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acute myeloide leukemia relapse

Lili Aslostovar, Allison L Boyd, Mohammed Almakadi, Tony J Collins, Darryl P Leong, Rommel G Tirona, Richard B Kim, Jim A Julian, Anargyros Xenocostas, Brian Leber, Mark N Levine, Ronan Foley, Mickie Bhatia
We completed a phase 1 dose-escalation trial to evaluate the safety of a dopamine receptor D2 (DRD2) antagonist thioridazine (TDZ), in combination with cytarabine. Thirteen patients 55 years and older with relapsed or refractory acute myeloid leukemia (AML) were enrolled. Oral TDZ was administered at 3 dose levels: 25 mg (n = 6), 50 mg (n = 4), or 100 mg (n = 3) every 6 hours for 21 days. Intermediate-dose cytarabine was administered on days 6 to 10. Dose-limiting toxicities (DLTs) included grade 3 QTc interval prolongation in 1 patient at 25 mg TDZ and neurological events in 2 patients at 100 mg TDZ (gait disturbance, depressed consciousness, and dizziness)...
August 14, 2018: Blood Advances
(no author information available yet)
The FDA approved ivosidenib for patients with IDH1 -mutant relapsed/refractory acute myeloid leukemia. The approval was based on results of a phase I trial in which 32.8% of patients treated with the drug had a complete remission or a complete remission with a partial hematologic recovery.
August 9, 2018: Cancer Discovery
Naghmeh Niktoreh, Beate Lerius, Martin Zimmermann, Bernd Gruhn, Gabriele Escherich, Jean-Pierre Bourquin, Michael Dworzak, Lucie Sramkova, Claudia Rossig, Ursula Creutzig, Dirk Reinhardt, Mareike Rasche
Despite intensified salvage treatments, children with relapsed/refractory acute myeloid leukemia have poor survival. We evaluated Gemtuzumab Ozogamicin (CD33-targeted drug) used on compassionate basis in patients diagnosed from 1995 until 2014 within Acute Myeloid Leukemia-Berlin-Frankfurt-Munster studies and identified 76 patients (<18 years) with highly-advanced and pretreated acute myeloid leukemia [refractory de novo acute myeloid leukemia (n=10), de novo acute myeloid leukemia refractory to relapse (1st early: n=41; 1st late: n=10; 2nd or more: n=10), and secondary acute myeloid leukemia (n=5)]...
August 9, 2018: Haematologica
Esther Onecha, Maria Linares, Inmaculada Rapado, Yanira Ruiz-Heredia, Pilar Martinez-Sanchez, Teresa Cedena, Marta Pratcorona, Jaime Perez Oteyza, Pilar Herrera, Eva Barragan, Pau Montesinos, Jose Antonio Garcia Vela, Elena Magro, Eduardo Anguita, Angela Figuera, Rosalia Riaza, Pilar Martinez-Barranco, Beatriz Sanchez-Vega, Josep Nomdedeu, Miguel Gallardo, Joaquin Martinez-Lopez, Rosa Ayala
A high proportion of patients with acute myeloid leukemia who achieve minimal residual disease (MRD) negative status ultimately relapse because a fraction of pathological clones remains undetected by standard methods. We designed and validated a high-throughput sequencing method for MRD assessment of cell clonotypes with mutations of NPM1, IDH1/2 and/or FLT3-SNVs. For clinical validation, 106 follow-up samples from 63 patients in complete remission were studied by NGS, evaluating the level of mutations detected at diagnosis...
August 9, 2018: Haematologica
Vikas Madan, Lin Han, Norimichi Hattori, Weoi Woon Teoh, Anand Mayakonda, Qiao-Yang Sun, Ling-Wen Ding, Hazimah Binte Mohd Nordin, Su Lin Lim, Pavithra Shyamsunder, Pushkar Dakle, Janani Sundaresan, Ngan B Doan, Masashi Sanada, Aiko Sato-Otsubo, Manja Meggendorfer, Henry Yang, Jonathan W Said, Seishi Ogawa, Torsten Haferlach, Der-Cherng Liang, Lee-Yung Shih, Tsuyoshi Nakamaki, Q Tian Wang, H Phillip Koeffler
Chromosomal translocation t(8;21)(q22;q22) which leads to generation of oncogenic RUNX1-RUNX1T1 (AML1-ETO) fusion is observed in about 10% of acute myelogenous leukemia (AML). To uncover somatic mutations that cooperate with t(8;21)-driven leukemia, we performed whole and targeted exome sequencing of an Asian cohort at diagnosis and relapse. We identified high frequency of truncating alterations in ASXL2 along with recurrent mutations of KIT, TET2, MGA, FLT3, and DHX15 in this subtype of AML. To investigate in-depth the role of ASXL2 in normal hematopoiesis, we utilized a mouse model of ASXL2 deficiency...
