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Curr Treat Options Oncol ; 23(3): 359-380, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35258791


OPINION STATEMENT: Treatment options in acute myeloid leukemia (AML) have improved significantly over the last decade with better understanding of disease biology and availability of a multitude of targeted therapies. The use of FLT3 inhibitors (FLT3i) in FLT3-mutated (FLT3mut) AML is one such development; however, the clinical decisions that govern their use and dictate the choice of the FLT3i are evolving. Midostaurin and gilteritinib are FDA-approved in specific situations; however, available data from clinical trials also shed light on the utility of sorafenib maintenance post-allogeneic stem cell transplantation (allo-SCT) and quizartinib as part of combination therapy in FLT3mut AML. The knowledge of the patient's concurrent myeloid mutations, type of FLT3 mutation, prior FLT3i use, and eligibility for allo-SCT helps to refine the choice of FLT3i. Data from ongoing studies will further precisely define their use and help in making more informed choices. Despite improvements in FLT3i therapy, the definitive aim is to enable the eligible patient with FLT3mut AML (esp. ITD) to proceed to allo-SCT with regimens containing FLT3i incorporated prior to SCT and as maintenance after SCT.

Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda , Humanos , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/genética , Mutação , Inibidores de Proteínas Quinases/uso terapêutico , Transplante Homólogo , Tirosina Quinase 3 Semelhante a fms/genética , Tirosina Quinase 3 Semelhante a fms/uso terapêutico
Leuk Lymphoma ; 61(3): 536-545, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31752577


Despite advances in understanding the pathogenesis of acute myeloid leukemia (AML), the standard therapy remained nearly unchanged for several decades. There have been many efforts to improve the response and survival by either increasing the cytarabine (ARA-C) dose or adding a third agent to the standard chemotherapy regimen. Several studies have evaluated the addition of cladribine (CdA) to standard induction, exploiting its property to potentiate ARA-C uptake. Response rates for combination regimens including CdA in relapsed/refractory (R/R) adults are approximately 50% and approximately 70% in de novo AML. Recently, a low intensity combination of CdA and ARA-C alternating with decitabine has shown promising results in older patients with AML. In this review, we will discuss the role of CdA in the treatment of AML, summarizing the recent clinical data regarding its incorporation into the induction therapy for adult AML.

Leucemia Mieloide Aguda , Preparações Farmacêuticas , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Cladribina/uso terapêutico , Citarabina/uso terapêutico , Humanos , Leucemia Mieloide Aguda/tratamento farmacológico , Indução de Remissão
Blood ; 134(14): 1132-1143, 2019 10 03.
Artigo em Inglês | MEDLINE | ID: mdl-31292114


T-cell prolymphocytic leukemia (T-PLL) is a rare, mature T-cell neoplasm with a heterogeneous clinical course. With the advent of novel treatment options that will potentially change the management of patients with T-PLL, it has become necessary to produce consensus guidelines for the design and conduct of clinical trials. The T-PLL International Study group (TPLL-ISG) set out to define standardized criteria for diagnosis, treatment indication, and evaluation of response. These criteria will facilitate comparison of results from clinical trials in T-PLL, and will thus support clinical decision making, as well as the approval of new therapeutics by healthcare authorities.

Leucemia Prolinfocítica de Células T/diagnóstico , Leucemia Prolinfocítica de Células T/terapia , Medula Óssea/patologia , Gerenciamento Clínico , Regulação Leucêmica da Expressão Gênica , Humanos , Imunofenotipagem , Leucemia Prolinfocítica de Células T/genética , Leucemia Prolinfocítica de Células T/patologia , Mutação , Estadiamento de Neoplasias , Linfócitos T/patologia
Oncotarget ; 10(12): 1250-1265, 2019 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-30815228


Acute myeloid leukemia (AML) is the most common form of acute leukemia in adults, affecting approximately 21,000 people annually (nearly 11,000 deaths) in the United States. B-cell lymphoma 2 (BCL-2) family proteins, notably myeloid cell leukemia-1 (MCL-1), have been associated with both the development and persistence of AML. MCL-1 is one of the predominant BCL-2 family members expressed in samples from patients with untreated AML. MCL-1 is a critical cell survival factor for cancer and contributes to chemotherapy resistance by directly affecting cell death pathways. Here, we review the role of MCL-1 in AML and the mechanisms by which the potent cyclin-dependent kinase 9 inhibitor alvocidib, through regulation of MCL-1, may serve as a rational therapeutic approach against the disease.

