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Acute T Lymphoblastic Leukemia

T N Gibson, S Beeput, J Gaspard, C George, D Gibson, N Jackson, V Leandre-Broome, N Palmer-Mitchell, C Alexis, J Bird-Compton, C Bodkyn, R Boyle, S McLean-Salmon, M Reece-Mills, C Sin Quee-Brown, U Allen, S Weitzman, V Blanchette, S Gupta
BACKGROUND: English-speaking Caribbean (ESC) childhood cancer outcomes are unknown. PROCEDURE: Through the SickKids-Caribbean Initiative (SCI), we established a multicenter childhood cancer database across seven centers in six ESC countries. Data managers entered patient demographics, disease, treatment, and outcome data. Data collection commenced in 2013, with retrospective collection to 2011 and subsequent prospective collection. RESULTS: A total of 367 children were diagnosed between 2011 and 2015 with a median age of 5...
August 9, 2018: Pediatric Blood & Cancer
Josée Golay, Simona Martinelli, Rachele Alzani, Sabrina Cribioli, Clara Albanese, Elisa Gotti, Bruna Pasini, Benedetta Mazzanti, Riccardo Saccardi, Alessandro Rambaldi, Martino Introna
BACKGROUND: Cytokine-induced killer cells (CIKs) are an advanced therapeutic medicinal product (ATMP) that has shown therapeutic activity in clinical trials but needs optimization. We developed a novel strategy using CIKs from banked cryopreserved cord blood units (CBUs) combined with bispecific antibody (BsAb) blinatumomab to treat CD19+ malignancies. METHODS: CB-CIKs were expanded in vitro and fully characterized in comparison with peripheral blood (PB)-derived CIKs...
August 6, 2018: Cytotherapy
Akanksha Bothale, Kalpana Bothale, Sadhana Mahore, Trupti Dongre
Extramedullary hematopoiesis (EMH) is a compensatory mechanism that occurs when the marrow is unable to maintain sufficient red cell mass. EMH generally occurs in the patients with deficient bone marrow hematopoiesis secondary to either peripheral red cell destruction or marrow replacement. Although EMH is known to occur in agnogenic myeloid metaplasia with myelofibrosis, chronic myelogenous leukemia, thalassemia, and infiltrative disorders, such as lymphomas, it is rare in acute leukemias. EMH is most commonly seen in the liver and spleen as a diffuse lesion...
July 2018: Journal of Cytology
Irene Scarfò, Maria Ormhøj, Matthew J Frigault, Ana P Castano, Selena Lorrey, Amanda A Bouffard, Alexandria van Scoyk, Scott J Rodig, Alexandra J Shay, Jon C Aster, Frederic I Preffer, David M Weinstock, Marcela V Maus
Chimeric antigen receptor (CAR) T cells have emerged as a novel form of treatment for patients with B-cell malignancies. In particular, anti-CD19 CAR T-cell therapy has effected impressive clinical responses in B-cell acute lymphoblastic leukemia (ALL) and diffuse large B-cell lymphoma (DLBCL). However, not all patients respond, and relapse with antigen loss has been observed in all patient subsets. Here, we report on the design and optimization of a novel CAR directed to the surface antigen CD37, which is expressed in B-cell non-Hodgkin Lymphomas, in chronic lymphocytic leukemia (CLL) and in some cases of cutaneous and peripheral T-cell lymphomas (CTCL and PTCL, respectively)...
August 8, 2018: Blood
Changshan Wang, Motohiko Oshima, Daisuke Sato, Hirotaka Matsui, Sho Kubota, Kazumasa Aoyama, Yaeko Nakajima-Takagi, Shuhei Koide, Jun Matsubayashi, Makiko Mochizuki-Kashio, Takako Nakano-Yokomizo, Jie Bai, Toshitaka Nagao, Akinori Kanai, Atsushi Iwama, Goro Sashida
Early T cell precursor acute lymphoblastic leukemia (ETP-ALL) is a new pathological entity with poor outcomes in T cell ALL (T-ALL) that is characterized by a high incidence of loss-of-function mutations in polycomb repressive complex 2 (PRC2) genes. We generated a mouse model of ETP-ALL by deleting Ezh2, one of the PRC2 genes, in p53-null hematopoietic cells. The loss of Ezh2 in p53-null hematopoietic cells impeded the differentiation of ETPs and eventually induced ETP-ALL-like disease in mice, indicating that PRC2 functions as a bona fide tumor suppressor in ETPs...
