scholarly journals How I treat FLT3-mutated AML

Blood ◽  
2017 ◽  
Vol 129 (5) ◽  
pp. 565-571 ◽  
Author(s):  
Keith W. Pratz ◽  
Mark Levis
Keyword(s):  
Myeloid Leukemia ◽  
Tandem Duplication ◽  
Kinase Inhibitors ◽  
Common Type ◽  
World Health ◽  
Distinct Entity ◽  
Internal Tandem Duplication ◽  
The World ◽  
Health Organization ◽  
Near Future

Abstract FLT3-mutated acute myeloid leukemia (AML), despite not being recognized as a distinct entity in the World Health Organization (WHO) classification system, is readily recognized as a particular challenge by clinical specialists who treat acute leukemia. This is especially true with regards to the patients harboring the most common type of FLT3 mutation, the internal tandem duplication (FLT3-ITD) mutation. Here we present 4 patient cases from our institution and discuss how our management reflects what we have learned about this subtype of the disease. We also reflect on how we anticipate the management might change in the near future, with the emergence of clinically useful tyrosine kinase inhibitors.

Clinico-pathologic characteristics and outcomes of the World Health Organization (WHO) provisional entity de novo acute myeloid leukemia with mutated RUNX1

2020 ◽  
Vol 33 (9) ◽  
pp. 1678-1689
Author(s):  
Andrés E. Quesada ◽  
Guillermo Montalban-Bravo ◽  
Rajyalakshmi Luthra ◽  
Keyur P. Patel ◽  
Koji Sasaki ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
World Health Organization ◽  
Myeloid Leukemia ◽  
De Novo ◽  
World Health ◽  
The World ◽  
Health Organization ◽  
Acute Myeloid

Quizartinib in the treatment of FLT3-internal-tandem duplication-positive acute myeloid leukemia

2019 ◽  
Vol 15 (34) ◽  
pp. 3885-3894 ◽  
Author(s):  
Shilpa Paul ◽  
Adam J DiPippo ◽  
Farhad Ravandi ◽  
Tapan M Kadia
Keyword(s):  
Acute Myeloid Leukemia ◽  
Tyrosine Kinase ◽  
Myeloid Leukemia ◽  
Tandem Duplication ◽  
Kinase Inhibitors ◽  
Single Agent ◽  
Tyrosine Kinase Domain ◽  
Missense Mutations ◽  
Internal Tandem Duplication ◽  
Acute Myeloid

FLT3 mutations, characterized by an internal-tandem duplication or missense mutations in the tyrosine kinase domain, are observed in a third of patients with newly diagnosed acute myeloid leukemia. FLT3-ITD mutations are associated with high relapse rates and short overall survival with conventional chemotherapy. Several tyrosine kinase inhibitors targeting FLT3 have been developed in an effort to improve survival and therapeutic options. This review focuses on quizartinib, a second-generation FLT3 inhibitor that has demonstrated efficacy and safety as a single agent and in combination with chemotherapy. We discuss its clinical development as well as its place in the treatment of FLT3-mutated acute myeloid leukemia among the other FLT3 inhibtors currently available and its mechanisms of resistance.

scholarly journals BCR-ABL1–like B-Acute Lymphoblastic Leukemia/Lymphoma: A Comprehensive Review

2019 ◽  
Vol 144 (2) ◽  
pp. 150-155 ◽  
Author(s):  
Sarika Jain ◽  
Anu Abraham
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
World Health Organization ◽  
Kinase Inhibitors ◽  
Lymphoblastic Leukemia ◽  
World Health ◽  
Comprehensive Review ◽  
The World ◽  
Health Organization ◽  
Stimulating Factor

Context.— In the 2016 update of the World Health Organization (WHO) classification of hematopoietic neoplasms, BCR-ABL1–like B-acute lymphoblastic leukemia/lymphoma (B-ALL) is added as a new provisional entity that lacks the BCR-ABL1 translocation but shows a pattern of gene expression very similar to that seen in B-ALL with BCR-ABL1. Objective.— To review the kinase-activating alterations and the diagnostic approach for BCR-ABL1–like B-ALL. Data Sources.— We provide a comprehensive review of BCR-ABL1–like B-ALL based on recent literature and the 2016 update of the World Health Organization classification of hematopoietic neoplasms. Conclusions.— Several types of kinase-activating alterations (fusions or mutations) are identified in BCR-ABL1–like B-ALL. The main categories are alterations in the ABL class family of genes, encompassing ABL1, ABL2, PDGFRB, PDGFRA (rare), and colony-stimulating factor 1 receptor (CSF1R) fusions, or the JAK2 class family of genes, encompassing alterations in JAK2, CRLF2, EPOR, and other genes in this pathway. These alterations determine the sensitivity to tyrosine kinase inhibitors. As a wide variety of genomic alterations are included in this category, the diagnosis of BCR-ABL1–like B-ALL is extremely complex. Stepwise algorithms and comprehensive unbiased testing are the 2 ways to approach the diagnosis of BCR-ABL1–like B-ALL.

