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1.
Rinsho Ketsueki ; 61(2): 103-109, 2020.
Artigo em Japonês | MEDLINE | ID: mdl-32147608

RESUMO

A 69-year-old woman with leukocytopenia and thrombocytopenia was referred to our hospital. Her bone marrow comprised 70.5% abnormal promyelocytes that were positive for myeloperoxidase/CD33/CD117 and CD13 (dim) and negative for CD2/CD34/CD56 and HLA-DR. Chromosome analysis of the bone marrow showed t (12;17;15) (p13;q21;q22), and fluorescence in situ hybridization revealed the PML-RARA fusion signal only on the derivative chromosome 15. The patient was diagnosed with acute promyelocytic leukemia (APL) with PML-RARA and was treated using all-trans retinoic acid (ATRA). In peripheral blood (PB), PML-RARA-positive polymorphonuclear cells (PMNs) appeared on the second week and became negative on the sixth week after treatment, whereas PML-RARA-negative PMNs started to increase in number on the sixth week. Molecular remission was confirmed on the 10th week. Quantitative evaluation of the differentiated leukemic cells of APL and recovered cells from normal hematopoiesis in PB can provide useful information for a safer induction therapy. No significant difference was noted in the kinetics of the leukemic cells under ATRA treatment as well as in the clinical features between our patient without RARA-PML and those with t (15;17), which is a cytogenetic evidence for the critical role of PML-RARA in the pathogenesis of APL.


Assuntos
Leucemia Promielocítica Aguda , Idoso , Cromossomos Humanos , Feminino , Humanos , Hibridização in Situ Fluorescente , Cinética , Leucemia Promielocítica Aguda/genética , Proteínas de Fusão Oncogênica , Translocação Genética , Tretinoína
2.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 28(1): 1-6, 2020 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-32027244

RESUMO

OBJECTIVE: To investigate the efficacy and safety of arsenic trioxide combined with ATRA and chemo- therapy for treatment of relapsed acute promyelocytic leukemia (APL) patients. METHODS: The clinic data of 25 patients with relapse APL treated in our hospital from 1996 to 2013 were collected and analyzed. Among the 25 patients, 15 patients suffered first-time hematological relapse (HR), and the other 10 patients showed first-time molecular relapse (MR). The patients with first-time replase were treated with ATO+ATRA+Anthracycline re-induction chemotherapy. The clinical features, complete remission (CR) rate, overall survival (OS), disease-free survival (DFS) and adverse events after re-induction therapy were analyzed. RESULTS: Fourteen of 15 hematological relapsed patients achieved the second-time hematological complete remission (CR2) after re-induction therapy except one patient died of bleeding complication during the re-induction. 8 of 14 patient showed molecular complete remission (CRm) after two cycles of therapy with this regimen. Totally, eleven out of the 14 HR patients were alive without disease till the last follow-up, and 3 of the 14 HR patients died because of bleeding complications. All of the 10 molecular relapsed patients received the second CRm after treated by the regimen. Among these 10 patients, 6 patients suffered only once relapse and continued with the molecular CR2 status, and for the other 4 patients with more than two-relapses, only 1 survived untill 89.3 months after achieved second-time CRm, and other 3 patients died because of bleeding complications. CONCLUSION: For relapsed APL patients, the treatment with ATO+ATRA+chemotherapy regimen after relapse still shows encouraging efficacy, no matter whether or not the application of ATO in the previous regimens. In addition, patients with more than two molecular relapses show a poor prognosis.


Assuntos
Arsenicais , Leucemia Promielocítica Aguda , Protocolos de Quimioterapia Combinada Antineoplásica , Trióxido de Arsênio , Humanos , Leucemia Promielocítica Aguda/tratamento farmacológico , Óxidos , Indução de Remissão , Resultado do Tratamento , Tretinoína
3.
J Cancer Res Clin Oncol ; 146(2): 485-492, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31686248

