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BACKGROUND: Fetal magnetic resonance imaging (MRI) and spectroscopy (MRS) provide a unique opportunity to non-invasively measure markers of neurodevelopment in survivors of twin-twin transfusion syndrome (TTTS). OBJECTIVE: To characterize fetal brain maturation after laser surgery for TTTS by measuring brain volumes and cerebral metabolite concentrations using fetal MRI + MRS. STUDY DESIGN: Prospective study of dual surviving fetuses treated with laser surgery for TTTS. At 4-5 postoperative weeks, fetal MRI was used together with novel image analysis to automatically extract major brain tissue volumes. Fetal MRS was used to measure major metabolite concentrations in the fetal brain. RESULTS: Twenty-one twin pairs were studied. The average (±SD) gestational age at MRI was 25.89 (±2.37) weeks. Total brain volume (TBV) was lower in the donors, although cerebral volumes were not different between twin pairs. Recipients showed lower proportions of cortical and cerebellar volumes, normalized to TBV and cerebral volumes. MRS data showed that biochemical differences between twin brains were related to discrepancy in their brain volumes. CONCLUSION: Although donors have a smaller TBV compared to recipients, proportionality of brain tissue volumes are preserved in donors. MRS maturational markers of fetal brain development show that recovery in donors persists 4 weeks after surgery.
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Encéfalo/diagnóstico por imagem , Terapias Fetais , Transfusão Feto-Fetal/cirurgia , Fotocoagulação a Laser , Adulto , Encéfalo/embriologia , Encéfalo/metabolismo , Feminino , Transfusão Feto-Fetal/diagnóstico por imagem , Transfusão Feto-Fetal/metabolismo , Humanos , Imageamento por Ressonância Magnética , Espectroscopia de Ressonância Magnética , Tamanho do Órgão , Gravidez , Recuperação de Função Fisiológica , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: The use of post-transplant cyclophosphamide (PTCy) is highly effective in preventing graft versus host disease (GVHD) for haploidentical allogeneic hematopoietic stem cell transplantation (allo-HSCT). There is limited data on the role of PTCy as GVHD prophylaxis in matched-sibling and fully matched-unrelated donor (MSD/MUD) allo-HSCT. METHODS: Our single-center retrospective study aims to compare outcomes of PTCy alone or in combination with mycophenolate mofetil and tacrolimus (PTCy/MMF/TAC) relative to methotrexate and tacrolimus (MTX/TAC). The primary endpoint of our study was GVHD-free, relapse free survival (GRFS). Secondary endpoints were overall survival (OS), disease free survival (DFS), and incidence of severe acute and chronic GVHD. We identified 74 adult patients who underwent MSD/MUD allo-HSCT at our institution from 2015 to 2023. RESULTS: Within our cohort, 33.8% (n = 25) received MTX/TAC, while 54.0% (n = 40) received PTCy/MMF/TAC, and 12.2% (n = 9) received PTCy alone. Patients receiving PTCY had the longest time to neutrophil engraftment relative to MTX/TAC (15 days vs. 12 days, P = .010). PTCy/MMF/TAC was associated with improved GRFS relative to MTX/TAC (hazard ratio [HR] = HR 0.42, 95% CI 0.19-0.93, P = .031), which persisted when controlling for age. Incidence of chronic GVHD was lower in the PTCy/MMF/TAC group compared to MTX/TAC (1-year 9.0% vs. 30.1%, HR 0.19, 95% CI 0.06-0.59, P = .005). However, OS and DFS were comparable across all groups. CONCLUSIONS: Our results demonstrate decreased rates of severe chronic GVHD resulting in improved GRFS when using PTCy/TAC/MTX as GVHD prophylaxis compared to MTX/TAC in MSD/MUD.
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INTRODUCTION: Detection of measurable residual disease (MRD) in adults with acute lymphoblastic leukemia (ALL) is a vital biomarker in risk prediction and treatment selection. Next-generation sequencing (NGS) offers greater sensitivity relative to multiparametric flow cytometry (MFC) and may be a better predictive tool for identifying ALL patients at risk of relapse. PATIENTS AND METHODS: This single-center retrospective study compares MRD detection by NGS versus MFC in 52 adult B- and T-ALL patients treated at our institution between 2018 and 2023. Pretreatment bone marrow samples were used for assay calibration, while post-treatment MRD assessment was completed up to 4.5 months after the first complete remission (CR1) using an MRD cutoff of 10-6 for distinguishing relapse risk. RESULTS: The 2-year cumulative incidence of relapse (CIR) among patients who were MRD positive using MFC and NGS was 39.5% and 46.2%, respectively. Unlike MFC, post-CR1 MRD positivity with NGS significantly predicted CIR (HR = 9.47, P = .028). In patients who were MRD negative by MFC, low levels of MRD detected by NGS distinguished patients at high risk of relapse (HR 10.3, P = .026, 2-year CIR 51.6%). CONCLUSION: Our data suggests that assessment of post-CR1 MRD using a highly sensitive NGS assay can identify ALL patients undergoing frontline therapy at increased risk of relapse and guide the use of adjuvant therapy.
