RESUMEN
Mobilization and collection of peripheral blood stem cells is part of the standard treatment procedure for non-Hodgkin's lymphoma patients eligible for high-dose chemotherapy with autologous stem cell transplantation. Mobilization is usually achieved with chemotherapy and/or cytokines, but plerixafor might be added in case of poor mobilization. Due to the high cost several institutions have developed their own management pathway to optimize use of plerixafor. Such models are however rarely generalizable; in a multi-center, European, non-interventional study, evaluating the impact of plerixafor in poor mobilizers, country specific differences in patient treatment and cost structure were obvious. For German centers, there was a non-significant reduction in the number of apheresis sessions carried out and in apheresis costs. In contrast to other European countries the majority of German Plerixafor patients were very poor mobilizing patients with initial CD34+ cell count ≤ 10/µl (40/51). In this group the number of apheresis sessions decreased from 2.1 to 1.6 sessions per patient (p = 0.01) and costs decreased from 6246 to 4758 (p = 0.01). Our results show that preemptive plerixafor use has a strong effect in poor mobilizers with an initial CD34+ cell count ≤ 10 cells/µl.
Asunto(s)
Movilización de Célula Madre Hematopoyética/economía , Compuestos Heterocíclicos , Linfoma no Hodgkin , Adulto , Anciano , Bencilaminas , Eliminación de Componentes Sanguíneos/economía , Costos y Análisis de Costo , Ciclamas , Femenino , Alemania , Compuestos Heterocíclicos/administración & dosificación , Compuestos Heterocíclicos/economía , Humanos , Recuento de Leucocitos , Linfoma no Hodgkin/sangre , Linfoma no Hodgkin/economía , Linfoma no Hodgkin/terapia , Masculino , Persona de Mediana Edad , Factores de TiempoRESUMEN
Plerixafor (Mozobil) in combination with granulocyte colony-stimulating factor (G-CSF) has shown to increase mobilization of peripheral blood stem cells (PBSC) as compared to G-CSF alone in patients undergoing autologous stem cell transplantation (ASCT). However, up to 25% of patients treated with G-CSF alone still fail mobilization. Adding plerixafor to poor mobilizers allows to rescue these patients from mobilization failure and to reduce the number of apheresis sessions. The goal of this retrospective study was to capture the impact of plerixafor on treatment outcome and on apheresis department efficiency. The latter was measured in terms of time-slots lost, that is, the number of apheresis sessions scheduled but not carried out due to poor mobilization, and the number of elective apheresis sessions performed for patients undergoing extracorporeal photopheresis (ECP). Hospital records of patients treated before and after introduction of plerixafor were collected and analyzed. With plerixafor, the mobilization failure rate dropped from 12% to 4% and the mean number of time-slots lost per patient dropped from 1.39 to 0.89. Additional drug costs due to plerixafor were partially balanced by a reduction in apheresis sessions, resulting in an additional cost of 759 per ASCT candidate. More importantly, with the use of plerixafor, the availability of time-slots turned from erratic to predictable such that freed capacity could be dedicated to other apheresis procedures. As a result, the number of ECP sessions increased from 0 in 2005 to 685 sessions in 2014.
Asunto(s)
Eliminación de Componentes Sanguíneos/estadística & datos numéricos , Movilización de Célula Madre Hematopoyética/métodos , Compuestos Heterocíclicos/uso terapéutico , Hospitales/normas , Bencilaminas , Eliminación de Componentes Sanguíneos/economía , Ciclamas , Quimioterapia Combinada/normas , Factor Estimulante de Colonias de Granulocitos/uso terapéutico , Compuestos Heterocíclicos/economía , Compuestos Heterocíclicos/farmacología , Humanos , Estudios RetrospectivosRESUMEN
Plerixafor is a CXC chemokine receptor (CXCR4) antagonist that mobilizes stem cells in the peripheral blood. It is indicated (in combination with granulocyte-colony stimulating factor [G-CSF]) to enhance the harvest of adequate quantities of cluster differentiation (CD) 34+ cells for autologous transplantation in patients with lymphoma or multiple myeloma whose cells mobilize poorly. Strategies for use include delayed re-mobilization after a failed mobilization attempt with G-CSF, and rescue or pre-emptive mobilization in patients in whom mobilization with G-CSF is likely to fail. Pre-emptive use has the advantage that it avoids the need to re-schedule the transplant procedure, with its attendant inconvenience, quality-of-life issues for the patient and cost of additional admissions to the transplant unit. UK experience from 2 major centers suggests that pre-emptive plerixafor is associated with an incremental drug cost of less than £2000 when averaged over all patients undergoing peripheral blood stem cell (PBSC) transplant. A CD34+ cell count of <15 µl-1 at the time of recovery after chemomobilization or after four days of G-CSF treatment, or an apheresis yield of <1 × 106 CD34+ cells/kg on the first day of apheresis, could be used to predict the need for pre-emptive plerixafor.