BCR-ABL1-like B-Lymphoblastic Leukemia/Lymphoma with FOXP1-ABL1 Rearrangement: Comprehensive Laboratory Identification Allowing Tyrosine Kinase Inhibitor Use

2019 ◽  
Vol 50 (4) ◽  
pp. 401-405
Author(s):  
Ashwini K Yenamandra ◽  
Saara Kaviany ◽  
Scott C Borinstein ◽  
Debra L Friedman ◽  
Alexandra E Kovach
Keyword(s):  
Kinase Inhibitor ◽  
Lymphoblastic Leukemia ◽  
Common Type ◽  
World Health ◽  
Rb1 Gene ◽  
Molecular Alterations ◽  
The World ◽  
Health Organization ◽  
Therapeutic Considerations

AbstractB-lymphoblastic leukemia/lymphoma (B-ALL) is the most common type of childhood cancer; it also occurs in teenagers and adults, in whom the prognosis is generally less favorable. Therapeutic and molecular advances have substantially improved the treatment for subtypes of B-ALL, such that subclassification by cytogenetic and molecular alterations is critical for risk stratification and management. Novel rearrangements involving ABL1, JAK2, EPO, and other kinases have been identified that may respond to inhibition akin to BCR-ABL1. This diverse group of leukemias has been recognized as a provisional entity in the 2016 revision of the World Health Organization (WHO) Classification of the Hematopoietic Neoplasms as B-lymphoblastic leukemia/lymphoma, BCR-ABL1–like (Ph-like B-ALL).Herein, we present cytogenetic and molecular analysis of a case of B-ALL in a 16-year-old Caucasian boy with t(3;9) FOXP1-ABL1 rearrangement and concurrent loss of IKZF1, CDKN2A, and RB1 gene loci, meeting WHO criteria for Ph-like ALL. This case highlights diagnostic, prognostic, and therapeutic considerations of this recently recognized entity.

scholarly journals Differences and Similarities between Coronaviruses: A Comparative Review

2021 ◽  
Vol 9 (4) ◽  
Author(s):  
Maad M. Mijwil ◽  
Ayser Shamil Alsaadi ◽  
Karan Aggarwal
Keyword(s):  
World Health ◽  
Infected People ◽  
The Past ◽  
Preventive Vaccine ◽  
Comparative Review ◽  
The World ◽  
Structural Differences ◽  
Health Organization ◽  
Near Future ◽  
Future Reference

Today, humans fight powerful and active viruses that never take hold and do not know defeat, named coronaviruses. These viruses have start in 2002 and continued to grow and have changed their chains dramatically until now. They are known for having many similar features in common, and there are also structural differences between them. The most important reason that has turned coronaviruses into a pandemic is that this disease is easily transmitted by droplets near infected people, which leads to the spread of this virus faster worldwide. The more details known about coronaviruses that have profoundly affected humanity in the past and present and the diseases they cause, the more benefit in help designing an immune response or preventive vaccine to these viruses in the near future. In this article, coronaviruses, how they have been started and spread, and what differences and similarities are between them will be briefly covered here. The information of this investigation is taken from articles and the world health organization and are reviewed here. The goal is to document this information for future reference.

scholarly journals Adherence to Immunization: Rebuttal of Vaccine Hesitancy

2020 ◽  
pp. 1-5
Author(s):  
Tamar Etzioni-Friedman ◽  
Amos Etzioni
Keyword(s):  
Adverse Effects ◽  
Public Health Problem ◽  
World Health ◽  
Vaccine Hesitancy ◽  
Major Public Health Problem ◽  
Immunodeficiency Virus ◽  
The World ◽  
Health Organization ◽  
Near Future ◽  
New Vaccines

Immunizations have been saving the lives of millions of people since they were first used by Edward Jenner in 1796, and new vaccines are being developed all the time. Hopefully, a new vaccine for coronavirus disease 2019 (COVID-19) will be developed in the near future, and perhaps even one for human immunodeficiency virus. Although the effectiveness of vaccinations has been proven over the years and adverse effects to currently available vaccinations are extremely rare, many people continue to defer immunizations for themselves and their families. According to the World Health Organization (WHO), this phenomenon, known as “vaccine hesitancy,” is a major public health problem globally. This review summarizes the unproven adverse effects of various vaccines and stresses the importance of enforcing vaccination policies to minimize vaccine hesitancy. Every effort should be made to improve existing vaccines and to produce new ones, according to carefully designed scientific preclinical and clinical trials. This is particularly important in today’s era, in light of the global transparency regarding vaccination development, and the potential for future pandemics such as COVID-19.

