanced interactions and ultimately lead to leukemogenesis. In this study, we analyze the expression of Rac1 protein in leukemia patients and determine its role in the abnormal behaviours of leukemic cells. Rac1 protein is overexpressed in primary acute myeloid leukemia cells as compared to normal bone marrow mononuclear cells. siRNA-mediated silencing of Rac1 in leukemia cell lines induced inhibition of cell migration, proliferation, and colony formation. Additionally, blocking Rac1 activity by an inhibitor of Rac1-GTPase, NSC23766, suppressed cell migration and growth. We conclude that overexpression of Rac1 contributes to the accelerated migration and high proliferation potential of leukemia cells, which could be implicated in leukemia development and progression.

  18. Overexpression of Rac1 in leukemia patients and its role in leukemia cell migration and growth

    International Nuclear Information System (INIS)

    Wang, Jiying; Rao, Qing; Wang, Min; Wei, Hui; Xing, Haiyan; Liu, Hang; Wang, Yanzhong; Tang, Kejing; Peng, Leiwen; Tian, Zheng; Wang, Jianxiang

    2009-01-01

    Rac1 belongs to the Rho family that act as critical mediators of signaling pathways controlling cell migration and proliferation and contributes to the interactions of hematopoietic stem cells with their microenvironment. Alteration of Rac1 might result in unbalanced interactions and ultimately lead to leukemogenesis. In this study, we analyze the expression of Rac1 protein in leukemia patients and determine its role in the abnormal behaviours of leukemic cells. Rac1 protein is overexpressed in primary acute myeloid leukemia cells as compared to normal bone marrow mononuclear cells. siRNA-mediated silencing of Rac1 in leukemia cell lines induced inhibition of cell migration, proliferation, and colony formation. Additionally, blocking Rac1 activity by an inhibitor of Rac1-GTPase, NSC23766, suppressed cell migration and growth. We conclude that overexpression of Rac1 contributes to the accelerated migration and high proliferation potential of leukemia cells, which could be implicated in leukemia development and progression.

  19. The value of the MDR1 reversal agent PSC-833 in addition to daunorubicin and cytarabine in the treatment of elderly patients with previously untreated acute myeloid leukemia (AML), in relation to MDR1 status at diagnosis

    NARCIS (Netherlands)

    B. van der Holt (Bronno); B. Löwenberg (Bob); A.K. Burnett (Alan); W.U. Knauf; J. Shepherd (John); P.P. Piccaluga; G.J. Ossenkoppele (Gert); G.E.G. Verhoef (Gregor); A. Ferrant (Augustin); M. Crump; D. Selleslag; M. Theobald (Matthias); M. Fey (Martin); E. Vellenga (Edo); M. Dugan; P. Sonneveld (Pieter)

    2005-01-01

    textabstractTo determine whether MDR1 reversal by the addition of the P-glycoprotein (P-gp) inhibitor PSC-833 to standard induction chemotherapy would improve event-free survival (EFS), 419 untreated patients with acute myeloid leukemia (AML) aged 60 years and older were randomized to receive 2

  20. Systematic screening at diagnosis of -5/del(5)(q31), -7, or chromosome 8 aneuploidy by interphase fluorescence in situ hybridization in 110 acute myelocytic leukemia and high-risk myelodysplastic syndrome patients: concordances and discrepancies with conventional cytogenetics.

    NARCIS (Netherlands)

    Beyer, V.; Castagne, C.; Muhlematter, D.; Parlier, V.; Gmur, J.; Hess, U.; Kovacsovics, T.; Meyer-Monard, S.; Tichelli, A.; Tobler, A.; Jacky, E.; Schanz, U.; Bargetzi, M.; Hagemeijer, A.; Witte, T.J.M. de; Melle, G. van; Jotterand-Bellomo, M.

    2004-01-01

    To assess the contribution of interphase fluorescence in situ hybridization (I-FISH) toward the detection of recurring unbalanced chromosomal anomalies at diagnosis, a systematic screening of -5/del(5)(q31), -7, and chromosome 8 aneuploidy was performed on 110 patients with acute myelocytic leukemia

  1. Use of glycosylated recombinant human G-CSF (lenograstim) during and/or after induction chemotherapy in patients 61 years of age and older with acute myeloid leukemia: final results of AML-13, a randomized phase-3 study.

    NARCIS (Netherlands)

    Amadori, S.; Suciu, S.; Jehn, U.; Stasi, R.; Thomas, X.; Marie, J.P.; Muus, P.; Lefrere, F.; Berneman, Z.; Fillet, G.; Denzlinger, C.; Willemze, R.; Leoni, P.; Leone, G.; Casini, M.; Ricciuti, F.; Vignetti, M.; Beeldens, F.; Mandelli, F.; Witte, T.J.M. de

    2005-01-01

    The role of glycosylated recombinant human granulocyte colony-stimulating factor (G-CSF) in the induction treatment of older adults with acute myeloid leukemia (AML) is still uncertain. In this trial, a total of 722 patients with newly diagnosed AML, median age 68 years, were randomized into 4

  2. An advanced preclinical mouse model for acute myeloid leukemia using patients' cells of various genetic subgroups and in vivo bioluminescence imaging.

    Directory of Open Access Journals (Sweden)

    Binje Vick

    Full Text Available Acute myeloid leukemia (AML is a clinically and molecularly heterogeneous disease with poor outcome. Adequate model systems are required for preclinical studies to improve understanding of AML biology and to develop novel, rational treatment approaches. Xenografts in immunodeficient mice allow performing functional studies on patient-derived AML cells. We have established an improved model system that integrates serial retransplantation of patient-derived xenograft (PDX cells in mice, genetic manipulation by lentiviral transduction, and essential quality controls by immunophenotyping and targeted resequencing of driver genes. 17/29 samples showed primary engraftment, 10/17 samples could be retransplanted and some of them allowed virtually indefinite serial transplantation. 5/6 samples were successfully transduced using lentiviruses. Neither serial transplantation nor genetic engineering markedly altered sample characteristics analyzed. Transgene expression was stable in PDX AML cells. Example given, recombinant luciferase enabled bioluminescence in vivo imaging and highly sensitive and reliable disease monitoring; imaging visualized minimal disease at 1 PDX cell in 10000 mouse bone marrow cells and facilitated quantifying leukemia initiating cells. We conclude that serial expansion, genetic engineering and imaging represent valuable tools to improve the individualized xenograft mouse model of AML. Prospectively, these advancements enable repetitive, clinically relevant studies on AML biology and preclinical treatment trials on genetically defined and heterogeneous subgroups.

  3. Population PK/PD model of homocysteine concentrations after high-dose methotrexate treatment in patients with acute lymphoblastic leukemia.

