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2.
Anticancer Res ; 40(10): 5707-5713, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32988896

RESUMO

BACKGROUND/AIM: Genetic variations of the non-coding RNA gene, ANRIL, have been associated with human diseases including cancer, type-2 diabetes, and atherosclerosis. In the present study, we investigated the potential associations of select ANRIL single nucleotide polymorphisms (SNPs) with overall survival and other clinical outcomes in adult patients with hematologic malignancies after allogeneic hematopoietic stem cell transplantation (allo-HSCT). PATIENTS AND METHODS: Genomic DNA was extracted from whole blood samples from 103 adult patients with hematologic malignancies who had received allo-HSCT followed by oral tacrolimus therapy. The genotypes of four select ANRIL SNPs, rs564398, rs1063192, rs2151280, and rs2157719 were determined using qRT-PCR-based genotyping assays. RESULTS: rs2151280 (C->T) in ANRIL was associated with worse overall survival in these patients (CT/CC vs. TT). Contrarily, rs2151280 and the other select ANRIL SNPs were not associated with death at Day-100 after transplantation, the incidence of graft-versus-host disease (GVHD), acute kidney injury (AKI), and neurotoxicity in the study cohort. CONCLUSION: rs2151280 represents a potential prognostic biomarker for overall survival in adult patients with hematologic malignancies after allo-HSCT.


Assuntos
Estudos de Associação Genética , Predisposição Genética para Doença , Neoplasias Hematológicas/genética , RNA Longo não Codificante/genética , Lesão Renal Aguda/etiologia , Lesão Renal Aguda/genética , Lesão Renal Aguda/patologia , Idoso , Feminino , Genótipo , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/genética , Doença Enxerto-Hospedeiro/patologia , Neoplasias Hematológicas/complicações , Neoplasias Hematológicas/patologia , Neoplasias Hematológicas/terapia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Intervalo Livre de Progressão , Tacrolimo/farmacocinética , Transplante Homólogo/efeitos adversos
3.
Anticancer Res ; 40(10): 5909-5917, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32988922

RESUMO

BACKGROUND/AIM: Cytomegalovirus (CMV) replication may cause life-threatening complications after allogeneic haematopoietic stem cell transplantation (allo-HSCT). The aim of the study was to characterize CMV events, and the outcome of letermovir (LTV) CMV prophylaxis. PATIENTS AND METHODS: In this retrospective analysis of patients treated with an allo-HSCT between 2010 and 2020, we determined plasma CMV events, as well as associated risk factors. RESULTS: We identified 423 patients who had undergone allo-HSCT between 2010 and 2020. CMV DNAemia was found in 130/423 (30.7%) of patients. CMV reactivation rate was significantly higher in patients with acute graft-versus-host disease, HLA mismatch, and CMV IgG seropositivity of donors and recipients. Among 42 patients receiving LTV prophylaxis those, 5 (11.9%) showed CMV DNAemia under LTV versus 87/353 (24.6%) in a control group. CONCLUSION: Despite the development of better approaches with weekly monitoring and early treatment initiation, CMV reactivations play an important role after allo-HSCT.


Assuntos
Acetatos/administração & dosagem , Infecções por Citomegalovirus/tratamento farmacológico , Citomegalovirus/efeitos dos fármacos , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Quinazolinas/administração & dosagem , Adulto , Idoso , Citomegalovirus/patogenicidade , Infecções por Citomegalovirus/sangue , Infecções por Citomegalovirus/etiologia , Infecções por Citomegalovirus/virologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Transplante Homólogo/efeitos adversos , Replicação Viral/efeitos dos fármacos
5.
Medicine (Baltimore) ; 99(31): e21431, 2020 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-32756151

