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Philadelphia positive Acute lymphoblastic leukemia

David Gómez-Almaguer, Edson René Marcos-Ramírez, Efreen Horacio Montaño-Figueroa, Guillermo J Ruiz-Argüelles, Carlos Roberto Best-Aguilera, María Del Carmen López-Sánchez, Esperanza Barrera-Chairez, José Luis López-Arrollo, Christian Omar Ramos-Peñafiel, Andrés León-Peña, Elías Eugenio González-López, Perla Edith Rivas-García, Carlos Alberto Tellez-Hinojosa, Andrés Gómez-De León, José Carlos Jaime-Pérez
BACKGROUND: The incidence of acute leukemia (AL) has increased. Its prognosis is variable and depends on several baseline characteristics with a highly heterogeneous presentation. In Mexico, large-scale descriptive studies have not yet been published; the objective of this study was to analyze the initial basic characteristics of patients diagnosed with AL in our population. PATIENTS AND METHODS: In this multicenter, retrospective study, 1018 patients ≥ 16 years of age and diagnosed with AL between 2009 and 2014, were included...
September 17, 2016: Clinical Lymphoma, Myeloma & Leukemia
Ankur Jain, Alka Khadwal, Gaurav Prakash, Nalini Gupta, Subhash Varma, Pankaj Malhotra
Testicular involvement in a case of acute lymphoblastic leukemia (ALL) is well reported, but occurrence of "isolated" malignant hydrocele is extremely uncommon. We herein report a case of a 22-year-old man who presented to our hematology clinic with fever and easy fatiguability of 2 weeks' duration. Examination revealed pallor, cervical lymphadenopathy, and bilateral scrotal swellings. He was diagnosed as a case of Philadelphia-positive ALL (B-cell type) based on peripheral smear, bone marrow examination, and flow cytometry of the marrow aspirate...
2016: Clinical Medicine Insights. Pathology
Nikolaos Papadantonakis, Anjali S Advani
This is an exciting time in the treatment of acute lymphoblastic leukemia (ALL) given the advances in the relapsed/refractory setting. The development of antibody treatments (including antibody drug conjugates with toxins) offers a different treatment approach compared with conventional chemotherapy regimens. Moreover, the use of bispecific T-cell-engager antibodies (BiTEs) such as blinatumomab harness the cytotoxic activity of T cells against CD19-positive lymphoblasts. Another strategy involves the use of chimeric antigen receptor (CAR) T cells...
October 2016: Therapeutic Advances in Hematology
He Li, Wanhua Zhang, Dongni Yi, Yuanxin Ye, Xueqiu Xiao
No abstract text is available yet for this article.
September 23, 2016: Leukemia & Lymphoma
Jessica T Leonard, Wendy Stock
No abstract text is available yet for this article.
November 2016: Biology of Blood and Marrow Transplantation
Hiroshi Ureshino, Atsujiro Nishioka, Kensuke Kojima, Haruna Kizuka, Haruhiko Sano, Takero Shindo, Yasushi Kubota, Toshihiko Ando, Shinya Kimura
Dasatinib has been associated with an increased risk of bleeding, with the most prominent risk noted in patients with advanced-stage chronic myeloid leukemia and thrombocytopenia. We herein report two cases of Philadelphia chromosome-positive acute lymphoblastic leukemia in which a subdural hematoma developed in association with low-dose (40-50 mg/day) dasatinib treatment and lumbar puncture for intrathecal methotrexate injection. Both patients were in complete remission, with normal platelet counts and coagulation status...
