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1.
Medicine (Baltimore) ; 99(35): e21376, 2020 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-32871864

RESUMO

BACKGROUND: COVID-19 is an international outbreak of the respiratory illness caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The diseases themselves, as well as the intensity of chemotherapy, lead to significant immunosuppression, leading hematological malignancy patients susceptible to infections. METHODS: This protocol will be performed according to the Meta-analysis of Observational Studies in Epidemiology (MOOSE) guidelines and reported follow the Cochrane Collaboration Handbook and the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. Electronic databases of PubMed, MEDLINE, Google Scholar, Web of science, Cochrane Library, EMBASE, CNKI, CMB, and Wangfang database from the inception to present will be comprehensively and systematically searched without limitations of language, date, and publication status. Observational, retrospective cohort, prospective case-control, cohort studies, cross-sectional studies, or clinical trials will be included. All assessment of study selection, data extraction, and study quality assessment will be independently performed by 2 reviewers. RevMan V.5.3 program and Stata V.12.0 software will be utilized for the methodological quality assessment and statistical analysis. RESULTS: The result of this systematic review will provide evidence for clinicians on the management of COVID-19 patients with hematological malignancy. CONCLUSION: This systematic review will help raise awareness and guide management of COVID-19 patients with hematological malignancy, as well as to improve outcomes in this population. ETHIC AND DISSEMINATION: The content of this article does not involve moral approval or ethical review because no individual data will be collected. PROSPERO REGISTRATION: CRD42020187493.


Assuntos
Antineoplásicos/farmacologia , Infecções por Coronavirus , Neoplasias Hematológicas , Pandemias , Administração dos Cuidados ao Paciente/métodos , Pneumonia Viral , Betacoronavirus , Comorbidade , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/terapia , Neoplasias Hematológicas/epidemiologia , Neoplasias Hematológicas/imunologia , Neoplasias Hematológicas/terapia , Humanos , Pneumonia Viral/epidemiologia , Pneumonia Viral/terapia , Projetos de Pesquisa , Revisões Sistemáticas como Assunto
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
7.
Lancet Haematol ; 7(9): e690-e696, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32791043

RESUMO

People living with HIV are a global population with increased cancer risk but their access to modern immunotherapies for cancer treatment has been limited by socioeconomic factors and inadequate research to support safety and efficacy in this population. These immunotherapies include immune checkpoint inhibitors and advances in cellular immunotherapy, particularly chimeric antigen receptor (CAR) T-cell therapy. Despite the field of cancer immunotherapy rapidly expanding with ongoing clinical trials, people with HIV are often excluded from such trials. In 2019, post-approval evaluation of anti-CD19 CAR T-cell therapy in people with HIV and aggressive B-cell lymphoma showed the feasibility of CAR T-cell therapy for cancer in this excluded group. Along with expanded treatment options for people with HIV is the ability to assess the effects of immunotherapy on the latent HIV reservoir, with certain immunotherapies showing the ability to alleviate this burden. This Series paper addresses the increased cancer burden in people with HIV, the increasing evidence for the safety and efficacy of immunotherapies in the context of HIV and cancer, and opportunities for novel applications of CAR-T therapy for the treatment of both haematological malignancies and HIV.


Assuntos
Infecções por HIV/patologia , Neoplasias Hematológicas/terapia , Receptores de Antígenos Quiméricos/metabolismo , Linfócitos T/transplante , Antígenos CD19/imunologia , Terapia Baseada em Transplante de Células e Tecidos , Infecções por HIV/complicações , Neoplasias Hematológicas/complicações , Neoplasias Hematológicas/mortalidade , Humanos , Imunoterapia Adotiva , Taxa de Sobrevida , Linfócitos T/citologia , Linfócitos T/metabolismo
8.
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
9.
Lancet HIV ; 7(9): e641-e651, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32791045

