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https://www.readbyqxmd.com/read/28721449/role-of-regulatory-t-cells-in-acute-myeloid-leukemia-patients-undergoing-relapse-preventive-immunotherapy
#1
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/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
#2
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
#3
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
#4
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/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
#5
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/28693523/inhibition-of-lin28b-impairs-leukemia-cell-growth-and-metabolism-in-acute-myeloid-leukemia
#6
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/28688919/haploidentical-hematopoietic-cell-transplant-with-post-transplant-cyclophosphamide-and-peripheral-blood-stem-cell-grafts-in-older-adults-with-aml-or-mds
#7
Michael Slade, John F DiPersio, Peter Westervelt, Ravi Vij, Mark A Schroeder, Rizwan Romee
Many hematologic malignancies are diseases of aging and the use of hematopoietic cell transplant (HCT) is growing rapidly among older adults. Modern post-transplant cyclophosphamide (PTCy) protocols with haploidentical (haplo) donors have dramatically expanded the donor pool for patients requiring HCT. Initial studies were performed with bone marrow grafts, which require the donor to undergo anesthesia during harvest. However, the use of mobilized peripheral blood stem cells (PBSC) may be desirable, especially with older donors...
July 5, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28682649/targeting-ras-signaling-in-aml-ralb-is-a-small-gtpase-with-big-potential
#8
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
#9
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/28679992/chemotherapy-for-a-child-with-relapsed-acute-myeloid-leukemia-complicated-with-persistent-hepatitis-c-virus-infection
#10
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
https://www.readbyqxmd.com/read/28673584/parp-inhibitors-in-acute-myeloid-leukaemia-therapy-how-a-synthetic-lethality-approach-can-be-a-valid-therapeutic-alternative
#11
Grigore Aristide Gafencu, Ciprian Ionuț Tomuleasa, Gabriel Ghiaur
Acute myeloid leukaemia (AML) is a malignancy in need of new therapeutic options. The current standard of care chemotherapy, leads to complete remission (CR) in the vast majority of adult patients under the age of 60. In contrast, CR rates in patients over the age of 60 reaches only 40-60%. While achievement of a CR is an important stepping stone in the treatment of AML, the majority of these patients experience relapse and die of their disease without adequate consolidation chemotherapy. Blood and marrow transplantation (BMT) can improve outcome in a select patient with AML but unfortunately, it is not a valid treatment option for the majority of older patients...
July 2017: Medical Hypotheses
https://www.readbyqxmd.com/read/28670893/osteopontin-b-and-c-isoforms-molecular-candidates-associated-with-leukemic-stem-cell-chemoresistance-in-acute-myeloid-leukemia
#12
Akram Mirzaei, Saeed Mohammadi, Seyed H Ghaffari, Mohsen Nikbakht, Davood Bashash, Kamran Alimoghaddam, Ardeshir Ghavamzadeh
Despite impressive advances in therapeutic approaches, long-term survival with acute myeloid leukemia (AML) is low as a result of treatment resistance and frequent relapse. Among multitude oncogenic proteins involved in acquisition of a chemo-resistanr phenotype, osteopontin (OPN) recently has attracted marked attention. In spite of the well-defined association between OPN expression and cure rate with solid tumors, there is a scarcity of information on any role of this protein in AML cases. Based on the critical role of OPN in cell survival, it seems reasonable to hypothesize that isoform expression levels may impact on regulation of apoptosis in AML cells in response to conventional chemotherapeutic drugs and its relation to relapse...
June 25, 2017: Asian Pacific Journal of Cancer Prevention: APJCP
https://www.readbyqxmd.com/read/28665351/specific-depletion-of-leukemic-stem-cells-can-micrornas-make-the-difference
#13
REVIEW
Tania Martiáñez Canales, David C de Leeuw, Eline Vermue, Gert J Ossenkoppele, Linda Smit
For over 40 years the standard treatment for acute myeloid leukemia (AML) patients has been a combination of chemotherapy consisting of cytarabine and an anthracycline such as daunorubicin. This standard treatment results in complete remission (CR) in the majority of AML patients. However, despite these high CR rates, only 30-40% (<60 years) and 10-20% (>60 years) of patients survive five years after diagnosis. The main cause of this treatment failure is insufficient eradication of a subpopulation of chemotherapy resistant leukemic cells with stem cell-like properties, often referred to as "leukemic stem cells" (LSCs)...
June 30, 2017: Cancers
https://www.readbyqxmd.com/read/28658145/central-hypothyroidism-in-a-pediatric-case-of-primary-acute-monoblastic-leukemia-with-central-nervous-system-infiltration-a-case-report
#14
Yuya Sato, Satomi Koyama, Shigeko Kuwashima, Masaya Kato, Mayuko Okuya, Keitaro Fukushima, Hidemitsu Kurosawa, Osamu Arisaka
RATIONALE: Central nervous system (CNS) leukemia is a frequent diagnosis in pediatric acute myeloblastic leukemia (AML) and includes neural symptoms. However, CNS leukemia is rarely associated with central hypsothyroidism. PATIENT CONCERNS AND DIAGNOSES: A 2-year-old female with AML with MLL rearrangement presented with CNS infiltration. Laboratory tests suggested the presence of central hypothyroidism (thyroid-stimulating hormone [TSH]: 0.48 mIU/ml, normal range 0...