2016: Internal Medicine
Sébastien Maury, Sylvie Chevret, Xavier Thomas, Dominik Heim, Thibaut Leguay, Françoise Huguet, Patrice Chevallier, Mathilde Hunault, Nicolas Boissel, Martine Escoffre-Barbe, Urs Hess, Norbert Vey, Jean-Michel Pignon, Thorsten Braun, Jean-Pierre Marolleau, Jean-Yves Cahn, Yves Chalandon, Véronique Lhéritier, Kheira Beldjord, Marie C Béné, Norbert Ifrah, Hervé Dombret
Background Treatment with rituximab has improved the outcome for patients with non-Hodgkin's lymphoma. Patients with B-lineage acute lymphoblastic leukemia (ALL) may also have the CD20 antigen, which is targeted by rituximab. Although single-group studies suggest that adding rituximab to chemotherapy could improve the outcome in such patients, this hypothesis has not been tested in a randomized trial. Methods We randomly assigned adults (18 to 59 years of age) with CD20-positive, Philadelphia chromosome (Ph)-negative ALL to receive chemotherapy with or without rituximab, with event-free survival as the primary end point...
September 15, 2016: New England Journal of Medicine
Guillermo José Ruiz-Delgado, Yahveth Cantero-Fortiz, Andrés Aurelio León-Peña, Mónica León-González, Ana Karen Nuñez-Cortés, Guillermo José Ruiz-Argüelles
BACKGROUND: In B-cell acute lymphoblastic leukemia, one of the most frequent cytogenetic alterations is the presence of the Philadelphia chromosome. Recently, newly identified genetic alterations have been studied, among them the IKZF1 deletion. IKZF1 encodes IKAROS, a zinc finger protein that plays an important role in hematopoiesis involving the regulation process of adhesion, cellular migration, and as a tumor suppressor. OBJECTIVE: We aimed to study the impact of IKAROS deletion in the evolution and prognosis of B-cell acute lymphoblastic leukemia...
July 2016: Revista de Investigación Clínica; Organo del Hospital de Enfermedades de la Nutrición
Daniela Renzi, Francesco Marchesi, Gottardo De Angelis, Loredana Elia, Emanuela Salvatorelli, Svitlana Gumenyuk, Francesca Palombi, Francesco Pisani, Atelda Romano, Antonio Spadea, Elena Papa, Marco Canfora, William Arcese, Andrea Mengarelli
We describe the case of a patient with a Philadelphia-positive (Ph+) acute lymphoblastic leukemia (ALL) treated with dasatinib plus steroids as the first-line therapy who achieved a molecular complete remission and then underwent a matched, unrelated donor allogeneic transplant. Five months after the transplant, he experienced a disease relapse with an T315I mutation, which was resistant to salvage chemotherapy. Once the details of the T315I mutation were acquired, we initiated ponatinib treatment at a standard dosage and observed a rapid decrease of minimal residual disease (MRD) at molecular assessment...
September 10, 2016: Chemotherapy
Jessica T Leonard, Joelle S J Rowley, Christopher A Eide, Elie Traer, Brandon Hayes-Lattin, Marc Loriaux, Stephen E Spurgeon, Brian J Druker, Jeffrey W Tyner, Bill H Chang
Treatment of Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph(+)ALL) remains a challenge. Although the addition of targeted tyrosine kinase inhibitors (TKIs) to standard cytotoxic therapy has greatly improved upfront treatment, treatment-related morbidity and mortality remain high. TKI monotherapy provides only temporary responses and renders patients susceptible to the development of TKI resistance. Thus, identifying agents that could enhance the activity of TKIs is urgently needed. Recently, a selective inhibitor of B cell lymphoma 2 (BCL-2), ABT-199 (venetoclax), has shown impressive activity against hematologic malignancies...
August 31, 2016: Science Translational Medicine
Giovanna Carrà, Davide Torti, Sabrina Crivellaro, Cristina Panuzzo, Riccardo Taulli, Daniela Cilloni, Angelo Guerrasio, Giuseppe Saglio, Alessandro Morotti
The Nuclear Factor-kappa B (NF-κB) family of transcription factors plays a key role in cancer pathogenesis due to the ability to promote cellular proliferation and survival, to induce resistance to chemotherapy and to mediate invasion and metastasis. NF-κB is recruited through different mechanisms involving either canonical (RelA/p50) or non-canonical pathways (RelB/p50 or RelB/p52), which transduce the signals originated from growth-factors, cytokines, oncogenic stress and DNA damage, bacterial and viral products or other stimuli...
