RESUMO
BACKGROUND: The molecular pathogenesis of acute myeloid leukemia (AML) was dramatically clarified over the latest two decades. Several important molecular markers were discovered in patients with AML that have helped to improve the risk stratification. However, developing new treatment strategies for relapsed/refractory acute myeloid leukemia (AML) is crucial due to its poor prognosis. PROCEDURE: To overcome this difficulty, we performed an assay for transposase-accessible chromatin with sequencing (ATAC-seq) in 10 AML patients with various gene alterations. ATAC-seq is based on direct in vitro sequencing adaptor transposition into native chromatin, and is a rapid and sensitive method for integrative epigenomic analysis. ATAC-seq analysis revealed increased accessibility of the DOCK1 gene in patients with AML harboring poor prognostic factors. Following the ATAC-seq results, quantitative reverse transcription polymerase chain reaction was used to measure DOCK1 gene expression levels in 369 pediatric patients with de novo AML. RESULTS: High DOCK1 expression was detected in 132 (37%) patients. The overall survival (OS) and event-free survival (EFS) among patients with high DOCK1 expression were significantly worse than those patients with low DOCK1 expression (3-year EFS: 34% vs. 60%, p < .001 and 3-year OS: 60% vs. 80%, p < .001). To investigate the significance of high DOCK1 gene expression, we transduced DOCK1 into MOLM14 cells, and revealed that cytarabine in combination with DOCK1 inhibitor reduced the viability of these leukemic cells. CONCLUSIONS: Our results indicate that a DOCK1 inhibitor might reinforce the effects of cytarabine and other anti-cancer agents in patients with AML with high DOCK1 expression.
Assuntos
Biomarcadores Tumorais , Leucemia Mieloide Aguda , Humanos , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/mortalidade , Leucemia Mieloide Aguda/patologia , Criança , Masculino , Feminino , Prognóstico , Pré-Escolar , Adolescente , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Lactente , Taxa de Sobrevida , Seguimentos , População do Leste Asiático , Proteínas rac de Ligação ao GTPRESUMO
Innovations in sequencing technology have led to the discovery of novel mutations that cause inherited diseases. However, many patients with suspected genetic diseases remain undiagnosed. Long-read sequencing technologies are expected to significantly improve the diagnostic rate by overcoming the limitations of short-read sequencing. In addition, Oxford Nanopore Technologies (ONT) offers adaptive sampling and computationally driven target enrichment technology. This enables more affordable intensive analysis of target gene regions compared to standard non-selective long-read sequencing. In this study, we developed an efficient computational workflow for target adaptive sampling long-read sequencing (TAS-LRS) and evaluated it through application to 33 genomes collected from suspected hereditary cancer patients. Our workflow can identify single nucleotide variants with nearly the same accuracy as the short-read platform and elucidate complex forms of structural variations. We also newly identified several SINE-R/VNTR/Alu (SVA) elements affecting the APC gene in two patients with familial adenomatous polyposis, as well as their sites of origin. In addition, we demonstrated that off-target reads from adaptive sampling, which is typically discarded, can be effectively used to accurately genotype common single-nucleotide polymorphisms (SNPs) across the entire genome, enabling the calculation of a polygenic risk score. Furthermore, we identified allele-specific MLH1 promoter hypermethylation in a Lynch syndrome patient. In summary, our workflow with TAS-LRS can simultaneously capture monogenic risk variants including complex structural variations, polygenic background as well as epigenetic alterations, and will be an efficient platform for genetic disease research and diagnosis.
RESUMO
Acute Myeloid Leukemia (AML) is the second most common type of leukemia in children. Recent advances in high-resolution genomic profiling techniques have uncovered the mutational landscape of pediatric AML as distinct from adult AML. Overall survival rates of children with AML have dramatically improved in the past 40 years, currently reaching 70% to 80% in developed countries. This was accomplished by the intensification of conventional chemotherapy, improvement in risk stratification using leukemia-specific cytogenetics/molecular genetics and measurable residual disease, appropriate use of allogeneic hematopoietic stem cell transplantation, and improvement in supportive care. However, the principle therapeutic approach for pediatric AML has not changed substantially for decades and improvement in event-free survival is rather modest. Further refinements in risk stratification and the introduction of emerging novel therapies to contemporary therapy, through international collaboration, would be key solutions for further improvements in outcomes.