RESUMO

People living with HIV or AIDS are at increased risk of Hodgkin and non-Hodgkin lymphoma compared with HIV-negative individuals. Data on the risk of multiple myeloma or leukaemia are inconsistent and of low quality but the risk does not seem to be increased. Specific haematological malignancies occur in different contexts of age, CD4 cell count, HIV control, viral co-infections, or chronic inflammation, and the expansion of combination antiretroviral therapy has led to varied demographic and epidemiological shifts among people with HIV. Increased use of combination antiretroviral therapy has substantially reduced the risks of diffuse large B-cell lymphoma, Burkitt lymphoma, and primary CNS lymphoma, and to a lesser extent, Hodgkin lymphoma. There is no effect of combination antiretroviral therapy use on multiple myeloma or leukaemia. Although many cases of HIV are in low-income and middle-income countries, high-quality epidemiological data for haematological malignancies from these regions are scarce. Closing this gap is an essential first step in decreasing mortality from HIV-associated haematological malignancies worldwide. Finally, although multicentric Castleman disease is not a neoplastic condition, it is an emerging precursor to neoplastic high-grade B-cell lymphoproliferation among people with HIV, especially for individuals on long-term combination antiretroviral therapy with well controlled HIV.


Assuntos
Infecções por HIV/complicações , Infecções por HIV/epidemiologia , Neoplasias Hematológicas/complicações , Neoplasias Hematológicas/epidemiologia , Infecções por HIV/diagnóstico , Infecções por HIV/tratamento farmacológico , Soropositividade para HIV , Neoplasias Hematológicas/diagnóstico , Neoplasias Hematológicas/terapia , Humanos , Incidência , Vigilância em Saúde Pública
10.
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
11.
Lancet Haematol ; 7(10): e737-e745, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32798473

RESUMO

BACKGROUND: Several small studies on patients with COVID-19 and haematological malignancies are available showing a high mortality in this population. The Italian Hematology Alliance on COVID-19 aimed to collect data from adult patients with haematological malignancies who required hospitalisation for COVID-19. METHODS: This multicentre, retrospective, cohort study included adult patients (aged ≥18 years) with diagnosis of a WHO-defined haematological malignancy admitted to 66 Italian hospitals between Feb 25 and May 18, 2020, with laboratory-confirmed and symptomatic COVID-19. Data cutoff for this analysis was June 22, 2020. The primary outcome was mortality and evaluation of potential predictive parameters of mortality. We calculated standardised mortality ratios between observed death in the study cohort and expected death by applying stratum-specific mortality rates of the Italian population with COVID-19 and an Italian cohort of 31 993 patients with haematological malignancies without COVID-19 (data up to March 1, 2019). Multivariable Cox proportional hazards model was used to identify factors associated with overall survival. This study is registered with ClinicalTrials.gov, NCT04352556, and the prospective part of the study is ongoing. FINDINGS: We enrolled 536 patients with a median follow-up of 20 days (IQR 10-34) at data cutoff, 85 (16%) of whom were managed as outpatients. 440 (98%) of 451 hospitalised patients completed their hospital course (were either discharged alive or died). 198 (37%) of 536 patients died. When compared with the general Italian population with COVID-19, the standardised mortality ratio was 2·04 (95% CI 1·77-2·34) in our whole study cohort and 3·72 (2·86-4·64) in individuals younger than 70 years. When compared with the non-COVID-19 cohort with haematological malignancies, the standardised mortality ratio was 41·3 (38·1-44·9). Older age (hazard ratio 1·03, 95% CI 1·01-1·05); progressive disease status (2·10, 1·41-3·12); diagnosis of acute myeloid leukaemia (3·49, 1·56-7·81), indolent non-Hodgin lymphoma (2·19, 1·07-4·48), aggressive non-Hodgkin lymphoma (2·56, 1·34-4·89), or plasma cell neoplasms (2·48, 1·31-4·69), and severe or critical COVID-19 (4·08, 2·73-6·09) were associated with worse overall survival. INTERPRETATION: This study adds to the evidence that patients with haematological malignancies have worse outcomes than both the general population with COVID-19 and patients with haematological malignancies without COVID-19. The high mortality among patients with haematological malignancies hospitalised with COVID-19 highlights the need for aggressive infection prevention strategies, at least until effective vaccination or treatment strategies are available. FUNDING: Associazione italiana contro le leucemie, linfomi e mieloma-Varese Onlus.