    Directory of Open Access Journals (Sweden)

    Hauke Rühs

    Full Text Available Elevated homocysteine concentrations have been associated with methotrexate-induced neurotoxicity. Based on methotrexate and homocysteine plasma concentrations of 494 children with acute lymphoblastic leukemia treated with high-dose methotrexate in the TOTAL XV study, a pharmacokinetic/pharmacodynamic (PK/PD model was built with NONMEM. Several compartment and indirect response models were investigated. The pharmacokinetic disposition of methotrexate was best described by a two-compartment model. Homocysteine concentrations were included by an indirect response model where methotrexate inhibition of the homocysteine elimination rate was described by an E(max model. The homocysteine baseline level was found to be age-dependent. Simulations revealed that folinate rescue therapy does not affect peak concentrations of homocysteine but leads to a modestly reduced homocysteine exposure. In conclusion, our PK/PD model describes the increase of methotrexate-induced HCY concentrations with satisfactory precision and can be applied to assess the effect of folinate regimens on the HCY concentration-time course.

  4. Epigenetic Modifications in Pediatric Acute Lymphoblastic Leukemia

    Directory of Open Access Journals (Sweden)

    Michael James Burke

    2014-05-01

    Full Text Available Aberrant epigenetic modifications are well-recognized drivers for oncogenesis. Pediatric acute lymphoblastic leukemia (ALL is no exception and serves as a model toward the significant impact these heritable alterations can have in leukemogenesis. In this brief review, we will focus on the main aspects of epigenetics which control leukemogenesis in pediatric ALL, mainly DNA methylation, histone modification and microRNA alterations. As we continue to gain better understanding of the driving mechanisms for pediatric ALL at both diagnosis and relapse, therapeutic interventions directed toward these pathways and mechanisms can be harnessed and introduced into clinical trials for pediatric ALL.

  5. Two-Stage Priming of Allogeneic Natural Killer Cells for the Treatment of Patients with Acute Myeloid Leukemia: A Phase I Trial.

    Directory of Open Access Journals (Sweden)

    Panagiotis D Kottaridis

    Full Text Available Human Natural Killer (NK cells require at least two signals to trigger tumor cell lysis. Absence of ligands providing either signal 1 or 2 provides NK resistance. We manufactured a lysate of a tumour cell line which provides signal 1 to resting NK cells without signal 2. The tumor-primed NK cells (TpNK lyse NK resistant Acute Myeloid Leukemia (AML blasts expressing signal 2 ligands. We conducted a clinical trial to determine the toxicity of TpNK cell infusions from haploidentical donors. 15 patients with high risk AML were screened, 13 enrolled and 7 patients treated. The remaining 6 either failed to respond to re-induction chemotherapy or the donor refused to undergo peripheral blood apheresis. The conditioning consisted of fludarabine and total body irradiation. This was the first UK trial of a cell therapy regulated as a medicine. The complexity of Good Clinical Practice compliance was underestimated and led to failures requiring retrospective independent data review. The lessons learned are an important aspect of this report. There was no evidence of infusional toxicity. Profound myelosuppression was seen in the majority (median neutrophil recovery day 55. At six months follow-up, three patients treated in Complete Remission (CR remained in remission, one patient infused in Partial Remission had achieved CR1, two had relapsed and one had died. One year post-treatment one patient remained in CR. Four patients remained in CR after treatment for longer than their most recent previous CR. During the 2 year follow-up six of seven patients died; median overall survival was 400 days post infusion (range 141–910. This is the first clinical trial of an NK therapy in the absence of IL-2 or other cytokine support. The HLA-mismatched NK cells survived and expanded in vivo without on-going host immunosuppression and appeared to exert an anti-leukemia effect in 4/7 patients treated.ISRCTN trial registry ISRCTN11950134.

  6. Characterization of the CDR3 structure of the Vβ21 T cell clone in patients with P210(BCR-ABL)-positive chronic myeloid leukemia and B-cell acute lymphoblastic leukemia.

    Science.gov (United States)

    Zha, Xianfeng; Chen, Shaohua; Yang, Lijian; Li, Bo; Chen, Yu; Yan, Xiaojuan; Li, Yangqiu

    2011-10-01

    The clonally expanded T cells identified in most cancer patients that respond to tumor-associated antigen such as P210(BCR-ABL) protein have definite, specific antitumor cytotoxicity. T cell receptor (TCR) Vβ CDR3 repertoire diversity was analyzed in patients with chronic myeloid leukemia (CML) and BCR-ABL(+) B-cell acute lymphoblastic leukemia (B-ALL) by GeneScan. A high frequency of oligoclonal expansion of the TCR Vβ21 subfamily was observed in the peripheral blood of CML and B-ALL patients. These clonally expanded Vβ21 T cells were correlated with the pathophysiologic process of CML. A conserved amino acid motif (SLxxV) was observed within the CDR3 region in only 3 patients with CML. Preferential usage of the Jβ segments was also observed in a minority of patients. The 3-dimensional structures of the CDR3 region containing the same motif or using the same Jβ segment displayed low similarity; on the contrary, the conformation of the CDR3 region containing no conserved motif in some T cell clones was highly similar. In conclusion, our findings indicate a high frequency of TCR Vβ21 subfamily expansion in p210(BCR-ABL)-positive CML and B-ALL patients. The characterization of the CDR3 structure was complex. Regrettably, at this time it was not possible to confirm that the Vβ21 T cell clones were derived from the stimulation of p210(BCR-ABL) protein. Copyright © 2011 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.

  7. Epigenetic analysis of childhood acute lymphoblastic leukemia.

    Science.gov (United States)

    Dunwell, Thomas L; Hesson, Luke B; Pavlova, Tatiana; Zabarovska, Veronika; Kashuba, Vladimir; Catchpoole, Daniel; Chiaramonte, Raffaella; Brini, Anna T; Griffiths, Mike; Maher, Eamonn R; Zabarovsky, Eugene; Latif, Farida

    2009-04-01

    We used a chromosome 3 wide NotI microarray for identification of epigenetically inactivated genes in childhood acute lymphoblastic leukemia (ALL). Three novel genes demonstrated frequent methylation in childhood ALL. PPP2R3A (protein phosphatase 2, regulatory subunit B", alpha) was frequently methylated in T (69%) and B (82%)-ALL. Whilst FBLN2 (fibulin 2) and THRB (thyroid hormone receptor, beta) showed frequent methylation in B-ALL (58%; 56% respectively), but were less frequently methylated in T-ALL (17% for both genes). Recently it was demonstrated that BNC1 (Basonuclin 1) and MSX1 (msh homeobox 1) were frequently methylated across common epithelial cancers. In our series of childhood ALL BNC1 was frequently methylated in both T (77%) and B-ALL (79%), whilst MSX1 showed T-ALL (25%) specific methylation. The methylation of the above five genes was cancer specific and expression of the genes could be restored in methylated leukemia cell lines treated with 5-aza-2'-deoxycytidine. This is the first report demonstrating frequent epigenetic inactivation of PPP2R3A, FBLN2, THRB, BNC1 and MSX1 in leukemia. The identification of frequently methylated genes showing cancer specific methylation will be useful in developing early cancer detection screens and for targeted epigenetic therapies.

  8. Epidemiologic study on survival of chronic myeloid leukemia and Ph(+) acute lymphoblastic leukemia patients with BCR-ABL T315I mutation

    DEFF Research Database (Denmark)

    Nicolini, Franck E; Mauro, Michael J; Martinelli, Giovanni

    2009-01-01

    The BCR-ABL T315I mutation represents a major mechanism of resistance to tyrosine kinase inhibitors (TKIs). The objectives of this retrospective observational study were to estimate overall and progression-free survival for chronic myeloid leukemia in chronic-phase (CP), accelerated-phase (AP...

