RESUMEN
Current therapies for high-grade TP53-mutated myeloid neoplasms (≥10% blasts) do not offer a meaningful survival benefit except allogeneic stem cell transplantation in the minority who achieve a complete response to first line therapy (CR1). To identify reliable pre-therapy predictors of complete response to first-line therapy (CR1) and outcomes, we assembled a cohort of 242 individuals with TP53-mutated myeloid neoplasms and ≥10% blasts with well-annotated clinical, molecular and pathology data. Key outcomes examined were CR1 & 24-month survival (OS24). In this elderly cohort (median age 68.2 years) with 74.0% receiving frontline non-intensive regimens (hypomethylating agents +/- venetoclax), the overall cohort CR1 rate was 25.6% (50/195). We additionally identified several pre-therapy factors predictive of inferior CR1 including male gender (P = 0.026), ≥2 autosomal monosomies (P < 0.001), -17/17p (P = 0.011), multi-hit TP53 allelic state (P < 0.001) and CUX1 co-alterations (P = 0.010). In univariable analysis of the entire cohort, inferior OS24 was predicated by ≥2 monosomies (P = 0.004), TP53 VAF > 25% (P = 0.002), TP53 splice junction mutations (P = 0.007) and antecedent treated myeloid neoplasm (P = 0.001). In addition, mutations/deletions in CUX1, U2AF1, EZH2, TET2, CBL, or KRAS ('EPI6' signature) predicted inferior OS24 (HR = 2.0 [1.5-2.8]; P < 0.0001). In a subgroup analysis of HMA +/-Ven treated individuals (N = 144), TP53 VAF and monosomies did not impact OS24. A risk score for HMA +/-Ven treated individuals incorporating three pre-therapy predictors including TP53 splice junction mutations, EPI6 and antecedent treated myeloid neoplasm stratified 3 prognostic distinct groups: intermediate, intermediate-poor, and poor with significantly different median (12.8, 6.0, 4.3 months) and 24-month (20.9%, 5.7%, 0.5%) survival (P < 0.0001). For the first time, in a seemingly monolithic high-risk cohort, our data identifies several baseline factors that predict response and 24-month survival.
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Mutación , Proteína p53 Supresora de Tumor , Humanos , Masculino , Femenino , Anciano , Proteína p53 Supresora de Tumor/genética , Persona de Mediana Edad , Anciano de 80 o más Años , Adulto , Pronóstico , Resultado del TratamientoRESUMEN
ABSTRACT: The optimal means of assessing candidacy of older adults (≥65 years) for chimeric antigen receptor T-cell (CAR-T) therapy are unknown. We explored the role of a geriatric assessment (GA)-guided multidisciplinary clinic (GA-MDC) in selecting and optimizing older adults for CAR-T. Sixty-one patients were evaluated in a GA-MDC (median age, 73 years; range, 58-83). A nonbinding recommendation ("proceed" or "decline") regarding suitability for CAR-T was provided for each patient based on GA results. Fifty-three patients ultimately received CAR-T (proceed, n = 47; decline, n = 6). Among patients who received B-cell maturation antigen (BCMA)-directed (n = 11) and CD19-directed CAR-T (n = 42), the median overall survival (OS) was 14.2 months and 16.6 months, respectively. GA uncovered high rates of geriatric impairment among patients proceeding to CAR-T therapy, with fewer impairments in those recommended "proceed." Patients recommended "proceed" had shorter median length of stay (17 vs 31 days; P = .05) and lower rates of intensive care unit admission (6% vs 50%; P = .01) than those recommended "decline." In patients receiving CD19- and BCMA-directed CAR-T therapy, a "proceed" recommendation was associated with superior OS compared with "decline" (median, 16.6 vs 11.4 months [P = .02]; and median, 16.4 vs 4.2 months [P = .03], respectively). When controlling for Karnofsky performance status, C-reactive protein, and lactate dehydrogenase at time of lymphodepletion, the GA-MDC treatment recommendation remained prognostic for OS (hazard ratio, 3.26; P = .04). Patients optimized via the GA-MDC without serious vulnerabilities achieved promising outcomes, whereas patients with high vulnerability experienced high toxicity and poor outcomes after CAR-T therapy.
