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Mixed phenotype acute leukemia

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https://www.readbyqxmd.com/read/29720486/international-cooperative-study-identifies-treatment-strategy-in-childhood-ambiguous-lineage-leukemia
#1
Ondrej Hrusak, Valerie De Haas, Jitka Stancikova, Barbora Vakrmanova, Iveta Janotova, Ester Mejstrikova, Vaclav Capek, Jan Trka, Marketa Zaliova, Ales Luks, Kirsten Bleckmann, Anja Möricke, Julie Irving, Benigna Konatkowska, Thomas B Alexander, Hiroto Inaba, Kjeld Schmiegelow, Simone Stokley, Zuzana Zemanova, Anthony V Moorman, Jorge Gabriel Rossi, Maria Sara Felice, Luciano Dalla-Pozza, Jessa Morales, Michael Dworzak, Barbara Buldini, Giuseppe Basso, Myriam Campbell, Maria Elena Cabrera, Neda Marinov, Sarah Elitzur, Shai Izraeli, Drorit Luria, Tamar Feuerstein, Alexandra Kolenova, Peter Svec, Olena Kreminska, Karen R Rabin, Sophia Polychronopoulou, Elaine da Costa, Hanne Vibeke Marquart, Antonis Kattamis, Richard Ratei, Dirk Reinhardt, John K Choi, Martin Schrappe, Jan Stary
Despite attempts to improve the definitions of ambiguous leukemia (ALAL) during the last two decades, general therapy recommendations are missing. Herein, we report a large cohort of children with ALAL and propose a treatment strategy. A retrospective multinational study iBFM-AMBI2012 on 233 cases of pediatric ALAL patients is presented. Survival statistics were used to compare the prognosis of subsets and types of treatment. Five-year event-free survival (5yEFS) of patients with acute lymphoblastic leukemia (ALL)-type primary therapy (80±4%) was superior to that of children who received acute myeloid leukemia (AML)-type or combined-type treatments (36±7...
May 2, 2018: Blood
https://www.readbyqxmd.com/read/29696242/fibroblast-growth-factor-23-induced-hypophosphatemia-in-acute-leukemia
#2
Rachel B Reinert, Dale Bixby, Ronald J Koenig
Fibroblast growth factor 23 (FGF23)-induced hypophosphatemia is a rare paraneoplastic syndrome of phosphate wasting that, if unrecognized, may cause tumor-induced osteomalacia. It is classically associated with benign mesenchymal tumors but occasionally has been found in patients with other malignancies. Hypophosphatemia has been associated with acute leukemia but has not previously been reported to be due to inappropriate FGF23 secretion. Here, we describe FGF23-induced severe hypophosphatemia and renal phosphate wasting associated with a mixed-phenotype Philadelphia chromosome-like acute leukemia in a previously healthy 22-year-old man...
May 1, 2018: Journal of the Endocrine Society
https://www.readbyqxmd.com/read/29686566/mixed-phenotypic-acute-leukemia
#3
John R Krause, Sarah Findeis
Mixed phenotypic acute leukemias (MPALs) are a heterogeneous group of rare leukemias constituting about 1% to 5% of all leukemias. MPAL is defined as an acute leukemia that demonstrates expression of a combination of antigens of different lineages so that it is not possible to assign a single lineage to that leukemia. These leukemias have been characterized by relative therapeutic resistance. We present a case of a woman with an acute MPAL diagnosed as a B/myeloid leukemia.
January 2018: Proceedings of the Baylor University Medical Center
https://www.readbyqxmd.com/read/29620650/durable-remission-in-a-patient-of-mixed-phenotype-acute-leukemia-with-philadelphia-chromosome-positive-treated-with-nilotinib-and-lenalidomide-a-case-report
#4
Binbin Lai, Qitian Mu, Huiling Zhu, Yi Wang, Yi Zhang, Kaihong Xu, Lixia Sheng, Guifang Ouyang
RATIONALE: Philadelphia chromosome-positive mixed phenotype acute leukemia (Ph+ MPAL) is a rare type of leukemia with poor prognosis. Tyrosine kinase inhibitors (TKIs) in combination with chemotherapy have significantly improved its remission rate. However, relapse remains the major obstacle to achieve long survival. Lenalidomide is a second-generation oral immunomodulatory drug that has been broadly applied in the treatment of various hematological malignancies. PATIENT CONCERNS: A 54-year-old Chinese male patient who complained of chest pain and fatigue for 20 days...
