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Qingkai Dai, Xiaojuan Liu, Hui Yang, Siqi Guo, Yuefang Wang, Luyun Peng, Lei Ye, Lan Chen, Chunqi Lai, Qi Chen, Ge Zhang, Yongmei Jiang
Detection of aberrant antigen expression in acute lymphoblastic leukemia (ALL) by flow cytometric is proposed for the quantification of minimal residual disease (MRD). There are few studies that investigate the stability of the antigen expression in children with B lineage ALL at the end of remission induction therapy and determine its prognostic impact. Between 2010 and 2015, 691 bone marrow specimens of childhood ALL were sent at diagnosis for immunophenotypic characterization, and follow-up samples for MRD were analyzed on day 33...
March 2, 2018: Leukemia Research
Cosimo Cumbo, Luciana Impera, Crescenzio Francesco Minervini, Paola Orsini, Luisa Anelli, Antonella Zagaria, Nicoletta Coccaro, Giuseppina Tota, Angela Minervini, Paola Casieri, Claudia Brunetti, Antonella Russo Rossi, Elisa Parciante, Giorgina Specchia, Francesco Albano
For monitoring minimal residual disease (MRD) in chronic myeloid leukemia (CML) the most recommended method is quantitative RT-PCR (RT-qPCR) for measuring BCR-ABL1 transcripts. Several studies reported that a DNA-based assay enhances the sensitivity of detection of the BCR-ABL1 genomic rearrangement, even if its characterization results difficult. We developed a DNA-based method for detecting and quantifying residual BCR-ABL1 positive leukemic stem cells in CML patients. We propose two alternative approaches: the first one is a fluorescence in situ hybridization (FISH)-based step followed by Sanger sequencing; the second one employs MinION, a single molecule sequencer based on nanopore technology...
February 16, 2018: Oncotarget
Łukasz Sędek, Prisca Theunissen, Elaine Sobral da Costa, Alita van der Sluijs-Gelling, Ester Mejstrikova, Giuseppe Gaipa, Alicja Sonsala, Magdalena Twardoch, Elen Oliveira, Michaela Novakova, Chiara Buracchi, Jacques J M van Dongen, Alberto Orfao, Vincent H J van der Velden, Tomasz Szczepański
BACKGROUND: Optimal discrimination between leukemic blasts and normal B-cell precursors (BCP) is critical for treatment monitoring in BCP acute lymphoblastic leukemia (ALL); thus identification of markers differentially expressed on normal BCP and leukemic blasts is required. METHODS: Multicenter analysis of CD73, CD86 and CD304 expression levels was performed in 282 pediatric BCP-ALL patients vs. normal bone marrow BCP, using normalized median fluorescence intensity (nMFI) values...
March 9, 2018: Journal of Immunological Methods
Maria S Yusseppone, Iara Rocchetta, Sebastian E Sabatini, Carlos M Luquet, Maria Del Carmen Ríos de Molina, Christoph Held, Doris Abele
Hypoxia in freshwater ecosystems is spreading as a consequence of global change, including pollution and eutrophication. In the Patagonian Andes, a decline in precipitation causes reduced lake water volumes and stagnant conditions that limit oxygen transport and exacerbate hypoxia below the upper mixed layer. We analyzed the molecular and biochemical response of the North Patagonian bivalve Diplodon chilensis after 10 days of experimental anoxia (<0.2 mg O2 /L), hypoxia (2 mg O2 /L), and normoxia (9 mg O2 /L)...
2018: Frontiers in Physiology
Zain A Bashey, Xu Zhang, Stacey Brown, Katelin Jackson, Lawrence E Morris, H Kent Holland, Asad Bashey, Scott R Solomon, Melhem Solh
Allografting from HLA-haploidentical donors (HID) is being increasingly utilized worldwide for patients lacking a conventional matched donor. However, its efficacy in older patients with AML and MDS is unclear. We analyzed 127 consecutive allografts for AML/MDS patients aged ≥ 60 years at our center to compare outcomes using HID to those of contemporaneous transplants using matched sibling (MRD) or matched unrelated (MUD) donors. Patient characteristics were similar except HID transplants were more likely in non-white patients and were more commonly performed with reduced intensity conditioning and a marrow graft...
