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2.
Gan To Kagaku Ryoho ; 51(3): 291-297, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38494811

RESUMO

An 84-year-old woman was diagnosed as having acute promyelocytic leukemia(APL)in July Year X-3. The test for promyelocytic leukemia- retinoic acid receptor alpha(PML-RARA)mRNA was positive, while that for CD56 was negative. Since her white blood cell( WBC) count was <3,000/µL, with a count of APL cells of <1,000/µL, she was started on monotherapy with all-trans retinoic acid(ATRA). In September Year X-3, complete hematological remission(CHR)was confirmed. she refused to provide consent for receiving consolidation therapy. In February Year X-2, hematological relapse occurred. She was started on re-induction therapy with arsenite(ATO), and in June Year X-2, complete molecular remission(CMR)was achieved. She was started on post-remission therapy with ATO. In August Year X-1, she developed molecular relapse and was started on tamibarotene(Am80). In October Year X-1, hematological relapse was detected, and the test for CD56 was positive. She was started on combined venetoclax(VEN)+azacitidine(AZA)(VEN+AZA). After completion of 1 course of treatment, CMR was achieved, but she developed hematological relapse after 5 courses of treatment. She died of gastrointestinal hemorrhage. This is considered a valuable case for accumulating information on the treatment of CD56-positive APL resistant to ATRA and ATO.


Assuntos
Compostos Bicíclicos Heterocíclicos com Pontes , Leucemia Promielocítica Aguda , Sulfonamidas , Humanos , Feminino , Idoso de 80 Anos ou mais , Leucemia Promielocítica Aguda/tratamento farmacológico , Trióxido de Arsênio/uso terapêutico , Azacitidina/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Tretinoína/uso terapêutico , Recidiva
3.
Cancer Rep (Hoboken) ; 7(3): e2035, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38507294

RESUMO

BACKGROUND: Recent advances in the treatment of acute promyelocytic leukemia (APML) have seen unprecedented improvements in patient outcomes. However, such rapid growth in understanding often leads to uncertainty regarding superiority among candidate treatment regimens, especially when further scrutinized from an epidemiological perspective. AIMS: The aim of this systematic review with epidemiological analysis was to identify and compare commonly utilized protocols for standard-risk APML with a particular focus on complete remission (CR), overall/disease-free survival (DFS), and reported adverse events. METHODS AND RESULTS: Medline, Scopus, and CINAHL were interrogated to identify studies utilizing all-trans retinoic acid (ATRA) in addition to arsenic trioxide (ATO) and/or anthracyclines such as idarubicin (IDA) in the treatment of de-novo APML. After collation of studies, an epidemiological analysis was subsequently performed to compare protocols with regards to outcomes of interest using number needed to benefit (NNB) and number needed to harm (NNH) measures. Seventeen articles, describing 12 distinct trials, were included in the analysis. These trials made use of three unique protocols; CR rates were 94%-100% for ATO/ATRA regimens, 95%-96% for ATO/ATRA/anthracycline regimens, and 89%-94% for ATRA/anthracycline regimens. Epidemiological analysis demonstrated NNB for CR was 9.09 (ATO/ATRA vs. ATRA/IDA) and 20.00 (ATO/ATRA vs. ATO/ATRA/IDA), NNH for neutropenia was -3.45 (ATO/ATRA vs. ATRA/IDA), and NNH for infection was -3.13 (ATO/ATRA vs. ATRA/IDA) and -1.89 (ATO/ATRA vs. ATO/ATRA/IDA). CONCLUSION: The ATO/ATRA regimen is superior to chemotherapy-containing protocols at inducing remission and promoting survival in patients with APML. The regimen is better tolerated than the proposed alternatives with fewer adverse events. Future research opportunities include quantifying APML epidemiology and pursuing oral arsenic as an option for simplification of therapeutic protocols.