RESUMO

PURPOSE: Early death (ED) is the main cause of acute promyelocytic leukemia (APL) treatment failure, and the ED rate is higher for elderly patients than that for young ones. To date, no studies have been found focusing on ED in elderly patients with APL. METHODS: This study retrospectively analyzed the clinical data of 409 consecutive patients with APL (139 patients ≥ 50 years old, 270 patients < 50 years old). All patients received arsenic trioxide alone as induction therapy. The baseline clinical characteristics and ED occurrence and predictors between elderly and young patients with APL were compared and analyzed. RESULTS: The clinical features of elderly patients at admission were not significantly different from those of young ones. The ED rate of elderly patients was significantly greater than that of young patients (23.74% vs 11.85%, P = 0.0018). Hemorrhage is the main cause of ED in elderly patients, followed by infection and differentiation syndrome. From the 15th to 30th days of treatment, elderly patients had a higher mortality rate than that of young patients (7.83% vs 2.06%, P = 0.009). Male, white blood cell (WBC) count > 10 × 109/L, fibrinogen < 1.0 g/L and low albumin levels were independent risk factors for ED in elderly patients, while ED was only correlated with WBC count, fibrinogen and creatinine levels in young patients. CONCLUSION: The results of this study may help design more rational treatment plans for elderly patients with APL based on early mortality risk to reduce the ED rate.


Assuntos
Trióxido de Arsênio/uso terapêutico , Leucemia Promielocítica Aguda/tratamento farmacológico , Leucemia Promielocítica Aguda/mortalidade , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/uso terapêutico , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Adulto Jovem
4.
Life Sci ; 242: 117229, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31887298

RESUMO

AIMS: Neutrophil elastase (NE) is a critical proteolytic enzyme that is involved in cancer. We previously reported high NE expression in peripheral blood neutrophils from acute promyelocytic leukemia (APL) patients. The present study aimed to elucidate the specific role and mechanisms of NE in APL development. MATERIALS AND METHODS: NE expression was detected in APL bone marrow samples and analyzed in the BloodSpot database. CCK-8 assay and flow cytometry were used to assess cell proliferation and cell cycle distribution, respectively. The expression levels of proliferation and differentiation markers were measured by Western blotting and quantitative real-time PCR. The co-expression and interaction of NE and p200 cut-like homeobox 1 (CUX1) were evaluated by indirect immunofluorescence, co-immunoprecipitation, and in situ proximity ligation assay. KEY FINDINGS: NE was highly expressed in APL bone marrow and blood neutrophils. NE overexpression promoted the proliferation and inhibited the differentiation of NB4 cells, whereas NE downregulation achieved the opposite results in U937 cells. Mechanistically, NE interacted with and effectively hydrolyzed the tumor suppressor p200 CUX1. Rescue experiments revealed that p200 CUX1 upregulation reversed the functional influence of NE on APL cells. SIGNIFICANCE: NE-mediated proteolysis of the tumor suppressor p200 CUX1 promotes APL progression. NE/p200 CUX1 axis is a novel and promising therapeutic target for APL treatment.


Assuntos
Proteínas de Homeodomínio/metabolismo , Leucemia Promielocítica Aguda/enzimologia , Elastase de Leucócito/metabolismo , Proteínas Repressoras/metabolismo , Fatores de Transcrição/metabolismo , Adolescente , Adulto , Western Blotting , Diferenciação Celular/fisiologia , Linhagem Celular Tumoral , Proliferação de Células/fisiologia , Feminino , Citometria de Fluxo , Técnica Indireta de Fluorescência para Anticorpo , Células HL-60 , Proteínas de Homeodomínio/fisiologia , Humanos , Imunoprecipitação , Leucemia Promielocítica Aguda/metabolismo , Elastase de Leucócito/fisiologia , Masculino , Proteólise , Reação em Cadeia da Polimerase em Tempo Real , Proteínas Repressoras/fisiologia , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Sincalida/metabolismo , Fatores de Transcrição/fisiologia , Células U937
5.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 27(6): 1786-1793, 2019 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-31839039

