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1.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 28(5): 1539-1544, 2020 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-33067951

RESUMO

OBJECTIVE: To detect the expression level of LncRNA XLOC_109948 in bone marrow and serum of patients with acute myeloid Leukemia (AML), to verify the consistency between the expression in bone marrow and serum and to explore the role of LncRNA XLOC_109948 expression in the occurrence a development of AML. METHODS: Bone marrow and peripheral blood samples were collected from 62 patients with AML, including 36 patients with AML (AML group), 26 AML patients with complete remission (AML-CR group), and peripheral blood from 20 healthy persons (control group) were also collected. The expression level of LncRNA XLOC_109948 was detected by real-time quantitative fluorescence PCR (qRT-PCR), and the relationship between its expression and clinical characteristics was analyzed. RESULTS: The expression of LncRNA XLOC_109948 in bone marrow and serum of AML patients was higher than that of AML patients with complete remission and healthy people (P<0.001). And there was no statistically significant difference between the AML-CR group and control group (P>0.05). The expression of LncRNA XLOC_109948 significantly decreased when AML patients reached to CR, and significantly increased when the disease relapsed (P<0.05). The expression of LncRNA XLOC_109948 significantly correlated with the clinicopathologic parameters of cytogenetics (P<0.05), but not significantly correlated with sex, age, WBC count, blast in bone marrow, FAB classification and other clinical characteristics (P>0.05). CONCLUSION: The expression of LncRNA XLOC_109948 in bone marrow and serum of AML patients is high, and its expression in time and sequence is consistent between bone marrow and serum, which can reflect the occurrence, development, chemotherapy efficacy and prognosis of AML patients.


Assuntos
Leucemia Mieloide Aguda , RNA Longo não Codificante , Medula Óssea , Humanos , Leucemia Mieloide Aguda/genética , Prognóstico , RNA Longo não Codificante/genética , Indução de Remissão
2.
Medicine (Baltimore) ; 99(40): e22404, 2020 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-33019416

RESUMO

BACKGROUND: Systemic lupus erythematosus (SLE), known as lupus, is a chronic autoimmune disease and there is no cure for SLE. The western medication can improve syndromes to some extent; however, severe adverse drug reactions appear at the same time. Recently, it is confirmed that Chinese medicine also can have an excellent clinical efficacy on SLE. METHODS AND ANALYSIS: The following databases will be searched for relevant information before July 2020: PubMed, Embase, Cochrane Library, Web of Science, and China National Knowledge Infrastructure. MAJOR RESULTS: levels of total remission rate, SLEDAI. Secondary results: The laboratory index about C3 levels, Hb levels, white blood cell levels, and adverse event. Data will be collected independently by 2 researchers, and the risk of bias in meta analysis will be evaluated according to "Cochrane Handbook for Systematic Reviews of Interventions." All data analysis will be conducted using Review Manager V.5.3. and Stata V.12.0. RESULTS: The curative effect and safety of Chinese herbal compound prescription treatment for SLE patients will be evaluated systematically. CONCLUSION: The systematic review of this study will summarize the currently published evidence of Chinese herbal compound prescription treatment for SLE to further guide its promotion and application. ETHICS AND DISSEMINATION: The private information from individuals will not be published. This systematic review also will not involve endangering participant rights. Ethical approval is not required. The results may be published in a peer-reviewed journal or disseminated in relevant conferences. OPEN SCIENCE FRAMEWORK (OSF)REGISTRATION NUMBER:: https://osf.io/wvfrx/.


Assuntos
Medicamentos de Ervas Chinesas/uso terapêutico , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/efeitos adversos , Hemoglobinas/análise , Humanos , Contagem de Leucócitos , Ensaios Clínicos Controlados Aleatórios como Assunto , Indução de Remissão , Projetos de Pesquisa
3.
Medicine (Baltimore) ; 99(36): e22061, 2020 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-32899072

RESUMO

INTRODUCTION: Nilotinib is a selective inhibitor of the BCR-ABL tyrosine kinase receptor and is used in the management of chronic myelogenous leukemia (CML). Nilotinib therapy at high doses is associated with elevated serum bilirubin levels. If the serum bilirubin level exceeds 3 times the upper limit of normal, the recommendation is to either adjust nilotinib dosage or temporarily discontinue the treatment. However, it is unclear whether hyperbilirubinemia indicates obvious liver histology damage. PATIENT CONCERNS: A 24-year-old man with confirmed CML was treated with nilotinib therapy and developed hyperbilirubinemia after the treatment. Although the first remission of the hyperbilirubinemia was achieved after dose adjustment, the hematological parameters deteriorated. Thus, we initiated an antineoplastic therapy (at the standard dose) until complete remission of the CML was achieved. The pathogenic mechanism of hyperbilirubinemia may be related to the inhibition of uridine diphosphate-glucuronosyltransferase (UGT1A1) activity. Liver histological analysis revealed no significant liver damage. In addition, the patient had no family history of hyperbilirubinemia and liver disease. DIAGNOSIS: The patient was admitted to our hospital under the diagnosis of hyperbilirubinemia, and histopathology by liver biopsy showed no obvious damage. We also detected a UGT1A1 mutation [ex1 c.686C > A (p.Pro229Gln)] in the patient and his mother. INTERVENTIONS: When the nilotinib dose was decreased to 300 mg daily, the total bilirubin (TBIL) level decreased to 30 to 50 µmol/L for 1 month. However, because the Bcr-Abl/Abl ratio did not correspond to the major molecular response (MMR; <0.1%), the nilotinib dose was readjusted to 400 mg daily. One week later, the TBIL and indirect bilirubin levels increased to 89 and 79 µmol/L, respectively. The levels of alanine transaminase and other liver functional indicators were normal. OUTCOMES: A Naranjo Adverse Drug Reaction (ADR) Probability Scale score of 13 indicates that hyperbilirubinemia is attributed to ADR caused by nilotinib rather than by drug-induced liver injury. CONCLUSION: Although reducing the nilotinib dose can alleviate the occurrence of hyperbilirubinemia, the effect of MMR is also reduced. Treatment of CML without dose adjustment or discontinuation of nilotinib therapy may be more advantageous.