  9. Leukemia

    International Nuclear Information System (INIS)

    Mabuchi, Kiyohiko; Kusumi, Shizuyo

    1992-01-01

    Leukemia is the first malignant disease found among A-bomb survivors. Leukemia registration has greatly contributed to epidemiological and hematological studies on A-bomb radiation-related leukemia and other hematopoietic diseases, consisting of community population and the RERF Life Span Study (LSS) sample (approximately 120,000 persons containing A-bomb survivors). Using the fixed LSS cohort, the prevalence rate of leukemia reached the peak during the years 1950-1954, and thereafter, it has been gradually decreased. However, risk patterns for leukemia are still unsolved: has leukemia risk increased in recent years?; are serial changes in leukemia risk influenced by age at the time of exposure (ATE)?; is there variation between Hiroshima and Nagasaki?; and others. To solve these questions, leukemia data are now under analysis using the revised DS86. Relative risk for leukemia, especially chronic myelogenous leukemia and acute lymphocytic leukemia (ALL), is found to be linearly increased with increasing bone marrow doses. Serial patterns of both excess risk and excess relative risk have revealed that leukemia risk is high at 5-10 years after A-bombing in younger A-bomb survivors ATE. The influence of age ATE on serial changes is noticeable in ALL. Another factor involved in the prevalence of leukemia is background (spontaneously developed leukemia), which is the recent interest because young A-bomb survivors ATE reach the cancer-prone age. (N.K.)

  10. Construction of protein profile classification model and screening of proteomic signature of acute leukemia

    OpenAIRE

    Xu, Yun; Zhuo, Jiacai; Duan, Yonggang; Shi, Benhang; Chen, Xuhong; Zhang, Xiaoli; Xiao, Liang; Lou, Jin; Huang, Ruihong; Zhang, Qiongli; Du, Xin; Li, Ming; Wang, Daping; Shi, Dunyun

    2014-01-01

    The French-American-British (FAB) and WHO classifications provide important guidelines for the diagnosis, treatment, and prognostic prediction of acute leukemia, but are incapable of accurately differentiating all subtypes, and not well correlated with the clinical outcomes. In this study, we performed the protein profiling of the bone marrow mononuclear cells from the patients with acute leukemia and the health volunteers (control) by surface enhanced laser desorption/ionization-time of flig...

  11. Association between the methylation status of theMGMTpromoter in bone marrow specimens and chemotherapy outcomes of patients with acute myeloid leukemia.

    Science.gov (United States)

    Hong, Qingxiao; Chen, Xiaoying; Ye, Huadan; Zhou, Annan; Gao, Yuting; Jiang, Danjie; Wu, Xiaodong; Tian, Bingru; Chen, Youfen; Wang, Ming; Xie, Jiping; Xia, Yongming; Duan, Shiwei

    2016-04-01

    The O(6)-methylguanine-DNA methyltransferase (MGMT ) gene is a tumor suppressor gene that is associated with the risk of developing acute myeloid leukemia (AML). However, the association between the methylation status of the MGMT promoter and the chemotherapeutic outcomes of patients with AML remains unknown. In the present study, 30 bone marrow samples derived from patients with AML were collected prior and subsequent to chemotherapy. The methylation status of the MGMT promoter in the bone marrow specimens was determined by methylation-specific polymerase chain reaction. The results indicated that the methylation status of the MGMT promoter was influenced by different chemotherapeutic regimens. The MGMT methylation status of M4 patients (3 out of 6) were more chemosensitive, compared with that of patients with other AML subtypes (M1, 1 out of 3; M2, 0 out of 8; M3, 3 out of 7; M5, 0 out of 3; and M6, 1 out of 3). Age-based analysis revealed that the group aged ≤60 years (7 out of 24 patients) exhibited more methylation changes than patients aged >60 years (1 out of 6). Male patients (4 out of 13) were more susceptible to chemotherapy-induced methylation changes than female patients (4 out of 17). Thus, the methylation status of the MGMT promoter may serve as a potential biomarker to predict the therapeutic outcomes in male AML patients. However, further studies in larger sample sets are required to confirm the present findings.

  12. Outcome of patients with relapsed/refractory acute lymphoblastic leukemia after blinatumomab failure: No change in the level of CD19 expression.

    Science.gov (United States)

    Jabbour, Elias; Düll, Johannes; Yilmaz, Musa; Khoury, Joseph D; Ravandi, Farhad; Jain, Nitin; Einsele, Hermann; Garcia-Manero, Guillermo; Konopleva, Marina; Short, Nicholas J; Thompson, Philip A; Wierda, William; Daver, Naval; Cortes, Jorge; O'brien, Susan; Kantarjian, Hagop; Topp, Max S

    2018-03-01

    Blinatumomab, a bi-specific T-cell engaging CD3-CD19 antibody construct, has shown significant activity in patients with relapsed/refractory (R/R) B-cell acute lymphoblastic leukemia (ALL). Despite this improvement, most patients relapse. Here, we describe the outcome of 68 patients with R/R ALL after failure of blinatumomab therapy: 38 (56%) blinatumomab refractory; 30 (44%) relapsing after initial response. After a median follow-up of 49 months, 9 (13%) patients remained alive. The median overall survival after blinatumomab failure was 5.2 months. At the time of failure, among 61 patients evaluated for immunophenotype, 56 (92%) had CD19-positive blasts; only five (8%) had ALL recurrence with CD19-negative disease. Two patients progressed with lower CD19 expression. In summary, the outcome of patients with R/R ALL after blinatumomab failure is poor and treatment of these patients remains an unmet medical need. Our findings indicate that blinatumomab therapy would not exclude a significant number of patients from the potential benefit of subsequent CD19-directed therapies such as chimeric antigen receptor T-cell therapy. © 2017 Wiley Periodicals, Inc.

  13. Leukemia-Initiating Cells in T-Cell Acute Lymphoblastic Leukemia

    OpenAIRE

    Tan, Shi Hao; Bertulfo, Fatima Carla; Sanda, Takaomi

    2017-01-01

    T-cell acute lymphoblastic leukemia (T-ALL) is a hematological malignancy characterized by the clonal proliferation of immature T-cell precursors. T-ALL has many similar pathophysiological features to acute myeloid leukemia, which has been extensively studied in the establishment of the cancer stem cell (CSC) theory, but the CSC concept in T-ALL is still debatable. Although leukemia-initiating cells (LICs), which can generate leukemia in a xenograft setting, have been found in both human T-AL...

  14. A phase I trial of vorinostat and alvocidib in patients with relapsed, refractory, or poor prognosis acute leukemia, or refractory anemia with excess blasts-2.

