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https://www.readbyqxmd.com/read/29349042/an-optimized-targeted-next-generation-sequencing-approach-for-sensitive-detection-of-single-nucleotide-variants
#1
S Stasik, C Schuster, C Ortlepp, U Platzbecker, M Bornhäuser, J Schetelig, G Ehninger, G Folprecht, C Thiede
Monitoring of minimal residual disease (MRD) has become an important clinical aspect for early relapse detection during follow-up care after cancer treatment. Still, the sensitive detection of single base pair point mutations via Next-Generation Sequencing (NGS) is hampered mainly due to high substitution error rates. We evaluated the use of NGS for the detection of low-level variants on an Ion Torrent PGM system. As a model case we used the c.1849G > T (p.Val617Phe) mutation of the JAK2-gene. Several reaction parameters (e...
May 2018: Biomolecular Detection and Quantification
https://www.readbyqxmd.com/read/29348314/oncogenetics-and-mrd-in-pediatric-t-all
#2
(no author information available yet)
No abstract text is available yet for this article.
January 18, 2018: Blood
https://www.readbyqxmd.com/read/29337223/sequential-conditioning-with-thiotepa-in-t-cell-replete-hematopoietic-stem-cell-transplantation-for-the-treatment-of-refractory-hematological-malignancies-comparison-with-matched-related-haplo-mismatched-and-unrelated-donors
#3
Rémy Duléry, Anne-Lise Ménard, Sylvain Chantepie, Jean El Cheikh, Sylvie François, Jérémy Delage, Federica Giannotti, Annalisa Ruggeri, Eolia Brissot, Giorgia Battipaglia, Florent Malard, Ramdane Belhocine, Simona Sestili, Anne Vekhoff, François Delhommeau, Oumédaly Reman, Ollivier Legrand, Myriam Labopin, Marie-Thérèse Rubio, Mohamad Mohty
The results of conventional allogeneic stem cell transplantation (SCT) in refractory hematological malignancies are poor. Sequential strategies have shown promising results in refractory acute myeloid leukemia (AML), but have not been validated in a haploidentical (Haplo) setting. We developed a new sequential approach combining chemotherapy with broad anti-tumor activity (thiotepa 10 mg/kg, etoposide 400 mg/m2, cyclophosphamide 1600 mg/m2 from Day-15 to -10), followed after 3 days of rest by reduced-intensity conditioning regimen (fludarabine 150 mg/m2, intravenous busulfan 6...
January 11, 2018: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/29335633/long-term-survival-among-patients-who-are-disease-free-at-1-year-post-allogeneic-hematopoietic-cell-transplantation-a-single-center-analysis-of-389-consecutive-patients
#4
Melhem M Solh, Asad Bashey, Scott R Solomon, Lawrence E Morris, Xu Zhang, Stacey Brown, H Kent Holland
Allogeneic hematopoietic cell transplantation (HCT) is associated with significant morbidity and mortality especially in the first year after HCT. In this study, we examine the long-term outcomes of patients who survived at least one year post HCT without evidence of relapse. We analyzed the records for 389 consecutive patients receiving an allogeneic transplant from 2005 to 2016 from a MRD, MUD, or haploidentical donor, who were alive and disease free at one year post-transplant. Patient characteristics and outcome parameters were extracted from our institutional database where they had been prospectively entered...
January 15, 2018: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/29330405/better-outcome-with-haploidentical-over-hla-matched-related-donors-in-patients-with-hodgkin-s-lymphoma-undergoing-allogeneic-haematopoietic-cell-transplantation-a-study-by-the-francophone-society-of-bone-marrow-transplantation-and-cellular-therapy
#5
Jordan Gauthier, Xavier Poiré, Anne-Claire Gac, Mathieu Leclerc, Thierry Guillaume, Yves Chalandon, Stéphanie Nguyen, Edouard Forcade, Caroline Régny, Jacques-Olivier Bay, Ali Bazarbachi, Pierre-Simon Rohrlich, Anne Huynh, Jonathan Farhi, Tony Marchand, Jean-Valère Malfuson, Sylvain Pilorge, Hélène Labussière-Wallet, Cécile Renard, Luc-Matthieu Fornecker, Marie Detrait, Rémy Duléry, Jérémy Delage, Anne-Lise Ménard, Amandine Charbonnier, Brigitte Nelken, Charlotte Jubert, Felipe Suarez, Régis Peffault de la Tour, Yves Beguin, Hélène Schoemans, Didier Blaise, Ibrahim Yakoub-Agha
The question of the best donor type between haploidentical (HAPLO) and matched-related donors (MRD) for patients with advanced HL receiving an allogeneic hematopoietic cell transplantation (allo-HCT) is still debated. Given the lack of data comparing these two types of donor in the setting of non-myeloablative (NMA) or reduced-intensity (RIC) allo-HCT, we performed a multicentre retrospective study using graft-vs.-host disease-free relapse-free survival (GRFS) as our primary endpoint. We analysed the data of 151 consecutive HL patients who underwent NMA or RIC allo-HCT from a HAPLO (N  =  61) or MRD (N  =  90) between January 2011 and January 2016...
