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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
#1
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/28696309/influenza-infection-triggers-disease-in-a-genetic-model-of-experimental-autoimmune-encephalomyelitis
#2
Stephen Blackmore, Jessica Hernandez, Michal Juda, Emily Ryder, Gregory G Freund, Rodney W Johnson, Andrew J Steelman
Multiple sclerosis (MS) is an autoimmune disease of the central nervous system. Most MS patients experience periods of symptom exacerbation (relapses) followed by periods of partial recovery (remission). Interestingly, upper-respiratory viral infections increase the risk for relapse. Here, we used an autoimmune-prone T-cell receptor transgenic mouse (2D2) and a mouse-adapted human influenza virus to test the hypothesis that upper-respiratory viral infection can cause glial activation, promote immune cell trafficking to the CNS, and trigger disease...
July 10, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28689102/monthly-methylprednisolone-in-combination-with-interferon-beta-or-glatiramer-acetate-for-relapsing-remitting-multiple-sclerosis-a-multicentre-single-blind-prospective-trial
#3
Serkan Ozakbas, Bilge Piri Cinar, Gorkem Kosehasanoğullari, Turhan Kahraman, Didem Oz, Behice Bircan Kursun
OBJECTIVES: Multiple sclerosis is usually clinically characterized by repeated subacute relapses followed by remissions. Corticosteroids are used for relapses, and this treatment has been shown to increase the speed of recovery from these. We aimed to evaluate the efficacy and safety of pulsed methylprednisolone given every month as an add-on therapy to interferon beta or glatiramer acetate in patients with relapsing-remitting multiple sclerosis. PATIENTS AND METHODS: This was a multi-center, examiner-blinded, prospective study...
June 27, 2017: Clinical Neurology and Neurosurgery
https://www.readbyqxmd.com/read/28679992/chemotherapy-for-a-child-with-relapsed-acute-myeloid-leukemia-complicated-with-persistent-hepatitis-c-virus-infection
#4
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/28664242/long-term-outcome-of-childhood-onset-complicated-nephrotic-syndrome-after-a-multicenter-double-blind-randomized-placebo-controlled-trial-of-rituximab
#5
Koichi Kamei, Kenji Ishikura, Mayumi Sako, Kunihiko Aya, Ryojiro Tanaka, Kandai Nozu, Hiroshi Kaito, Koichi Nakanishi, Yoshiyuki Ohtomo, Kenichiro Miura, Shori Takahashi, Tetsuji Morimoto, Wataru Kubota, Shuichi Ito, Hidefumi Nakamura, Kazumoto Iijima
BACKGROUND: Although rituximab effectively prevents relapses of complicated frequently relapsing nephrotic syndrome (FRNS) and steroid-dependent nephrotic syndrome (SDNS), data of long-term outcomes and safety are limited. METHODS: Fifty-one patients (age, 3-38 years) with childhood-onset complicated FRNS or SDNS, who received rituximab in investigator-initiated multicenter prospective trials were enrolled. Rituximab was administered at 375 mg/m(2) once weekly for 4 weeks, and immunosuppressive agents were discontinued according to the study protocol...
June 29, 2017: Pediatric Nephrology: Journal of the International Pediatric Nephrology Association
https://www.readbyqxmd.com/read/28647744/effectiveness-of-supported-self-help-in-recurrent-depression-a-randomized-controlled-trial-in-primary-care
#6
Karolien E M Biesheuvel-Leliefeld, Sandra M A Dijkstra-Kersten, Digna J F van Schaik, Harm W J van Marwijk, Filip Smit, Henriette E van der Horst, Claudi L H Bockting
BACKGROUND: The burden and economic consequences of depression are high, mostly due to its recurrent nature. Due to current budget and time restraints, a preventive, low- cost, accessible minimal intervention is much needed. In this study, we evaluated the effectiveness of a supported self-help preventive cognitive therapy (S-PCT) added to treatment as usual (TAU) in primary care, compared to TAU alone. METHODS: We conducted a randomized controlled trial among 248 patients with a history of depression, currently in full or partial remission or recovery...