RESUMO

RATIONALE: The use of autologous hematopoietic stem cell transplantation (AHSCT) for autoimmune diseases has become the first indication for transplant in nonmalignant disease. Mucormycosis is a rare invasive infection with increasing incidence in patients treated with AHSCT. We report the first case of pulmonary mucormycosis following AHSCT for systemic sclerosis (SSc). PATIENT CONCERNS: A 24-year-old woman with rapidly progressive diffuse cutaneous SSc presented with an acute respiratory distress syndrome 6 days after AHSCT. DIAGNOSES: The results of clinical and computed tomography scan were consistent with pulmonary mucormycosis and the diagnosis was confirmed by a positive Mucorales Polymerase Chain Reaction on a peripheral blood sample. INTERVENTIONS AND OUTCOMES: Early antifungal therapy by intravenous amphotericin B provided rapid improvement within 4 days and sustained recovery after 2 years of follow-up. LESSONS: With the progressively increasing use of AHSCT and other stem cell therapy for treatment of severe SSc and other autoimmune diseases, the potential onset of rare post-transplant fungal infections, such as mucormycosis, requires careful patient monitoring and better awareness of early initiation of adequate therapy.


Assuntos
Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Mucormicose/etiologia , Esclerodermia Difusa/etiologia , Escleroderma Sistêmico/terapia , Transplante Autólogo/efeitos adversos , Doença Aguda , Administração Intravenosa , Assistência ao Convalescente , Anfotericina B/administração & dosagem , Anfotericina B/uso terapêutico , Antifúngicos/administração & dosagem , Antifúngicos/uso terapêutico , Feminino , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Pneumopatias Fúngicas/diagnóstico por imagem , Pneumopatias Fúngicas/microbiologia , Pneumopatias Fúngicas/patologia , Mucorales/genética , Síndrome do Desconforto Respiratório do Adulto/etiologia , Esclerodermia Difusa/patologia , Transplante Autólogo/métodos , Resultado do Tratamento , Adulto Jovem
6.
Medicine (Baltimore) ; 99(34): e21571, 2020 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-32846764

RESUMO

Post-transplantation cyclophosphamide (PTCy) and antithymocyte-globulin (ATG) are the most commonly used regimens for prophylaxis of graft-versus-host disease (GVHD). We compared these 2 regimens in human leukocyte antigen (HLA)-matched unrelated donor hematopoietic stem cell transplantation (HSCT) patients with hematological malignancies. We retrospectively analyzed consecutive adult patients with hematological malignancies who underwent HLA-matched unrelated donor-HSCT at Chungnam National University Hospital (Daejeon, South Korea) between January 2013 and January 2019. Patients who received a second transplantation or who had refractory disease were excluded. We included 34 patients (12 and 22 in the PTCy and ATG groups respectively). All graft sources were peripheral blood stem cells. The estimated 20-month overall survival rates were 75.0% for PTCy and 81.6% for ATG patients (P = .792), and the 20-month relapse rates were 41.7% and 34.3% (P = .491), respectively. The cumulative incidences of grade 2 to 4 acute GVHD were 16.7% and 30.6% (P = .551), respectively; the estimated 20-month limited and extensive chronic GVHD rates were 59.1% and 78.8% (P = .718), respectively; and the estimated 20-month extensive chronic GVHD rates were 12.5% and 16.7% (P = .718), respectively. The neutrophil engraftment time was similar in both groups [median (range), 15.0 (12.0-17.0) and 14.0 (12.0-19.0) days, respectively; P = .961]. However, ATG was more expensive than PTCy [median (range), US$4,062 (US$2,215-6,647) for ATG vs US$51.80 (US$43.20-69.20) for PTCy; P < .001]. In conclusion, PTCy and ATG afforded similar clinical outcomes after HLA-matched unrelated donor transplantation but PTCy was less expensive.


