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Pediatric Acute Lymphoblastic Leukemia

David M Cordas Dos Santos, Juliane Eilers, Alfonso Sosa Vizcaino, Elena Orlova, Martin Zimmermann, Martin Stanulla, Martin Schrappe, Kathleen Börner, Dirk Grimm, Martina U Muckenthaler, Andreas E Kulozik, Joachim B Kunz
BACKGROUND: Deletions of 6q15-16.1 are recurrently found in pediatric T-cell acute lymphoblastic leukemia (T-ALL). This chromosomal region includes the mitogen-activated protein kinase kinase kinase 7 (MAP3K7) gene which has a crucial role in innate immune signaling and was observed to be functionally and prognostically relevant in different cancer entities. Therefore, we correlated the presence of MAP3K7 deletions with clinical parameters in a cohort of 327 pediatric T-ALL patients and investigated the function of MAP3K7 in the T-ALL cell lines CCRF-CEM, Jurkat and MOLT-4...
June 18, 2018: BMC Cancer
María Lilia Adriana Juárez-López, Marlen Nicolett Solano-Silva, Rodolfo Fragoso-Ríos, Francisco Murrieta-Pruneda
Background: Pediatric patients with acute lymphoblastic leukemia (ALL) usually develop oral manifestations due to the disease itself, as well as side effects of chemotherapy that severely affect their health and quality of life. The aim of this paperis to determine the prevalence of oral diseases in pediatric all patients with and without chemotherapy and its relation to the different phases of chemotherapy. Methods: A cross-sectional observational study was conducted in 103 pediatric patients with all between 3-15 years...
March 2018: Revista Médica del Instituto Mexicano del Seguro Social
Charlene Rae, William Furlong, David Feeny, Rana Couchman, Lewis Silverman, Stephen Sallan, Caroline Laverdiere, Luis Clavell, Bruno Michon, Kara Kelly, Eric Larsen, Eleanor Pullenayegum, Uma Athale, Ronald Barr
Health-related quality of life (HRQL) improved progressively during therapy and beyond in children treated for acute lymphoblastic leukemia on the Dana-Farber Cancer Institute (DFCI) 95-01 protocol. This study aimed to validate that trajectory in a successor study (DFCI 00-01) and to compare the HRQL of patients in the 2 studies. Children aged above 5 years were assessed during each phase of treatment (N=4) and 2 years after completion of therapy. Health status and HRQL were measured using Health Utilities Index (HUI) instruments, HUI2 and HUI3...
June 12, 2018: Journal of Pediatric Hematology/oncology
Agata Pastorczak, Lukasz Sedek, Marcin Braun, Joanna Madzio, Alicja Sonsala, Magdalena Twardoch, Wojciech Fendler, Karin Nebral, Joanna Taha, Marta Bielska, Patryk Gorniak, Magdalena Romiszewska, Michal Matysiak, Katarzyna Derwich, Monika Lejman, Jerzy Kowalczyk, Wanda Badowska, Maciej Niedzwiecki, Bernarda Kazanowska, Katarzyna Muszynska-Roslan, Grazyna Sobol-Milejska, Grazyna Karolczyk, Andrzej Koltan, Tomasz Ociepa, Tomasz Szczepanski, Wojciech Młynarski
We prospectively examined whether surface expression of Cytokine Receptor-Like Factor 2 (CRLF2) on leukemic blasts is associated with survival and induction treatment response in pediatric B-cell precursor acute lymphoblastic leukemia (BCP-ALL) patients. Flow cytometric analysis of bone marrow-derived leukemia cells revealed that 7.51% (29/286) of 386 pediatric BCP-ALL patients were CRLF2-positive (CRLF2pos) at diagnosis. The median minimal residual disease (MRD) was lower in CRLF2pos than CRLF2-negative (CRLF2neg) patients on day 15 (MRD15) after induction therapy [0...