January 12, 2018: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/29330221/minimal-measurable-residual-disease-in-aml-consensus-document-from-eln-mrd-working-party
#6
Gerrit J Schuurhuis, Michael Heuser, Sylvie Freeman, Marie-Christine Béné, Francesco Buccisano, Jacqueline Cloos, David Grimwade, Torsten Haferlach, Robert K Hills, Christopher S Hourigan, Jeffrey L Jorgensen, Wolfgang Kern, Francis Lacombe, Luca Maurillo, Claude Preudhomme, Bert A van der Reijden, Christian Thiede, Adriano Venditti, Paresh Vyas, Brent L Wood, Roland B Walter, Konstanze Döhner, Gail J Roboz, Gert J Ossenkoppele
Measurable residual disease (MRD, previously termed minimal residual disease) is an independent, post-diagnosis, prognostic indicator in acute myeloid leukemia (AML) that is important for risk stratification and treatment planning, in conjunction with other well-established clinical, cytogenetic, and molecular data assessed at diagnosis. MRD can be evaluated using a variety of multi-parameter flow cytometry (MFC) and molecular protocols but, to date, these approaches have not been qualitatively or quantitatively standardized, making their use in clinical practice challenging...
January 12, 2018: Blood
https://www.readbyqxmd.com/read/29318644/description-and-prognostic-significance-of-the-kinetics-of-minimal-residual-disease-status-in-adults-with-acute-lymphoblastic-leukemia-treated-with-hypercvad
#7
Ryan D Cassaday, Philip A Stevenson, Brent L Wood, Pamela S Becker, Paul C Hendrie, Brenda M Sandmaier, Jerald L Radich, Andrei R Shustov
HyperCVAD is a commonly-used regimen for adults with newly-diagnosed acute lymphoblastic leukemia (ALL). However, relatively little is known about the application of minimal residual disease (MRD) detection with this treatment. To address this, we studied 142 adults with ALL treated with hyperCVAD over a 10-year period who had MRD assessed by either multi-parameter flow cytometry or (for patients with Philadelphia chromosome positive ALL) reverse transcriptase polymerase chain reaction for the BCR-ABL1 translocation...
January 10, 2018: American Journal of Hematology
https://www.readbyqxmd.com/read/29316245/flow-cytometric-aberrancies-in-plasma-cell-myeloma-and-mgus-correlation-with-laboratory-parameters
#8
Sarika Gupta, Nitin J Karandikar, Timothy Ginader, Andrew M Bellizzi, Carol J Holman
BACKGROUND: Multiparametric flow cytometry (MFC) is a useful tool for diagnosis of plasma cell dyscrasias and assessment of minimal residual disease (MRD) in plasma cell myeloma (PCM). However, the immunophenotypic differences between the clonal plasma cells (PCs) of plasma cell myeloma (PCM) and those of monoclonal gammopathy of undetermined significance (MGUS) as well as the correlation of these flow cytometric markers with pertinent laboratory parameters have not been evaluated. METHODS: We retrospectively identified all newly diagnosed treatment-naive PCM and MGUS patients between 09/2014 and 06/2015 who underwent 10-color flow-cytometric evaluation: CD45, CD38, CD138, cKappa, cLambda, CD19, CD27, CD28, CD56, CD117...