Assuntos
Arsenicais , Leucemia Promielocítica Aguda , Humanos , Leucemia Promielocítica Aguda/tratamento farmacológico , Leucemia Promielocítica Aguda/epidemiologia , Leucemia Promielocítica Aguda/induzido quimicamente , Antraciclinas/efeitos adversos , Arsenicais/efeitos adversos , Óxidos/efeitos adversos , Resultado do Tratamento , Tretinoína/efeitos adversos , Antibióticos Antineoplásicos
4.
Nucleus ; 15(1): 2321265, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38411156

RESUMO

Promyelocytic leukemia (PML) nuclear bodies, membrane-less organelles in the nucleus, play a crucial role in cellular homeostasis. These dynamic structures result from the assembly of scaffolding PML proteins and various partners. Recent crystal structure analyses revealed essential self-interacting domains, while liquid-liquid phase separation contributes to their formation. PML bodies orchestrate post-translational modifications, particularly stress-induced SUMOylation, impacting target protein functions. Serving as hubs in multiple signaling pathways, they influence cellular processes like senescence. Dysregulation of PML expression contributes to diseases, including cancer, highlighting their significance. Therapeutically, PML bodies are promising targets, exemplified by successful acute promyelocytic leukemia treatment with arsenic trioxide and retinoic acid restoring PML bodies. Understanding their functions illuminates both normal and pathological cellular physiology, guiding potential therapies. This review explores recent advancements in PML body biogenesis, biochemical activity, and their evolving biological roles.


Assuntos
Leucemia Promielocítica Aguda , Corpos Nucleares da Leucemia Promielocítica , Humanos , Proteínas Nucleares/metabolismo , Proteína da Leucemia Promielocítica/genética , Proteína da Leucemia Promielocítica/metabolismo , Fatores de Transcrição/química , Fatores de Transcrição/metabolismo , Leucemia Promielocítica Aguda/tratamento farmacológico , Leucemia Promielocítica Aguda/metabolismo , Leucemia Promielocítica Aguda/patologia
5.
Cancer Prev Res (Phila) ; 17(2): 47-49, 2024 02 02.
Artigo em Inglês | MEDLINE | ID: mdl-38303649

RESUMO

From risk association between acute promyelocytic leukemia (APL) and obese-overweight individuals, Mazzarella and colleagues hypothesized that a high-fat diet (HFD) promotes development of APL. Using mouse APL model (PML-RARα knock-in), the authors demonstrated that linoleic acid drives activation of PPARδ in hematopoietic progenitors, and that activation of PPARδ increases proliferation of progenitor cells with PML-RARA expression toward APL. Involvements of PPARδ on regulation of stem cell renewal and proliferation were shown in colorectal cancers earlier, but this study newly demonstrates in hematopoietic progenitors, while suggesting use of diet rich in linoleic acid with caution. See related article by Mazzarella et al., p. 59.


Assuntos
Leucemia Promielocítica Aguda , PPAR delta , Camundongos , Animais , Leucemia Promielocítica Aguda/genética , Leucemia Promielocítica Aguda/metabolismo , Dieta Hiperlipídica/efeitos adversos , Ácido Linoleico , Proteínas de Fusão Oncogênica , Tretinoína
6.
J Ethnopharmacol ; 326: 117778, 2024 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-38310990

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: In China, the Chinese patent drug Realgar-Indigo naturalis Formula (RIF) is utilized for the therapy of acute promyelocytic leukemia (APL). Comprising four traditional Chinese herb-Realgar, Indigo naturalis, Salvia miltiorrhiza, and Pseudostellaria heterophylla-it notably includes tetra-arsenic tetra-sulfide, indirubin, tanshinone IIa, and total saponins of Radix Pseudostellariae as its primary active components. Due to its arsenic content, RIF distinctly contributes to the therapy for APL. However, the challenge of arsenic resistance in APL patients complicates the clinical use of arsenic agents. Interestingly, RIF demonstrates a high remission rate in APL patients, suggesting that its efficacy is not significantly compromised by arsenic resistance. Yet, the current state of research on RIF's ability to reverse arsenic resistance remains unclear. AIM OF THE STUDY: To investigate the mechanism of different combinations of the compound of RIF in reversing arsenic resistance in APL. MATERIALS AND METHODS: The present study utilized the arsenic-resistant HL60-PMLA216V-RARα cell line to investigate the effects of various RIF compounds, namely tetra-arsenic tetra-sulfide (A), indirubin (I), tanshinone IIa (T), and total saponins of Radix Pseudostellariae (S). The assessment of cell viability, observation of cell morphology, and evaluation of cell apoptosis were performed. Furthermore, the mitochondrial membrane potential, changes in the levels of PMLA216V-RARα, apoptosis-related factors, and the PI3K/AKT/mTOR pathway were examined, along with autophagy in all experimental groups. Meanwhile, we observed the changes about autophagy after blocking the PI3K or mTOR pathway. RESULTS: Tanshinone IIa, indirubin and total saponins of Radix Pseudostellariae could enhance the effect of tetra-arsenic tetra-sulfide down-regulating PMLA216V-RARα, and the mechanism was suggested to be related to inhibiting mTOR pathway to activate autophagy. CONCLUSIONS: We illustrated that the synergistic effect of different compound combinations of RIF can regulate autophagy through the mTOR pathway, enhance cell apoptosis, and degrade arsenic-resistant PMLA216V-RARα.