May 25, 2018: Oncotarget
Maria Gabelli, Marco Zecca, Chiara Messina, Elisa Carraro, Barbara Buldini, Attilio Maria Rovelli, Franca Fagioli, Alice Bertaina, Edoardo Lanino, Claudio Favre, Marco Rabusin, Arcangelo Prete, Mimmo Ripaldi, Walter Barberi, Fulvio Porta, Maurizio Caniglia, Stella Santarone, Paolo D'Angelo, Giuseppe Basso, Franco Locatelli
Relapse of acute lymphoblastic leukemia (ALL) may occur in extramedullary sites, mainly central nervous system (CNS) and testis. Optimal post-remissional treatment for isolated extramedullary relapse (IEMR) is still controversial. We collected data of children treated with hematopoietic stem cell transplantation (HSCT) for ALL IEMR from 1990 to 2015 in Italy. Among 281 patients, 167 had a relapse confined to CNS, 73 to testis, 14 to mediastinum, and 27 to other organs. Ninety-seven patients underwent autologous HSCT, 79 received allogeneic HSCT from a matched family donor, 75 from a matched unrelated donor, and 30 from an HLA-haploidentical donor...
June 13, 2018: Bone Marrow Transplantation
Nicolas Boissel, André Baruchel
Adolescent and young adult (AYA) patients with acute lymphoblastic leukemia (ALL) are recognized as a unique population with specific characteristics and needs. In adolescents aged 15-20 years old, the use of full pediatric protocols is supported by many comparative studies of pediatric and adult cooperative groups. In young adults, growing evidence suggests that pediatric-inspired or even fully pediatric approaches may also dramatically improve outcomes, leading to long-term survival rates of almost 70%, despite diminishing indications of hematopoietic stem cell transplantation...
June 12, 2018: Blood
Amitabh Singh, Lesa Dawman, Rachna Seth
Aim of Study: Hemophagocytic lymphohistiocytosis (HLH) is a rare disorder of immune dysregulation resulting in abnormal T-cell activation and inflammatory cytokine production which produces a constellation of clinical features unique to HLH. Pediatric secondary HLH is usually triggered by infection, malignancy, or rheumatological disorders. The diagnosis of malignancy-associated HLH (MA-HLH) poses a difficult challenge as clinical features may be attributed to the underlying disease or chemotherapy...
April 2018: Journal of Cancer Research and Therapeutics
Jason R Schwartz, Michael P Walsh, Jing Ma, Tamara Lamprecht, Shuoguo Wang, Gang Wu, Susana Raimondi, Brandon Triplett, Jeffery Klco
Donor-derived hematologic malignancies are rare complications of hematopoietic cell transplantation (HCT). Although these are commonly either a myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML), in general, they are a heterogeneous group of diseases and a unified mechanism for their development has remained elusive. Here we report next generation sequencing, including whole exome sequencing (WES), whole genome sequencing (WGS), and targeted sequencing, of a case of donor-derived MDS (dMDS) following HCT for high-risk B-lymphoblastic leukemia (B-ALL) in an adolescent...
June 11, 2018: Cold Spring Harbor Molecular Case Studies
Motohiro Kato
The prognosis of pediatric acute lymphoblastic leukemia (ALL) has dramatically improved, both basic research and clinical studies are continuously conducted in pursuit of further improvement. Recent advances in genomic analysis technology have enabled us to comprehensively identify genomic alterations in leukemic cells and thus have contributed to the better understanding of the molecular pathogenesis underlying ALL development. These genomic alterations can be applied not only as prognostic factors but also as therapeutic targets...
2018: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
Fumihiko Hayakawa
For a long time, treatment for adult acute lymphoblastic leukemia (ALL) lacked significant improvements. Since 2000, new approaches, such as the treatments of adolescent and young adult ALL using pediatric-like protocols and Ph+ ALL treatments using tyrosine kinase inhibitor-combined chemotherapies. Further improvements are expected from the use of pediatric-like protocols to whole adults, and the use of newly approved anti-cancer drugs, such as inotuzumab ozogamicin and blinatumomab. Furthermore, comprehensive genetic analyses using next generation sequencing technology have recently discovered new recurrent fusion genes of ALL, such as DUX4 fusion genes, ZNF384 fusion genes, and MEF2D fusion genes...
2018: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
Sonia Douamba, Fatimata Diallo, Kisito Nagalo, Laure Tamini, Lassina Dao, Fla Kouéta, Diarra Yé
Introduction: acute lymphoblastic leukemia (ALL) is being diagnosed in an increasing number of children in our Department. In the developed countries, the treatment of this hematologic malignancy can cure almost 80% of children. In developing countries, few studies focus on acute leukemias in children. The results of cancer treatments in children are disappointing in most African countries, with a survival rate of 10-15%. This study aimed to investigate the clinical, biological, therapeutic and evolutionary features of ALL in children...