    Science.gov (United States)

    Holkova, Beata; Supko, Jeffrey G; Ames, Matthew M; Reid, Joel M; Shapiro, Geoffrey I; Perkins, Edward Brent; Ramakrishnan, Viswanathan; Tombes, Mary Beth; Honeycutt, Connie; McGovern, Renee M; Kmieciak, Maciej; Shrader, Ellen; Wellons, Martha D; Sankala, Heidi; Doyle, Austin; Wright, John; Roberts, John D; Grant, Steven

    2013-04-01

    This phase I study was conducted to identify the maximum-tolerated dose (MTD) of alvocidib when combined with vorinostat in patients with relapsed, refractory, or poor prognosis acute leukemia, or refractory anemia with excess blasts-2. Secondary objectives included investigating the pharmacokinetic and pharmacodynamic effects of the combination. Patients received vorinostat (200 mg orally, three times a day, for 14 days) on a 21-day cycle, combined with 2 different alvocidib administration schedules: a 1-hour intravenous infusion, daily × 5; or a 30-minute loading infusion followed by a 4-hour maintenance infusion, weekly × 2. The alvocidib dose was escalated using a standard 3+3 design. Twenty-eight patients were enrolled and treated. The alvocidib MTD was 20 mg/m(2) (30-minute loading infusion) followed by 20 mg/m(2) (4-hour maintenance infusion) on days one and eight, in combination with vorinostat. The most frequently encountered toxicities were cytopenias, fatigue, hyperglycemia, hypokalemia, hypophosphatemia, and QT prolongation. Dose-limiting toxicities (DLT) were cardiac arrhythmia-atrial fibrillation and QT prolongation. No objective responses were achieved although 13 of 26 evaluable patients exhibited stable disease. Alvocidib seemed to alter vorinostat pharmacokinetics, whereas alvocidib pharmacokinetics were unaffected by vorinostat. Ex vivo exposure of leukemia cells to plasma obtained from patients after alvocidib treatment blocked vorinostat-mediated p21(CIP1) induction and downregulated Mcl-1 and p-RNA Pol II for some specimens, although parallel in vivo bone marrow responses were infrequent. Alvocidib combined with vorinostat is well tolerated. Although disease stabilization occurred in some heavily pretreated patients, objective responses were not obtained with these schedules. ©2013 AACR.

  15. [Acute unclassified leukemia with bone marrow necrosis].

    Science.gov (United States)

    Uoshima, N; Yamazaki, N; Iinuma, S; Kimura, S; Wada, K; Kobayashi, Y; Ozawa, M; Horiuchi, H; Maruo, N; Kondo, M

    1991-01-01

    Massive bone marrow necrosis was seen in a 42-year-old male with acute leukemia. In December, 1988, on admission, laboratory data revealed pancytopenia and a high level of serum LDH and ALKP. Bone marrow aspiration resulted in dry-tap and showed bone marrow necrosis in the bone marrow biopsy specimen. A bone marrow scintigraphy with 111In faintly visualized the bone marrow but visualized area was expanded in the extremities compared with normal subjects. The second bone marrow biopsy showed proliferation of blasts. In the middle of March, blasts began to appear in peripheral blood. The blasts were cytochemically negative for POX, Es, PAS, AcP, TdT and had surface markers CD3-, CD19-, CD33-, CD13-, LCA-, HLA-DR-. Even by investigation on rearrangement of the immunoglobulin heavy chain region, an origin of the blasts could not be determined. In April, the number of blasts in peripheral blood increased and hepatosplenomegaly developed rapidly. Therefore, he was put on the chemotherapy with vincristine and prednisolone, but he died of cerebral hemorrhage. The autopsy revealed widespread bone marrow necrosis. It has rarely been reported that massive bone marrow necrosis is found prior to the occurrence of acute unclassified leukemia.

  16. Nanomedicine approaches in acute lymphoblastic leukemia.

    Science.gov (United States)

    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. Copyright © 2016 Elsevier B.V. All rights reserved.

  17. A phase 2 study of MK-0457 in patients with BCR-ABL T315I mutant chronic myelogenous leukemia and philadelphia chromosome-positive acute lymphoblastic leukemia

    DEFF Research Database (Denmark)

    Seymour, J F; Kim, D W; Rubin, E

    2014-01-01

    leukemia (ALL) with the T315I mutation. Adults with Ph+ chronic phase (CP)-, accelerated phase (AP)- or blast phase (BP)-CML, or ALL and documented BCR-ABL T315I mutation were treated with a 5-day continuous infusion of MK-0457 administered every 14 days at 40 mg/m(2)/h, 32 mg/m(2)/h or 24 mg/m(2)/h. Fifty...

  18. Outcomes and changes in code status of patients with acute myeloid leukemia undergoing induction chemotherapy who were transferred to the intensive care unit.

    Science.gov (United States)

    Ahmed, Tamjeed; Koch, Abby L; Isom, Scott; Klepin, Heidi D; Bishop, Jonathan M; Ellis, Leslie R; Berenzon, Dmitriy; Howard, Dianna; Lyerly, Susan; Powell, Bayard L; Pardee, Timothy S

    2017-11-01

    Patients with Acute Myeloid Leukemia (AML) have compromised marrow function and chemotherapy causes further suppression. As a result complications are frequent, and patients may require admission to the intensive care unit (ICU). How codes status changes when these events occur and how those changes influence outcome are largely unknown. Outcomes for adult patients with AML, undergoing induction chemotherapy, and transferred to the ICU between January 2000 and December 2013 were analyzed. 94 patients were included. Median survival was 1.3 months. At 3 and 6 months overall survival (OS) was 27% and 18% respectively. Respiratory failure was the most common reason for transfer to ICU (88%), with 63% requiring mechanical ventilation at transfer. Other reasons included: cardiac arrest (18%), septic shock (17%), hypotension (9%), and acute renal failure (9%). The most frequent interventions were mechanical ventilation in 85%, vasopressors in 62%, and hemodialysis in 30%. Following transfer 55 patients (58%) had a change in code status. Overall, 46 patients (49%) changed from Full Code (FC) to Comfort Care (CC), 7 (7%) from FC to Do Not Resuscitate (DNR), and 2 (2%) from DNR to CC. For the entire cohort, ICU mortality (IM) was 61% and hospital mortality (HM) was 71%. For FC or DNR patients, IM was 30% and HM was 41%. For CC patients, IM was 90% and HM was 100%. Overall, 27 patients (29%) survived to discharge. Of those discharged, 22 (81%) were alive at 3 months and 17 (63%) were alive at 6 months. In conclusion, patients that required ICU admission during induction chemotherapy have a poor prognosis. Code status changed during the ICU stay for the majority of patients and always to a less aggressive status. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. Successful Administration of Recombinant Human Soluble Thrombomodulin α (Recomodulin for Disseminated Intravascular Coagulation during Induction Chemotherapy in an Elderly Patient with Acute Monoblastic Leukemia Involving the t(9;11(p22;q23 MLL/AF9 Translocation

    Directory of Open Access Journals (Sweden)

    Kazutaka Takagi

    2011-01-01

    Full Text Available Patients with acute myelogenous leukemia complicate with disseminated intravascular coagulation (DIC, not only at the time of the initially leukemia diagnosis, but also during induction chemotherapy. In Japan, recently, a recombinant human soluble thrombomodulin alpha (Recomodulin has been introduced as a new type of anti-DIC agent for clinical use in patients with hematological cancer or infectious disease. We describe a 67-year-old female case in which 25,600 units of Recomodulin for 6 days were successfully administered for both initially complicating and therapy-induced DIC without any troubles of bleeding in an acute monoblastic leukemia (AML-M5a patient with the MLL gene translocation. Furthermore, the levels of DIC biomarkers recovered rapidly after the Recomodulin treatment. Our case suggests that DIC control using Recomodulin is one of the crucial support-therapies during remission induction chemotherapy in patients with acute leukemia of which type tends to complicate extramedullary or extranodal infiltration having potential to onset DIC.

