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Relapsed acute myeloid leukemia

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https://www.readbyqxmd.com/read/28729150/impact-of-dendritic-cell-recovery-on-outcomes-after-umbilical-cord-blood-and-sibling-donor-transplantation-for-hematologic-malignancies
#1
Waseem Touma, Claudio G Brunstein, Michael R Verneris, Qing Cao, Julie Curtsinger, Jeffrey S Miller, Veronika Bachanova
Dendritic cells (DCs) orchestrate immune responses after allogeneic hematopoietic cell transplantation (HCT). We studied the association of donor myeloid DCs (mDCs) and plasmacytoid DCs (pDCs) recovery in the landmark analysis of umbilical cord blood (UCB) and matched related donor (RD) HCT. Eighty patients (42 UCB and 38 RD recipients) with a day 100 (D+100) blood sample were included in the analysis. Median age was 51 years (20-71). Most patients had acute leukemia (50%) or lymphoma (23%) and received reduced-intensity conditioning (75%)...
July 17, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28725544/successful-haploidentical-stem-cell-transplantation-with-prophylactic-administration-of-liposomal-amphotericin-b-after-invasive-pulmonary-zygomycosis
#2
Testuro Ochi, Yuta Katayama, Takeshi Okatani, Ryota Imanaka, Kohei Kyo, Mitsuhiro Itagaki, Shinya Katsutani, Koji Iwato, Hideki Asaoku
A 54-year-old woman with acute myeloid leukemia (AML) achieved complete remission by induction chemotherapy, but developed zygomycosis after consolidation therapy. As zygomycosis could not be cured by liposomal amphotericin B and micafungin, left lower lobectomy was performed. As AML relapsed 7 months after onset, she received haploidentical stem cell transplantation under administration of liposomal amphotericin B. Despite experiencing severe acute graft-versus-host disease, she remains alive with no relapse of either zygomycosis or AML...
December 2017: Medical Mycology Case Reports
https://www.readbyqxmd.com/read/28721449/role-of-regulatory-t-cells-in-acute-myeloid-leukemia-patients-undergoing-relapse-preventive-immunotherapy
#3
Frida Ewald Sander, Malin Nilsson, Anna Rydström, Johan Aurelius, Rebecca E Riise, Charlotta Movitz, Elin Bernson, Roberta Kiffin, Anders Ståhlberg, Mats Brune, Robin Foà, Kristoffer Hellstrand, Fredrik B Thorén, Anna Martner
Regulatory T cells (Tregs) 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(+) Tregs during immunotherapy and to determine the potential impact of Tregs on relapse risk and survival...
July 18, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28719902/serum-hyaluronic-acid-levels-are-altered-in-acute-leukemia-patients-potential-prognostic-implications
#4
Eleni Anagnostopoulou, Chrysanthi Papanastasopoulou, Maria Papastamataki, Antonia Kotsiou, Zoi Topouzoglou, Nikolaos Anagnostopoulos, Nikolaos Sitaras
BACKGROUND: Studies on the serum concentration of hyaluronic acid (HA) in newly diagnosed patients with acute myeloid leukemia (AML), B-acute lymphoblastic leukemia (B-ALL), and mantle-cell lymphoma (MCL) are scarce. In this study, we focused on investigating whether HA could serve as a possible prognostic marker in patients with AML, B-ALL, and MCL. METHODS: The serum concentration of HA was measured in a total of 51 patients with newly diagnosed AML, B-ALL, and MCL...
July 19, 2017: Acta Haematologica
https://www.readbyqxmd.com/read/28718728/a-phase-i-ii-randomized-trial-of-clofarabine-or-fludarabine-added-to-idarubicin-and-cytarabine-for-adults-with-relapsed-or-refractory-acute-myeloid-leukemia
#5
Nicholas J Short, Hagop Kantarjian, Farhad Ravandi, Xuelin Huang, Lianchun Xiao, Guillermo Garcia-Manero, William Plunkett, Varsha Gandhi, Koji Sasaki, Naveen Pemmaraju, Naval G Daver, Gautam Borthakur, Nitin Jain, Marina Konopleva, Zeev Estrov, Tapan M Kadia, William G Wierda, Courtney D DiNardo, Mark Brandt, Susan M O'Brien, Jorge E Cortes, Elias Jabbour
The purine nucleoside analogues clofarabine and fludarabine are active in acute myeloid leukemia (AML). We conducted a phase I/II randomized study of idarubicin and cytarabine with either clofarabine (CIA) or fludarabine (FIA) for relapsed or refractory AML. Clofarabine 15 mg/m(2) was identified as the recommended phase II dose. Eighty-one patients were assigned using adaptive randomization to CIA (n = 48) or FIA (n = 33). The complete response (CR)/CR without platelet recovery rate did not differ between CIA and FIA (38% versus 30%, respectively; p = ...