Asunto(s)
Quimioradioterapia/métodos , Consenso , Movilización de Célula Madre Hematopoyética/métodos , Compuestos Heterocíclicos/uso terapéutico , Neoplasias/tratamiento farmacológico , Bencilaminas , Ciclamas , Movilización de Célula Madre Hematopoyética/economía , Compuestos Heterocíclicos/economía , Humanos , Neoplasias/terapia , Trasplante de Células Madre de Sangre Periférica/métodos , Células Madre de Sangre Periférica/efectos de los fármacos , Premedicación , Trasplante Autólogo , Reino UnidoRESUMEN
Cyclophosphamide plus G-CSF (C+G-CSF) is one of the most widely used stem cell (SC) mobilization regimens for patients with multiple myeloma (MM). Plerixafor plus G-CSF (P+G-CSF) has demonstrated superior SC mobilization efficacy when compared with G-CSF alone and has been shown to rescue patients who fail mobilization with G-CSF or C+G-CSF. Despite the proven efficacy of P+G-CSF in upfront SC mobilization, its use has been limited, mostly due to concerns of high price of the drug. However, a comprehensive comparison of the efficacy and cost effectiveness of SC mobilization using C+G-CSF versus P+G-CSF is not available. In this study, we compared 111 patients receiving C+G-CSF to 112 patients receiving P+G-CSF. The use of P+G-CSF was associated with a higher success rate of SC collection defined as ⩾5 × 10(6) CD34+ cells/kg (94 versus 83%, P=0.013) and less toxicities. Thirteen patients in the C+G-CSF arm were hospitalized owing to complications while none in the P+G-CSF group. C+G-CSF was associated with higher financial burden as assessed using institutional-specific costs and charges (P<0.001) as well as using Medicare reimbursement rates (P=0.27). Higher rate of hospitalization, increased need for salvage mobilization, and increased G-CSF use account for these differences.
Asunto(s)
Ciclofosfamida , Factor Estimulante de Colonias de Granulocitos , Movilización de Célula Madre Hematopoyética/economía , Trasplante de Células Madre Hematopoyéticas/economía , Compuestos Heterocíclicos , Mieloma Múltiple , Autoinjertos , Bencilaminas , Costos y Análisis de Costo , Ciclamas , Ciclofosfamida/administración & dosificación , Ciclofosfamida/economía , Femenino , Factor Estimulante de Colonias de Granulocitos/administración & dosificación , Factor Estimulante de Colonias de Granulocitos/economía , Compuestos Heterocíclicos/administración & dosificación , Compuestos Heterocíclicos/economía , Humanos , Masculino , Mieloma Múltiple/economía , Mieloma Múltiple/terapiaRESUMEN
Plerixafor is an effective haematopoietic stem cell mobilising agent in candidates for autologous transplantation, including patients with myeloma and lymphoma. Here we compare 98 plerixafor recipients in the PHANTASTIC trial with 151 historic controls mobilised by conventional chemotherapy (each with granulocyte colony-stimulating factor, G-CSF). Seventy (71.4%) plerixafor-mobilised patients achieved the composite primary endpoint of ≥4 × 10(6) CD34+ cells kg(-1) in ≤2 aphereses and no clinically significant neutropenia, compared to 48 (31.8%) historic controls (P < 0.001), and this significant advantage was maintained in scenario analyses testing components of this composite endpoint. A patient-level cost analysis was undertaken for 249 patients, which included the cost of remobilising patients where initial mobilisation had failed. Combined mean treatment cost for plerixafor mobilised patients was £12,679 compared with £11,694 for historical controls. However, plerixafor produces an average saving of £3,828 per lymphoma patient but average cost increase by £5,245 per myeloma patient. The present data demonstrate cost-effectiveness for plerixafor as a first line mobilisation agent, certainly for lymphoma patients, where substantial resource savings and achievement of the primary endpoint are likely. J. Clin. Apheresis 31:434-442, 2016. © 2015 Wiley Periodicals, Inc.
Asunto(s)
Movilización de Célula Madre Hematopoyética/métodos , Compuestos Heterocíclicos/uso terapéutico , Bencilaminas , Análisis Costo-Beneficio , Costos y Análisis de Costo , Ciclamas , Factor Estimulante de Colonias de Granulocitos/economía , Factor Estimulante de Colonias de Granulocitos/uso terapéutico , Movilización de Célula Madre Hematopoyética/economía , Compuestos Heterocíclicos/economía , Estudio Históricamente Controlado , Humanos , Linfoma/economía , Linfoma/terapia , Mieloma Múltiple/economía , Mieloma Múltiple/terapiaRESUMEN
BACKGROUND AIMS: Hematopoietic cell mobilization with granulocyte-colony stimulating factor (G-CSF) and plerixafor results in superior CD34+ cell yield compared with G-CSF alone in patients with myeloma and lymphoma. However, plerixafor-based approaches may be associated with high costs. Several institutions use a "just-in-time" plerixafor approach, in which plerixafor is only administered to patients likely to fail mobilization with G-CSF alone. Whether such an approach is cost-effective is unknown. METHODS: We evaluated 136 patients with myeloma or lymphoma who underwent mobilization with 2 approaches of plerixafor utilization. Between January 2010 and October 2012, 76 patients uniformly received mobilization with G-CSF and plerixafor. Between November 2012 and June 2014, 60 patients were mobilized with plerixafor administered only to those patients likely to fail mobilization with G-CSF alone. RESULTS: The routine plerixafor group had a higher median peak peripheral blood CD34+ cell count (62 versus 29 cells/µL, P < 0.001) and a higher median day 1 CD34+ yield (2.9 × 10(6) CD34+ cells/kg versus 2.1 × 10(6) CD34+ cells/kg, P = 0.001). The median total CD34+ collection was higher with routine plerixafor use (5.8 × 10(6) CD34+ cells/kg versus 4.5 × 10(6) CD34+ cells/kg, P = 0.007). In the "just-in-time" group, 40% (n = 24) completed adequate collection without plerixafor. There was no difference in mobilization failure rates. The mean plerixafor doses used was lower with "just-in-time" approach (1.3 versus 2.1, P = 0.0002). The mean estimated cost in the routine plerixafor group was higher (USD 27,513 versus USD 23,597, P = 0.01). DISCUSSION: Our analysis demonstrates that mobilization with a just-in-time plerixafor approach is a safe, effective, and cost-efficient strategy for HPC collection.
