RESUMEN
The therapeutic efficacy of donor lymphocyte infusions (DLIs) given after allogeneic hematopoietic cell transplantation (HCT) is limited by risk of graft-versus-host disease (GVHD). Post-transplantation cyclophosphamide (PTCy) effectively prevents severe GVHD, but there are limited data on outcomes of DLIs given to PTCy-treated patients. We reviewed 162 consecutive PTCy-treated patients transplanted between 2015-2022 within the Center for Immuno-Oncology at the National Cancer Institute. Of 38 DLIs given to 21 patients after 22 HCTs, few DLIs were associated with toxicities of acute GVHD (7.8%), cytokine release syndrome (CRS, 7.8%), or chronic GVHD (2.6%), and all occurred in those receiving serotherapy-containing pre-HCT conditioning (50% of HCTs). Seven DLIs resulted in complete response (18.4%), with 5 of these given after HCTs using serotherapy-containing conditioning. Excluding infectious indications, complete response to DLIs given after transplants with versus without serotherapy-containing pre-HCT conditioning were 30% and 4.3%, respectively. Two patients received DLI for infection and experienced complete resolution without GVHD or CRS, although the efficacy cannot be definitively attributable to the DLI. DLIs given to PTCy-treated patients had low toxicity but limited efficacy, although pre-HCT serotherapy may modulate both toxicity and response. Novel strategies are needed to enhance the therapeutic efficacy of post-transplant cellular therapies without aggravating GVHD.
RESUMEN
Although an expanding array of effective treatments has resulted in recent improvement in survival of patients with mantle cell lymphoma (MCL), outcomes remain heterogeneous, and identification of prognostic factors remains a priority. We assessed the prognostic impact of time to progression of disease (POD) after first-line therapy among 455 patients with relapsed MCL. Patients were categorized by duration of first remission as PRF/POD6, defined as progressive disease during induction or POD within 6 months of diagnosis (n = 65; 14%); POD6-24, defined as POD between 6 and 24 months after diagnosis (n = 153; 34%); and POD>24, defined as POD >24 months after diagnosis (n = 237; 53%). The median overall survival from POD (OS2) was 1.3 years (95% confidence interval [CI], 0.9-2.4) for patients with PRF/POD6, 3 years (95% CI, 2-6.8) for those with POD6-24, and 8 years (95% CI, 6.2-NR) for those with POD>24. Median OS2 was inferior in patients with early POD (defined as PRF/POD6 or POD6-24) after both intensive and less intensive frontline treatment. The prognostic performance of time until POD was replicated in an independent cohort of 245 patients with relapsed MCL, with median OS2 of 0.3 years (95% CI, 0.1-0.5) for PRF/POD6, 0.8 years (95% CI, 0.6-0.9) for POD6-24, and 2.4 years (95% CI 2.1-2.7) for POD>24. Early POD is associated with inferior OS2 in patients with relapsed MCL, identifying a high-risk population for future prospective studies.
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Linfoma de Células del Manto , Adulto , Humanos , Linfoma de Células del Manto/diagnóstico , Linfoma de Células del Manto/tratamiento farmacológico , Pronóstico , Estudios Prospectivos , Recurrencia , Resultado del TratamientoRESUMEN
Clinical outcomes and predictors of survival in patients with newly diagnosed mantle cell lymphoma (MCL) treated in the rituximab era (2000-2015) at 12 US academic centers were assessed to identify determinants of survival across age groups. Objectives were to characterize and compare practice patterns, outcomes and prognostic factors for survival in younger patients (age < 65) and older patients (age ≥ 65 years). Among 1162 patients included, 697 were younger and 465 were older. In younger patients, 2-year progression free survival (PFS) and overall survival (OS) rates were 79% and 92% respectively; blastoid histology, ECOG ≥ 2, and lack of maintenance rituximab (MR) remained statistically relevant to poor OS on univariate analysis (UVA) and multivariate analysis (MVA). In older patients, 2-year PFS and OS rates were 67% and 86% respectively; lack of maintenance rituximab remained significantly associated with inferior PFS and OS on UVA and MVA (p < 0.001). Two-year PFS rates were 79%, and 67% and 2-year OS rates were 92% and 86% for ages < 65 and ≥ 65 respectively (p < 0.001). First-line high-dose cytarabine exposure and/or MR lessened the negative impact of age on survival. Taken collectively, survival outcomes for older patients remain inferior to those of younger patients in the rituximab era. However, maintenance rituximab and potentially high-dose cytarabine-based induction can mitigate the negative impact of age on survival.
