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BACKGROUND: Consensus definitions for the diagnosis of invasive fungal diseases (IFDs) were updated in 2020 to increase the certainty of IFD for inclusion in clinical trials, for instance by increasing biomarker cutoff limits to define positivity. To date, there is a paucity of data as to the impact of the revised definitions on clinical trials. METHODS: In this study, we sought to determine the impact of the new definitions on classifying invasive aspergillosis (IA), the most common invasive mold disease in immunocompromised patients. We reclassified 226 proven and probable IA cases plus 139 possible IFD cases in the Aspergillus Technology Consortium (AsTeC) and in an antifungal prophylaxis trial (BMT CTN 0101) using the new criteria. RESULTS: Fewer cases met the more stringent diagnostic 2020 criteria after applying the reclassification criteria to define probable IA. Of 188 evaluable probable cases, 41 (22%) were reclassified to 40 possible IA and 1 probable IFD. Reclassification to possible IFD occurred in 22% of hematologic malignancy (HM) patients, 29% of hematopoietic cell transplant (HCT) patients, and in no lung transplant (LT) patients. Date of diagnosis was established a median (range) of 3 (1-105) days later in 15% of probable IA cases using the new criteria. Applying the new definitions to the BMT CTN 0101 trial, the power to detect the same odds ratio decreased substantially. CONCLUSIONS: The updated IA consensus definitions may impact future trial designs, especially for antifungal prophylaxis studies.
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Acute graft-versus-host disease (aGVHD) contributes to poor outcomes and increased healthcare resource utilization (HRU) after allogeneic hematopoietic stem cell transplantation (HCT). However, HRU and the economic burden of aGVHD based on severity of the disease is not well characterized. Our study cohort comprised 290 adults who underwent allogeneic HCT between 2010 and 2018. Costs, HRU, and all-cause mortality in the 100-day and 365-day periods after HCT were compared between patients with aGVHD and those without aGVHD. The impact of aGVHD severity and gastrointestinal (GI) involvement on mortality, HRU, and economic burden was also evaluated. Medical costs and total hospital length of stay (LOS) were retrieved from administrative data that allocate costs to services based on departmental input for resource use and were adjusted to 2018 dollars. The Wilcoxon rank-sum test was used to compare the number of inpatient days and total costs. Multivariable linear regression was fitted on log-transformed costs. Compared with patients without aGVHD, those with aGVHD had a significantly greater median hospital LOS (28 days versus 22 days) and higher rates of intensive care unit (ICU) admission (13% versus 6%) and rehospitalization (59% versus 38%) during the first 100 days post-HCT. The presence of grade I-II aGVHD significantly prolonged the hospital LOS by a median of 3 days and increased the readmission rate by 18%, whereas grade III-IV aGVHD was associated with a nearly 30% increase in the readmission rate and a doubling of inpatient LOS, ICU admission rate, and mortality in the first 100 days post-HCT. Compared with the absence of aGVHD, lower GI involvement in aGVHD was also associated with increased risk of readmission (30%) and twice as many inpatient days, doubling the likelihood of ICU admission and mortality over the first 100 days. Similar findings were observed over days 101 to 365 post-HCT. The mean cost attributable to aGVHD regardless of grade was $60,923 in the first 100 days post-HCT. This cost varied by grade. The mean aGVHD- attributable costs were $18,071 for grade I, $36,115 for grade II and $120,929 for grade III/IV aGVHD and $114,668 for aGVHD involving the lower GI tract. In the 101- to 365-day period, the mean attributable aGVHD cost regardless of grade was $17,527. This cost also varied by grade. There were no additional aGVHD-attributable costs for grade I, but the mean aGVHD-attributable costs were $9743 for grade II, $62,220 for grade III/IV, and $55,724 for aGVHD with lower GI involvement compared with the controls without aGVHD. High-grade aGVHD and GI involvement in aGVHD, especially lower GI aGVHD, is associated with a considerably increased mortality and healthcare economic burden. Therefore, it is imperative that new therapeutic strategies be developed for this patient population.