Asunto(s)
Factor Estimulante de Colonias de Granulocitos/farmacología , Movilización de Célula Madre Hematopoyética/métodos , Compuestos Heterocíclicos/farmacología , Linfoma/tratamiento farmacológico , Mieloma Múltiple/tratamiento farmacológico , Adulto , Anciano , Antígenos CD34/metabolismo , Bencilaminas , Análisis Costo-Beneficio , Ciclamas , Femenino , Factor Estimulante de Colonias de Granulocitos/inmunología , Movilización de Célula Madre Hematopoyética/economía , Células Madre Hematopoyéticas/metabolismo , Compuestos Heterocíclicos/economía , Humanos , Linfoma/patología , Masculino , Persona de Mediana Edad , Mieloma Múltiple/patología , Resultado del Tratamiento , Adulto JovenRESUMEN
BACKGROUND: High-dose chemotherapy supported with autologous stem cell transplantation is a standard therapeutic option for a subset of patients with lymphoid malignancies. Cell procurement is nowadays done almost exclusively through cytapheresis, after mobilization of hematopoietic stem and progenitor cells (HSPCs) from the marrow to peripheral blood (PB). The egress of HSPCs out of hematopoietic niches occurs in various physiologic or nonhomeostatic situations; pharmacologic approaches include the administration of acutely myelosuppressive agents or hematopoietic growth factors such as recombinant human granulocyte-colony-stimulating factor (rHuG-CSF). The introduction of plerixafor, a first-of-its-class molecule that reversibly inhibits the interaction between the chemokine CXCL-12 (also known as SDF-1) and its receptor CXCR-4, has offered new opportunities for the so-called "poor mobilizers" who achieve insufficient mobilization and/or collection with conventional approaches. STUDY DESIGN AND METHODS: Because of the lack of consensus on a definition for poor mobilizers and the relatively high cost of plerixafor, French competent authorities have mandated a postmarketing survey on its use in routine practice. RESULTS AND CONCLUSION: We report here the results of this nationwide survey that confirms the clinical efficacy of plerixafor, even in the subset of patients who barely increased PB CD34+ cell count in response to rHuG-CSF-containing mobilization regimen. Furthermore, analysis of this registry showed that despite heterogeneity in medical practices, the early-"on-demand" or "preemptive"-introduction of plerixafor was widely used and did not result in an excess of prescriptions, beyond its expected use at the time when marketing authorization was granted.
Asunto(s)
Movilización de Célula Madre Hematopoyética/métodos , Trasplante de Células Madre Hematopoyéticas , Compuestos Heterocíclicos/administración & dosificación , Adulto , Anciano , Autoinjertos , Bencilaminas , Quimiocina CXCL12/antagonistas & inhibidores , Quimiocina CXCL12/sangre , Ciclamas , Femenino , Francia , Movilización de Célula Madre Hematopoyética/economía , Compuestos Heterocíclicos/economía , Humanos , Masculino , Persona de Mediana Edad , Receptores CXCR4/antagonistas & inhibidores , Receptores CXCR4/sangreRESUMEN
The optimal stem cell mobilization regimen for patients with multiple myeloma (MM) remains undefined. We retrospectively compared our experience in hematopoietic cell mobilization in 83 MM patients using fractionated high-dose CY and G-CSF with G-CSF plus preemptive plerixafor. All patients in the CY group (n=56) received fractionated high-dose CY (5 g/m(2) divided into five doses of 1 g/m(2) every 3 h) with G-CSF. All patients in the plerixafor group (n=27) received G-CSF and plerixafor preemptively based on an established algorithm. Compared with plerixafor, CY use was associated with higher total CD34+ cell yield (7.5 × 10(6) vs 15.5 × 10(6) cells/kg, P=0.005). All patients in both groups yielded ⩾4 × 10(6) CD34+ cells/kg. Conversely, CY use was associated with high frequency of febrile neutropenia, blood and platelet transfusions need and hospitalizations. The average total cost of mobilization in Lebanon was slightly higher in the plerixafor group ($7886 vs $7536; P=0.16). Our data indicate robust stem cell mobilization in MM patients with either fractionated high-dose CY and G-CSF or G-CSF alone with preemptive plerixafor. The chemo-mobilization approach was associated with twofold stem cell yield, slightly lower cost but significantly increased toxicity.