March 9, 2018: Bone Marrow Transplantation
Małgorzata Szostakowska, Michał Szymczyk, Kalina Badowska, Barbara Tudek, Anna Fabisiewicz
The main cause of death in mantle cell lymphoma (MCL) patients is relapse due to undetermined minimal residual disease (MRD) and therefore monitoring MRD is crucial for making the best treatment decisions. The gold standard method for MRD analysis is the quantitative polymerase chain reaction. The most commonly used molecular markers for measuring MRD in MCL are: t(11;14)(q13;p32) translocation or CCND1 expression and IGH rearrangement. Such markers can, however, be found in other B cell non-Hodgkin lymphomas...
March 8, 2018: Medical Oncology
Tyler F Marcet, Natalie L Cápiro, Lawrence A Morris, Sayed M Hassan, Yi Yang, Frank E Löffler, Kurt D Pennell
Thermal treatment of soil and groundwater may provide an in situ source of soluble organic compounds and hydrogen (H2 ) that could stimulate microbial reductive dechlorination (MRD) at sites impacted by chlorinated solvents. The objectives of this study were to identify and quantify the release of electron donors and fermentable precursors during soil heating and to estimate availability of these compounds following thermal treatment. Fourteen solid materials containing <0.01 to 63.81 wt % organic carbon (OC) were incubated at 30, 60, or 90 °C for up to 180 d, leading to the release of direct electron donors (i...
March 8, 2018: Environmental Science & Technology
Xiangchou Yang, Rongxin Yao, Hong Wang
Studies employing mouse transplantation have illustrated the role of aldehyde dehydrogenase (ALDH) defining hematopoietic stem cells (HSCs) and leukemia stem cells (LSCs). Besides being a molecular marker, ALDH mediates drug resistance in AML, which induces poor prognosis of the patients. In AML patients, either CD34+ ALDHbr population or CD34+ CD38- ALDHint population was found to denote LSCs and minimal residual disease (MRD). A bunch of reagents targeting ALDH directly or indirectly have been evaluated. ATRA, disulfiram, and dimethyl ampal thiolester (DIMATE) are all shown to be potential candidates to open new perspective for AML treatment...
2018: BioMed Research International
Ji Li, Chang Wang, Xiaoliang Liu, Qiuju Liu, Hai Lin, Chunshui Liu, Fengyan Jin, Yan Yang, Ou Bai, Yehui Tan, Sujun Gao, Wei Li
To evaluate nutritional status in adult patients with acute leukemia (AL) using patient-generated subjective global assessment (PG-SGA) and to investigate the influence of nutritional status on prognosis.We observationally investigated 68 adult patients with newly diagnosed AL who received PG-SGA at the First Hospital of Jilin University between May 2013 and July 2015. Clinical features, chemotherapy regimens, biochemical indexes, body composition, complete remission (CR) rate, minimal residual disease (MRD), survival time, and side-effects of chemotherapy were compared between patients with and without severe malnutrition...
January 2018: Medicine (Baltimore)
E Tsitsikov, M H Harris, L B Silverman, S E Sallan, O K Weinberg
INTRODUCTION: Minimal residual disease (MRD) in B lymphoblastic leukemia has been demonstrated to be a powerful predictor of clinical outcome in numerous studies in both children and adults. In this study, we evaluated 86 pediatric patients with both diagnostic and remission flow cytometry studies and compared expression of CD81, CD58, CD19, CD34, CD20, and CD38 in the detection of MRD. METHODS: We evaluated 86 patients with B lymphoblastic leukemia who had both diagnostic studies and remission studies for the presence of MRD using multicolor flow cytometry...