  20. Features of children temperament with acute lymphoblastic leukemia

    Directory of Open Access Journals (Sweden)

    N. A. Kornetov

    2013-01-01

    Full Text Available The temperament characteristics were studied in 86 children with acute lymphoblastic leukemia (ALL at the age of 3–16 years. Research was conducted using standardized and adapted to the Russian-speaking population of parental questionnaires for children of different age groups (Kolpakov V.G. et al., 1993. Statistically significant differences in temperament ALL patients from healthy children installed and feature of temperament, which is most often seen in children with conduct disorder are installed. The need for psychological and/or psychiatric counseling this category of patients is substantiated.

  1. Collagen XVIII Mutation in Knobloch Syndrome with Acute Lymphoblastic Leukemia

    Science.gov (United States)

    Mahajan, Vinit B.; Olney, Ann Haskins; Garrett, Penny; Chary, Ajit; Dragan, Ecaterina; Lerner, Gary; Murray, Jeffrey; Bassuk, Alexander G.

    2010-01-01

    Knobloch syndrome (KNO) is caused by mutations in the collagen XIII gene (COL18A1) and patients develop encephalocele and vitreoretinal degeneration. Here we report an El Salvadorian family where two sisters showed features of KNO. One of the siblings also developed acute lymphoblastic leukemia. DNA sequencing of COL18A1revealed a homozygous, 2-base pair deletion (c3514-3515delCT) in exon 41, which leads to abnormal collagen XVIII and deficiency of its proteolytic cleavage product endostatin. KNO patients with mutations in COL18A1 may be at risk for endostatin-related conditions including malignancy. PMID:20799329

  2. Total body irradiation in a patient with fragile X syndrome for acute lymphoblastic leukemia in preparation for stem cell transplantation: A case report and literature review.

    Science.gov (United States)

    Collins, D T; Mannina, E M; Mendonca, M

    2015-10-01

    Fragile X syndrome (FXS) is a congenital disorder caused by expansion of CGG trinucleotide repeat at the 5' end of the fragile X mental retardation gene 1 (FMR1) on the X chromosome that leads to chromosomal instability and diminished serum levels of fragile X mental retardation protein (FMRP). Afflicted individuals often have elongated features, marfanoid habitus, macroorchidism and intellectual impairment. Evolving literature suggests the condition may actually protect from malignancy while chromosomal instability would presumably elevate the risk. Increased sensitivity to ionizing radiation should also be predicted by unstable sites within the DNA. Interestingly, in this report, we detail a patient with FXS diagnosed with acute lymphoblastic leukemia treated with induction followed by subsequent cycles of hyper-CVAD (cyclophosphamide, vincristine, doxorubicin, dexamethasone) with a complete response who then was recommended to undergo peripheral stem cell transplantation. The patient underwent total body irradiation (TBI) as a component of his conditioning regimen and despite the concern of his clinicians, developed minimal acute toxicity and successful engraftment. The pertinent literature regarding irradiation of patients with FXS is also reviewed. © 2015 Wiley Periodicals, Inc.

  3. Prognostic significance of complex karyotype and monosomal karyotype in adult patients with acute lymphoblastic leukemia treated with risk-adapted protocols.

    Science.gov (United States)

    Motlló, Cristina; Ribera, Josep-María; Morgades, Mireia; Granada, Isabel; Montesinos, Pau; González-Campos, José; Fernández-Abellán, Pascual; Tormo, Mar; Bethencourt, Concepción; Brunet, Salut; Hernández-Rivas, Jesús-María; Moreno, María-José; Sarrà, Josep; Del Potro, Eloy; Barba, Pere; Bernal, Teresa; Grande, Carlos; Grau, Javier; Cervera, José; Feliu, Evarist

    2014-12-15

    The karyotype is a predictor of outcomes in adults with acute lymphoblastic leukemia (ALL). The unfavorable prognostic significance of complex karyotype (CK) has been reported, whereas the prognostic relevance of monosomal karyotype (MK) has not been consistently evaluated. We aimed to assess the prognostic value of CK and MK in adults with ALL treated with risk-adapted protocols of the Spanish PETHEMA Group. The karyotypes of 881 adult ALL patients treated according to the protocols of the PETHEMA Group between 1993 and 2012 were centrally reviewed. CK and MK were assessed according to Moorman's criteria, and Breem's criteria, respectively. Specific analyses according to the risk groups and to the presence of t(9:22) were performed. Of 364 evaluable patients 33 (9.2%) had CK, and 68 of 535 evaluable patients (12.8%) had MK. Complete remission rate, remission duration, and overall survival were not significantly different according to the presence of CK or MK in the whole series, according to the B or T lineage, in the high-risk group, or in patients with t(9;22), regardless of imatinib treatment, and in patients who received chemotherapy alone or chemotherapy followed by stem cell transplantation Our study shows that CK and MK were not associated with a worse prognosis in adult patients with ALL treated with risk-adapted or subtype-oriented protocols. In patients with Ph+ ALL, MK did not have an impact on prognosis irrespective of imatinib treatment. © 2014 American Cancer Society.

  4. Correlation of the microculture-kinetic drug-induced apoptosis assay with patient outcomes in initial treatment of adult acute myelocytic leukemia.

    Science.gov (United States)

    Strickland, Stephen A; Raptis, Anastasios; Hallquist, Allan; Rutledge, James; Chernick, Michael; Perree, Mathieu; Talbott, Mahsa S; Presant, Cary A

    2013-03-01

    Overall survival (OS) with acute myeloid leukemia (AML) remains poor. Determining prognostic factors will help in selecting patients for appropriate treatments. Our aim was to determine whether the level of drug-induced apoptosis (chemosensitivity) demonstrated by the microculture-kinetic drug-induced apoptosis (MiCK) assay significantly predicted outcomes after standard AML induction therapy. A total of 109 patients with untreated AML had blood and/or bone marrow aspirate samples analyzed for anthracycline-induced apoptosis using the MiCK assay. The amount of apoptosis observed over 48 h was determined and expressed as kinetic units of apoptosis (KU). Complete remission (CR) was significantly higher (72%) in patients with high idarubicin-induced apoptosis >3 KU compared to patients with apoptosis ≤ 3 KU (p = 0.01). Multivariate analysis showed the only significant variables to be idarubicin-induced apoptosis and karyotype. Median overall survival of patients with idarubicin-induced apoptosis >3 KU was 16.1 months compared to 4.5 months in patients with apoptosis ≤ 3 KU (p = 0.004). Multivariate analysis showed the only significant variable to be idarubicin-induced apoptosis. Chemotherapy-induced apoptosis measured by the MiCK assay demonstrated significant correlation with outcomes and appears predictive of complete remission and overall survival for patients receiving standard induction chemotherapy.