Asunto(s)
Factor Estimulante de Colonias de Granulocitos/economía , Movilización de Célula Madre Hematopoyética/economía , Trasplante de Células Madre Hematopoyéticas/economía , Compuestos Heterocíclicos/economía , Mieloma Múltiple/economía , Adulto , Anciano , Autoinjertos , Bencilaminas , Costos y Análisis de Costo , Ciclamas , Femenino , Factor Estimulante de Colonias de Granulocitos/administración & dosificación , Movilización de Célula Madre Hematopoyética/métodos , Compuestos Heterocíclicos/administración & dosificación , Humanos , Líbano , Masculino , Persona de Mediana Edad , Mieloma Múltiple/terapia , Estudios RetrospectivosAsunto(s)
Amiloidosis , Factor Estimulante de Colonias de Granulocitos , Movilización de Célula Madre Hematopoyética/economía , Células Madre Hematopoyéticas , Compuestos Heterocíclicos , Amiloidosis/economía , Amiloidosis/terapia , Bencilaminas , Costos y Análisis de Costo , Ciclamas , Femenino , Factor Estimulante de Colonias de Granulocitos/administración & dosificación , Factor Estimulante de Colonias de Granulocitos/economía , Compuestos Heterocíclicos/administración & dosificación , Compuestos Heterocíclicos/economía , Humanos , Masculino , Estudios RetrospectivosRESUMEN
The objectives of this study were to 1) quantify effects of metaphylactic treatment for bovine respiratory disease (BRD) on growth performance, carcass characteristics, and lung lesion prevalence and severity; 2) evaluate the association of lung lesion prevalence and severity with carcass characteristics; and 3) evaluate effects of therapeutic treatment on carcass characteristics and lung lesion prevalence and severity. The study was conducted at a commercial feedlot in the Texas Panhandle in which steers (n = 2,336) initially weighing 312.1 ± 9.6 kg were sourced from auction markets and allocated in a randomized complete block design to 1 of 3 treatments (no metaphylactic [no antimicrobial drug {ND}] treatment, tilmicosin at 10 mg/kg BW [TIL], and tulathromycin at 2.5 mg/kg BW [TUL]). Lungs of all steers were evaluated during harvest to assess presence and severity of pneumonic lesions in the anteroventral lobes and the presence and severity of pleural adherences. Compared to the ND treatment, steers treated via metaphylactic therapy had greater (P < 0.05) metaphylactic cost, ADG, shrunk final BW, dressed carcass yield, HCW, 12th rib fat, calculated empty body fat (EBF), and gross revenue, concurrent with reduced (P < 0.05) BRD treatment costs and financial losses from BRD death and railed cattle, cumulatively resulting in greater financial returns. Lung lesions were present in 64.3% of lungs and were distributed similarly between metaphylactic treatments (63.9%) and ND (65.1%) cattle. Steers with advanced lung lesions present at harvest were associated with reduced (P < 0.05) HCW, KPH, 12th rib fat, calculated yield grades, marbling scores, and calculated EBF as compared to steers without lung lesions. Steers pulled for BRD had increased (P < 0.01) incidence of advanced lung lesions, mortality, and railers with decreased (P < 0.05) HCW, 12th rib fat, KPH, marbling score, calculated EBF, and percentage choice carcasses when compared to non-BRD event steers. From the results of this study, controlling BRD through the use of metaphylactic treatments on arrival in heavier cattle improved financial returns primarily driven by reductions in cost of death loss and railers.
Asunto(s)
Composición Corporal/efectos de los fármacos , Complejo Respiratorio Bovino/epidemiología , Bovinos/crecimiento & desarrollo , Disacáridos/uso terapéutico , Compuestos Heterocíclicos/uso terapéutico , Tilosina/análogos & derivados , Tejido Adiposo/efectos de los fármacos , Animales , Antibacterianos/economía , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Profilaxis Antibiótica/veterinaria , Complejo Respiratorio Bovino/economía , Complejo Respiratorio Bovino/prevención & control , Análisis Costo-Beneficio , Disacáridos/economía , Disacáridos/farmacología , Compuestos Heterocíclicos/economía , Compuestos Heterocíclicos/farmacología , Pulmón/patología , Masculino , Prevalencia , Distribución Aleatoria , Índice de Severidad de la Enfermedad , Texas , Resultado del Tratamiento , Tilosina/economía , Tilosina/farmacología , Tilosina/uso terapéuticoRESUMEN
INTRODUCTION: About 99% of all autologous transplants are now performed with blood stem cells. G-CSF alone or combined with chemotherapy have been used to mobilize CD34(+) cells. Plerixafor is a novel drug used for mobilization purposes. AREAS COVERED: We have evaluated recent data in regard to plerixafor use in predicted or proven poor mobilizers. In addition, we have looked for preemptive strategies to optimize the use of this expensive drug. Also cost-efficacy issues and effects of plerixafor on graft composition and post-transplant outcomes will be discussed. EXPERT OPINION: Plerixafor added to G-CSF is superior than G-CSF alone for mobilization of CD34(+) cells. This combination is also efficient in patients who have failed a previous mobilization attempt with other methods or in patients with risk factors for poor mobilization. Addition of plerixafor to G-CSF or chemotherapy plus G-CSF mobilization in patients who appear to mobilize poorly is under active investigation and algorithms for a preemptive use of this expensive agent have been proposed. Grafts collected after plerixafor appear to contain more lymphoid cells than the grafts collected without it. Whether this affects post-transplant outcomes such as immune reconstitution and risk of relapse needs to be evaluated.