January 6, 2018: Cytometry. Part B, Clinical Cytometry
https://www.readbyqxmd.com/read/29297965/the-impact-of-alternative-donor-types-on-viral-infections-in-pediatric-hematopoietic-stem-cell-transplantation
#9
D Atay, A Akcay, F Erbey, G Ozturk
Viral infections remain one of the most important complications following allogeneic HSCT. Few reports compare virus infection between different donor types in pediatric patients. We retrospectively analyzed viral infections and the outcome of one hundred and seventy-one pediatric patients (median 7.38 years) who underwent allogeneic HSCT from matched related donor (MRD, n = 71), 10 of 10 HLA allele-matched unrelated donors (MUD1; n = 29), 9 of 10 HLA allele-matched unrelated donors (MUD2; n = 40), and haploidentical donors (n = 31)...
January 3, 2018: Pediatric Transplantation
https://www.readbyqxmd.com/read/29297932/inhibition-of-novel-gcn5-atm-axis-restricts-the-onset-of-acquired-drug-resistance-in-leukemia
#10
Sameer Salunkhe, Saket V Mishra, Jyothi Nair, Samadri Ghosh, Neha Choudhary, Ekjot Kaur, Sanket Shah, Ketaki Patkar, Dev Anand, Navin Khattry, Syed K Hasan, Shilpee Dutt
Leukemia is majorly treated by topoisomerase inhibitors that induce DNA double strand breaks (DSB) resulting in cell death. Consequently, modulation of DSB repair pathway renders leukemic cells resistant to therapy. Since we do not fully understand the regulation of DSB repair acquired by resistant cells, targeting these cells has been a challenge. Here we investigated the regulation of DSB repair pathway in Early Drug Resistant Population (EDRP) and Late Drug Resistant Population (LDRP). We found that doxorubicin induced equal DSBs in parent and EDRP cells however; cell death is induced only in the parent cells...
January 3, 2018: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29296964/alternative-donors-for-allogeneic-hematopoietic-stem-cell-transplantation-in-poor-risk-aml-in-cr1
#11
Jurjen Versluis, Myriam Labopin, Annalisa Ruggeri, Gerard Socie, Depei Wu, Liisa Volin, Didier Blaise, Noel Milpied, Charles Craddock, Ibrahim Yakoub-Agha, Johan Maertens, Per Ljungman, Anne Huynh, Mauricette Michallet, Eric Deconinck, Patrice Chevallier, Jakob Passweg, Fabio Ciceri, Mohamad Mohty, Jan J Cornelissen, Arnon Nagler
Allogeneic hematopoietic stem cell transplantation (alloHSCT) remains the treatment of choice to consolidate remission in patients with poor-risk acute myeloid leukemia (AML). With increasing alternative donors available, the preferred donor or stem cell source is debated. We set out to study outcome in recipients of alloHSCT with poor-risk AML in first complete remission (CR1) by donor type. A total of 6545 adult patients with poor-risk AML in CR1 receiving an alloHSCT using matched related donor (MRD, n = 3511) or alternative donors, including 10/10 (n = 1959) or 9/10 matched unrelated donors (MUDs, n = 549), umbilical cord blood (UCB) grafts (n = 333), or haplo-identical (haplo) donors (n = 193) were compared...
February 28, 2017: Blood Advances
https://www.readbyqxmd.com/read/29296895/minimal-residual-disease-in-adult-all-technical-aspects-and-implications-for-correct-clinical-interpretation
#12
REVIEW
Monika Brüggemann, Michaela Kotrova
Nowadays, minimal residual disease (MRD) is accepted as the strongest independent prognostic factor in acute lymphoblastic leukemia (ALL). It can be detected by molecular methods that use leukemia-specific or patient-specific molecular markers (fusion gene transcripts, or immunoglobulin/T-cell receptor [IG/TR] gene rearrangements), and by multi-parametric flow cytometry. The sensitivity and specificity of these methods can vary across treatment time points and therapeutic settings. Thus, knowledge of the principles and limitations of each technology is of the utmost importance for correct interpretation of MRD results...