Assuntos
Abietanos , Arsênio , Arsenicais , Medicamentos de Ervas Chinesas , Leucemia Promielocítica Aguda , Saponinas , Humanos , Arsênio/efeitos adversos , Leucemia Promielocítica Aguda/tratamento farmacológico , Leucemia Promielocítica Aguda/induzido quimicamente , Fosfatidilinositol 3-Quinases , Arsenicais/farmacologia , Arsenicais/uso terapêutico , Sulfetos/farmacologia , Sulfetos/uso terapêutico , Saponinas/uso terapêutico
8.
Turk J Haematol ; 41(1): 1-8, 2024 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-38374587

RESUMO

Objective: Acute promyelocytic leukemia (APL) is associated with an elevated risk of developing disseminated intravascular coagulation (DIC). The purpose of this study was to assess the outcomes of hospitalizations related to DIC in APL and their impact on healthcare. Materials and Methods: This study entailed a cross-sectional and retrospective analysis of the US National Inpatient Sample database. We identified adults with APL and categorized them into groups of patients with and without DIC. Our focus areas included in-hospital mortality, length of stay, charges, and complications associated with DIC. Unadjusted odds ratios/coefficients were computed in univariate analysis, followed by adjusted odds ratios (aOR)/coefficients from multivariate analysis that accounted for confounding factors. Results: Our analysis revealed that APL patients with DIC had a substantially higher aOR for mortality (aOR: 6.68, 95% confidence interval [CI]: 4.76-9.37, p<0.001) and a prolonged length of stay (coefficient: 10.28 days, 95% CI: 8.48-12.09, p<0.001) accompanied by notably elevated total hospital charges (coefficient: $215,512 [95% CI: 177,368-253,656], p<0.001), thereby emphasizing the reality of extended medical care and economic burden. The presence of DIC was associated with increased odds of sepsis, vasopressor support, pneumonia, acute respiratory failure, intubation/mechanical ventilation, and acute kidney injury, reflecting heightened vulnerability to these complications. Patients with DIC demonstrated significantly higher odds ratios for major bleeding, intracranial hemorrhage, gastrointestinal bleeding, red blood cell transfusion, platelet transfusion, fresh frozen plasma transfusion, and cryoprecipitate transfusion, highlighting the pronounced hematological risks posed by DIC. Conclusion: This study has revealed the significant associations between DIC in APL and various outcomes, underscoring the clinical and economic implications of these conditions. The hematological risks further increase patients' vulnerability to bleeding events and the need for transfusions.


Assuntos
Coagulação Intravascular Disseminada , Leucemia Promielocítica Aguda , Adulto , Humanos , Leucemia Promielocítica Aguda/complicações , Leucemia Promielocítica Aguda/epidemiologia , Leucemia Promielocítica Aguda/terapia , Coagulação Intravascular Disseminada/epidemiologia , Coagulação Intravascular Disseminada/etiologia , Coagulação Intravascular Disseminada/terapia , Estudos Retrospectivos , Transfusão de Componentes Sanguíneos/efeitos adversos , Estudos Transversais , Plasma , Hemorragia , Hospitais , Atenção à Saúde
9.
Nat Commun ; 15(1): 1423, 2024 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-38365836

RESUMO

Acute promyelocytic leukemia (APL) represents a paradigm for targeted differentiation therapy, with a minority of patients experiencing treatment failure and even early death. We here report a comprehensive single-cell analysis of 16 APL patients, uncovering cellular compositions and their impact on all-trans retinoic acid (ATRA) response in vivo and early death. We unveil a cellular differentiation hierarchy within APL blasts, rooted in leukemic stem-like cells. The oncogenic PML/RARα fusion protein exerts branch-specific regulation in the APL trajectory, including stem-like cells. APL cohort analysis establishes an association of leukemic stemness with elevated white blood cell counts and FLT3-ITD mutations. Furthermore, we construct an APL-specific stemness score, which proves effective in assessing early death risk. Finally, we show that ATRA induces differentiation of primitive blasts and patients with early death exhibit distinct stemness-associated transcriptional programs. Our work provides a thorough survey of APL cellular hierarchies, offering insights into cellular dynamics during targeted therapy.


