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Relapsed acute myeloid leukemia

Ting-Juan Zhang, Jiang Lin, Jing-Dong Zhou, Xi-Xi Li, Wei Zhang, Hong Guo, Zi-Jun Xu, Yang Yan, Ji-Chun Ma, Jun Qian
Oncogenic role of miR-19 family has been identified in human cancers especially in lymphoid malignancies. However, to date, little studies investigated the role of miR-19 family in myeloid malignancies. Herein, we examined miR-19a/b expression and explored its clinical significance in de novo acute myeloid leukemia (AML). The detection of miR-19a/b expression was performed by real-time quantitative PCR in bone marrow mononuclear cells of 113 patients and 42 healthy donors. Both miR-19a/b levels were significantly increased in AML patients in contrast to controls...
October 12, 2017: Gene
Abu-Sayeef Mirza, Jeffrey E Lancet, Kendra Sweet, Eric Padron, Javier Pinilla-Ibarz, Lisa Nardelli, Christopher Cubitt, Alan F List, Rami S Komrokji
INTRODUCTION: No standard salvage chemotherapy regimen is available for relapsed or refractory (RR) acute myeloid leukemia (AML). Preclinical data have suggested synergy in vitro between cytarabine and imatinib mesylate (IM) on AML cell growth inhibition. After demonstrating the safety and feasibility in a phase I study, we conducted a phase II clinical study of CLAG (cladribine, cytarabine, granulocyte colony-stimulating factor) regimen combined with IM for patients with RR-AML. PATIENTS AND METHODS: We performed a single-institution 2-stage phase II study...
September 19, 2017: Clinical Lymphoma, Myeloma & Leukemia
Jing-Dong Zhou, Dong-Ming Yao, Xi-Xi Li, Ting-Juan Zhang, Wei Zhang, Ji-Chun Ma, Hong Guo, Zhao-Qun Deng, Jiang Lin, Jun Qian
The prognostic value of RAS mutations has been systematically investigated in acute myeloid leukemia (AML). However, clinical significance of RAS expressions in AML remains poorly determined. To explore the clinical significance, we analyzed KRAS and NRAS expressions in 143 de novo AML patients by real-time quantitative PCR. KRAS and NRAS expressions were significantly up-regulated in AML patients. KRAS and NRAS mutations were identified in 4% (6/143) and 8% (12/143) of these patients, respectively. However, no significant association was observed between RAS mutations and expressions...
September 12, 2017: Oncotarget
Alice C Ceacareanu, George K Nimako, Zachary A P Wintrob
OBJECTIVE: To evaluate whether metformin's cancer-related benefits reported in patients with solid tumors (ST) are also present in acute myeloid leukemia (AML) patients. METHODS: Baseline demographic and clinical history for all diabetes mellitus patients newly diagnosed with AML or cancer of the breast, ovary, prostate, gastrointestinal tract, lung, or kidney at Roswell Park Cancer Institute in Buffalo, NY (January 2003-December 2010, n = 924) was collected. Overall survival (OS) and disease-free survival (DFS) were assessed by Kaplan-Meier (KM) analysis and Cox proportional hazards regression (hazard ratio [HR])...
July 2017: Journal of Research in Pharmacy Practice
Dima El-Sharkawi, Duncan Sproul, Christopher G Allen, Andrew Feber, Melissa Wright, Robert K Hills, David C Linch, Rosemary E Gale
Although CEBPA double-mutated (CEBPADM) acute myeloid leukemia is considered to be favorable-risk disease, relapse remains a major cause of treatment failure. Most CEBPADM patients have a classic biallelic mutant combination with an N-terminal mutation leading to production of p30 protein plus a C-terminal loss-of-function in-frame indel mutation (CEBPAClassic-DM), but approximately one-third of cases have one or more non-classic mutations, with diverse combinations reported, and there is little information on the consequences of such mutants...
October 12, 2017: Haematologica
Frederick R Appelbaum, Irwin D Bernstein
On September 1, 2017, the U.S. Food and Drug Administration (FDA) approved gemtuzumab ozogamicin for the treatment of adults with newly diagnosed CD33+ acute myeloid leukemia and for patients aged 2 years and older with CD33+ AML who have experienced a relapse or who have not responded to initial treatment. This signals a new chapter in the long and unusual story of gemtuzumab ozogamicin (GO), which was the first antibody-drug conjugate approved for human use by the FDA.
October 11, 2017: Blood
Tracy Murphy, Karen Wl Yee
Acute myeloid leukemia (AML) is the most common acute forms of leukemia in adults. It has a poor long-term survival with a high relapse rate and at relapse, is commonly resistant to available therapies. The current combination of daunorubicin (DNR) for three days and cytarabine (Ara-C) as a continuous infusion for seven days, more commonly known as '3+7' has remained essentially unaltered over the last forty-four years and remains the standard induction regimen internationally. Areas covered: This paper will briefly review clinically important trials related to '3+7'...