Asunto(s)
Movimiento Celular/efectos de los fármacos , Movilización de Célula Madre Hematopoyética/métodos , Trasplante de Células Madre Hematopoyéticas , Células Madre Hematopoyéticas/efectos de los fármacos , Compuestos Heterocíclicos/uso terapéutico , Animales , Antígenos CD34/metabolismo , Autoinjertos , Bencilaminas , Biomarcadores/metabolismo , Análisis Costo-Beneficio , Ciclamas , Costos de los Medicamentos , Movilización de Célula Madre Hematopoyética/economía , Células Madre Hematopoyéticas/metabolismo , Compuestos Heterocíclicos/efectos adversos , Compuestos Heterocíclicos/economía , Humanos , Resultado del TratamientoRESUMEN
Plerixafor effectively mobilizes hematopoietic stem cells (HSCs). However, most patients' cells are successfully collected using traditional strategies and there is limited cost-effectiveness data. The objectives of this study were to: (1) summarize the published reports of mobilization using a plerixafor-based strategy during compassionate access programs and (2) describe the Canadian experience with plerixafor during its availability by Health Canada's Special Access Program. A literature search identified reports of plerixafor-based mobilization during compassionate access programs. Overall, successful collection of at least 2 × 10(6) CD34+ cells/kg was achieved in ~75% of patients, and about two-thirds of patients went on to HSCT. A greater proportion of patients had successful collections when plerixafor was used in the upfront or preemptive settings. Plerixafor was made available by Health Canada's SAP from September 2008 to December 2010. In 96 of 132 (73%) patients, there was successful collection of at least 2 × 10(6) CD34+ cells/kg. Ninety-nine (75%) patients went on to receive an autologous transplant. Plerixafor-based mobilization is effective in perceived poor mobilizers. The optimal way to incorporate plerixafor into a mobilization strategy, however, remains to be determined. Centre-specific analysis of resource utilization may help to identify the most cost-effective way to implement various plerixafor-based mobilization strategies.
Asunto(s)
Movilización de Célula Madre Hematopoyética/métodos , Compuestos Heterocíclicos/uso terapéutico , Adulto , Anciano , Antígenos CD34/metabolismo , Protocolos de Quimioterapia Combinada Antineoplásica , Autoinjertos , Bencilaminas , Canadá , Ensayos de Uso Compasivo , Análisis Costo-Beneficio , Ciclamas , Femenino , Neoplasias Hematológicas/tratamiento farmacológico , Neoplasias Hematológicas/terapia , Movilización de Célula Madre Hematopoyética/economía , Trasplante de Células Madre Hematopoyéticas/métodos , Células Madre Hematopoyéticas/efectos de los fármacos , Células Madre Hematopoyéticas/inmunología , Compuestos Heterocíclicos/economía , Humanos , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
INTRODUCTION: Plerixafor is a novel mobilizing agent of peripheral blood stem cells (PBSCs) in lymphoma and multiple myeloma (MM) patients whose cells mobilize poorly. Due to the substantial cost associated with its use, we aimed to compare the effectiveness and cost effectiveness of Plerixafor + GCSF (PG) versus GCSF ± Chemotherapy (GC) as salvage mobilization regimens. METHODS: The charts of consecutive lymphoma and MM patients who had undergone at least one previous attempt of PBSCs mobilization that failed or resulted in an insufficient cell dose for transplant between 2007 and 2010 were retrospectively reviewed. Patients identified received salvage mobilization with GC (prior to 2009) or PG after Plerixafor's FDA approval. Data collected included demographics, medical histories, apheresis yields and transplant outcome. The cost effectiveness analysis was from the perspective of the Jordanian Ministry of Health. The incremental cost effectiveness ratio (ICER) was calculated by dividing the difference in cost by the difference in effectiveness for the two regimens. RESULTS: Five patients received GC and twelve received PG. A minimum CD34+ cell dose of 2 × 10(6) cells/kg was collected from 8 patients (67%) in the PG group compared to 3 (60%) in the GC group (p=0.79). The average costs were US$8570 and US$25,700 for the GC group and the PG group, respectively. The ICER was US$244,714 per successful stem cell collection. CONCLUSION: Salvage Plerixafor use showed a non-significant improvement in PBSCs collection with a significant increase in cost. Prospective comparative effectiveness studies are warranted to inform the optimal salvage mobilization regimen. To our knowledge, this is the first study from the Middle East to describe the effectiveness and cost effectiveness of Plerixafor.