August 22, 2016: Oncotarget
Xavier Thomas, Maël Heiblig
In Philadelphia chromosome-positive (Ph(+)) acute lymphoblastic leukemia (ALL), the BCR-ABL translocation is the main transforming event; consequently, it is targeted by ABL-tyrosine kinase inhibitors (TKIs), the first of which to be identified was imatinib mesylate. There are now four newer TKIs, three so-called second-generation inhibitors and one third generation inhibitor, all of which are more potent than imatinib in in vitro assays. Areas covered: This paper reviews the current knowledge on the function of BCR-ABL...
November 2016: Expert Opinion on Drug Discovery
Yoshimasa Kamoda, Kiyotaka Izumi, Futoshi Iioka, Takashi Akasaka, Fumihiko Nakamura, Chiyuki Kishimori, Katsuyo Tsuda, Katsuhiro Fukutsuka, Atsuko Okumura, Masahiko Hayashida, Hitoshi Ohno
Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) may include the lymphoid blast crisis of chronic myeloid leukemia (CML-BC). We applied fluorescence in situ hybridization (FISH) of the BCR-ABL fusion gene to peripheral blood and/or bone marrow smears to determine whether the fusion was restricted to mononuclear cell nuclei or if segmented cell nuclei representing mature neutrophils also carried the fusion (Seg-FISH). Among 20 patients with Ph+ ALL without a prior diagnosis of CML, 9 were Seg-FISH+ and 11 were Seg-FISH-...
2016: Acta Haematologica
David J Dorer, Ronald K Knickerbocker, Michele Baccarani, Jorge E Cortes, Andreas Hochhaus, Moshe Talpaz, Frank G Haluska
Ponatinib is approved for adults with refractory chronic myeloid leukemia or Philadelphia chromosome-positive acute lymphoblastic leukemia, including those with the T315I BCR-ABL1 mutation. We pooled data from 3 clinical trials (N=671) to determine the impact of ponatinib dose intensity on the following adverse events: arterial occlusive events (cardiovascular, cerebrovascular, and peripheral vascular events), venous thromboembolic events, cardiac failure, thrombocytopenia, neutropenia, hypertension, pancreatitis, increased lipase, increased alanine aminotransferase, increased aspartate aminotransferase, rash, arthralgia, and hypertriglyceridemia...
September 2016: Leukemia Research
Takanobu Morishita, Fumihiko Hayakawa, Keiki Sugimoto, Mizuho Iwase, Hideyuki Yamamoto, Daiki Hirano, Yuki Kojima, Naoto Imoto, Tomoki Naoe, Hitoshi Kiyoi
Cell lines have been used for drug discovery as useful models of cancers; however, they do not recapitulate cancers faithfully, particularly from the viewpoints of microenvironmental independence. Patient-derived xenografts (PDX) are established by the transfer of primary tumor cells directly from patients into immunodeficient mice and can provide primary-like tumor cells of the amount needed at the desired time. We developed a high-throughput drug screening system using PDX cells and performed drug screening using the PDX cells of Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL)...
August 2, 2016: Oncotarget
Federico Lussana, Tamara Intermesoli, Francesca Gianni, Cristina Boschini, Arianna Masciulli, Orietta Spinelli, Elena Oldani, Manuela Tosi, Anna Grassi, Margherita Parolini, Ernesta Audisio, Chiara Cattaneo, Roberto Raimondi, Emanuele Angelucci, Irene Maria Cavattoni, Anna Maria Scattolin, Agostino Cortelezzi, Francesco Mannelli, Fabio Ciceri, Daniele Mattei, Erika Borlenghi, Elisabetta Terruzzi, Claudio Romani, Renato Bassan, Alessandro Rambaldi
Allogeneic stem cell transplantation (alloHSCT) in first complete remission (CR1) remains the consolidation therapy of choice in Philadelphia-positive (Ph+) acute lymphoblastic leukemia (ALL). The prognostic value of measurable levels of minimal residual disease (MRD) at time of conditioning is a matter of debate. We analyzed the predictive relevance of MRD levels before transplantation on the clinical outcome of Ph+ ALL patients treated with chemotherapy and imatinib in 2 consecutive prospective clinical trials...
