Abstract:
:Phosphatidylinositol-3-kinase (PI3K) signaling plays a crucial role in oncogene-mediated tumor growth and proliferation. Buparlisib (BKM120) is an oral pan-class I PI3K inhibitor. This phase I study was conducted to determine the dose limiting toxicity (DLT) and maximum tolerated dose (MTD) of BKM120 in patients (pts) with relapsed/refractory acute leukemias. Fourteen pts (12 acute myeloid leukemia, 1 acute lymphoblastic leukemia, and 1 mixed phenotype leukemia) were enrolled. Twelve pts received BKM-120 80 mg/day and two 100 mg/day. The MTD was 80 mg/day. Of the 14 patients treated, the best response was stable disease in one patient that lasted 82 days. The median survival for all patients was 75 days (range 10-568). Three patients with a 3q26 chromosome abnormality had a significantly improved median survival of 360 days (range 278-568) as compared to a median survival of 57 days (range, 10-125) among the 11 other patients. The most frequent drug-related toxicities included confusion, mucositis, dysphagia, and fatigue. Western blot profiling revealed a decrease in p-pS6K/total pS6K in 5/7 (71%) available patient samples with a mean quantitative inhibition of 65% (range, 32-100%) and a decrease in p-FOXO3/total FOXO3 in 4/6 (67%) samples with a mean quantitative inhibition of 93% (range, 89-100%). BKM120 administered at 80 mg/day showed modest efficacy and was tolerable in advanced acute leukemias. Am. J. Hematol. 92:7-11, 2017. © 2016 Wiley Periodicals, Inc.
journal_name
Am J Hematoljournal_title
American journal of hematologyauthors
Ragon BK,Kantarjian H,Jabbour E,Ravandi F,Cortes J,Borthakur G,DeBose L,Zeng Z,Schneider H,Pemmaraju N,Garcia-Manero G,Kornblau S,Wierda W,Burger J,DiNardo CD,Andreeff M,Konopleva M,Daver Ndoi
10.1002/ajh.24568subject
Has Abstractpub_date
2017-01-01 00:00:00pages
7-11issue
1eissn
0361-8609issn
1096-8652journal_volume
92pub_type
杂志文章abstract::ASXL1 and SRSF2 mutations in AML are frequently found in patients with preexisting myeloid malignancies and are individually associated with poor outcomes. In this multi-institutional retrospective analysis, we assessed the genetic features and clinical outcomes of 43 patients with ASXL1mut SRSF2mut AML and compared o...
journal_title:American journal of hematology
pub_type: 杂志文章
doi:10.1002/ajh.26110
更新日期:2021-01-27 00:00:00
abstract::This review focuses on the initial clinical descriptions and subsequent investigation of the syndrome of recurrent infections associated with neutrophil membrane glycoprotein deficiencies. Characterization of the missing group of three glycoprotein heterodimers and their role in adhesion-related neutrophil function is...
journal_title:American journal of hematology
pub_type: 杂志文章,评审
doi:10.1002/ajh.2830310416
更新日期:1989-08-01 00:00:00
abstract::A 56-year-old man was admitted to our hospital with leukocytosis, anemia, and thrombocytopenia. Acute monoblastic leukemia was diagnosed. Two subsequent courses of consolidation chemotherapy consisted of conventional doses of cytarabine and intermediate-dose cytarabine. Intermediate-dose cytarabine was infused intrave...
journal_title:American journal of hematology
pub_type: 杂志文章
doi:10.1002/ajh.20772
更新日期:2007-04-01 00:00:00
abstract::A patient with Felty's syndrome (FS) and persistent profound neutropenia developed recurrent infections and sepsis syndrome. No impairment of granulocyte-macrophage colony development was observed in vitro. Marrow morphology revealed an absence of mature neutrophil forms despite administration of granulocyte-colony st...
