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Relapsed acute myeloid leukemia

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https://www.readbyqxmd.com/read/29690909/targeting-chemotherapy-resistant-leukemia-by-combining-dnt-cellular-therapy-with-conventional-chemotherapy
#1
Branson Chen, Jong Bok Lee, Hyeonjeong Kang, Mark D Minden, Li Zhang
BACKGROUND: While conventional chemotherapy is effective at eliminating the bulk of leukemic cells, chemotherapy resistance in acute myeloid leukemia (AML) is a prevalent problem that hinders conventional therapies and contributes to disease relapse, and ultimately patient death. We have recently shown that allogeneic double negative T cells (DNTs) are able to target the majority of primary AML blasts in vitro and in patient-derived xenograft models. However, some primary AML blast samples are resistant to DNT cell therapy...
April 24, 2018: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/29686911/secondary-hlh-case-report-highlighting-clinical-challenges
#2
Riad El Fakih, Said Y Mohamed, Randa Alnounou, Ghada Elgohary
A 19-year-old patient with relapsed acute myeloid leukemia (AML) developed severe and prolonged cytopenia and unexplained jaundice and fever after salvage chemotherapy. His workup revealed hemophagocytosis on the bone marrow biopsy. He was treated for HLH (hemophagocytic lymphohistiocytosis) secondary to AML and chemotherapy. The patient died on day 56 after starting his salvage chemotherapy. Unexpectedly, after his death, the microbiology laboratory reported positive mycobacterial growth from a bronchoalveolar lavage (BAL) sample taken during the workup of his fever...
2018: Case Reports in Hematology
https://www.readbyqxmd.com/read/29685952/hypomethylating-agents-in-relapsed-and-refractory-aml-outcomes-and-their-predictors-in-a-large-international-patient-cohort
#3
Maximilian Stahl, Michelle DeVeaux, Pau Montesinos, Raphael Itzykson, Ellen K Ritchie, Mikkael A Sekeres, John D Barnard, Nikolai A Podoltsev, Andrew M Brunner, Rami S Komrokji, Vijaya R Bhatt, Aref Al-Kali, Thomas Cluzeau, Valeria Santini, Amir T Fathi, Gail J Roboz, Pierre Fenaux, Mark R Litzow, Sarah Perreault, Tae Kon Kim, Thomas Prebet, Norbert Vey, Vivek Verma, Ulrich Germing, Juan Miguel Bergua, Josefina Serrano, Steven D Gore, Amer M Zeidan
Although hypomethylating agents (HMAs) are frequently used in the frontline treatment of older acute myeloid leukemia (AML) patients, little is known about their effectiveness in relapsed or primary treatment-refractory (RR)-AML. Using an international multicenter retrospective database, we studied the effectiveness of HMAs in RR-AML and evaluated for predictors of response and overall survival (OS). A total of 655 patients from 12 centers received azacitidine (57%) or decitabine (43%), including 290 refractory (44%) and 365 relapsed (56%) patients...
April 24, 2018: Blood Advances
https://www.readbyqxmd.com/read/29684687/arsenic-trioxide-inhibits-proliferation-and-induced-apoptosis-of-leukemia-stem-cells-with-drug-resistance
#4
Chunxia Liu, Hulai Wei, Xiaojian Yao, Bei Liu, Yaming Xi, Li Zhao
Acute myeloid leukemia (AML) patients show high relapse rates and some develop conventional chemotherapy resistance. Leukemia Stem Cells (LSCs) are the main player for AML relapses and drug resistance. K562/ADM cell, a leukemia resistant cell subtype, was used as leukemia multidrug resistant model to explore drug resistance of leukemia cells. We found that CD34+ CD38- , CD34+ CD38- CD123+ , cell surface markers of LSCs were significantly high expressed in K562/ADM cell, not in K562 cell with less drug resistance; compared with LSCs from K562, multidrug resistance protein P-gp and BCRP expression were significantly higher in K562/ADM cell...
