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acute myeloide leukemia relapse

Masamichi Isobe, Takaaki Konuma, Seiko Kato, Susumu Tanoue, Mai Mizusawa, Maki Oiwa-Monna, Satoshi Takahashi, Arinobu Tojo
The different effects of pre-engraftment syndrome (PES) and acute graft-versus-host disease (GVHD) on transplant outcomes after cord blood transplantation (CBT) are unclear. We retrospectively evaluated the impact of PES and acute GVHD on relapse and survival after single CBT for 138 adult patients with hematological malignancies in our institute between 2004 and 2016. Multivariate analysis demonstrated that development of grade III to IV acute GVHD, particularly gut or liver involvement of acute GVHD, significantly contributed to higher non-relapse mortality (P<0...
February 13, 2019: Biology of Blood and Marrow Transplantation
Ralf Buettner, Le Xuan Truong Nguyen, Bijender Kumar, Corey Morales, Chao Liu, Lisa S Chen, Tea Pemovska, Timothy W Synold, Joycelynne Palmer, Ryan Thompson, Ling Li, Dinh Hoa Hoang, Bin Zhang, Lucy Ghoda, Claudia Kowolik, Mika Kontro, Calum Leitch, Krister Wennerberg, Xiaochun Xu, Ching-Cheng Chen, David Horne, Varsha Gandhi, Vinod Pullarkat, Guido Marcucci, Steven T Rosen
Nucleoside analogs represent the backbone of several distinct chemotherapy regimens for acute myeloid leukemia (AML) and combination with tyrosine kinase inhibitors has improved survival of AML patients, including those harboring the poor-risk FLT3-ITD mutation. Although these compounds are effective in killing proliferating blasts, they lack activity against quiescent leukemia stem cells (LSCs), which contributes to initial treatment refractoriness or subsequent disease relapse. The reagent 8-chloro-adenosine (8-Cl-Ado) is a ribose-containing, RNA-directed nucleoside analog that is incorporated into newly transcribed RNA rather than in DNA, causing inhibition of RNA transcription...
February 15, 2019: Journal of Cellular Physiology
Kirsten Tryde Macklon
INTRODUCTION: Ovarian tissue cryopreservation (OTC) is increasingly offered to women in need of fertility preservation. However, little is known about the risk of these women dying before they use the preserved material. MATERIAL AND METHODS: From 1999 to 2016, 927 girls and women underwent OTC in our center, prior to receiving gonadotoxic treatment. All patients were without disseminated disease and with an estimated chance of survival after 5 years of > 50%...
February 15, 2019: Acta Obstetricia et Gynecologica Scandinavica
Felicetto Ferrara, Federica Lessi, Orsola Vitagliano, Erika Birkenghi, Giuseppe Rossi
Considerable progress has been made in the treatment of acute myeloid leukemia (AML). However, current therapeutic results are still unsatisfactory in untreated high-risk patients and poorer in those with primary refractory or relapsed disease. In older patients, reluctance by clinicians to treat unfit patients, higher AML cell resistance related to more frequent adverse karyotype and/or precedent myelodysplastic syndrome, and preferential involvement of chemorefractory early hemopoietic precursors in the pathogenesis of the disease further account for poor prognosis, with median survival lower than six months...
February 14, 2019: Cancers
Sinem Namdaroglu, Ali Hakan Kaya, Hikmettullah Batgi, Omur Kayikci, Mehmet Sinan Dal, Dicle Iskender, Merih Kizil Cakar, Emre Tekgunduz, Fevzi Altuntas
Post-transplant cyclophosphamide has become a promising medical option after allogeneic HSCT. In this study we aimed to evaluate the efficacy of cyclophosphamide and cyclosporine combination in acute and chronic graft-versus-host disease (GvHD) prophylaxis in acute myeloid leukemia (AML) cases scheduled for allogeneic hematopoietic stem cell transplantation (allo-HSCT). Retrospective analysis of data from 40 cases who underwent allogeneic HSCT under GvHD prophylaxis with cyclophosphamide and cyclosporine combination between April 2016 and August 2017 was made...