August 6, 2018: Journal of Clinical Investigation
Junko Takita
Despite an improvement in the prognosis of pediatric T-cell acute lymphoblastic leukemia (T-ALL), the outcome of patients with relapse or refractory T-ALL remains dismal. Activating mutations of the NOTCH pathway and the loss-of-function mutations of CDKN2A are frequent genetic alterations in T-ALL; however, these changes exert no prognostic impact. Furthermore, several gene fusions, including STIL-TAL1, were recently detected in T-ALL; however, other genetic events are necessary for the development of T-ALL...
2018: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
Takaomi Sanda
Super-enhancers comprise of clusters of enhancers that are typically defined by the ChIP-seq analysis for active histone marks. Although the biological significance of super-enhancers is still controversial, this concept is gaining prominence as useful characteristics of genes that play crucial roles in normal development and pathogenesis of cancer. In various cancer cells, super-enhancers are often associated with genes involved in carcinogenesis. For example, in T-cell acute lymphoblastic leukemia, the oncogenic transcription factor TAL1 and its regulatory partners (GATA3, RUNX1 and MYB) are regulated by super-enhancers; these genes are sensitive to transcriptional inhibition, for example, via the pharmacological approach using a small-molecule CDK7 inhibitor...
2018: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
Shiro Ide, Shin Ohara, Morihiro Inoue, Jian Hua, Masao Hagihara
A 77-year-old male with hyperleukocytosis and thrombocytopenia was diagnosed with Philadelphia chromosome (Ph) -negative B-cell acute lymphoblastic leukemia (ALL) ; he was treated with induction chemotherapy. Despite an initial complete remission, hyperleukocytosis was returned 18 months later. A bone marrow smear revealed a substantial increase in the number of myeloid cells with each stage of differentiation, which was markedly different from the initial presentation, resulting in the diagnosis of Ph-negative myelodysplastic syndrome/myeloproliferative neoplasm (MDS/MPN)...
2018: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
Kathleen W Phelan, Anjali S Advani
PURPOSE OF REVIEW: Treatment options for patients with acute lymphoblastic leukemia (ALL) beyond standard chemotherapy have grown significantly in recent years. In this review, we highlight new targeted therapies in ALL, with an emphasis on immunotherapy. RECENT FINDINGS: Major advances include antibody-based therapies, such as naked monoclonal antibodies, antibody-drug conjugates and bispecific T cell engaging (BiTE) antibodies, as well as adoptive cellular therapies such as chimeric antigen receptor (CAR) T cells...
August 4, 2018: Current Hematologic Malignancy Reports
Sarah Nikiforow, Tao Wang, Michael Hemmer, Stephen Spellman, Görgün Akpek, Joseph H Antin, Sung Won Choi, Yoshihiro Inamoto, Hanna J Khoury, Margaret MacMillan, David I Marks, Ken Meehan, Hideki Nakasone, Taiga Nishihori, Richard Olsson, Sophie Paczesny, Donna Przepiorka, Vijay Reddy, Ran Reshef, Hélène Schoemans, Ned Waller, Daniel Weisdorf, Baldeep Wirk, Mary Horowitz, Amin Alousi, Daniel Couriel, Joseph Pidala, Mukta Arora, Corey Cutler
Upper gastrointestinal acute graft-versus-host disease is reported in approximately 30% of hematopoietic stem cell transplant recipients developing acute graft-versus-host disease. Currently classified as Grade II in Consensus criteria, upper gastrointestinal acute graft-versus-host disease is often treated with systemic immunosuppression. We reviewed the Center for International Blood and Marrow Transplant Research database to assess prognostic implications of upper gastrointestinal acute graft-versus-host disease in isolation or with other acute graft-versus-host disease manifestations...
