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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
Salah Aref, Emad Azmy, Kadry El-Bakry, Lobna Ibrahim, Sherin Abdel Aziz
This study aimed to determine the prognostic impact of CD200 and CD56 expression in pediatric B cell acute lymphoblastic leukemia (B-ALL) patients, both of which have been implicated in immune tolerance and previously suggested as independent risk factors. CD200 has a central role in immune tolerance that protects stem cells and other critical tissues from immune damage. The expression of CD200/CD56 in leukemic blasts were assessed in leukemic blasts before chemotherapy in 43 bone marrow (BM) and/or peripheral blood (PB) samples by flow cytometry...
August 2017: Pediatric Hematology and Oncology
Joshua Wolf, Li Tang, Patricia M Flynn, Ching-Hon Pui, Aditya H Gaur, Yilun Sun, Hiroto Inaba, Tracy Stewart, Randall T Hayden, Hana Hakim, Sima Jeha
Background: Infection is the most important cause of treatment-related morbidity and mortality in pediatric patients treated for acute lymphoblastic leukemia (ALL). Although routine in adults with leukemia, antibacterial prophylaxis is controversial in pediatrics because of insufficient evidence for its efficacy or antibiotic choice and concerns about promoting antibiotic resistance and Clostridium difficile infection. Methods: This was a single-center, observational cohort study of patients with newly diagnosed ALL, comparing prospectively collected infection-related outcomes in patients who received no prophylaxis, levofloxacin prophylaxis, or other prophylaxis during induction therapy on the total XVI study...
November 13, 2017: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
Eolia Brissot, Myriam Labopin, Matthias Stelljes, Gerhard Ehninger, Rainer Schwerdtfeger, Jürgen Finke, Hans-Jochem Kolb, Arnold Ganser, Kerstin Schäfer-Eckart, Axel R Zander, Donald Bunjes, Stephan Mielke, Wolfgang A Bethge, Noël Milpied, Peter Kalhs, Igor-Woflgang Blau, Nicolaus Kröger, Antonin Vitek, Martin Gramatzki, Ernst Holler, Christoph Schmid, Jordi Esteve, Mohamad Mohty, Arnon Nagler
BACKGROUND: Primary refractory acute myeloid leukemia (PRF-AML) is associated with a dismal prognosis. Allogeneic stem cell transplantation (HSCT) in active disease is an alternative therapeutic strategy. The increased availability of unrelated donors together with the significant reduction in transplant-related mortality in recent years have opened the possibility for transplantation to a larger number of patients with PRF-AML. Moreover, transplant from unrelated donors may be associated with stronger graft-mediated anti-leukemic effect in comparison to transplantations from HLA-matched sibling donor, which may be of importance in the setting of PRF-AML...
June 24, 2017: Journal of Hematology & Oncology
T Terwilliger, M Abdul-Hay
Acute lymphoblastic leukemia (ALL) is the second most common acute leukemia in adults, with an incidence of over 6500 cases per year in the United States alone. The hallmark of ALL is chromosomal abnormalities and genetic alterations involved in differentiation and proliferation of lymphoid precursor cells. In adults, 75% of cases develop from precursors of the B-cell lineage, with the remainder of cases consisting of malignant T-cell precursors. Traditionally, risk stratification has been based on clinical factors such age, white blood cell count and response to chemotherapy; however, the identification of recurrent genetic alterations has helped refine individual prognosis and guide management...
June 30, 2017: Blood Cancer Journal
Yishai Ofran, Shai Izraeli
Recent comprehensive genetic studies revealed numerous genetic aberrations underlying a group of high-risk leukemias that share a specific activated kinase gene expression pattern. These ALLs were first recognized by the expression profile similar to that of Philadelphia chromosome-positive ALL and currently can be sub-classified by the main aberrantly activated kinase in the leukemic cells. We herein review the biological mechanisms and diagnostic and clinical challenges presented by these leukemias.
March 2017: Blood Reviews
Joy Benadiba, Celia Rosilio, Marielle Nebout, Vera Heimeroth, Zouhour Neffati, Alexandra Popa, Didier Mary, Emmanuel Griessinger, Véronique Imbert, Nicolas Sirvent, Jean-François Peyron
Iron is an essential nutrient, acting as a catalyst for metabolic reactions that are fundamental to cell survival and proliferation. Iron complexed to transferrin is delivered to the metabolism after endocytosis via the CD71 surface receptor. We found that transformed cells from a murine PTEN-deficient T-cell lymphoma model and from T-cell acute lymphoblastic leukemia/lymphoma (T-ALL/T-LL) cell lines overexpress CD71. As a consequence, the cells developed an addiction toward iron whose chelation by deferoxamine (DFO) dramatically affected their survival to induce apoptosis...
