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Chronic lymphoblastic leukemia

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https://www.readbyqxmd.com/read/29773429/real-life-experience-with-ponatinib-in-chronic-myeloid-leukemia-a-multicenter-observational-study
#1
Adi Shacham-Abulafia, Pia Raanani, David Lavie, Yulia Volchek, Ron Ram, Ilana Helman, Liat Shargian, Anna Gourevitch, Evgeni Chubar, Roy Ratzon, Uri Rozovski
BACKGROUND: The strict recruitment criteria of patients for clinical trials often lead to reduced generalizability of the findings. We studied how ponatinib is used outside clinical trials in patients with chronic myeloid leukemia (CML). PATIENTS AND METHODS: The present retrospective study included all patients with a diagnosis of CML who had received ponatinib in 7 medical centers in Israel. RESULTS: From 2011 to 2016, we identified 37 patients with CML who had received ponatinib, 21 in the chronic phase and 16 in the advanced phase...
May 7, 2018: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/29772458/phenotyping-and-target-expression-profiling-of-cd34-cd38-and-cd34-cd38-stem-and-progenitor-cells-in-acute-lymphoblastic-leukemia
#2
Katharina Blatt, Ingeborg Menzl, Gregor Eisenwort, Sabine Cerny-Reiterer, Harald Herrmann, Susanne Herndlhofer, Gabriele Stefanzl, Irina Sadovnik, Daniela Berger, Alexandra Keller, Alexander Hauswirth, Gregor Hoermann, Michael Willmann, Thomas Rülicke, Heinz Sill, Wolfgang R Sperr, Christine Mannhalter, Junia V Melo, Ulrich Jäger, Veronika Sexl, Peter Valent
Leukemic stem cells (LSCs) are an emerging target of curative anti-leukemia therapy. In acute lymphoblastic leukemia (ALL), LSCs frequently express CD34 and often lack CD38. However, little is known about markers and targets expressed in ALL LSCs. We have examined marker- and target expression profiles in CD34+ /CD38- LSCs in patients with Ph+ ALL (n = 22) and Ph- ALL (n = 27) by multi-color flow cytometry and qPCR. ALL LSCs expressed CD19 (B4), CD44 (Pgp-1), CD123 (IL-3RA), and CD184 (CXCR4) in all patients tested...
May 14, 2018: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/29766234/the-severe-cytokine-release-syndrome-in-phase-i-trials-of-cd19-car-t-cell-therapy-a-systematic-review
#3
REVIEW
Zhen Jin, Rufang Xiang, Kai Qing, Xiaoyang Li, Yunxiang Zhang, Lining Wang, Hongming Zhu, Yuanfei Mao, Zizhen Xu, Junmin Li
CD19 chimeric antigen receptor (CAR) T cell therapy has shown impressive results in treating acute lymphoblastic leukemia (B-ALL), chronic lymphoblastic leukemia (B-CLL), and B-cell non-Hodgkin lymphoma (B-NHL) over the past few years. Meanwhile, the cytokine release syndrome (CRS), which could be moderate or even life-threatening, has emerged as the most significant adverse effect in the clinical course of this novel targeting immunotherapy. In this systematic review, we analyzed the incidence of severe CRS in 19 clinical trials selected from studies published between 2010 and 2017...
May 15, 2018: Annals of Hematology
https://www.readbyqxmd.com/read/29743179/a-cd19-cd3-bispecific-antibody-for-effective-immunotherapy-of-chronic-lymphocytic-leukemia-in-the-ibrutinib-era
#4
Hannah R Robinson, Junpeng Qi, Erika M Cook, Cydney Nichols, Eman L Dadashian, Chingiz Underbayev, Sarah E M Herman, Nakhle S Saba, Keyvan Keyvanfar, Clare Sun, Inhye E Ahn, Sivasubramanian Baskar, Christoph Rader, Adrian Wiestner
The Bruton's tyrosine kinase inhibitor ibrutinib induces high rates of clinical response in chronic lymphocytic leukemia (CLL). However, there remains a need for adjunct treatments to deepen response and to overcome drug resistance. Blinatumomab, a CD19/CD3 bispecific antibody (bsAb) designed in the BiTE® format, is FDA approved for the treatment of relapsed or refractory B-cell precursor acute lymphoblastic leukemia. Due to its short half-life of 2.1 hours, blinatumomab requires continuous intravenous dosing for efficacy...
