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The prevalence of mixed hepatitis C virus (HCV) genotype infection in a representative Canadian HCV cohort is reported and virological response with direct acting antiviral (DAA) treatment was evaluated. 3272 HCV-positive participants were enrolled, of which 2945 (90.0%) initiated DAA therapy. 0.8% were identified with mixed genotype infection. Overall sustained virological response (SVR) was 99.1% and did not differ based on mixed genotype status. Any historical disadvantage to achieving cure with HCV treatment in mixed genotype infection has been overcome by current DAA regimens.
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Sinusoidal obstruction syndrome/veno-occlusive disease (SOS/VOD) is a life-threatening complication which can develop after haemopoietic stem cell transplantation (HSCT) and some antibody-drug conjugates. Several SOS/VOD diagnostic and management guidelines exist, with the most recent and refined being the European Society for Blood and Marrow Transplantation adult and paediatric guidelines. Timely diagnosis and effective management (including the availability of therapeutic options) significantly contribute to improved patient outcomes. In Australia and New Zealand, there is variability in clinical practice and access to SOS/VOD therapies. This review aims to summarise the current evidence for SOS/VOD diagnosis, prevention and treatment and to provide recommendations for SOS/VOD in the context of contemporary Australasian HSCT clinical practice.
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Patients with post-haemopoietic stem cell transplant or chimeric antigen receptor T -cell (CAR-T) therapy face a significant risk of morbidity and mortality from coronavirus disease 2019 because of their immunosuppressed state. As case numbers in Australia and New Zealand continue to rise, guidance on management in this high-risk population is needed. Whilst we have learned much from international colleagues who faced high infection rates early in the pandemic, guidance relevant to local health system structures, medication availability and emerging therapies is essential to equip physicians to manage our patients optimally.
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COVID-19 , Transplante de Células-Tronco Hematopoéticas , Receptores de Antígenos Quiméricos , Humanos , Receptores de Antígenos Quiméricos/uso terapêutico , Nova Zelândia/epidemiologia , Linfócitos TRESUMO
BACKGROUND: ABL-class fusions including NUP214-ABL1 and EBF1-PDGFRB occur in high risk acute lymphoblastic leukaemia (ALL) with gene expression patterns similar to BCR-ABL-positive ALL. Our aim was to evaluate new DNA-based measurable residual disease (MRD) tests detecting these fusions and IKZF1-deletions in comparison with conventional immunoglobulin/T-cell receptor (Ig/TCR) markers. METHODS: Precise genomic breakpoints were defined from targeted or whole genome next generation sequencing for ABL-fusions and BCR-ABL1. Quantitative PCR assays were designed and used to re-measure MRD in remission bone marrow samples previously tested using Ig/TCR markers. All MRD testing complied with EuroMRD guidelines. RESULTS: ABL-class patients had 46% 5year event-free survival and 79% 5year overall survival. All had sensitive fusion tests giving high concordance between Ig/TCR and ABL-class fusion results (21 patients, n = 257 samples, r2 = 0.9786, P < 0.0001) and Ig/TCR and IKZF1-deletion results (9 patients, n = 143 samples, r2 = 0.9661, P < 0.0001). In contrast, in BCR-ABL1 patients, Ig/TCR and BCR-ABL1 tests were discordant in 32% (40 patients, n = 346 samples, r2 = 0.4703, P < 0.0001) and IKZF1-deletion results were closer to Ig/TCR (25 patients, n = 176, r2 = 0.8631, P < 0.0001). CONCLUSIONS: MRD monitoring based on patient-specific assays detecting gene fusions or recurrent assays for IKZF1-deletions is feasible and provides good alternatives to Ig/TCR tests to monitor MRD in ABL-class ALL.