  5. Identification of a subset of patients with acute myeloid leukemia characterized by long-term in vitro proliferation and altered cell cycle regulation of the leukemic cells.

    Science.gov (United States)

    Hatfield, Kimberley Joanne; Reikvam, Håkon; Bruserud, Øystein

    2014-11-01

    The malignant cell population of acute myeloid leukemia (AML) includes a small population of stem/progenitor cells with long-term in vitro proliferation. We wanted to compare long-term AML cell proliferation for unselected patients, investigate the influence of endothelial cells on AML cell proliferation and identify biological characteristics associated with clonogenic capacity. Cells were cultured in medium supplemented with recombinant growth factors FMS-like tyrosine kinase-3 ligand, stem cell factor, IL-3, G-CSF and thrombopoietin. The colony-forming unit assay was used to estimate the number of progenitors in AML cell populations after 35 days of culture, and microarray was used to study global gene expression profiles between AML patients. Long-term cell proliferation was observed in 7 of 31 patients, whereas 3 additional patients showed long-term proliferation after endothelial cell coculture. Patient-specific differences in constitutive cytokine release were maintained during cell culture. Patients with long-term proliferation showed altered expression in six cell cycle-related genes (HMMR, BUB1, NUSAP1, AURKB, CCNF, DLGAP5), two genes involved in DNA replication (TOP2A, RFC3) and one gene with unknown function (LHFPL2). We identified a subset of AML patients characterized by long-term in vitro cell proliferation and altered expression of cell cycle regulators that may be potential candidates for treatment of AML.

  6. TP53 mutations in de novo acute myeloid leukemia patients: longitudinal follow-ups show the mutation is stable during disease evolution.

    Science.gov (United States)

    Hou, H-A; Chou, W-C; Kuo, Y-Y; Liu, C-Y; Lin, L-I; Tseng, M-H; Chiang, Y-C; Liu, M-C; Liu, C-W; Tang, J-L; Yao, M; Li, C-C; Huang, S-Y; Ko, B-S; Hsu, S-C; Chen, C-Y; Lin, C-T; Wu, S-J; Tsay, W; Chen, Y-C; Tien, H-F

    2015-07-31

    The TP53 mutation is frequently detected in acute myeloid leukemia (AML) patients with complex karyotype (CK), but the stability of this mutation during the clinical course remains unclear. In this study, TP53 mutations were identified in 7% of 500 patients with de novo AML and 58.8% of patients with CK. TP53 mutations were closely associated with older age, lower white blood cell (WBC) and platelet counts, FAB M6 subtype, unfavorable-risk cytogenetics and CK, but negatively associated with NPM1 mutation, FLT3/ITD and DNMT3A mutation. Multivariate analysis demonstrated that TP53 mutation was an independent poor prognostic factor for overall survival and disease-free survival among the total cohort and the subgroup of patients with CK. A scoring system incorporating TP53 mutation and nine other prognostic factors, including age, WBC counts, cytogenetics and gene mutations, into survival analysis proved to be very useful to stratify AML patients. Sequential study of 420 samples showed that TP53 mutations were stable during AML evolution, whereas the mutation was acquired only in 1 of the 126 TP53 wild-type patients when therapy-related AML originated from different clone emerged. In conclusion, TP53 mutations are associated with distinct clinic-biological features and poor prognosis in de novo AML patients and are rather stable during disease progression.

  7. Intensive consolidation with G-CSF support: Tolerability, safety, reduced hospitalization, and efficacy in acute myeloid leukemia patients ≥60 years.

    Science.gov (United States)

    Sperr, Wolfgang R; Herndlhofer, Susanne; Gleixner, Karoline; Girschikofsky, Michael; Weltermann, Ansgar; Machherndl-Spandl, Sigrid; Sliwa, Thamer; Poehnl, Rainer; Buxhofer-Ausch, Veronika; Strecker, Karin; Hoermann, Gregor; Knoebl, Paul; Jaeger, Ulrich; Geissler, Klaus; Kundi, Michael; Valent, Peter

    2017-10-01

    The aim of this study was to evaluate the efficacy and feasibility of intensified consolidation therapy employing fludarabine and ARA-C in cycle 1 and intermediate-dose ARA-C (IDAC) in cycles 2 through 4, in elderly acute myeloid leukemia (AML) patients and to analyze the effects of pegfilgrastim on the duration of neutropenia, overall toxicity, and hospitalization-time during consolidation in these patients. Thirty nine elderly patients with de novo AML (median age 69.9 years) who achieved complete remission (CR) after induction-chemotherapy were analyzed. To examine the effect of pegfilgrastim on neutropenia and hospitalization, we compared cycles 2 and 4 where pegfilgrastim was given routinely from day 6 (IDAC-P) with cycle 3 where pegfilgrastim was only administered in case of severe infections and/or prolonged neutropenia. All four planned cycles were administered in 23/39 patients (59.0%); 5/39 patients (12.8%) received 3 cycles, 3/39 (7.7%) 2 cycles, and 8/39 (20.5%) one consolidation-cycle. The median duration of severe neutropenia was 7 days in cycle 2 (IDAC-P), 11.5 days in cycle 3 (IDAC), and 7.5 days in cycle 4 (IDAC-P) (P consolidation can be administered in AML patients ≥60, and those who are consolidation shortens the time of neutropenia and hospitalization in these patients. © 2017 Wiley Periodicals, Inc.

  8. Derepression of the Iroquois Homeodomain Transcription Factor Gene IRX3 Confers Differentiation Block in Acute Leukemia

    Directory of Open Access Journals (Sweden)

    Tim D.D. Somerville

    2018-01-01

    Full Text Available The Iroquois homeodomain transcription factor gene IRX3 is expressed in the developing nervous system, limb buds, and heart, and transcript levels specify obesity risk in humans. We now report a functional role for IRX3 in human acute leukemia. Although transcript levels are very low in normal human bone marrow cells, high IRX3 expression is found in ∼30% of patients with acute myeloid leukemia (AML, ∼50% with T-acute lymphoblastic leukemia, and ∼20% with B-acute lymphoblastic leukemia, frequently in association with high-level HOXA gene expression. Expression of IRX3 alone was sufficient to immortalize hematopoietic stem and progenitor cells (HSPCs in myeloid culture and induce lymphoid leukemias in vivo. IRX3 knockdown induced terminal differentiation of AML cells. Combined IRX3 and Hoxa9 expression in murine HSPCs impeded normal T-progenitor differentiation in lymphoid culture and substantially enhanced the morphologic and phenotypic differentiation block of AML in myeloid leukemia transplantation experiments through suppression of a terminal myelomonocytic program. Likewise, in cases of primary human AML, high IRX3 expression is strongly associated with reduced myelomonocytic differentiation. Thus, tissue-inappropriate derepression of IRX3 contributes significantly to the block in differentiation, which is the pathognomonic feature of human acute leukemias.

  9. Gemtuzumab ozogamicin (Mylotarg) as single-agent treatment for frail patients 61 years of age and older with acute myeloid leukemia: final results of AML-15B, a phase 2 study of the European Organisation for Research and Treatment of Cancer and Gruppo Italiano Malattie Ematologiche dell'Adulto Leukemia Groups.