Assuntos
Soro Antilinfocitário/uso terapêutico , Ciclofosfamida/uso terapêutico , Doença Enxerto-Hospedeiro/prevenção & controle , Imunossupressores/uso terapêutico , Adolescente , Adulto , Idoso , Feminino , Doença Enxerto-Hospedeiro/etiologia , Neoplasias Hematológicas/mortalidade , Neoplasias Hematológicas/terapia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , República da Coreia/epidemiologia , Estudos Retrospectivos , Adulto Jovem
7.
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
8.
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
9.
Virology ; 548: 168-173, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32838938

RESUMO

Clinical significance of the cytomegalovirus (CMV) genotypes in patients undergoing allogeneic hematopoietic stem cell transplant (HSCT) has been evaluated mostly in adults. The studies of diverse CMV glycoprotein B (gB) and N (gN) genotype variants in transplanted children and adolescents are lacking. We analyzed the investment of gB and gN genotype variants in the HSCTed children and their relation to clinical complications and disease outcome. The cohort included forty two pediatric recipients of the HSCT. Patients positive for CMV DNAemia (24/42, 57.1%) were genotyped. The gB4 and gN1 genotype variants predominated and were evidenced in 7/18 (38.9%) and 9/19 (47.4%) patients, respectively. The graft-versus-host disease (GvHD) predominated in children with viremia (p < 0.05). Frequencies of the gB and gN genotypes contrasted those reported in recent studies. The GvHD scaled strongly with CMV reactivation whereas viral loads were uncorrelated to medical complications and treatment outcomes.


Assuntos
Infecções por Citomegalovirus/virologia , Citomegalovirus/isolamento & purificação , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Complicações Pós-Operatórias/virologia , Proteínas do Envelope Viral/genética , Adolescente , Adulto , Criança , Pré-Escolar , Estudos de Coortes , Citomegalovirus/classificação , Citomegalovirus/genética , Citomegalovirus/metabolismo , Feminino , Genótipo , Doença Enxerto-Hospedeiro/virologia , Humanos , Masculino , Transplante Homólogo/efeitos adversos , Proteínas do Envelope Viral/metabolismo , Adulto Jovem
10.
Dermatol Online J ; 26(6)2020 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-32815687

RESUMO

To date, only twenty cases of cutaneous legionellosis have been reported. Cutaneous legionellosis has heterogeneous manifestations including abscesses, nodules, and cellulitis. The detection of most cutaneous Legionella species requires specific diagnostic cultures and assays. Herein, we report a case of cutaneous legionella in a hematopoietic cell transplantation recipient with culture-negative nodules unresponsive to empiric antibiotics. We also discuss the varied morphology of cutaneous legionellosis and important diagnostic considerations.


Assuntos
Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Hospedeiro Imunocomprometido , Legionella , Legionelose/patologia , Dermatopatias Bacterianas/patologia , Adulto , Idoso , Antibacterianos/uso terapêutico , Criança , Diagnóstico Diferencial , Feminino , Humanos , Legionella/isolamento & purificação , Legionelose/diagnóstico , Legionelose/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Dermatopatias Bacterianas/diagnóstico , Dermatopatias Bacterianas/tratamento farmacológico
11.
Lancet HIV ; 7(9): e652-e660, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32791046

RESUMO

Haemopoietic cell transplantation is established as a standard treatment approach for people living with HIV who have haematological malignancies with poor prognosis. Studies with autologous and allogeneic haemopoietic cell transplantation suggest that HIV status does not adversely affect outcomes, provided that there is adequate infection prophylaxis. Attention to possible drug-drug interactions is important. Allogeneic haemopoietic cell transplantation substantially reduces the long-term HIV reservoir when complete donor chimerism is established. When transplants from CCR5Δ32 homozygous donors are used, HIV cure is possible.