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Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Atención a la Salud , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Humanos , Aceptación de la Atención de Salud , Estudios RetrospectivosRESUMEN
Patients with myelodysplastic syndromes (MDS) or acute myeloid leukemia (AML) are generally older and have more comorbidities. Therefore, identifying personalized treatment options for each patient early and accurately is essential. To address this, we developed a computational biology modeling (CBM) and digital drug simulation platform that relies on somatic gene mutations and gene CNVs found in malignant cells of individual patients. Drug treatment simulations based on unique patient-specific disease networks were used to generate treatment predictions. To evaluate the accuracy of the genomics-informed computational platform, we conducted a pilot prospective clinical study (NCT02435550) enrolling confirmed MDS and AML patients. Blinded to the empirically prescribed treatment regimen for each patient, genomic data from 50 evaluable patients were analyzed by CBM to predict patient-specific treatment responses. CBM accurately predicted treatment responses in 55 of 61 (90%) simulations, with 33 of 61 true positives, 22 of 61 true negatives, 3 of 61 false positives, and 3 of 61 false negatives, resulting in a sensitivity of 94%, a specificity of 88%, and an accuracy of 90%. Laboratory validation further confirmed the accuracy of CBM-predicted activated protein networks in 17 of 19 (89%) samples from 11 patients. Somatic mutations in the TET2, IDH1/2, ASXL1, and EZH2 genes were discovered to be highly informative of MDS response to hypomethylating agents. In sum, analyses of patient cancer genomics using the CBM platform can be used to predict precision treatment responses in MDS and AML patients.
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Biología Computacional/métodos , Genómica/instrumentación , Leucemia Mieloide Aguda/genética , Síndromes Mielodisplásicos/genética , Adulto , Anciano , Anciano de 80 o más Años , Biología Computacional/estadística & datos numéricos , Variaciones en el Número de Copia de ADN/genética , Metilación de ADN/efectos de los fármacos , Proteínas de Unión al ADN/genética , Dioxigenasas , Proteína Potenciadora del Homólogo Zeste 2/genética , Femenino , Humanos , Isocitrato Deshidrogenasa/genética , Leucemia Mieloide Aguda/terapia , Masculino , Persona de Mediana Edad , Mutación , Síndromes Mielodisplásicos/terapia , Ensayos Clínicos Controlados no Aleatorios como Asunto , Medicina de Precisión/instrumentación , Valor Predictivo de las Pruebas , Estudios Prospectivos , Proteínas Proto-Oncogénicas/genética , Proteínas Represoras/genética , Sensibilidad y Especificidad , Factores de Transcripción/genética , Resultado del TratamientoRESUMEN
One critical factor impeding successful management of invasive aspergillosis (IA) is the lack of reliable biomarkers to assess therapeutic response. We hypothesized that changes in certain host biomarkers reflect the nature of infection status and disease progression. Upon primary IA diagnosis, these disease status biomarkers can be monitored to track response to antifungal therapy and provide early markers that prognosticate likelihood of response. Herein, we analyzed serum levels of three prominent host disease status biomarkers C-reactive protein (CRP), haptoglobin (Hp), and annexin A1 (ANXA1) in IA patients during antifungal therapy. A total of 81 serial serum samples were collected at five or six different time points relative to IA diagnosis from 15 probable IA patients (10 acute leukemia [AL] and five hematopoietic stem cell transplantation [HSCT]). Of note, different biomarker profiles were observed in AL and HSCT patients, as not only levels of markers were significantly lower in HSCT patients but also more prominent interconnections among markers were observed in AL patients. Using a composite evaluation, patients were categorized as responders, nonresponders, and stable cases at last specimen. For AL responders, typical biomarker profiles were high initially but rapidly decreased for CRP and Hp post antifungal therapy, while low initial ANXA1 values were restored to normal levels after treatment. In contrast, CRP and Hp were persistently elevated whilst ANXA1 remained low throughout therapy in AL non-responders. As a pilot proof-of-concept study, our work demonstrates the great potential of using host biomarkers to monitor early therapeutic response in leukemia patients.