March 2, 2018: Leukemia Research
https://www.readbyqxmd.com/read/29684565/thiotepa-based-intensified-reduced-intensity-conditioning-adult-double-unit-cord-blood-hematopoietic-stem-cell-transplantation-results-in-decreased-relapse-rate-and-improved-survival-compared-to-transplantation-following-standard-reduced-intensity-conditioning
#5
Prashant Sharma, Daniel A Pollyea, Clayton A Smith, Enkhtsetseg Purev, Manali Kamdar, Bradley Haverkos, Daniel Sherbenou, Rachel Rabinovitch, Andrew Hammes, Jonathan A Gutman
The "Minnesota" reduced intensity conditioning (RIC) cord-blood transplantation (CBT) regimen (standard-RIC) of fludarabine (Flu, 200mg/m2 ), cyclophosphamide (Cy, 50mg/kg), and 200cGy or 300cGy total body irradiation (TBI) is the most published RIC CBT regimen. Though well tolerated, high relapse rates remain a concern with this regimen. Intensification of conditioning may reduce relapse without increasing transplant related mortality (TRM). We performed a retrospective cohort comparison of outcomes in adult patients who underwent first double-unit CBT with standard-RIC as compared to the intensified regimen of fludarabine 150mg/m2 , cyclophosphamide 50mg/kg, thiotepa 10mg/kg and 400cGy TBI (intensified-RIC)...
April 20, 2018: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/29684564/deep-npm1-sequencing-following-allogeneic-hematopoietic-cell-transplantation-improves-risk-assessment-in-adults-with-npm1-mutated-aml
#6
Yi Zhou, Megan Othus, Roland B Walter, Elihu H Estey, David Wu, Brent L Wood
Relapse is the major cause of death in patients with acute myeloid leukemia (AML) after allogeneic hematopoietic cell transplant (HCT). Measurable residual disease (MRD) detected by multiparameter flow cytometry (MFC) before and after HCT is a strong, independent risk factor for relapse. As next generation sequencing (NGS) is increasingly applied in AML MRD detection, it remains to be determined if NGS can improve prediction of post-HCT relapse. Herein, we investigated pre-HCT MRD detected by MFC and NGS in 59 adult patients with NPM1-mutated AML in morphologic remission; 45 of the 59 had post-HCT MRD determined by MFC and NGS around day 28...
April 20, 2018: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/29682375/myeloid-sarcoma-after-allogenic-stem-cell-transplantation-for-acute-myeloid-leukemia-successful-consolidation-treatment-approaches-in-two-patients
#7
Silje Johansen, Hilde Kollsete Gjelberg, Aymen Bushra Ahmed, Øystein Bruserud, Håkon Reikvam
Myeloid sarcoma is an extramedullary (EM) manifestation (i.e., manifestation outside the bone marrow) of acute myeloid leukemia (AML); it is assumed to be relatively uncommon and can be the only manifestation of leukemia relapse after allogenic stem cell transplantation (allo-SCT). An EM sarcoma can manifest in any part of the body, although preferentially manifesting in immunological sanctuary sites as a single or multiple tumors. The development of myeloid sarcoma after allo-SCT is associated with certain cytogenetic abnormalities, developing of graft versus host disease (GVHD), and treatment with donor lymphocytes infusion (DLI)...
2018: Case Reports in Oncological Medicine
https://www.readbyqxmd.com/read/29682194/a-novel-dual-pan-pim-flt3-inhibitor-sel24-exhibits-broad-therapeutic-potential-in-acute-myeloid-leukemia
#8
Wojciech Czardybon, Renata Windak, Aniela Gołas, Michał Gałęzowski, Aleksandra Sabiniarz, Izabela Dolata, Magdalena Salwińska, Paweł Guzik, Magdalena Zawadzka, Ewelina Gabor-Worwa, Bożena Winnik, Małgorzata Żurawska, Ewa Kolasińska, Ewelina Wincza, Marta Bugaj, Monika Danielewicz, Eliza Majewska, Milena Mazan, Grzegorz Dubin, Monika Noyszewska-Kania, Ewa Jabłońska, Maciej Szydłowski, Tomasz Sewastianik, Bartosz Puła, Anna Szumera-Ciećkiewicz, Monika Prochorec-Sobieszek, Elżbieta Mądro, Ewa Lech-Marańda, Krzysztof Warzocha, Jerome Tamburini, Przemysław Juszczyński, Krzysztof Brzózka
Fms-like tyrosine kinase 3 internal tandem duplication (FLT3-ITD) is one of the most common genetic lesions in acute myeloid leukemia patients (AML). Although FLT3 tyrosine kinase inhibitors initially exhibit clinical activity, resistance to treatment inevitably occurs within months. PIM kinases are thought to be major drivers of the resistance phenotype and their inhibition in relapsed samples restores cell sensitivity to FLT3 inhibitors. Thus, simultaneous PIM and FLT3 inhibition represents a promising strategy in AML therapy...