Assuntos
Infecções por HIV/complicações , Transplante de Células-Tronco Hematopoéticas , Terapia Antirretroviral de Alta Atividade , Gerenciamento Clínico , Suscetibilidade a Doenças , Predisposição Genética para Doença , Doença Enxerto-Hospedeiro/etiologia , Infecções por HIV/tratamento farmacológico , Infecções por HIV/imunologia , Infecções por HIV/virologia , Neoplasias Hematológicas/complicações , Neoplasias Hematológicas/terapia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/métodos , Homozigoto , Humanos , Mutação , Receptores CCR5 , Transplante Autólogo , Transplante Homólogo , Resultado do Tratamento
12.
Nat Commun ; 11(1): 3617, 2020 07 17.
Artigo em Inglês | MEDLINE | ID: mdl-32680998

RESUMO

Multiple myeloma (MM) progression is characterized by the seeding of cancer cells in different anatomic sites. To characterize this evolutionary process, we interrogated, by whole genome sequencing, 25 samples collected at autopsy from 4 patients with relapsed MM and an additional set of 125 whole exomes collected from 51 patients. Mutational signatures analysis showed how cytotoxic agents introduce hundreds of unique mutations in each surviving cancer cell, detectable by bulk sequencing only in cases of clonal expansion of a single cancer cell bearing the mutational signature. Thus, a unique, single-cell genomic barcode can link chemotherapy exposure to a discrete time window in a patient's life. We leveraged this concept to show that MM systemic seeding is accelerated at relapse and appears to be driven by the survival and subsequent expansion of a single myeloma cell following treatment with high-dose melphalan therapy and autologous stem cell transplant.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Evolução Clonal/efeitos dos fármacos , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Mieloma Múltiplo/patologia , Recidiva Local de Neoplasia/patologia , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/genética , Progressão da Doença , Relação Dose-Resposta a Droga , Humanos , Masculino , Melfalan/administração & dosagem , Melfalan/efeitos adversos , Pessoa de Meia-Idade , Mieloma Múltiplo/diagnóstico por imagem , Mieloma Múltiplo/genética , Mieloma Múltiplo/terapia , Mutação/efeitos dos fármacos , Invasividade Neoplásica/genética , Invasividade Neoplásica/patologia , Recidiva Local de Neoplasia/diagnóstico por imagem , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/terapia , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Análise de Célula Única , Análise Espaço-Temporal , Transplante Autólogo/efeitos adversos , Sequenciamento Completo do Genoma
14.
Gulf J Oncolog ; 1(33): 7-18, 2020 May.
Artigo em Inglês | MEDLINE | ID: covidwho-485461

RESUMO

The outbreak of coronavirus disease 2019 (COVID-19) has become a public health emergency of major international concern. In December 2019, an outbreak of atypical pneumonia known as COVID-19 was identified in Wuhan, China. The newly identified zoonotic coronavirus, severe acute respiratory syndrome coronavirus-2 (SARSCoV-2), is characterized by rapid human-to-human transmission. Acute lymphoblastic leukemia (ALL) patients are often in need for intensive chemotherapy to induce remission that will be complicated with prolonged period of cytopenias. They are often recalled to the hospital for treatment and disease surveillance. These patients may be immunocompromised due to the underlying malignancy or anti-cancer therapy. ALL patients are at higher risk of developing life-threatening infections. Several factors increase the risk of infection and the presence of multiple risk factors in the same patient is common. Cancer patients had an estimated 2-fold increased risk of contracting SARS-CoV-2 than the general population. With the World Health Organization declaring the novel coronavirus outbreak a pandemic, there is an urgent need to address the impact of such pandemic on ALL patients. This include changes to resource allocation, clinical care, and the consent process during a pandemic. Currently and due to limited data, there are no international guidelines to address the optimal management of ALL patients in any infectious pandemic. In this review, we will address the potential challenges associated with managing ALL patients during the COVID-19 infection pandemic with suggestions of some practical approaches, focusing on screening asymptomatic ALL patients, diagnostic and response evaluation and choice of chemotherapy in different scenarios and setting and use of hematopoietic stem cell transplantation (HSCT).