November 28, 2017: Blood Advances
https://www.readbyqxmd.com/read/29296837/baseline-mutational-patterns-and-sustained-mrd-negativity-in-patients-with-high-risk-smoldering-myeloma
#13
Sham Mailankody, Dickran Kazandjian, Neha Korde, Mark Roschewski, Elisabet Manasanch, Manisha Bhutani, Nishant Tageja, Mary Kwok, Yong Zhang, Adriana Zingone, Laurence Lamy, Rene Costello, Candis Morrison, Malin Hultcrantz, Austin Christofferson, Megan Washington, Martin Boateng, Seth M Steinberg, Maryalice Stetler-Stevenson, William D Figg, Elli Papaemmanuil, Wyndham H Wilson, Jonathan J Keats, Ola Landgren
Early results of a prospective phase 2 clinical trial of carfilzomib, lenalidomide, and dexamethasone followed by lenalidomide maintenance in high-risk smoldering myeloma showed promising results that were previously published. Here, we provide novel insights into the genetic landscape of high-risk smoldering myeloma and information on sustained minimal residual disease (MRD) negativity with an expanded cohort of patients. Eighteen patients with high-risk smoldering myeloma were enrolled between 29 May 2012, and 14 January 2014...
October 10, 2017: Blood Advances
https://www.readbyqxmd.com/read/29296758/inotuzumab-ozogamicin-in-adults-with-relapsed-or-refractory-cd22-positive-acute-lymphoblastic-leukemia-a-phase-1-2-study
#14
Daniel J DeAngelo, Wendy Stock, Anthony S Stein, Andrei Shustov, Michaela Liedtke, Charles A Schiffer, Erik Vandendries, Katherine Liau, Revathi Ananthakrishnan, Joseph Boni, A Douglas Laird, Luke Fostvedt, Hagop M Kantarjian, Anjali S Advani
This study evaluated the safety, antitumor activity, pharmacokinetics, and pharmacodynamics of inotuzumab ozogamicin (InO) for CD22-positive relapsed/refractory acute lymphoblastic leukemia. In phase 1, patients received InO 1.2 (n = 3), 1.6 (n = 12), or 1.8 (n = 9) mg/m2 per cycle on days 1, 8, and 15 over a 28-day cycle (≤6 cycles). The recommended phase 2 dose (RP2D) was confirmed (expansion cohort; n = 13); safety and activity of InO were assessed in patients receiving the RP2D in phase 2 (n = 35) and in all treated patients (n = 72)...
June 27, 2017: Blood Advances
https://www.readbyqxmd.com/read/29296748/immune-signatures-associated-with-improved-progression-free-and-overall-survival-for-myeloma-patients-treated-with-ahsct
#15
Christine M Ho, Philip L McCarthy, Paul K Wallace, Yali Zhang, Ahmad Fora, Patrick Mellors, Joseph D Tario, Benjamin L S McCarthy, George L Chen, Sarah A Holstein, Sophia R Balderman, Xuefang Cao, Bruno Paiva, Theresa Hahn
Multiple therapeutic options exist for multiple myeloma (MM), including autologous hematopoietic stem cell transplantation (AHSCT). Measurement of minimal residual disease (MRD) and immune reconstitution is rapidly becoming an integral part of the care of MM patients. We investigated comprehensive immune profiling (IP) associated with progression-free survival (PFS) and overall survival (OS). From August 2007 to January 2014, 101 consecutive MM patients underwent peripheral blood IP and marrow MRD testing before and approximately 100 days after AHSCT...
June 27, 2017: Blood Advances
https://www.readbyqxmd.com/read/29296716/mrd-detection-in-multiple-myeloma-comparison-between-mskcc-10-color-single-tube-and-euroflow-8-color-2-tube-methods
#16
Mikhail Roshal, Juan A Flores-Montero, Qi Gao, Maesa Koeber, Jessica Wardrope, Brian G M Durie, Ahmet Dogan, Alberto Orfao, Ola Landgren
In patients with multiple myeloma, obtaining posttreatment minimal residual disease (MRD) negativity is associated with longer progression-free survival and overall survival. Here, we compared the diagnostic performance of a single 10-color tube with that of a EuroFlow 8-color 2-tube panel for MRD testing. Bone marrow samples from 41 multiple myeloma patients were tested in parallel using the 2 approaches. Compared with the sum of the cells from the EuroFlow two 8-color tubes, the Memorial Sloan Kettering Cancer Center (MSKCC) single 10-color tube had a slight reduction in total cell number with a mean ratio of 0...