Asunto(s)
Factor Estimulante de Colonias de Granulocitos/economía , Factor Estimulante de Colonias de Granulocitos/uso terapéutico , Compuestos Heterocíclicos/economía , Compuestos Heterocíclicos/uso terapéutico , Linfoma/tratamiento farmacológico , Mieloma Múltiple/tratamiento farmacológico , Adulto , Bencilaminas , Análisis Costo-Beneficio , Ciclamas , Femenino , Humanos , Linfoma/economía , Masculino , Persona de Mediana Edad , Mieloma Múltiple/economía , Estudios Prospectivos , Estudios Retrospectivos , Adulto JovenRESUMEN
To date, no prospective study on Plerixafor 'on-demand' in combination with chemotherapy and granulocyte colony-stimulating factor (G-CSF) has been reported. We present an interim analysis of the first prospective study in which Plerixafor was administered on-demand in patients affected by multiple myeloma and lymphoma who received high dose cyclophosphamide or DHAP (dexamethasone, cytarabine, cisplatin) plus G-CSF to mobilize peripheral blood stem cells (PBSC). One hundred and two patients were evaluable for response. A cohort of 240 patients receiving the same mobilizing chemotherapy was retrospectively studied. Failure to mobilize CD34(+) cells in peripheral blood was reduced by 'on-demand' strategy compared to conventional mobilization; from 13·0 to 3·0% (P = 0·004). Failure to harvest CD34(+) cells 2 × 10(6) /kg decreased from 20·9 to 4·0% (P = 0·0001). The on-demand Plerixafor strategy also resulted in a lower rate of mobilization failure (P = 0·03) and harvest failure (P = 0·0008) when compared to a 'bias-adjusted set of controls'. Evaluation of economic costs of the two strategies showed that the overall cost of the two treatments were comparable when salvage mobilizations were taken into account. When in combination with cyclophosphamide or DHAP plus G-CSF, the 'on-demand' use of Plerixafor showed, in comparison to conventionally treated patients, a significant improvement in mobilization of PBSC with no increase in overall cost.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Factor Estimulante de Colonias de Granulocitos/administración & dosificación , Movilización de Célula Madre Hematopoyética/métodos , Compuestos Heterocíclicos/administración & dosificación , Linfoma/terapia , Mieloma Múltiple/terapia , Trasplante de Células Madre de Sangre Periférica/métodos , Adulto , Anciano , Bencilaminas , Eliminación de Componentes Sanguíneos/economía , Eliminación de Componentes Sanguíneos/métodos , Ciclamas , Femenino , Factor Estimulante de Colonias de Granulocitos/economía , Movilización de Célula Madre Hematopoyética/economía , Compuestos Heterocíclicos/economía , Humanos , Linfoma/tratamiento farmacológico , Linfoma/cirugía , Masculino , Persona de Mediana Edad , Mieloma Múltiple/tratamiento farmacológico , Mieloma Múltiple/cirugía , Trasplante de Células Madre de Sangre Periférica/economía , Estudios Prospectivos , Estudios Retrospectivos , Adulto JovenRESUMEN
The goal of this study was to determine the clinical and economic impact of using tulathromycin as first line treatment for bovine respiratory disease (BRD) compared with other commonly used antimicrobials. Two decision trees were developed simulating the consequences of treating cattle at high risk of developing BRD [control model (CM)] or cattle with first clinical BRD episode [treatment model (TM)]. As comparators florfenicol and tilmicosin were considered in both models whereas enrofloxacin was included in the TM because it was only labeled for treatment of BRD at the time of development of the calculators. A total of 5 (CM) and 10 (TM) comparative clinical studies that reported efficacy data for the selected drugs and indications were identified as suitable for model population. The following outcomes were considered: first treatment success, number of subsequent BRD treatments, chronics, and mortalities. Cost parameters were considered from the perspective of the producer and included treatment costs (first treatment and retreatments) and costs of chronics and deaths derived from published sources for 2010 (default). The models allowed the estimation of clinical and economic consequences according to each individual trial outcomes. Treatment with tulathromycin resulted in more first treatment successes and fewer removals (chronics and deaths) in all comparisons. The average total number of antimicrobial treatments required for the management of BRD was also least with tulathromycin as first treatment option. Because of better efficacy, total costs over the entire study periods were always lowest with tulathromycin. Depending on the study selected as the basis for the efficacy evaluation, cost savings with tulathromycin were calculated in the CM between US$21.00 and $47.86 (vs. florfenicol) and $11.37 and $72.64 (vs. tilmicosin); cost savings in the TM ranged between $28.47 and $143.87 (vs. florfenicol) and $7.75 and $84.91 (vs. tilmicosin) as well as between $23.22 and $47.82 (vs. enrofloxacin), with the ranges reflecting a variety of settings in different trials. Thus, the higher drug costs of tulathromycin were more than offset by reduced BRD treatments, chronics, and mortalities in the herd. Fewer BRD episodes in cattle treated with tulathromycin not only contributes to overall savings in BRD management but also reduces the necessity of repeated antibiotic treatment, supporting prudent use of antimicrobials in livestock.
Asunto(s)
Antibacterianos/uso terapéutico , Complejo Respiratorio Bovino/tratamiento farmacológico , Disacáridos/uso terapéutico , Brotes de Enfermedades/veterinaria , Compuestos Heterocíclicos/uso terapéutico , Animales , Antibacterianos/economía , Complejo Respiratorio Bovino/epidemiología , Bovinos , Análisis Costo-Beneficio , Técnicas de Apoyo para la Decisión , Disacáridos/economía , Brotes de Enfermedades/economía , Femenino , Compuestos Heterocíclicos/economía , Vivienda para Animales , Masculino , Modelos Económicos , Estados Unidos/epidemiologíaRESUMEN
Peripheral blood stem cells (PBSCs) are preferred source of hematopoietic stem cells for autologous transplantation. Mobilization of PBSCs using chemotherapy and/or granulocyte colony-stimulating factor (G-CSF) however fails in around 20%. Combining G-CSF with plerixafor increases the mobilizations success. We compared cost-effectiveness of following schemes: the use of plerixafor "on demand" (POD) during the first mobilization in all patients with inadequate response, the remobilization with plerixafor following failure of the first standard mobilization (SSP), and the standard (re)mobilization scheme without plerixafor (SSNP). Decision tree models populated with data from a first-of-a-kind patient registry in six Czech centers (n = 93) were built to compare clinical benefits and direct costs from the payer's perspective. The success rates and costs for POD, SSP and SSNP mobilizations were; 94.9%, $7,197; 94.7%, $8,049; 84.7%, $5,991, respectively. The direct cost per successfully treated patient was $7,586, $8,501, and $7,077, respectively. The cost of re-mobilization of a poor mobilizer was $5,808 with G-CSF only and $16,755 if plerixafor was added. The total cost of plerixafor "on-demand" in the sub-cohort of poor mobilizers was $17,120. Generally, plerixafor improves the mobilization success by 10% and allows an additional patient to be successfully mobilized for incremental $11,803. Plerixafor is better and cheaper if used "on demand" than within a subsequent remobilization.