Assuntos
Doença Hepática Crônica Induzida por Substâncias e Drogas/diagnóstico , Proteínas de Fusão bcr-abl/antagonistas & inibidores , Leucemia Mielogênica Crônica BCR-ABL Positiva/complicações , Inibidores de Proteínas Quinases/efeitos adversos , Pirimidinas/efeitos adversos , Idoso , Antineoplásicos/uso terapêutico , Doença Hepática Crônica Induzida por Substâncias e Drogas/patologia , China/epidemiologia , Feminino , Glucuronosiltransferase/efeitos dos fármacos , Glucuronosiltransferase/genética , Humanos , Hiperbilirrubinemia/induzido quimicamente , Japão/epidemiologia , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Mães , Mutação , Inibidores de Proteínas Quinases/uso terapêutico , Pirimidinas/uso terapêutico , Indução de Remissão , Adulto Jovem
4.
Ann Hematol ; 99(11): 2539-2546, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32939674

RESUMO

Decitabine is a hypomethylating drug that is used to treat myelodysplastic syndrome (MDS) at a recommended dose and schedule (20 mg/m2 per day, for 5 consecutive days). However, due to its relatively high incidence of side effects and its effects on neoplastic cells, many studies have begun to explore the clinical application of a low dose of decitabine for treating MDS. In this retrospective study, we examined the effects of a very-low-dose decitabine schedule for treating MDS. A total of 13 patients diagnosed with de novo MDS received a schedule of intravenous decitabine administration at 6 mg/m2 per day for 7 days, repeated every 4 weeks. The complete response rate was 30.8%, and the overall response rate was 69.2%. In patients with complete remission, the median time to granulocyte recovery greater than 0.5 × 109/L during complete remission (CR) was 15 days. In patients with remission, the median time to granulocyte recovery greater than 0.5 × 109/L was 10.5 days. The 1-year survival rate was 72.7% and the median survival was 28.0 months. In summary, we demonstrated that a very-low-dose decitabine schedule has an appreciable response and survival rate, as well as appreciable tolerance and medical compliance for treating MDS.


Assuntos
Decitabina/administração & dosagem , Síndromes Mielodisplásicas , Idoso , Idoso de 80 Anos ou mais , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/sangue , Síndromes Mielodisplásicas/tratamento farmacológico , Síndromes Mielodisplásicas/mortalidade , Indução de Remissão , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida
5.
Medicine (Baltimore) ; 99(35): e21938, 2020 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-32871937

RESUMO

RATIONALE: Aggressive variant of splenic marginal zone lymphoma (AV-SMZL) is a very rare disease that is often associated with TP53 mutations and has a poor prognosis. On the other hand, recent advances in genome sequencing techniques enable us to understand the molecular characteristics of rare cancers such as AV-SMZL. Here we present a case of AV-SMZL analyzed using a genetic test. PATIENT CONCERNS: A 66-year-old woman was admitted with splenomegaly and lymphocytosis. Computed tomography revealed marked splenomegaly without lymphadenopathy in any other areas. The serum soluble interleukin-2 receptor (sIL-2R) level was significantly elevated. Peripheral and bone marrow blood tests showed an increase in abnormal lymphocytes. DIAGNOSIS: A splenectomy revealed an SMZL pattern with increased numbers of large cells and mitotic cells and a high Ki-67 positivity rate, which led to a diagnosis of AV-SMZL. Although TP53 mutation was not detected, mutations in NOTCH2, NCOA4, PTEN, EPHA3, and KMT2D were identified. Among these, the mutations in NCOA4, PTEN, and EPHA3 were novel pathogenic mutations in SMZL, which suggests they may be related to the aggressiveness and persistence of the disease. INTERVENTIONS: The patient was administered a rituximab-containing regimen and rituximab-maintenance therapy. OUTCOMES: The patient continues to exhibit a complete response. LESSONS: This is a case of AV-SMZL in which a cancer panel test successfully detected genetic alterations that are potentially associated with its pathogenesis. These findings suggest that genetic analysis is useful for making diagnoses as well as for determining treatment strategies in AV-SMZL.


Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linfoma de Zona Marginal Tipo Células B/diagnóstico , Linfoma de Zona Marginal Tipo Células B/tratamento farmacológico , Rituximab/uso terapêutico , Neoplasias Esplênicas/diagnóstico , Neoplasias Esplênicas/tratamento farmacológico , Idoso , Análise Mutacional de DNA , Feminino , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Linfoma de Zona Marginal Tipo Células B/genética , Linfoma de Zona Marginal Tipo Células B/cirurgia , Mutação , Indução de Remissão , Esplenectomia , Neoplasias Esplênicas/genética , Neoplasias Esplênicas/cirurgia
6.
Ann Hematol ; 99(11): 2589-2598, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32892275

RESUMO

The induction therapy containing ixazomib, an oral proteasome inhibitor, has shown favorable efficacy and safety in clinical trials, but its experience in real-life remains limited. In routine practice, few patients received ixazomib-based induction therapy due to reasons including (1) patients' preference on oral regimens, (2) concerns on adverse events (AEs) of other intravenous/subcutaneous regimens, (3) requirements for less center visits, and (4) fears of COVID-19 and other infectious disease exposures. With the aim of assessing the real-life effectiveness and safety of ixazomib-based induction therapy, we performed this multi-center, observational study on 85 newly diagnosed multiple myeloma (NDMM) patients from 14 medical centers. Ixazomib-based regimens included ixazomib-lenalidomide-dexamethasone (IRd) in 44.7% of patients, ixazomib-dexamethasone (Id) in 29.4%, and Id plus another agent (doxorubicin, cyclophosphamide, thalidomide, or daratumumab) in 25.9%. Different ixazomib-based therapies were applied due to (1) financial burdens or limitations on local health insurance coverage, (2) concerns on treatment tolerance, and (3) drug accessibility issue. Ten patients received ixazomib maintenance. The median age was 67 years; 43.5% had ISS stage III disease; 48.2% had an Eastern Cooperative Oncology Group performance score ≥ 2; and 17.6% with high-risk cytogenetic abnormalities. Overall response rate for all 85 patients was 95.3%, including 65.9% very good partial response or better and 29.5% complete responses. The median time to response was 30 days. The response rate was similar across different ixazomib-based regimens. Median progression-free survival was not reached. Severe AEs (≥ grade 3) were reported in 29.4% of patients. No grade 3/4 peripheral neuropathy (PN) occurred. Patients received a median of 6 (range 1-20) cycles of ixazomib treatment; 56.6% remained on treatment at data cutoff; 15.3% discontinued treatment due to intolerable AEs. These results support that the ixazomib-based frontline therapy was highly effective with acceptable toxicity in routine practice and the ixazomib oral regimens could be good alternative options for NDMM patients.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Compostos de Boro/administração & dosagem , Glicina/análogos & derivados , Mieloma Múltiplo/tratamento farmacológico , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Adolescente , Adulto , Idoso , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Compostos de Boro/efeitos adversos , Ciclofosfamida/administração & dosagem , Ciclofosfamida/efeitos adversos , Dexametasona/administração & dosagem , Dexametasona/efeitos adversos , Doxorrubicina/administração & dosagem , Doxorrubicina/efeitos adversos , Esquema de Medicação , Feminino , Glicina/administração & dosagem , Glicina/efeitos adversos , Humanos , Lenalidomida/administração & dosagem , Lenalidomida/efeitos adversos , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/mortalidade , Mieloma Múltiplo/patologia , Estadiamento de Neoplasias , Doenças do Sistema Nervoso Periférico/diagnóstico , Doenças do Sistema Nervoso Periférico/fisiopatologia , Indução de Remissão , Análise de Sobrevida , Talidomida/administração & dosagem , Talidomida/efeitos adversos , Resultado do Tratamento
8.
Cochrane Database Syst Rev ; 9: CD012658, 2020 09 06.
Artigo em Inglês | MEDLINE | ID: mdl-32909630