RESUMO

OBJECTIVE: To investigate the effect of reactive oxygen species (ROS) on GDC-0152-induced apoptosis and autophagy of acute promyelocytic leukemia cell line NB4. METHODS: Different concentrations of GDC-0152 combined with Z-VAD-FMK was applied to NB4 cells. Cell proliferation was detected by CCK8 method. Apoptosis rate, autophagy and ROS level were detected by flow cytometry. The autophagy was observed by Cyto-ID staining fluorescence microscopy, and flow cytometry were used to detect the fluorescence expression. The expression of autophagy-related protein LC3B was detected by Western blot. RESULTS: GDC-0152 increased proliferation inhibition rate and apoptosis rate in NB4 cells (P<0.05); GDC-0152 induced increase of ROS level of NB4 cells; GDC-0152 increased autophagy of NB4 cells that was found by Cyto-ID staining fluorescence microscopy and flow cytometry (P<0.05). Western blot showed that GDC-0152 increased LC3B expression in NB4 cells and promoted the conversion of LC3BI to LC3BII; as compared with GDC-0152 (100 ng/ml), GDC-0152 (100 ng/ml) combined with ROS inhibitor YCG063 (10 µmol/L) decreased apoptosis and autophagy (P<0.05). CONCLUSION: GDC-0152 inhibits cell proliferation by inducing apoptosis and autophagy of NB4 cells. ROS can promote GDC-0152-induced apoptosis and autophagy of NB4 cells.


Assuntos
Apoptose , Autofagia , Linhagem Celular Tumoral , Cicloexanos , Humanos , Leucemia Promielocítica Aguda , Pirróis , Espécies Reativas de Oxigênio
6.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 27(6): 2024-2029, 2019 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-31839078

RESUMO

Abstract  Among myeloid leukemias, the acute promyelocytic leukemia (APL) was found to be specifically sensitive to all-trans retinoic acid (ATRA), almost all APL patients respond to ATRA therapy. The ATRA induces remission of APL patients by stimulating the differentiation of the leukemia cells. However, with the long-term application of ATRA alone, ATRA resistance has become one of the main causes of chemotherapy failure in the patients with acute promyelocytic leukemia. At present, the mechanism of ATRA-resistance is not completely clear, this review discusses the mechanism of drug-resistance in terms of signal pathways, genes, proteins and enzyme.


Assuntos
Leucemia Promielocítica Aguda , Antineoplásicos , Diferenciação Celular , Humanos , Tretinoína
7.
Rinsho Ketsueki ; 60(10): 1431-1435, 2019.
Artigo em Japonês | MEDLINE | ID: mdl-31695003

RESUMO

We report a 55-year-old man who began undergoing hemodialysis for polycystic kidney disease 17 years ago. Because pancytopenia and susceptibility to infection were identified, a bone marrow biopsy was performed, resulting in a diagnosis of acute promyelocytic leukemia (APL). All-trans retinoic acid (ATRA) treatment was initiated, but promyelocytic leukemia/retinoic acid receptor alpha gene fusion without remission was identified by fluorescence in situ hybridization. We administered ATRA/arsenic trioxide (ATO) combination therapy for therapy-resistant APL and confirmed molecular genetic remission. The ATRA/ATO combination therapy was continued, obtaining complete remission 2 years after commencement of treatment. Cystic infections continued during ATRA/ATO combination therapy, similar to infections before APL morbidity, and there were no adverse events leading to treatment discontinuation. ATRA/ATO combination therapy is considered a safe and effective treatment for therapy-resistant APL patients on hemodialysis.


Assuntos
Trióxido de Arsênio/uso terapêutico , Leucemia Promielocítica Aguda/tratamento farmacológico , Tretinoína/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica , Humanos , Hibridização in Situ Fluorescente , Masculino , Pessoa de Meia-Idade , Doenças Renais Policísticas , Indução de Remissão , Diálise Renal , Resultado do Tratamento
8.
Zhonghua Xue Ye Xue Za Zhi ; 40(10): 843-847, 2019 Oct 14.
Artigo em Chinês | MEDLINE | ID: mdl-31775484