October 11, 2017: Expert Opinion on Pharmacotherapy
Constanza Bay, Tamara González, Gonzalo Munoz, Paulette Legarraga, Cecilia Vizcaya, Katia Abarca
There are very few reports of pediatric patients with infections by dematiaceous filamentous fungi. In this publication we report a case of invasive fungal infection of the nasal septum by Curvularia spicifera in a pediatric patient with acute myeloid leukemia. The patient presented with a painful scabby wound in the nasal vestibule. Culture and universal PCR were consistent with Curvularia spicifera. Early management with surgical debridement and bi-associated antifungal therapy achieved complete resolution of the lesions, with no evidence of dissemination and relapses...
June 2017: Revista Chilena de Infectología: órgano Oficial de la Sociedad Chilena de Infectología
Brian N Dang, Satiro De Oliveira, LaVette Bowles, Theodore B Moore
BACKGROUND: Patients with chronic graft-versus-host disease (cGVHD) following allogeneic transplant for myeloid leukemias seem to experience a reduced risk of relapse than comparable patients without cGVHD. It is unclear to what extent extramedullary sites are impacted by a graft-versus-leukemia effect. DESIGN/METHOD: Case Series and review of the literature. RESULTS: We present 2 cases of pediatric patients with Acute Myelogenous Leukemia who developed isolated testicular relapse more than a year following hematopoietic stem cell transplantation despite having had extensive cGVHD...
October 4, 2017: Journal of Pediatric Hematology/oncology
Fatere Seyedalipour, Ava Mansouri, Mohammad Vaezi, Kheirollah Gholami, Kazem Heidari, Molouk Hadjibabaie, Ardeshir Ghavamzadeh
Background: Although several studies have supported a preventive and therapeutic role of vitamin D (Vit D) for different types of cancers, we face insufficient documentation in acute myeloid leukemia (AML). So, we examined whether the serum calcidiol (25(OH)D) levels at the time of induction therapy have any impact on response and relapse in AML patients. Materials and Methods: Blood samples were collected from 65 patients on days 0 and 28(th) of treatment to evaluate serum concentration of 25(OH)D and its effects on complete remission (CR) achievement, relapse rate and hospitalization length...
July 1, 2017: International Journal of Hematology-oncology and Stem Cell Research
Haiguo Zhang, Chengfang Zhang, Rui Feng, Haixia Zhang, Min Gao, Ling Ye
Acute myeloid leukemia (AML) is a common myelogenous malignancy in adults that is often characterized by disease relapse. The pathophysiological mechanism of AML has not yet been elucidated. The present study aimed to identify the crucial microRNAs (miRNAs/miRs) and target genes in AML, and to uncover the potential oncogenic mechanism of AML. miRNA and mRNA expression-profiling microarray datasets were downloaded from the Gene Expression Omnibus database. Differential expression analysis was performed and a regulatory network between miRNAs and target genes was constructed...
October 2017: Oncology Letters
Céline Bouvy, Adeline Wannez, Julie Laloy, Christian Chatelain, Jean-Michel Dogné
The treatment of acute leukemia is still challenging due in part to the development of resistance and relapse. This chemotherapeutics resistance is established by clonal selection of resistant variants of the cancer cells. Recently, a horizontal transfer of chemo-resistance among cancer cells via extracellular vesicles (EVs) has been suggested. The aim of this research was to investigate the role of EVs in chemo-resistance in acute myeloid leukemia. For this purpose, the sensitive strain of the promyelocytic leukemia HL60 cell line was studied along with its multi-resistant strain, HL60/AR that overexpresses the multidrug resistance protein 1 (MRP-1)...
September 25, 2017: Leukemia Research
Kazuki Terada, Hiroki Yamaguchi, Toshimitsu Ueki, Kensuke Usuki, Yutaka Kobayashi, Kenji Tajika, Seiji Gomi, Saiko Kurosawa, Keiki Miyadera, Taichiro Tokura, Ikuko Omori, Atushi Marumo, Yusuke Fujiwara, Shunsuke Yui, Takeshi Ryotokuji, Yoshiki Osaki, Kunihito Arai, Tomoaki Kitano, Fumiko Kosaka, Satoshi Wakita, Hayato Tamai, Takahiro Fukuda, Koiti Inokuchi
TP53 gene abnormality has been reported to be an unfavorable prognostic factor in acute myeloid leukemia (AML). However, almost all studies of TP53 gene abnormality so far have been limited to mutation searches in the DNA binding domain. As there have been few reports examining both mutation and deletion over the full-length of the TP53 gene, the clinical characteristics of TP53 gene abnormality have not yet been clearly established. In this study, TP53 gene mutation was observed in 7.3% of the total 412 de novo AML cases (33 mutations in 30 cases), with mutation outside the DNA binding domain in eight cases (27%)...