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Proteínas de Fusão bcr-abl , Leucemia-Linfoma Linfoblástico de Células Precursoras , Criança , Proteínas de Fusão bcr-abl/genética , Humanos , Imunoglobulinas , Neoplasia Residual/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Receptores de Antígenos de Linfócitos T/genéticaRESUMO
To achieve the World Health Organization's goal of eliminating hepatitis C (HCV) by 2030 requires enhanced HCV testing and treatment among people who use drugs (PWUD). Micro-elimination of HCV is a strategy to target HCV testing and treatment efforts to specific segments of the population. From February to December 2018 nurses initiated a "seek & treat" micro-elimination approach, increasing outreach and removing barriers to accessing HCV treatment in a clinic setting by testing and treating individuals, including PWUD, where they live. The aim of this study was to evaluate the proportion of clients with HCV antibodies and HCV RNA and the response to direct acting agent (DAA therapy) among people who live at or have social connections to local supportive housing sites through this nurse-led micro-elimination project in Victoria, Canada. A chart review of electronic medical records and case management documentation was used to collect relevant data of participants treated with DAA therapy, identified through specific housing site testing and outreach interventions. In total, 180 people were tested for HCV antibodies, 72 (40%) were antibody positive: 51 (28%) were RNA positive, 13 (7%) had spontaneously cleared and 8 (4%) had been previously treated. Of the 51 that were currently living with HCV, 43 people were started on treatment, 39 have achieved sustained virologic response (SVR). By providing treatment to clients in their homes and with their friends, clinicians have been able to treat clients, including those with limited contact with the health care system.
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Usuários de Drogas , Hepatite C Crônica , Hepatite C , Abuso de Substâncias por Via Intravenosa , Antivirais/uso terapêutico , Hepacivirus , Hepatite C/tratamento farmacológico , Hepatite C/prevenção & controle , Anticorpos Anti-Hepatite C/uso terapêutico , Hepatite C Crônica/tratamento farmacológico , Habitação , Humanos , Papel do Profissional de Enfermagem , RNA/uso terapêutico , Abuso de Substâncias por Via Intravenosa/complicaçõesRESUMO
BACKGROUND: The aim of this analysis was to calculate the incidence of hepatitis C virus (HCV) reinfection and associated factors among 2 clinical trials of HCV direct-acting antiviral treatment in people with recent injecting drug use or currently receiving opioid agonist therapy (OAT). METHODS: Participants who achieved an end-of-treatment response in 2 clinical trials of people with recent injecting drug use or currently receiving OAT (SIMPLIFY and D3FEAT) enrolled between March 2016 and February 2017 in 8 countries were assessed for HCV reinfection, confirmed by viral sequencing. Incidence was calculated using person-time of observation and associated factors were assessed using Cox proportional hazard models. RESULTS: Seventy-three percent of the population at risk of reinfection (n = 177; median age, 48 years; 73% male) reported ongoing injecting drug use. Total follow-up time at risk was 254 person-years (median, 1.8 years; range, 0.2-2.8 years). Eight cases of reinfection were confirmed for an incidence of 3.1/100 person-years (95% confidence interval [CI], 1.6-6.3) overall and 17.9/100 person-years (95% CI, 5.8-55.6) among those who reported sharing needles/syringes. Younger age and needle/syringe sharing were associated with HCV reinfection. CONCLUSIONS: These data demonstrate the need for ongoing monitoring and improved strategies to prevent HCV reinfection following successful treatment among people with ongoing injecting drug use to achieve HCV elimination. CLINICAL TRIALS REGISTRATION: NCT02336139 and NCT02498015.