June 2017: Leukemia & Lymphoma
Judith Feucht, Simone Kayser, David Gorodezki, Mohamad Hamieh, Michaela Döring, Franziska Blaeschke, Patrick Schlegel, Hans Bösmüller, Leticia Quintanilla-Fend, Martin Ebinger, Peter Lang, Rupert Handgretinger, Tobias Feuchtinger
T-cell immunotherapies are promising options in relapsed/refractory B-precursor acute lymphoblastic leukemia (ALL). We investigated the effect of co-signaling molecules on T-cell attack against leukemia mediated by CD19/CD3-bispecific T-cell engager. Primary CD19+ ALL blasts (n≥10) and physiologic CD19+CD10+ bone marrow precursors were screened for 20 co-signaling molecules. PD-L1, PD-1, LAG-3, CD40, CD86, CD27, CD70 and HVEM revealed different stimulatory and inhibitory profiles of pediatric ALL compared to physiologic cells, with PD-L1 and CD86 as most prominent inhibitory and stimulatory markers...
November 22, 2016: Oncotarget
Trishana Nayiager, Ronald D Barr, Loretta Anderson, Amy Cranston, John Hay
Inadequate physical activity (PA) and elevated overweight/obesity (OW/OB) rates are common in survivors of cancer in childhood, especially acute lymphoblastic leukemia (ALL). Bony morbidity, including fractures, is also prevalent among survivors of ALL. This study examined the interrelationships of PA, measured in hours by the Habitual Activity Estimation Scale; OW/OG, defined by body mass index; and fractures (yes/no) in survivors of ALL (n=75) more than 10 years after diagnosis. All had been treated using protocols of the Dana Farber Cancer Institute Childhood ALL Consortium...
January 2017: Journal of Pediatric Hematology/oncology
Francesco Ceppi, Derek Stephens, Barbara S den Hollander, Joerg Krueger, James Whitlock, Lillian Sung, Johann Hitzler
BACKGROUND: Treatment of acute lymphoblastic leukemia (ALL) in children with Down syndrome (DS) is associated with a higher incidence of life-threatening infections compared to the overall pediatric population. The objective of this study was to describe infections and identify risk factors of microbiologically documented infections at a sterile site in children with DS during chemotherapy for ALL. PROCEDURE: We conducted a single-institution retrospective review of infectious episodes encountered by patients with DS during primary treatment for ALL...
November 2016: Pediatric Blood & Cancer
Kjeld Schmiegelow, Jacob Nersting, Stine Nygaard Nielsen, Mats Heyman, Finn Wesenberg, Jon Kristinsson, Kim Vettenranta, Henrik Schrøeder, Richard Weinshilboum, Katrine Lykke Jensen, Kathrine Grell, Susanne Rosthoej
BACKGROUND: 6-Mercaptopurine (6MP) and methotrexate (MTX) based maintenance therapy is a critical phase of childhood acute lymphoblastic leukemia treatment. Wide interindividual variations in drug disposition warrant frequent doses adjustments, but there is a lack of international consensus on dose adjustment guidelines. PROCEDURE: To identify relapse predictors, we collected 28,255 data sets on drug doses and blood counts (median: 47/patient) and analyzed erythrocyte (Ery) levels of cytotoxic 6MP/MTX metabolites in 9,182 blood samples (median: 14 samples/patient) from 532 children on MTX/6MP maintenance therapy targeted to a white blood cell count (WBC) of 1...
December 2016: Pediatric Blood & Cancer
Min Xia, Hong Zhang, Zhenghua Lu, Yuan Gao, Xuelian Liao, Hong Li
The aim of this study was to identify key markers of minimal residual disease (MRD) in childhood Acute Lymphoblastic Leukemia (ALL). Bone marrow samples were collected at presentation from 139 patients with newly diagnosed B-lineage ALL. On the basis of the expression of CD19, CD10, and CD34 antigens by bone marrow cells, combined with the terminal deoxynucleotide transferase (TdT), CD38, CD45, CD58, CD21, CD66c, CD22, and CD33 expression patterns characterized at diagnosis, leukemia-associated immunophenotypes (LAIPs) were identified...
August 2016: Journal of Pediatric Hematology/oncology
Kristin A Loiselle, Joseph R Rausch, Sarah Bidwell, Sarah Drake, Stella M Davies, Ahna L H Pai
BACKGROUND: Advances in hematopoietic stem cell transplantation (HSCT) have contributed to increased survival for pediatric patients. However, there are inconsistent findings regarding the impact of HSCT on health-related quality of life (HRQOL) outcomes for children. This study aimed to establish trajectories of HRQOL following HSCT and identify predictors of the HRQOL course. PROCEDURE: Ninety caregivers of a child who received HSCT (mean age = 6.42 years) for various oncologic, immunologic, and metabolic conditions completed questionnaires regarding family psychosocial functioning and child HRQOL at the time of discharge from HSCT and follow-up HRQOL at four additional time points...