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Anexina A1/metabolismo , Antifúngicos/uso terapéutico , Aspergilosis/tratamiento farmacológico , Biomarcadores/análisis , Proteína C-Reactiva/metabolismo , Haptoglobinas/metabolismo , Infecciones Fúngicas Invasoras/tratamiento farmacológico , Adulto , Anciano , Aspergilosis/sangre , Aspergilosis/etiología , Biomarcadores/sangre , Femenino , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Humanos , Infecciones Fúngicas Invasoras/sangre , Infecciones Fúngicas Invasoras/diagnóstico , Infecciones Fúngicas Invasoras/etiología , Cinética , Leucemia Mieloide Aguda/complicaciones , Masculino , Persona de Mediana Edad , PronósticoRESUMEN
We analyzed late fatal infections (LFIs) in allogeneic stem cell transplantation (HCT) recipients reported to the Center for International Blood and Marrow Transplant Research. We analyzed the incidence, infection types, and risk factors contributing to LFI in 10,336 adult and 5088 pediatric subjects surviving for ≥2 years after first HCT without relapse. Among 2245 adult and 377 pediatric patients who died, infections were a primary or contributory cause of death in 687 (31%) and 110 (29%), respectively. At 12 years post-HCT, the cumulative incidence of LFIs was 6.4% (95% confidence interval [CI], 5.8% to 7.0%) in adults, compared with 1.8% (95% CI, 1.4% to 2.3%) in pediatric subjects; P < .001). In adults, the 2 most significant risks for developing LFI were increasing age (20 to 39, 40 to 54, and ≥55 years versus 18 to 19 years) with hazard ratios (HRs) of 3.12 (95% CI, 1.33 to 7.32), 3.86 (95% CI, 1.66 to 8.95), and 5.49 (95% CI, 2.32 to 12.99) and a history of chronic graft-versus-host disease GVHD (cGVHD) with ongoing immunosuppression at 2 years post-HCT compared with no history of GVHD with (HR, 3.87; 95% CI, 2.59 to 5.78). In pediatric subjects, the 3 most significant risks for developing LFI were a history of cGVHD with ongoing immunosuppression (HR, 9.49; 95% CI, 4.39 to 20.51) or without ongoing immunosuppression (HR, 2.7; 95% CI, 1.05 to 7.43) at 2 years post-HCT compared with no history of GVHD, diagnosis of inherited abnormalities of erythrocyte function compared with diagnosis of acute myelogenous leukemia (HR, 2.30; 95% CI, 1.19 to 4.42), and age >10 years (HR, 1.92; 95% CI, 1.15 to 3.2). This study emphasizes the importance of continued vigilance for late infections after HCT and institution of support strategies aimed at decreasing the risk of cGVHD.