RESUMO

BACKGROUND: In the absence of treatment, endometrial hyperplasia (EH) can progress to endometrial cancer, particularly in the presence of histologic nuclear atypia. The development of EH results from exposure of the endometrium to oestrogen unopposed by progesterone. Oral progestogens have been used as treatment for EH without atypia, and in some cases of EH with atypia in women who wish to preserve fertility or who cannot tolerate surgery. EH without atypia is associated with a low risk of progression to atypia and cancer; EH with atypia is where the cells are structurally abnormal, and has a higher risk of developing cancer. Oral progestogen is not always effective at reversing the hyperplasia, can be associated with side effects, and depends on patient adherence. The levonorgestrel-intrauterine system (LNG-IUS) is an alternative method of administration of progestogen and may have some advantages over non-intrauterine progestogens. OBJECTIVES: To evaluate the effectiveness and safety of the levonorgestrel intrauterine system (LNG-IUS) in women with endometrial hyperplasia (EH) with or without atypia compared to medical treatment with non-intrauterine progestogens, placebo, surgery or no treatment. SEARCH METHODS: We searched the following databases: the Cochrane Gynaecology and Fertility Group (CGF) Specialised Register, CENTRAL, MEDLINE, Embase, CINAHL and PsycINFO, and conference proceedings of 10 relevant organisations. We handsearched references in relevant published studies. We also searched ongoing trials in ClinicalTrials.gov, the World Health Organization International Clinical Trials Registry, and other trial registries. We performed the final search in May 2020. SELECTION CRITERIA: Randomised controlled trials (RCTs) and cross-over trials of women with a histological diagnosis of endometrial hyperplasia with or without atypia comparing LNG-IUS with non-intrauterine progestogens, placebo, surgery or no treatment. DATA COLLECTION AND ANALYSIS: Two review authors independently performed study selection, risk of bias assessment and data extraction. Our primary outcome measures were regression of EH and adverse effects associated with the LNG-IUS device (such as pelvic inflammatory disease, device expulsion, uterine perforation) when compared to treatment with non-intrauterine progestogens, placebo, surgery or no treatment. Secondary outcomes included hysterectomy, hormone-related adverse effects (such as bleeding/spotting, pelvic pain, breast tenderness, ovarian cysts, weight gain, acne), withdrawal from treatment due to adverse effects, satisfaction with treatment, and cost or resource use. We rated the overall quality of evidence using GRADE methods. MAIN RESULTS: Thirteen RCTs (1657 women aged 22 to 75 years) met the inclusion criteria. Two studies had insufficient data for meta-analysis, thus the quantitative analysis included 11 RCTs. All trials evaluated treatment duration of six months or less. The evidence ranged from very low to moderate quality: the main limitations were risk of bias (associated with lack of blinding and poor reporting of study methods), inconsistency and imprecision. LNG-IUS versus non-intrauterine progestogens Primary outcomes Regression of endometrial hyperplasia The LNG-IUS probably improves regression of EH compared with non-intrauterine progestogens at short-term follow-up (up to six months) (OR 2.94, 95% CI 2.10 to 4.13; I² = 0%; 10 RCTs, 1108 participants; moderate-quality evidence). This suggests that if regression of EH following treatment with a non-intrauterine progestogen is assumed to be 72%, regression of EH following treatment with LNG-IUS would be between 85% and 92%. Regression of EH may be improved by LNG-IUS compared with non-intrauterine progestogens at long-term follow-up (12 months) (OR 3.80, 95% CI 1.75 to 8.23; 1 RCT, 138 participants; low-quality evidence), Adverse effects associated with LNG-IUS There was insufficient evidence to determine device-related adverse effects; only one study reported on expulsion with insufficient data for analysis. Secondary outcomes The LNG-IUS may be associated with fewer hysterectomies (OR 0.26, 95% CI 0.15 to 0.46; I² = 19%; 4 RCTs, 452 participants; low-quality evidence), fewer withdrawals from treatment due to hormone-related adverse effects (OR 0.41, 95% CI 0.12 to 1.35; I² = 0%; 4 RCTs, 360 participants; low-quality evidence) and improved patient satisfaction with treatment (OR 5.28, 95% CI 2.51 to 11.10; I² = 0%; 2 RCTs, 202 participants; very low-quality evidence) compared to non-intrauterine progestogens. The LNG-IUS may be associated with more bleeding/spotting (OR 2.13, 95% CI 1.33 to 3.43; I² = 78%; 3 RCTs, 428 participants) and less nausea (OR 0.52, 95% CI 0.28 to 0.95; I² = 0%; 3 RCTs, 428 participants) compared to non-intrauterine progestogens. Data from single trials for mood swings and fatigue had a similar direction of effect as for bleeding/spotting, nausea and weight gain. There was insufficient evidence to determine cost or resource use. LNG-IUS versus no treatment Regression of endometrial hyperplasia One study demonstrated that the LNG-IUS is associated with regression of EH without atypia (OR 78.41, 95% CI 22.86 to 268.97; I² = 0%; 1 RCT, 190 participants; moderate-quality evidence) compared with no treatment. This study did not report on any other review outcome. AUTHORS' CONCLUSIONS: There is moderate-quality evidence that treatment with LNG-IUS used for three to six months is probably more effective than non-intrauterine progestogens at reversing EH in the short term (up to six months) and long term (up to two years). Adverse effects (device-related and hormone-related) were poorly and incompletely reported across studies. Very low quality to low-quality evidence suggests the LNG-IUS may reduce the risk of hysterectomy, and may be associated with more bleeding/spotting, less nausea, less withdrawal from treatment due to adverse effects, and increased satisfaction with treatment, compared to non-intrauterine progestogens. There was insufficient evidence to reach conclusions regarding device-related adverse effects, or cost or resource use.


