RESUMEN
BACKGROUND: We investigated the prognostic value of baseline positron emission tomography (PET) parameters for patients with treatment-naïve follicular lymphoma (FL) in the phase III RELEVANCE trial, comparing the immunomodulatory combination of lenalidomide and rituximab (R2) versus R-chemotherapy (R-chemo), with both regimens followed by R maintenance therapy. PATIENTS AND METHODS: Baseline characteristics of the entire PET-evaluable population (n = 406/1032) were well balanced between treatment arms. The maximal standard uptake value (SUVmax) and the standardized maximal distance between tow lesions (SDmax) were extracted, the standardized distance between two lesions the furthest apart, were extracted. The total metabolic tumor volume (TMTV) was computed using the 41% SUVmax method. RESULTS: With a median follow-up of 6.5 years, the 6-year progression-free survival (PFS) was 57.8%, the median TMTV was 284 cm3, SUVmax was 11.3 and SDmax was 0.32 m-1, with no significant difference between arms. High TMTV (>510 cm3) and FLIPI were associated with an inferior PFS (P = 0.013 and P = 0.006, respectively), whereas SUVmax and SDmax were not (P = 0.08 and P = 0.12, respectively). In multivariable analysis, follicular lymphoma international prognostic index (FLIPI) and TMTV remained significantly associated with PFS (P = 0.0119 and P = 0.0379, respectively). These two adverse factors combined stratified the overall population into three risk groups: patients with no risk factors (40%), with one factor (44%), or with both (16%), with a 6-year PFS of 67.7%, 54.5%, and 41.0%, respectively. No significant interaction between treatment arms and TMTV or FLIPI (P = 0.31 or P = 0.59, respectively) was observed. The high-risk group (high TMTV and FLIPI 3-5) had a similar PFS in both arms (P = 0.45) with a median PFS of 68.4% in the R-chemo arm versus 71.4% in the R2 arm. CONCLUSIONS: Baseline TMTV is predictive of PFS, independently of FLIPI, in patients with advanced FL even in the context of antibody maintenance.
Asunto(s)
Linfoma Folicular , Humanos , Linfoma Folicular/diagnóstico por imagen , Linfoma Folicular/tratamiento farmacológico , Carga Tumoral , Pronóstico , Supervivencia sin Progresión , Tomografía de Emisión de Positrones , Fluorodesoxiglucosa F18 , Estudios Retrospectivos , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodosRESUMEN
The consensus panel 2 (CP2) of the 11th International Workshop on Waldenström's macroglobulinemia (IWWM-11) has reviewed and incorporated current data to update the recommendations for treatment approaches in patients with relapsed or refractory WM (RRWM). The key recommendations from IWWM-11 CP2 include: (1) Chemoimmunotherapy (CIT) and/or a covalent Bruton tyrosine kinase (cBTKi) strategies are important options; their use should reflect the prior upfront strategy and are subject to their availability. (2) In selecting treatment, biological age, co-morbidities and fitness are important; nature of relapse, disease phenotype and WM-related complications, patient preferences and hematopoietic reserve are also critical factors while the composition of the BM disease and mutational status (MYD88, CXCR4, TP53) should also be noted. (3) The trigger for initiating treatment in RRWM should utilize knowledge of patients' prior disease characteristics to avoid unnecessary delays. (4) Risk factors for cBTKi related toxicities (cardiovascular dysfunction, bleeding risk and concurrent medication) should be addressed when choosing cBTKi. Mutational status (MYD88, CXCR4) may influence the cBTKi efficacy, and the role of TP53 disruptions requires further study) in the event of cBTKi failure dose intensity could be up titrated subject to toxicities. Options after BTKi failure include CIT with a non-cross-reactive regimen to one previously used CIT, addition of anti-CD20 antibody to BTKi, switching to a newer cBTKi or non-covalent BTKi, proteasome inhibitors, BCL-2 inhibitors, and new anti-CD20 combinations are additional options. Clinical trial participation should be encouraged for all patients with RRWM.