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Evaluación Geriátrica , Inmunoterapia Adoptiva , Humanos , Anciano , Anciano de 80 o más Años , Masculino , Femenino , Inmunoterapia Adoptiva/efectos adversos , Inmunoterapia Adoptiva/métodos , Persona de Mediana Edad , Receptores Quiméricos de AntígenosAsunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica , Compuestos Bicíclicos Heterocíclicos con Puentes , Antígeno CD47 , Sulfonamidas , Humanos , Compuestos Bicíclicos Heterocíclicos con Puentes/uso terapéutico , Compuestos Bicíclicos Heterocíclicos con Puentes/administración & dosificación , Sulfonamidas/uso terapéutico , Sulfonamidas/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Resultado del Tratamiento , Antígeno CD47/antagonistas & inhibidores , Masculino , Resistencia a Antineoplásicos , Anciano , Persona de Mediana Edad , Femenino , Recurrencia Local de Neoplasia/tratamiento farmacológico , Recurrencia Local de Neoplasia/patología , Adulto , Trastornos Mieloproliferativos/tratamiento farmacológico , Trastornos Mieloproliferativos/diagnósticoRESUMEN
BACKGROUND: CD19-targeted chimeric antigen receptor (CAR) T-cell therapy has become a standard of care in relapsed/refractory (R/R) aggressive large B-cell non-Hodgkin lymphomas (B-NHL) though the majority of recipients do not receive durable disease benefit, prompting the need to better define risk factors for relapse/progression. OBJECTIVES: We performed a single-center, retrospective analysis of patients treated with commercial CAR T-cell therapy to evaluate the impact of tumor burden, as measured by whole-body metabolic tumor volume (MTV) from 18F fluorodeoxyglucose PET imaging, on treatment outcomes. STUDY DESIGN: Sixty-one patients treated with CAR T-cell therapy for R/R B-NHL between May 2016 and November 2021 were included. RESULTS: Using a receiver operating characteristic curve-based MTV optimization cutoff of 450 mL, 1-year progression-free survival (PFS) was 22% for high MTV versus 54% for low MTV (P < .01), and 1-year overall survival (OS) was 37% and 73%, respectively (P = .01). In a subset of 46 patients, residual MTV of less than 106 mL at the day 30 (D30) disease assessment was associated with significantly improved outcomes (1-year OS 85% vs. 13%, P < .01). Incorporation of pretreatment MTV to the International Prognostic Index (IPI) scoring system significantly distinguished 2-year PFS and OS outcomes by 3 risk groups. CONCLUSIONS: Our findings suggest that both pretreatment and D30 MTV are predictive of outcomes among R/R B-NHL patients treated with CAR T-cell therapy. These data indicate that efforts to reduce pretreatment tumor burden may improve longitudinal clinical outcomes. Furthermore, D30 postinfusion MTV quantification may aid clinicians in optimally identifying patients at high-risk for progression, and in whom closer disease monitoring should be considered. MTV also adds prognostic value to patients with high-risk IPI and holds promise for incorporation in novel risk scoring systems which can identify patients prior to CAR T-cell therapy at highest risk of adverse outcomes.
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Linfoma de Células B Grandes Difuso , Humanos , Pronóstico , Carga Tumoral , Linfoma de Células B Grandes Difuso/diagnóstico , Linfoma de Células B Grandes Difuso/terapia , Linfoma de Células B Grandes Difuso/metabolismo , Inmunoterapia Adoptiva/efectos adversos , Estudios Retrospectivos , Recurrencia Local de Neoplasia , Fluorodesoxiglucosa F18RESUMEN
ABSTRACT: TP 53-mutated myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) are among the most lethal malignancies, characterized by dismal outcomes with currently available therapies. Allogeneic hematopoietic cell transplantation (allo-HCT) is widely thought to be the only treatment option to offer durable disease control. However, outcomes with allo-HCT in this context are quite poor, calling into question the utility of transplantation. In this review, we summarize the latest data on allo-HCT outcomes in this subgroup, evaluating the limitations of available evidence; we review the molecular heterogeneity of this disease, delineating outcomes based on distinct biological features to aid in patient selection; and we critically examine whether allo-HCT should be routinely applied in this disease on the basis of currently available data. We propose that the exceptionally poor outcomes of patients with TP53-mutated MDS/AML with biallelic loss and/or adverse-risk cytogenetics should motivate randomized-controlled trials of HCT vs non-HCT to determine whether transplantation can prolong survival and/or positively impact other clinically relevant outcomes such as patient-reported outcomes or healthcare resource utilization in this disease subset. Without dedicated prospective randomized trials, selecting who may actually derive benefit from allo-HCT for TP53-mutated MDS/AML can be described as ambiguous guesswork and must be carefully contemplated.