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Hepatite C Crônica , Hepatite C , Preparações Farmacêuticas , Abuso de Substâncias por Via Intravenosa , Antivirais/uso terapêutico , Feminino , Hepacivirus , Hepatite C/tratamento farmacológico , Hepatite C/epidemiologia , Hepatite C Crônica/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva , Reinfecção , Abuso de Substâncias por Via Intravenosa/complicações , Abuso de Substâncias por Via Intravenosa/tratamento farmacológicoRESUMO
We report on the Australian experience of blinatumomab for treatment of 24 children with relapsed/refractory precursor B-cell acute lymphoblastic leukaemia (B-ALL) and high-risk genetics, resulting in a minimal residual disease (MRD) response rate of 58%, 2-year progression-free survival (PFS) of 39% and 2-year overall survival of 63%. In total, 83% (n = 20/24) proceeded to haematopoietic stem cell transplant, directly after blinatumomab (n = 12) or following additional salvage therapy (n = 8). Four patients successfully received CD19-directed chimeric antigen receptor T-cell therapy despite prior blinatumomab exposure. Inferior 2-year PFS was associated with MRD positivity (20%, n = 15) and in KMT2A-rearranged infants (15%, n = 9). Our findings highlight that not all children with relapsed/refractory B-ALL respond to blinatumomab and factors such as blast genotype may affect prognosis.
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Anticorpos Biespecíficos/uso terapêutico , Antineoplásicos/uso terapêutico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Austrália , Criança , Feminino , Humanos , Masculino , Recidiva Local de Neoplasia/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia , Estudos Retrospectivos , Resultado do TratamentoRESUMO
INTRODUCTION: Viral infections pose a serious risk for children undergoing hematopoietic stem cell transplant (HSCT). There are few published case series of prevalence, risk factors, and outcomes examining multiple viruses simultaneously, and no pediatric Australasian data published to date. We describe the real-life experience of viremia in pediatric HSCT in a single tertiary center. METHODS: All episodes of viremia in children undergoing HSCT between 2000 and 2018 were identified by matching HSCT patients' unique identification numbers with positive blood polymerase chain reaction (PCR) results for human adenovirus (HAdV), cytomegalovirus (CMV), Epstein-Barr virus (EBV), and human herpes virus 6 (HHV-6). Paper or electronic charts and electronic pathology results were used to extract the study variables. RESULTS: Viremia was detected in 177/445 (39.8%) HSCT episodes, of which 46% were allogeneic and 19% autologous transplants. Viremia was disseminated in 96 (21.6%) episodes, with 80 (18%) having more than one virus. HAdV was detected in 108 (24.3% of total episodes) and frequently in autologous transplants, CMV in 71 (16.0%), EBV in 60 (13.5%), and HHV-6 in 38 (8.5%). Of 174 children, 19 (10.9%) died of a viral-associated cause, with viral mortality highest in CMV (18.3%), lowest in HHV-6 (2.6%) with HAdV and EBV similar (6.6% and 6.7%). Adenoviral (but not other virus) dissemination was significantly associated with lower lymphocyte count at time of first detection. CMV dissemination and death were significantly associated with initial and highest CMV viral loads (copies/mL). CONCLUSION: This study presents the first pediatric-specific Australasian data for viremia in HSCT. Findings may help guide clinicians in prophylaxis and treatment decisions.
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Infecções por Citomegalovirus , Infecções por Vírus Epstein-Barr , Transplante de Células-Tronco Hematopoéticas , Transplante de Medula Óssea , Criança , Infecções por Citomegalovirus/epidemiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Herpesvirus Humano 4 , Humanos , Estudos Retrospectivos , Transplante Homólogo , Viremia/epidemiologiaRESUMO
Population-based cancer registries (PBCRs) generate measures of cancer incidence and survival that are essential for cancer surveillance, research, and cancer control strategies. In 2014, the Toronto Paediatric Cancer Stage Guidelines were developed to standardise how PBCRs collect data on the stage at diagnosis for childhood cancer cases. These guidelines have been implemented in multiple jurisdictions worldwide to facilitate international comparative studies of incidence and outcome. Robust stratification by risk also requires data on key non-stage prognosticators (NSPs). Key experts and stakeholders used a modified Delphi approach to establish principles guiding paediatric cancer NSP data collection. With the use of these principles, recommendations were made on which NSPs should be collected for the major malignancies in children. The 2014 Toronto Stage Guidelines were also reviewed and updated where necessary. Wide adoption of the resultant Paediatric NSP Guidelines and updated Toronto Stage Guidelines will enhance the harmonisation and use of childhood cancer data provided by PBCRs.