April 2018: Medicine (Baltimore)
https://www.readbyqxmd.com/read/29550836/therapy-for-children-and-adults-with-mixed-phenotype-acute-leukemia-a-systematic-review-and-meta-analysis
#5
REVIEW
Maria Maruffi, Richard Sposto, Matthew J Oberley, Lynn Kysh, Etan Orgel
The rarity of mixed-phenotype acute leukemia (MPAL) has resulted in diffuse literature consisting of small case series, thus precluding a consensus treatment approach. We conducted a meta-analysis and systematic review to investigate the association of treatment type (acute lymphoblastic leukemia [ALL], acute myeloid leukemia [AML], or "hybrid" regimens), disease response, and survival. We searched seven databases from inception through June 2017 without age or language restriction. Included studies reported sufficient treatment detail for de novo MPAL classified according to the well-established European Group for Immunological Characterization of Acute Leukemias (EGIL) or World Health Organization (WHO2008) criteria...
February 27, 2018: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/29546454/an-update-on-classification-genetics-and-clinical-approach-to-mixed-phenotype-acute-leukemia-mpal
#6
REVIEW
Maliha Khan, Rabbia Siddiqi, Kiran Naqvi
Mixed phenotype acute leukemia (MPAL) is an uncommon diagnosis, representing only about 2-5% of acute leukemia cases. The blast cells of MPAL express multilineage immunophenotypic markers and may have a shared B/T/myeloid phenotype. Due to historical ambiguity in the diagnosis of MPAL, the genetics and clinical features of this disease remain poorly characterized. Based on the 2008 and 2016 World Health Organization classifications, myeloid lineage is best determined by presence of myeloperoxidase, while B and T lymphoid lineages are demonstrated by CD19 and cytoplasmic CD3 expression...
June 2018: Annals of Hematology
https://www.readbyqxmd.com/read/29492206/mixed-phenotype-acute-leukemia-contains-heterogeneous-genetic-mutations-by-next-generation-sequencing
#7
Andrés E Quesada, Zhihong Hu, Mark J Routbort, Keyur P Patel, Rajyalakshmi Luthra, Sanam Loghavi, Zhuang Zuo, C Cameron Yin, Rashmi Kanagal-Shamanna, Sa A Wang, Jeffrey L Jorgensen, L Jeffrey Medeiros, Chi Young Ok
Mixed phenotype acute leukemia (MPAL) is an uncommon manifestation of acute leukemia. The aim of this study is to further characterize the genetic landscape of de novo cases of MPAL that fulfill the 2016 World Health Organization (WHO) classification criteria for this entity. We identified 14 cases examined by next generation sequencing (NGS) using 28 ( n = 10), 53 ( n = 3) or 81 ( n = 1) gene panels: 7 cases with a B-cell/myeloid (B/My) immunophenotype, 6 T-cell/myeloid (T/My) immunophenotype, and 1 B-cell/T-cell (B/T) immunophenotype...
February 2, 2018: Oncotarget
https://www.readbyqxmd.com/read/29423036/salvaged-allogeneic-hematopoietic-stem-cell-transplantation-for-pediatric-chemotherapy-refractory-acute-leukemia
#8
Jingbo Wang, Lei Yuan, Haoyu Cheng, Xinhong Fei, Yumin Yin, Jiangying Gu, Song Xue, Junbao He, Fan Yang, Xiaocan Wang, Yixin Yang, Weijie Zhang
There is an ongoing debate concerning the performance of salvaged allogeneic hematopoietic stem cell transplantation (allo-HSCT) in pediatric patients with acute refractory leukemia, in whom the prognosis is quite dismal. Few studies have ever been conducted on this subject. This may be partly due to missed opportunities by majority of the patients in such situations. To investigate the feasibility, evaluate the efficiency, and identify the prognostic factors of allo-HSCT in this sub-setting, the authors performed a single institution-based retrospective analysis...
January 9, 2018: Oncotarget
https://www.readbyqxmd.com/read/29415942/-initial-presentation-of-lymphoblastic-crisis-in-a-pediatric-chronic-myelogenous-leukemia-patient
#9
Kosuke Akiyama, Shohei Yamamoto, Yumiko Sugishita, Ryota Kaneko, Naoko Okamoto, Masaya Koganesawa, Sachio Fujita, Ryosuke Matsuno, Daisuke Toyama, Keiichi Isoyama
A 9-year-old girl was referred to our hospital because of facial palsy. Both physical and blood examination revealed hepatosplenomegaly and leukocytosis, respectively. A bone marrow examination demonstrated marked hypercellularity involving myeloblasts and lymphoblasts. Based on these results, we suspected mixed phenotype acute leukemia. However, her leukemic blasts expressed B-cell antigens, and a chromosomal analysis of her bone marrow cells revealed the following karyotype: 46, XX, t (9;22) (q34;q11.2). All her neutrophils were positive for the breakpoint cluster region-Abelson murine leukemia viral oncogene homolog 1 fusion protein...