May 9, 2018: Blood
https://www.readbyqxmd.com/read/29739773/graft-versus-host-disease-in-recipients-of-male-unrelated-donor-compared-with-parous-female-sibling-donor-transplants
#5
Anita J Kumar, Soyoung Kim, Michael T Hemmer, Mukta Arora, Stephen R Spellman, Joseph A Pidala, Daniel R Couriel, Amin M Alousi, Mahmoud D Aljurf, Jean-Yves Cahn, Mitchell S Cairo, Corey S Cutler, Shatha Farhan, Usama Gergis, Gregory A Hale, Shahrukh K Hashmi, Yoshihiro Inamoto, Rammurti T Kamble, Mohamed A Kharfan-Dabaja, Margaret L MacMillan, David I Marks, Hideki Nakasone, Maxim Norkin, Muna Qayed, Olle Ringden, Harry C Schouten, Kirk R Schultz, Melhem M Solh, Takanori Teshima, Alvaro Urbano-Ispizua, Leo F Verdonck, Robert Peter Gale, Betty K Hamilton, Navneet S Majhail, Alison W Loren
Optimal donor selection is critical for successful allogeneic hematopoietic cell transplantation (HCT). Donor sex and parity are well-established risk factors for graft-versus-host disease (GVHD), with male donors typically associated with lower rates of GVHD. Well-matched unrelated donors (URDs) have also been associated with increased risks of GVHD as compared with matched sibling donors. These observations raise the question of whether male URDs would lead to more (or less) favorable transplant outcomes as compared with parous female sibling donors...
May 8, 2018: Blood Advances
https://www.readbyqxmd.com/read/29697355/genetic-variation-of-costimulatory-molecules-including-cytotoxic-t-lymphocyte-antigen-4-inducible-t-cell-costimulator-cluster-differentiation-28-and-programmed-cell-death-1-genes-in-iranian-patients-with-leukemia
#6
Mani Ramzi, Nargess Arandi, Mahdiyar Iravani Saadi, Ramin Yaghobi, Bita Geramizadeh
OBJECTIVES: There are limited studies about the possible relationship between genetic variations of costimulatory genes and susceptibility to hematologic malignancies like leukemia and lymphoma. MATERIALS AND METHODS: This cross-sectional study included 59 leukemia patients. The polymorphisms of costimulatory molecules, including the CTLA-4 gene (-318 C/T, -1722 T/C, -1661 A/G, +49 A/G), PD-1 gene (1.3 A/G, 1.9 C/T), ICOS gene (1720 C/T), and CD28 gene (17 C/T), were analyzed by polymerase chain reaction-restriction fragment length polymorphism methods...
April 26, 2018: Experimental and Clinical Transplantation
https://www.readbyqxmd.com/read/29692582/institutional-based-tumor-registry-of-hematopoietic-malignancies-a-4-years-preliminary-report-from-karachi
#7
Sadia Sultan, Syed Mohammed Irfan, Navaira Ali, Neesha Nawaz
BACKGROUND: Pakistan has a population of over 198 million making it the world's sixth populous country. However, operational population-based cancer registries in Pakistan are lacking. Limited data are available based on institutional or Karachi Cancer Registry from Karachi; however, no exclusive registry for hematological malignancies is established till date. Hence, we decided to conduct a database analysis to determine the frequencies of various hematological cancers in our tertiary care center in Karachi...