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Guias como Assunto/normas , Neoplasias/terapia , Pediatria/tendências , Prognóstico , Criança , Atenção à Saúde , Humanos , Estadiamento de Neoplasias , Neoplasias/epidemiologia , Sistema de RegistrosRESUMO
BACKGROUND: This study investigated adherence and associated factors among people with recent injection drug use (IDU) or current opioid agonist therapy (OAT) and compared once-daily to twice-daily hepatitis C virus (HCV) direct-acting antiviral (DAA) therapy. METHODS: SIMPLIFY and D3FEAT are international, multicenter studies that recruited participants with recent IDU (previous 6 months; SIMPLIFY, D3FEAT) or current OAT (D3FEAT) between March 2016 and February 2017 in 8 countries. Participants received sofosbuvir/velpatasvir (once daily; SIMPLIFY) or paritaprevir/ritonavir/ombitasvir, dasabuvir (twice daily) ± ribavirin (D3FEAT) for 12 weeks administered in electronic blister packs. We evaluated overall adherence (proportion of prescribed doses taken) and nonadherence (<90% adherent) between dosing patterns. RESULTS: Of 190 participants, 184 (97%) completed treatment. Median adherence was 92%, with higher adherence among those receiving once-daily vs twice-daily therapy (94% vs 87%, P = .005). Overall, 40% of participants (n = 76) were nonadherent (<90% adherent). Recent stimulant injecting (odds ratio [OR], 2.48 [95% confidence interval {CI}, 1.28-4.82]), unstable housing (OR, 2.18 [95% CI, 1.01-4.70]), and twice-daily dosing (OR, 2.81 [95% CI, 1.47-5.36]) were associated with nonadherence. Adherence decreased during therapy. Sustained virologic response was high in nonadherent (89%) and adherent populations (95%, P = .174), with no difference in SVR between those who did and did not miss 7 consecutive doses (92% vs 93%, P = .897). CONCLUSIONS: This study demonstrated high adherence to once- and twice-daily DAA therapy among people with recent IDU or currently receiving OAT. Nonadherence described did not impact treatment outcomes, suggesting forgiveness to nonadherence.
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Hepatite C Crônica , Hepatite C , Preparações Farmacêuticas , Analgésicos Opioides/uso terapêutico , Anilidas/uso terapêutico , Antivirais/uso terapêutico , Quimioterapia Combinada , Hepacivirus , Hepatite C/tratamento farmacológico , Hepatite C Crônica/tratamento farmacológico , Humanos , Ribavirina/uso terapêutico , Resposta Viral SustentadaRESUMO
Total body irradiation (TBI)/cyclophosphamide (CY) is a standard-of-care conditioning regimen in allogeneic hematopoietic stem cell transplant (HSCT) for pediatric acute lymphoblastic leukemia (ALL). This study sought to identify whether the addition of thiotepa (TT) to TBI/CY improves HSCT outcomes for pediatric patients with ALL. A retrospective analysis was performed on 347 pediatric ALL patients who underwent HSCT between 1995 and 2015, with 242 receiving TBI/CY/TT and 105 patients receiving TBI/CY. There were no statistical differences in age, donor source, or complete remission status between the 2 groups. Comparison of the TBI/CY/TT versus TBI/CY groups demonstrated no difference in transplant-related mortality at 1 (11% versus 11%), 5 (13% versus 16%), or 10 years (16% versus 16%). There was lower relapse in the TBI/CY/TT group at 1 (14% versus 26%), 5 (24% versus 36%), 10 (26% versus 37%), and 15 years (26% versus 37%) (P= .02) but was not statistically significant on multivariate analysis. The TBI/CY/TT group showed a trend toward improved disease-free survival (DFS) at 5 (59% versus 47%), 10 (56% versus 46%), and 15 years (49% versus 40%) (P = .05) but was not statistically significant on multivariate analysis. Comparing overall survival at 5 (62% versus 53%), 10 (57% versus 50%), and 15 years (50% versus 44%) demonstrated no statistical difference between the 2 groups. The addition of thiotepa to TBI/CY demonstrated no increase in transplant-related mortality for pediatric ALL HSCT but was unable to demonstrate significant benefit in disease control. Minimal residual disease status remained the key risk factor impacting both relapse and DFS. More studies are warranted to better clarify the benefits of using thiotepa in conditioning for ALL HSCT.