RESUMO

Objective: To investigate the genetic screening methods for cryptic acute promyelocytic leukemia (APL) to further explore its clinical prognosis. Methods: From June 2016 to November 2018, we collected 373 newly diagnosed APL cases. The patients were retrospected by the results of PML-RARα detections both by RT-PCR and i-FISH, those who harbored positive PML-RARα detection by RT-PCR and negative by i-FISH were chosen. Metaphase FISH and Sanger sequencing were further performed to verify these results. Results: A total of 7 cryptic APL cases were discovered. These cases had tiny fragment of RARα inserted into PML in chromosome 15, formed ins (15;17) . The 7 cryptic APL cases had no PML-RARα gene subtype specificity, involving 5 cases in L subtype, 1 case in S subtype and 1 case in V subtype respectively. After the treatment of retinoic acid and arsenic or anthracyclines, 6 cases achieved complete remission, 1 case died of intracranial hemorrhage on the 6th day of therapy. Conclusion: The size and covering position of PML-RARα probe should be taken into account when PML-RARα was performed by FISH on APL patients. Furthermore, combination with Metaphase FISH could improve the recognition of cryptic APL. There were no differences between the cryptic and common APL patients in terms of clinical features and treatment choices. Cryptic APL patients also had a good response to the therapy of retinoic acid and arsenic or anthracyclines.


Assuntos
Leucemia Promielocítica Aguda , Cromossomos Humanos Par 15 , Cromossomos Humanos Par 17 , Citogenética , Humanos , Hibridização in Situ Fluorescente , Leucemia Promielocítica Aguda/genética , Proteínas de Fusão Oncogênica , Receptor alfa de Ácido Retinoico , Tretinoína
10.
Zhongguo Dang Dai Er Ke Za Zhi ; 21(11): 1073-1078, 2019 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-31753087

RESUMO

OBJECTIVE: To study the clinical effect of the SCMC APL-2010 regimen in the treatment of acute promyelocytic leukemia (APL) in children. METHODS: A retrospective analysis was performed for the clinical data of 44 children with APL who received treatment with the SCMC APL-2010 regimen between April 2010 and July 2016. The Kaplan-Meier survival analysis was used to evaluate event-free survival (EFS) rate and overall survival (OS) rate. RESULTS: Of the 44 children with APL, 42 (95%) achieved a complete remission (CR) after one course of treatment and 1 achieved CR after two courses of treatment, with an overall CR rate of 98%. The 9-year EFS and OS rates were 96%±3% and 97.7%±2.2% respectively. As for adverse events, 41 (93%) had infection, 29 (66%) had granulocyte reduction, 12 (27%, 1 died) had differentiation syndrome, 16 (36%) had liver dysfunction, 12 (27%) had adverse gastrointestinal reactions, and 7 (16%) had QT prolongation, 1 (2%) had orchitis, and no secondary neoplasm was observed. CONCLUSIONS: Children with APL receiving the SCMC APL-2010 regimen have a good prognosis and can achieve a long-term survival, while treatment-related infection is commonly seen.


Assuntos
Leucemia Promielocítica Aguda , Protocolos de Quimioterapia Combinada Antineoplásica , Criança , Intervalo Livre de Doença , Humanos , Masculino , Indução de Remissão , Estudos Retrospectivos , Resultado do Tratamento , Tretinoína
11.
Drug Deliv ; 26(1): 1058-1067, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31735064

RESUMO

Realgar and (-)-Epigallocatechin-3-gallate (EGCG) are natural medicines that inhibit cancer cell growth, resulting in inhibition of formation and development of tumors. The anticancer effects of realgar and EGCG were greatly improved following formulation as nanoparticles. EGCG has received increased attention as a drug carrier. The aim of this study was to prepare a new nanomedicine, (EGCG-RNPs), in which encapsulated nano-realgar. EGCG-RNPs were prepared by coprecipitation and characterized by transmission electron microscopy (TEM), differential scanning calorimetry (DSC), particle size and zeta potential, X-ray diffraction, Fourier transform infrared spectroscopy (FTIR) and in vitro release. Furthermore, we evaluated the antiproliferative effects of EGCG-RNPs on HL-60 cells in vitro, antitumor effect by intratumoral injection of EGCG-RNPs into solid tumors derived from APL HL-60 cells in vivo. Possible mechanisms were evaluated using uptake and efflux experiments in HL-60 cells. The results showed that the average particle size and zeta potentials of EGCG-RNPs was 200.3 ± 1.23 nm and -46.8 ± 1.31 mV. Controlled release of EGCG-RNPs was sustained and continued up to 72 h in vitro. Compared with nano-realgar and EGCG + RNPs (EGCG and nano-realgar physical mixing), EGCG-RNPs significantly inhibited growth of HL-60 cells. In a solid tumor model, EGCG-RNPs decreased tumor volumes, with an inhibitory rate of 60.18% at a dose of 70 mg · kg-1. The mechanisms of antitumor improvement may correlate with the increased uptake of realgar and prolonged the retention time of realgar in HL-60 cells due to EGCG as a carrier. EGCG-RNPs could enhance anticancer therapeutic efficacy for acute promyelocytic leukemia.