    NARCIS (Netherlands)

    Amadori, S.; Suciu, S.; Stasi, R.; Willemze, R.; Mandelli, F.; Selleslag, D.; Denzlinger, C.; Muus, P.; Stauder, R.; Berneman, Z.; Pruijt, J.F.M.; Nobile, F.; Cassibba, V.; Marie, J.P.; Beeldens, F.; Baila, L.; Vignetti, M.; Witte, T.J.M. de

    2005-01-01

    The therapeutic activity and toxicity profile of gemtuzumab ozogamicin were assessed in 40 patients >60 years of age with acute myeloid leukemia (AML) who were not considered eligible for conventional chemotherapy because of advanced age or poor performance status. The drug was administered at

  10. Multiplex fusion gene testing in pediatric acute myeloid leukemia.

    Science.gov (United States)

    Iijima-Yamashita, Yuka; Matsuo, Hidemasa; Yamada, Miho; Deguchi, Takao; Kiyokawa, Nobutaka; Shimada, Akira; Tawa, Akio; Takahashi, Hiroyuki; Tomizawa, Daisuke; Taga, Takashi; Kinoshita, Akitoshi; Adachi, Souichi; Horibe, Keizo

    2018-01-01

    Gene abnormalities, particularly chromosome rearrangements generating gene fusion, are associated with clinical characteristics and prognosis in pediatric acute myeloid leukemia (AML). Karyotyping is generally performed to enable risk stratification, but the results are not always consistent with those of reverse transcription-polymerase chain reaction (RT-PCR), and more accurate and rapid methods are required. A total of 487 samples from de novo AML patients enrolled in the Japanese Pediatric Leukemia/Lymphoma Study Group (JPLSG) AML-05 study (n = 448), and from acute promyelocytic leukemia (APL) patients enrolled in the JPLSG AML-P05 study (n = 39) were available for this investigation. Multiplex quantitative RT-PCR was performed to detect eight important fusion genes: AML1(RUNX1)-ETO(RUNX1T1), CBFB-MYH11, MLL(KMT2A)-AF9(MLLT3), MLL-ELL, MLL-AF6(MLLT4), FUS(TLS)-ERG, NUP98-HOXA9, and PML-RARA. Fusion genes were detected in 207 (46.2%) of the 448 AML-05 patient samples. After exclusion of two samples with PML-RARA, no chromosomal abnormalities were identified on karyotyping in 19 of 205 patients (9.3%) positive for fusion genes on RT-PCR. Fusion genes were confirmed on fluorescence in situ hybridization (FISH) in 11 of these 19 patients. In contrast, fusion genes were detected in 37 of 39 patients (94.9%) from the AML-P05 study, and 33 of these results were consistent with the karyotyping. There were discrepancies in four patients (10.8%), three with normal karyotypes and one in whom karyotyping was not possible. All four of these patients were PML-RARA positive on FISH. Multiplex quantitative RT-PCR-based fusion gene screening may be effective for diagnosis of pediatric AML. © 2017 Japan Pediatric Society.

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

    Directory of Open Access Journals (Sweden)

    Sarita Rani Jaiswal

    2016-01-01

    Full Text Available Allogeneic hematopoietic stem cell transplantation (HSCT remains a curative option for children with high risk and advanced acute leukemia. Yet availability of matched family donor limits its use and although matched unrelated donor or mismatched umbilical cord blood (UCB are viable options, they fail to meet the global need. Haploidentical family donor is almost universally available and is emerging as the alternate donor of choice in adult patients. However, the same is not true in the case of children. The studies of haploidentical HSCT in children are largely limited to T cell depleted grafts with not so encouraging results in advanced leukemia. At the same time, emerging data from UCBT are challenging the existing paradigm of less stringent HLA match requirements as perceived in the past. The use of posttransplantation cyclophosphamide (PTCY has yielded encouraging results in adults, but data in children is sorely lacking. Our experience of using PTCY based haploidentical HSCT in children shows inadequacy of this approach in younger children compared to excellent outcome in older children. In this context, we discuss the current status of haploidentical HSCT in children with acute leukemia in a global perspective and dwell on its future prospects.

  12. Efficacy and safety analysis by age cohort of inotuzumab ozogamicin in patients with relapsed or refractory acute lymphoblastic leukemia enrolled in INO-VATE.

    Science.gov (United States)

    Jabbour, Elias J; DeAngelo, Daniel J; Stelljes, Matthias; Stock, Wendy; Liedtke, Michaela; Gökbuget, Nicola; O'Brien, Susan; Wang, Tao; Paccagnella, M Luisa; Sleight, Barbara; Vandendries, Erik; Advani, Anjali S; Kantarjian, Hagop M

    2018-01-30

    Inotuzumab ozogamicin (InO) has demonstrated efficacy and tolerability in patients aged 18 to 78 years with relapsed/refractory acute lymphoblastic leukemia (ALL) in the INO-VATE trial. This subset analysis compared the efficacy and safety of InO in younger and older patients. Intent-to-treat analyses of morphologic responses and overall survival (OS) included 326 randomized patients, and safety assessments included 307 patients receiving 1 or more doses of the study treatment. Of the 326 patients, 164 received InO at a starting dose of 1.8 mg/m 2 /cycle (0.8 mg/m 2 on day 1 and 0.5 mg/m 2 on days 8 and 15 of a 21- to 28-day cycle [≤6 cycles]); 60 patients were aged ≥55 years, and 104 were aged <55 years. For older and younger patients, the median duration of InO therapy and the types and frequencies of adverse events of any grade were generally similar. Although the remission rates, median duration of remission (DOR), and progression-free survival were similar with InO for those aged <55 years and those aged ≥55 years, OS was longer for younger patients (median, 8.6 vs 5.6 months; hazard ratio, 0.610). Among patients proceeding to hematopoietic stem cell transplantation after InO treatment (28% of older patients and 58% of younger patients), the incidence of veno-occlusive disease was greater in older patients (41% vs 17%). The study database was not locked at the time of this analysis. InO was tolerable in older patients with relapsed/refractory ALL. Although OS was longer for younger patients versus older patients, InO demonstrated high response rates with similar DOR in the 2 age groups. Cancer 2018. © 2018 American Cancer Society. © 2018 American Cancer Society.

  13. Cranial computerized tomography in children suffering from acute leukemia

    International Nuclear Information System (INIS)

    Metz, O.

    1981-01-01

    Cranial computerized (axial) tomography permits a more complete neurologic supervision of children with acute leukemia and a better knowledge of the frequency and varieties of cerebral complications in leukemia. Endocranial complications in acute leukemia are essentially infiltrative, hemorrhagic, infectious or iatrogenic. Cranial computerized tomography can demonstrate cerebral changes in meningeal leukemia, hemorrhages, calcifications, brain atrophy or leukencephalopathy. The preliminary results of cranial computerized tomography in childhood leukemia suggest that the iatrogenic main lesion of the brain due to combined radiation-chemotherapy is atrophy whereas that of the intrathecal cytostatic therapy is demyelination. Accurate diagnostics and control of possible cerebral complications in therapy of leukemia is essentially for appropriate therapeutic management. For that cranial computerized tomography is the best method to a effective supervision of the brain. (author)

  14. Chromosomal differences between acute nonlymphocytic leukemia in patients with prior solid tumors and prior hematologic malignancies. A study of 14 cases with prior breast cancer

    International Nuclear Information System (INIS)

    Mamuris, Z.; Dumont, J.; Dutrillaux, B.; Aurias, A.