March 2, 2018: International Journal of Laboratory Hematology
Martin Stanulla, Elif Dagdan, Marketa Zaliova, Anja Möricke, Chiara Palmi, Giovanni Cazzaniga, Cornelia Eckert, Geertruy Te Kronnie, Jean-Pierre Bourquin, Beat Bornhauser, Rolf Koehler, Claus R Bartram, Wolf-Dieter Ludwig, Kirsten Bleckmann, Stefanie Groeneveld-Krentz, Denis Schewe, Stefanie V Junk, Laura Hinze, Norman Klein, Christian P Kratz, Andrea Biondi, Arndt Borkhardt, Andreas Kulozik, Martina U Muckenthaler, Giuseppe Basso, Maria Grazia Valsecchi, Shai Izraeli, Britt-Sabina Petersen, Andre Franke, Petra Dörge, Doris Steinemann, Oskar A Haas, Renate Panzer-Grümayer, Hélène Cavé, Richard S Houlston, Gunnar Cario, Martin Schrappe, Martin Zimmermann
Purpose Somatic deletions that affect the lymphoid transcription factor-coding gene IKZF1 have previously been reported as independently associated with a poor prognosis in pediatric B-cell precursor (BCP) acute lymphoblastic leukemia (ALL). We have now refined the prognostic strength of IKZF1 deletions by analyzing the effect of co-occurring deletions. Patients and Methods The analysis involved 991 patients with BCP ALL treated in the Associazione Italiana Ematologia ed Oncologia Pediatrica-Berlin-Frankfurt-Muenster (AIEOP-BFM) ALL 2000 trial with complete information for copy number alterations of IKZF1, PAX5, ETV6, RB1, BTG1, EBF1, CDKN2A, CDKN2B, Xp22...
March 2, 2018: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
Philip A Thompson
No abstract text is available yet for this article.
March 1, 2018: Blood
Francesco Buccisano, Luca Maurillo, Maria Ilaria Del Principe, Ambra Di Veroli, Eleonora De Bellis, Annalisa Biagi, Anangiulia Zizzari, Valentina Rossi, Vito Rapisarda, Sergio Amadori, Maria Teresa Voso, Francesco Lo-Coco, William Arcese, Adriano Venditti
Response to therapy is affected by the genetic heterogeneity of acute myeloid leukemia (AML) and persistence of leukemic cells below the threshold of morphological complete remission (mCR). Such persistence is called minimal (or measurable) residual disease (MRD). Areas covered: MRD assessment allows early identification of patients who are at high risk of relapse and who should timely receive aggressive therapy (e.g. allogeneic stem cell transplantation) and of those with a good quality mCR in whom an aggressive front-line therapy can be spared, avoiding the harm of excessive treatment toxicity...
March 2, 2018: Expert Review of Hematology
Michael Lam, Jonathan M Loree, Allan Anderson Pereira Lima, Yun Shin Chun, Scott Kopetz
Current trial design is challenged by the advancement of technologies that have enabled deeper understanding of the molecular drivers of colorectal cancer (CRC). The speed of trial testing and the ability to test larger volumes of promising novel agents in the face of smaller populations identified by molecular profiling are challenges posed to clinical studies. Master protocols that utilize umbrella designs are equipped to deal with potential biomarker and matched treatments simultaneously. Although complex in nature, they increase trial efficiency by utilizing shared screening platforms, test multiple treatments together, and simplify regulatory submission and reporting under a common protocol...
February 27, 2018: Current Treatment Options in Oncology
Robert J Kreitman, Martin S Tallman, Tadeusz Robak, Steven Coutre, Wyndham H Wilson, Maryalice Stetler-Stevenson, David J FitzGerald, Linda Santiago, Guozhi Gao, Mark C Lanasa, Ira Pastan
Anti-CD22 moxetumomab pasudotox achieved 46% complete remissions (CRs) in previously reported phase I testing in relapsed/refractory hairy cell leukemia (HCL; n=28). The importance of minimal residual disease (MRD) after CR in HCL is unknown. A 21-patient extension cohort received 50 µg/kg every other day for 3 doses in 4-week cycles. These patients plus 12 previously reported at this upper dose level received 143 cycles without dose-limiting toxicity. The combined 33-patient cohort achieved 64% CR and 88% overall response rates, with median CR duration of 42...