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Transplante de Células-Tronco Hematopoéticas , Leucemia-Linfoma Linfoblástico de Células Precursoras , Criança , Ciclofosfamida/uso terapêutico , Intervalo Livre de Doença , Humanos , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Estudos Retrospectivos , Tiotepa , Condicionamento Pré-Transplante , Irradiação Corporal TotalRESUMO
BACKGROUND AND AIMS: Double balloon enteroscopy (DBE) has revolutionised the diagnosis and treatment of small bowel (SB) conditions. However, deep SB insertion can be challenging in patients with a history of abdominal surgery and a two-step procedure is required when findings are not amenable to endoscopic therapy. This case series reports the development of laparoscopically assisted DBE (LA-DBE) using single incision laparoscopic surgery (SILS). METHODS: Retrospective review of LA-DBE procedures performed in a single tertiary centre over 6 years. RESULTS: Seventeen patients (median age: 40 years, male 41%) underwent 17 LA-DBE procedures. The approach was oral in 13 and rectal in 4. Laparoscopic approach was standard (multi-port) in the first four cases, SILS was then used in all subsequent patients (13/17). Indications for LA-DBE were previously failed standard DBE (n = 16) and need for a combined procedure (n = 1). Indications for DBE were Peutz-Jeghers syndrome (PJS) (n = 10), suspected submucosal/polypoid lesion at small bowel imaging (n = 5) and obscure gastrointestinal bleeding (OGIB) with vascular abnormalities seen at capsule endoscopy (n = 2). In 1/17 the suggested pathology on imaging was not identified. Therapy was applied in 15/17 (88%) cases. Diagnoses were PJS polyps (n = 8), neuroendocrine tumour (NET) (n = 2), PJS and NET (n = 1), transmural arteriovenous malformation (n = 1), angioectesia (n = 1), inflammatory polyp (n = 1), leiomyoma (n = 1) and Meckel's diverticulum (n = 1). The median (range) procedure time was 147 (84-210) mins. Median (range) length of stay post-procedure was 2 (1-19) days. Three patients developed complications. The 30-day mortality rate was 0%. CONCLUSIONS: LA-DBE is a safe, effective and minimally invasive procedure that can be applied for the management of selected patients with small bowel pathology. A SILS approach allows all therapeutic modalities to be available, including conversion to intraoperative enteroscopy (IOE), laparoscopic small bowel resection and laparotomy.
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Enteroscopia de Duplo Balão/métodos , Enteropatias/cirurgia , Intestino Delgado/cirurgia , Laparoscopia/métodos , Adulto , Feminino , Hemorragia Gastrointestinal/cirurgia , Humanos , Tempo de Internação , Masculino , Divertículo Ileal/cirurgia , Pessoa de Meia-Idade , Síndrome de Peutz-Jeghers/cirurgia , Estudos Retrospectivos , Ferida CirúrgicaRESUMO
This consensus document outlines the recommendations from the Australasian Society of Clinical Immunology and Allergy Transplantation and Primary Immunodeficiency group for the diagnosis and management of patients with severe combined immunodeficiency. It also provides a proposed framework for the early investigation, management and supportive care prior to haematopoietic stem cell transplantation.