Asunto(s)
Factor Estimulante de Colonias de Granulocitos/economía , Movilización de Célula Madre Hematopoyética/economía , Compuestos Heterocíclicos/economía , Linfoma/economía , Mieloma Múltiple/economía , Trasplante de Células Madre de Sangre Periférica/economía , Adolescente , Adulto , Anciano , Bencilaminas , Niño , Preescolar , Análisis Costo-Beneficio , Ciclamas , Citaféresis/estadística & datos numéricos , Checoslovaquia , Árboles de Decisión , Femenino , Factor Estimulante de Colonias de Granulocitos/uso terapéutico , Gastos en Salud , Movilización de Célula Madre Hematopoyética/métodos , Compuestos Heterocíclicos/uso terapéutico , Humanos , Lactante , Tiempo de Internación/estadística & datos numéricos , Linfoma/cirugía , Masculino , Persona de Mediana Edad , Modelos Económicos , Mieloma Múltiple/cirugía , Resultado del Tratamiento , Adulto JovenRESUMEN
Studies comparing the efficacy and cost of peripheral blood stem and progenitor cells mobilization with low-dose cyclophosphamide (LD-CY) and granulocyte-colony stimulating factor (G-CSF) against plerixafor and G-CSF, in multiple myeloma (MM) patients treated in the novel therapy-era are not available. Herein, we report mobilization outcomes of 107 patients who underwent transplantation within 1-year of starting induction chemotherapy with novel agents. Patients undergoing mobilization with LD-CY (1.5 gm/m(2)) and G-CSF (n = 74) were compared against patients receiving plerixafor and G-CSF (n = 33). Compared to plerixafor, LD-CY was associated with a significantly lower median peak peripheral blood CD34+ cell count (68/µL vs. 36/µL, P = 0.048), and lower CD34+ cell yield on day 1 of collection (6.9 × 10(6)/kg vs. 2.4 × 10(6)/kg, P = 0.001). Six patients (8.1%) in the LD-CY group experienced mobilization failure, compared to none in the plerixafor group. The total CD34+ cell yield was significantly higher in the plerixafor group (median 11.6 × 10(6)/kg vs. 7 × 10(6)/kg; P-value = 0.001). Mobilization with LD-CY was associated with increased (albeit statistically non-significant) episodes of febrile neutropenia (5.4% vs. 0%; P = 0.24), higher use of intravenous antibiotics (6.7% vs. 3%; P = 0.45), and need for hospitalizations (9.4% vs. 3%; P = 0.24). The average total cost of mobilization in the plerixafor group was significantly higher compared to the LD-CY group ($28,980 vs. $19,626.5 P-value < 0.0001). In conclusion, in MM plerixafor-based mobilization has superior efficacy, but significantly higher mobilization costs compared to LD-CY mobilization. Our data caution against the use of LD-CY in MM patients for mobilization, especially after induction with lenalidomide-containing regimens.
Asunto(s)
Ciclofosfamida/administración & dosificación , Factor Estimulante de Colonias de Granulocitos/administración & dosificación , Movilización de Célula Madre Hematopoyética/métodos , Compuestos Heterocíclicos/administración & dosificación , Mieloma Múltiple/terapia , Trasplante de Células Madre de Sangre Periférica/métodos , Adulto , Anciano , Antibacterianos/administración & dosificación , Antibacterianos/economía , Antígenos CD34/metabolismo , Antineoplásicos/administración & dosificación , Antineoplásicos/economía , Bencilaminas , Ácidos Borónicos/administración & dosificación , Ácidos Borónicos/economía , Bortezomib , Estudios de Cohortes , Ciclamas , Ciclofosfamida/economía , Femenino , Factor Estimulante de Colonias de Granulocitos/economía , Costos de la Atención en Salud , Movilización de Célula Madre Hematopoyética/economía , Compuestos Heterocíclicos/economía , Humanos , Lenalidomida , Leucocitos Mononucleares/citología , Masculino , Persona de Mediana Edad , Pirazinas/administración & dosificación , Pirazinas/economía , Talidomida/administración & dosificación , Talidomida/análogos & derivados , Talidomida/economía , Factores de Tiempo , Acondicionamiento Pretrasplante/métodos , Resultado del TratamientoRESUMEN
The addition of plerixafor to G-CSF decreases the risk of failed stem cell collection, but at considerable extra cost. Using a logistic regression model based on 354 autologous mobilizations, we have identified a local minimum peripheral blood CD34 count at which the probability of a successful collection is 50%. This seems an appropriate CD34 count at which to add immediate salvage plerixafor.