July 18, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28711727/a-chemotherapy-only-regimen-of-busulfan-melphalan-and-fludarabine-and-rabbit-atg-followed-by-allogeneic-t-cell-depleted-hematopoietic-stem-cell-transplants-for-the-treatment-of-myeloid-malignancies
#6
Barbara Spitzer, Ann A Jakubowski, Esperanza B Papadopoulos, Kirsten Fuller, Patrick D Hilden, James W Young, Juliet Barker, Guenther Koehne, Miguel-Angel Perales, Katharine C Hsu, Marcel R M van den Brink, Nancy A Kernan, Susan E Prockop, Andromachi Scaradavou, Hugo Castro-Malaspina, Richard J O'Reilly, Farid Boulad
We sought to develop a myeloablative chemotherapeutic regimen to secure consistent engraftment of T-cell depleted (TCD) hematopoietic stem cell transplants (HSCT) without the need for total body irradiation, thereby reducing toxicity, while maintaining low rates of GvHD and without increasing relapse. We investigated the myeloablative combination of busulfan and melphalan, with the immunosuppressive agents fludarabine and rabbit anti-thymocyte gloubin (r-ATG) as cytoreduction prior to a T-cell depleted HSCT...
July 12, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28710776/outcomes-of-patients-diagnosed-with-acute-myeloid-leukemia-after-solid-organ-transplantation
#7
Konstantinos Lontos, Mounzer Agha, Anastasios Raptis, Jing-Zhou Hou, Rafic Farah, Robert L Redner, Annie Im, Kathleen A Dorritie, Alison Sehgal, James Rossetti, Melissa Saul, William E Gooding, Abhinav Humar, Michael Boyiadzis
Organ transplant recipients are at an increased risk for subsequent cancer including acute myeloid leukemia (AML). Treatment of AML following solid transplantation represents a clinical challenge since most patients have significant co-morbidities at the time of AML diagnosis. In the current study, we evaluated the treatment and outcomes of patients who developed AML following solid organ transplantation at our institution and reviewed the literature on outcomes for these patients. The study cohort consisted of 14 patients (median age 66 years, range 52-77 years) with newly diagnosed AML following solid organ transplantation...
July 14, 2017: Clinical Transplantation
https://www.readbyqxmd.com/read/28710745/the-pan-bcl2-inhibitor-at101-activates-the-intrinsic-apoptotic-pathway-and-causes-dna-damage-in-acute-myeloid-leukemia-stem-like-cells
#8
Leisi Zhang, Yong Zhou, Kai Chen, Pengcheng Shi, Yin Li, Manman Deng, Zhiwu Jiang, Xiangmeng Wang, Peng Li, Bing Xu
BACKGROUND: Leukemia stem cells (LSCs) are considered to be the cause of treatment failure and relapse in acute myeloid leukemia (AML). Overexpression of the Bcl-2 family of anti-apoptotic proteins such as Bcl-2, Bcl-xl, and Mcl-1 accounts for survival and self-renewal of LSCs. AT101 binds to the BH3 motif of all Bcl-2 family anti-apoptotic proteins and demonstrates anti-tumor activity in multiple types of tumor. Thus, we hypothesized that this agent might have the potential to deplete LSCs...
July 14, 2017: Targeted Oncology
https://www.readbyqxmd.com/read/28710059/a-foxo1-induced-oncogenic-network-defines-the-aml1-eto-pre-leukemic-program
#9
Shan Lin, Anetta Ptasinska, Xiaoting Chen, Mahesh Shrestha, Salam A Assi, Paulynn S Chin, Maria R Imperato, Bruce Aronow, Jingsong Zhang, Matthew T Weirauch, Constanze Bonifer, James C Mulloy
Understanding and blocking the self-renewal pathway of pre-leukemia stem cells could prevent acute myeloid leukemia (AML) relapse. In this study we show that increased FOXO1 represents a critical mechanism driving aberrant self-renewal in pre-leukemic cells expressing the t(8;21)-associated oncogene AML1-ETO (AE). Though generally considered as a tumor suppressor, FOXO1 is consistently upregulated in t(8;21) AML. Expression of FOXO1 in human CD34+ cells promotes a pre-leukemic state with enhanced self-renewal and dysregulated differentiation...