2017: Psychotherapy and Psychosomatics
https://www.readbyqxmd.com/read/28645776/selective-inhibition-of-flt3-by-gilteritinib-in-relapsed-or-refractory-acute-myeloid-leukaemia-a-multicentre-first-in-human-open-label-phase-1-2-study
#7
Alexander E Perl, Jessica K Altman, Jorge Cortes, Catherine Smith, Mark Litzow, Maria R Baer, David Claxton, Harry P Erba, Stan Gill, Stuart Goldberg, Joseph G Jurcic, Richard A Larson, Chaofeng Liu, Ellen Ritchie, Gary Schiller, Alexander I Spira, Stephen A Strickland, Raoul Tibes, Celalettin Ustun, Eunice S Wang, Robert Stuart, Christoph Röllig, Andreas Neubauer, Giovanni Martinelli, Erkut Bahceci, Mark Levis
BACKGROUND: Internal tandem duplication mutations in FLT3 are common in acute myeloid leukaemia and are associated with rapid relapse and short overall survival. The clinical benefit of FLT3 inhibitors in patients with acute myeloid leukaemia has been limited by rapid generation of resistance mutations, particularly in codon Asp835 (D835). We aimed to assess the highly selective oral FLT3 inhibitor gilteritinib in patients with relapsed or refractory acute myeloid leukaemia. METHODS: In this phase 1-2 trial, we enrolled patients aged 18 years or older with acute myeloid leukaemia who either were refractory to induction therapy or had relapsed after achieving remission with previous treatment...
June 20, 2017: Lancet Oncology
https://www.readbyqxmd.com/read/28630708/what-happens-after-treatment-a-systematic-review-of-relapse-remission-and-recovery-in-anorexia-nervosa
#8
REVIEW
Sahib S Khalsa, Larissa C Portnoff, Danyale McCurdy-McKinnon, Jamie D Feusner
BACKGROUND: Relapse after treatment for anorexia nervosa (AN) is a significant clinical problem. Given the level of chronicity, morbidity, and mortality experienced by this population, it is imperative to understand the driving forces behind apparently high relapse rates. However, there is a lack of consensus in the field on an operational definition of relapse, which hinders precise and reliable estimates of the severity of this issue. The primary goal of this paper was to review prior studies of AN addressing definitions of relapse, as well as relapse rates...
2017: Journal of Eating Disorders
https://www.readbyqxmd.com/read/28604667/single-agent-gvhd-prophylaxis-with-tacrolimus-after-post-transplant-high-dose-cyclophosphamide-is-a-valid-option-for-haploidentical-transplantation-in-adults-with-hematological-malignancies
#9
A Esquirol, M J Pascual, M Ortiz, J L Piñana, C Ferra, I Garcia Cadenas, I Vilades, S Brunet, R Martino, J Sierra
Eighty-one patients with high-risk hematological malignancies received unmanipulated haploidentical stem cell transplants (haploSCT) using the same protocol at four Spanish institutions. The conditioning regimen was thiotepa, busulfan and fludarabine; following bone marrow or peripheral blood infusion. GvHD prophylaxis with high-dose cyclophosphamide on days +3 and +4, and IV tacrolimus from day +5 was administered. 62% were in complete remission, 17% had received previous allogeneic SCT and 44% had a high-very high refined disease risk index...
June 12, 2017: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/28555084/mitoxantrone-etoposide-and-cytarabine-following-epigenetic-priming-with-decitabine-in-adults-with-relapsed-refractory-acute-myeloid-leukemia-or-other-high-grade-myeloid-neoplasms-a-phase-1-2-study
#10
A B Halpern, M Othus, E M Huebner, S A Buckley, E L Pogosova-Agadjanyan, K F Orlowski, B L Scott, P S Becker, P C Hendrie, T L Chen, M-E M Percival, E H Estey, D L Stirewalt, R B Walter
DNA methyltransferase inhibitors sensitize leukemia cells to chemotherapeutics. We therefore conducted a phase 1/2 study of mitoxantrone, etoposide and cytarabine following 'priming' with 5-10 days of decitabine (dec/MEC) in 52 adults (median age 55 (range: 19-72) years) with relapsed/refractory acute myeloid leukemia (AML) or other high-grade myeloid neoplasms. During dose escalation in cohorts of 6-12 patients, all dose levels were well tolerated. As response rates appeared similar with 7 and 10 days of decitabine, a 7-day course was defined as the recommended phase 2 dose (RP2D)...
May 30, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28540755/persistent-cytogenetic-abnormalities-in-patients-undergoing-intensive-chemotherapy-for-acute-myeloid-leukemia
#11
Lalit Saini, Joseph Brandwein, Artur Szkotak, Sunita Ghosh, Irwindeep Sandhu
We evaluated the impact of bone marrow sample characteristics on the detection of persistent cytogenetic abnormalities (PCA) following induction chemotherapy for acute myeloid leukemia (AML). PCA's were identified in 20.4% of patients and were more common with complete remission without count recovery (CRi) vs. those with count recovery (CR, 45.8 vs. 13.5%, p = .001), with  >2% blasts vs.  ≤2% blasts (42 vs. 12%, p =  .001) and with hypocellular trephine biopsies relative to those with normo/hypercellular biopsies (42...