journal_title:American journal of hematology
pub_type: 杂志文章
doi:10.1002/ajh.2830430415
更新日期:1993-08-01 00:00:00
abstract::Acetylsalicylic acid (ASA) is currently recommended as an antithrombotic for patients with essential thrombocythemia (ET) who are at an increased risk of thrombotic events. However, ASA is also associated with an increased risk of bleeding in these patients as compared to the risk of bleeding in other patients treated...
journal_title:American journal of hematology
pub_type: 杂志文章
doi:10.1002/(sici)1096-8652(199804)57:4<277::aid-ajh2>
更新日期:1998-04-01 00:00:00
abstract::Sickle cell (SS) disease is a complex of various genetic conditions. In some, homozygosity for the beta S gene may be present alone or in combination with the heterozygous or homozygous alpha-thalassemia-2 condition. Such combinations might ameliorate the clinical and hematological condition of the patient. The same m...
journal_title:American journal of hematology
pub_type: 杂志文章,评审
doi:10.1002/ajh.2830060210
更新日期:1979-01-01 00:00:00
abstract::We measured the plasma level of fibrinogen in 560 patients with disseminated intravascular coagulation (DIC) and evaluated its relationship with outcome and with other hemostatic markers. Forty-seven percent of patients had >200 mg/dL of plasma fibrinogen and 24% had <100 mg/dl of plasma fibrinogen, suggesting that pl...
journal_title:American journal of hematology
pub_type: 杂志文章
doi:10.1002/ajh.10249
更新日期:2003-01-01 00:00:00
abstract::Polycythemia vera (PCV) and multiple myeloma are both clonal disorders of hematopoietic stem cells. The simultaneous occurrence of these diseases in an individual patient is rare. A case of synchronous PCV and smoldering myeloma is presented and the literature is reviewed. The issues of clinical importance in this unu...
journal_title:American journal of hematology
pub_type: 杂志文章,评审
doi:10.1002/ajh.2830440311
更新日期:1993-11-01 00:00:00
abstract::Granulysin is a newly identified CTL/NK cell-related cytotoxic protein, which is secreted in both constitutive and Ca-dependent manner. To evaluate its significance in stem-cell transplantation (SCT), serum granulysin was measured by newly established ELISA method in 26 patients undergoing SCT (21 allogeneic and 5 aut...
journal_title:American journal of hematology
pub_type: 杂志文章
doi:10.1002/ajh.20570
更新日期:2006-05-01 00:00:00
abstract:OVERVIEW:Evidence suggests that even patients aged 70 or above benefit from specific AML therapy. The fundamental decision in AML then becomes whether to recommend standard or investigational treatment. This decision must rest on the likely outcome of standard treatment. Hence we review factors that predict treatment r...
journal_title:American journal of hematology
pub_type: 杂志文章,评审
doi:10.1002/ajh.23834
更新日期:2014-11-01 00:00:00
abstract::Transfusion-related acute lung injury (TRALI) is associated with administration of all plasma containing blood products. We present a 14-year-old adolescent diagnosed with idiopathic thrombocytopenic purpura who developed acute respiratory insufficiency compatible with TRALI within 5 hr following intravenous anti-D. F...
journal_title:American journal of hematology
pub_type: 杂志文章
doi:10.1002/ajh.21185
更新日期:2008-08-01 00:00:00
abstract::Chronic transfusion therapy is the treatment of choice for preventing stroke recurrence in children with sickle cell disease (SCD). The majority of children affected by this devastating complication live in the developing world where access to regular blood transfusions may be impractical. Since 2000, in the absence o...
journal_title:American journal of hematology
pub_type: 杂志文章
doi:10.1002/ajh.22142
更新日期:2011-10-01 00:00:00
abstract::The effect of the synthetic vasopressin derivative 1-desamino-8D-arginine vasopressin (DDAVP = desmopressin) on bleeding time was studied in three patients with Hermansky Pudlak syndrome. A good response was observed in this type of storage pool disease. DDAVP might be useful in managing the bleeding disorder found in...