Assuntos
Leucemia Promielocítica Aguda , Humanos , Leucemia Promielocítica Aguda/genética , Leucemia Promielocítica Aguda/metabolismo , Tretinoína/farmacologia , Diferenciação Celular , Linhagem Celular Tumoral , Proteínas de Fusão Oncogênica/genética , Proteínas de Fusão Oncogênica/metabolismo
12.
Cell Commun Signal ; 22(1): 127, 2024 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-38360674

RESUMO

All-trans retinoic acid (ATRA) is the most relevant and functionally active metabolite of Vitamin-A. From a therapeutic standpoint, ATRA is the first example of pharmacological agent exerting its anti-tumor activity via a cell differentiating action. In the clinics, ATRA is used in the treatment of Acute Promyelocytic Leukemia, a rare form of myeloid leukemia with unprecedented therapeutic results. The extraordinary effectiveness of ATRA in the treatment of Acute Promyelocytic Leukemia patients has raised interest in evaluating the potential of this natural retinoid in the treatment of other types of neoplasias, with particular reference to solid tumors.The present article provides an overview of the available pre-clinical and clinical studies focussing on ATRA as a therapeutic agent in the context of breast cancer from a holistic point of view. In detail, we focus on the direct effects of ATRA in breast cancer cells as well as the underlying molecular mechanisms of action. In addition, we summarize the available information on the action exerted by ATRA on the breast cancer micro-environment, an emerging determinant of the progression and invasive behaviour of solid tumors. In particular we discuss the recent evidences of ATRA activity on the immune system. Finally, we analyse and discuss the results obtained with the few ATRA-based clinical trials conducted in the context of breast cancer.


Assuntos
Antineoplásicos , Neoplasias da Mama , Leucemia Promielocítica Aguda , Humanos , Feminino , Leucemia Promielocítica Aguda/tratamento farmacológico , Leucemia Promielocítica Aguda/metabolismo , Leucemia Promielocítica Aguda/patologia , Neoplasias da Mama/patologia , Tretinoína/farmacologia , Tretinoína/metabolismo , Linhagem Celular Tumoral , Diferenciação Celular , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Microambiente Tumoral
13.
Cell Mol Life Sci ; 81(1): 68, 2024 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-38289472

RESUMO

Aminopeptidase N/CD13, a membrane-bound enzyme upregulated in tumor vasculature and involved in angiogenesis, can be used as a receptor for the targeted delivery of drugs to tumors through ligand-directed targeting approaches. We describe a novel peptide ligand (VGCARRYCS, called "G4") that recognizes CD13 with high affinity and selectivity. Enzymological and computational studies showed that G4 is a competitive inhibitor that binds to the catalytic pocket of CD13 through its N-terminal region. Fusing the peptide C-terminus to tumor necrosis factor-alpha (TNF) or coupling it to a biotin/avidin complex causes loss of binding and inhibitory activity against different forms of CD13, including natural or recombinant ectoenzyme and a membrane form expressed by HL60 promyelocytic leukemia cells (likely due to steric hindrance), but not binding to a membrane form of CD13 expressed by endothelial cells (ECs). Furthermore, G4-TNF systemically administered to tumor-bearing mice exerted anticancer effects through a CD13-targeting mechanism, indicating the presence of a CD13 form in tumor vessels with an accessible binding site. Biochemical studies showed that most CD13 molecules expressed on the surface of ECs are catalytically inactive. Other functional assays showed that these molecules can promote endothelial cell adhesion to plates coated with G4-avidin complexes, suggesting that the endothelial form of CD13 can exert catalytically independent biological functions. In conclusion, ECs express a catalytically inactive form of CD13 characterized by an accessible conformation that can be selectively targeted by G4-protein conjugates. This form of CD13 may represent a specific target receptor for ligand-directed targeted delivery of therapeutics to tumors.