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Trasplante de Células Madre Hematopoyéticas , Leucemia Mieloide Aguda , Síndromes Mielodisplásicos , Humanos , Inutilidad Médica , Estudios Prospectivos , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Síndromes Mielodisplásicos/terapia , Proteína p53 Supresora de TumorAsunto(s)
Síndrome de Bronquiolitis Obliterante , Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Humanos , Trasplante Haploidéntico/efectos adversos , Ciclofosfamida , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Enfermedad Injerto contra Huésped/etiologíaRESUMEN
Obesity and its attendant pathophysiological alterations have long been implicated in promoting cancer development and in the modulation of antitumor immunologic responses, but little is known about their impact on outcomes after cellular immunotherapy. In this issue, Rejeski and colleagues report that intrinsic host factors including body composition and nutritional status may predict response after chimeric antigen receptor T-cell therapy in patients with relapsed lymphomas. These data highlight the clinical relevance of these factors on treatment outcomes and will hopefully motivate interventional studies of prehabilitation and nutritional optimization in these patients. See related article by Rejeski et al., p. 707 (1).
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Inmunoterapia Adoptiva , Sarcopenia , Humanos , Inmunoterapia Adoptiva/efectos adversos , Receptores de Antígenos de Linfocitos T/inmunología , Linfocitos T/inmunología , Estado Nutricional , Sarcopenia/etiología , Distribución Tisular , Composición CorporalRESUMEN
Since 2017, the number of agents for acute myeloid leukemia (AML) has rapidly expanded. Given the increased therapeutic options, better identification of high-risk subsets of AML and more refined approaches to patient fitness assessment, the decisions surrounding selection of intensive chemotherapy versus lower-intensity treatment have grown increasingly more nuanced. In this review, we present available data for both standard and investigational approaches in the initial treatment of AML using an intensive chemotherapy backbone or a lower-intensity approach. We summarize management strategies in newly diagnosed secondary AML, considerations around allogeneic stem-cell transplantation, and the role of maintenance therapy. Finally, we highlight important areas of future investigation and novel agents that may hold promise in combination with standard therapies.
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Trasplante de Células Madre Hematopoyéticas , Leucemia Mieloide Aguda , Humanos , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Inducción de RemisiónRESUMEN
Endothelial activation and stress index (EASIX) predicts nonrelapse mortality (NRM) when assessed before hematopoietic cell transplantation (HCT). We sought to determine whether changes in EASIX after HCT may be an informative marker of NRM. We evaluated 509 adults who underwent reduced intensity, unmodified (N = 149, 29%), or myeloablative ex vivo CD34+-selected allogeneic HCT (allo-HCT) (N = 306, 71%) between 2008 and 2016. Patients who underwent unmodified allo-HCT received tacrolimus-based graft-versus-host disease (GVHD) prophylaxis, whereas CD34+-selected patients received no planned immunosuppression. EASIX (lactate dehydrogenase × creatinine/platelet count) was calculated continuously until 1-year after HCT. Log transformation using base 2 (log2) was applied to all EASIX variables to reduce skew. In total, 360 patients (71%) received CD34+-selected and 149 (29%) unmodified allo-HCT. Among all patients, EASIX scores increased rapidly, peaked at day +8, then declined rapidly until day +33. Thereafter, scores declined gradually but remained above the pre-HCT baseline. In unmodified HCT, scores appeared higher over time than in CD34+-selected patients. EASIX discrimination of NRM was highest around day +180 (concordance index = 0.85) in both platforms, but the prognostic impact of EASIX across time points differed between the 2 platforms. Mean EASIX scores were higher in men (mean log2 +0.52) and in patients who developed grade 2 to 4 GVHD (+0.81) and lower in patients who received matched vs mismatched donors (-0.81, all P < .01). EASIX scores are dynamic and variably concordant with NRM when analyzed longitudinally, and patterns differ between HCT platforms. Compared to pre-HCT evaluation, post-HCT EASIX scores may better predict risk of NRM as patients acquire additional endothelial injury and toxicities.