Asunto(s)
Antineoplásicos , Macroglobulinemia de Waldenström , Humanos , Macroglobulinemia de Waldenström/tratamiento farmacológico , Macroglobulinemia de Waldenström/genética , Factor 88 de Diferenciación Mieloide/genética , Consenso , Recurrencia Local de Neoplasia/inducido químicamente , Recurrencia Local de Neoplasia/tratamiento farmacológico , Antineoplásicos/uso terapéuticoRESUMEN
Consensus Panel 5 (CP5) of the 11th International Workshop on Waldenstrom's Macroglobulinemia (IWWM-11; held in October 2022) was tasked with reviewing the current data on the coronavirus disease-2019 (COVID-19) prophylaxis and management in patients with Waldenstrom's Macroglobulinemia (WM). The key recommendations from IWWM-11 CP5 included the following: Booster vaccines for SARS-CoV-2 should be recommended to all patients with WM. Variant-specific booster vaccines, such as the bivalent vaccine for the ancestral Wuhan strain and the Omicron BA.4.5 strain, are important as novel mutants emerge and become dominant in the community. A temporary interruption in Bruton's Tyrosine Kinase-inhibitor (BTKi) or chemoimmunotherapy before vaccination might be considered. Patients under treatment with rituximab or BTK-inhibitors have lower antibody responses against SARS-CoV-2; thus, they should continue to follow preventive measures, including mask wearing and avoiding crowded places. Patients with WM are candidates for preexposure prophylaxis, if available and relevant to the dominant SARS-CoV-2 strains in a specific area. Oral antivirals should be offered to all symptomatic WM patients with mild to moderate COVID-19 regardless of vaccination, disease status or treatment, as soon as possible after the positive test and within 5 days of COVID-19-related symptom onset. Coadministration of ibrutinib or venetoclax with ritonavir should be avoided. In these patients, remdesivir offers an effective alternative. Patients with asymptomatic or oligosymptomatic COVID-19 should not interrupt treatment with a BTK inhibitor. Infection prophylaxis is essential in patients with WM and include general preventive measures, prophylaxis with antivirals and vaccination against common pathogens including SARS-CoV-2, influenza, and S. pneumoniae.
Asunto(s)
COVID-19 , Macroglobulinemia de Waldenström , Humanos , Macroglobulinemia de Waldenström/tratamiento farmacológico , Macroglobulinemia de Waldenström/prevención & control , Macroglobulinemia de Waldenström/diagnóstico , Vacunas contra la COVID-19 , Consenso , SARS-CoV-2 , Antivirales/uso terapéuticoRESUMEN
BACKGROUND: Current radiological assessments of 18fluorodeoxyglucose-positron emission tomography (FDG-PET) imaging data in diffuse large B-cell lymphoma (DLBCL) can be time consuming, do not yield real-time information regarding disease burden and organ involvement, and hinder the use of FDG-PET to potentially limit the reliance on invasive procedures (e.g. bone marrow biopsy) for risk assessment. METHODS: Our aim is to enable real-time assessment of imaging-based risk factors at a large scale and we propose a fully automatic artificial intelligence (AI)-based tool to rapidly extract FDG-PET imaging metrics in DLBCL. On availability of a scan, in combination with clinical data, our approach generates clinically informative risk scores with minimal resource requirements. Overall, 1268 patients with previously untreated DLBCL from the phase III GOYA trial (NCT01287741) were included in the analysis (training: n = 846; hold-out: n = 422). RESULTS: Our AI-based model comprising imaging and clinical variables yielded a tangible prognostic improvement compared to clinical models without imaging metrics. We observed a risk increase for progression-free survival (PFS) with hazard ratios [HR] of 1.87 (95% CI: 1.31-2.67) vs 1.38 (95% CI: 0.98-1.96) (C-index: 0.59 vs 0.55), and a risk increase for overall survival (OS) (HR: 2.16 (95% CI: 1.37-3.40) vs 1.40 (95% CI: 0.90-2.17); C-index: 0.59 vs 0.55). The combined model defined a high-risk population with 35% and 42% increased odds of a 4-year PFS and OS event, respectively, versus the International Prognostic Index components alone. The method also identified a subpopulation with a 2-year Central Nervous System (CNS)-relapse probability of 17.1%. CONCLUSION: Our tool enables an enhanced risk stratification compared with IPI, and the results indicate that imaging can be used to improve the prediction of central nervous system relapse in DLBCL. These findings support integration of clinically informative AI-generated imaging metrics into clinical workflows to improve identification of high-risk DLBCL patients. TRIAL REGISTRATION: Registered clinicaltrials.gov number: NCT01287741.