Primary low-grade myofibroblastic sarcoma: A rare case report of this tumor in the orbit and literature review

2020 ◽  
pp. 112067212097039
Author(s):  
Lijuan Tang ◽  
Hua Xu ◽  
Huanhuan Gao ◽  
Huasheng Yang ◽  
Shuxia Chen ◽  
...  
Keyword(s):  
Case Report ◽  
Rare Case ◽  
World Health ◽  
Low Grade ◽  
Distinct Entity ◽  
Myofibroblastic Sarcoma ◽  
The World ◽  
Rare Case Report ◽  
Health Organization ◽  
Myofibroblastic Differentiation

Low-grade myofibroblastic sarcoma (LGMS) is an exceedingly rare, malignant tumor with myofibroblastic differentiation. It frequently occurs in the oral cavity and extremities, despite being classified as a distinct entity by the World Health Organization (WHO). Here, we report a rare case of orbital LGMS occurring in an 11-month-old baby with a 3.2 × 2.4 × 2.1 cm mass. LGMS was diagnosed based on the histological and immunohistochemical findings. Previous literature suggests that surgical resection with clear margins is an appropriate method for the treatment of LGMS, and combined adjuvant therapy (local radiotherapy with or without chemotherapy) can improve the prognosis, but further studies are needed.

scholarly journals Acquired Myelodysplasia or Myelodysplastic Syndrome: Clearing the Fog

2013 ◽  
Vol 2013 ◽  
pp. 1-11 ◽  
Author(s):  
Ethan A. Natelson ◽  
David Pyatt
Keyword(s):  
Myeloid Leukemia ◽  
Myeloproliferative Neoplasms ◽  
Bone Marrow Failure ◽  
Myeloproliferative Disorders ◽  
World Health ◽  
Clinical Settings ◽  
Hematologic Disorders ◽  
Immune Mediated ◽  
The World ◽  
Health Organization

Myelodysplastic syndromes (MDS) are clonal myeloid disorders characterized by progressive peripheral blood cytopenias associated with ineffective myelopoiesis. They are typically considered neoplasms because of frequent genetic aberrations and patient-limited survival with progression to acute myeloid leukemia (AML) or death related to the consequences of bone marrow failure including infection, hemorrhage, and iron overload. A progression to AML has always been recognized among the myeloproliferative disorders (MPD) but occurs only rarely among those with essential thrombocythemia (ET). Yet, the World Health Organization (WHO) has chosen to apply the designation myeloproliferative neoplasms (MPN), for all MPD but has not similarly recommended that all MDS become the myelodysplastic neoplasms (MDN). This apparent dichotomy may reflect the extremely diverse nature of MDS. Moreover, the term MDS is occasionally inappropriately applied to hematologic disorders associated with acquired morphologic myelodysplastic features which may rather represent potentially reversible hematological responses to immune-mediated factors, nutritional deficiency states, and disordered myelopoietic responses to various pharmaceutical, herbal, or other potentially myelotoxic compounds. We emphasize the clinical settings, and the histopathologic features, of such AMD that should trigger a search for a reversible underlying condition that may be nonneoplastic and not MDS.

scholarly journals NPM1 MUTATED, BCR-ABL1 POSITIVE MYELOID NEOPLASMS: REVIEW OF LITERATURE

2020 ◽  
Vol 12 (1) ◽  
pp. e2020083
Author(s):  
Gianfranco Catalano ◽  
Pasquale Niscola ◽  
Cristina Banella ◽  
Daniela Diverio ◽  
Malgorzata Monika Trawinska ◽  
...  
Keyword(s):  
Myeloid Leukemia ◽  
Kinase Inhibitors ◽  
Chimeric Protein ◽  
Break Point ◽  
World Health ◽  
Founder Mutations ◽  
Molecular Features ◽  
Hematological Cancers ◽  
Health Organization ◽  
Inhibition Of Differentiation

Break point cluster region - Abelson (BCR-ABL1) chimeric protein and mutated Nucleophosmin (NPM1) are often present in hematological cancers, but they rarely coexist in the same disease. Both anomalies are considered founder mutations causing inhibition of differentiation and apoptosis, but BCR-ABL1 could act as a secondary mutation conferring a proliferative advantage to a pre-neoplastic clone. The 2016 World Health Organization (WHO) classification lists the provisional acute myeloid leukemia (AML) with BCR-ABL1, which must be diagnosed differentially from the rare blast phase (BP) onset of a chronic myeloid leukemia (CML), mainly because of the different therapeutic approach in the use of tyrosine kinase inhibitors (TKI). Here we review all published cases since 1975 and describe a case from our institution in order to discuss the clinical and molecular features of this rare combination, and report the latest acquisition about an occurrence that could pertain either to the rare AML BCR-ABL1 positive or the even rarer CML-BP with mutated NPM1 at onset.

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