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Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Adulto , Masculino , Humanos , Enfermedad Injerto contra Huésped/diagnóstico , Enfermedad Injerto contra Huésped/etiología , Trasplante Homólogo/efectos adversos , Análisis de Supervivencia , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Antígenos CD34RESUMEN
Allogeneic hematopoietic stem cell transplantation (Allo-HCT) remains the only curative treatment for myelofibrosis (MF). Transplantation in patients with MF is mostly done using a reduced intensity conditioning regimen with calcineurin inhibitors for graft versus host disease (GVHD) prophylaxis. Here we sought to evaluate outcomes of patients who underwent an ex vivo CD34+ -selected allo-HCT using myeloablative conditioning (MAC). Twenty-seven patients were included in this retrospective analysis. All patients were conditioned with busulfan, melphalan and fludarabine and antithymocyte globulin to prevent graft rejection. G-CSF mobilized peripheral blood stem cell grafts were depleted of T-cells using immunomagnetic CD34+ selection by CliniMACS device. Median follow-up among survivors was 50.6 months. The estimated 3-year overall survival, relapse free survival and the combined endpoint of GVHD/relapse free survival were 88% (95% CI, 75-100%), 80% (95% CI, 66-98%) and 74% (95% CI, 59-93%), respectively. The cumulative incidence of grade II-IV acute GVHD at day 100 was 33.3% (95% CI 16.4-51.3%), and two patients suffered chronic GVHD. There were no cases of primary graft failure. However, delayed graft failure occurred in two patients. We conclude that CD34+ selected allo-HCT with a MAC resulted in high survival rates in this cohort of patients with MF.
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Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Mielofibrosis Primaria , Antígenos CD34 , Enfermedad Injerto contra Huésped/prevención & control , Trasplante de Células Madre Hematopoyéticas/métodos , Humanos , Mielofibrosis Primaria/terapia , Estudios Retrospectivos , Acondicionamiento Pretrasplante/métodos , Trasplante HomólogoRESUMEN
An evidence-based triage plan for cellular therapy distribution is critical in the face of emerging constraints on healthcare resources. We evaluated the impact of treatment delays related to COVID-19 on patients scheduled to undergo hematopoietic cell transplantation (HCT) or chimeric antigen receptor T-cell (CAR-T) therapy at our center. Data were collected in real time between March 19 and May 11, 2020, for patients who were delayed to cellular therapy. We evaluated the proportion of delayed patients who ultimately received cellular therapy, reasons for not proceeding to cellular therapy, and changes in disease and health status during delay. A total of 85 patients were delayed, including 42 patients planned for autologous HCT, 36 patients planned for allogeneic HCT, and 7 patients planned for CAR-T therapy. Fifty-six of these patients (66%) since received planned therapy. Five patients died during the delay. The most common reason for not proceeding to autologous HCT was good disease control in patients with plasma cell dyscrasias (75%). The most common reason for not proceeding to allogeneic HCT was progression of disease (42%). All patients with acute leukemia who progressed had measurable residual disease (MRD) at the time of delay, whereas no patient without MRD at the time of delay progressed. Six patients (86%) ultimately received CAR-T therapy, including 3 patients who progressed during the delay. For patients with high-risk disease such as acute leukemia, and particularly those with MRD at the time of planned HCT, treatment delay can result in devastating outcomes and should be avoided if at all possible.