journal_title:American journal of hematology
pub_type: 杂志文章
doi:10.1002/ajh.2830300307
更新日期:1989-03-01 00:00:00
abstract::Seventy-three patients with hereditary spherocytosis (HS) (58 nonsplenectomized, 15 splenectomized) were studied to evaluate iron status and the adequacy of iron availability for erythropoiesis. Splenectomized patients, who had hemoglobin levels in the normal or upper normal range, had higher levels of serum iron, tra...
journal_title:American journal of hematology
pub_type: 杂志文章
doi:10.1002/ajh.2830310202
更新日期:1989-06-01 00:00:00
abstract::Several studies reported improved outcomes of adolescents and young adults (AYA) with acute lymphoblastic leukemia (ALL) treated with pediatric-based ALL regimens. This prompted the prospective investigation of a pediatric Augmented Berlin-Frankfurt-Münster (ABFM) regimen, and its comparison with hyper-fractionated cy...
journal_title:American journal of hematology
pub_type: 杂志文章
doi:10.1002/ajh.24419
更新日期:2016-08-01 00:00:00
abstract::Transformation to secondary myelofibrosis (MF) occurs as part of the natural history of polycythemia vera (PPV-MF) and essential thrombocythemia (PET-MF). Although primary (PMF) and secondary MF are considered similar diseases and managed similarly, there are few studies specifically focused on the latter. The aim of ...
journal_title:American journal of hematology
pub_type: 杂志文章,多中心研究
doi:10.1002/ajh.24377
更新日期:2016-07-01 00:00:00
abstract::Immunomodulatory drugs (IMiDs) are a cornerstone in the treatment of multiple myeloma (MM), but specific markers to predict outcome are still missing. Recent work pointed to a prognostic role for IMiD target genes (e.g. CRBN). Moreover, indirect activity of IMiDs on immune cells correlated with outcome, raising the po...
journal_title:American journal of hematology
pub_type: 杂志文章
doi:10.1002/ajh.24634
更新日期:2017-03-01 00:00:00
abstract::We evaluated T-lymphocyte functions in the peripheral blood of a patient with B-cell chronic lymphocytic leukemia after transformation to large cell lymphoma (Richter's syndrome). A subpopulation of E-rosette adherent cells were found with T-lymphocytic surface markers (OKT3+/8+/4+), monocytic characteristics (latex i...
journal_title:American journal of hematology
pub_type: 杂志文章
doi:10.1002/ajh.2830200312
更新日期:1985-11-01 00:00:00
abstract::We have developed a rapid approach to detect the two most common alpha-thalassemia-2 (alpha-thal-2) determinants by the polymerase chain reaction (PCR) technique, which takes a few hours to complete. Specific oligonucleotides selectively amplify appropriate segments of the chromosome with the deletion and the normal c...
journal_title:American journal of hematology
pub_type: 杂志文章
doi:10.1002/ajh.2830460309
更新日期:1994-07-01 00:00:00
abstract::Several histone deacetylase inhibitors (HDACi), including vorinostat, have been approved for the therapy of cutaneous T-cell lymphoma (CTCL). Emerging data suggest that HDACi may exert immune suppressive effects which would be disadvantageous for therapy of CTCL. We describe a patient with Sezary syndrome who was moni...
journal_title:American journal of hematology
pub_type: 杂志文章
doi:10.1002/ajh.22231
更新日期:2012-02-01 00:00:00
abstract::Granulocyte macrophage-colony-stimulating factor (GM-CSF) has shown promise as a means of alleviating leukopenia associated with a wide variety of disorders. It is currently undergoing evaluation as an adjunct to bone marrow transplantation but its use in patients with metabolic disorders, such as Hurler's syndrome (H...
journal_title:American journal of hematology
pub_type: 杂志文章
doi:10.1002/ajh.2830410411
更新日期:1992-12-01 00:00:00
abstract::The second generation BCR/ABL kinase inhibitor nilotinib is increasingly used for the treatment of imatinib-resistant chronic myeloid leukemia (CML). So far, nilotinib is considered a well-tolerated drug with little if any side effects, although an increase in the fasting glucose level has been reported. We examined a...