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Betacoronavirus/patogenicidade , Infecções por Coronavirus/virologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Hospedeiro Imunocomprometido , Infecções Oportunistas/virologia , Pneumonia Viral/virologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Betacoronavirus/imunologia , Tomada de Decisão Clínica , Técnicas de Laboratório Clínico , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/transmissão , Procedimentos Clínicos , Técnicas de Apoio para a Decisão , Humanos , Infecções Oportunistas/diagnóstico , Infecções Oportunistas/imunologia , Infecções Oportunistas/transmissão , Pandemias , Pneumonia Viral/diagnóstico , Pneumonia Viral/imunologia , Pneumonia Viral/transmissão , Leucemia-Linfoma Linfoblástico de Células Precursoras/imunologia , Medição de Risco , Fatores de Risco
15.
Gulf J Oncolog ; 1(33): 7-18, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32476644

RESUMO

The outbreak of coronavirus disease 2019 (COVID-19) has become a public health emergency of major international concern. In December 2019, an outbreak of atypical pneumonia known as COVID-19 was identified in Wuhan, China. The newly identified zoonotic coronavirus, severe acute respiratory syndrome coronavirus-2 (SARSCoV-2), is characterized by rapid human-to-human transmission. Acute lymphoblastic leukemia (ALL) patients are often in need for intensive chemotherapy to induce remission that will be complicated with prolonged period of cytopenias. They are often recalled to the hospital for treatment and disease surveillance. These patients may be immunocompromised due to the underlying malignancy or anti-cancer therapy. ALL patients are at higher risk of developing life-threatening infections. Several factors increase the risk of infection and the presence of multiple risk factors in the same patient is common. Cancer patients had an estimated 2-fold increased risk of contracting SARS-CoV-2 than the general population. With the World Health Organization declaring the novel coronavirus outbreak a pandemic, there is an urgent need to address the impact of such pandemic on ALL patients. This include changes to resource allocation, clinical care, and the consent process during a pandemic. Currently and due to limited data, there are no international guidelines to address the optimal management of ALL patients in any infectious pandemic. In this review, we will address the potential challenges associated with managing ALL patients during the COVID-19 infection pandemic with suggestions of some practical approaches, focusing on screening asymptomatic ALL patients, diagnostic and response evaluation and choice of chemotherapy in different scenarios and setting and use of hematopoietic stem cell transplantation (HSCT).


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Betacoronavirus/patogenicidade , Infecções por Coronavirus/virologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Hospedeiro Imunocomprometido , Infecções Oportunistas/virologia , Pneumonia Viral/virologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Betacoronavirus/imunologia , Tomada de Decisão Clínica , Técnicas de Laboratório Clínico , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/transmissão , Procedimentos Clínicos , Técnicas de Apoio para a Decisão , Humanos , Infecções Oportunistas/diagnóstico , Infecções Oportunistas/imunologia , Infecções Oportunistas/transmissão , Pandemias , Pneumonia Viral/diagnóstico , Pneumonia Viral/imunologia , Pneumonia Viral/transmissão , Leucemia-Linfoma Linfoblástico de Células Precursoras/imunologia , Medição de Risco , Fatores de Risco
16.
Ann Hematol ; 99(7): 1655-1665, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32524200

RESUMO

Second allogeneic hematopoietic stem cell transplantation (allo-HSCT) has a low survival outcome and a high non-relapse mortality (NRM) rate which is a major obstacle to this treatment. We hypothesized that the status of malnourishment after first allo-HSCT as represented by the geriatric nutritional risk index (GNRI) could be used as a prognostic factor to determine the outcomes of second allo-HSCT. A total of 108 patients with a median age of 42 (range, 17-69) years, who received second allo-HSCT for disease recurrence after first allo-HSCT from our institution, were included in this study. Low GNRI had a significant impact on NRM at 2 years after second allo-HSCT: 56.9% in patients with GNRI ≤ 92 compared with 27.5% in patients with GNRI > 92 (P = 0.002). In multivariate analysis, GNRI of ≤ 92 was the only significant factor for NRM (hazard ratio [HR] 2.29, 95% confidence interval [CI] 1.15-4.56, P = 0.018). High-risk disease status at second allo-HSCT (HR 2.74, 95% CI 1.46-5.14, P = 0.002) and GNRI of ≤ 92 (HR 1.70, 95% CI 1.02-2.82, P = 0.042) were identified as significant factors for overall survival (OS). A score of 1 was assigned to each factor, and the OS rate at 2 years after second allo-HSCT decreased according to the score: 53.0% in patients with score 0, 32.3% with score 1, and 2.5% with score 2 (P < 0.001). In conclusion, GNRI could be a useful predictor for the outcomes of second allo-HSCT. A prospective study in other cohorts is warranted to validate the findings of our study.