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COVID-19 , Trasplante de Células Madre Hematopoyéticas , Inmunoterapia Adoptiva , Pandemias , SARS-CoV-2 , Tiempo de Tratamiento , Adulto , Anciano , Aloinjertos , Amiloidosis/terapia , Anemia Aplásica/terapia , COVID-19/complicaciones , COVID-19/epidemiología , COVID-19/transmisión , Defensa Civil , Infección Hospitalaria/epidemiología , Infección Hospitalaria/prevención & control , Progresión de la Enfermedad , Práctica Clínica Basada en la Evidencia/organización & administración , Femenino , Trasplante de Células Madre Hematopoyéticas/estadística & datos numéricos , Humanos , Control de Infecciones/métodos , Transmisión de Enfermedad Infecciosa de Profesional a Paciente , Leucemia/mortalidad , Leucemia/patología , Leucemia/terapia , Masculino , Persona de Mediana Edad , Enfermedades Mielodisplásicas-Mieloproliferativas/mortalidad , Enfermedades Mielodisplásicas-Mieloproliferativas/terapia , Neoplasia Residual , Neoplasias/mortalidad , Neoplasias/terapia , Ciudad de Nueva York/epidemiología , Asignación de Recursos , Tiempo de Tratamiento/estadística & datos numéricos , Trasplante Autólogo , Triaje/organización & administración , Adulto JovenRESUMEN
Clonal hematopoiesis (CH) describes somatic mutations in hematopoietic stem and progenitor cells resulting in clonal expansion in individuals with no overt hematologic disease. Since CH increases in an age-related manner, understanding its role in hematopoietic cell transplantation (HCT) has become increasingly relevant to an aging transplant population. Multiple factors distinguish post-transplant hematopoiesis from unperturbed, steady-state hematopoiesis, including the influence of immunosuppressants, cytotoxic reagents, and marked proliferative stress, all of which may enhance or diminish the opportunity for clonal expansion. We reviewed the available clinical evidence on the consequences of CH at time of transplant in patients undergoing autologous HCT, and the impact of donor and recipient CH on allogeneic HCT outcomes. In the absence of evidence-based guidelines, we share our suggestions for managing donors and recipients found to have CH. Large-scale studies are needed to guide an evidence-based, uniform approach for the management of CH in the setting of HCT.
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Hematopoyesis Clonal , Hematopoyesis , Trasplante de Células Madre Hematopoyéticas , Toma de Decisiones Clínicas , Manejo de la Enfermedad , Progresión de la Enfermedad , Enfermedad Injerto contra Huésped/etiología , Enfermedades Hematológicas/diagnóstico , Enfermedades Hematológicas/etiología , Enfermedades Hematológicas/mortalidad , Enfermedades Hematológicas/terapia , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Trasplante de Células Madre Hematopoyéticas/métodos , Células Madre Hematopoyéticas/citología , Células Madre Hematopoyéticas/metabolismo , Humanos , Pronóstico , Donantes de Tejidos , Trasplante Autólogo , Trasplante Homólogo , Resultado del TratamientoRESUMEN
OBJECTIVES: We sought to examine the natural history of geriatric assessment (GA) and quality of life (QOL) domains among adults age ≥ 50 years undergoing autologous hematopoietic cell transplantation (autoHCT). MATERIALS AND METHODS: A QOL tool and cancer-specific GA were completed before autoHCT in patients ≥50 years, and at 100 days, six months, and one year post-transplant. RESULTS: One hundred eighty-four patients completed the pre-transplant QOL/GA assessment, 169 (92%) completed the 100-day assessment, 162 (88%) completed the six-month assessment, and 145 (79%) completed the twelve-month assessment. Functional status, as measured by instrumental activities of daily living (IADL), decreased from baseline to day 101 (mean change -0.42 points, 95% CI, -0.75 to -0.09, p = 0.01) but returned to baseline by one year. Physical function as measured by Medical Outcomes Study-Physical Health (MOS-PH) increased by mean of 3.27 points (95% CI, -0.02 to 6.56, p = 0.05) by one year. Physician-rated KPS improved by one year, but patient-rated KPS did not. No QOL metric deteriorated from baseline. Baseline factors predictive of IADL and MOS-PH as measured over time included comorbidities and disease status at transplant. IADL and MOS-PH as measured over time were not significantly associated with age. CONCLUSIONS: AutoHCT for adults age ≥ 50 years resulted in an initial decrease in functional status, with subsequent improvement back to baseline by one year. Physical health and QOL measures were improved or unchanged over time. AutoHCT is well tolerated in well selected older patients, using patient reported geriatric metrics as outcomes.