August 3, 2018: Haematologica
Renate De Smedt, Sofie Peirs, Julie Morscio, Filip Matthijssens, Juliette Roels, Lindy Reunes, Beatrice Lintermans, Steven Goossens, Tim Lammens, Nadine Van Roy, Aurore Touzart, Silvia Jenni, Yi-Chien Tsai, Federica Lovisa, Lara Mussolin, Valentina Serafin, Filip Van Nieuwerburgh, Dieter Deforce, Anne Uyttebroeck, Thomas Tousseyn, Birgit Burkhardt, Wolfram Klapper, Barbara De Moerloose, Yves Benoit, Elizabeth Macintyre, Jean-Pierre Bourquin, Giuseppe Basso, Benedetta Accordi, Beat Bornhauser, Jules Meijerink, Peter Vandenberghe, Pieter Van Vlierberghe
No abstract text is available yet for this article.
August 3, 2018: Haematologica
Ryan J Mattison
On March 29, 2018, blinatumomab (Blincyto, Amgen) received an accelerated expanded approval for the treatment of adult and pediatric patients with B-cell precursor acute lymphoblastic leukemia (ALL) who are in first or second complete remission (CR) and have minimal residual disease (MRD). Blinatumomab was first approved for use in adult patients (in December 2014) and later in pediatric patients (in September 2016) with relapsed or refractory Philadelphia chromosome (Ph)-negative B-cell precursor ALL; the approval was expanded in July 2017 to include patients with Ph-positive disease...
June 2018: Clinical Advances in Hematology & Oncology: H&O
Yulia Olshanskaya, Anna Kazakova, Grigory Tsaur, Elena Zerkalenkova, Olga Soldatkina, Eugenia Aprelova, Olga Plekhanova, Tatiana Gindina, Dmitry Mercur'ev, Ildar Barhkatov, Ludmila Baidun, Oleg Bydanov, Svetlana Lagoiko, Gesche Tallen, Julia Rumiantseva, Alexander Rumiantsev, Alexander Karachunskii, Guenter Henze
The prognostic significance of genetic lesions in T-cell ALL still needs to be elucidated. Karyotyping and FISH were performed in samples from 120 patients with T-cell ALL registered in the trial Moscow-Berlin 2008. Most frequent rearrangements were TLX3 (N = 29; 24%) and TAL1 (N = 18; 15%), followed by KMT2A (N = 6; 5%), TLX1 (N = 5; 4.2%), and 11p13-15 (N = 5; 4.2%). In 16.7% of patients, the karyotype was normal, and in 30.8% 'other' aberrations were seen. Patients with a normal karyotype, TAL1, or KMT2A rearrangements had the most favorable outcome (probability of event free survival (pEFS): 82% ± 6%), while prognosis for patients with TLX3 and TLX1 rearrangements and 'other' aberrations was less favorable (pEFS: 62% ± 6%)...
August 1, 2018: Leukemia & Lymphoma
Matthew Torre, Isaac H Solomon, Claire L Sutherland, Sarah Nikiforow, Daniel J DeAngelo, Richard M Stone, Henrikas Vaitkevicius, Ilene A Galinsky, Robert F Padera, Nikolaus Trede, Sandro Santagata
Chimeric antigen receptor (CAR) T cells are a new and powerful class of cancer immunotherapeutics that have shown potential for the treatment of hematopoietic malignancies. The tremendous promise of this approach is tempered by safety concerns, including potentially fatal neurotoxicity, sometimes but not universally associated with cytokine release syndrome. We describe the postmortem examination of a brain from a 21-year-old patient with relapsed pre-B cell acute lymphoblastic leukemia (ALL) who died from fulminant cerebral edema following CAR T-cell infusion...
July 6, 2018: Journal of Neuropathology and Experimental Neurology
Ya-Zhe Wang, Le Hao, Yan Chang, Qian Jiang, Hao Jiang, Le-Ping Zhang, Ling-Ling He, Xiao-Ying Yuan, Ya-Zhen Qin, Xiao-Jun Huang, Yan-Rong Liu
A seven-color panel was used to detect minimal residual disease (MRD) in T cell acute lymphoblastic leukemia (T-ALL) via flow cytometry (FCM). Its availability and clinical significance were studied in T-ALL patients with newly diagnosed (n = 64), relapsed (n = 48) and morphologically complete remission (n = 103). The following four features were used to identify immature cCD3+ T cells: CD34+, TdT+, but mCD3-/dim+, and CD45dim+. Among these features, either TdT or CD34 expression was the most useful and were found in 93...