March 30, 2018: Oncotarget
https://www.readbyqxmd.com/read/29680875/salvage-regimens-using-conventional-chemotherapy-agents-for-relapsed-refractory-adult-aml-patients-a-systematic-literature-review
#9
REVIEW
Juan Eduardo Megías-Vericat, David Martínez-Cuadrón, Miguel Ángel Sanz, Pau Montesinos
Prognosis in relapsed and refractory acute myeloid leukemia (R/R AML) patients is dismal, with no satisfactory and standard salvage chemotherapy regimen. We performed a systematic review in order to analyze the clinical outcomes reported with conventional chemotherapy schemes in adult patients with R/R AML. To have a better understanding of the R/R ground, we included studies in R/R AML adult population at any disease stage (i.e., primary refractory as well as first relapse or beyond). Study selection included a total number of 157 out of 850 records, with a wide variety of schedules...
April 21, 2018: Annals of Hematology
https://www.readbyqxmd.com/read/29678639/transplant-outcomes-for-secondary-acute-myeloid-leukemia-alwp-of-the-ebmt-study
#10
Salyka Sengsayadeth, Myriam Labopin, Ariane Boumendil, Finke Jürgen, Ganser Arnold, Stelljes Matthias, Ehninger Gerhard, Beelen Dietrich, Niederwieser Dietger, Blaise Didier, Dreger Peter, Ghulam Mufti, Chevallier Patrice, Audrey Mailhol, Katie S Gatwood, Norbert Gorin, Jordi Esteve, Fabio Ciceri, Frederic Baron, Christoph Schmid, Sebastian Giebel, Mohamad Mohty, Bipin N Savani, Arnon Nagler
Secondary acute myeloid leukemia (sAML) has been associated with inferior outcomes compared to de novo AML. Little is known about patient risk factors and outcomes in sAML after allogeneic hematopoietic stem cell transplantation (HCT), thus this large systemic analysis of the EBMT registry was performed. This study included 4997 patients with sAML who received HCT from 2000-2016. In univariate analysis, the 2-year cumulative incidence of chronic graft versus host disease (GVHD), relapse (RI), and non-relapse mortality (NRM) were 33...
April 17, 2018: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/29670208/allohsct-for-inv-3-q21-q26-t-3-3-q21-q26-aml-a-report-from-the-acute-leukemia-working-party-of-the-european-society-for-blood-and-marrow-transplantation
#11
Kazimierz Halaburda, Myriam Labopin, Mohamed Houhou, Dietger Niederwieser, Jürgen Finke, Liisa Volin, Johan Maertens, Jan J Cornelissen, Noel Milpied, Gernot Stuhler, Nicolaus Kröger, Jordi Esteve, Mohamad Mohty, Arnon Nagler
Acute myeloid leukemia with inv(3)(q21;q26.2)/t(3;3)(q21;q26.2) (3q26 AML) is a rare disease with poor prognosis and median survival of <1 year. To evaluate allogeneic stem cell transplantation (alloHSCT) in the treatment of 3q26 AML, we studied 98 patients reported to the European Society for Blood and Marrow Transplantation between 1995 and 2013. Majority of patients were transplanted using peripheral blood, from unrelated donors and after myeloablative conditioning. Fifty-three patients were transplanted with active disease and 45 in complete remission...
April 18, 2018: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/29669568/social-preferences-for-health-states-associated-with-acute-myeloid-leukemia-for-patients-undergoing-treatment-in-the-united-kingdom
#12
Nacho Castejón, Joseph C Cappelleri, Jesús Cuervo, Kathryn Lang, Priyanka Mehta, Ruth Mokgokong, Carla Mamolo
BACKGROUND: Health state (HS) utility values for patients with acute myeloid leukemia (AML), a hematological malignancy, are not available in the United Kingdom (UK). This study aims to develop clinically sound HSs for previously untreated patients with AML and to assign utility values based on preferences of the general UK population. METHODS: This study was conducted in the UK and comprised 2 stages. During the first stage, AML HSs were drafted based on evidence from a literature review of AML clinical and health-related quality-of-life studies (published January 2000-June 2016) and patient-reported outcome measures previously used in this population...