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Trasplante de Células Madre Hematopoyéticas , Calidad de Vida , Actividades Cotidianas , Anciano , Evaluación Geriátrica , Humanos , Trasplante AutólogoRESUMEN
Telehealth involves the use of telecommunication and information technology for the delivery of clinical care and may be a mechanism to alleviate the burden of visits faced by patients undergoing hematopoietic cell transplantation (HCT). Few studies have evaluated the feasibility and acceptability of telehealth visits in the care of HCT patients. We conducted 27 telehealth visits with 25 patients undergoing HCT using a videoconferencing system that allows for real-time, 2-way interactions and administered satisfaction surveys to patients and providers. Of the 25 patients included in the study, 20 (80%) and 5 (20%) were undergoing autologous and allogeneic HCT, respectively. The telehealth visits were distributed as follows: 3 inpatient visits upon admission for HCT; 11 inpatient visits between 2 and 14 days post-HCT; 4 inpatient visits prior to discharge after HCT; 8 outpatient, post-HCT follow-up visits; and 1 handoff to a community oncologist. Out of a total of 54 provider assessments, 7 providers (13%) were unable to complete some part of the physical examination, but no provider reported being unable to manage patients' symptoms through telehealth. Eighty-one percent of patients were either satisfied or very satisfied with the telemedicine session. Overall satisfaction was higher among patients than providers (mean scores 4.12 versus 2.64; scale 1 to 5, with 1 = very poor to 5 = excellent). Technological barriers resulting in delays and suboptimal physical examination were largely responsible for provider dissatisfaction. The use of telehealth to deliver comprehensive follow-up care to HCT patients is feasible across different HCT types but is dependent upon quality of data streaming and videoconferencing technologies.
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Trasplante de Células Madre Hematopoyéticas , Telemedicina , Humanos , Proyectos Piloto , Encuestas y Cuestionarios , Comunicación por VideoconferenciaRESUMEN
Although the use of geriatric assessment (GA) in the allogeneic hematopoietic cell transplantation (HCT) setting has been reported, few studies have evaluated the impact of patient-reported function on autologous HCT (autoHCT) outcomes. In this study, GA, including the administration of Functional Assessment of Cancer Therapy-Bone Marrow Transplant (FACT-BMT) quality of life tool, was performed in 184 patients age ≥50 years (median age, 61 years; range, 50 to 75 years) before autoHCT. Associations among GA findings, quality of life metrics, and post-transplantation outcomes were evaluated using Cox regression. Indications for autoHCT included multiple myeloma (73%), non-Hodgkin lymphoma (20%), and other disorders (7%). The median progression-free survival (PFS) was 28 months, whereas the median overall survival (OS) was not reached. In unadjusted analysis, both PFS and OS were significantly associated with 5 GA components: limitation in instrumental activities of daily living, patient-reported Karnofsky Performance Status (KPS), and the Physical, Functional, and BMT subscale scores of the FACT-BMT. In multivariate analysis, 3 components-limitation in instrumental activities of daily living, patient-reported KPS, and FACT-BMT Physical subscale-remained predictive of both PFS and OS when adjusted for age, provider-reported KPS, disease status, and HCT comorbidity index. In older adults undergoing autoHCT, limitation in any 1 of 3 patient-reported measures of functional status was independently associated with inferior PFS and OS, even after adjusting for known prognostic factors.
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Trasplante de Células Madre Hematopoyéticas/métodos , Medición de Resultados Informados por el Paciente , Calidad de Vida , Acondicionamiento Pretrasplante/métodos , Trasplante Autólogo/métodos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Análisis de SupervivenciaRESUMEN
Necrotizing (malignant) otitis externa (NOE) is a rare and invasive infection originating in the external acoustic meatus seen most commonly in diabetes and other immunocompromised states. After a protracted course, disease can smolder and extend into the mastoid, skull base, dural sinuses, and intracranially. We present a case of NOE complicated by mastoiditis, dural sinus thrombosis, and Bezold's abscess in an uncontrolled diabetic presenting with a prolonged course of facial nerve palsy. We stress the importance of maintaining a high index of clinical suspicion for NOE in diabetic patients and offering timely, aggressive treatment to mitigate its complications.