June 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28655785/a-small-molecule-inhibitor-of-wee1-azd1775-synergizes-with-olaparib-by-impairing-homologous-recombination-and-enhancing-dna-damage-and-apoptosis-in-acute-leukemia
#15
Tamara B Garcia, Jonathan C Snedeker, Dmitry Baturin, Lori Gardner, Susan P Fosmire, Chengjing Zhou, Craig T Jordan, Sujatha Venkataraman, Rajeev Vibhakar, Christopher C Porter
Although some patients with acute leukemia have good prognoses, the prognosis of adult and pediatric patients who relapse or cannot tolerate standard chemotherapy is poor. Inhibition of WEE1 with AZD1775 has been shown to sensitize cancer cells to genotoxic chemotherapies including cytarabine in AML and T-ALL. Inhibition of WEE1 impairs homologous recombination by indirectly inhibiting BRCA2. Thus, we sought to determine if AZD1775 could sensitize cells to the PARP1/2 inhibitor olaparib. We found that combined treatment with AZD1775 and olaparib was synergistic in AML and ALL cells, and this combination impaired proliferative capacity upon drug withdrawal...
June 27, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28655096/-a-retrospective-analysis-of-prognosis-in-favorable-risk-acute-myeloid-leukemia-patients-with-different-consolidation-regimens
#16
H Y Wang, X B Bao, X W Tang, A N Sun, D P Wu, H X Zhou, H Y Qiu
Objective: To explore the impact on prognosis in favorable-risk acute myeloid leukemia (AML) patients with different consolidation regimens after first complete remission (CR(1)). Methods: A total of 107 cases of non-refractory adult AML from January 2010 to June 2015 in single center were enrolled in the study. HD-Ara-C group (38 cases) as the control group, we explore the prognosis in three consolidation regimens, including micro-transplantation (16 cases) , autologous transplantation (auto-PBSCT, 14 cases) , allogeneic transplantation (allo-HSCT, 39 cases)...
June 14, 2017: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
https://www.readbyqxmd.com/read/28654205/driving-toward-precision-medicine-for-acute-leukemias-are-we-there-yet
#17
Clement Chung, Hilary Ma
Despite recent progress in the understanding of the molecular basis of acute leukemias, treatment options for these diseases have not shown significant changes over the last few decades. In this review, we present a nonexhaustive key summary of the current cytogenetic and molecular changes associated with acute leukemias in disease prognostication and potential targeted therapies. An emerging paradigm is that many genetic or molecular alterations target similar signal transduction, transcriptional, and epigenetic pathways...
June 27, 2017: Pharmacotherapy
https://www.readbyqxmd.com/read/28650455/clinical-impact-of-nk-cell-reconstitution-after-reduced-intensity-conditioned-unrelated-cord-blood-transplantation-in-patients-with-acute-myeloid-leukemia-analysis-of-a-prospective-phase-ii-multicenter-trial-on-behalf-of-the-soci%C3%A3-t%C3%A3-fran%C3%A3-aise-de-greffe-de
#18
S Nguyen, A Achour, L Souchet, S Vigouroux, P Chevallier, S Furst, A Sirvent, J-O Bay, G Socié, P Ceballos, A Huynh, J Cornillon, S Francois, F Legrand, I Yakoub-Agha, G Michel, N Maillard, G Margueritte, S Maury, M Uzunov, C-E Bulabois, M Michallet, L Clement, C Dauriac, K Bilger, J Lejeune, V Béziat, V Rocha, B Rio, S Chevret, V Vieillard
Unrelated cord blood transplantation (UCBT) after a reduced intensity conditioning regimen (RIC) has extended the use of UCB in elderly patients and those with co-morbidities without an HLA-identical donor, although post-transplant relapse remains a concern in high-risk acute myeloid leukemia (AML) patients. HLA incompatibilities between donor and recipient might enhance the alloreactivity of natural killer (NK) cells after allogeneic hematopoietic stem-cell transplantation (HSCT). We studied the reconstitution of NK cells and KIR-L mismatch in 54 patients who underwent a RIC-UCBT for AML in CR in a prospective phase II clinical trial...
June 26, 2017: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/28646565/complete-molecular-remission-in-relapsed-and-refractory-acute-myeloid-leukaemia-with-mll-af9-treated-with-chidamide-based-chemotherapy
#19
Y Lun, J-J Yang, Y Wu
WHAT IS KNOWN AND OBJECTIVE: The mixed lineage leukaemia (MLL) gene translocations are found in approximately 10% of adults with acute myeloid leukaemia (AML) and are markers of poor prognosis. As the best reported response in relapsed and refractory MLL-rearranged AML is around 40%, reinduction treatment is very challenging for those patients. CASE DESCRIPTION: We report a case of relapsed and refractory AML with MLL-AF9, who did not respond to FLAG (fludarabine, cytarabine, granulocyte colony stimulating factor) regimen reinduction treatment, but achieved complete response and molecular remission after chidamide-based chemotherapy...
June 23, 2017: Journal of Clinical Pharmacy and Therapeutics
https://www.readbyqxmd.com/read/28643044/pd-1-signaling-and-inhibition-in-aml-and-mds
#20
REVIEW
Faysal Haroun, Sade A Solola, Samah Nassereddine, Imad Tabbara
Acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) are clinically and molecularly heterogeneous clonal myeloid disorders with a poor prognosis especially in the relapsed refractory setting and in patients above the age of 60. While allogeneic hematopoietic stem cell transplantation (ASCT) is a potentially curative approach, high relapse, morbidity, and mortality rates necessitate the development of alternative therapies. Immune checkpoint inhibitors unmask tumoral immune tolerance and have demonstrated efficacy in the treatment of chemotherapy-resistant hematologic and solid malignancies...
June 22, 2017: Annals of Hematology
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