February 27, 2018: Blood
Huda Salman, Xiao Shuai, Anh Thu Nguyen-Lefebvre, Banabihari Giri, Mingqiang Ren, Michael Rauchman, Lynn Robbins, Wei Hou, Hasan Korkaya, Yupo Ma
Similar signaling pathways could operate in both normal hematopoietic stem and progenitor cells (HSPCs) and leukemia stem cells (LSCs). Thus, targeting LSCs signaling without substantial toxicities to normal HSPCs remains challenging. SALL1, is a member of the transcriptional network that regulates stem cell pluripotency, and lacks significant expression in most adult tissues, including normal bone marrow (NBM). We examined the expression and functional characterization of SALL1 in NBM and in acute myeloid leukemia (AML) using in vitro and in vivo assays...
January 26, 2018: Oncotarget
Inhye E Ahn, Mohammed Z H Farooqui, Xin Tian, Janet Valdez, Clare Sun, Susan Soto, Jennifer Lotter, Stephanie Housel, Maryalice Stetler-Stevenson, Constance M Yuan, Irina Maric, Katherine R Calvo, Pia Nierman, Thomas E Hughes, Nakhle S Saba, Gerald E Marti, Stefania Pittaluga, Sarah E M Herman, Carsten U Niemann, Lone B Pedersen, Christian H Geisler, Richard Childs, Georg Aue, Adrian Wiestner
Safety and efficacy of ibrutinib (420mg) in chronic lymphocytic leukemia (CLL) were evaluated in a phase II study; 51 patients had TP53 aberration (TP53 cohort) and 35 were enrolled for age ≥ 65 years (elderly cohort). Both cohorts included patients with treatment-naïve (TN) and relapsed/refractory (RR) CLL. With the median follow-up of 4.8 years, 49 (57.0%) of 86 patients remain on study. Treatment was discontinued for progressive disease in 20 (23.3%) patients and for adverse events in 5 (5.8%). Atrial fibrillation occurred in 18 (20...
February 26, 2018: Blood
Zachary D Epstein-Peterson, Sean M Devlin, Eytan M Stein, Elihu Estey, Martin S Tallman
PURPOSE: Measurable residual disease (MRD) has prognostic importance for patients with acute myeloid leukemia (AML). How leukemia providers incorporate MRD into routine practice remains undefined. PATIENTS AND METHODS: A survey was developed and distributed to a large sample of leukemia physicians. Demographic information was collected along with details concerning MRD practices. A multivariable logistic regression model evaluated provider characteristics predictive of MRD utilization...
February 13, 2018: Leukemia Research
Sumit Gupta, Meenakshi Devidas, Mignon L Loh, Elizabeth A Raetz, Si Chen, Cindy Wang, Patrick Brown, Andrew J Carroll, Nyla A Heerema, Julie M Gastier-Foster, Kimberly P Dunsmore, Eric C Larsen, Kelly W Maloney, Leonard A Mattano, Stuart S Winter, Naomi J Winick, William L Carroll, Stephen P Hunger, Michael J Borowitz, Brent L Wood
Minimal residual disease (MRD) after initial therapy is integral to risk stratification in B-precursor and T-precursor acute lymphoblastic leukemia (B-ALL, T-ALL). Although MRD determines depth of remission, remission remains defined by morphology. We determined the outcomes of children with discordant assessments of remission by morphology vs. flow cytometry using patients age 1-30.99 years enrolled on Children's Oncology Group ALL trials who underwent bone marrow assessment at the end of induction (N = 9350)...
February 23, 2018: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
Z Meidani, M Farzandipour, A Davoodabadi, A Farrokhian, D Kheirkhah, M Sharifi, M E Khanghani
We investigated the effects of reinforced audit and feedback on the medical record documentation (MRD) of 35 surgical residents at a tertiary university hospital. In three phases (pre-intervention, 3 and 9-month post-intervention), 525 medical records were assessed. An educational guideline assisting residents to record more accurate MRD was developed. The MRD rate in the pre-intervention and immediate post-intervention phases had changed significantly. The MRD rate in the pre-intervention and 9 months after cessation of intervention was not statistically significant...
September 2017: Journal of the Royal College of Physicians of Edinburgh
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