2018: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
https://www.readbyqxmd.com/read/29398816/stodtmeister-cells-polymorphs-with-pelger-hu%C3%A3-t-anomaly-showing-faggots-in-mixed-phenotypic-acute-leukemia-t-myeloid
#10
Tushar Sehgal, Pawan Singh, Esha Kaul
"Faggot" cells, named for the resemblance of multiple Auer rods to a bundle of sticks, are often considered sine qua non for acute promyelocytic leukemia. However, blasts in other acute myeloid leukemias rarely also show faggot cells. This case demonstrates faggot cells in stodtmeister cells in mixed phenotypic acute leukemia. In addition to being uncommon, this case also highlights the importance of immunophenotyping and genetic analysis in avoiding misdiagnosis and inappropriate therapy.
January 2018: Indian Journal of Hematology & Blood Transfusion
https://www.readbyqxmd.com/read/29223952/isolated-myeloperoxidase-expression-in-pediatric-b-myeloid-mixed-phenotype-acute-leukemia-is-linked-with-better-survival
#11
LETTER
Sunil S Raikar, Sunita I Park, Traci Leong, David L Jaye, Frank G Keller, John T Horan, William G Woods
No abstract text is available yet for this article.
February 1, 2018: Blood
https://www.readbyqxmd.com/read/29207878/cd20-cd19-bispecific-car-t-cells-for-the-treatment-of-b-cell-malignancies
#12
Alexandra Martyniszyn, Ann-Christin Krahl, Maya C André, Andreas A Hombach, Hinrich Abken
The treatment of leukemia/lymphoma by chimeric antigen receptor (CAR) redirected T cells with specificity for CD19 induced complete remissions in the majority of patients, with a realistic hope for cure. However, recent follow-up data revealed a substantial risk of relapse through leukemic cells that lack the CAR targeted antigen. In this situation, a bispecific CAR with binding domains for CD19 and CD20 is aimed at recognizing leukemic cells with only one cognate antigen. The anti-CD20-CD19 bispecific CAR induced a full T-cell response upon engagement of CD19 or CD20 on target cells showing a true "OR" gate recognition in redirecting T-cell activation...
December 2017: Human Gene Therapy
https://www.readbyqxmd.com/read/29200701/a-rare-extramedullary-and-extralymphoid-presentation-of-mixed-phenotypic-blastic-hematolymphoid-neoplasm-a-study-of-two-cases
#13
Kiran Ghodke, Prashant Tembhare, Nikhil Patkar, P G Subramanian, Brijesh Arora, Sumeet Gujral
Mixed phenotype acute leukemia (MPAL) is a rare hematolymphoid neoplasm, representing only 3%-5% of acute leukemia. Although MPAL has been sufficiently described in the literature, its extramedullary presentation as a solitary lesion without leukemic (bone marrow [BM]) involvement is rarely described. We are presenting two cases of mixed phenotypic blastic hematolymphoid neoplasms without leukemic involvement at disease presentation in 8-year-old female and 21-year-old male patients. Both the cases had extralymphatic bone involvement in the form of solitary bone lesion...
July 2017: Indian Journal of Medical and Paediatric Oncology
https://www.readbyqxmd.com/read/29164065/transcriptional-and-microenvironmental-regulation-of-lineage-ambiguity-in-leukemia
#14
REVIEW
Tianyuan Hu, Rebecca Murdaugh, Daisuke Nakada
Leukemia is characterized by the uncontrolled production of leukemic cells and impaired normal hematopoiesis. Although the combination of chemotherapies and hematopoietic stem cell transplantation has significantly improved the outcome of leukemia patients, a proportion of patients still suffer from relapse after treatment. Upon relapse, a phenomenon termed "lineage switch" is observed in a subset of leukemia patients, in which conversion of lymphoblastic leukemia to myeloid leukemia or vice versa is observed...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/29140408/philadelphia-chromosome-like-mixed-phenotype-acute-leukemia-demonstrating-p2ry8-crlf2-fusion-and-jak1-mutation
#15
Sarah M Choi, John K Frederiksen, Charles W Ross, Dale L Bixby, Lina Shao
Objectives: Philadelphia chromosome-like (Ph-like) genetic alterations define a subset of B lymphoblastic leukemia/lymphoma (B-ALL), which represents a separate provisional entity in the World Health Organization 2016 updated classification. However, these alterations have not been described outside the context of B-ALL. Methods: Cytogenomic array and molecular analysis identified a Ph-like signature in a mixed-phenotype acute leukemia (MPAL), B/myeloid, confirmed using conventional immunophenotypic and cytochemical analysis...