Assuntos
Betacoronavirus , Infecções por Coronavirus/epidemiologia , Neoplasias Hematológicas/epidemiologia , Pandemias , Pneumonia Viral/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Comorbidade , Infecções por Coronavirus/tratamento farmacológico , Feminino , Seguimentos , Neoplasias Hematológicas/terapia , Humanos , Pacientes Internados , Itália/epidemiologia , Leucemia/epidemiologia , Leucemia/terapia , Linfoma não Hodgkin/epidemiologia , Linfoma não Hodgkin/terapia , Masculino , Pessoa de Meia-Idade , Transtornos Mieloproliferativos/epidemiologia , Transtornos Mieloproliferativos/terapia , Neoplasias de Plasmócitos/epidemiologia , Neoplasias de Plasmócitos/terapia , Estudos Retrospectivos , Fatores de Risco , Adulto Jovem
12.
Cancer Treat Rev ; 89: 102071, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32717620

RESUMO

Haplo-identical transplant is being increasingly used in patients who do not have a readily available matched related or unrelated donor. Post-transplant cyclophosphamide's use due to its simplicity and documented efficacy has made this approach readily employable across diverse transplant centres across the globe. The outcomes of regimens used for conditioning in recipients of bone marrow are at times in variance to that from more commonly employed G-CSF mobilised peripheral stem cell (PBSC). This review highlights various conditioning regimens used in PBSC recipients, with emphasis on toxicities, practicalities and transplant related outcomes of relapse, non-relapse mortality and graft versus host disease.


Assuntos
Ciclofosfamida/administração & dosagem , Fator Estimulador de Colônias de Granulócitos/farmacologia , Neoplasias Hematológicas/terapia , Transplante de Células-Tronco de Sangue Periférico/métodos , Células-Tronco de Sangue Periférico/efeitos dos fármacos , Condicionamento Pré-Transplante/métodos , Haplótipos , Mobilização de Células-Tronco Hematopoéticas/métodos , Imunossupressores/administração & dosagem , Células-Tronco de Sangue Periférico/citologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Transplante Homólogo
13.
Cancer Sci ; 111(9): 3367-3378, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32619037

RESUMO

Although next-generation sequencing-based panel testing is well practiced in the field of cancer medicine for the identification of target molecules in solid tumors, the clinical utility and clinical issues surrounding panel testing in hematological malignancies have yet to be fully evaluated. We conducted a multicenter prospective clinical sequencing study to verify the feasibility of a panel test for hematological tumors, including acute myeloid leukemia, acute lymphoblastic leukemia, multiple myeloma, and diffuse large B-cell lymphoma. Out of 96 eligible patients, 79 patients (82%) showed potentially actionable findings, based on the clinical sequencing assays. We identified that genetic alterations with a strong clinical significance were found at a higher frequency in terms of diagnosis (n = 60; 63%) and prognosis (n = 61; 64%) than in terms of therapy (n = 8; 8%). Three patients who harbored a germline mutation in either DDX41 (n = 2) or BRCA2 (n = 1) were provided with genetic counseling. At 6 mo after sequencing, clinical actions based on the diagnostic (n = 5) or prognostic (n = 3) findings were reported, but no patients were enrolled in a clinical trial or received targeted therapies based on the sequencing results. These results suggest that panel testing for hematological malignancies would be feasible given the availability of useful diagnostic and prognostic information. This study is registered with the UMIN Clinical Trial Registry (UMIN000029879, multiple myeloma; UMIN000031343, adult acute myeloid leukemia; UMIN000033144, diffuse large B-cell lymphoma; and UMIN000034243, childhood leukemia).