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Antineoplásicos Inmunológicos/uso terapéutico , Linfoma de Células del Manto/tratamiento farmacológico , Rituximab/uso terapéutico , Factores de Edad , Anciano , Femenino , Humanos , Linfoma de Células del Manto/epidemiología , Masculino , Persona de Mediana Edad , Supervivencia sin Progresión , Estudios Retrospectivos , Análisis de Supervivencia , Resultado del TratamientoRESUMEN
INTRODUCTION: While most patients with mantle cell lymphoma (MCL) receive therapy shortly after diagnosis, a subset of patients with indolent-behaving disease can safely defer treatment. In this subgroup, we evaluated the importance of treatment intensity in patients with MCL who defer initial therapy. METHODS: Out of 1134 patients with MCL from 12 academic centers, we analyzed 219 patients who initiated therapy at least 90 days after diagnosis. Patients who received induction with high-dose cytarabine and/or autologous stem cell transplantation (ASCT) in first remission were considered to have received intensive therapy (n = 88) while all other approaches were non-intensive (n = 131). RESULTS: There was no difference in progression-free (PFS; P = .224) or overall survival (OS; P = .167) in deferred patients who received non-intensive vs. intensive therapy. Additionally, univariate and multivariate Cox proportional hazards models were performed for PFS and OS. Treatment at an academic center (HR 0.43, P = .015) was associated with improved OS in both univariate and multivariate models, while intensity of treatment was not associated with improved OS in either model. CONCLUSIONS: These results indicate that intensified initial treatment is not associated with improved survival after deferring initial therapy, although prospective studies are needed to determine which of these patients with MCL may benefit from intensive therapy.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Citarabina/uso terapéutico , Trasplante de Células Madre Hematopoyéticas/métodos , Linfoma de Células del Manto/terapia , Anciano , Ciclofosfamida/uso terapéutico , Dexametasona/uso terapéutico , Supervivencia sin Enfermedad , Doxorrubicina/uso terapéutico , Femenino , Humanos , Linfoma de Células del Manto/mortalidad , Linfoma de Células del Manto/patología , Masculino , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Inducción de Remisión/métodos , Estudios Retrospectivos , Tiempo de Tratamiento , Trasplante Autólogo , Vincristina/uso terapéuticoRESUMEN
Innovative strategies are needed to reduce the hypertension epidemic among African Americans. Reach Out was a faith-collaborative, mobile health, randomized, pilot intervention trial of four mobile health components to reduce high blood pressure (BP) compared to usual care. It was designed and tested within a community-based participatory research framework among African Americans recruited and randomized from churches in Flint, Michigan. The purpose of this pilot study was to assess the feasibility of the Reach Out processes. Feasibility was assessed by willingness to consent (acceptance of randomization), proportion of weeks participants texted their BP readings (intervention use), number lost to follow-up (retention), and responses to postintervention surveys and focus groups (acceptance of intervention). Of the 425 church members who underwent BP screening, 94 enrolled in the study and 73 (78%) completed the 6-month outcome assessment. Median age was 58 years, and 79% were women. Participants responded with their BPs on an average of 13.7 (SD = 10.7) weeks out of 26 weeks that the BP prompts were sent. All participants reported satisfaction with the intervention. Reach Out, a faith-collaborative, mobile health intervention was feasible. Further study of the efficacy of the intervention and additional mobile health strategies should be considered.