February 14, 2019: Scientific Reports
Ping Chen, Weiwu Zhan, Bin Wang, Peidong You, Qing Jin, Diyu Hou, Xiaoting Wang, Ruolan You, Hong Zou, Yuanzhong Chen, Huifang Huang
Relapse of minimal residual disease (MRD) is a major problem after conventional chemotherapy in patients with acute myeloid leukemia (AML). The bone marrow stroma can protect AML cells from insults of chemotherapy, partly contributing to AML relapse. Arsenic trioxide (ATO) is the main component of arsenical traditional Chinese medicines and has been widely used for the treatment of hematologic malignancies particularly acute promyelocytic leukemia over the past three decades. ATO acts through a direct arsenic binding to cysteine residues in zinc fingers located in promyelocytic leukemia protein (PML), thus killing the leukemia stem cells (LSCs)...
February 11, 2019: Experimental Cell Research
Nicole A McNeer, John Philip, Heather Geiger, Rhonda E Ries, Vincent-Philippe Lavallée, Michael Walsh, Minita Shah, Kanika Arora, Anne-Katrin Emde, Nicolas Robine, Todd A Alonzo, E Anders Kolb, Alan S Gamis, Malcolm Smith, Daniela Se Gerhard, Jaime Guidry-Auvil, Soheil Meshinchi, Alex Kentsis
Acute myeloid leukemias (AML) are characterized by mutations of tumor suppressor and oncogenes, involving distinct genes in adults and children. While certain mutations have been associated with the increased risk of AML relapse, the genomic landscape of primary chemotherapy-resistant AML is not well defined. As part of the TARGET initiative, we performed whole-genome DNA and transcriptome RNA and miRNA sequencing analysis of pediatric AML with failure of induction chemotherapy. We identified at least three genetic groups of patients with induction failure, including those with NUP98 rearrangements, somatic mutations of WT1 in the absence of apparent NUP98 mutations, and additional recurrent variants including those in KMT2C and MLLT10...
February 13, 2019: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
Krzysztof Giannopoulos
The modest successes of targeted therapies along with the curative effects of allogeneic hematopoietic stem cell transplantation (alloHSCT) in acute myeloid leukemia (AML) stimulate the development of new immunotherapies. One of the promising methods of immunotherapy is the activation of immune response by the targeting of negative control checkpoints. The two best-known inhibitory immune checkpoints are cytotoxic T-lymphocyte antigen-4 (CTLA-4) and the programmed cell death protein 1 receptor (PD-1). In AML, PD-1 expression is observed in T-cell subpopulations, including T regulatory lymphocytes...
February 12, 2019: Journal of Clinical Medicine
Isabel S Jerchel, Alex Q Hoogkamer, Ingrid M Ariës, Judith M Boer, Nicolle J M Besselink, Marco J Koudijs, Rob Pieters, Monique L den Boer
The FGF receptor signaling pathway is recurrently involved in the leukemogenic processes. Oncogenic fusions of FGFR1 with various fusion partners were described in myeloid proliferative neoplasms, and overexpression and mutations of FGFR3 are common in multiple myeloma. In addition, fibroblast growth factors are abundant in the bone marrow, and they were shown to enhance the survival of acute myeloid leukemia cells. Here we investigate the effect of FGFR stimulation on pediatric BCP-ALL cells in vitro, and search for mutations with deep targeted next-generation sequencing of mutational hotspots in FGFR1, FGFR2, and FGFR3...
February 12, 2019: Scientific Reports
Marco S Nobile, Thalia Vlachou, Simone Spolaor, Daniela Bossi, Paolo Cazzaniga, Luisa Lanfrancone, Giancarlo Mauri, Pier Giuseppe Pelicci, Daniela Besozzi
Motivation: Acute myeloid leukemia is one of the most common hematological malignancies, characterized by high relapse and mortality rates. The inherent intra-tumor heterogeneity in acute myeloid leukemia is thought to play an important role in disease recurrence and resistance to chemotherapy. Although experimental protocols for cell proliferation studies are well established and widespread, they are not easily applicable to in vivo contexts, and the analysis of related time-series data is often complex to achieve...