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Trasplante de Células Madre Hematopoyéticas , Terapia de Inmunosupresión/efectos adversos , Infecciones/mortalidad , Leucemia Mieloide Aguda , Adolescente , Adulto , Factores de Edad , Anciano , Aloinjertos , Niño , Preescolar , Enfermedad Crónica , Femenino , Humanos , Incidencia , Lactante , Recién Nacido , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/mortalidad , Leucemia Mieloide Aguda/terapia , Masculino , Persona de Mediana Edad , Factores de TiempoAsunto(s)
Antígenos CD34/sangre , Trasplante de Células Madre Hematopoyéticas , Leucemia Mieloide Aguda , Síndromes Mielodisplásicos , Quimera por Trasplante/sangre , Aloinjertos , Femenino , Estudios de Seguimiento , Humanos , Leucemia Mieloide Aguda/sangre , Leucemia Mieloide Aguda/terapia , Masculino , Síndromes Mielodisplásicos/sangre , Síndromes Mielodisplásicos/terapia , Neoplasia Residual , Estudios ProspectivosRESUMEN
Mucormycosis is an aggressive, life-threatening infection caused by fungi in the order Mucorales. The current diagnosis of mucormycosis relies on mycological cultures, radiology and histopathology. These methods lack sensitivity and are most definitive later in the course of infection, resulting in the prevention of timely intervention. PCR-based approaches have shown promising potential in rapidly diagnosing mucormycosis. The spore coating protein homolog encoding CotH genes are uniquely and universally present among Mucorales. Thus, CotH genes are potential targets for the rapid diagnosis of mucormycosis. We infected mice with different Mucorales known to cause human mucormycosis and investigated whether CotH could be PCR amplified from biological fluids. Uninfected mice and those with aspergillosis were used to determine the specificity of the assay. CotH was detected as early as 24 h postinfection in plasma, urine, and bronchoalveolar lavage (BAL) samples from mice infected intratracheally with Rhizopus delemar, Rhizopus oryzae, Mucor circinelloides, Lichtheimia corymbifera, or Cunninghamella bertholletiae but not from samples taken from uninfected mice or mice infected with Aspergillus fumigatus Detection of CotH from urine samples was more reliable than from plasma or BAL fluid. Using the receiver operating characteristic method, the sensitivity and the specificity of the assay were found to be 90 and 100%, respectively. Finally, CotH was PCR amplified from urine samples of patients with proven mucormycosis. Thus, PCR amplification of CotH is a promising target for the development of a reliable, sensitive, and simple method of early diagnosis of mucormycosis.
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Mucorales/aislamiento & purificación , Mucormicosis/diagnóstico , Reacción en Cadena de la Polimerasa , Animales , Aspergilosis/diagnóstico , Aspergilosis/genética , ADN de Hongos/análisis , ADN de Hongos/genética , Proteínas Fúngicas/genética , Humanos , Ratones , Mucorales/genética , Mucormicosis/genética , Reproducibilidad de los Resultados , Sensibilidad y EspecificidadRESUMEN
Relapsed acute myeloid leukemia (AML) is a significant challenge after allogeneic hematopoietic cell transplant (HCT). Multiparameter flow cytometry (MFC), conventional cytogenetics (CG), and fluorescence in situ hybridization (FISH) are routinely performed on bone marrow specimens prior to HCT to assess disease status. We questioned the extent by which pre-HCT evidence of minimal residual disease (MRD) detected by these standard assays, corresponded with post-HCT relapse. We conducted a single center, retrospective study of 166 AML patients who underwent HCT. Thirty-eight of one hundred sixty-six (23%) patients in complete remission (CR) or CR with incomplete count recovery (CRi) had MRD detectable by MFC, CG, or FISH. MRD was more frequently seen in patients with poor risk karyotype at diagnosis (P = 0.011). MRD-negative patients (MRDneg) had significantly longer overall survival (OS) and relapse-free survival than patients who were MRD positive (MRDpos) (P = 0.002 and 0.013, respectively). In patients with MRDpos prior to HCT, the presence of acute graft vs. host disease (GVHD) (grade ≥ 2) or chronic GVHD significantly improved progression free survival (PFS) (hazard ratio (HR) = 0.053 (95% confidence interval (CI): 0.01-0.279), P = 0.0005) and OS (HR = 0.211 (95% CI: 0.081-0.547), P = 0.0014).