April 18, 2018: Health and Quality of Life Outcomes
https://www.readbyqxmd.com/read/29668549/epigenetic-therapy-in-a-patient-with-down-syndrome-and-refractory-acute-myeloid-leukemia
#13
Kerri Becktell, Kerri Houser, Michael J Burke
Acute myeloid leukemia (AML) associated with Down syndrome (DS-AML) is a unique entity of AML with superior treatment response and overall survival compared with children with non-DS-AML. Despite good outcomes in DS-AML, those who relapse or have refractory disease have poor survival. Successful treatment of these patients is challenged by increased incidence of treatment-related toxicities often encountered with high-dose chemotherapy. Here we report the experience of epigenetic modifying agents (decitabine and vorinostat) followed by fludarabine, cytarabine, and granulocyte colony stimulating growth factor for a child with refractory DS-AML...
April 17, 2018: Journal of Pediatric Hematology/oncology
https://www.readbyqxmd.com/read/29665944/-current-status-and-challenges-of-car-t-immunotherapy-in-hematologic-malignancies-review
#14
Xin Cheng, Ya-Jie Wang, Shuai Feng, Ya-Yun Wu, Tong-Hua Yang, Xun Lai
The chimeric antigen receptor (CAR) T cell therapy has gradually became a new trend in the treatment of refractory and relapsed hematologic malignancies by developing for 30 years. With the exciting development of genetic engineering, CAR-T technology has subjected to 4 generations of innovation. Structure of CAR-T started from a single signal molecule to 2 or more than 2 co-stimulatory molecules, and then coding the CAR gene or promoter. CAR-T can specifically recognize tumor antigens, and does not be restricted by major histocompatibility complex (MHC), thus making a breakthrough in clinical treatment...
April 2018: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/29665938/-research-and-applications-progress-of-lenalidomide-in-relapsed-refractory-blood-system-diseases-review
#15
Wen-Jing Fan, Zhi-Qiao Fan, Tao Wu, Hai Bai
Lenalidomide, a novel immunomodulatory agent, is a kind of thalidomide derivatives, which shows a good efficacy and safety for hematological system diseases. This review is aimed to evaluate the efficacy and safety of lenalidomide in treatment of patients with multiple myeloma, chronic lymphocytic leukemia, acute myeloid leukemia, non-Hodgkin's lymphoma, classical Hodgkin's lymphoma and POEMS syndrome at their replased or refractory state. At the same time, this review focuses on the newest clinical research and the latest application progress of lenalidomide for relapsed or refractory hematological system diseases...
April 2018: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/29663558/usefulness-of-bcor-gene-mutation-as-a-prognostic-factor-in-acute-myeloid-leukemia-with-intermediate-cytogenetic-prognosis
#16
Kazuki Terada, Hiroki Yamaguchi, Toshimitsu Ueki, Kensuke Usuki, Yutaka Kobayashi, Kenji Tajika, Seiji Gomi, Saiko Kurosawa, Riho Saito, Yutaka Furuta, Keiki Miyadera, Taichiro Tokura, Atushi Marumo, Ikuko Omori, Masahiro Sakaguchi, Yusuke Fujiwara, Shunsuke Yui, Takeshi Ryotokuji, Kunihito Arai, Tomoaki Kitano, Satoshi Wakita, Takahiro Fukuda, Koiti Inokuchi
BCOR gene is a transcription regulatory factor that plays an essential role in normal hematopoiesis. The wider introduction of next-generation sequencing technology has led to reports in recent years of mutations in the BCOR gene in acute myeloid leukemia (AML), but the related clinical characteristics and prognosis are not sufficiently understood. We investigated the clinical characteristics and prognosis of 377 de novo AML cases with BCOR or BCORL1 mutation. BCOR or BCORL1 gene mutations were found in 28 cases (7...