Assuntos
Anticoncepcionais Femininos/administração & dosagem , Dispositivos Intrauterinos Medicados , Levanogestrel/administração & dosagem , Adulto , Idoso , Viés , Anticoncepcionais Femininos/efeitos adversos , Hiperplasia Endometrial/tratamento farmacológico , Hiperplasia Endometrial/patologia , Hiperplasia Endometrial/cirurgia , Feminino , Humanos , Histerectomia/estatística & dados numéricos , Expulsão de Dispositivo Intrauterino , Dispositivos Intrauterinos Medicados/efeitos adversos , Levanogestrel/efeitos adversos , Pessoa de Meia-Idade , Náusea/etiologia , Pacientes Desistentes do Tratamento/estatística & dados numéricos , Satisfação do Paciente/estatística & dados numéricos , Progestinas/administração & dosagem , Progestinas/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Indução de Remissão , Fatores de Tempo , Hemorragia Uterina/etiologia , Ganho de Peso , Adulto Jovem
9.
Rinsho Ketsueki ; 61(8): 922-928, 2020.
Artigo em Japonês | MEDLINE | ID: mdl-32908056

RESUMO

In 2018, two novel antibody therapies, inotuzumab ozogamicin (InO) and blinatumomab, against relapsed or refractory acute lymphoblastic leukemia were approved in Japan. In InO, the antitumor drug ozogamicin is conjugated to the anti-CD22 antibody. Blinatumomab is a bispecific T cell engager antibody comprising the variable regions of the anti-CD19 and the anti-CD3 antibodies. The remission rate of InO is about 75%; however, the frequency of sinusoidal obstruction syndrome is increased when allogeneic hematopoietic cell transplantation is performed after InO treatment. Blinatumomab has a remission rate of 45-70%. The management of cytokine release syndrome during blinatumomab treatment is required in certain cases. Although both the treatments have higher remission and negativity of minimal residual disease rates compared to those in conventional chemotherapy, it is difficult to maintain remission in the long term. Allogeneic hematopoietic stem cell transplantation should be performed as commonly as possible.


Assuntos
Anticorpos/uso terapêutico , Leucemia-Linfoma Linfoblástico de Células Precursoras , Antineoplásicos , Humanos , Inotuzumab Ozogamicina , Japão , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Indução de Remissão
10.
BMJ Case Rep ; 13(9)2020 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-32938656

RESUMO

The COVID-19 pandemic that attracted global attention in December 2019 is well known for its clinical picture that is consistent with respiratory symptoms. Currently, the available medical literature describing the neurological complications of COVID-19 is gradually emerging. We hereby describe a case of a 31-year-old COVID-19-positive patient who was admitted on emergency basis. His clinical presentation was primarily neurological, rather than the COVID-19's classical respiratory manifestations. He presented with acute behavioural changes, severe confusion and drowsiness. The cerebrospinal fluid analysis was consistent with COVID-19 encephalitis, as well as the brain imaging. This experience confirms that neurological manifestations might be expected in COVID-19 infections, despite the absence of significant respiratory symptoms. Whenever certain red flags are raised, physicians who are involved in the management of COVID-19 should promptly consider the possibility of encephalitis. Early recognition of COVID-19 encephalitis and timely management may lead to a better outcome.


Assuntos
Infecções por Coronavirus/complicações , Encefalite Viral/líquido cefalorraquidiano , Pneumonia Viral/complicações , Adulto , Infecções por Coronavirus/tratamento farmacológico , Encefalite Viral/diagnóstico , Encefalite Viral/tratamento farmacológico , Encefalite Viral/virologia , Humanos , Masculino , Pandemias , Pneumonia Viral/tratamento farmacológico , Indução de Remissão
11.
Ann Hematol ; 99(10): 2351-2356, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32865607

RESUMO

Lenalidomide (Len) and dexamethasone (dex) therapy is a standard therapy in patients with multiple myeloma. Elderly or unfit patients may reduce Len or dex doses to prevent toxicities that lead to treatment discontinuation. However, there have been few studies evaluating the efficacy and safety of lower doses of Len and dex. We conducted a phase II study of 1.5-year low-dose Len and dex therapy following melphalan and prednisolone (MP), the number of which cycles was determined by a response within 9 cycles. The Len dose was 10 mg daily and the dex dose was 20 mg weekly, which were continued for 1.5 years. Twenty-one patients were enrolled. The median number of cycles of MP was 3 (range, 2-9). The overall response rate was 81% and a very good partial response or better was achieved in 33.3% of patients. The median follow-up time for survivors was 70.5 months (range, 42-83 months), the median progression-free survival (PFS) was 27 months (95% CI, 21-33 months), and the median overall survival was not reached. Grade 3 or 4 adverse events were observed in 28.6% of patients. In conclusion, the low-dose Len and dex therapy safely achieved comparable efficacies to the standard-dose regimen in elderly patients with newly diagnosed multiple myeloma. UMIN000007889.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Mieloma Múltiplo/tratamento farmacológico , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Anemia/induzido quimicamente , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Dexametasona/administração & dosagem , Dexametasona/efeitos adversos , Relação Dose-Resposta a Droga , Esquema de Medicação , Neutropenia Febril/induzido quimicamente , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Lenalidomida/administração & dosagem , Lenalidomida/efeitos adversos , Masculino , Melfalan/administração & dosagem , Melfalan/efeitos adversos , Pessoa de Meia-Idade , Mieloma Múltiplo/genética , Prednisolona/administração & dosagem , Prednisolona/efeitos adversos , Intervalo Livre de Progressão , Indução de Remissão , Resultado do Tratamento , Adulto Jovem
12.
Nat Commun ; 11(1): 4458, 2020 09 07.
Artigo em Inglês | MEDLINE | ID: mdl-32895383

RESUMO

In rodent models of type 2 diabetes (T2D), sustained remission of hyperglycemia can be induced by a single intracerebroventricular (icv) injection of fibroblast growth factor 1 (FGF1), and the mediobasal hypothalamus (MBH) was recently implicated as the brain area responsible for this effect. To better understand the cellular response to FGF1 in the MBH, we sequenced >79,000 single-cell transcriptomes from the hypothalamus of diabetic Lepob/ob mice obtained on Days 1 and 5 after icv injection of either FGF1 or vehicle. A wide range of transcriptional responses to FGF1 was observed across diverse hypothalamic cell types, with glial cell types responding much more robustly than neurons at both time points. Tanycytes and ependymal cells were the most FGF1-responsive cell type at Day 1, but astrocytes and oligodendrocyte lineage cells subsequently became more responsive. Based on histochemical and ultrastructural evidence of enhanced cell-cell interactions between astrocytes and Agrp neurons (key components of the melanocortin system), we performed a series of studies showing that intact melanocortin signaling is required for the sustained antidiabetic action of FGF1. These data collectively suggest that hypothalamic glial cells are leading targets for the effects of FGF1 and that sustained diabetes remission is dependent on intact melanocortin signaling.