May 25, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28520640/twenty-four-month-follow-up-of-tocilizumab-therapy-for-refractory-uveitis-related-macular-edema
#12
Marina Mesquida, Blanca Molins, Victor Llorenç, María V Hernández, Gerard Espinosa, Maite Sainz de la Maza, Alfredo Adán
BACKGROUND: To report the 24-month efficacy and safety of the interleukin-6 receptor antagonist tocilizumab (TCZ) for refractory uveitis-related macular edema (ME). METHODS: Data were obtained by standardized chart review. Patients with quiescent uveitis seen at a single tertiary referral center, for whom ME was the principal cause of reduced visual acuity. OUTCOME MEASURES: Central foveal thickness measured by optical coherence tomography; degree of anterior and posterior chamber; inflammation (Standardization of Uveitis Nomenclature Working Group criteria); and visual acuity (Snellen and logarithm of the minimum angle of resolution) were recorded in all patients during TCZ therapy at months 1, 3, 6, 12, 18, and 24...
May 16, 2017: Retina
https://www.readbyqxmd.com/read/28490811/high-efficacy-and-safety-of-low-dose-cd19-directed-car-t-cell-therapy-in-51-refractory-or-relapsed-b-acute-lymphoblastic-leukemia-patients
#13
J Pan, J F Yang, B P Deng, X J Zhao, X Zhang, Y H Lin, Y N Wu, Z L Deng, Y L Zhang, S H Liu, T Wu, P H Lu, D P Lu, A H Chang, C R Tong
Refractory or relapsed B lymphoblastic leukemia (B-ALL) patients have a dismal outcome with current therapy. We treated 42 primary refractory/hematological relapsed (R/R) and 9 refractory minimal residual disease by flow cytometry (FCM-MRD(+)) B-ALL patients with optimized second generation CD19-directed CAR-T cells. The CAR-T-cell infusion dosages were initially ranged from 0.05 to 14 × 10(5)/kg and were eventually settled at 1 × 10(5)/kg for the most recent 20 cases. 36/40 (90%) evaluated R/R patients achieved complete remission (CR) or CR with incomplete count recovery (CRi), and 9/9 (100%) FCM-MRD(+) patients achieved MRD(-)...
May 15, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28484463/immune-effector-recovery-in-chronic-myeloid-leukemia-and-treatment-free-remission
#14
REVIEW
Amy Hughes, Agnes S M Yong
Chronic myeloid leukemia (CML) is a hematological cancer, characterized by a reciprocal chromosomal translocation between chromosomes 9 and 22 [t(9;22)], producing the Bcr-Abl oncogene. Tyrosine kinase inhibitors (TKIs) represent the standard of care for CML patients and exert a dual mode of action: direct oncokinase inhibition and restoration of effector-mediated immune surveillance, which is rendered dysfunctional in CML patients at diagnosis, prior to TKI therapy. TKIs such as imatinib, and more potent second-generation nilotinib and dasatinib induce a high rate of deep molecular response (DMR, BCR-ABL1 ≤ 0...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28479972/medication-adherence-among-nigerians-with-schizophrenia-correlation-between-clinico-demographic-factors-and-quality-of-life
#15
Oluseun P Ogunnubi, Andrew T Olagunju, Olatunji F Aina, Njideka U Okubadejo
Medication adherence contributes significantly to symptom remission, recovery and wellbeing in mental illnesses. We evaluated how medication adherence correlates with clinico-demographic factors and quality of life (QoL) in a sample of Nigerians with schizophrenia. This descriptive cross-sectional study involved 160 randomly selected participants with confirmed diagnosis of schizophrenia based on MINI International Neuropsychiatric Interview. Data on socio-demographic and clinical characteristics of participants were collected with a questionnaire...
March 22, 2017: Mental Illness
https://www.readbyqxmd.com/read/28434126/relapse-of-nephrotic-syndrome-during-post-rituximab-peripheral-blood-b-lymphocyte-depletion
#16
Mai Sato, Koichi Kamei, Masao Ogura, Kenji Ishikura, Shuichi Ito
BACKGROUND: Rituximab is effective against complicated childhood steroid-dependent nephrotic syndrome (SDNS). Peripheral blood B-lymphocyte (B-cell) depletion is strongly correlated with persistent remission, relapse rarely occurring during B-cell depletion; however, we have encountered several such patients. METHODS: We retrospectively analyzed the characteristics and clinical course of 82 patients with SDNS treated with rituximab from January 2007 to December 2012 in our institution...