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Negro o Afroamericano/estadística & datos numéricos , Investigación Participativa Basada en la Comunidad/métodos , Promoción de la Salud/métodos , Hipertensión/prevención & control , Telemedicina/métodos , Adulto , Presión Sanguínea , Estudios de Factibilidad , Femenino , Humanos , Hipertensión/etnología , Masculino , Michigan , Persona de Mediana Edad , Proyectos Piloto , Encuestas y CuestionariosRESUMEN
Clinical classification of early dementia and mild cognitive impairment (MCI) is imprecise. We reported previously that molecular imaging classification of early dementia and MCI with dual amyloid and dopamine terminal positron emission tomography differs significantly from expert clinical classification. We now report pathological diagnoses in a substantial subset of our previously imaged subjects. Among 36 subjects coming to autopsy, imaging classifications and pathological diagnosis were concordant in 33 cases (κ = 0.85). This approach enhanced specificity of Alzheimer's disease diagnosis. The strong concordance of imaging-based classifications and pathological diagnoses suggests that this imaging approach will be useful in establishing more accurate and convenient classification biomarkers for dementia research.
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Amiloide/metabolismo , Demencia/clasificación , Demencia/diagnóstico por imagen , Dopamina/metabolismo , Anciano , Anciano de 80 o más Años , Enfermedad de Alzheimer/diagnóstico por imagen , Autopsia , Biomarcadores , Disfunción Cognitiva/diagnóstico por imagen , Femenino , Humanos , Enfermedad por Cuerpos de Lewy/patología , Masculino , Persona de Mediana Edad , Pruebas Neuropsicológicas , Lóbulo Parietal/patología , Tomografía de Emisión de Positrones , Proteinopatías TDP-43/patologíaRESUMEN
BACKGROUND AND PURPOSE: Little is known about how regions vary in their use of thrombolysis (intravenous tissue-type plasminogen activator and intra-arterial treatment) for acute stroke. We sought to determine regional variation in thrombolysis treatment and investigate the extent to which regional variation is accounted for by patient demographics, regional factors, and elements of stroke systems of care. METHODS: Retrospective cross-sectional study of all fee-for-service Medicare patients with ischemic stroke admitted via the Emergency Department from 2007 to 2010 who were assigned to 1 of 3436 hospital service areas. Multilevel logistic regression was used to estimate regional thrombolysis rates, determine the variation in thrombolysis treatment attributable to the region and estimate thrombolysis treatment rates and disability prevented under varied improvement scenarios. RESULTS: There were 844 241 ischemic stroke admissions of which 3.7% received intravenous tissue-type plasminogen activator and 0.5% received intra-arterial stroke treatment without or without intravenous tissue-type plasminogen activator over the 4-year period. The unadjusted proportion of patients with ischemic stroke who received thrombolysis varied from 9.3% in the highest treatment quintile compared with 0% in the lowest treatment quintile. Measured demographic and stroke system factors were weakly associated with treatment rates. Region accounted for 7% to 8% of the variation in receipt of thrombolysis treatment. If all regions performed at the level of 75th percentile region, ≈7000 additional patients with ischemic stroke would be treated with thrombolysis. CONCLUSIONS: There is substantial regional variation in thrombolysis treatment. Future studies to determine features of high-performing thrombolysis treatment regions may identify opportunities to improve thrombolysis rates.
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Servicio de Urgencia en Hospital/tendencias , Beneficios del Seguro/tendencias , Medicare/tendencias , Accidente Cerebrovascular/epidemiología , Accidente Cerebrovascular/terapia , Terapia Trombolítica/tendencias , Anciano , Anciano de 80 o más Años , Estudios Transversales , Femenino , Humanos , Masculino , Estudios Retrospectivos , Accidente Cerebrovascular/diagnóstico , Resultado del Tratamiento , Estados Unidos/epidemiologíaRESUMEN
Objective. Sweat collected for testing should have quantity not sufficient (QNS) rate of ≤10% in babies ≤3 months of age. Michigan (MI) cystic fibrosis (CF) centers' QNS rates were 12% to 25% in 2009. This project was initiated to reduce sweat QNS rates in MI. Methods/Steps. (a) Each center's sweat testing procedures were reviewed by a consultant. (b) Each center received a report with recommendations to improve QNS rates. (c) Technicians visited other participating centers to observe their procedures. Results. A total of 778 infants were identified as positive via CF newborn screening over a 2-year period. The mean age at time of sweat test was 23.2 days (SD ± 13.0 days). The overall QNS percent decreased from 14.4% to 9.5% (P = .04) during the study. Conclusion. This project and teamwork approach led to a decrease of sweat test QNS rates, opportunities to solve a common problem, and improved quality of care.