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Transplante de Células-Tronco Hematopoéticas , Síndromes de Imunodeficiência , Imunodeficiência Combinada Severa , Austrália , Humanos , Síndromes de Imunodeficiência/diagnóstico , Síndromes de Imunodeficiência/terapia , Nova Zelândia , Imunodeficiência Combinada Severa/diagnóstico , Imunodeficiência Combinada Severa/terapiaRESUMO
OBJECTIVES: Gay, bisexual, and other men who have sex with men (gbMSM) are 131 times more likely to acquire HIV compared with other Canadian men. Pre-Exposure Prophylaxis (PrEP) for HIV has the potential to reduce or eliminate disparities in HIV acquisition among key affected populations. This paper aims to discuss the feasibility and utility of a nurse-led PrEP program administered by the Cool Aid Community Health Centre (CACHC) in Victoria, British Columbia as a public health PrEP program was initiated. DESIGN, SAMPLE AND MEASUREMENTS: A retrospective chart review of 124 gbMSM patients accessing PrEP at CACHC in 2018 collected information on patient demographics, STI testing results, and PrEP prescription pick-ups at 3 time points. RESULTS: Ninety-nine (79.8%) patients have continued on PrEP, as defined as having picked up their second 90-day PrEP prescription. Both older age and having an Sexually Transmitted Infection after PrEP enrolment were significantly associated with staying on PrEP; decreased risk perceptions contributed most to clinic-level discontinuance. Very few patients who stayed on PrEP have transitioned to their own General Practitioner. CONCLUSIONS: Patients appear to recognize their risk and are continuing on PrEP to reduce their risk of HIV. As evidenced by ability to recruit and maintain patients, we conclude that nurse-led PrEP at community health centres supports access and uptake of essential health services to optimize individual and population health.
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Infecções por HIV , Profilaxia Pré-Exposição , Minorias Sexuais e de Gênero , Canadá , Serviços de Saúde Comunitária , Infecções por HIV/epidemiologia , Infecções por HIV/prevenção & controle , Homossexualidade Masculina , Humanos , Masculino , Papel do Profissional de Enfermagem , Profilaxia Pré-Exposição/métodos , Estudos RetrospectivosRESUMO
BACKGROUND: Approximately one-third of children with acute myeloid leukemia (AML) relapse, requiring re-treatment and allogeneic hematopoietic stem cell transplantation (HSCT). Although achieving second complete remission (CR2) prior to HSCT is desirable, once CR2 is attained, it is unclear if there is any benefit from further chemotherapy prior to HSCT. Moreover, although pre-HSCT minimal residual disease (MRD) has prognostic value in acute lymphoblastic leukemia, the benefit of MRD reduction after achieving CR prior to HSCT is less clear for AML. PROCEDURE: To address these questions, we analyzed data from pediatric transplant centers in Australia and New Zealand concerning relapsed childhood AML cases occurring between 1998 and 2013. Given the retrospective nature of our analysis and assay data available, we analyzed patients on the basis of measurable residual disease (MeRD) by any methodology, rather than MRD in the conventional sense. RESULTS: We observed improved overall survival (OS) in children receiving two chemotherapy cycles, compared to one cycle or three or more cycles pre-HSCT. Improved OS with two cycles remained significant for patients without MeRD after cycle 1. CONCLUSIONS: These data suggest that a second chemotherapy cycle pre-HSCT may improve survival by lowering disease burden. Prospective trials assessing strategies to reduce pre-HSCT MRD in relapsed childhood AML are warranted.