Assuntos
Avaliação Geriátrica/métodos , Neoplasias Hematológicas/diagnóstico , Neoplasias Hematológicas/terapia , Transplante de Células-Tronco Hematopoéticas , Desnutrição/diagnóstico , Estado Nutricional , Adolescente , Adulto , Idoso , Feminino , Doença Enxerto-Hospedeiro/complicações , Doença Enxerto-Hospedeiro/diagnóstico , Doença Enxerto-Hospedeiro/mortalidade , Indicadores Básicos de Saúde , Neoplasias Hematológicas/mortalidade , Neoplasias Hematológicas/patologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Masculino , Desnutrição/etiologia , Desnutrição/mortalidade , Desnutrição/patologia , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Recidiva , Retratamento/efeitos adversos , Retratamento/métodos , Estudos Retrospectivos , Fatores de Risco , Análise de Sobrevida , Transplante Homólogo/efeitos adversos , Transplante Homólogo/métodos , Adulto Jovem
18.
BMC Infect Dis ; 20(1): 400, 2020 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-32503449

RESUMO

BACKGROUND: Pneumocystis carinii pneumonia (PCP) prophylaxis is recommended after hematopoietic stem cell transplantation (HSCT). In patients who are unable to take first-line prophylaxis, trimethoprim/sulfamethoxazole, aerosolized pentamidine is recommended. This drug may not, however, be available at all institutions, and its administration requires special techniques. Therefore, intravenous pentamidine (IVP) has been used in adult patients as an alternative, despite limited data. We evaluated the effectiveness and tolerability of IVP for PCP prophylaxis in adult patients who had undergone HSCT. METHODS: A single-center retrospective study was conducted of adult patients who had undergone allogenic or autologous HSCT between January 2014 and September 2018 and had received at least three doses of IVP for PCP prophylaxis. The IVP dose was 4 mg/kg administered monthly. Data on PCP infection and adverse reactions were collected from both patients' electronic medical records and the pharmacy adverse drug reactions documentation system. Patients were followed from the start of IVP up to 6 months after discontinuation of therapy. A confirmed PCP infection was defined as radiographic evidence of PCP and positive staining of a respiratory specimen. Descriptive statistics were used to analyze the study outcomes. RESULTS: During the study period, 187 patients were included. The median age was 36.4 years (range, 18-64), 58% were male, and 122 (65%) had received allogeneic HSCT while the remainder autologous HSCT. The median number of IVP doses administered per patient was 5 (range, 3-29). During the study period, none of the patients had evidence of confirmed PCP infection. However; there were two cases with high clinical suspicion of PCP infection (i.e. required anti-pneumocystis therapy) and one reported case of central nervous system toxoplasmosis while receiving IVP for PCP prophylaxis. Only one case of nausea associated with IVP administration was reported. CONCLUSIONS: In a cohort of adult patients with HSCT who received IVP for PCP prophylaxis, there was no evidence of confirmed PCP infection, and the treatment appeared to be well tolerated. Prospective studies should be conducted to confirm the efficacy and tolerability of IVP.