Assuntos
Antígenos CD13 , Células Endoteliais , Leucemia Promielocítica Aguda , Animais , Camundongos , Antígenos CD13/antagonistas & inibidores , Ligantes
14.
Ann Hematol ; 103(4): 1181-1185, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38294534

RESUMO

Acute promyelocytic leukemia (APL) is a specific subtype of acute myeloid leukemia that is distinguished by the chromosomal translocation t(15;17)(q24;q21), which leads to the fusion of the promyelocytic leukemia (PML) gene with the retinoic acid receptor alpha (RARA). Recently, we identified a novel fusion gene in APL, RARA::ankyrin repeat domain 34C (ANKRD34C), identified its functions by morphological, cytogenetic, molecular biological and multiplex fluorescence in situ hybridization analyses, and demonstrated the potential therapeutic effect clinically and experimentally of all-trans retinoic acid (ATRA); the findings have important implications for the diagnosis and treatment of atypical APL.


Assuntos
Leucemia Promielocítica Aguda , Humanos , Leucemia Promielocítica Aguda/diagnóstico , Leucemia Promielocítica Aguda/genética , Leucemia Promielocítica Aguda/tratamento farmacológico , Hibridização in Situ Fluorescente , Tretinoína/uso terapêutico , Receptor alfa de Ácido Retinoico/genética , Proteínas de Transporte/genética , Translocação Genética , Proteínas de Fusão Oncogênica/genética , Proteínas de Fusão Oncogênica/metabolismo
15.
Medicine (Baltimore) ; 103(1): e36619, 2024 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-38181249

RESUMO

RATIONALE: Acute promyelocytic leukaemia (APL) is a rare subtype of acute myelogenous leukaemia. With advances in treatment regimens, namely, introduction of all-trans-retinoicacid, outcomes have drastically improved, its side effects should not be ignored. Mycosis fungoides is one of the side effects of all-trans-retinoicacid treatment, but it may also be a clinical manifestation before disease progression. However, it rarely appears and is easily overlooked. This leads to being easily misled during the treatment process, affecting the treatment plan, and resulting in adverse consequences. Therefore, early identification and judgment can not only provide appropriate treatment options, but also prevent and treat further disease progression. PATIENT CONCERNS: The patient was hospitalized for pancytopaenia. After completing the examination, the patient was finally diagnosed with acute promyelocytic leukaemia (acute myelogenous leukaemia-M3). We administered tretinoin and arsenous acid. Evaluation of the treatment effect on the 7th day after chemotherapy showed that the bone marrow morphology showed complete remission. After the second course of chemotherapy, the patient developed red miliary macular papules, which gradually worsened. After completing relevant inspections, Considering that the cases was complicated with skin mycosis fungoides, the patient was treated with budesonide ointment and methylprednisolone as chemotherapy. DIAGNOSES: Upon examination, the patient was initially diagnosed with acute promyelocytic leukaemia. Evaluation of the treatment effect on the 7th day after chemotherapy showed that the bone marrow morphology showed complete remission. After the second course of chemotherapy, we discovered the patient was diagnosed with skin mycosis fungoides. INTERVENTIONS: Systemic chemotherapy is first given when a patient was diagnosed with acute promyelocytic leukaemia. After the patient happened skin mycosis fungoides, We have adjusted the treatment plan and supplemented it with other treatment plans based on the original chemotherapy, After 2 months of treatment, his condition gradually improved. OUTCOMES: All-trans-retinoicacid in the treatment of APL must be given attention because mycosis fungoides should not only be distinguished from infectious diseases but also be further assessed with regard to disease progression and metastasis. LESSONS: Acute promyelocytic leukemia needs to be treated with arsenic trioxide. All-trans-retinoicacid in the treatment of APL must be given attention mycosis fungoides. Early diagnosis can guide accurate treatment, which is of great help in alleviating the pain of patients and improving the cure rate.