Assuntos
Antineoplásicos/química , Antineoplásicos/farmacologia , Catequina/análogos & derivados , Leucemia Promielocítica Aguda/tratamento farmacológico , Nanopartículas/química , Varredura Diferencial de Calorimetria/métodos , Catequina/química , Catequina/farmacologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Portadores de Fármacos/química , Células HL-60 , Humanos , Nanomedicina/métodos , Tamanho da Partícula
13.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 27(5): 1380-1386, 2019 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-31607287

RESUMO

OBJECTIVE: To investigate the effect of chromosomal karyotype on the prognosis of patients with acute promyelocytic leukemia (APL) in condition of the maintenance treatment based on arsenic trioxide. METHODS: The patients with acute promyelocytic leukemia for last 12 years in our hospital were retrospectively collected. The patients mainly treated with arsenic trioxide in maintenance protocol were selected and followed up. All the patients were divided into 3 groups according to cytogenetic data: single t (15; 17) group, t (15; 17) with additional chromosomal abnormality (ACA) group, and normal karyotype group. Then, the prognostic significance of ACAs and complex karyotype were investigated in APL patients. RESULTS: There were 57 cases in the single t (15; 17) group, in which 8 cases died in the first month after induction treatment with early mortality rate of 14%. There were 21 patients in t (15; 17) with ACA group, in which 4 cases died in the first month with early mortality rate of 19%. There were 15 cases in normal chromosome group, in which 5 cases died in the first month with the early mortality rate of 33.3%. There was no statistical difference in the early mortality among 3 groups. All the remaining 76 patients achieved complete hematological remission. These patients were followed up. The median follow-up time was 43.9 months. Among them, only 2 patients in single t (15; 17) group and 1 patient in t (15; 17) with ACA group relapsed. No patient relapsed in normal karyotype group. The relapse rate was 3.5% in single t (15; 17) group and 4.2% in t (15; 17) with ACA group, respectively. There was no statistical difference in the overall survival and disease-free survival rates among 3 groups. Further analysis showed that the patients with complex chromosome karyotypes had lower relapse-free survival rates, but overall survival rates were not significantly different in 3 group. CONCLUSION: In general, ACA can not affect the prognosis of patients with acute promyelocytic leukemia in condition of the maintenance treatment based on arsenic trioxide, but the complex chromosomal karyotype may reduce the relapse-free survival rates.


Assuntos
Trióxido de Arsênio/uso terapêutico , Leucemia Promielocítica Aguda , Humanos , Cariótipo , Leucemia Promielocítica Aguda/tratamento farmacológico , Prognóstico , Indução de Remissão , Estudos Retrospectivos , Resultado do Tratamento , Tretinoína
14.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 27(5): 1696-1700, 2019 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-31607334

RESUMO

Abstract  The promyelocytic leukemia (PML) gene encoded PML protein as a tumor suppressor protein, plays important roles in the occurrence and development of various cancers including acute promyelocytic leukemia. Recent studies have indicated that there are a variety of post-translational modifications of the PML protein, such as SUMOylation, ubiquitination, phosphorylation, and acetylation in cells. These modifications of the PML protein can directly affect the formation of PML nuclear bodies (PML-NBs), repair DNA damage, and modulate cell apoptosis. Furthermore, the abnormal modifications of PML not only result in the occurrence of hematopoietic tumors, but also are closely related to the drug-resistance of cancer. Therefore, investigating the post-translational modifications of PML is significant to uncover the mechanism of formation and functions of PML-NBs, thus contributing to the prevention and treatment of related hematopoietic tumors. In this review, the characteristics of the post-translational modifications of PML protein and the relationship between these modifications and functions of PML-NBs are summarized so as to provide the potential targets for the treatment of related cancers.