Assuntos
Antifúngicos/uso terapêutico , Pentamidina/uso terapêutico , Pneumonia por Pneumocystis/prevenção & controle , Adolescente , Adulto , Antifúngicos/efeitos adversos , Antifúngicos/farmacologia , Comorbidade , Feminino , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Infusões Intravenosas , Masculino , Pessoa de Meia-Idade , Pentamidina/efeitos adversos , Pentamidina/farmacologia , Pneumocystis carinii/efeitos dos fármacos , Pneumonia por Pneumocystis/diagnóstico , Pneumonia por Pneumocystis/microbiologia , Estudos Retrospectivos , Transplante Autólogo , Transplante Homólogo , Adulto Jovem
19.
J Cancer Res Clin Oncol ; 146(11): 2967-2978, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32507973

RESUMO

PURPOSE: This study investigated the frequency and characteristics of sarcopenia among patients after allogeneic hematopoietic stem cell transplantation (allo-HSCT) with a specific focus on the chronic graft-versus-host disease (cGVHD) population and its association with malnutrition, vitamin D and clinical characteristics. METHODS: We assessed sarcopenia, vitamin D levels, and nutritional status in 73 patients who underwent allo-HSCT, of which 45 were diagnosed with cGVHD. Sarcopenia was diagnosed according to the European Working Group on Sarcopenia in Older People (EWGSOP) criteria. RESULTS: Sarcopenia was diagnosed in 19.2% of patients after allo-HSCT with statistically no significant difference between cGVHD and non-cGVHD patients. The risk factor for sarcopenia was the male gender. Sarcopenia in allo-HSCT patients correlated strongly with malnutrition and with current corticosteroid treatment (p < 0.005). Among cGVHD patients sarcopenia additionally correlated strongly with the number of prior systemic immunosuppressive therapy lines (p < 0.005) and moderately with the intensity of immunosuppression, cGVHD severity global rating assessed by both the health care provider and the patient and joint and fascia cGVHD involvement (p < 0.05). Vitamin D deficiency was found in more than 54.8% of patients, but the correlation to sarcopenia was not found. CONCLUSION: Sarcopenia was found to be common in long term survivors of allo-HSCT independently of the cGVHD diagnosis. Prospective longitudinal studies are needed for a better understanding of factors affecting the development of sarcopenia after allo-HSCT.


Assuntos
Doença Enxerto-Hospedeiro/epidemiologia , Doença Enxerto-Hospedeiro/etiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Sarcopenia/epidemiologia , Adulto , Idoso , Aloenxertos , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estado Nutricional , Sarcopenia/etiologia , Vitamina D/sangue , Adulto Jovem
20.
Farm. hosp ; 44(3): 87-91, mayo-jun. 2020. tab
Artigo em Espanhol | IBECS | ID: ibc-192339

RESUMO

OBJETIVO: Medir la adherencia a la profilaxis del fallo secundario del implante (ciclosporina, tacrolimus, sirolimus), de la enfermedad injerto contra receptor (ciclosporina, tacrolimus, sirolimus, micofenolato) y de las infecciones (posaconazol, voriconazol, valganciclovir) en el paciente sometido a trasplante alogénico de progenitores hematopoyéticos. Compa-rar la incidencia de complicaciones agudas en función de la adherencia.MÉTODO: Estudio observacional retrospectivo en pacientes sometidos a trasplante alogénico de progenitores hematopoyéticos desde mayo de 2017 hasta mayo de 2018, entre el día 0 y +100 postrasplante. La adherencia a micofenolato, tacrolimus, sirolimus, posaconazol, voriconazol y valganciclovir se evaluó mediante los registros de dispensación del servicio de farmacia, siempre que fuera posible. Se definió como paciente adherente aquel con un porcentaje de adherencia igual o superior al 95%. La evaluación de la adherencia a ciclosporina se realizó mediante medida de los niveles plasmáticos. Se definió como paciente no adherente aquel cuyos niveles plasmáticos de ciclosporina fueran inferiores a 100 ng/ml en alguna medida entre los días 0 y +100, en ausencia de factores asociados que lo justificaran. La asociación entre adherencia e incidencia de complicaciones agudas (fallo secundario del implante, enfermedad injerto contra receptor aguda e infección) se estimó mediante la odds ratio y su intervalo de confianza del 95%. RESULTADOS: Se incluyó a 46 pacientes. Todos comenzaron profilaxis inmunosupresora con ciclosporina; en el 8,7% se cambió a tacrolimus o sirolimus por toxicidad. Todos los pacientes recibieron ciclosporina para la profilaxis de la enfermedad injerto contra receptor. En el 41,3% de los casos también se administró micofenolato. El 82,6% fueron adherentes a la profilaxis del fallo de injerto. En cuanto a la profilaxis de enfermedad injerto contra receptor, resultó adherente el 80,4%. Todos los pacientes resultaron adherentes a la profilaxis infecciosa. La incidencia de enfermedad injerto contra receptor aguda de los pacientes adherentes a la profilaxis fue del 45,9% frente al 55,6% en los no adherentes (odds ratio 0,68; intervalo de confianza del 95% 0,157-2,943; p = 0,718). CONCLUSIONES: Los pacientes sometidos a trasplante alogénico de progenitores hematopoyéticos presentan una aceptable adherencia a la profilaxis de complicaciones agudas, pero existe un considerable porcentaje de pacientes que no toman su tratamiento adecuadamente. La correcta adherencia a los inmunosupresores parece disminuir el riesgo de sufrir enfermedad injerto contra receptor aguda