Expert Rev Hematol ; 10(5): 433-448, 2017 05.
Artigo em Inglês | MEDLINE | ID: mdl-28452257


INTRODUCTION: The past decade or longer has witnessed an acceleration in our understanding of previously developed immune system and clonal evolution mechanisms, and the genesis of more novel concepts of telomere attrition. Many of these concepts are steadily finding their way into translation in various aspects of clinical practice, and provide prospects to improve AA management and inform therapeutic strategy development. In this review, we intend to discuss the pathophysiology and treatments with an emphasis on most recent developments to provide an update on our understanding of disease mechanisms. Areas covered: A literature search was undertaken addressing various aspects of pathophysiology with a focus on the role of immune system repertoire, telomeres and mutational events surrounding AA. We also reviewed upon the temporal evolution of treatment strategies in AA to the contemporary management of today and commented briefly upon the more recently investigated novel therapies and their expanding niche especially in the transplant and salvage setting. Expert commentary: Immune-mediated destruction of hematopoietic stem and progenitor cells, leading to a marrow devoid of hematopoietic elements, and peripheral pancytopenia are the hallmarks of AA. Recent studies have shed light on another facet of the disease - as a clonal disorder characterized by karyotypic abnormalities, genomic instability, telomere attrition, and recurrent somatic mutations reminiscent of myeloid malignancies. Further understanding of this underlying pathophysiology can help in improving prognostication and treatment of this disease.

Anemia Aplástica , Cariótipo Anormal , Anemia Aplástica/genética , Anemia Aplástica/metabolismo , Anemia Aplástica/fisiopatologia , Anemia Aplástica/terapia , Instabilidade Genômica , Células-Tronco Hematopoéticas/metabolismo , Humanos , Telômero/genética , Telômero/metabolismo
Am J Hematol ; 89(10): 964-8, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24990142


Despite being considered "good-risk" acute myelogenous leukemia (AML), long term outcomes in core binding factor (CBF) AML suggest room for improvement. We report on a regimen consisting of fludarabine, cytarabine, granulocyte colony stimulating factor, and low dose gemtuzumab ozogamicin (FLAG-GO) as front-line therapy of patients with CBF AML. Forty-five patients were enrolled (median age 48 years). Remission rate was 95% with 5% induction deaths. The overall survival (OS) and relapse free survival (RFS) probability at 3 years are 78% and 85%, respectively. FLAG-GO regimen results in high rates of RFS and OS in CBF AML. Our data along with recent data from several large groups strongly argues in favor of incorporation of gemtuzumab ozogamicin in frontline regimens for CBF AML.

Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Fatores de Ligação ao Core , Leucemia Mieloide Aguda/tratamento farmacológico , Adulto , Idoso , Aminoglicosídeos/administração & dosagem , Aminoglicosídeos/efeitos adversos , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Citarabina/administração & dosagem , Citarabina/efeitos adversos , Intervalo Livre de Doença , Feminino , Gemtuzumab , Fator Estimulador de Colônias de Granulócitos e Macrófagos/administração & dosagem , Fator Estimulador de Colônias de Granulócitos e Macrófagos/efeitos adversos , Humanos , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/mortalidade , Masculino , Pessoa de Meia-Idade , Taxa de Sobrevida , Vidarabina/administração & dosagem , Vidarabina/efeitos adversos , Vidarabina/análogos & derivados