April 2018: Journal of Laboratory Physicians
https://www.readbyqxmd.com/read/29666622/chemotactic-cues-for-notch1-dependent-leukemia
#8
REVIEW
Erich Piovan, Valeria Tosello, Alberto Amadori, Paola Zanovello
The NOTCH signaling pathway is a conserved signaling cascade that regulates many aspects of development and homeostasis in multiple organ systems. Aberrant activity of this signaling pathway is linked to the initiation and progression of several hematological malignancies, exemplified by T-cell acute lymphoblastic leukemia (T-ALL). Interestingly, frequent non-mutational activation of NOTCH1 signaling has recently been demonstrated in B-cell chronic lymphocytic leukemia (B-CLL), significantly extending the pathogenic significance of this pathway in B-CLL...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29665944/-current-status-and-challenges-of-car-t-immunotherapy-in-hematologic-malignancies-review
#9
Xin Cheng, Ya-Jie Wang, Shuai Feng, Ya-Yun Wu, Tong-Hua Yang, Xun Lai
The chimeric antigen receptor (CAR) T cell therapy has gradually became a new trend in the treatment of refractory and relapsed hematologic malignancies by developing for 30 years. With the exciting development of genetic engineering, CAR-T technology has subjected to 4 generations of innovation. Structure of CAR-T started from a single signal molecule to 2 or more than 2 co-stimulatory molecules, and then coding the CAR gene or promoter. CAR-T can specifically recognize tumor antigens, and does not be restricted by major histocompatibility complex (MHC), thus making a breakthrough in clinical treatment...
April 2018: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/29664513/vitiligo-type-cutaneous-manifestation-of-chronic-graft-versus-host-disease-case-report
#10
Karla Gálvez, Paula Muñoz, Valentina Vera, Claudio Arce
INTRODUCTION: Graft-versus-host disease (GVHD) is caused by a pathologic and destructive response of the organism as a result of the interaction between donor immunocompetent T lymphocytes and the recipient tisular antigens. It's considered the most serious complication of hematopoietic stem cell transplantation, most frequently described after bone marrow transplantation (BMT). The skin is usually the first and most commonly affected organ, in both acute and chronic, with a variable clinical spectrum of presentation...
February 2018: Revista Chilena de Pediatría
https://www.readbyqxmd.com/read/29663189/a-characteristic-flow-cytometric-pattern-with-broad-forward-scatter-and-narrowed-side-scatter-helps-diagnose-immune-thrombocytopenia-itp
#11
Raita Araki, Ryosei Nishimura, Rie Kuroda, Toshihiro Fujiki, Shintaro Mase, Kazuhiro Noguchi, Yasuhiro Ikawa, Hideaki Maeba, Akihiro Yachie
Various disorders cause severe thrombocytopenia, which can lead to critical hemorrhage. Procedures that rapidly support the diagnosis and risk factors for serious bleeding were explored, with a focus on immune thrombocytopenia (ITP). Twenty-five patients with thrombocytopenia, including 13 with newly diagnosed ITP, 3 with chronic ITP, 6 with aplastic anemia (AA), and 3 with other thrombocytopenia (one acute myeloid leukemia, one acute lymphoblastic leukemia, and one hemophagocytic lymphohistiocytosis), were reviewed...
April 16, 2018: International Journal of Hematology
https://www.readbyqxmd.com/read/29650292/novel-compounds-that-target-lipoprotein-lipase-and-mediate-growth-arrest-in-acute-lymphoblastic-leukemia
#12
Rajesh R Nair, Werner J Geldenhuys, Debbie Piktel, Prabodh Sadana, Laura F Gibson
Over the past decade, the therapeutic strategies employed to treat B-precursor acute lymphoblastic leukemia (ALL) have been progressively successful in treating the disease. Unfortunately, the treatment associated dyslipidemia, either acute or chronic, is very prevalent and a cause for decreased quality of life in the surviving patients. To overcome this hurdle, we tested a series of cylopropanecarboxamides, a family demonstrated to target lipid metabolism, for their anti-leukemic activity in ALL. Several of the compounds tested showed anti-proliferative activity, with one, compound 22, inhibiting both Philadelphia chromosome negative REH and Philadelphia chromosome positive SupB15 ALL cell division...
March 23, 2018: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/29616647/epidemiology-of-malignant-hemopathies-recorded-in-hospitals-in-cameroon
#13
P T Moueleu Ngalagou, E Ngouadjeu Dongho Tsakeu, F Ngo Sack, E C Eboumbou Moukoko, Y Konn Jolly, H Luma
Data about malignant blood diseases are sparse in Cameroon. Their epidemiology was studied in patients at the General Hospital of Douala (GHD) and the Yaoundé Central Hospital (CHY) from 2004 through 2014. The variables we studied were social and demographic (age, sex, occupation, marital status), clinical (reasons for consultation, clinical signs, year of diagnosis), and biological (blood count, myelogram and blood smear, immunophenotyping, biopsy, and cytogenetics). In all, 4409 files were reviewed and 454 cases identified, documented and confirmed (248 in GHD and 206 in CHY)...