2018: Pan African Medical Journal
Françoise Huguet, Sylvie Chevret, Thibaut Leguay, Xavier Thomas, Nicolas Boissel, Martine Escoffre-Barbe, Patrice Chevallier, Mathilde Hunault, Norbert Vey, Caroline Bonmati, Stéphane Lepretre, Jean-Pierre Marolleau, Thomas Pabst, Philippe Rousselot, Agnès Buzyn, Jean-Yves Cahn, Véronique Lhéritier, Marie C Béné, Vahid Asnafi, Eric Delabesse, Elizabeth Macintyre, Yves Chalandon, Norbert Ifrah, Hervé Dombret
Purpose To evaluate randomly the role of hyperfractionated cyclophosphamide (hyper-C) dose intensification in adults with newly diagnosed Philadelphia chromosome-negative acute lymphoblastic leukemia treated with a pediatric-inspired protocol and to determine the upper age limit for treatment tolerability in this context. Patients and Methods A total of 787 evaluable patients (B/T lineage, 525 and 262, respectively; median age, 36.1 years) were randomly assigned to receive a standard dose of cyclophosphamide or hyper-C during first induction and late intensification...
June 4, 2018: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
Katsuyoshi Koh, Motohiro Kato, Akiko M Saito, Akiko Kada, Hirohide Kawasaki, Yasuhiro Okamoto, Toshihiko Imamura, Keizo Horibe, Atsushi Manabe
B-cell precursor acute lymphoblastic leukemia is the most common pediatric malignancy, but its treatment needs to be modified to cause low acute toxicity and few late complications with a high cure rate. In this trial, we will stratify patients with B-cell precursor acute lymphoblastic leukemia into standard, intermediate and high risk groups according to prognostic factors. In addition, we will establish an evaluation system for minimal residual disease that will enable us to stratify patients based on minimal residual disease in subsequent clinical trials...
May 30, 2018: Japanese Journal of Clinical Oncology
Han-Seung Park, Dae-Young Kim, Eun-Ji Choi, Jung-Hee Lee, Je-Hwan Lee, Mijin Jeon, Young-Ah Kang, Young-Shin Lee, Miee Seol, Young-Uk Cho, Seongsoo Jang, Hyun-Sook Chi, Kyoo-Hyung Lee, Chan-Jeoung Park
The prognosis of adult acute lymphoblastic leukemia is much worse than that of pediatric acute lymphoblastic leukemia, even when patients achieve complete remission. Early response to treatment can be an important alternative indicator of treatment outcomes. The purpose of our current study was to identify the prognostic value of the blast percentage of the induction interim bone marrow, which might predict relapse-free survival and overall survival in patients with adult acute lymphoblastic leukemia. A retrospective analysis was performed on 80 adult patients diagnosed with Philadelphia chromosome-negative acute lymphoblastic leukemia from 1994 to 2011...
June 1, 2018: Acta Haematologica
Sri Mulatsih, Iwan Dwiprahasto, Sutaryo
Objective: Medical Safety Practice (MSP) is a safe procedure in medication process. It is important to investigate the use of MSP among childhood cancer patients because pediatric oncology is a high-risk area for potentially harmful adverse events. The purpose of this study is to determine the effects of the implementation of MSP in chemotherapy on the incidence of medication errors in childhood ALL patient at Dr. Sardjito Hospital, including in 1) transcribing, 2) administering, 3) monitoring, 4) the incidence of adverse drugs events...
May 26, 2018: Asian Pacific Journal of Cancer Prevention: APJCP
Jessica H Guadarrama-Orozco, Guillermo R Cantú-Quintanilla, Diana Ávila-Montiel, Myriam Altamirano-Bustamante, Ingris Peláez-Ballestas, Cristina Caballero-Velarde, Luis E Juárez-Villegas, Nahúm de la Vega-Morell, Javier Kelly-García, Adalberto de Hoyos-Bermea, Elisa Dorantes-Acosta, José D Gamboa-Marrufo, Onofre Muñoz-Hernández, Juan Garduño-Espinosa
Background: Laws refer that minors do not have the capability to give informed consent for their own medical attention. However, there are special conditions in which they are allowed to decide about their health. The greater the judgement and experience limitations in minors, the less weight is given to the values and objectives they express. Also, the more adverse consequences might be, the higher the level of authority that is demanded to decide on behalf of the minor, thus granting the State the capability to guarantee the well-being of the minor...