July 27, 2018: Leukemia Research
Stuart E Siegel, Anjali Advani, Nita Seibel, Lori Muffly, Wendy Stock, Selina Luger, David R Freyer, Dan Douer, Rebecca H Johnson, Daniel J DeAngelo, Brandon Hayes-Lattin, Mark Lewis, Jerry J Jaboin, Bijal Shah, Peter F Coccia, Archie Bleyer
For young adults with acute lymphoblastic leukemia, pediatric-based regimens are likely to provide the following when compared to hyper-CVAD regimens: better disease control, less hospitalization time, diminished acute toxicities, decreased financial cost, more quality-adjusted life years, and fewer adverse late effects such as infertility, myelodysplasia and second malignant neoplasms. There are also reasons to expect less cardiac and cognitive dysfunction after pediatric regimens. The improved quality and quantity of life associated with pediatric regimens renders them preferable to hyper-CVAD regimens for the treatment of Philadelphia-negative B-precursor or T-cell acute lymphoblastic leukemia and lymphoblastic lymphoma in young adults...
July 30, 2018: American Journal of Hematology
Stepan Hrabovsky, Frantisek Folber, Jan M Horacek, Olga Stehlikova, Hana Jelinkova, Cyril Salek, Michael Doubek
BACKGROUND: Minimal residual disease (MRD) is an important prognostic maker in acute lymphoblastic leukemia (ALL). However, few data comparing the measurement of adult ALL MRD using different methods in daily practice are available. We conducted an analysis comparing the importance of flow cytometry (FCM) and real-time quantitative polymerase chain reaction (PCR) in the assessment of MRD in adult ALL. PATIENTS AND METHODS: Fifty-six consecutive adult patients with both Philadelphia-negative and -positive ALL treated according to an intensive protocol were enrolled in the study...
July 4, 2018: Clinical Lymphoma, Myeloma & Leukemia
T Leigh Spencer Noakes, Thomas S Przybycien, Amanda Forwell, Connor J Nicholls, Yu-Qing Zhou, Darci T Butcher, Rosanna Weksberg, Sharon L Guger, Brenda J Spiegler, Russell J Schachar, Johann Hitzler, Shinya Ito, Ellen van der Plas, Brian J Nieman
PURPOSE: Chemotherapy for childhood acute lymphoblastic leukemia (ALL) can cause late-appearing side effects in survivors that affect multiple organs, including the heart and brain. However, the complex ALL treatment regimen makes it difficult to isolate the causes of these side effects and impossible to separate the contributions of individual chemotherapy agents by clinical observation. Using a mouse model, we therefore assessed each of eight representative, systemically-administered ALL chemotherapy agents for their impact on post-natal brain development and heart function...
July 27, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Markus Poukka, Tiina Lund-Aho, Päivi Raittinen, Atte Nikkilä, Katri Kivinen, Tuija Lundán, Kimmo Porkka, Olli Lohi
We describe a patient with Down syndrome whose precursor B-cell acute lymphoblastic leukemia cells expressed INPP5D-ABL1 fusion gene that resulted in a reciprocal chromosome translocation t(2;9)(q27;q34). The fusion gene was present as a small subclone in the primary disease but was first identified at relapse when the subclone had expanded into a major clone. At relapse, the patient responded poorly to conventional induction chemotherapy but a transient morphologic remission was achieved after administration of imatinib monotherapy...
July 24, 2018: Journal of Pediatric Hematology/oncology
Cuiping Zhang, Angelo D'Alessandro, Ashley M Wellendorf, Fatima Mohmoud, Juana Serrano-Lopez, John P Perentesis, Kakajan Komurov, Gabriela Alexe, Kimberly Stegmaier, Jeffrey A Whitsett, H Leighton Grimes, Jose A Cancelas
High-risk B-cell acute lymphoblastic leukemia (B-ALL) remains a therapeutic challenge despite advances in the use of tyrosine kinase inhibitors and chimeric-antigen-receptor engineered T cells. Lymphoblastic-leukemia precursors are highly sensitive to oxidative stress. KLF5 is a member of the Krüppel-like family of transcription factors. KLF5 expression is repressed in B-ALL, including BCR-ABL1+ B-ALL. Here, we demonstrate that forced expression of KLF5 in B-ALL cells bypasses the imatinib resistance which is not associated with mutations of BCR-ABL...
July 3, 2018: Oncotarget
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