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Trasplante de Células Madre Hematopoyéticas , Leucemia Mieloide Aguda/patología , Leucemia Mieloide Aguda/cirugía , Neoplasia Residual/patología , Neoplasia Residual/cirugía , Adulto , Anciano , Análisis Citogenético , Supervivencia sin Enfermedad , Femenino , Citometría de Flujo , Enfermedad Injerto contra Huésped , Humanos , Estimación de Kaplan-Meier , Leucemia Mieloide Aguda/mortalidad , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/mortalidad , Recurrencia Local de Neoplasia/patología , Recurrencia Local de Neoplasia/cirugía , Neoplasia Residual/mortalidad , Pronóstico , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Trasplante Homólogo , Resultado del TratamientoRESUMEN
Although bone marrow evaluation on day 14 after initiation of induction chemotherapy (D14 BM) is a widely accepted practice in patients with acute myeloid leukemia (AML), it has suboptimal predictive value for predicting complete remission. We retrospectively analyzed pretreatment characteristics and post-induction response in a cohort of AML patients to determine if adding clinical and laboratory characteristics can improve the predictive value of the D14 BM evaluation. Among 297 patients treated for AML at the single institution 183 patients (61%) had leukemia-positive D14 BM. Of those, 94 were given reinduction chemotherapy and 89 were not. Of the 89 patients who did not receive reinduction, 32 (36%) subsequently achieved complete remission (CR) or complete remission with incomplete count recovery (CRi), and 57 (64%) had persistent disease. Persistent disease after positive D14 BM was more likely associated with higher percentage of D14 myeloblasts, a history of relapsed disease before induction, and higher risk disease compared to patients who subsequently achieved CR. Age, diagnostic white blood cell count, and the D14 BM cellularity did not influence the subsequent likelihood of achieving remission in patients with a positive D14 BM. A new mathematical equation was created and resulted in a positive predictive value of 83%, negative predictive value 90% and accuracy 88% for correctly identifying remission status after positive D14 BM in AML. The accuracy of predicting response using these additional parameters was significantly higher than without (0.88 vs. 0.80, P=0.002). Our new model provides better accuracy for predicting the likelihood of achieving remission and if validated in future studies may be useful for managing AML patients.
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Leucemia Mieloide Aguda/patología , Inducción de Remisión , Adulto , Anciano , Biopsia , Médula Ósea/patología , Células Precursoras de Granulocitos/patología , Humanos , Persona de Mediana Edad , Modelos Teóricos , Valor Predictivo de las Pruebas , Pronóstico , Estudios Retrospectivos , Factores de Tiempo , Adulto JovenRESUMEN
Therapeutic strategies for multiple myeloma (MM) have changed dramatically over the past decade. Thus, the role of hematopoietic stem cell transplantation (HCT) must be considered in the context of this evolution. In this evidence-based review, we have critically analyzed the data from the most recent clinical trials to better understand how to incorporate HCT and when HCT is indicated. We have provided our recommendations based on strength of evidence with the knowledge that ongoing clinical trials make this a dynamic field. Within this document, we discuss the decision to proceed with autologous HCT, factors to consider before proceeding to HCT, the role of tandem autologous HCT, post-HCT maintenance therapy, and the role of allogeneic HCT for patients with MM.
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Rayos gamma/uso terapéutico , Trasplante de Células Madre Hematopoyéticas/métodos , Mieloma Múltiple/terapia , Agonistas Mieloablativos/uso terapéutico , Acondicionamiento Pretrasplante/métodos , Factores de Edad , Aberraciones Cromosómicas , Manejo de la Enfermedad , Medicina Basada en la Evidencia , Humanos , Mieloma Múltiple/genética , Mieloma Múltiple/patología , Ensayos Clínicos Controlados Aleatorios como Asunto , Factores de Tiempo , Trasplante Autólogo , Trasplante HomólogoRESUMEN
In this prospective phase II clinical trial, multiple myeloma (MM) patients were randomized to receive a second (tandem) autologous stem cell transplantation (ASCT) based on whether they achieved a partial response or worse (≤PR) following initial ASCT (ASCT1). Patients who achieved a very good partial response or better (≥VGPR) had salvage ASCT at relapse. Seventy-five patients received conditioning therapy and ASCT1. A total of 44 patients (59%) achieved ≥VGPR, whereas 31 patients entered ≤PR and were offered tandem ASCT. In all, 20 patients agreed to tandem ASCT. Demographic and clinical characteristics were similar between the two cohorts except for median lactate dehydrogenase (LDH) (P = 0.0141) and percentage of marrow plasma cells before ASCT1 (P = 0.0047), both lower in the ≥VGPR group. Intent to treat analysis showed that patients who achieved ≥VGPR to ASCT1 had a trend toward improved progression-free survival (PFS) (37 vs. 26 months, P = 0.078) and superior overall survival (OS) (not reached vs. 50 months, P = 0.0073). Patients with ≤PR who declined tandem transplantation had shortened PFS (20 vs. 28 months, P = 0.05) but similar OS (53 vs. 57.5 months, P = 0.29) compared to those who received it. Thus, a favorable clinical response to ASCT1 identifies a low-risk group with superior long-term prognosis despite similar PFS.