Assuntos
Leucemia Promielocítica Aguda , Humanos , Corpos de Inclusão Intranuclear , Proteínas Nucleares , Proteína da Leucemia Promielocítica , Processamento de Proteína Pós-Traducional
16.
DNA Cell Biol ; 38(11): 1374-1386, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31599655

RESUMO

This study was conducted using TagSNPs to systematically explore the relationship between ARID5B polymorphisms and the occurrence, clinical characterization, and prognosis of acute myeloid leukemia (AML). A total of 569 unrelated AML patients and 410 healthy individuals from West China were recruited, and ARID5B TagSNPs were genotyped using iMLDR® (improved multiplex ligation detection reaction). It was found that the association of ARID5B polymorphisms with AML was most significant in acute promyelocytic leukemia (APL), and exclusively in males, the mutant alleles of rs6415872, rs2393726, rs7073837, rs10821936, and rs7089424 were found to increase the risk of developing APL in men, the odds ratio (OR) were 1.36, 1.74, 1.45, 1.53, and 1.56 (all p < 0.05), respectively. Haplotype analysis revealed that haplotype [AACCG] increased the risk of male APL with an OR of 1.53 (95% confidence interval: 1.10-2.14, p = 0.012). Besides, there was a strong positive additive interaction between rs6415872 and rs10821936, rs7089424, respectively, and cases attributed to the interaction of rs6415872, rs10821936, and rs7089424 accounted for 100%. Furthermore, ARID5B single nucleotide polymorphisms were found associated with clinical features of AML, and rs6415872 was shown to be an independent prognosis factor in APL patients. Besides, dual luciferase report assay showed that rs6415872 may affect the binding activity of PPARG with ARID5B. ARID5B polymorphisms contribute to male APL risk, clinical feature, and prognosis, suggesting the importance of ARDI5B in AML pathogenesis and development, and the gender and subtype preference may prompt some specific mechanisms of ARID5B. Besides, ARID5B polymorphisms might be a potential prognosis biomarker.


Assuntos
Proteínas de Ligação a DNA/genética , Leucemia Promielocítica Aguda/diagnóstico , Leucemia Promielocítica Aguda/genética , Polimorfismo de Nucleotídeo Único , Fatores de Transcrição/genética , Adulto , Estudos de Casos e Controles , Feminino , Predisposição Genética para Doença , Genótipo , Células HEK293 , Humanos , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/epidemiologia , Leucemia Mieloide Aguda/genética , Leucemia Promielocítica Aguda/epidemiologia , Desequilíbrio de Ligação , Masculino , Pessoa de Meia-Idade , Prognóstico , Caracteres Sexuais , Análise de Sobrevida
17.
Pediatr Hematol Oncol ; 36(7): 399-409, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31530209

RESUMO

We studied the outcomes of children with APL treated by the Beijing Children's Hospital's (BCH) acute promyelocytic leukemia (APL) 2005 protocol (BCH-APL2005). The clinical data of 77 patients enrolled from January 2005 to June 2015 were analyzed retrospectively. The hematologic complete remission (CR) rate and overall survival (OS) rate were evaluated between standard-risk (SR) and high-risk (HR) groups. Prognostic factors and complications were investigated in these two groups. CR in the SR and HR groups was 96.4% (54/56) and 85.7% (18/21), respectively, while the 10-year OS was 94.6% (53/56) and 76.2% (16/21), respectively. The cumulative incidence of early death was 6.5% (5/77), and the SR and HR groups were 1.8% (1/56) and 19.0% (4/21), respectively. Only two patients relapsed, and the relapse rate was 2.6% (2/77). According to Kaplan-Meier analysis, the SR group had a significantly better long-term survival than HR counterparts (p= .016). Initial leukocyte count was the only prognostic factor (p= .016) by univariate analysis, while other factors, such as FLT3-ITD and platelet count, had no correlation with prognosis. In addition, early deaths were mainly due to intracranial hemorrhage. Although the combination of all-trans retinoic acid (ATRA) and chemotherapy can improve the outcome of APL patients, the early deaths and anthracycline-related cardiac toxicity were relatively higher in our study. Current efforts focus on reducing or even avoiding chemotherapy in APL children and rest on the frontline regimen of intravenous arsenic trioxide or oral realgar-indigo naturalis formula plus ATRA, which is the direction for APL treatment.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Leucemia Promielocítica Aguda/tratamento farmacológico , Leucemia Promielocítica Aguda/mortalidade , Criança , Pré-Escolar , China , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Leucemia Promielocítica Aguda/sangue , Contagem de Leucócitos , Masculino , Contagem de Plaquetas , Taxa de Sobrevida
19.
Semin Thromb Hemost ; 45(6): 612-621, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31370070