August 9, 2018: Haematologica
Nicolas Duployez, Alice Marceau-Renaut, Céline Villenet, Arnaud Petit, Alexandra Rousseau, Stanley W K Ng, Agnès Paquet, Fanny Gonzales, Adeline Barthélémy, Frédéric Leprêtre, Nicolas Pottier, Brigitte Nelken, Gérard Michel, André Baruchel, Yves Bertrand, Guy Leverger, Hélène Lapillonne, Martin Figeac, John E Dick, Jean C Y Wang, Claude Preudhomme, Meyling Cheok
Despite constant progress in prognostic risk stratification, children with acute myeloid leukemia (AML) still relapse. Treatment failure and subsequent relapse have been attributed to acute myeloid leukemia-initiating cells (LSC), which harbor stem cell properties and are inherently chemoresistant. Although pediatric and adult AML represent two genetically very distinct diseases, we reasoned that common LSC gene expression programs are shared and consequently, the highly prognostic LSC17 signature score recently developed in adults may also be of clinical interest in childhood AML...
August 8, 2018: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
Vipul Sheth, Myriam Labopin, Jonathan Canaani, Liisa Volin, Arne Brecht, Arnold Ganser, Jiri Mayer, Hélène Labussière-Wallet, Jörg Bittenbring, Roni Shouval, Bipin Savani, Mohammad Mohty, Arnon Nagler
FLAMSA followed by sequential reduced intensity conditioning and treosulfan/fludarabine are frequently used conditioning approaches used in centers of the European Society for Blood and Marrow Transplantation (EBMT) for older patients with acute myeloid leukemia (AML). It is currently unknown whether any of these regimens is superior to the others in terms of disease control and toxicity. Using the Acute Leukemia Working Party/EBMT multicenter registry we compared the outcomes of AML patients 45-65 of age transplanted between the years 2007 and 2016...
August 7, 2018: Bone Marrow Transplantation
Ling Wang, Raynier Devillier, Ming Wan, Justine Decroocq, Liang Tian, Sabine Fürst, Li-Ning Wang, Norbert Vey, Xing Fan, Didier Blaise, Jiong Hu
The purpose of the study was to evaluate the feasibility of conditioning regimen with sequential chemotherapy (FLAG-IDA), followed by Fludarabine (5 days) + Busulfan (3 days) by parallel analysis of patients with refractory acute myeloid leukemia (AML) from two transplantation centers in China and France. A total of 47 refractory AML with median bone marrow blast of 35% (1-90%) and median age at 42 years (16-62) were enrolled. Thirteen patients received peripheral stem cell transplantation (HSCT) from HLA-matched sibling donor, while 18 and 16 from unrelated or haplo-identical donors, respectively...
August 6, 2018: Bone Marrow Transplantation
Esther Schuler, Natalie Zadrozny, Sabine Blum, Thomas Schroeder, Corinna Strupp, Barbara Hildebrandt, Andrea Kündgen, Norbert Gattermann, Carlo Aul, Mustafa Kondakci, Guido Kobbe, Rainer Haas, Ulrich Germing
Intensive chemotherapy (IC) used to be a common treatment approach for patients with higher-risk myelodysplastic syndromes (MDS) or acute myeloid leukemia after MDS (sAML). We conducted a retrospective analysis of 299 patients, including a matched pair analysis comparing 96 patients receiving IC with 96 patients not undergoing IC, in order to evaluate the impact of IC on overall survival (OS) and to identify factors that influence remission rates and OS. Complete remission (CR) after first induction chemotherapy was reached in 50% of patients...