OBJECTIVE: To measure adherence to cyclosporine, tacrolimus and siroli-mus prophylaxis against secondary graft failure; cyclosporine, tacrolimus, sirolimus and mycophenolate prophylaxis against graft-versus-host disease; and posaconazole, voriconazole, valganciclovir prophylaxis against infec-tion in patients undergo to transplantation of haematopoietic stem cells; and to analise the incidence of acute complications based on adherence.METHOD: Retrospective observational study of patients who underwent allo-geneic haematopoietic stem cell transplantation between May 2017 and May 2018. Analyses were carried out between 0 and +100 days post-engraftment.Whenever possible, adherence to mycophenolate, tacrolimus, sirolimus, posaconazole, voriconazole and valganciclovir was evaluated by means of the dispensation records of the Pharmacy Department of our hospital. To be considered adherent, patients should have proved an adherence rate equal to or higher than 95%. Adherence to cyclosporine was determi-ned based on serum levels. Patients were considered to be non-adherent if their cyclosporine serum concentrations dropped below 100 ng/mL at any time between days 0 and +100, in the absence of any specific justifying circumstances. The association between adherence and the incidence of acute complications (secondary graft failure, acute graft-versus-host disease and infection) was determined by means of the odds ratio (confidence interval: 95%). RESULTS: The study sample was made up by 46 patients, all of whom were started on immunosuppressive cyclosporine prophylaxis; 8.7% needed to be switched to tacrolimus or sirolimus due to toxicity issues. All the pa-tients received cyclosporine as prophylaxis against graft-versus-host disea-se. Mycophenolate was also administered in 41.3% of cases. A total of 82.6% patients were found to be adherent to their prophylaxis treatment against graft failure and 80.4% were found to be adherent to prophylaxis against graft-versus-host disease. All patients were adherent to anti-infection prophylaxis. The incidence of acute graft-versus-host disease in prophylaxis-adherent patients was 45.9%, compared with 55.6% for non-adherent pa-tients (odds ratio 0.68; confidence interval: 95% 0.157-2.943; p = 0.718). CONCLUSIONS: Patients undergoing allogeneic haematopoietic stem cell transplantation demonstrated acceptable adherence to prophylaxis aga-inst acute complications, although a considerable percentage of patients was found not to take their medication as prescribed. Correct adherence to immunosuppressants seems to reduce the risk of developing acute graft-versus-host disease


Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Cooperação e Adesão ao Tratamento , Transplante Homólogo , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Doença Enxerto-Hospedeiro/tratamento farmacológico , Ciclosporina/uso terapêutico , Estudos Retrospectivos , Tacrolimo/uso terapêutico , Sirolimo/uso terapêutico , Assistência Farmacêutica , Razão de Chances , Intervalos de Confiança , Imunossupressores/uso terapêutico , Antibioticoprofilaxia
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