    1989-01-01

    A cytogenetic study of 14 patients with secondary acute nonlymphocytic leukemia (S-ANLL) with prior treatment for breast cancer is reported. The chromosomes recurrently involved in numerical or structural anomalies are chromosomes 7, 5, 17, and 11, in decreasing order of frequency. The distribution of the anomalies detected in this sample of patients is similar to that observed in published cases with prior breast or other solid tumors, though anomalies of chromosome 11 were not pointed out, but it significantly differs from that of the S-ANLL with prior hematologic malignancies. This difference is principally due to a higher involvement of chromosome 7 in patients with prior hematologic malignancies and of chromosomes 11 and 17 in patients with prior solid tumors. A genetic determinism involving abnormal recessive alleles located on chromosomes 5, 7, 11, and 17 uncovered by deletions of the normal homologs may be a cause of S-ANLL. The difference between patients with prior hematologic malignancies or solid tumors may be explained by different constitutional mutations of recessive genes in the two groups of patients

  15. Therapy-Related Myelodysplastic Syndrome Following Treatment for Childhood Acute Lymphoblastic Leukemia: Outcome of Patients Registered in the EWOG-MDS 98/06 Studies

    DEFF Research Database (Denmark)

    Strahm, Birgitte; Amann, Roland; De Moerloose, Barbara

    Objective: Therapy-related myelodysplastic syndrome (tMDS) following treatment of childhood acute lymphoblastic leukemia (ALL) is one of the most frequently observed secondary malignancies in survivors of childhood cancer. Allogeneic stem cell transplantation (SCT) is the only curative treatment....... This analysis was performed to asses the outcome of patients with tMDS following treatment for childhood ALL reported to the EWOG-MDS study group. Patients and Transplant Procedure: Forty-three patients (19 male/24 female) were diagnosed with tMDS between August 1989 and August 2009. The median age at diagnosis...... was 8.9 yrs (3.4–20.5). The median interval from diagnosis of ALL to the diagnosis of tMDS was 3.3 yrs (1.7–7.0). Five patients did not receive SCT and died due to progressive disease at a median of 5.6 mo after diagnosis. Thirty-eight patients were transplanted. One patient was excluded from...

  16. Final report of a phase II study of imatinib mesylate with hyper-CVAD for the front-line treatment of adult patients with Philadelphia chromosome-positive acute lymphoblastic leukemia

    Science.gov (United States)

    Daver, Naval; Thomas, Deborah; Ravandi, Farhad; Cortes, Jorge; Garris, Rebecca; Jabbour, Elias; Garcia-Manero, Guillermo; Borthakur, Gautam; Kadia, Tapan; Rytting, Michael; Konopleva, Marina; Kantarjian, Hagop; O’Brien, Susan

    2015-01-01

    We have previously reported on the efficacy and tolerability of hyper-CVAD regimen (cyclophosphamide, vincristine, Adriamycin, and dexamethasone) and imatinib followed by imatinib-based consolidation/maintenance therapy in 20 patients with newly diagnosed Philadelphia-positive acute lymphoblastic leukemia. Here, we present the 13-year follow up of our study. Fifty-four patients with newly diagnosed Philadelphia-positive acute lymphoblastic leukemia were enrolled: 39 (72%) with de novo disease, 6 (11%) whose disease was primary refractory after induction (without a tyrosine kinase inhibitor), and 9 (17%) in complete remission after one course of induction therapy (without tyrosine kinase inhibitor). Forty-two (93%) of the 45 patients treated for active disease achieved complete remission, one achieved complete remission with incomplete recovery of platelets, one achieved partial remission and one died during induction. Nineteen (35%) patients are alive and 18 are in complete remission. The 5-year overall survival rate for all patients was 43%. Significant negative predictors of overall survival were age over 60 years, p190 molecular transcript, and active disease at enrollment. Sixteen (30%) patients underwent allogeneic stem cell transplantation. Median overall survival was not significantly greater for patients who underwent transplant. Patients with residual molecular disease at three months had improved complete remission duration with transplant. The median time to hematologic recovery and severe toxicities with combination were not significantly different from those observed with conventional chemotherapy. Only one patient discontinued therapy due to toxicity. HyperCVAD chemotherapy and imatinib is an effective regimen for Philadelphia-positive acute lymphoblastic leukemia. Transplant may not be indicated in all patients with Philadelphia-positive acute lymphoblastic leukemia. (clinicaltrials.gov identifier: NCT00038610) PMID:25682595

  17. Delayed elimination of high-dose methotrexate and use of carboxypeptidase G2 in pediatric patients during treatment for acute lymphoblastic leukemia

    DEFF Research Database (Denmark)

    Svahn, Thommy; Mellgren, Karin; Harila-Saari, Arja

    2017-01-01

    negative acute lymphoblastic leukemia (ALL) were treated according to the Nordic Organization for Pediatric Hematology and Oncology (NOPHO) ALL 2008 protocol, including administration of six to eight high-dose (5 g/m(2) /24 hr) Mtx (HDMtx) courses. The protocol includes recommendations for CPDG2...

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

    DEFF Research Database (Denmark)

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

    2015-01-01

    Childhood acute lymphoblastic leukemia survival approaches 90%. New strategies are needed to identify the 10–15% who evade cure. We applied targeted, sequencing-based genotyping of 25 000 to 34 000 preselected potentially clinically relevant singlenucleotide polymorphisms (SNPs) to identify host...

  19. Hydrocortisone as an intervention for dexamethasone-induced adverse effects in pediatric patients with acute lymphoblastic leukemia: results of a double-blind, randomized controlled trial

    NARCIS (Netherlands)

    L.T. Warris (Lidewij); M.M. van den Heuvel-Eibrink (Marry); F.K. Aarsen (Femke); S. Pluijm (Saskia); M. Bierings (Marc); Van Bos, C.D. (Cor Den); C.M. Zwaan (Christian Michel); Thygesen, H.H. (Helene H.); W.J.E. Tissing (Wim); M.A. Veening (Margreet A.); R. Pieters (Rob); E.L.T. van den Akker (Erica)

    2016-01-01

    textabstractPurpose Dexamethasone is a key component in the treatment of pediatric acute lymphoblastic leukemia (ALL), but can induce serious adverse effects. Recent studies have led to the hypothesis that neuropsychological adverse effects may be a result of cortisol depletion of the cerebral

  20. Vascular endothelial growth factor secretion is an independent prognostic factor for relapse-free survival in pediatric acute myeloid leukemia patients

    NARCIS (Netherlands)

    de Bont, ESJM; Fidler, [No Value; Meeuwsen, T; Scherpen, F; Hahlen, K; Kamps, WA

    Substantial improvements in long-term survival have been made with acute myeloid leukemia (AML). However, the overall success rate in treatment of AML is around 50%, despite intensive chemotherapeutic regimens. AML cell survival seems to be related to vascular endothelial growth factor (VEGF). The