August 4, 2018: Annals of Hematology
Haowen Xiao, Li Li, Yan Pang, Yuanbin Wu, Zujun Jiang, Zenghui Liu, Jiulong Wu, Yang Xiao, Fen Huang, Qifa Liu, Hang Zhang, Yi Luo, He Huang
We describe the first multicenter prospective study to assess the efficacy, safety, and immune reconstitution of a novel sequential transplant approach in 24 patients with primary induction failure/relapsed acute myeloid leukemia (AML). The sequential regimen consisted of cladribine 5 mg/m2 /day and cytarabine 2 g/m2 /day for 5 days and mitoxantrone 7 mg/m2 /day for 3 days, followed by myeloablative allogeneic hematopoietic stem cell transplantation (allo-HSCT) using intravenous busulfan (3.2 mg/kg/day) for 4 days and cyclophosphamide (60 mg/kg/day) for 2 days...
August 4, 2018: Annals of Hematology
Lane H Miller, Cheng-Kui Qu, Melinda Pauly
The relationship between the hematopoietic stem cell (HSC) population and its surrounding bone marrow microenvironment is a rapidly evolving area of research. Normal HSC processes rely heavily on a complex communication network involving various marrow niches. While leukemogenesis largely results from abnormal genetic activity within the leukemia stem cell itself, mounting evidence indicates a significant contributory role played by marrow niche dysregulation. Furthermore, numerous instances of activating or inactivating germline mutations within marrow microenvironment cells have been shown to be sufficient for development of myelodysplastic syndrome (MDS), myeloproliferative neoplasm (MPN), and acute myeloid leukemia (AML), even in the context of wild type HSCs...
August 1, 2018: Experimental Hematology
Xiao-Dong Mo, Yu Wang, Xiao-Hui Zhang, Lan-Ping Xu, Chen-Hua Yan, Huan Chen, Yu-Hong Chen, Ya-Zhen Qin, Kai-Yan Liu, Xiao-Jun Huang
BACKGROUND: RUNX1-RUNX1T1 transcript levels were established as a powerful marker for predicting relapse in patients with t(8;21) acute myeloid leukemia (AML). We aimed to identify the efficacy of minimal residual disease (MRD)-directed interferon-alpha (IFN-α) treatment in patients with t(8;21) AML who were positive for MRD after allogeneic hematopoietic stem cell transplantation (allo-HSCT; n =42). SUBJECTS, MATERIALS, AND METHODS: MRD-positive status was defined as a <4...
August 3, 2018: Oncologist
Ji-Hao Zhou, Hai-Qing Lin, Qi Shen, Li-Na Hu, Guo-Qiang Li, Xiong-Fei Sun, Xin-You Zhang
In this study, we compared the efficacy of mitoxantrone in combination with intermediate-dose cytarabine (HAM) with that of high-dose cytarabine alone (HiDAC) as consolidation regimens in non-acute promyelocytic leukemia (APL) acute myeloid leukemia patients with favorable and intermediate cytogenetics. A total of 62 patients from Shenzhen People's Hospital were enrolled in this study. All patients enrolled received standard induction chemotherapy and achieved the first complete remission (CR1). In these patients, 24 received HiDAC and 38 received HAM as consolidation...
February 2018: Current medical science
Daniela Magliulo, Rosa Bernardi, Samantha Messina
Acute myeloid leukemia (AML) is a heterogeneous hematopoietic malignancy characterized by the accumulation of incompletely differentiated progenitor cells (blasts) in the bone marrow and blood, and by suppression of normal hematopoiesis. It has recently become apparent that the AML genome is characterized by recurrent mutations and dysregulations in epigenetic regulators. These mutations frequently occur before the onset of full blown leukemia, at the pre-leukemic phase, and persist in residual disease that remains after therapeutic intervention, thus suggesting that targeting the AML epigenome may help to eradicate minimal residual disease and prevent relapse...
2018: Frontiers in Oncology
Corina Schneidawind, Volker Hagmaier, Christoph Faul, Lothar Kanz, Wolfgang Bethge, Dominik Schneidawind
Allogeneic hematopoietic cell transplantation (HCT) is the treatment of choice for high-risk myeloid and lymphoid leukemias. Relapse after allogeneic HCT is associated with a dismal prognosis and further therapeutic options are limited. One potential curative approach is a second allogeneic HCT. However, there is no consensus about optimal transplant modalities, suitable patients, and entities. We performed a retrospective analysis of our institutional database to evaluate risk factors that influence survival after a second allogeneic HCT for the treatment of relapsed acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL)...