February 1, 2018: Médecine et Santé Tropicales
https://www.readbyqxmd.com/read/29603136/anti-thymocyte-globulin-improves-survival-free-from-relapse-and-graft-versus-host-disease-after-allogeneic-peripheral-blood-stem-cell-transplantation-in-patients-with-philadelphia-negative-acute-lymphoblastic-leukemia-an-analysis-by-the-acute-leukemia-working
#14
Tomasz Czerw, Myriam Labopin, Sebastian Giebel, Gérard Socié, Liisa Volin, Nathalie Fegueux, Tamás Masszi, Didier Blaise, Sridhar Chaganti, Jan J Cornelissen, Jakob Passweg, Johan Maertens, Maija Itälä-Remes, Depei Wu, Mohamad Mohty, Arnon Nagler
BACKGROUND: Mobilized peripheral blood stem cells are currently the predominant source of grafts for allogeneic transplantation (allogeneic peripheral blood stem cell transplantation [allo-PBSCT]), although, in comparison with bone marrow, their use is associated with an increased risk of chronic graft-versus-host disease (cGVHD). Attempts to reduce the incidence of cGVHD include the addition of anti-thymocyte globulin (ATG) to the pretransplant conditioning regimen. METHODS: The goal of this retrospective study was to analyze the effect of ATG on allo-PBSCT outcomes for adults with Philadelphia-negative acute lymphoblastic leukemia (Ph-neg ALL)...
March 30, 2018: Cancer
https://www.readbyqxmd.com/read/29574915/cyclophosphamide-versus-etoposide-in-combination-with-total-body-irradiation-as-conditioning-regimen-for-adult-patients-with-ph-negative-acute-lymphoblastic-leukemia-undergoing-allogeneic-stem-cell-transplant-on-behalf-of-the-alwp-of-the-ebmt
#15
Anna Czyz, Myriam Labopin, Sebastian Giebel, Gerard Socié, Jane Apperley, Liisa Volin, Péter Reményi, Ibrahim Yakoub-Agha, Kim Orchard, Mauricette Michallet, Gernot Stuhler, Sridhar Chaganti, Martin Murray, Mahmoud Aljurf, Adrian Bloor, Jacob Passweg, Jürgen Finke, Mohamad Mohty, Arnon Nagler
Allogeneic hematopoietic cell transplantation (alloHCT) with myeloablative conditioning based on total body irradiation (TBI) is widely used for the treatment of adults with acute lymphoblastic leukemia (ALL). TBI is most frequently administered in combination with either cyclophosphamide (Cy/TBI) or etoposide (Vp/TBI). The goal of this study was to retrospectively compare these two regimens. Adult patients with Ph-negative ALL treated with alloHCT in first or second complete remission who received Cy/TBI (n=1346) or Vp/TBI (n=152) conditioning were included in the analysis...
March 25, 2018: American Journal of Hematology
https://www.readbyqxmd.com/read/29567798/ponatinib-efficacy-and-safety-in-philadelphia-chromosome-positive-leukemia-final-5-year-results-of-the-phase-2-pace-trial
#16
Jorge E Cortes, Dong-Wook Kim, Javier Pinilla-Ibarz, Philipp D le Coutre, Ronald Paquette, Charles Chuah, Franck E Nicolini, Jane F Apperley, H Jean Khoury, Moshe Talpaz, Daniel J DeAngelo, Elisabetta Abruzzese, Delphine Rea, Michele Baccarani, Martin C Müller, Carlo Gambacorti-Passerini, Stephanie Lustgarten, Victor M Rivera, Frank G Haluska, François Guilhot, Michael W Deininger, Andreas Hochhaus, Timothy P Hughes, Neil P Shah, Hagop M Kantarjian
Ponatinib has potent activity against native and mutant BCR-ABL1, including BCR-ABL1T315I The pivotal phase 2 PACE trial evaluated efficacy and safety of ponatinib at a starting dose of 45 mg once daily in 449 patients with chronic myeloid leukemia (CML) or Philadelphia chromosome-positive acute lymphoblastic leukemia resistant/intolerant to dasatinib or nilotinib, or with BCR ABL1T315I This analysis focuses on chronic-phase CML (CP-CML) patients (n=270) with 56.8-month median follow-up. Among 267 evaluable patients, 60%, 40%, and 24% achieved major cytogenetic response (MCyR), major molecular response (MMR), and MR4...