November 20, 2017: American Journal of Clinical Pathology
https://www.readbyqxmd.com/read/29137234/the-af4-mll-fusion-transiently-augments-multilineage-hematopoietic-engraftment-but-is-not-sufficient-to-initiate-leukemia-in-cord-blood-cd34-cells
#16
Cristina Prieto, Rolf Marschalek, Alessa Kühn, Adelheid Bursen, Clara Bueno, Pablo Menéndez
The translocation t(4;11)(q21;q23) is the hallmark genetic abnormality associated with infant pro-B acute lymphoblastic leukemia (B-ALL) and has the highest frequency of rearrangement in Mixed-lineage leukemia (MLL) leukemias. Unlike other MLL translocations, MLL-AF4-induced proB-ALL is exceptionally difficult to model in mice/humans. Previous work has investigated the relevance of the reciprocal translocation fusion protein AF4-MLL for t(4;11) leukemia, finding that AF4-MLL is capable of inducing proB-ALL without requirement for MLL-AF4 when expressed in murine hematopoietic stem/progenitor cells (HSPCs)...
October 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29118508/treatment-of-unilateral-zone-i-cytomegalovirus-retinitis-in-acute-lymphoblastic-leukemia-with-oral-valganciclovir-and-intravitreal-ganciclovir
#17
Koushik Tripathy, Kanhaiya Mittal, Pradeep Venkatesh, Sameer Bakhshi, Rohan Chawla
Cytomegalovirus retinitis (CMVR) is an opportunistic infection seen in immunocompromised patients, especially suffering from acquired immune deficiency syndrome. It is uncommonly seen in hematological malignancies and in patients on immunosuppressants. The authors present a 12-year-old girl with unilateral CMVR who was on maintenance phase therapy for mixed phenotype (B/myeloid) leukemia. Serology for human immunodeficiency virus was negative. The child was successfully treated with oral valganciclovir and repeated intravitreal ganciclovir injections...
September 2017: Oman Journal of Ophthalmology
https://www.readbyqxmd.com/read/29112013/cancer-therapy-associated-lymphoproliferative-disorders-an-under-recognized-type-of-immunodeficiency-associated-lymphoproliferative-disorder
#18
Sergio Pina-Oviedo, Roberto N Miranda, L Jeffrey Medeiros
We describe the clinicopathologic features of 17 patients who had a hematologic malignancy of various types, were treated, and subsequently developed a lymphoproliferative disorder (LPD). There were 10 men and 7 women with a median age of 59 years (range, 36 to 83 y). The primary hematologic neoplasms included: 5 chronic lymphocytic leukemia/small lymphocytic lymphoma, 3 plasma cell myeloma, 2 acute monoblastic leukemia, and 1 case each of mixed-phenotype acute leukemia, chronic myeloid leukemia, splenic marginal zone lymphoma, follicular lymphoma, mantle cell lymphoma, T-cell prolymphocytic leukemia, and peripheral T-cell lymphoma...
January 2018: American Journal of Surgical Pathology
https://www.readbyqxmd.com/read/29089646/automated-database-guided-expert-supervised-orientation-for-immunophenotypic-diagnosis-and-classification-of-acute-leukemia
#19
L Lhermitte, E Mejstrikova, A J van der Sluijs-Gelling, G E Grigore, L Sedek, A E Bras, G Gaipa, E Sobral da Costa, M Novakova, E Sonneveld, C Buracchi, T de Sá Bacelar, J G Te Marvelde, A Trinquand, V Asnafi, T Szczepanski, S Matarraz, A Lopez, B Vidriales, J Bulsa, O Hrusak, T Kalina, Q Lecrevisse, M Martin Ayuso, M Brüggemann, J Verde, P Fernandez, L Burgos, B Paiva, C E Pedreira, J J M van Dongen, A Orfao, V H J van der Velden
Precise classification of acute leukemia (AL) is crucial for adequate treatment. EuroFlow has previously designed an AL orientation tube (ALOT) to guide towards the relevant classification panel (T-cell acute lymphoblastic leukemia (T-ALL), B-cell precursor (BCP)-ALL and/or acute myeloid leukemia (AML)) and final diagnosis. Now we built a reference database with 656 typical AL samples (145 T-ALL, 377 BCP-ALL, 134 AML), processed and analyzed via standardized protocols. Using principal component analysis (PCA)-based plots and automated classification algorithms for direct comparison of single-cells from individual patients against the database, another 783 cases were subsequently evaluated...
November 1, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/29072953/mixed-phenotype-acute-leukemia-diagnostic-criteria-and-pitfalls
#20
REVIEW
Nathan J Charles, Daniel F Boyer
Mixed-phenotype acute leukemia (MPAL) is a heterogeneous category in the World Health Organization classification that comprises acute leukemias with discrete admixed populations of myeloid and lymphoid blasts ("bilineal") or with extensive coexpression of lymphoid and myeloid markers in a single blast population ("biphenotypic"). Flow cytometric findings suggestive of MPAL are often met with consternation by pathologists and oncologists alike, owing to unfamiliarity with the disease and uncertainty about how MPAL fits into established paradigms for treatment of acute leukemia...
November 2017: Archives of Pathology & Laboratory Medicine
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