Asunto(s)
Movilización de Célula Madre Hematopoyética/métodos , Compuestos Heterocíclicos/uso terapéutico , Linfoma/terapia , Mieloma Múltiple/terapia , Trasplante de Células Madre/métodos , Trasplante Autólogo/métodos , Antígenos CD34/metabolismo , Bencilaminas , Eliminación de Componentes Sanguíneos , Peso Corporal , Análisis Costo-Beneficio , Ciclamas , Factor Estimulante de Colonias de Granulocitos/economía , Factor Estimulante de Colonias de Granulocitos/uso terapéutico , Movilización de Célula Madre Hematopoyética/economía , Compuestos Heterocíclicos/economía , Humanos , Leucemia Mieloide Aguda/terapia , Linfoma no Hodgkin/terapia , Análisis de Regresión , Estudios Retrospectivos , Trasplante de Células Madre/economía , Trasplante Autólogo/economía , Resultado del TratamientoRESUMEN
The effectiveness of stem cell mobilization with G-CSF in lymphoma patients is suboptimal. We reviewed our institutional experience using chemomobilization with etoposide (VP-16; 375 mg/m(2) on days +1 and +2) and G-CSF (5 µg/kg twice daily from day +3 through the final day of collection) in 159 patients with lymphoma. This approach resulted in successful mobilization (>2 × 10(6) CD34+ cells collected) in 94% of patients (83% within 4 apheresis sessions). Fifty-seven percent of patients yielded at least 5 × 10(6) cells in îº2 days and were defined as good mobilizers. The regimen was safe with a low rate of rehospitalization. Average costs were $14 923 for good mobilizers and $27 044 for poor mobilizers (P<0.05). Using our data, we performed a 'break-even' analysis that demonstrated that adding two doses of Plerixafor to predicted poor mobilizers at the time of first CD34+ cell count would achieve cost neutrality if the frequency of good mobilizers were to increase by 21%, while the frequency of good mobilizers would need to increase by 25% if three doses of Plerixafor were used. We conclude that chemomobilization with etoposide and G-CSF in patients with lymphoma is effective, with future opportunities for cost-neutral improvement using novel agents.
Asunto(s)
Antineoplásicos Fitogénicos , Etopósido , Movilización de Célula Madre Hematopoyética/economía , Trasplante de Células Madre Hematopoyéticas/economía , Enfermedad de Hodgkin , Linfoma no Hodgkin , Adulto , Anciano , Fármacos Anti-VIH/administración & dosificación , Fármacos Anti-VIH/economía , Antineoplásicos Fitogénicos/administración & dosificación , Antineoplásicos Fitogénicos/economía , Autoinjertos , Bencilaminas , Costos y Análisis de Costo , Ciclamas , Etopósido/administración & dosificación , Etopósido/economía , Femenino , Factor Estimulante de Colonias de Granulocitos/administración & dosificación , Factor Estimulante de Colonias de Granulocitos/economía , Movilización de Célula Madre Hematopoyética/métodos , Trasplante de Células Madre Hematopoyéticas/métodos , Compuestos Heterocíclicos/administración & dosificación , Compuestos Heterocíclicos/economía , Enfermedad de Hodgkin/economía , Enfermedad de Hodgkin/terapia , Humanos , Linfoma no Hodgkin/economía , Linfoma no Hodgkin/terapia , Masculino , Persona de Mediana EdadRESUMEN
Historically, up to 30% of patients were unable to collect adequate numbers of peripheral blood stem cells (PBSCs) for autologous stem cell transplantation (ASCT). Plerixafor in combination with granulocyte colony-stimulating factor (G-CSF) has shown superior results in mobilizing peripheral blood (PB) CD34+ cells in comparison to G-CSF alone, but its high cost limits general use. We developed and evaluated risk-adapted algorithms for optimal utilization of plerixafor. In plerixafor-1, PBSC mobilization was commenced with G-CSF alone, and if PB CD34 on day 4 or day 5 was <10/µL, plerixafor was administered in the evening, and apheresis commenced the next day. In addition, if on any day, the daily yield was <0.5 × 10(6) CD34/kg, plerixafor was added. Subsequently, the algorithm was revised (plerixafor-2) with lower thresholds. If day-4 PB CD34 <10/µL for single or <20/µL for multiple transplantations, or day-1 yield was <1.5 × 10(6) CD34/kg, or any subsequent daily yield was <0.5 × 10(6) CD34/kg, plerixafor was added. Three time periods were analyzed for results and associated costs: January to December 2008 (baseline cohort; 319 mobilization attempts in 278 patients); February to November 2009 (plerixafor-1; 221 mobilization attempts in 216 patients); and December 2009 to June 2010 (plerixafor-2; 100 mobilization attempts in 98 patients). Plerixafor-2 shows a significant improvement in PB CD34 collection, increased number of patients reaching minimum and optimal goals, fewer days of apheresis, and fewer days of mobilization/collection, albeit at increased costs. In conclusion, although the earlier identification of ineffective PBSC mobilization and initiation of plerixafor (plerixafor-2) increases the per-patient costs of PBSC mobilization, failure rates, days of apheresis, and total days of mobilization/collection are lower.