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Peripheral blood progenitor cell mobilization practices vary significantly among institutions. Effective mobilization regimens include growth factor alone, chemotherapy and growth factor combined, and, more recently, incorporation of plerixafor with either approach. Many institutions have developed algorithms to improve stem cell mobilization success rates and cost-effectiveness. However, an optimal stem cell mobilization regimen has not been defined. Practical guidelines are needed to address important clinical questions, including which growth factor is optimal, what chemotherapy and dose is most effective, and when to initiate leukapheresis. We present recommendations, based on a comprehensive review of the literature, from the American Society of Blood and Marrow Transplantation.
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Movilización de Célula Madre Hematopoyética/métodos , Trasplante de Células Madre Hematopoyéticas/métodos , Células Madre/metabolismo , Acondicionamiento Pretrasplante/métodos , Trasplante Autólogo/métodos , Trasplante Homólogo/métodos , Guías como Asunto , Humanos , Estados UnidosRESUMEN
Hematopoietic stem cell transplantation (HCT) is a potentially life-saving therapy for patients with malignant and nonmalignant disease states. This article reviews the current published literature on the dosing of pharmacologic agents used for HCT preparative regimens with specific focus on the obese patient population. The review found that dose adjustments for obesity have, to date, been based empirically or extrapolated from published data in the nontransplantation patient population. As a result, the Committee determined that clear standards or dosing guidelines are unable to be made for the obese population because Level I and II evidence are unavailable at this time. Instead, the Committee provides a current published literature review to serve as a platform for conditioning agent dose selection in the setting of obesity. A necessary goal should be to encourage future prospective trials in this patient population because further information is needed to enhance our knowledge of the pharmacokinetics and pharmacodynamics of conditioning agents in the setting of obesity.
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Trasplante de Médula Ósea , Enfermedades Hematológicas , Trasplante de Células Madre Hematopoyéticas , Agonistas Mieloablativos , Obesidad , Acondicionamiento Pretrasplante , Humanos , Suero Antilinfocítico/uso terapéutico , Busulfano/uso terapéutico , Ciclofosfamida/uso terapéutico , Citarabina/uso terapéutico , Esquema de Medicación , Cálculo de Dosificación de Drogas , Etopósido/uso terapéutico , Enfermedades Hematológicas/complicaciones , Enfermedades Hematológicas/patología , Enfermedades Hematológicas/terapia , Melfalán/uso terapéutico , Agonistas Mieloablativos/uso terapéutico , Obesidad/complicaciones , Obesidad/patología , Obesidad/terapiaRESUMEN
Autologous hematopoietic stem cell transplantation (aHSCT) is a well-established treatment for malignancies such as multiple myeloma (MM) and lymphomas. Various changes in the field over the past decade, including the frequent use of tandem aHSCT in MM, the advent of novel therapies for the treatment of MM and lymphoma, and the addition of new stem cell mobilization techniques, have led to the need to reassess current stem cell mobilization strategies. Mobilization failures with traditional strategies are common and result in delays in treatment and increased cost and resource utilization. Recently, plerixafor-containing strategies have been shown to significantly reduce mobilization failure rates, but the ideal method to maximize stem cell yields and minimize costs associated with collection has not yet been determined. A panel of experts convened to discuss the currently available data on autologous hematopoietic stem cell mobilization and transplantation and to devise guidelines to optimize mobilization strategies. Herein is a summary of their discussion and consensus.