April 16, 2018: Genes, Chromosomes & Cancer
https://www.readbyqxmd.com/read/29662244/refined-graft-versus-host-disease-relapse-free-survival-in-transplant-from-hla-identical-related-or-unrelated-donors-in-acute-myeloid-leukemia
#17
Giorgia Battipaglia, Annalisa Ruggeri, Myriam Labopin, Liisa Volin, Didier Blaise, Gerard Socié, Reza Tabrizi, Jan J Cornelissen, Ardeshir Ghavamzadeh, Anne Huynh, Depei Wu, Ibrahim Yakoub-Agha, Johan Maertens, Patrice Chevallier, Mohamad Mohty, Arnon Nagler
Refined graft-versus-host disease (GVHD)/relapse-free survival (GRFS) considers main outcomes of allogeneic stem cell transplant (HSCT), estimating long-term survival without significant morbidity as a surrogate of HSCT success. We compared GRFS in 5059 adults with acute myeloid leukemia (AML), undergoing HSCT in first complete remission from 2000 to 2015 either from a matched sibling (MSD, n = 3731) or unrelated donor (MUD, n = 1328). Median age was 49 (range: 18-76) years. Median follow-up was 32 and 60 months in MSD and MUD, respectively (p < 0...
April 16, 2018: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/29661755/a-cd123-targeting-antibody-drug-conjugate-imgn632-designed-to-eradicate-aml-while-sparing-normal-bone-marrow-cells
#18
Yelena Kovtun, Gregory E Jones, Sharlene Adams, Lauren Harvey, Charlene A Audette, Alan Wilhelm, Chen Bai, Lingyun Rui, Rassol Laleau, Fenghua Liu, Olga Ab, Yulius Setiady, Nicholas C Yoder, Victor S Goldmacher, Ravi V J Chari, Jan Pinkas, Thomas Chittenden
The outlook for patients with refractory/relapsed acute myeloid leukemia (AML) remains poor, with conventional chemotherapeutic treatments often associated with unacceptable toxicities, including severe infections due to profound myelosuppression. Thus there exists an urgent need for more effective agents to treat AML that confer high therapeutic indices and favorable tolerability profiles. Because of its high expression on leukemic blast and stem cells compared with normal hematopoietic stem cells and progenitors, CD123 has emerged as a rational candidate for molecularly targeted therapeutic approaches in this disease...
April 24, 2018: Blood Advances
https://www.readbyqxmd.com/read/29661208/unmanipulated-haploidentical-in-comparison-with-matched-unrelated-donor-stem-cell-transplantation-in-patients-60-years-and-older-with-acute-myeloid-leukemia-a-comparative-study-on-behalf-of-the-alwp-of-the-ebmt
#19
Nicole Santoro, Myriam Labopin, Federica Giannotti, Gerard Ehninger, Dietger Niederwieser, Arne Brecht, Matthias Stelljes, Nicolaus Kröger, Herman Einsele, Matthias Eder, Michael Hallek, Bertram Glass, Jürgen Finke, Fabio Ciceri, Mohamad Mohty, Annalisa Ruggeri, Arnon Nagler
BACKGROUND: Acute myeloid leukemia (AML) is both more common and with more biologically aggressive phenotype in the elderly. Allogenic stem cell transplantation (allo-SCT) is the best treatment option in fit patients. Either HLA-matched unrelated donor (MUD) or haploidentical (Haplo) donor are possible alternative for patients in need. METHODS: We retrospectively compared non-T-cell-depleted Haplo (n = 250) to 10/10 MUD (n = 2589) in AML patients ≥ 60 years...
April 16, 2018: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/29660836/final-results-of-a-phase-2-open-label-study-of-indisulam-idarubicin-and-cytarabine-in-patients-with-relapsed-or-refractory-acute-myeloid-leukemia-and-high-risk-myelodysplastic-syndrome
#20
Rita Assi, Hagop M Kantarjian, Tapan M Kadia, Naveen Pemmaraju, Elias Jabbour, Nitin Jain, Naval Daver, Zeev Estrov, Taisuke Uehara, Takashi Owa, Jorge E Cortes, Gautam Borthakur
BACKGROUND: Indisulam possesses anticancer properties through down-regulation of various cell-cycle checkpoint molecules, thereby blocking the phosphorylation of retinoblastoma protein and inducing p53 and p21. Indisulam exhibits synergy with nucleoside analogs and topoisomerase inhibitors. METHODS: The authors designed a phase 2 study of indisulam in combination with idarubicin and cytarabine in patients who had relapsed/refractory acute myeloid leukemia AML and high-risk myelodysplastic syndrome...
April 16, 2018: Cancer
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