Assuntos
Diabetes Mellitus Experimental/dietoterapia , Diabetes Mellitus Tipo 2/tratamento farmacológico , Fator 1 de Crescimento de Fibroblastos/administração & dosagem , Hipoglicemiantes/administração & dosagem , Hipotálamo/efeitos dos fármacos , Proteínas Recombinantes/administração & dosagem , Proteína Relacionada com Agouti/metabolismo , Animais , Astrócitos/efeitos dos fármacos , Astrócitos/metabolismo , Glicemia/análise , Comunicação Celular , Núcleo Celular/efeitos dos fármacos , Núcleo Celular/metabolismo , Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Experimental/etiologia , Diabetes Mellitus Experimental/patologia , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/etiologia , Diabetes Mellitus Tipo 2/patologia , Dieta Hiperlipídica/efeitos adversos , Sacarose na Dieta/administração & dosagem , Sacarose na Dieta/efeitos adversos , Humanos , Hipotálamo/citologia , Hipotálamo/patologia , Injeções Intraventriculares , Leptina/genética , Masculino , Melanocortinas/metabolismo , Hormônios Estimuladores de Melanócitos/administração & dosagem , Camundongos , Camundongos Knockout , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Oligodendroglia/efeitos dos fármacos , Oligodendroglia/metabolismo , RNA-Seq , Receptor Tipo 4 de Melanocortina/genética , Receptores de Melanocortina/antagonistas & inibidores , Receptores de Melanocortina/metabolismo , Indução de Remissão/métodos , Transdução de Sinais/efeitos dos fármacos , Análise de Célula Única , Técnicas Estereotáxicas , Transcriptoma/efeitos dos fármacos
13.
N Engl J Med ; 383(12): 1117-1128, 2020 09 17.
Artigo em Inglês | MEDLINE | ID: mdl-32937045

RESUMO

BACKGROUND: In adults with active lupus nephritis, the efficacy and safety of intravenous belimumab as compared with placebo, when added to standard therapy (mycophenolate mofetil or cyclophosphamide-azathioprine), are unknown. METHODS: In a phase 3, multinational, multicenter, randomized, double-blind, placebo-controlled, 104-week trial conducted at 107 sites in 21 countries, we assigned adults with biopsy-proven, active lupus nephritis in a 1:1 ratio to receive intravenous belimumab (at a dose of 10 mg per kilogram of body weight) or matching placebo, in addition to standard therapy. The primary end point at week 104 was a primary efficacy renal response (a ratio of urinary protein to creatinine of ≤0.7, an estimated glomerular filtration rate [eGFR] that was no worse than 20% below the value before the renal flare (pre-flare value) or ≥60 ml per minute per 1.73 m2 of body-surface area, and no use of rescue therapy), and the major secondary end point was a complete renal response (a ratio of urinary protein to creatinine of <0.5, an eGFR that was no worse than 10% below the pre-flare value or ≥90 ml per minute per 1.73 m2, and no use of rescue therapy). The time to a renal-related event or death was assessed. RESULTS: A total of 448 patients underwent randomization (224 to the belimumab group and 224 to the placebo group). At week 104, significantly more patients in the belimumab group than in the placebo group had a primary efficacy renal response (43% vs. 32%; odds ratio, 1.6; 95% confidence interval [CI], 1.0 to 2.3; P = 0.03) and a complete renal response (30% vs. 20%; odds ratio, 1.7; 95% CI, 1.1 to 2.7; P = 0.02). The risk of a renal-related event or death was lower among patients who received belimumab than among those who received placebo (hazard ratio, 0.51; 95% CI, 0.34 to 0.77; P = 0.001). The safety profile of belimumab was consistent with that in previous trials. CONCLUSIONS: In this trial involving patients with active lupus nephritis, more patients who received belimumab plus standard therapy had a primary efficacy renal response than those who received standard therapy alone. (Funded by GlaxoSmithKline; BLISS-LN ClinicalTrials.gov number, NCT01639339.).


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Imunossupressores/uso terapêutico , Nefrite Lúpica/tratamento farmacológico , Adulto , Anticorpos Monoclonais Humanizados/efeitos adversos , Azatioprina/uso terapêutico , Creatinina/urina , Ciclofosfamida/uso terapêutico , Método Duplo-Cego , Quimioterapia Combinada , Inibidores Enzimáticos/uso terapêutico , Feminino , Taxa de Filtração Glomerular , Humanos , Imunossupressores/efeitos adversos , Infusões Intravenosas , Análise de Intenção de Tratamento , Nefrite Lúpica/mortalidade , Masculino , Ácido Micofenólico/uso terapêutico , Indução de Remissão
14.
Medicine (Baltimore) ; 99(38): e22328, 2020 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-32957400

RESUMO

BACKGROUND: Lupus nephritis (LN) remains a predominant cause of morbidity and mortality in SLE. Here we performed a meta-analysis to evaluate the efficacy and safety of the induction treatment with mycophenolate mofetil (MMF) and cyclophosphamide (CYC) for LN. METHODS: Relevant literature was searched by computer from the establishment of the database to November 2019. A meta-analysis was conducted to analysis the efficacy and safety between mycophenolate mofetil and cyclophosphamide as induction therapy in LN patients. The primary end-point was response to urine protein, serum creatinine (Scr) and serum complement C3, and the secondary end-points were complete remission and adverse reactions. RESULTS: Eighteen articles were selected for the final meta-analysis, involving 1989 patients with LN, of which the renal biopsy result could be classified into class III-V according to the standards of WHO/ISN. The results revealed that MMF was superior to CYC in increasing the level of serum complement C3 [SMD = 0.475, 95%CI (0.230-0.719)] and complete remission [RR = 1.231, 95%CI (1.055-1.437)]. Furthermore, the subgroup analysis showed that it was in Asian patients, rather than in Caucasian patients, that CYC exerted a better effect on lowering the level of urine protein (UPRO) than MMF [SMD = 0.405, 95%CI (0.081-0.730)]. Besides, when the initial UPRO level was less than 4 g/day, the effect of CYC was better than MMF [SMD = 0.303, 95%CI (0.014-0.591)]. There was no significant difference between MMF and CYC in improving Scr [SMD = 0.090, 95%CI (-0.060-0.239)]. When it came to the comparison of safety between MMF and CYC, the meta-analysis showed that MMF was superior to CYC in decreasing infection in Caucasian patients [RR = 0.727, 95%CI (0.532-0.993)], reducing the risk of leukopenia and menstrual abnormalities in Asian patients and lowering the frequency of gastrointestinal symptoms [RR = 0.639, 95%CI (0.564-0.724)], independent of race. CONCLUSIONS: MMF precedes CYC in improving serum complement C3 and complete remission regardless of race, as well as shows fewer adverse drug reactions in the induction treatment of LN belonging to type III-V. But for Asian patients or those initial UPRO levels are less than 4 g/day, CYC may be superior to MMF.