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Autoimmune lymphoproliferative syndrome (ALPS) is a disease of lymphocyte homeostasis caused by FAS-mediated apoptotic pathway dysfunction and is characterized by non-malignant lymphoproliferation with an increased number of TCRαß+CD4-CD8- double-negative T cells (αßDNTs). Conversely, RAS-associated leukoproliferative disease (RALD), which is caused by gain-of-functional somatic variants in KRAS or NRAS, is considered a group of diseases with a similar course. Herein, we present a 7-year-old Japanese female of RALD harboring NRAS variant that aggressively progressed to juvenile myelomonocytic leukemia (JMML) with increased αßDNTs. She eventually underwent hematopoietic cell transplantation due to acute respiratory distress which was caused by pulmonary infiltration of JMML blasts. In general, αßDNTs have been remarkably increased in ALPS; however, FAS pathway gene abnormalities were not observed in this case. This case with RALD had repeated shock/pre-shock episodes as the condition progressed. This shock was thought to be caused by the presence of a high number of αßDNTs. The αßDNTs observed in this case revealed high CCR4, CCR6, and CD45RO expressions, which were similar to Th17. These increased Th17-like αßDNTs have triggered the inflammation, resulting in the pathogenesis of shock, because Th17 secretes pro-inflammatory cytokines such as interleukin (IL)-17A and granulocyte-macrophage colony-stimulating factor. The presence of IL-17A-secreting αßDNTs has been reported in systemic lupus erythematosus (SLE) and Sjögren's syndrome. The present case is complicated with SLE, suggesting the involvement of Th17-like αßDNTs in the disease pathogenesis. Examining the characteristics of αßDNTs in RALD, JMML, and ALPS may reveal the pathologies in these cases.
Assuntos
Síndrome Linfoproliferativa Autoimune , Lúpus Eritematoso Sistêmico , Transtornos Linfoproliferativos , Feminino , Humanos , Criança , Síndrome Linfoproliferativa Autoimune/diagnóstico , Síndrome Linfoproliferativa Autoimune/genética , Linfócitos T CD4-Positivos , Receptores de Antígenos de Linfócitos T alfa-beta/genéticaRESUMO
BACKGROUND: Second malignant neoplasms (SMNs) are one of the most severe late complications after pediatric cancer treatment. However, the effect of genetic variation on SMNs remains unclear. In this study, we revealed germline genetic factors that contribute to the development of SMNs after treatment of pediatric solid tumors. METHODS: We performed whole-exome sequencing in 14 pediatric patients with SMNs, including three brain tumors. RESULTS: Our analysis revealed that five of 14 (35.7%) patients had pathogenic germline variants in cancer-predisposing genes (CPGs), which was significantly higher than in the control cohort (p < 0.01). The identified genes with variants were TP53 (n = 2), DICER1 (n = 1), PMS2 (n = 1), and PTCH1 (n = 1). In terms of the type of subsequent cancer, leukemia and multiple episodes of SMN had an exceptionally high rate of CPG pathogenic variants. None of the patients with germline variants had a family history of SMN development. Mutational signature analysis showed that platinum drugs contributed to the development of SMN in three cases, which suggests the role of platinum agents in SMN development. CONCLUSIONS: We highlight that overlapping effects of genetic background and primary cancer treatment contribute to the development of second cancers after treatment of pediatric solid tumors. A comprehensive analysis of germline and tumor samples may be useful to predict the risk of secondary cancers.
Assuntos
Neoplasias Encefálicas , Leucemia , Segunda Neoplasia Primária , Criança , Humanos , Segunda Neoplasia Primária/epidemiologia , Segunda Neoplasia Primária/genética , Prevalência , Platina , Neoplasias Encefálicas/complicações , Mutação em Linhagem Germinativa , Predisposição Genética para Doença , Ribonuclease III/genética , RNA Helicases DEAD-box/genéticaRESUMO
6-Mercaptopurine (6-MP) is widely used for the treatment of paediatric leukaemia and lymphoma. Recently, germline variants in the NUDT15 gene have been identified as one of the major genetic causes for 6-MP-associated adverse effects such as myelosuppression. Patients with hypomorphic NUDT15 variants accumulate excessive levels of DNA-incorporated thioguanine in white blood cells, resulting in severe myelosuppression. Although preclinical studies suggest that these variants may influence the protein stability of NUDT15, this has not been directly characterised in patients. In this study, we report the development of a series of novel monoclonal antibodies against NUDT15, using which we quantitatively assessed NUDT15 protein levels in 37 patients with acute lymphoblastic leukaemia treated with 6-MP, using sandwich enzyme-linked immunosorbent assay (ELISA). The NUDT15 genotype was highly correlated with its protein levels (p < 0.0001), with homozygous and compound heterozygous patients showing exceedingly low NUDT15 expression. There was a positive correlation between NUDT15 protein level and 6-MP tolerance (r = 0.631, p < 0.0001). In conclusion, our results point to low NUDT15 protein abundance as the biochemical basis for NUDT15-mediated 6-MP intolerance, thus providing a phenotypic readout of inherited NUDT15 deficiency.