July 14, 2017: Blood
https://www.readbyqxmd.com/read/28705639/genetic-and-epigenetic-heterogeneity-and-the-impact-on-cancer-relapse
#10
REVIEW
Tanzim Hassan, Ebrahim Afshinnekoo, Shixiu Wu, Christopher E Mason
Acute myeloid leukemia (AML) is an aggressive hematopoietic malignancy with an exceedingly poor prognosis, showing a 5-year overall survival rate of 40-45% in the young and a 5-year survival rate of below 10% in the elderly (>60y). Though a high percentage of patients enter complete remission following chemotherapeutic intervention, the majority of patients relapse within three years. Such stark prognostic outcomes highlight the need for additional clinical research, basic discovery, and molecular delineation of the etiologies and mechanisms behind responses to therapy that lead to relapse...
July 10, 2017: Experimental Hematology
https://www.readbyqxmd.com/read/28701479/on-the-origin-of-relapse-in-aml
#11
Brian A Jonas
Preexisting therapy-resistant leukemia stem cell populations underlie the cellular origin of relapse in acute myeloid leukemia.
July 12, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28696354/a-case-of-aml-characterized-by-a-novel-t-4-15-q31-q22-translocation-that-confers-a-growth-stimulatory-response-to-retinoid-based-therapy
#12
Justin M Watts, Aymee Perez, Lutecia Pereira, Yao-Shan Fan, Geoffrey Brown, Francisco Vega, Kevin Petrie, Ronan T Swords, Arthur Zelent
Here we report the case of a 30-year-old woman with relapsed acute myeloid leukemia (AML) who was treated with all-trans retinoic acid (ATRA) as part of investigational therapy (NCT02273102). The patient died from rapid disease progression following eight days of continuous treatment with ATRA. Karyotype analysis and RNA-Seq revealed the presence of a novel t(4;15)(q31;q22) reciprocal translocation involving the TMEM154 and RASGRF1 genes. Analysis of primary cells from the patient revealed the expression of TMEM154-RASGRF1 mRNA and the resulting fusion protein, but no expression of the reciprocal RASGRF1-TMEM154 fusion...
July 11, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28694637/isolated-intracranial-myeloid-sarcoma-occurring-as-relapse-in-acute-myeloid-leukemia
#13
Geetha Narayanan, Lali V Soman, Lakshmi Haridas, Harish Sugathan
Myeloid sarcoma (MS) or chloroma is a rare extramedullary tumor composed of extramedullary proliferation of blasts of granulocytic, monocytic, erythroid, or megakaryocytic lineage occurring at sites outside the bone marrow. MS occurs in 2%-8% of patients with acute myeloid leukemia (AML), sometimes it occurs as the presenting manifestation of relapse in a patient in remission. We describe the case of a young male with AML in remission for 6 years presenting with central nervous system symptoms. Magnetic resonance imaging showed an extra-axial altered intensity lesion in the parasagittal parietal region, infiltrating anterosuperiorly into anterior falx, and posterosuperior aspect of the superior sagittal sinus...
July 2017: Journal of Neurosciences in Rural Practice
https://www.readbyqxmd.com/read/28693523/inhibition-of-lin28b-impairs-leukemia-cell-growth-and-metabolism-in-acute-myeloid-leukemia
#14
Jianbiao Zhou, Chonglei Bi, Ying Qing Ching, Jing-Yuan Chooi, Xiao Lu, Jessie Yiying Quah, Sabrina Hui-Min Toh, Zit-Liang Chan, Tuan Zea Tan, Phyllis Sy Chong, Wee-Joo Chng
BACKGROUND: Current conventional chemotherapy for acute myeloid leukemia (AML) can achieve remission in over 70% of patients, but a majority of them will relapse within 5 years despite continued treatment. The relapse is postulated to be due to leukemia stem cells (LSCs), which are different from normal hematopoietic stem cells (HSCs). LIN28B is microRNA regulator and stem cell reprogramming factor. Overexpression of LIN28B has been associated with advance human malignancies and cancer stem cells (CSCs), including AML...
July 11, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28692033/spontaneous-loss-of-b-lineage-transcription-factors-leads-to-pre-b-leukemia-in-ebf1-bcl-xl-tg-mice
#15
J A Ramírez-Komo, M A Delaney, D Straign, K Lukin, M Tsang, B M Iritani, J Hagman
Early B-cell factor 1 (EBF1) plays a central role in B-cell lineage specification and commitment. Loss of this critical transcription factor is strongly associated with high-risk, relapsed and therapy-resistant B-cell-acute lymphoblastic leukemia, especially in children. However, Ebf1 haploinsufficient mice exhibit a normal lifespan. To determine whether prolonged survival of B cells would enable tumorigenesis in Ebf1 haploinsufficient animals, we generated Ebf1(+/-)Bcl-xL(Tg) mice, which express the anti-apoptotic factor Bcl-xL in B cells...