Assuntos
Ciclofosfamida/uso terapêutico , Nefrite Lúpica/tratamento farmacológico , Ácido Micofenólico/uso terapêutico , Adulto , Feminino , Humanos , Masculino , Ensaios Clínicos Controlados Aleatórios como Assunto , Indução de Remissão
15.
Artigo em Inglês | MEDLINE | ID: mdl-32942345

RESUMO

Background: There is a paucity of studies on treatment of childhood-onset bipolar disorder and its associated comorbidities, which leads to a wide diversity of opinion on choice and sequencing of treatment options. Methods: From December 2018 to January 2019, a graphic depiction of medications and weekly ratings of symptoms of mania, depression, anxiety, attention-deficit/hyperactivity disorder (ADHD), and oppositional behavior that parents had rated on their 9-year-old child over a period of several years was sent to experts in child and adult bipolar disorder. These responding medical doctors (MDs, 8 child and 18 adult psychiatrists) rated a comprehensive list of medications that they would choose (and with what priority) to treat the child's now improved mood (mania and depression) but continued mild to moderate symptoms of anxiety, ADHD, and oppositional behavior. Results: In the whole group, the drugs most highly endorsed were lamotrigine: 69%, lithium: 62%, lurasidone: 62%, quetiapine: 54%, aripiprazole: 46%, and valproate: 42%. Among the antidepressants, 38% endorsed a selective serotonin reuptake inhibitor, 12% a serotonin-norepinephrine reuptake inhibitor, and 27% bupropion. Of the child MDs, 75% suggested increasing the 1-mg dose of risperidone, while few adult MDs suggested this. Conversely, 56% of the adult MDs suggested using valproate, while only 1 child MD did so. There was little consensus on how to manage ADHD symptoms unresponsive to methylphenidate 36 mg/d. How these treatment options were sequenced also varied widely. Conclusions: There was wide variation in suggestions on to how to treat persistent symptoms of anxiety, ADHD, and oppositional behavior in a child whose mania and depression had been brought under good control. We surmise that this great diversity in recommendations among experts in child and adult bipolar disorder stems at least partially from inadequate literature on treatment and that a new emphasis on funding and conducting studies on efficacy and effectiveness is needed.


Assuntos
Transtornos de Ansiedade/tratamento farmacológico , Transtornos de Deficit da Atenção e do Comportamento Disruptivo/tratamento farmacológico , Transtorno Bipolar/tratamento farmacológico , Psicotrópicos/uso terapêutico , Transtorno do Deficit de Atenção com Hiperatividade/tratamento farmacológico , Transtorno Bipolar/terapia , Criança , Consenso , Feminino , Humanos , Prevenção Primária , Indução de Remissão
16.
Cochrane Database Syst Rev ; 8: CD000544, 2020 08 28.
Artigo em Inglês | MEDLINE | ID: mdl-32856298

RESUMO

BACKGROUND: Oral 5-aminosalicylic acid (5-ASA; also known as mesalazine or mesalamine) preparations were intended to avoid the adverse effects of sulfasalazine (SASP) while maintaining its therapeutic benefits. In an earlier version of this review, we found that 5-ASA drugs were more effective than placebo for maintenance of remission of ulcerative colitis (UC), but had a significant therapeutic inferiority relative to SASP. In this version, we have rerun the search to bring the review up to date. OBJECTIVES: To assess the efficacy, dose-responsiveness, and safety of oral 5-ASA compared to placebo, SASP, or 5-ASA comparators for maintenance of remission in quiescent UC and to compare the efficacy and safety of once-daily dosing of oral 5-ASA with conventional (two or three times daily) dosing regimens. SEARCH METHODS: We performed a literature search for studies on 11 June 2019 using MEDLINE, Embase, and the Cochrane Library. In addition, we searched review articles and conference proceedings. SELECTION CRITERIA: We included randomized controlled trials with a minimum treatment duration of six months. We considered studies of oral 5-ASA therapy for treatment of participants with quiescent UC compared with placebo, SASP, or other 5-ASA formulations. We also included studies that compared once-daily 5-ASA treatment with conventional dosing of 5-ASA and 5-ASA dose-ranging studies. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. The primary outcome was the failure to maintain clinical or endoscopic remission. Secondary outcomes were adherence, adverse events (AE), serious adverse events (SAE), withdrawals due to AEs, and withdrawals or exclusions after entry. Trials were separated into five comparison groups: 5-ASA versus placebo, 5-ASA versus SASP, once-daily dosing versus conventional dosing, 5-ASA (balsalazide, Pentasa, and olsalazine) versus comparator 5-ASA formulation (Asacol and Salofalk), and 5-ASA dose-ranging. We calculated the risk ratio (RR) and 95% confidence interval (CI) for each outcome. We analyzed data on an intention-to-treat basis, and used GRADE to assess the overall certainty of the evidence. MAIN RESULTS: The search identified 44 studies (9967 participants). Most studies were at low risk of bias. Ten studies were at high risk of bias. Seven of these studies were single-blind and three were open-label. 5-ASA is more effective than placebo for maintenance of clinical or endoscopic remission. About 37% (335/907) of 5-ASA participants relapsed at six to 12 months compared to 55% (355/648) of placebo participants (RR 0.68, 95% CI 0.61 to 0.76; 8 studies, 1555 participants; high-certainty evidence). Adherence to study medication was not reported for this comparison. SAEs were reported in 1% (6/550) of participants in the 5-ASA group compared to 2% (5/276) of participants in the placebo group at six to 12 months (RR 0.60, 95% CI 0.19 to 1.84; 3 studies, 826 participants; low-certainty evidence). There is probably little or no difference in AEs at six to 12 months' follow-up (RR 0.93, 95% CI 0.73 to 1.18; 5 studies, 1132 participants; moderate-certainty evidence). SASP is more effective than 5-ASA for maintenance of remission. About 48% (416/871) of 5-ASA participants relapsed at six to 18 months compared to 43% (336/784) of SASP participants (RR 1.14, 95% CI 1.03 to 1.27; 12 studies, 1655 participants; high-certainty evidence). Adherence to study medication and SAEs were not reported for this comparison. There is probably little or no difference in AEs at six to 12 months' follow-up (RR 1.07, 95% CI 0.82 to 1.40; 7 studies, 1138 participants; moderate-certainty evidence). There is little or no difference in clinical or endoscopic remission rates between once-daily and conventionally dosed 5-ASA. About 37% (717/1939) of once-daily participants relapsed over 12 months compared to 39% (770/1971) of conventional-dosing participants (RR 0.94, 95% CI 0.88 to 1.01; 10 studies, 3910 participants; high-certainty evidence). There is probably little or no difference in medication adherence rates. About 10% (106/1152) of participants in the once-daily group failed to adhere to their medication regimen compared to 8% (84/1154) of participants in the conventional-dosing group (RR 1.18, 95% CI 0.72 to 1.93; 9 studies, 2306 participants; moderate-certainty evidence). About 3% (41/1587) of participants in the once-daily group experienced a SAE compared to 2% (35/1609) of participants in the conventional-dose group at six to 12 months (RR 1.20, 95% CI 0.77 to 1.87; moderate-certainty evidence). There is little or no difference in the incidence of AEs at six to 13 months' follow-up (RR 0.98, 95% CI 0.92 to 1.04; 8 studies, 3497 participants; high-certainty evidence). There may be little or no difference in the efficacy of different 5-ASA formulations. About 44% (158/358) of participants in the 5-ASA group relapsed at six to 18 months compared to 41% (142/349) of participants in the 5-ASA comparator group (RR 1.08, 95% CI 0.91 to 1.28; 6 studies, 707 participants; low-certainty evidence). AUTHORS' CONCLUSIONS: There is high-certainty evidence that 5-ASA is superior to placebo for maintenance therapy in UC. There is high-certainty evidence that 5-ASA is inferior compared to SASP. There is probably little or no difference between 5-ASA and placebo, and 5-ASA and SASP in commonly reported AEs such as flatulence, abdominal pain, nausea, diarrhea, headache, and dyspepsia. Oral 5-ASA administered once daily has a similar benefit and harm profile as conventional dosing for maintenance of remission in quiescent UC.