Assuntos
Mercaptopurina , Pirofosfatases , Criança , Humanos , Anticorpos Monoclonais/uso terapêutico , Mercaptopurina/efeitos adversos , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Pirofosfatases/genética , Tioguanina/uso terapêuticoRESUMO
The purpose of this study is to establish a treatment with appropriate intensity for children (<16 years old at diagnosis) with de novo acute myeloid leukemia (excluding acute promyelocytic leukemia and myeloid leukemia associated with Down syndrome) according to a risk stratification based on recurrent leukemic cytogenetic abnormalities and flow-cytometric minimal residual disease at end of initial induction chemotherapy and to validate the safety and efficacy of gemtuzumab ozogamicin (GO)-combined post-induction chemotherapy for the non-low-risk (non-LR) patients. The primary endpoint of this phase III study is three-year disease-free survival rate, which will be compared between the GO and non-GO arms of the non-LR (intermediate-risk and high-risk [HR]) patients. All HR patients will be allocated to allogeneic hematopoietic stem cell transplantation in first remission. This trial has been registered at the Japan Registry of Clinical Trials (jRCTs041210015).
Assuntos
Quimioterapia de Indução , Leucemia Mieloide Aguda , Adolescente , Aminoglicosídeos/efeitos adversos , Anticorpos Monoclonais Humanizados/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Criança , Gemtuzumab , Humanos , Neoplasia Residual/tratamento farmacológico , Medição de RiscoRESUMO
We investigated genome-wide DNA methylation patterns in 64 pediatric patients with acute myeloid leukemia (AML). Based on unsupervised clustering with the 567 most variably methylated cytosine guanine dinucleotide (CpG) sites, patients were categorized into 4 clusters associated with genetic alterations. Clusters 1 and 3 were characterized by the presence of known favorable prognostic factors, such as RUNX1-RUNX1T1 fusion and KMT2A rearrangement with low MECOM expression, and biallelic CEBPA mutations (all 8 patients), respectively. Clusters 2 and 4 comprised patients exhibiting molecular features associated with adverse outcomes, namely internal tandem duplication of FLT3 (FLT3-ITD), partial tandem duplication of KMT2A, and high PRDM16 expression. Depending on the methylation values of the 1243 CpG sites that were significantly different between FLT3-ITD+ and FLT3-ITD- AML, patients were categorized into 3 clusters: A, B, and C. The STAT5-binding motif was most frequently found close to the 1243 CpG sites. All 8 patients with FLT3-ITD in cluster A harbored high PRDM16 expression and experienced adverse events, whereas only 1 of 7 patients with FLT3-ITD in the other clusters experienced adverse events. PRDM16 expression levels were also related to DNA methylation patterns, which were drastically changed at the cutoff value of PRDM16/ABL1 = 0.10. The assay for transposase-accessible chromatin sequencing of AMLs supported enhanced chromatin accessibility around genomic regions, such as HOXB cluster genes, SCHIP1, and PRDM16, which were associated with DNA methylation changes in AMLs with FLT3-ITD and high PRDM16 expression. Our results suggest that DNA methylation levels at specific CpG sites are useful to support genetic alterations and gene expression patterns of patients with pediatric AML.