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Transplante de Células-Tronco Hematopoéticas/mortalidade , Leucemia Mieloide Aguda/terapia , Recidiva Local de Neoplasia/terapia , Neoplasia Residual/terapia , Adolescente , Austrália , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Lactente , Recém-Nascido , Leucemia Mieloide Aguda/patologia , Masculino , Recidiva Local de Neoplasia/patologia , Neoplasia Residual/patologia , Prognóstico , Sistema de Registros , Indução de Remissão , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
TCR α+ ß+ /CD19+ cell depletion is an emerging technique for ex vivo graft manipulation in HSCT. We report 20 pediatric patients who underwent TCR α+ ß+ /CD19+ cell-depleted HSCT in four Australian centers. Conditioning regimen was dependent on HSCT indication, which included immunodeficiency (n = 14), Fanconi anemia (n = 3), and acute leukemia (n = 3). Donor sources were haploidentical parent (n = 17), haploidentical sibling (n = 2), or matched unrelated donor (n = 1). Mean cell dose was 8.2 × 108 /kg TNC, 12.1 × 106 /kg CD34+ cells, and 0.4 × 105 /kg TCR α+ ß+ cells. All patients achieved primary neutrophil and platelet engraftment, with average time to neutrophil engraftment 11 days (range 8-22) and platelet engraftment 24 days (range 12-69). TRM at 1 year was 15%. Rate of grade II-IV aGVHD at 1 year was 20% with no grade III-IV aGVHD seen. CMV reactivation occurred in 81% of CMV-positive recipients, with one patient developing CMV disease. Average time to CD4 recovery (>400 × 106 /L) was 258 days. Overall survival for the cohort at 5 years was 80%. This report highlights the initial experience of TCR α+ ß+ /CD19+ cell-depleted HSCT in Australian centers, with high rates of engraftment, low rates of aGVHD, and acceptable TRM.
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Separação Celular , Transplante de Células-Tronco Hematopoéticas/métodos , Receptores de Antígenos de Linfócitos T alfa-beta/metabolismo , Condicionamento Pré-Transplante , Adolescente , Antígenos CD19/metabolismo , Austrália , Criança , Pré-Escolar , Anemia de Fanconi/terapia , Feminino , Doença Enxerto-Hospedeiro , Humanos , Síndromes de Imunodeficiência/terapia , Lactente , Leucemia/terapia , Masculino , Neutrófilos/citologia , Pediatria , Recidiva , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Chronic granulomatous disease (CGD) can be cured by allogeneic hemopoietic stem cell transplantation (HSCT). Complications include graft failure, graft-versus-host disease (GVHD), infection, and transplant-related mortality; therefore, reduced-intensity conditioning regimens are being used to improve outcomes. In this retrospective study, the aim was to determine the outcome of treosulfan-based conditioning in HSCT for pediatric patients with CGD. The following data were collected: risk features pre-HSCT, additional conditioning agents, donor type and stem cell source, toxicity, engraftment, GVHD, chimerism, viral reactivation, post-HSCT complications, length of follow-up, and outcome. Seventy patients (median age, 107 months; interquartile range [IQR], 46-232 months) from 16 centers worldwide were transplanted between 2006 and 2015. Ninety-one percent had high-risk features. Fifty-seven HLA-matched donors, 12 HLA-mismatched donors, and 1 CD3(+)TCR αß/CD19 depleted parental haploidentical transplants were performed. No major toxicity was reported. Median times to neutrophil and platelet engraftment were 17 (IQR, 15-35) and 16 (IQR, 13-50) days. At a median follow-up of 34 months (IQR, 13-102 months), the overall survival was 91.4%, and event-free survival was 81.4%. The cumulative incidence of acute grade III-IV GVHD was 12%. Nine patients developed chronic GVHD. When split cell chimerism was available, 95% or more myeloid donor chimerism was documented in 80% of surviving patients. Secondary graft failure occurred in 12% of patients. Treosulfan-containing conditioning regimens can be used safely in HSCT for children with CGD and high-risk clinical features, achieving excellent survival with high myeloid chimerism. Further studies are needed to compare with other regimens and evaluate the long-term outcome, particularly on fertility.