Assuntos
Ácidos Aminossalicílicos/administração & dosagem , Anti-Inflamatórios não Esteroides/administração & dosagem , Colite Ulcerativa/tratamento farmacológico , Quimioterapia de Manutenção/métodos , Mesalamina/administração & dosagem , Administração Oral , Anti-Inflamatórios não Esteroides/efeitos adversos , Viés , Colite Ulcerativa/prevenção & controle , Esquema de Medicação , Humanos , Adesão à Medicação/estatística & dados numéricos , Pacientes Desistentes do Tratamento/estatística & dados numéricos , Placebos/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Recidiva , Indução de Remissão/métodos , Sulfassalazina/administração & dosagem , Sulfassalazina/efeitos adversos
17.
N Engl J Med ; 383(7): 617-629, 2020 08 13.
Artigo em Inglês | MEDLINE | ID: mdl-32786187

RESUMO

BACKGROUND: Older patients with acute myeloid leukemia (AML) have a dismal prognosis, even after treatment with a hypomethylating agent. Azacitidine added to venetoclax had promising efficacy in a previous phase 1b study. METHODS: We randomly assigned previously untreated patients with confirmed AML who were ineligible for standard induction therapy because of coexisting conditions, because they were 75 years of age or older, or both to azacitidine plus either venetoclax or placebo. All patients received a standard dose of azacitidine (75 mg per square meter of body-surface area subcutaneously or intravenously on days 1 through 7 every 28-day cycle); venetoclax (target dose, 400 mg) or matching placebo was administered orally, once daily, in 28-day cycles. The primary end point was overall survival. RESULTS: The intention-to-treat population included 431 patients (286 in the azacitidine-venetoclax group and 145 in the azacitidine-placebo [control] group). The median age was 76 years in both groups (range, 49 to 91). At a median follow-up of 20.5 months, the median overall survival was 14.7 months in the azacitidine-venetoclax group and 9.6 months in the control group (hazard ratio for death, 0.66; 95% confidence interval, 0.52 to 0.85; P<0.001). The incidence of complete remission was higher with azacitidine-venetoclax than with the control regimen (36.7% vs. 17.9%; P<0.001), as was the composite complete remission (complete remission or complete remission with incomplete hematologic recovery) (66.4% vs. 28.3%; P<0.001). Key adverse events included nausea of any grade (in 44% of the patients in the azacitidine-venetoclax group and 35% of those in the control group) and grade 3 or higher thrombocytopenia (in 45% and 38%, respectively), neutropenia (in 42% and 28%), and febrile neutropenia (in 42% and 19%). Infections of any grade occurred in 85% of the patients in the azacitidine-venetoclax group and 67% of those in the control group, and serious adverse events occurred in 83% and 73%, respectively. CONCLUSIONS: In previously untreated patients who were ineligible for intensive chemotherapy, overall survival was longer and the incidence of remission was higher among patients who received azacitidine plus venetoclax than among those who received azacitidine alone. The incidence of febrile neutropenia was higher in the venetoclax-azacitidine group than in the control group. (Funded by AbbVie and Genentech; VIALE-A ClinicalTrials.gov number, NCT02993523.).


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Azacitidina/administração & dosagem , Compostos Bicíclicos Heterocíclicos com Pontes/administração & dosagem , Leucemia Mieloide Aguda/tratamento farmacológico , Sulfonamidas/administração & dosagem , Idoso , Idoso de 80 Anos ou mais , Azacitidina/efeitos adversos , Compostos Bicíclicos Heterocíclicos com Pontes/efeitos adversos , Método Duplo-Cego , Feminino , Seguimentos , Humanos , Análise de Intenção de Tratamento , Estimativa de Kaplan-Meier , Leucemia Mieloide Aguda/mortalidade , Leucopenia/induzido quimicamente , Masculino , Pessoa de Meia-Idade , Pneumonia/etiologia , Recidiva , Indução de Remissão , Sulfonamidas/efeitos adversos , Trombocitopenia/induzido quimicamente
18.
Lancet Oncol ; 21(9): 1201-1212, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32791048

RESUMO

BACKGROUND: Findings of retrospective studies suggest that sorafenib maintenance post-transplantation might reduce relapse in patients with FLT3 internal tandem duplication (FLT3-ITD) acute myeloid leukaemia undergoing allogeneic haematopoietic stem-cell transplantation. We investigated the efficacy and tolerability of sorafenib maintenance post-transplantation in this population. METHODS: We did an open-label, randomised phase 3 trial at seven hospitals in China. Eligible patients (aged 18-60 years) had FLT3-ITD acute myeloid leukaemia, were undergoing allogeneic haematopoietic stem-cell transplantation, had an Eastern Cooperative Oncology Group performance status of 0-2, had composite complete remission before and after transplantation, and had haematopoietic recovery within 60 days post-transplantation. Patients were randomly assigned (1:1) to sorafenib maintenance (400 mg orally twice daily) or non-maintenance (control) at 30-60 days post-transplantation. Randomisation was done with permuted blocks (block size four) and implemented through an interactive web-based randomisation system. The primary endpoint was the 1-year cumulative incidence of relapse in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, NCT02474290; the trial is complete. FINDINGS: Between June 20, 2015, and July 21, 2018, 202 patients were enrolled and randomly assigned to sorafenib maintenance (n=100) or control (n=102). Median follow-up post-transplantation was 21·3 months (IQR 15·0-37·0). The 1-year cumulative incidence of relapse was 7·0% (95% CI 3·1-13·1) in the sorafenib group and 24·5% (16·6-33·2) in the control group (hazard ratio 0·25, 95% CI 0·11-0·57; p=0·0010). Within 210 days post-transplantation, the most common grade 3 and 4 adverse events were infections (25 [25%] of 100 patients in the sorafenib group vs 24 [24%] of 102 in the control group), acute graft-versus-host-disease (GVHD; 23 [23%] of 100 vs 21 [21%] of 102), chronic GVHD (18 [18%] of 99 vs 17 [17%] of 99), and haematological toxicity (15 [15%] of 100 vs seven [7%] of 102). There were no treatment-related deaths. INTERPRETATION: Sorafenib maintenance post-transplantation can reduce relapse and is well tolerated in patients with FLT3-ITD acute myeloid leukaemia undergoing allogeneic haematopoietic stem-cell transplantation. This strategy could be a suitable therapeutic option for patients with FLT3-ITD acute myeloid leukaemia. FUNDING: None.