Assuntos
Biomarcadores Tumorais , Estudos de Associação Genética , Predisposição Genética para Doença , Neoplasias Hematológicas/diagnóstico , Neoplasias Hematológicas/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Biologia Computacional/métodos , Feminino , Estudos de Associação Genética/métodos , Testes Genéticos , Mutação em Linhagem Germinativa , Neoplasias Hematológicas/terapia , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Adulto Jovem
14.
Curr Res Transl Med ; 68(3): 111-118, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32620465

RESUMO

The pandemic of coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is spreading rapidly across the world. Currently, the COVID-19 pandemic is affecting the continuity of essential routine healthcare services and procedures, including chimeric antigen receptor T-cell (CAR-T) therapy, a life-saving option for patients with relapsed/refractory (R/R) hematologic malignancies. Due to the rapid disease progression of hematological malignancies, there is an urgent need to manufacture and utilize CAR T-cells. However, CAR-T treatment has become extraordinarily challenging during this COVID-19 pandemic. Thus, many medical and technical factors must now be taken into consideration before, during, and after CAR-T therapy. The purpose of this review is to provide brief suggestions for rational decision-making strategies in evaluating and selecting CAR T-cell treatment and appropriate CAR T-cell products, and protective strategies for medical staff and patients to prevent infection in the midst of the current COVID-19 pandemic.


Assuntos
Infecções por Coronavirus/prevenção & controle , Assistência à Saúde/organização & administração , Neoplasias Hematológicas/terapia , Imunoterapia Adotiva , Controle de Infecções/organização & administração , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Receptores de Antígenos de Linfócitos T/imunologia , Betacoronavirus/fisiologia , Infecções por Coronavirus/epidemiologia , Assistência à Saúde/métodos , Assistência à Saúde/normas , Assistência à Saúde/tendências , Neoplasias Hematológicas/epidemiologia , Humanos , Imunoterapia Adotiva/métodos , Imunoterapia Adotiva/tendências , Controle de Infecções/métodos , Controle de Infecções/normas , Controle de Infecções/tendências , Pneumonia Viral/epidemiologia , Serviços Preventivos de Saúde/métodos , Serviços Preventivos de Saúde/organização & administração , Serviços Preventivos de Saúde/normas , Serviços Preventivos de Saúde/tendências
15.
Lancet HIV ; 7(9): e602-e610, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32649866

RESUMO

BACKGROUND: Allogeneic blood or marrow transplantation (alloBMT) is a potentially life-saving treatment for individuals with HIV and haematological malignancies; challenges include identifying donors and maintaining antiretroviral therapy (ART). The objectives of our study were to investigate interventions to expand donor options and to prevent ART interruptions for patients with HIV in need of alloBMT. METHODS: This single-arm, interventional trial took place at the Johns Hopkins Sidney Kimmel Comprehensive Cancer Center (Baltimore, MD, USA). Individuals with HIV who were at least 18 years of age and referred for alloBMT for a standard clinical indication were eligible. The only exclusion criterion was a history of documented resistance to enfuvirtide. We used post-transplant cyclophosphamide as graft-versus-host disease (GVHD) prophylaxis to expand donor options and an optimised ART strategy of avoiding pharmacoenhancers and adding subcutaneous enfuvirtide during post-transplant cyclophosphamide and during oral medication intolerance. Our primary outcome was the proportion of participants who maintained ART through day 60 after alloBMT. We measured the HIV latent reservoir using a quantitative viral outgrowth assay. This study is registered on ClinicalTrials.gov, NCT01836068. FINDINGS: Between June 1, 2013, and August 27, 2015, nine patients who were referred for transplant provided consent. Two patients had relapsed malignancy before donor searches were initiated. Seven patients had suitable donors identified (two matched sibling, two matched unrelated, two haploidentical, and one single-antigen mismatched unrelated) and proceeded to alloBMT. All patients maintained ART through day 60 and required ART changes (median 1, range 1-3) in the first 90 days. One patient stopped ART and developed HIV rebound with grade 4 meningoencephalitis at day 146. Among six patients who underwent alloBMT and had longitudinal measurements available, the HIV latent reservoir was not detected post-alloBMT in four patients with more than 95% donor chimerism, consistent with a 2·06-2·54 log10 reduction in the HIV latent reservoir. In the two patients with less than 95% donor chimerism, the HIV latent reservoir remained stable. INTERPRETATION: By using post-transplant cyclophosphamide as GVHD prophylaxis, we successfully expanded alloBMT donor options for patients with HIV. Continuing ART with a regimen that includes enfuvirtide post-alloBMT was safe, but life-threatening viral rebound can occur with ART interruption. FUNDING: amfAR (the Foundation for AIDS Research), Johns Hopkins University Center for AIDS Research, and National Cancer Institute.