Asunto(s)
Fluorodesoxiglucosa F18 , Linfoma de Células B Grandes Difuso , Inteligencia Artificial , Automatización , Ensayos Clínicos Fase III como Asunto , Humanos , Linfoma de Células B Grandes Difuso/diagnóstico por imagen , Linfoma de Células B Grandes Difuso/patología , Recurrencia Local de Neoplasia , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Tomografía de Emisión de Positrones/métodos , Pronóstico , Medición de Riesgo , Carga TumoralRESUMEN
Progressive multifocal leukoencephalopathy (PML) is a generally fatal infection of the cerebrum by the JC virus. It occurs in a range of primary and secondary immunosuppressed states and has become more common with AIDS and increasing the use of immunosuppressive therapies. Recently, Ibrutinib, a Bruton's Tyrosine Kinase Inhibitor (BTKi), has also been associated with PML. Here, we describe the case of a 77-year-old man treated for relapsed Chronic Lymphocytic Leukemia (CLL) with Ibrutinib, who eventually developed a fatal cerebellar granule cell variant of PML confirmed on autopsy. The case adds to the growing body of literature finding such an association with BTKis and highlights the importance of clinical vigilance in patients receiving such therapy.
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Leucemia Linfocítica Crónica de Células B , Leucoencefalopatía Multifocal Progresiva , Linfoma de Células B , Adenina/análogos & derivados , Anciano , Humanos , Leucemia Linfocítica Crónica de Células B/complicaciones , Leucemia Linfocítica Crónica de Células B/diagnóstico , Leucemia Linfocítica Crónica de Células B/tratamiento farmacológico , Leucoencefalopatía Multifocal Progresiva/diagnóstico , Leucoencefalopatía Multifocal Progresiva/etiología , Linfoma de Células B/complicaciones , Masculino , Piperidinas/uso terapéuticoAsunto(s)
Melfalán , Mieloma Múltiple , Adulto , Humanos , Mieloma Múltiple/tratamiento farmacológico , Obesidad , Trasplante AutólogoRESUMEN
Hypogonadotrophic hypogonadism is due to impaired or reduced gonadotrophin secretion from the pituitary gland. In the absence of any anatomical or functional lesions of the pituitary or hypothalamic gland, the hypogonadotrophic hypogonadism is referred to as idiopathic hypogonadotrophic hypogonadism (IHH). We present a case of a young lady born to consanguineous parents who was found to have IHH due to a rare gene mutation. Learning points: The genetic basis of a majority of cases of IHH remains unknown.IHH can have different clinical endocrine manifestations.Patients can present late to the healthcare service because of unawareness and stigmata associated with the clinical features.Family members of affected individuals can be affected to varying degrees.