February 7, 2019: Bioinformatics
Xiao-Ning Gao, Ji Lin, Li-Jun Wang, Fei Li, Hong-Hua Li, Shu-Hong Wang, Wen-Rong Huang, Chun-Ji Gao, Li Yu, Dai-Hong Liu
Donor lymphocyte infusion (DLI) might be used prophylactically to reduce relapse after allogeneic hematopoietic stem cell transplantation for very high-risk leukemia/lymphoma without effective targeted therapy. To compare the safety and efficacy of prophylactic DLI for prevention of relapse after allogeneic peripheral blood stem cell transplantation from haploidentical donors (HID-SCT) and matched-sibling donors (MSD-SCT) in patients with very high-risk acute myeloid leukemia (AML), we performed a retrospective analysis in a cohort of 21 HID-SCT and 13 MSD-SCT recipients, displaying similar baseline characteristics except for donor's gender distribution...
February 12, 2019: Annals of Hematology
Yahya Daneshbod, Leila Kohan, Vahideh Taghadosi, Olga K Weinberg, Daniel A Arber
Acute myeloid leukemia (AML) patients with a complex karyotype (CK-AML) show at least 3 unrelated clonal cytogenetic abnormalities with notoriously poor outcome. Such cases fall into either AML with myelodysplasia-related changes or therapy-related AML in the current World Health Organization classification of AML. Allogeneic stem cell transplantation is one of the only treatment modalities that can provide a long-term survival benefit and is recommended as a consolidative treatment in patients who are able to achieve complete remission...
February 11, 2019: Current Treatment Options in Oncology
Lucas Touzet, Florent Dumezy, Christophe Roumier, Céline Berthon, Claire Bories, Bruno Quesnel, Claude Preudhomme, Thomas Boyer
CD9 is a cell surface protein and belongs to the tetraspanin family. Its role in carcinomagenesis has been widely studied in solid tumors but remains controversial, depending on the cancer type. Although CD9 seems to be associated with unfavorable outcome and disease progression in acute lymphoblastic leukemia (ALL), this marker has not yet been studied in acute myeloid leukemia (AML). First, we explored its prognostic role and its association with biological factors in a cohort of 112 AML patients treated with intensive chemotherapy...
February 10, 2019: Cancer Medicine
Susanne Hofmann, Maria-Luisa Schubert, Lei Wang, Bailin He, Brigitte Neuber, Peter Dreger, Carsten Müller-Tidow, Michael Schmitt
Despite high response rates after initial chemotherapy in patients with acute myeloid leukemia (AML), relapses occur frequently, resulting in a five-year-survival by <30% of the patients. Hitherto, allogeneic hemotopoietic stem cell transplantation (allo-HSCT) is the best curative treatment option in intermediate and high risk AML. It is the proof-of-concept for T cell-based immunotherapies in AML based on the graft-versus-leukemia (GvL)-effect, but it also bears the risk of graft-versus-host disease. CD19-targeting therapies employing chimeric antigen receptor (CAR) T cells are a breakthrough in cancer therapy...
February 6, 2019: Journal of Clinical Medicine
Marie Sébert, Aline Renneville, Cécile Bally, Pierre Peterlin, Odile Beyne-Rauzy, Laurence Legros, Marie-Pierre Gourin, Laurence Sanhes, Eric Wattel, Emmanuel Gyan, Sophie Park, Aspasia Stamatoullas, Anne Banos, Kamel Laribi, Simone Jueliger, Luke Bevan, Fatiha Chermat, Rosa Sapena, Olivier Nibourel, Cendrine Chaffaut, Sylvie Chevret, Claude Preudhomme, Lionel Adès, Pierre Fenaux
High-risk myelodysplastic syndrome/acute myeloid leukemia patients have a very poor survival after azacitidine failure. Guadecitabine (SGI-110) is a novel subcutaneous hypomethylating agent, which results in extended decitabine exposure. This multicenter phase II study evaluated the efficacy and safety of guadecitabine in high-risk myelodysplastic syndrome and low blast count acute myeloid leukemia patients refractory or relapsing after azacitidine. We included 56 patients with a median age of 75 years (IQR 69-76)...