October 4, 2017: Annals of Hematology
Xiao-Xue Wang, Rui Zhang, Yan Li
BACKGROUND MicroRNAs (miRNAs) play an important role in the development and progression of acute myeloid leukemia (AML). The miR-148/152 family has been reported to be express differently in various kinds of tumors. We investigated the expression level of the miR-148/152 family in AML patients and their clinical significance. MATERIAL AND METHODS Expression levels of the miR-148/152 family in 80 patients with newly diagnosed AML and 20 healthy participants were analyzed by qRT-PCR. We also evaluated the relationship between the expression levels of the miR-148/152 family and clinicopathological features of AML patients...
October 5, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
Hikaru Kobayashi
Prognosis for refractory or relapsed acute myeloid leukemia (AML) patients is poor, and allogeneic hematopoietic stem cell transplantation (HSCT) is currently the only salvage option with curative potential for these patients. As the outcome of allogeneic HSCT in patients without complete remission (CR) status is unsatisfactory, it is important to attain a second CR before HSCT. An aggressive re-induction therapy for relapsed or refractory AML patients is often accompanied with severe infectious complications due to profound myelosuppression, which makes subsequent HSCT challenging...
2017: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
Frédéric Baron, Annalisa Ruggeri, Eric Beohou, Myriam Labopin, Mohamad Mohty, Jaime Sanz, Stephane Vigouroux, Sabine Furst, Alberto Bosi, Patrice Chevallier, Jan J Cornelissen, Mauricette Michallet, Jorge Sierra, Dimitrios Karakasis, Bipin N Savani, Eliane Gluckman, Arnon Nagler
BACKGROUND: The efficacy of umbilical cord blood transplantation (UCBT) as treatment for acute myeloid leukemia (AML) relies on immune-mediated graft-versus-leukemia effects. Previous studies have suggested a strong association between graft-versus-host disease (GVHD) occurrence and graft-versus-leukemia effects after allogeneic hematopoietic cell transplantation. METHODS: Here, we evaluated the kinetics of relapse rate in correlation to GVHD occurrence after UCBT...
October 4, 2017: Journal of Internal Medicine
Vlad Voin, Shehzad Khalid, Sebastian Shrager, R Shane Tubbs, Robert Greiner, Krishnamoorthy Thamburaj, Elias Rizk
Extramedullary tumors composed of myeloblasts or monoblasts can present in various locations. Patients with a history of acute myeloid leukemia (AML) can present with neuropathic pain and no evidence of relapse of their leukemia. Neuroleukemiosis is a form of extramedullary tumor present in the peripheral nervous systems (PNS) of leukemia patients. We report two AML patients who were in remission and later presented with neurological symptoms due to neuroleukemiosis with negative bone marrow biopsies.
July 31, 2017: Curēus
Seiichiro Katagiri, Tomohiro Umezu, Kenko Azuma, Michiyo Asano, Daigo Akahane, Hideki Makishima, Kenichi Yoshida, Yosaku Watatani, Kenichi Chiba, Satoru Miyano, Seishi Ogawa, Junko H Ohyashiki, Kazuma Ohyashiki
No abstract text is available yet for this article.
October 3, 2017: Leukemia & Lymphoma
Lukas Gaksch, Karl Kashofer, Ellen Heitzer, Franz Quehenberger, Shruti Daga, Sybille Hofer, Iris Halbwedl, Ricarda Graf, Nina Krisper, Gerald Hoefler, Armin Zebisch, Heinz Sill, Albert Wölfler
Despite achieving complete remission after intensive therapy, most patients with cytogenetically normal (CN) AML relapse due to the persistence of submicroscopic residual disease. In this pilot study, we hypothesized that detection of leukemia-specific mutations following consolidation treatment using a targeted parallel sequencing approach predicts relapse. We included 34 AML patients of whom diagnostic material and remission bone marrow slides after at least one cycle of consolidation were available. Isolated DNA was screened for mutations in 19 genes using an Ion Torrent sequencing platform...
September 29, 2017: American Journal of Hematology
Amir T Fathi, Traci M Blonquist, Daniela Hernandez, Philip C Amrein, Karen K Ballen, Malgorzata McMasters, David E Avigan, Robin Joyce, Emma K Logan, Gabriela Hobbs, Andrew M Brunner, Christelle Joseph, Ashley M Perry, Meghan Burke, Tanya Behnan, Julia Foster, Meghan K Bergeron, Jenna A Moran, Aura Y Ramos, Tina T Som, Jessica Rae, Kaitlyn M Fishman, Kristin L McGregor, Christine Connolly, Donna S Neuberg, Mark J Levis
BACKGROUND: Cabozantinib, a tyrosine kinase inhibitor of FMS-like tyrosine kinase 3 (FLT3), MET, AXL, vascular endothelial growth factor receptor, and KIT, is approved for use in multiple malignancies. We assessed the safety and tolerability of cabozantinib in AML, given up-regulation of multiple relevant pathways. METHODS: Adults were eligible if they were 18 years old or older with relapsed/refractory AML or if they were 70 years old or older with newly diagnosed AML but were ineligible for conventional therapy...
September 28, 2017: Cancer
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