May 9, 2017: Blood Advances
https://www.readbyqxmd.com/read/29289758/comparison-of-autologous-stem-cell-transplantation-versus-haploidentical-donor-stem-cell-transplantation-for-favorable-and-intermediate-risk-acute-myeloid-leukemia-patients-in-first-complete-remission
#17
Jia Chen, Lingyi Yang, Yi Fan, Yang Xu, Yue Han, Xiaowen Tang, Huiying Qiu, Chengcheng Fu, Miao Miao, Feng Chen, Depei Wu
Stem cell transplantation (SCT) is an attractive post-remission treatment option for patients with intermediate-risk acute myeloid leukemia (AML) and for some favorable-risk AML patients with additional non-genetic risk factors. Autologous SCT (auto-SCT) and haplo-identical donor SCT (haplo-SCT) are the widely used alternatives in case of a lack of a human leukocyte antigen (HLA)-matched donor. However, limited data have been published on the direct comparison between these two transplant types. Based on the transplantation database in our center, we conducted a retrospective study involving patients with favorable- and intermediate-risk AML in first complete remission (CR1), according to the NCCN guideline...
December 28, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/29284596/measurable-residual-disease-detection-by-high-throughput-sequencing-improves-risk-stratification-for-pediatric-b-all
#18
Brent Wood, David Wu, Beryl Crossley, Yunfeng Dai, David Williamson, Charles Gawad, Michael J Borowitz, Meenakshi Devidas, Kelly W Maloney, Eric Larsen, Naomi Winick, Elizabeth Raetz, William L Carroll, Stephen P Hunger, Mignon Loh, Harlan Robins, Ilan Kirsch
Early response to induction chemotherapy is an important prognostic factor in B lymphoblastic leukemia (B-ALL). Here, we compare high throughput sequencing (HTS) of IGH and TRG genes versus flow cytometry (FC) for measurable residual disease (MRD) detection at the end of induction chemotherapy in pediatric patients with newly diagnosed B-ALL. 619 paired pretreatment and end of induction bone marrow samples from Children's Oncology Group (COG) studies AALL0331 (clinicaltrials.gov NCT00103285) (standard-risk; SR with MRD by FC at any level) and AALL0232 (clinicaltrials...
December 28, 2017: Blood
https://www.readbyqxmd.com/read/29279357/successful-outcome-following-allogeneic-hematopoietic-stem-cell-transplantation-in-adults-with-primary-immunodeficiency
#19
Thomas A Fox, Ronjon Chakraverty, Siobhan Burns, Benjamin Carpenter, Kirsty Thomson, David Lowe, Adele Fielding, Karl Peggs, Panagiotis Kottaridis, Benjamin Uttenthal, Venetia Bigley, Matthew Buckland, Victoria Grandage, Shari Denovan, Sarah Grace, Julia Dahlstrom, Sarita Workman, Andrew Symes, Stephen Mackinnon, Rachael Hough, Emma Morris
INTRODUCTION: The primary immunodeficiencies (PID), rare inherited diseases characterised by severe dysfunction of immunity have been successfully treated by allogeneic hematopoietic stem cell transplantation (Allo-HSCT) in childhood. Controversy exists regarding optimal timing and use of Allo-HSCT in adults, due to lack of experience and previous poor outcomes. MATERIALS AND METHODS: 29 consecutive adult patients, with a mean age at transplant of 24 years (range 17-50) underwent Allo-HSCT...
December 26, 2017: Blood
https://www.readbyqxmd.com/read/29273915/cyclin-d1-mrna-as-a-molecular-marker-for-minimal-residual-disease-monitoring-in-patients-with-mantle-cell-lymphoma
#20
M Lokvenc, Marketa Kalinova, K Forsterova, P Klener, M Trneny, E Fronkova, R Kodet
Chromosomal translocation t(11;14)(q13;q32) is a characteristic molecular marker of mantle cell lymphoma (MCL) and leads to the fusion of the immunoglobulin heavy chain enhancer-promoter with the cyclin D1 gene. Both aberrant cyclin D1 expression and underlying chromosomal aberration may be used as molecular targets for monitoring minimal residual disease (MRD). The present study aims to assess the usefulness of quantitative cyclin D1 gene expression compared to the standardised but more technologically demanding DNA-based method for immunoglobulin heavy chain (IGH) or t(11;14) clone-specific gene rearrangement quantification in a cohort of bone marrow (BM) and peripheral blood (PB) samples from patients with MCL...
December 22, 2017: Annals of Hematology
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