July 10, 2017: Oncogenesis
https://www.readbyqxmd.com/read/28687223/how-to-prevent-relapse-after-allogeneic-hematopoietic-stem-cell-transplantation-in-patients-with-acute-leukemia-and-myelodysplastic-syndrome
#16
REVIEW
N Yafour, F Beckerich, C E Bulabois, P Chevallier, E Daguindau, C Dumesnil, T Guillaume, A Huynh, S Masouridi Levrat, A L Menard, C Pautas, X Poiré, A Ravinet, M Michallet, A Bazarbachi
Disease relapse remains the first cause of mortality of hematological malignancies after allogeneic hematopoietic stem cell transplantation (allo-HCT). The risk of recurrence is elevated in acute myeloid leukemia (AML) patients with high-risk cytogenetic or molecular abnormalities, as well as when allo-HCT is performed in patients with refractory hematological malignancies or with persistent molecular or radiological (PET-CT scan) residual disease. For high risk AML and myelodysplasia (MDS), a post transplant maintenance strategy is possible, using hypomethylating agents or tyrosine kinase inhibitors (TKI) anti-FLT3 when the target is present...
July 4, 2017: Current Research in Translational Medicine
https://www.readbyqxmd.com/read/28682649/targeting-ras-signaling-in-aml-ralb-is-a-small-gtpase-with-big-potential
#17
Emily J Pomeroy, Craig E Eckfeldt
Acute myeloid leukemia (AML) is a devastating malignancy for which novel treatment approaches are desperately needed. Ras signaling is an attractive therapeutic target for AML because a large proportion of AMLs have mutations in NRAS, KRAS, or genes that activate Ras signaling, and key Ras effectors are activated in virtually all AML patient samples. This has inspired efforts to develop Ras-targeted treatment strategies for AML. Due to the inherent difficulty and disappointing efficacy of targeting Ras proteins directly, many have focused on inhibiting Ras effector pathways...
July 6, 2017: Small GTPases
https://www.readbyqxmd.com/read/28680951/health-related-quality-of-life-of-patients-with-acute-myeloid-leukemia-a-systematic-literature-review
#18
REVIEW
Ellen E Korol, Sisi Wang, Karissa Johnston, Farhad Ravandi-Kashani, Mark Levis, Floortje van Nooten
INTRODUCTION: Patients with acute myeloid leukemia (AML), especially those with relapsed or refractory AML, have poor clinical prognosis and outcomes. Health-related quality of life (HRQoL) assessments have become increasingly important in oncology, aiding in identifying and informing supportive therapy needs during treatment and beyond; however, HRQoL in hematology, and AML in particular, has received relatively minor attention. The aim was to identify and summarize estimates of HRQoL in patients with AML, including patients with relapsed or refractory AML...
2017: Oncology and Therapy
https://www.readbyqxmd.com/read/28680749/tumor-priming-converts-nk-cells-to-memory-like-nk-cells
#19
Marina Pal, Lisa Schwab, Anastasiya Yermakova, Emily M Mace, Rainer Claus, Ann-Christin Krahl, Jeanette Woiterski, Udo F Hartwig, Jordan S Orange, Rupert Handgretinger, Maya C André
Fascinating earlier evidence suggests an intrinsic capacity of human natural killer (NK) cells to acquire adaptive immune features in the context of cytomegalovirus (CMV) infection or pro-inflammatory cytokine stimulation. Since the role of memory NK cells in cancer has so far remained elusive and adoptive NK cell transfer in relapsing pediatric acute B cell precursor leukemia (BCP-ALL) patients awaits improvement, we asked the question whether tumor-priming could promote the generation of memory NK cells with enhanced graft-vs...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28679992/chemotherapy-for-a-child-with-relapsed-acute-myeloid-leukemia-complicated-with-persistent-hepatitis-c-virus-infection
#20
Shunsuke Kimura, Shinsuke Hirabayashi, Daisuke Hasegawa, Wakako Sumiya, Megumi Seya, Toshihiro Matsui, Yuri Yoshimoto, Yosuke Hosoya, Nobuyoshi Mori, Akira Matsui, Atsushi Manabe
An 8-year-old Mongolian female was diagnosed with acute myeloid leukemia (AML) and treated at a hospital in Mongolia according to the BFM-AML2004 SR protocol. Although complete remission (CR) was achieved, chemotherapy was interrupted because of shortage of drugs. The patient moved to Japan 7 months after diagnosis. Screening for viral infection revealed the presence of hepatitis C virus (HCV) antibody and RNA. At 11 months after initial diagnosis, the patient experienced bone marrow relapse and a RUNX1-RUNX1T1 fusion transcript was detected...
2017: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
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