journal_title:American journal of hematology
pub_type: 临床试验,杂志文章
doi:10.1002/ajh.22037
更新日期:2011-07-01 00:00:00
abstract::In addition to transferrin, ferritin can also function as a source of iron for heme synthesis (Gelvin D, et al. Blood 1996;88:3200-3207; Meyron-Holtz EG, et al. Blood 1999;94:3205-3211). In the present study we investigate the effect of external ferritin on the proliferation and hemoglobinization of human erythroid pr...
journal_title:American journal of hematology
pub_type: 杂志文章
doi:10.1002/ajh.10355
更新日期:2003-07-01 00:00:00
abstract::Celecoxib, a specific cyclooxygenase-2 (Cox-2) inhibitor, has been shown to possess antitumor activity in a variety of cancer cells. However, the antitumor activity of celecoxib in hematopoietic tumors, especially in chronic myeloid leukemia (CML), has not been well established. This study was designed to investigate ...
journal_title:American journal of hematology
pub_type: 杂志文章
doi:10.1002/ajh.20542
更新日期:2006-04-01 00:00:00
abstract::By using Dexter-type long-term marrow cultures (D-LTMC), it has been shown previously that hematopoietic progenitor cells (HPC) from patients with aplastic anemia (AA) have a deficient proliferation in vitro. The studies reported to date, however, have focused exclusively on granulomonocytic progenitors and no informa...
journal_title:American journal of hematology
pub_type: 杂志文章
doi:10.1002/(sici)1096-8652(199810)59:2<149::aid-ajh8>
更新日期:1998-10-01 00:00:00
abstract::Pure red cell aplasia (PRCA) sometimes accompanies thymoma. Herein, we report a PRCA patient with thymoma with a clonal disorder of T cells. A 55-year-old man presented with anemia and anterior mediastinum tumor. The laboratory study revealed hemoglobin 8.2 g/dl; leukocytes 15.8 x 10(9)/L with 76.5% neutrophils, 20.0%...
journal_title:American journal of hematology
pub_type: 杂志文章
doi:10.1002/(sici)1096-8652(199704)54:4<324::aid-ajh12
更新日期:1997-04-01 00:00:00
abstract::Invasive fungal disease (IFD) is a significant cause of morbidity and mortality in patients undergoing treatment for acute leukemia (AL). Antifungal prophylactic strategies are associated with significant toxicities and cost. We performed a retrospective study of the incidence and risk factors for IFD among patients n...
journal_title:American journal of hematology
pub_type: 杂志文章
doi:10.1002/ajh.21776
更新日期:2010-09-01 00:00:00
abstract::Individuals with more than one defect in natural coagulant/anticoagulant systems have been postulated to be at an increased risk for thrombotic events. We report a case of combined protein S and C deficiency in a young woman, which resulted in fatal arterial mesenteric thrombosis. The role of coagulation defects in ar...
journal_title:American journal of hematology
pub_type: 杂志文章
doi:10.1002/(sici)1096-8652(199807)58:3<246::aid-ajh17
更新日期:1998-07-01 00:00:00
abstract::In this study, we further established the role of interleukin-1 alpha (IL-1 alpha), interleukin-1 beta, tumor necrosis factor-alpha (TNF-alpha), and interferon-alpha (IFN-alpha) as regulators of proliferation of acute myeloid leukemia (AML) cells. AML cells from 8 of 15 patients incorporated high levels of 3H-thymidin...
journal_title:American journal of hematology
pub_type: 杂志文章
doi:10.1002/ajh.2830400402
更新日期:1992-08-01 00:00:00
abstract::A 36-year-old white man was found to have low erythrocyte acetylcholinesterase activity. Plasma cholinesterase activity was normal. The propositus had mild anemia and moderate elliptocytosis, but was asymptomatic. A sister, brother, father, and nephew were hematologically normal, but had slightly subnormal red cell ac...
journal_title:American journal of hematology
pub_type: 杂志文章
doi:10.1002/ajh.2830070403
更新日期:1979-01-01 00:00:00