November 2016: Biology of Blood and Marrow Transplantation
Wei Ye, Zhiwu Jiang, Xiaoyun Lu, Xiaomei Ren, Manman Deng, Shouheng Lin, Yiren Xiao, Simiao Lin, Suna Wang, Baiheng Li, Yi Zheng, Peilong Lai, Jianyu Weng, Donghai Wu, Yuguo Ma, Xudong Chen, Zhesheng Wen, Yaoyu Chen, Xiaoyan Feng, Yangqiu Li, Pentao Liu, Xin Du, Duanqing Pei, Yao Yao, Bing Xu, Ke Ding, Peng Li
Available therapeutic options for advanced B cell precursor acute lymphoblastic leukemia (pre-B ALL) are limited. Many lead to neutropenia, leaving patients at risk of life-threatening infections and result in bad outcomes. New treatment options are needed to improve overall survival. We previously showed that GZD824, a novel BCR-ABL tyrosine kinase inhibitor, has anti-tumor activity in Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia cells and tumor models. Here, we show that GZD824 decreases cell viability, induces cell-cycle arrest, and causes apoptosis in pre-B ALL cells...
July 28, 2016: Oncotarget
Koji Sasaki, Elias J Jabbour, Farhad Ravandi, Nicholas J Short, Deborah A Thomas, Guillermo Garcia-Manero, Naval G Daver, Tapan M Kadia, Marina Y Konopleva, Nitin Jain, Ghayas C Issa, Vicki Jeanis, Haim G Moore, Rebecca S Garris, Naveen Pemmaraju, Jorge E Cortes, Susan M O'Brien, Hagop M Kantarjian
BACKGROUND: The clinical efficacy of hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone (HCVAD) plus ponatinib has not been compared with that of HCVAD plus dasatinib in patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) in a randomized clinical trial. METHODS: The authors analyzed 110 patients with newly diagnosed Ph+ ALL who were enrolled in 2 consecutive, prospective, phase 2 clinical trials of frontline HCVAD with either dasatinib (63 patients) or ponatinib (47 patients)...
August 1, 2016: Cancer
Thanh-Phuong Nguyen, Sowmya Nanjappa, Manjunath Muddaraju, John N Greene
The first case of pulmonary talcosis or talc pneumoconiosis related to inhalation of talc during its extraction and processing in mines was described by Thorel in 1896. Pulmonary talcosis is most commonly seen secondary to occupational exposure or intravenous (IV) drug abuse and, occasionally, in excessive use of cosmetic talc. Based on literature review, there has been an increase in reported incidents of pulmonary talcosis due to various forms of exposure to the mineral. We report an 82-year-old man who is diagnosed with Philadelphia chromosome positive pre-B cell acute lymphoblastic leukemia (ALL) treated with palliative imatinib who presented with chronic hemoptysis and dyspnea shortly after his diagnosis...
2016: Case Reports in Medicine
Kshitij Joshi, Harsha Panchal, Sonia Parikh, Gaurang Modi, Avinash Talele, Asha Anand, Urmila Uparkar, Nitin Joshi, Itesh Khatawani
The author describes paediatric case of relapsed acute lymphoblastic leukaemia (ALL) presented as aleukemic leukaemia cutis (ALC). A 2 year old child was admitted in tertiary oncology centre. He suffered from pre B cell ALL with absent Philadelphia chromosome. This patient received multiagent induction chemotherapy as per Berlin-Frankfurt-Munster (BFM) protocol for ALL. He achieved remission after 28 days of treatment. Subsequently he presented with multiple skin lesions in the form of multiple small erythematous violaceous macules, papules, plaques and nodules on face, chest and back regions...
June 2016: Indian Journal of Hematology & Blood Transfusion
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