April 22, 2017: Clinical and Experimental Nephrology
https://www.readbyqxmd.com/read/28417553/calcineurin-inhibitor-free-strategies-for-prophylaxis-and-treatment-of-gvhd-in-children-with-posterior-reversible-encephalopathy-syndrome-after-stem-cell-transplantation
#17
Vered Shkalim-Zemer, Osnat Konen, Yoel Levinsky, Orli Michaeli, Anat Yahel, Aviva Krauss, Isaac Yaniv, Jerry Stein
BACKGROUND: Posterior reversible encephalopathy syndrome (PRES) is a distinct clinico-radiologic entity that can occur following allogeneic hematopoietic stem cell transplantation, often in the context of treatment with calcineurin inhibitors (CNIs). PROCEDURE: We describe the results of CNI-free management of 14 children with PRES and review the clinical and radiologic manifestations of their presentation. RESULTS: Discontinuation of CNIs usually resulted in remission of PRES, but patients with established graft versus host disease (GVHD) at the time when treatment was changed often experienced progressive GVHD despite administration of immune suppressive and modulating treatments...
April 18, 2017: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/28409853/a-phase-1-study-of-the-cxcr4-antagonist-plerixafor-in-combination-with-high-dose-cytarabine-and-etoposide-in-children-with-relapsed-or-refractory-acute-leukemias-or-myelodysplastic-syndrome-a-pediatric-oncology-experimental-therapeutics-investigators-consortium
#18
Todd M Cooper, Edward Allan Racela Sison, Sharyn D Baker, Lie Li, Amina Ahmed, Tanya Trippett, Lia Gore, Margaret E Macy, Aru Narendran, Keith August, Michael J Absalon, Jessica Boklan, Jessica Pollard, Daniel Magoon, Patrick A Brown
BACKGROUND: Plerixafor, a reversible CXCR4 antagonist, inhibits interactions between leukemic blasts and the bone marrow stromal microenvironment and may enhance chemosensitivity. A phase 1 trial of plerixafor in combination with intensive chemotherapy in children and young adults with relapsed or refractory acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), and myelodysplastic syndrome (MDS) was performed to determine a tolerable and biologically active dose. PROCEDURE: Plerixafor was administered daily for 5 days at four dose levels (6, 9, 12, and 15 mg/m(2) /dose) followed 4 hr later by high-dose cytarabine (every 12 hr) and etoposide (daily)...
April 14, 2017: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/28402581/akt-inhibitor-mk-2206-in-combination-with-bendamustine-and-rituximab-in-relapsed-or-refractory-chronic-lymphocytic-leukemia-results-from-the-n1087-alliance-study
#19
Jeremy T Larsen, Tait D Shanafelt, Jose F Leis, Betsy LaPlant, Tim Call, Adam Pettinger, Curtis Hanson, Charles Erlichman, Thomas Matthew Habermann, Craig Reeder, Daniel Nikcevich, Deborah Bowen, Michael Conte, Justin Boysen, Charla Secreto, Connie Lesnick, Renee Tschumper, Diane Jelinek, Neil E Kay, Wei Ding
Akt is a downstream target of B cell receptor signaling and is a central regulator of CLL cell survival. We aim to investigate the safety and efficacy of the Akt inhibitor MK-2206 in combination with bendamustine and rituximab (BR) in relapsed and/or refractory CLL in a phase I/II study. A standard phase I design was used with cohorts of three plus three patients to determine the maximum tolerated dose (MTD) of MK-2206 in combination with BR in relapsed CLL. Single-agent MK-2206 (weekly dosed) was administered one-week in advance before BR on cycle 1 and subsequently was given with BR at the same time for cycle 2-6...
August 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/28395942/ex-vivo-t-cell-depleted-allogeneic-stem-cell-transplantation-for-hematologic-malignancies-the-search-for-an-optimum-transplant-t-cell-dose-and-t-cell-add-back-strategy
#20
Prathima Anandi, Xin Tian, Sawa Ito, Pawel Muranski, Puja D Chokshi, Noelle Watters, Upneet Chawla, Nancy Hensel, David F Stroncek, Minoo Battiwalla, A John Barrett
BACKGROUND: T-cell depletion (TCD) of allogeneic stem cell transplants (SCT) can reduce graft-versus-host disease but may negatively affect transplant outcome by delaying immune recovery. To optimize TCD in HLA-matched siblings with hematologic malignancies, we explored varying the transplant CD3+ T-cell dose between 2 and 50 × 10(4)/kg (corresponding to 3-4 log depletion) and studied the impact of 0-6 × 10(7)/kg CD3+ donor lymphocyte infusion (DLI) "add-back" on immune recovery post-SCT...
April 7, 2017: Cytotherapy
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