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Transplante de Células-Tronco Hematopoéticas , Leucemia-Linfoma Linfoblástico de Células Precursoras , Adulto , Humanos , Estudos Retrospectivos , Citometria de Fluxo , Doença Aguda , Recidiva , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Neoplasia Residual/diagnóstico , Neoplasia Residual/terapia , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Transplante de Células-Tronco Hematopoéticas/métodosRESUMO
PURPOSE: The phase III Cancer and Leukemia Group B (CALGB)/SWOG 80405 trial found no difference in overall survival (OS) in patients with metastatic colorectal cancer receiving first-line chemotherapy in combination with either bevacizumab or cetuximab. We investigated the potential prognostic and predictive value of HER2 amplification and gene expression using next-generation sequencing (NGS) and NanoString data. PATIENTS AND METHODS: Primary tumor DNA from 559 patients was profiled for HER2 amplification by NGS (FoundationOne CDx). Tumor tissue from 925 patients was tested for NanoString gene expression using an 800-gene panel. OS and progression-free survival (PFS) were the time-to-event end points. RESULTS: High HER2 expression (dichotomized at median) was associated with longer PFS (11.6 v 10 months, P = .012) and OS (32 v 25.3 months, P = .033), independent of treatment. An OS benefit for cetuximab versus bevacizumab was observed in the high HER2 expression group (P = .02), whereas a worse PFS for cetuximab was seen in the low-expression group (P = .019). When modeled as a continuous variable, increased HER2 expression was associated with longer OS (hazard ratio [HR], 0.83 [95% CI, 0.75 to 0.93]; adjusted P = .0007) and PFS (HR, 0.82 [95% CI, 0.74 to 0.91]; adjusted P = .0002), reaching a plateau effect after the median. In patients with HER2 expression lower than median, treatment with cetuximab was associated with worse PFS (HR, 1.38 [95% CI, 1.12 to 1.71]; adjusted P = .0027) and OS (HR, 1.28 [95% CI, 1.02 to 1.59]; adjusted P = .03) compared with that with bevacizumab. A significant interaction between HER2 expression and the treatment arm was observed for OS (Pintx = .017), PFS (Pintx = .048), and objective response rate (Pintx = .001). CONCLUSION: HER2 gene expression was prognostic and predictive in CALGB/SWOG 80405. HER2 tumor expression may inform treatment selection for patients with low HER2 favoring bevacizumab- versus cetuximab-based therapies.
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Protocolos de Quimioterapia Combinada Antineoplásica , Bevacizumab , Cetuximab , Neoplasias Colorretais , Receptor ErbB-2 , Humanos , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Neoplasias Colorretais/mortalidade , Receptor ErbB-2/metabolismo , Receptor ErbB-2/genética , Feminino , Masculino , Pessoa de Meia-Idade , Bevacizumab/uso terapêutico , Bevacizumab/administração & dosagem , Cetuximab/uso terapêutico , Cetuximab/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Prognóstico , Idoso , Adulto , Intervalo Livre de Progressão , Biomarcadores Tumorais/genética , Regulação Neoplásica da Expressão Gênica , Metástase NeoplásicaRESUMO
BACKGROUND: Hematopoietic stem cell transplantation (HSCT) is a pivotal treatment for high-risk acute lymphocytic leukemia (ALL), although limited by suitable human leukocyte antigen (HLA)-matched sibling donors (MSD). This study evaluates the impact of donor selection on outcomes in post-HSCT Hispanic B-cell ALL patients. METHODOLOGY: This single-center retrospective study evaluates outcomes in 88 adult Hispanic B-cell ALL patients who underwent haploidentical, MSD, or MUD myeloablative HSCT between 2013 and 2023. RESULTS: Compared to Haploidentical transplants, MSD exhibited worse cumulative incidence of relapse (CIR) (HR = 3.39; P = 0.014) and disease-free survival (DFS) (HR = 2.44; P = 0.048) whereas MUD outcomes did not differ. This effect persisted even when controlling for pre-HSCT stage and Minimal residual disease (MRD) status. In addition, Ph-like was a significant predictor of worse DFS (HR = 3.60; P=0.014) and CIR (HR = 2.97; P=0.035) on multivariate analysis. Older donor age correlated with worse GVHD-free, relapse-free survival (GRFS) in haploidentical transplants (HR = 1.05; P=0.036). CONCLUSION: Our data highlights improved outcomes with younger, haploidentical donors among Hispanic B-cell ALL patients undergoing myeloablative HSCT. This underscores the importance of donor selection in optimizing outcomes for ALL patients.
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Seleção do Doador , Transplante de Células-Tronco Hematopoéticas , Hispânico ou Latino , Condicionamento Pré-Transplante , Humanos , Transplante de Células-Tronco Hematopoéticas/métodos , Feminino , Masculino , Adulto , Estudos Retrospectivos , Pessoa de Meia-Idade , Condicionamento Pré-Transplante/métodos , Adulto Jovem , Adolescente , Doadores de Tecidos , Doença Enxerto-Hospedeiro/etiologia , Leucemia-Linfoma Linfoblástico de Células Precursoras B/terapia , Leucemia-Linfoma Linfoblástico de Células Precursoras B/mortalidade , Intervalo Livre de Doença , Resultado do Tratamento , Irmãos , Taxa de SobrevidaRESUMO
There are currently no studies examining healthcare access and utilization by Syrian Americans. A better understanding of the determinants of healthcare utilization among this group could help aid in the design of culturally competent programs. A self-administered survey was distributed at events across Southern California and Jacksonville, Florida from January 2018 to May 2019. Statistical analysis utilized multivariate regressions. Insurance coverage was associated with a preference for speaking Arabic (OR 0.433, p = 0.02) and increased length of residency (OR 1.04, p = 0.02). Routine checkup was associated with female sex (OR 1.97, p = 0.001), age (OR 1.05, p < 0.001), and insurance coverage (OR 6.96, p < 0.001). Colonoscopy compliance rate was 43.3% and positively associated with higher education (OR 2.70, p = 0.002), routine checkup (OR 7.61, p = 0.009) and increased length of residency (OR 1.06, p < 0.001). Syrian Americans may benefit from further health promotion campaigns with regard to insurance coverage, preventative care and cancer screenings.