RESUMEN
BACKGROUND: Elderly patients with diffuse large B-cell lymphoma (DLBCL) have an inferior prognosis, due in part to advanced age and pre-existing comorbidities, with reduced tolerability and deliverability of standard R-CHOP chemotherapy. AIMS: To examine the deliverability, toxicity and efficacy of R-CHOP and the prevalence of the germinal and non-germinal phenotype DLBCL in an elderly Australian cohort. METHODS: This retrospective analysis included patients ≥75 years diagnosed with DLBCL. Comprehensive chemotherapy and toxicity data were collected for patients treated with R-CHOP. Baseline demographics and chemotherapy characteristics were compared with progression-free (PFS) and overall survival (OS). Immunohistochemical staining identified the prevalence of the non-germinal centre (non-GCB) phenotype. RESULTS: Of the 111 patients, 92 (83%) commenced R-CHOP with 26/92 (28%) receiving ≤4 cycles. Median average relative dose (ARD) was 0.80 (0.07-1.17). Median average relative dose intensity (ARDI) was 0.89 (0.33-1.18). Serious adverse events occurred in 77% of patients with ≥Gd3 adverse events in 74%. Overall response rate was 85%. Two-year PFS was 63% and OS 74%. ARD and performance status ≥2 were significant prognostic factors for PFS and OS but not ARDI. Non-GCB-phenotype was identified in 44/72 (61%) of patients with immunohistochemical data. CONCLUSION: Despite high response rates and respectable survival estimates, the absence of standard therapy in 17% of patients, and dose reductions and serious toxicity of R-CHOP in this Australian cohort highlights the need for the development of less toxic yet efficacious treatments for very elderly patients with DLBCL. The high prevalence of the non-GCB phenotype highlights the potential value of targeted biological therapy for this demographic.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Sistemas de Liberación de Medicamentos/métodos , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Linfoma de Células B Grandes Difuso/mortalidad , Anciano , Anciano de 80 o más Años , Anticuerpos Monoclonales de Origen Murino/administración & dosificación , Australia/epidemiología , Ciclofosfamida/administración & dosificación , Doxorrubicina/administración & dosificación , Femenino , Humanos , Linfoma de Células B Grandes Difuso/diagnóstico , Masculino , Prednisona/administración & dosificación , Estudios Retrospectivos , Rituximab , Tasa de Supervivencia/tendencias , Resultado del Tratamiento , Vincristina/administración & dosificaciónRESUMEN
BACKGROUND: Anticancer drugs are often expensive and are contributing to the growing cost of cancer care. Concerns have been raised about the effect rising costs may have on availability of new anticancer drugs. AIM: This study aims to determine the recent changes in the costs of anticancer drugs in Australia. METHODS: Publicly available expenditure and prices paid by the Australian Pharmaceutical Benefits Scheme (PBS) for anticancer drugs from 2000 to 2012 were reviewed. The measures used to determine changes in cost were total PBS expenditure and average price paid by the PBS per prescription for anticancer drugs and for all PBS listed drugs. An estimated monthly price paid for newly listed anticancer drugs was also calculated. RESULTS: Annual PBS expenditure on anticancer drugs rose from A$65 million in 1999-2000 to A$466 million in 2011-2012; an average increase of 19% per annum. The average price paid by the PBS per anticancer drug prescription, adjusted for inflation, increased 133% from A$337 to A$786. The real average annual increase in the price per anticancer drug prescription was more than double that for all other PBS drugs combined (7.6% vs 2.8%, difference 4.8%, 95% confidence interval -0.4% to 10.1%, P = 0.07). The median price for a month's treatment of the new anticancer drugs listed was A$4919 (range A$1003 to A$12 578, 2012 prices). CONCLUSIONS: PBS expenditure and the price of anticancer drugs in Australia rose substantially from 2000 to 2012. Dealing with these burgeoning costs will be a major challenge for our health system and for those affected by cancer.
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Antineoplásicos/economía , Costos de los Medicamentos/tendencias , Seguro de Servicios Farmacéuticos/economía , Antineoplásicos/provisión & distribución , Australia , Utilización de Medicamentos , Humanos , Inflación Económica , Neoplasias/tratamiento farmacológico , Neoplasias/economíaRESUMEN
PURPOSE: We sought the attitudes of people with a cancer experience to using best case, worst case, and typical scenarios for survival to explain life expectancy. METHODS: Oncology clinic attendees and Breast Cancer Network Australia (BCNA) members completed a survey describing two formats for explaining life expectancy to a hypothetical patient with advanced cancer-providing either three scenarios for survival or just the median survival time. RESULTS: Characteristics of the 505 respondents from outpatient clinics (n = 251) and BCNA (n = 254) were median age of 58 years, female 74 %, and breast primary 64 %. More respondents agreed that explaining three scenarios (vs. median survival) would make sense (93 vs. 75 %), be helpful (93 vs. 69 %), convey hope (68 vs. 44 %), and reassure (60 vs. 40 %), while fewer respondents agreed that explaining three scenarios (vs. median survival) would upset people (24 vs. 36 %); all p values < 0.001. Most respondents agreed that each scenario should be presented: best case 89 %, worst case 82 %, and typical 92 %. For information about their own prognosis, 88 % preferred all three scenarios and 5 % a single estimate of the median. Respondents with higher education were more likely to agree that presenting three scenarios would be helpful (95 vs. 90 %, p = 0.05). Respondents with breast cancer were more likely to agree that explaining three scenarios would upset people (31 vs. 13 %, p < 0.001). CONCLUSIONS: Most respondents judged presentation of best case, worst case, and typical scenarios preferable and more helpful and reassuring than presentation of just the median survival time when explaining life expectancy to patients with advanced cancer.