July 31, 2018: Annals of Hematology
Jennifer Hibma, Beverly Knight
BACKGROUND AND OBJECTIVE: Gemtuzumab ozogamicin is an antibody-drug conjugate composed of the anti-CD33 monoclonal antibody hP67.6 covalently linked to N-acetyl-gamma-calicheamicin dimethylhydrazide, a potent cytotoxic antibiotic. The aim of this study was to characterize the population pharmacokinetics of gemtuzumab ozogamicin, represented by total hP67.6 antibody and unconjugated calicheamicin, in adult patients with acute myeloid leukemia to support drug dosing strategies and explore intrinsic and extrinsic factors that may influence exposure...
July 30, 2018: Clinical Pharmacokinetics
Miriam Marquis, Cyrielle Beaubois, Vincent-Philippe Lavallée, Michal Abrahamowicz, Coraline Danieli, Sébastien Lemieux, Imran Ahmad, Andrew Wei, Stephen B Ting, Shaun Fleming, Anthony Schwarer, David Grimwade, William Grey, Robert K Hills, Paresh Vyas, Nigel Russell, Guy Sauvageau, Josée Hébert
In acute myeloid leukemia (AML), risk stratification based on cytogenetics and mutation profiling is essential but remains insufficient to select the optimal therapy. Accurate biomarkers are needed to improve prognostic assessment. We analyzed RNA sequencing and survival data of 430 AML patients and identified HMGA2 as a novel prognostic marker. We validated a quantitative PCR test to study the association of HMGA2 expression with clinical outcomes in 358 AML samples. In this training cohort, HMGA2 was highly expressed in 22...
July 19, 2018: Blood Cancer Journal
W Liu, Y Li, Z X Qiu, Y Yin, Y H Sun, W L Xu, Q Wang, Z Y Liang, Y J Dong, L H Wang, Q N Cen, M J Wang, W S Wang, J P Ou, H Y Ren
Objective: To investigate the therapeutic effects of allogeneic hematopoietic stem cell transplantation (allo-HSCT) with FLAG sequential busulfan/cyclophosphamide(Bu/Cy) conditioning regimen for refractory/relapsed acute myeloid leukemia. Methods: From February 2012 to June 2017, 21 patients with refractory/relapsed acute myeloid leukemia underwent allo-HSCT with FLAG sequential Bu/Cy conditioning regimen. Transplantation-related complications and clinical outcome were retrospectively analyzed. Results: After conditioning, no hepatic veno-occlusive disease (VOD) and grade Ⅲ hemorrhagic cystitis occurred...
August 1, 2018: Zhonghua Nei Ke za Zhi [Chinese Journal of Internal Medicine]
Francesca Lorentino, Myriam Labopin, Massimo Bernardi, Fabio Ciceri, Gerard Socié, Jan J Cornelissen, Jordi Esteve, Annalisa Ruggeri, Liisa Volin, Ibrahim Yacoub-Agha, Charles Craddock, Jacob Passweg, Didier Blaise, Tobias Gedde-Dahl, Monica Poiani, Nathalie Fegueux, Mohamad Mohty, Arnon Nagler
Allogeneic hematopoietic stem cell transplantation (HSCT) is the most powerful therapy preventing relapse in patients with adverse cytogenetics acute myeloid leukemia (AML) in first complete remission (CR1). In the absence of a matched related donor, potential alternatives include 10/10, 9/10 HLA-matched unrelated (UD) or haploidentical (Haplo) donors. We analyzed clinical outcomes of patients undergoing T-cell repleted Haplo (n=74), 10/10 UD (n=433) and 9/10 UD HSCT (n=123) from 2007 to 2015, reported to the EBMT Registry...
July 30, 2018: American Journal of Hematology
Sravanthi Ravulapati, Craig Siegel, Ameesh Dara, Jack M Lionberger
We present an unusual case of myeloid sarcoma with ascites and abdominal pain in which initial clinical, laboratory, and imaging studies suggested a gastrointestinal malignancy or lymphoma. Subsequent detection of leukemic ascites and blasts in a gastric, small bowel, and skin biopsy supported a diagnosis of myeloid sarcoma. Bone marrow biopsy revealed 15% blasts, and cytogenetics with an inversion 16 rearrangement was diagnostic of acute myeloid leukemia (AML). Positron emission tomography-computed tomography performed at presentation to stage a presumptive lymphoma found later utility in following the burden of extramedullary disease...
May 14, 2018: Hematology Reports
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