October 2016: Pediatric Blood & Cancer
Claire Edwin, Joanne Dean, Laura Bonnett, Kate Phillips, Russell Keenan
Composition of tumour immune cell infiltrates correlates with response to treatment and overall survival (OS) in several cancer settings. We retrospectively examined immune cells present in diagnostic bone marrow aspirates from paediatric patients with B-cell acute lymphoblastic leukaemia. Our analysis identified a sub-group (∼30% of patients) with >2.37% CD20 and >6.05% CD7 expression, which had 100% OS, and a sub-group (∼30% of patients) with ≤2.37% CD20 and ≤6.05% CD7 expression at increased risk of treatment failure (66...
October 2016: Pediatric Blood & Cancer
Kee K Yeo, Paul S Gaynon, Cecilia H Fu, Alan S Wayne, Weili Sun
BACKGROUND: Children with relapsed acute lymphoblastic leukemia (ALL) typically receive vincristine-prednisone-L-asparaginase-doxorubicin reinduction chemotherapy similar to contemporary induction regimens. However, up to 20% of patients are unable to receive vincristine-prednisone-L-asparaginase-doxorubicin secondary to asparaginase intolerance. We report our experience with a promising reinduction regimen for children with relapsed ALL who are unable to receive asparaginase. PATIENTS AND METHODS: This is a single institution, retrospective review of the safety and activity of bortezomib, dexamethasone, mitoxantrone, and vinorelbine (BDMV) in patients with relapsed ALL...
July 2016: Journal of Pediatric Hematology/oncology
Eric C Larsen, Meenakshi Devidas, Si Chen, Wanda L Salzer, Elizabeth A Raetz, Mignon L Loh, Leonard A Mattano, Catherine Cole, Alisa Eicher, Maureen Haugan, Mark Sorenson, Nyla A Heerema, Andrew A Carroll, Julie M Gastier-Foster, Michael J Borowitz, Brent L Wood, Cheryl L Willman, Naomi J Winick, Stephen P Hunger, William L Carroll
PURPOSE: Survival for children and young adults with high-risk B-acute lymphoblastic leukemia has improved significantly, but 20% to 25% of patients are not cured. Children's Oncology Group study AALL0232 tested two interventions to improve survival. PATIENTS AND METHODS: Between January 2004 and January 2011, AALL0232 enrolled 3,154 participants 1 to 30 years old with newly diagnosed high-risk B-acute lymphoblastic leukemia. By using a 2 × 2 factorial design, 2,914 participants were randomly assigned to receive dexamethasone (14 days) versus prednisone (28 days) during induction and high-dose methotrexate versus Capizzi escalating-dose methotrexate plus pegaspargase during interim maintenance 1...
July 10, 2016: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
Rosa Nguyen, Sima Jeha, Yinmei Zhou, Xueyuan Cao, Cheng Cheng, Deepa Bhojwani, Patrick Campbell, Scott C Howard, Jeffrey Rubnitz, Raul C Ribeiro, John T Sandlund, Tanja Gruber, Hiroto Inaba, Ching-Hon Pui, Monika L Metzger
BACKGROUND: Hyperleukocytosis in children with acute lymphoblastic leukemia (ALL) has been associated with early morbidity and mortality. The use of leukapheresis in these children treated with contemporary therapy remains controversial. PROCEDURE: We analyzed clinical data from patients enrolled onto frontline protocols for ALL (Total Therapy XV and XVI) between 2003 and 2014. We documented adverse events within the first 14 days in patients with a white blood cell (WBC) count ≥200 × 10(9) /l and reviewed their management...
September 2016: Pediatric Blood & Cancer
(no author information available yet)
BACKGROUND: Leukemia accounts for nearly a third of childhood cancers in Canada, with acute lymphoblastic leukemia (ALL) comprising nearly 80% of cases. Identification of prognostic factors that allow risk stratification and tailored treatment have improved overall survival. However, nearly a quarter of patients considered standard risk on the basis of conventional prognostic factors still relapse, and relapse is associated with increased morbidity and mortality. Relapse is thought to result from extremely low levels of leukemic cells left over once complete remission is reached, termed minimal residual disease (MRD)...
2016: Ontario Health Technology Assessment Series
M Belmonte, C Hoofd, A P Weng, V Giambra
T-Cell acute lymphoblastic leukemia (t-all) is a malignancy of white blood cells, characterized by an uncontrolled accumulation of T-cell progenitors. During leukemic progression, immature T cells grow abnormally and crowd into the bone marrow, preventing it from making normal blood cells and spilling out into the bloodstream. Recent studies suggest that only discrete cell populations that possess the ability to recreate the entire tumour might be responsible for the initiation and propagation of t-all. Those unique cells are commonly called "cancer stem cells" or, in the case of hematopoietic malignancies, "leukemia stem cells" (lscs)...
February 2016: Current Oncology
A Lu, Y Fang, X Du, Y Li, Z Cai, K Yu, L Zhao, B Wang, J Wu, Y Cheng, Y Zuo, Y Jia, F Tan, L Ding, J Lu, L Zhang, X Huang
No abstract text is available yet for this article.
February 26, 2016: Blood Cancer Journal
2016-04-20 07:13:01
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