2018: Boletín Médico del Hospital Infantil de México
Matthew J Oberley, Paul S Gaynon, Deepa Bhojwani, Michael A Pulsipher, Rebecca A Gardner, Matthew C Hiemenz, Jianling Ji, Jennifer Han, Maurice R G O'Gorman, Alan S Wayne, Gordana Raca
A pediatric patient diagnosed initially with B-lymphoblastic leukemia (B-ALL) relapsed with lineage switch to acute myeloid leukemia (AML) after chimeric antigen receptor T-cell (CAR-T) therapy and hematopoietic stem cell transplant . A TCF3-ZNF384 fusion was identified at diagnosis, persisted through B-ALL relapse, and was also present in the AML relapse cell population. ZNF384-rearrangements define a molecular subtype of B-ALL characterized by a pro-B-cell immunophenotype; furthermore, ZNF384-rearrangements are prevalent in mixed-phenotype acute leukemias...
May 24, 2018: Pediatric Blood & Cancer
Aubree Boulet-Craig, Philippe Robaey, Julie Laniel, Laurence Bertout, Simon Drouin, Maja Krajinovic, Caroline Laverdière, Daniel Sinnett, Serge Sultan, Sarah Lippé
BACKGROUND: Acute lymphoblastic leukemia (ALL) is the most common cancer in children. Because of major improvements in treatment protocols, the survival rate now exceeds 80%. However, ALL treatments can cause long-term neurocognitive sequelae, which negatively impact academic achievement and quality of life. Therefore, cognitive sequelae need to be carefully evaluated. The DIVERGT is a battery of tests proposed as a screening tool, sensitive to executive function impairments in children and adolescent cancer survivors...
May 24, 2018: Pediatric Blood & Cancer
Motohiro Kato, Mio Kurata, Junya Kanda, Koji Kato, Daisuke Tomizawa, Kazuko Kudo, Nao Yoshida, Kenichiro Watanabe, Hiroyuki Shimada, Jiro Inagaki, Katsuyoshi Koh, Hiroaki Goto, Keisuke Kato, Yuko Cho, Yuki Yuza, Atsushi Ogawa, Keiko Okada, Masami Inoue, Yoshiko Hashii, Takanori Teshima, Makoto Murata, Yoshiko Atsuta
Graft-versus-host disease (GVHD) occasionally leads to morbidity and mortality but is thought to reduce the risk of relapses in patients with a hematological malignancy. However, information on the effect of GVHD in pediatric leukemia is limited. Using a nationwide registry, we retrospectively analyzed 1526 children who underwent allogeneic stem cell transplantation for leukemia. Grades 0-I acute GVHD were associated with a higher relapse rate at three years after transplantation, at 25.4 and 24.3%, respectively, than grades II, III, or IV acute GVHD at 18...
May 24, 2018: Bone Marrow Transplantation
Leanne M Ward, Jinhui Ma, Bianca Lang, Josephine Ho, Nathalie Alos, Mary Ann Matzinger, Nazih Shenouda, Brian Lentle, Jacob L Jaremko, Beverly Wilson, David Stephure, Robert Stein, Anne Marie Sbrocchi, Celia Rodd, Victor Lewis, Sara Israels, Ronald M Grant, Conrad V Fernandez, David B Dix, Elizabeth A Cummings, Robert Couch, Elizabeth Cairney, Ronald Barr, Sharon Abish, Stephanie A Atkinson, John Hay, Frank Rauch, David Moher, Kerry Siminoski, Jacqueline Halton
Osteoporotic fractures are a significant cause of morbidity in acute lymphoblastic leukemia (ALL). Our objective was to determine the incidence and predictors of fractures and recovery from osteoporosis in pediatric ALL over 6 years following glucocorticoid initiation. Vertebral fractures (VF) and vertebral body reshaping were assessed on annual spine radiographs, low-trauma non-VF were recorded at regular intervals and spine bone mineral density (BMD) was captured every 6 months for 4 years and then annually...
May 22, 2018: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
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