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Movilización de Célula Madre Hematopoyética/métodos , Trasplante de Células Madre Hematopoyéticas , Compuestos Heterocíclicos/uso terapéutico , Enfermedad de Hodgkin/terapia , Linfoma no Hodgkin/terapia , Mieloma Múltiple/terapia , Bencilaminas , Ciclamas , Filgrastim , Factor Estimulante de Colonias de Granulocitos/uso terapéutico , Factor Estimulante de Colonias de Granulocitos y Macrófagos/uso terapéutico , Movilización de Célula Madre Hematopoyética/normas , Enfermedad de Hodgkin/inmunología , Enfermedad de Hodgkin/mortalidad , Humanos , Linfoma no Hodgkin/inmunología , Linfoma no Hodgkin/mortalidad , Mieloma Múltiple/inmunología , Mieloma Múltiple/mortalidad , Polietilenglicoles , Proteínas Recombinantes/uso terapéutico , Análisis de Supervivencia , Trasplante AutólogoRESUMEN
PURPOSE: The cost-effectiveness of voriconazole versus fluconazole prophylaxis against fungal infections in hematopoietic cell transplant (HCT) recipients is investigated. METHODS: A decision-analytic model was developed to estimate the drug costs associated with planned or supplemental prophylaxis and empirical therapy and the costs of treating suspected or documented invasive fungal infections (IFIs) in HCT recipients. Published clinical trial data on 599 patients who received 100-180 days of prophylactic therapy with voriconazole or fluconazole were used to model specified IFI-prevention and mortality outcomes; 6-month, 12-month, and lifetime incremental cost-effectiveness ratios (ICERs) were estimated, with a bootstrap analysis performed to reffect the uncertainty of the clinical trial data. RESULTS: Estimated mean total prophylaxis and IFI-related costs associated with voriconazole versus fluconazole prophylaxis over 12 months were higher in the entire study population and among patients receiving HCT for diagnoses other than acute myeloid leukemia (AML) but were not significantly different for patients with AML. The cost per IFI avoided ($66,919) and the cost per life-year gained ($5,453) were lower among patients with AML who received voriconazole relative to the full study population. ICERs were more favorable for voriconazole over a 6-month time frame and when modeling was conducted using generic price data. Assuming a threshold value of $50,000 for one year of life gained, the calculated probability of voriconazole being cost-effective was 33% for the full study population and 85% for the AML subgroup. CONCLUSION: The decision model indicated that voriconazole prophylaxis was cost-effective for patients undergoing allogeneic HCT for AML.
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Antifúngicos/economía , Técnicas de Apoyo para la Decisión , Fluconazol/economía , Trasplante de Células Madre Hematopoyéticas/economía , Micosis/economía , Pirimidinas/economía , Triazoles/economía , Antifúngicos/uso terapéutico , Estudios de Casos y Controles , Estudios de Cohortes , Análisis Costo-Beneficio , Método Doble Ciego , Fluconazol/uso terapéutico , Estudios de Seguimiento , Trasplante de Células Madre Hematopoyéticas/métodos , Humanos , Micosis/tratamiento farmacológico , Micosis/epidemiología , Pirimidinas/uso terapéutico , Trasplante Homólogo , Triazoles/uso terapéutico , VoriconazolRESUMEN
Adequate hematopoietic stem cell (HSC) mobilization and collection is required prior to proceeding with high dose chemotherapy and autologous hematopoietic stem cell transplant. Cytokines such as G-CSF, GM-CSF, and peg-filgrastim, alone or in combination with plerixafor, and after chemotherapy have been used to mobilize HSCs. Studies have shown that the efficiency of HSC mobilization and collection may vary when different methods of mobilization are used. No studies have shown that survival is significantly affected by the method of mobilization, but some studies have suggested that cost and resource utilization may be different between different mobilization techniques. After the FDA approval of plerixafor with G-CSF to mobilize HSCs many transplant centers became concerned about the cost of HSC mobilization. A panel of experts was convened ant this paper reviews the current literature on the pharmacoeconomics of HSC mobilization.