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Bussulfano/análogos & derivados , Doença Granulomatosa Crônica , Transplante de Células-Tronco Hematopoéticas , Condicionamento Pré-Transplante/métodos , Doença Aguda , Adolescente , Adulto , Aloenxertos , Plaquetas/metabolismo , Bussulfano/administração & dosagem , Criança , Pré-Escolar , Intervalo Livre de Doença , Feminino , Seguimentos , Sobrevivência de Enxerto/efeitos dos fármacos , Doença Enxerto-Hospedeiro/sangue , Doença Enxerto-Hospedeiro/mortalidade , Doença Granulomatosa Crônica/sangue , Doença Granulomatosa Crônica/mortalidade , Doença Granulomatosa Crônica/terapia , Humanos , Lactente , Masculino , Neutrófilos/metabolismo , Taxa de SobrevidaRESUMO
Minimal residual disease (MRD) during early chemotherapy is a powerful predictor of relapse in acute lymphoblastic leukaemia (ALL) and is used in children to determine eligibility for allogeneic haematopoietic stem cell transplantation (HSCT) in first (CR1) or later complete remission (CR2/CR3). Variables affecting HSCT outcome were analysed in 81 children from the ANZCHOG ALL8 trial. The major cause of treatment failure was relapse, with a cumulative incidence of relapse at 5 years (CIR) of 32% and treatment-related mortality of 8%. Leukaemia-free survival (LFS) and overall survival (OS) were similar for HSCT in CR1 (LFS 62%, OS 83%, n = 41) or CR2/CR3 (LFS 60%, OS 72%, n = 40). Patients achieving bone marrow MRD negativity pre-HSCT had better outcomes (LFS 83%, OS 92%) than those with persistent MRD pre-HSCT (LFS 41%, OS 64%, P < 0·0001) or post-HSCT (LFS 35%, OS 55%, P < 0·0001). Patients with B-other ALL had more relapses (CIR 50%, LFS 41%) than T-ALL and the main precursor-B subtypes including BCR-ABL1, KMT2A (MLL), ETV6-RUNX1 (TEL-AML1) and hyperdiploidy >50. A Cox multivariate regression model for LFS retained both B-other ALL subtype (hazard ratio 4·1, P = 0·0062) and MRD persistence post-HSCT (hazard ratio 3·9, P = 0·0070) as independent adverse prognostic variables. Persistent MRD could be used to direct post-HSCT therapy.
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Transplante de Células-Tronco Hematopoéticas/métodos , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Criança , Terapia Combinada , Feminino , Deleção de Genes , Humanos , Fator de Transcrição Ikaros/genética , Estimativa de Kaplan-Meier , Masculino , Proteínas de Neoplasias/genética , Neoplasia Residual , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia , Prognóstico , Recidiva , Condicionamento Pré-Transplante/métodos , Resultado do TratamentoAssuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Leucemia Mieloide Aguda/tratamento farmacológico , Adolescente , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Azacitidina/administração & dosagem , Azacitidina/efeitos adversos , Criança , Pré-Escolar , Decitabina/administração & dosagem , Decitabina/efeitos adversos , Feminino , Humanos , Lactente , Leucemia Mieloide Aguda/patologia , MasculinoRESUMO
BACKGROUND AND AIM: Factors influencing reading time and detection of lesions include the view mode (VM) and frame rate (FR) applied during reading of small bowel capsule endoscopy images. The aims of this study were to examine the impact of VM and FR on reading time and lesion detection using a standardized, single-type lesion model. METHODS: A selected video clip containing a known number of positive images (n = 60) of small bowel angioectasias was read using nine different combinations of VM and FR (VM1, VM2, and VM4 × FR10, FR15, and FR25) in randomized order by six capsule endoscopists. Readers were asked to count all positive images of angioectasias (maximum number of positive images, MPIs) seen during reading. The main outcome measurements were effect of VM and FR on reading time and lesion detection. RESULTS: Mean MPIs for all VM2 and VM4 were 36 (60 %) and 38 (64 %). They were significantly higher than VM1 of 24 (40 %) (P = 0.011, 0.008). A statistical difference was found when the total MPIs at FR10 were compared to FR15 (P = 0.008) and to FR25 (P < 0.001). CONCLUSIONS: Both VM and FR significantly influence lesion detection during capsule endoscopy reading.