Assuntos
Metilação de DNA , Leucemia Mieloide Aguda , Criança , Cromatina , Humanos , Leucemia Mieloide Aguda/genética , MutaçãoRESUMO
The effect of genetic variation on second malignant neoplasms (SMNs) remains unclear. First, we identified the pathogenic germline variants in cancer-predisposing genes among 15 children with SMNs after childhood leukemia/lymphoma using whole-exome sequencing. Because the prevalence was low, we focused on the association between SMNs and NUDT15 in primary acute lymphoblastic leukemia (ALL) cases. NUDT15 is one of the 6-mercaptopurine (6-MP) metabolic genes, and its variants are common in East Asian individuals. The prevalence of NUDT15 hypomorphic variants was higher in patients with SMNs (n = 14; 42.9%) than in the general population in the gnomAD database (19.7%; P = .042). In the validation study with a cohort of 438 unselected patients with ALL, the cumulative incidence of SMNs was significantly higher among those with (3.0%; 95% confidence interval [CI], 0.6% to 9.4%) than among those without NUDT15 variants (0.3%; 95% CI, 0.0% to 1.5%; P = .045). The 6-MP dose administered to patients with ALL with a NUDT15 variant was higher than that given to those without SMNs (P = .045). The 6-MP-related mutational signature was observed in SMN specimens after 6-MP exposure. In cells exposed to 6-MP, a higher level of 6-MP induced DNA damage in NUDT15-knockdown induced pluripotent stem cells. Our study indicates that NUDT15 variants may confer a risk of SMNs after treatment with 6-MP in patients with ALL.
Assuntos
Segunda Neoplasia Primária , Leucemia-Linfoma Linfoblástico de Células Precursoras , Antimetabólitos Antineoplásicos/uso terapêutico , Criança , Humanos , Incidência , Segunda Neoplasia Primária/epidemiologia , Segunda Neoplasia Primária/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/epidemiologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Pirofosfatases/genética , Pirofosfatases/uso terapêuticoRESUMO
Human herpesvirus 6 (HHV-6) is one of the life-threatening infectious complications with significant morbidity and mortality following hematopoietic stem cell transplantation (HSCT). Clinically, the diagnosis of HHV-6 encephalitis can be challenging due to a lack of specific symptoms and definitive diagnostic tests. We report a pediatric HSCT recipient who developed late-onset HHV-6 encephalitis without typical radiographic findings. The routine viral infection monitoring protocol contributed to the prompt diagnosis of HHV-6 encephalitis and early therapeutic intervention. The patient was treated successfully without any neurological complications attributable to HHV-6 encephalitis. HHV-6 encephalitis should remain in the differential diagnosis as an important but treatable disease, even for several months after HSCT and even without radiographic findings. Whenever HHV-6 encephalitis is suspected, antivirals should be initiated promptly to prevent its complications.
Assuntos
Antivirais/uso terapêutico , Testes Diagnósticos de Rotina/métodos , Diagnóstico Precoce , Encefalite Viral/diagnóstico , Encefalite Viral/terapia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Herpesvirus Humano 6 , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/terapia , Infecções por Roseolovirus/diagnóstico , Infecções por Roseolovirus/terapia , Criança , Pré-Escolar , Diagnóstico Diferencial , Encefalite Viral/etiologia , Encefalite Viral/virologia , Humanos , Masculino , Complicações Pós-Operatórias/etiologia , Infecções por Roseolovirus/etiologia , Infecções por Roseolovirus/virologia , Transplante HomólogoRESUMO
Some studies have shown that sedative antihistamines prolong febrile seizure duration. Although the collective evidence is still mixed, the Japanese Society of Child Neurology released guidelines in 2015 that contraindicated the use of sedative antihistamines in patients with febrile seizure. Focused on addressing limitations of previous studies, we conducted a cross-sectional study to evaluate the relationship between febrile seizure duration and the use of sedative antihistamines. Data were collected from patients who visited St. Luke's International Hospital due to febrile seizure between August 2013 and February 2016. Patients were divided into groups based on their prescribed medications: sedative antihistamine, nonsedative antihistamine, and no antihistamine. Seizure duration was the primary outcome and was examined using multivariate analyses. Of the 426 patients included, sedative antihistamines were administered to 24 patients. The median seizure duration was approximately 3 minutes in all three groups. There was no statistical difference in the bivariate (p = 0.422) or multivariate analyses (p = 0.544). Our results do not support the relationship between sedative antihistamine use and prolonged duration of febrile seizure. These results suggest that the use of antihistamines may be considered for patients with past history of febrile seizure, when appropriate.