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Movilización de Célula Madre Hematopoyética/economía , Trasplante de Células Madre Hematopoyéticas/economía , Economía Farmacéutica , Movilización de Célula Madre Hematopoyética/métodos , Trasplante de Células Madre Hematopoyéticas/métodos , HumanosRESUMEN
Survival after hematopoietic stem cell transplantation (HSCT) has improved and the number of allogeneic HSCTs performed annually in the United States is expected to reach 10,000 by 2015. The National Marrow Donor Program created the System Capacity Initiative to formulate mechanisms to care for the growing number of HSCT recipients. One proposed method to increase capacity is utilization of pharmacists to manage drug therapy via collaborative practice agreements (CPAs). Pharmacists have managed drug therapy in oncology patients with CPAs for decades; however, there are limited HSCT centers that employ this practice. Engaging in collaborative practice and billing agreements with credentialed pharmacists to manage therapeutic drug monitoring, chronic medical conditions, and supportive care in HSCT recipients may be cost-effective and enable physicians to spend more time on new or more complex patients. The goal of this paper is to provide a framework for implementation of a CPA and address how it may improve HSCT program capacity.
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Trasplante de Células Madre Hematopoyéticas , Práctica Asociada/organización & administración , Farmacéuticos/organización & administración , Médicos/organización & administración , Conducta Cooperativa , Monitoreo de Drogas , Humanos , Trasplante Homólogo , Estados UnidosRESUMEN
The National Marrow Donor Program, in partnership with the American Society for Blood and Marrow Transplantation, sponsored and organized a series of symposia to identify complex issues affecting the delivery of hematopoietic cell transplantation (HCT) and to collaboratively develop options for solutions. "Hematopoietic Cell Transplantation in 2020: A System Capacity Initiative" used a deliberative process model to engage professional organizations, experts, transplant centers, and stakeholders in a national collaborative effort. Year 2 efforts emphasized data analysis and identification of innovative ideas to increase HCT system efficiency, address future capacity requirements, and ensure adequate reimbursement for HCT programs to meet the projected need for HCT. This report highlights the deliberations and recommendations of Year 2 and the associated symposium held in September 2011.
Asunto(s)
Atención a la Salud , Adhesión a Directriz , Trasplante de Células Madre Hematopoyéticas , Sociedades Médicas , Donantes de Tejidos , Congresos como Asunto , Atención a la Salud/economía , Atención a la Salud/métodos , Atención a la Salud/organización & administración , Femenino , Adhesión a Directriz/economía , Adhesión a Directriz/organización & administración , Adhesión a Directriz/normas , Humanos , MasculinoRESUMEN
PURPOSE OF REVIEW: Antibiotic prophylaxis has been found to have multiple benefits in patients receiving intensive chemotherapy at high risk for infection. Interest continues in identifying what additional groups of high-risk patients might potentially benefit from its use. However, concerns about the potential emergence of antibiotic resistance have led to multiple recent studies exploring this issue. RECENT FINDINGS: The use of antibiotic prophylaxis in pediatric leukemia, myelodysplastic syndromes, and hematopoietic stem cell transplant populations has been evaluated in recent studies. Several centers have noted increased rates of antibiotic resistance in patients receiving prophylaxis. SUMMARY: Several single-center studies have emphasized the concern for the emergence of antibiotic resistance associated with the routine use of fluoroquinolone prophylaxis. The potential for antibiotic resistance continues to be worrisome and warrants further ongoing studies.