RESUMO

Despite the improved therapeutic advances in the management of acute promyelocytic leukemia (APL), a significant early mortality during induction, also referred to as early death (ED), remains an obstacle for further improvement in outcome. Hemorrhagic complications are the most common cause of morbidity and mortality. Perturbed hemostatic dysfunction is present as the result of abnormalities in both the coagulation and the fibrinolytic systems. The activation of coagulation is distinct from the classical disseminated intravascular coagulation. Multiple abnormalities in the fibrinolytic system have recently been identified. The most significant change is increased production of tissue plasminogen activator (tPA) and its receptor annexin A2 by the APL promyelocytes. Among the hemorrhagic complications, intracranial hemorrhage predominates. The pathogenesis of this catastrophic event is elucidated by new evidence of adverse effect of tissue plasminogen activator (tPA) on the brain, including both the plasmin-dependent and plasmin-independent pathways. In order to address the hemorrhagic complications, a thorough understanding of the hemostatic dysfunction is essential. In this article, our current concept of the abnormal hemostasis in APL is reviewed. The failure to reduce the early death rate, despite the introduction of effective therapy, will also be discussed.


Assuntos
Fibrinólise/imunologia , Hemostasia/imunologia , Leucemia Promielocítica Aguda/mortalidade , Humanos , Morbidade , Taxa de Sobrevida
20.
G Ital Nefrol ; 36(4)2019 Jul 24.
Artigo em Italiano | MEDLINE | ID: mdl-31373469

RESUMO

Differentiation syndrome (DS), previously known as retinoic acid syndrome or ATRA (all-trans retinoic acid) or ATO (arsenic trioxide) syndrome, is a life-threatening complication of the therapy with differentiating agents in patients with acute promyelocytic leukemia (APL). The latter is a rare subtype of acute myeloid leukemia and represents a hematological emergency. The clinical manifestations of DS, after induction therapy with differentiating agents, include unexplained fever, acute respiratory distress with interstitial pulmonary infiltrates, unexplained hypotension, peripheral edema, congestive heart failure and acute renal failure. The therapy is based on early intravenous administration of high-dose dexamethasone, in order to counteract the cytokine storm responsible for the DS. Among the supportive measures for the management of DS, furosemide (in 87% of patients) and dialysis (12% of patients) are used to manage acute renal failure, peripheral and pulmonary edema. We describe a case of acute renal failure, treated with haemodialysis, in a young patient with APL and an early and severe DS after induction therapy. This is a rare condition, not well known among nephrologists, where early recognition and treatment are crucial for the prognosis.


Assuntos
Lesão Renal Aguda/induzido quimicamente , Antineoplásicos/efeitos adversos , Trióxido de Arsênio/efeitos adversos , Leucemia Promielocítica Aguda/tratamento farmacológico , Tretinoína/efeitos adversos , Lesão Renal Aguda/terapia , Adulto , Dexametasona/uso terapêutico , Edema/induzido quimicamente , Febre de Causa Desconhecida/induzido quimicamente , Humanos , Hipotensão/induzido quimicamente , Quimioterapia de Indução/efeitos adversos , Masculino , Diálise Renal , Síndrome do Desconforto Respiratório do Adulto/induzido quimicamente , Síndrome
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