Assuntos
Doença Enxerto-Hospedeiro/epidemiologia , Leucemia Mieloide Aguda/tratamento farmacológico , Sorafenibe/administração & dosagem , Tirosina Quinase 3 Semelhante a fms/genética , Adolescente , Adulto , China/epidemiologia , Intervalo Livre de Doença , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/tratamento farmacológico , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/patologia , Feminino , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/genética , Doença Enxerto-Hospedeiro/patologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Leucemia Mieloide Aguda/epidemiologia , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/patologia , Masculino , Pessoa de Meia-Idade , Inibidores de Proteínas Quinases , Indução de Remissão , Sorafenibe/efeitos adversos , Sequências de Repetição em Tandem/genética , Transplante Homólogo/efeitos adversos , Adulto Jovem
19.
Ann Hematol ; 99(10): 2255-2263, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32766934

RESUMO

We aimed to clarify the clinical characteristics, prognostic factors, and effectiveness of the HLH-94/2004 regimens and hematopoietic stem cell transplantation (HSCT) in pediatric patients with primary hemophagocytic lymphohistiocytosis (pHLH) in China. A retrospective analysis was performed on 38 patients with pHLH at Beijing Children's Hospital. PRF1 (34.2%) and UNC13D (31.6%) were the most common mutations in the pHLH. Thirty-eight patients were treated with the HLH-94/2004 regimens after diagnosis. Twenty-six patients (72.2%) responded to first-line treatment (complete response: 55.5%, partial response: 16.7%). The median survival time was 23 months. The overall survival (OS) rate at 3 years was 74.7%. There was no significant difference in the response rate (72% vs. 63.6%, P = 0.703) or 3-year OS (83.6% vs. 66.7%, P = 0.443) between the patients treated with the HLH-94 regimen and those treated with the HLH-2004 regimen. The incidences of all side effects in patients treated with the HLH-94 or HLH-2004 regimen were 32.0% and 18.2%, respectively (P = 0.394). Among 15 patients treated with HSCT, neither the preconditioning regimen nor the donor type affected patient prognosis (P = 0.205 and P = 0.161, respectively). The disease status (remission or nonremission) before preconditioning did not affect prognosis or the incidence of GVHD. Furthermore, a higher bilirubin level (≥ 30 µmol/L) was correlated with a poorer prognosis in pHLH patients (P = 0.026). The effectiveness rates of the HLH-94 and HLH-2004 regimens, chemotherapy, and HSCT were similar in pHLH patients. A bilirubin level ≥ 30 µmol/L might be an adverse prognostic factor in pHLH.


Assuntos
Ciclosporina/uso terapêutico , Doxorrubicina/uso terapêutico , Etoposídeo/uso terapêutico , Transplante de Células-Tronco Hematopoéticas , Linfo-Histiocitose Hemofagocítica/terapia , Metilprednisolona/uso terapêutico , Criança , Pré-Escolar , China/epidemiologia , Terapia Combinada , Intervalo Livre de Doença , Quimioterapia Combinada , Seguimentos , Doença Enxerto-Hospedeiro/epidemiologia , Doença Enxerto-Hospedeiro/etiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Lactente , Recém-Nascido , Estimativa de Kaplan-Meier , Linfo-Histiocitose Hemofagocítica/tratamento farmacológico , Linfo-Histiocitose Hemofagocítica/epidemiologia , Linfo-Histiocitose Hemofagocítica/genética , Prognóstico , Indução de Remissão , Estudos Retrospectivos , Condicionamento Pré-Transplante , Resultado do Tratamento
20.
PLoS One ; 15(8): e0235503, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32760083

RESUMO

PURPOSE: We evaluated the outcomes of decitabine as first-line treatment in older patients with acute myeloid leukemia (AML) and investigated the predictors, including a baseline mini nutritional assessment short form (MNA-SF) score, of response and survival. PATIENTS AND METHODS: Between 2010 and 2018, 96 AML patients aged 65 and above who received decitabine treatment at 6 centers in Korea were retrospectively evaluated. Response rates, hematologic improvements (HI), progression-free survival (PFS), and overall survival (OS) were analyzed. RESULTS: The median age at diagnosis was 73.9 years, and the median number of decitabine treatments administered to the patients was 4 (range, 1-29). Of 85 patients, 15 patients (17.6%) achieved complete remission (CR) or CR with incomplete blood count recovery. Twelve patients (14.1%) showed partial remission (PR), and 18 (21.2%) demonstrated HI without an objective response. The median PFS and OS were 7.0 (95% confidence interval [CI], 4.9-9.0) and 10.6 (95% CI, 7.7-13.5%) months, respectively. In multivariate analyses, MNA-SF score ≥ 8 and the absence of peripheral blood (PB) blasts were significant predictors for improved PFS and OS. CONCLUSIONS: For older patients with newly diagnosed AML, a high MNA-SF score and the absence of PB blasts were independently associated with improved survival.


Assuntos
Antimetabólitos Antineoplásicos/administração & dosagem , Decitabina/administração & dosagem , Leucemia Mieloide Aguda/tratamento farmacológico , Indução de Remissão/métodos , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Antimetabólitos Antineoplásicos/efeitos adversos , Contagem de Células Sanguíneas , Medula Óssea/patologia , Decitabina/efeitos adversos , Esquema de Medicação , Feminino , Humanos , Leucemia Mieloide Aguda/sangue , Leucemia Mieloide Aguda/mortalidade , Leucemia Mieloide Aguda/patologia , Masculino , Avaliação Nutricional , Intervalo Livre de Progressão , República da Coreia/epidemiologia , Estudos Retrospectivos , Perda de Peso
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