Assuntos
Antagonistas dos Receptores Histamínicos H1/farmacologia , Avaliação de Resultados em Cuidados de Saúde , Convulsões Febris/tratamento farmacológico , Estado Epiléptico/tratamento farmacológico , Adolescente , Adulto , Idoso , Criança , Estudos Transversais , Feminino , Antagonistas dos Receptores Histamínicos H1/administração & dosagem , Humanos , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
Antiseizure prophylaxis is required during busulfan administration for hematopoietic stem cell transplantation. However, antiseizure agents such as benzodiazepines and phenytoin may produce adverse effects through interaction with other drugs. We retrospectively assessed the prophylactic efficacy and safety of levetiracetam and clonazepam against busulfan-induced seizures between 2013 and 2018. Thirty patients (after 2015) received levetiracetam, and 13 patients (before 2015) received clonazepam in this study. Levetiracetam was well-tolerated and had a significantly lower frequency of adverse effects, such as somnolence, compared with clonazepam, although two patients in the levetiracetam group experienced seizures. Levetiracetam is a feasible option for preventing busulfan-induced seizures.
Assuntos
Bussulfano/efeitos adversos , Clonazepam/uso terapêutico , Transplante de Células-Tronco Hematopoéticas , Levetiracetam/uso terapêutico , Convulsões/induzido quimicamente , Convulsões/prevenção & controle , Adolescente , Criança , Pré-Escolar , Clonazepam/administração & dosagem , Feminino , Humanos , Levetiracetam/administração & dosagem , Masculino , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Peripheral blood stem cell transplantation (PBSCT) is being increasingly performed as an alternative to bone marrow transplantation (BMT); however, PBSCT has not been proven to have equivalent outcome to BMT. We conducted a meta-analysis to compare survival rates and treatment-related complications between PBSCT and BMT for pediatric hematologic malignancies. We searched Medline, Embase plus Embase classics, and the Cochrane Central Register of Controlled Trials for the terms "hematopoietic stem cell transplantation" AND "allogeneic transplantation" AND "children", including randomized controlled studies and cohort studies without language limitations. We identified 7 of 5368 studies for inclusion in our meta-analysis. The cohorts of these studies included a total of 4328 patients, 3185 who underwent BMT and 1143 who underwent PBSCT. Five-year overall survival was similar in the 2 groups (PBSCT, 56.2%; BMT, 63.5%; relative risk [RR], 1.17; 95% confidence interval [CI], .91 to 1.52), as was the 5-year event-free survival (PBSCT, 49.9%; BMT, 57.2%; RR, 1.14; 95% CI, .93 to 1.39). The incidences of nonrelapse mortality and chronic graft-versus-host disease were higher in the PBSCT group compared with the BMT group (RR, 1.73; 95% CI, 1.50 to 1.99 versus RR, 1.55; 95% CI, 1.18 to 2.03). This meta-analysis found insufficient evidence to conclude that peripheral blood stem cells are equivalent to bone marrow. The results indicate that bone marrow can still be a preferred donor source for pediatric hematologic malignancies.
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Transplante de Medula Óssea , Doença Enxerto-Hospedeiro , Neoplasias Hematológicas , Transplante de Células-Tronco de Sangue Periférico , Adolescente , Aloenxertos , Criança , Pré-Escolar , Doença Crônica , Intervalo Livre de Doença , Feminino , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/mortalidade , Doença Enxerto-Hospedeiro/prevenção & controle , Neoplasias Hematológicas/mortalidade , Neoplasias Hematológicas/terapia , Humanos , Masculino , Taxa de SobrevidaRESUMO
Acute promyelocytic leukemia (APL) is cytogenetically characterized by the t(15;17) (q24;q21), although cases without this translocation exist. These cases are referred to as "cryptic" or "masked" translocations. Additionally, fewer than 5% of APL cases have another partner gene fused to the RARA gene. The TBL1XR1-RARA fusion gene has recently been reported as a novel RARA-associated fusion gene. We report a case with TBL1XR1-RARA and a masked translocation that was not detected by conventional tests for RARA-associated translocations. Three-year-old girl was diagnosed with APL based morphological findings, although conventional tests for RARA-associated chimeric genes were negative. She received all-trans retinoic acid treatment, but that was not effective. She achieved a complete remission (CR) by conventional multidrug chemotherapy, but had extramedullary relapse 2 years after onset. She underwent cord blood transplantation (CBT) in her second CR and is currently alive. To investigate the underlying pathogenesis of this unique case, we performed whole-genome sequencing and found a cryptic insertion of RARA gene into the TBL1XR1 gene. The transcript of the chimeric gene, TBL1XR1-RARA, was confirmed as an in-frame fusion by RT-PCR. In conclusion, we found using next-generation sequencing (NGS) a TBL1XR1-RARA fusion in a child with variant APL without the classic karyotype. Cryptic insertion could also occur in cases other than APL with PML-RARA. Variant APL has many variants and NGS analysis should therefore be considered for APL variant cases, even for those without RARA translocation detected by conventional analysis.