Assuntos
Transplante de Medula Óssea , Ciclofosfamida/uso terapêutico , Infecções por HIV/complicações , Neoplasias Hematológicas/complicações , Neoplasias Hematológicas/terapia , Adulto , Terapia Antirretroviral de Alta Atividade , Transplante de Medula Óssea/efeitos adversos , Transplante de Medula Óssea/métodos , Terapia Combinada , Ciclofosfamida/administração & dosagem , Ciclofosfamida/efeitos adversos , Estudos de Viabilidade , Feminino , Doença Enxerto-Hospedeiro/diagnóstico , Doença Enxerto-Hospedeiro/etiologia , Infecções por HIV/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade , Condicionamento Pré-Transplante , Transplante Homólogo , Resultado do Tratamento , Carga Viral
19.
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
20.
Ann Hematol ; 99(8): 1883-1893, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32572523

RESUMO

In allogeneic hematopoietic stem cell transplantation recipients, cytomegalovirus (CMV) infection can cause overt CMV-associated disease, which is a main cause of transplantation-associated mortality. CMV infection correlates closely with donor's type. We therefore examined whether risk factors of CMV reactivation and clinical endpoints in patients with hematologic malignancies after allogeneic peripheral blood stem cell transplantation (PBSCT) differed between using matched-sibling donors (MSD-SCT) and haploidentical donors (HID-SCT). In this retrospective cohort study, we enrolled in 200 consecutive patients received an unmanipulated G-CSF-mobilized allogeneic PBSCT. Ninety (45%) patients received MSD-SCT and 110 (55%) received HID-SCT. Quantitative PCR was used for monitoring of CMV reactivation after transplantation. One-year cumulative incidence of CMV DNAemia was 55.0%, ranging from 23.5% in MSD-SCT group to 81.0% in HID-SCT group (p < 0.001). Although univariate analyses showed that non-myeloid malignancies, disease in complete remission status at transplantation, pretreatment with antithymocyte globulin, HLA-haploidentical donors, male donors, previous Epstein-Barr virus DNAemia, and absolute lymphocyte count on day 30 < 0.6 × 109/L were respectively associated with CMV reactivation after transplantation in total cohort of recipients (all p < 0.05), haploidentical donors were found to be the only independent predictor in multivariate analyses (Hazard ratio = 6.4, p < 0.001). Furthermore, univariate analyses revealed that non-myeloid malignancies and previous Epstein-Barr virus DNAemia were respectively associated with CMV reactivation in MSD-SCT recipients, and female was associated with CMV reactivation in HID-SCT recipients (all p < 0.05). In HID-SCT recipients, but not MSD-SCT recipients, previous CMV DNAemia was associated with a lower cumulative incidence of acute graft-versus-host disease (49.2% vs. 72.6%, p < 0.001). CMV DNAemia did not play a role in the relapse rate, but it was strongly associated with an increased risk of non-relapse mortality either in total cohort of recipients (30.5% vs. 13.7%; p = 0.003) or in the HID-SCT subgroup (36.0% vs. 16.7%; p = 0.030). Relapse-free survival and overall survival in total cohort of recipients with CMV DNAemia were both inferior to those without CMV DNAemia (45.3% vs. 57.6% and 54.8% vs. 65.8%, respectively; both p < 0.05). However, in subgroup analysis according to donor's type, neither relapse-free survival nor overall survival was impacted by CMV status (both p > 0.05). This study addressed differences in incidence, risk factors, and associations with clinical outcomes of CMV reactivation after haploidentical versus matched-sibling PBSCT.


Assuntos
Infecções por Citomegalovirus/mortalidade , Citomegalovirus/fisiologia , Neoplasias Hematológicas , Transplante de Células-Tronco de Sangue Periférico , Irmãos , Ativação Viral , Adolescente , Adulto , Aloenxertos , Criança , Intervalo Livre de Doença , Feminino , Neoplasias Hematológicas/mortalidade , Neoplasias Hematológicas/terapia , Neoplasias Hematológicas/virologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida
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