Assuntos
Dermatomicoses , Leucemia Promielocítica Aguda , Micose Fungoide , Neoplasias Cutâneas , Humanos , Leucemia Promielocítica Aguda/diagnóstico , Leucemia Promielocítica Aguda/tratamento farmacológico , Micose Fungoide/diagnóstico , Micose Fungoide/tratamento farmacológico , Pele , Progressão da Doença , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/tratamento farmacológico
18.
Biol Trace Elem Res ; 202(1): 122-132, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37097388

RESUMO

Arsenic trioxide (ATO)-induced hepatotoxicity is often observed in acute promyelocytic leukemia (APL) patients and decreases therapeutic effect of ATO. Thus, concerns over hepatotoxicity have been raised. The aim of this study was to explore some noninvasive clinical indicators that can be used to guide the individualized application of ATO in the future. APL patients treated with ATO were identified retrospectively via electronic health records at our hospital from August 2014 through August 2019. APL patients without hepatotoxicity were selected as controls. The association between putative risk factors and ATO-induced hepatotoxicity was estimated with ORs and 95% CIs, which were calculated using the chi-square test. The subsequent multivariate analysis was performed using logistic regression analysis. In total, 58.04% of patients experienced ATO-induced hepatotoxicity during the first week. Elevated hemoglobin (OR 8.653, 95% CI, 1.339-55.921), administration of nonprophylactic hepatoprotective agents (OR 36.455, 95% CI, 7.409-179.364), non-single-agent ATO to combat leukocytosis (OR 20.108, 95% CI, 1.357-297.893) and decreased fibrinogen (OR 3.496, 95% CI, 1.127-10.846) were found to be statistically significant risk factors for ATO-induced hepatotoxicity. The area under the ROC curve values were 0.846 for "overall ATO-induced hepatotoxicity" and 0.819 for "early ATO-induced hepatotoxicity." The results revealed that hemoglobin ≥ 80 g/L, nonprophylactic hepatoprotective agents, and non-single-agent ATO and fibrinogen < 1 g/L are risk factors for ATO-induced hepatotoxicity in newly diagnosed APL patients. These findings can enhance the clinical diagnosis of hepatotoxicity. Prospective studies should be performed in the future to validate these findings.


Assuntos
Antineoplásicos , Arsenicais , Doença Hepática Induzida por Substâncias e Drogas , Leucemia Promielocítica Aguda , Humanos , Trióxido de Arsênio/efeitos adversos , Leucemia Promielocítica Aguda/tratamento farmacológico , Leucemia Promielocítica Aguda/induzido quimicamente , Leucemia Promielocítica Aguda/diagnóstico , Estudos Retrospectivos , Estudos Prospectivos , Fibrinogênio/uso terapêutico , Hemoglobinas , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Óxidos/efeitos adversos , Arsenicais/efeitos adversos , Antineoplásicos/efeitos adversos , Tretinoína/uso terapêutico
20.
Leuk Lymphoma ; 65(3): 378-382, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38054837

RESUMO

Arsenic trioxide (ATO)-based regimens are standard in acute promyelocytic leukemia (APL). ATO-related nephrotoxicity has not been reported. We reviewed APL patients treated with ATO to identify cases of acute kidney injury (AKI). Clinically significant cases were characterized. Multivariate analysis was performed to identify predictors of idiopathic, clinically significant AKI. One hundred and eight patients were included. ATO dose was 0.15 mg/kg/day using actual body weight with no dose cap. Thirty-one (28.7%) AKI cases were identified, 10 (32.3%) clinically significant. Six were idiopathic; five required dialysis. The proportion with significant, idiopathic AKI was 15.8% in patients receiving >15mg ATO versus 0% in those receiving ≤15mg (p = 0.001). On multivariate analysis, only ATO dose was a significant predictor of clinically significant AKI (odds ratio of 1.91, 95%CI, 1.19-3.07, p = 0.007). High-dose ATO may be associated with significant nephrotoxicity. We recommend that ATO dose be capped at 15 mg to minimize toxicity for this curable disease.


Assuntos
Injúria Renal Aguda , Arsenicais , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Leucemia Promielocítica Aguda , Humanos , Trióxido de Arsênio/efeitos adversos , Leucemia Promielocítica Aguda/complicações , Leucemia Promielocítica Aguda/diagnóstico , Leucemia Promielocítica Aguda/tratamento farmacológico , Tretinoína/efeitos adversos , Obesidade/complicações , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/diagnóstico , Injúria Renal Aguda/epidemiologia , Arsenicais/efeitos adversos , Óxidos/efeitos adversos
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