Assuntos
Leucemia Promielocítica Aguda/genética , Receptores Citoplasmáticos e Nucleares/genética , Proteínas Repressoras/genética , Receptor alfa de Ácido Retinoico/genética , Pré-Escolar , Feminino , Fusão Gênica/genética , Humanos , Mutação INDEL/genética , Cariótipo , Cariotipagem , Leucemia Promielocítica Aguda/metabolismo , Proteína da Leucemia Promielocítica/genética , Receptores Citoplasmáticos e Nucleares/metabolismo , Proteínas Repressoras/metabolismo , Receptor alfa de Ácido Retinoico/metabolismo , Translocação Genética/genética , Sequenciamento Completo do GenomaAssuntos
Actinina/genética , Histona-Lisina N-Metiltransferase/genética , Proteína de Leucina Linfoide-Mieloide/genética , Proteínas de Fusão Oncogênica/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras B/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras B/patologia , Humanos , Lactente , PrognósticoRESUMO
Infant acute lymphoblastic leukemia with lysine (K)-specific methyltransferase 2A (KMT2A) rearrangements usually has a poor prognosis regardless of the fusion partners of KMT2A. However, the prognosis of pediatric acute myeloid leukemia (AML) with KMT2A rearrangements depends on its translocation partners. We herein report the case of a 9-month-old boy with a KMT2A-USP2 fusion, which required diagnosis by whole transcriptome sequencing after the failure of detection of known translocation partners by conventional screening approaches. As this first report of a patient with AML with a KMT2A-USP2 fusion illustrates, identification of the partners in all patients with KMT2A-rearranged AML is critical to elucidate the outcomes associated with specific rearrangements and to develop appropriate treatment strategies. Moreover, development of additional methods to detect specific translocation partners of KMT2A and leukemia-specific targeting drugs is important to improve further the outcomes of KMT2A-rearranged AML.
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Endopeptidases/genética , Histona-Lisina N-Metiltransferase/genética , Leucemia Mieloide Aguda/genética , Proteína de Leucina Linfoide-Mieloide/genética , Fusão Oncogênica , Transcriptoma , Humanos , Lactente , Leucemia Mieloide Aguda/patologia , Masculino , Ubiquitina TiolesteraseRESUMO
BACKGROUND: Varicella zoster virus (VZV) disease is a common complication after hematopoietic cell transplantation (HCT). The mortality rate for disseminated VZV infection is 34%. Acyclovir has been used for the prophylaxis of VZV disease after HCT, but the effectiveness of prophylaxis is controversial. We conducted a meta-analysis of the incidence of VZV disease within the first 1 year after acyclovir prophylaxis had been discontinued and assessed the risk of VZV disease during acyclovir prophylaxis. METHODS: Medline, EMBASE plus EMBASE classics, and the Cochrane Central Register of Controlled Trials were used for a systematic search. The inclusion criteria were both randomized controlled trials and cohort studies that described the effectiveness of acyclovir as prophylaxis against VZV disease after allogeneic HCT. RESULTS: We included seven studies involving a total of 2265 patients. No mortality by VZV was identified. Acyclovir prophylaxis significantly reduced the rate of VZV infection within the first 1 year after discontinuation (risk ratio: 0.38, 95% confidence interval (CI): 0.29-0.51). The risk of VZV disease during acyclovir prophylaxis was also reduced (risk ratio: 0.17, 95% CI: 0.12-0.24). Both short-term and long-term prophylaxis reduced the incidence of VZV infection (RR: 0.51, 95% CI: 0.30-0.86 vs RR: 0.34, 95% CI: 0.22-0.54). Low-dose acyclovir (<400 mg/d) is sufficient to reduce the risk of VZV disease. CONCLUSION: This study showed that acyclovir prophylaxis reduced VZV infection after HCT with no fatal cases and acyclovir prophylaxis is beneficial. No significant adverse effects occurred and no delayed VZV disease was identified.