February 7, 2019: Haematologica
Ron Ram, Christof Scheid, Odelia Amit, Jens Markus Chemnitz, Yakir Moshe, Michael Hallek, Dominik Wolf, Irit Avivi, Udo Holtick
Primary refractory acute myeloid leukemia is associated with a dismal prognosis. The fludarabine, amsacrine, and cytarabine-reduced-intensity conditioning protocol (total body irradiation or treosulfan-based) has been described to be an effective approach in patients with refractory leukemia undergoing allogeneic hematopoietic cell transplantation . A modified protocol (without amsacrine) has been also used recently. We retrospectively analyzed the transplantation characteristics and outcomes of all consecutive patients between the years 2003 and 2017 (n=51) diagnosed with primary refractory acute myeloid leukemia who underwent transplantation at the University of Cologne and the Tel Aviv Medical Center...
February 7, 2019: Haematologica
Nahoko Hatsumi, Shuichi Miyawaki, Takahiro Yamauchi, Akihiro Takeshita, Norio Komatsu, Noriko Usui, Yukihiro Arai, Fumihiro Ishida, Takeshi Morii, Yasuhiko Kano, Michinori Ogura, Shinichiro Machida, Kazuhiro Nishii, Sumihisa Honda, Kazunori Ohnishi, Tomoki Naoe
Given the poor prognosis of patients with relapsed/refractory acute myeloid leukemia (AML), better therapy is needed. Fludarabine enhances the efficacy of Ara-C (cytarabine) by increasing intracellular Ara-C-triphosphate. The FLAG (fludarabine, high-dose Ara-C, supported with granulocyte colony-stimulating factor) regimen has been tested for use in AML patients by other investigators. In the phase II study reported here, we evaluated the efficacy and toxicity of FLAGM therapy (FLAG with mitoxantrone), further intensified by adding mitoxantrone, based on the results of a phase I study by our group...
February 6, 2019: International Journal of Hematology
Rebecca A Myers, Scott Wirth, Sherry Williams, Patrick J Kiel
Acute myeloid leukemia (AML) is a hematologic malignancy that affects predominantly older patients, with a median age of diagnosis around 67. Overall prognosis is poor; however, novel targeted therapies that can potentially improve outcomes in these patients have emerged in recent years. Mutations in isocitrate dehydrogenase (IDH) occur in 20% of AML diagnoses. IDH2 performs a crucial role in cellular metabolism, and when this enzyme is inhibited, the cell cannot rid itself of endogenous products and is thus marked for apoptosis...
May 2018: Journal of the Advanced Practitioner in Oncology
Giorgia Battipaglia, Ariane Boumendil, Myriam Labopin, Fabio Ciceri, Johanna Tischer, Matthias Stelljes, Gerhard Ehninger, Dietrich Beelen, Jürgen Finke, Maria Teresa Van Lint, Matthias Eder, Boris Afanasyev, Renato Fanin, Mohamad Mohty, Annalisa Ruggeri, Arnon Nagler
Refractory or relapsed acute myeloid leukemia (R/R-AML) has poor prognosis. Allogeneic hematopoietic stem-cell transplantation (HSCT) may provide cure in this scenario. We compared outcomes of HSCT from HLA-identical (HLA-id, n = 1654) sibling or haploidentical (Haplo, n = 389) donors in patients with R/R-AML, performed during the period 2007-2015. The Haplo group included patients receiving an unmanipulated graft (post-transplant cyclophosphamide, n = 278; in vivo T-cell depletion, n = 95; or both, n = 16)...
February 4, 2019: Bone Marrow Transplantation
Marco Cerrano, Raphael Itzykson
PURPOSE OF REVIEW: The extensive genomic characterization of acute myeloid leukemia (AML) led to the identification of a vast number of potential therapeutic targets. We review relevant data that have led to recent approval of new targeted therapies in AML and discuss the most promising drugs currently in development in this disease. RECENT FINDINGS: New formulations of cytotoxic agents, namely CPX-351 and gemtuzumab ozogamicin, improve the outcome of defined subgroup of patients...
February 4, 2019: Current Oncology Reports
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