March 22, 2018: Blood
https://www.readbyqxmd.com/read/29505472/cutaneous-t-cell-lymphoma-a-novel-manifestation-of-pdgfra-rearranged-neoplasm
#17
Amir Behdad, Pamela Allen, Xinyan Lu, Xiaolong Alan Zhou, Joan Guitart, Qing Chen, Barbara Pro
Patients with PDGFRA-rearranged hematopoietic neoplasms typically present with chronic eosinophilic leukemia and rarely with acute myeloid leukemia or T-lymphoblastic lymphoma. However, mature T-cell lymphoma has not been previously associated with PDGFRA aberrations. We report a patient who presented with simultaneous T-lymphoblastic lymphoma, focal myeloid proliferation, and cutaneous cytotoxic T-cell lymphoma refractory to chemotherapy. The presence of myeloid and lymphoid lineages prompted genetic and molecular studies...
February 21, 2018: American Journal of Dermatopathology
https://www.readbyqxmd.com/read/29501750/mixed-phenotype-t-b-myeloid-extramedullary-blast-crisis-as-an-initial-presentation-of-chronic-myelogenous-leukemia
#18
Xin Qing, Annie Qing, Ping Ji, Samuel W French, Holli Mason
BACKGROUND: Chronic myelogenous leukemia (CML) is a myeloproliferative disorder characterized by the Philadelphia (Ph) chromosome generated by the reciprocal translocation t(9,22)(q34;q11). The natural progression of the disease follows a biphasic or triphasic course. Most cases of CML are diagnosed in the chronic phase. Extramedullary blast crisis rarely occurs during the course of CML, and is extremely rare as the initial presentation of CML. CASE PRESENTATION: Here, we report the case of a 32-year-old female with enlarged neck lymph nodes and fatigue...
April 2018: Experimental and Molecular Pathology
https://www.readbyqxmd.com/read/29499750/grading-of-cytokine-release-syndrome-associated-with-the-car-t-cell-therapy-tisagenlecleucel
#19
REVIEW
David Porter, Noelle Frey, Patricia A Wood, Yanqiu Weng, Stephan A Grupp
BACKGROUND: Anti-CD19 CAR T cell therapy has demonstrated high response rates in patients with relapsed or refractory (r/r) B cell malignancies but is associated with significant toxicity. Cytokine release syndrome (CRS) is the most significant complication associated with CAR T cell therapy, and it is critical to have a reproducible and easy method to grade CRS after CAR T cell infusions. DISCUSSION: The Common Terminology Criteria for Adverse Events scale is inadequate for grading CRS associated with cellular therapy...
March 2, 2018: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/29498925/dasatinib-in-pediatric-patients-with-chronic-myeloid-leukemia-in-chronic-phase-results-from-a-phase-ii-trial
#20
Lia Gore, Pamela R Kearns, Maria Lucia de Martino, Lee, Carmino Antonio De Souza, Yves Bertrand, Nobuko Hijiya, Linda C Stork, Nack-Gyun Chung, Rocio Cardenas Cardos, Tapan Saikia, Franca Fagioli, Jong Jin Seo, Judith Landman-Parker, Donna Lancaster, Andrew E Place, Karen R Rabin, Mariana Sacchi, Rene Swanink, C Michel Zwaan
Purpose Safe, effective treatments are needed for pediatric patients with chronic myeloid leukemia in chronic phase (CML-CP). Dasatinib is approved for treatment of adults and children with CML-CP. A phase I study determined suitable dosing for children with Philadelphia chromosome-positive (Ph+) leukemias. Methods CA180-226/NCT00777036 is a phase II, open-label, nonrandomized prospective trial of patients < 18 years of age receiving dasatinib. There are three cohorts: (1) imatinib-resistant/intolerant CML-CP, (2) imatinib-resistant/intolerant CML in accelerated/blast phase or Ph+ acute lymphoblastic leukemia (n = 17), and (3) newly diagnosed CML-CP treated with tablets or powder for oral suspension...
May 1, 2018: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
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