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Esperanza de Vida , Oncología Médica/métodos , Neoplasias/psicología , Prioridad del Paciente/psicología , Revelación de la Verdad , Factores de Edad , Anciano , Instituciones de Atención Ambulatoria , Neoplasias de la Mama/patología , Neoplasias de la Mama/psicología , Instituciones Oncológicas , Escolaridad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Estadificación de Neoplasias , Neoplasias/patología , Nueva Gales del Sur , Prioridad del Paciente/estadística & datos numéricos , Relaciones Profesional-Paciente , Pronóstico , Análisis de SupervivenciaRESUMEN
Autologous stem cell transplantation (ASCT) has a well-established role in the treatment of haematological malignancies. Stem cells are commonly collected following salvage chemotherapy although there may be advantages in collecting earlier in the disease course. A 'rainy day' harvest (RDH) refers to the collection of autologous haemopoietic stem cells for long-term storage. Although there are few data to support RDH, there is increasing evidence that such harvests are being carried out, creating storage pressures in stem cell laboratories across New South Wales. The Bone Marrow Transplant Network New South Wales conducted a three-staged exercise to develop consensus-based RDH guidelines. Using available evidence, guidelines were developed supporting RDH for specific patients with acute and chronic myeloid leukaemias, follicular and other lymphomas, and multiple myeloma. Physician agreement with these disease-specific guidelines ranged between 58 and 100%. These consensus guidelines will improve equity of access to appropriate RDH and assist the planning of future storage requirements in New South Wales.
Asunto(s)
Trasplante de Células Madre , Células Madre , Recolección de Tejidos y Órganos , Predicción , Humanos , Nueva Gales del Sur , Guías de Práctica Clínica como Asunto , Trasplante AutólogoRESUMEN
OBJECTIVE: To investigate subacute cardiac toxicity in patients with normal baseline cardiac function following autologous haematopoietic stem cell transplantation. DESIGN: Prospective observational study. PATIENT AND METHODS: Thirty-two consecutive patients (mean (SD) age 60 (11) years) with normal left ventricular ejection fraction (LVEF >or=50%) undergoing autologous haematopoietic stem cell transplantation were studied. Transthoracic echocardiography (including colour tissue Doppler imaging-derived myocardial velocities, strain and strain rates), troponin-T and B-type natriuretic peptide (BNP) and clinical details were recorded at baseline, after conditioning chemotherapy and serially over 6 weeks from the day of transplantation. RESULTS: The mean (SD) LVEF at baseline was 62 (6)% and decreased to 55 (16)%, 6 weeks after transplantation (p = 0.007). Cardiac toxicity (>or=10% absolute decline of LVEF to an LVEF Asunto(s)
Trasplante de Células Madre Hematopoyéticas/efectos adversos
, Disfunción Ventricular Izquierda/etiología
, Enfermedad Aguda
, Anciano
, Antineoplásicos/efectos adversos
, Velocidad del Flujo Sanguíneo
, Ecocardiografía Doppler
, Femenino
, Neoplasias Hematológicas/terapia
, Humanos
, Masculino
, Persona de Mediana Edad
, Válvula Mitral/fisiopatología
, Estudios Prospectivos
, Edema Pulmonar/etiología
, Volumen Sistólico
, Acondicionamiento Pretrasplante/efectos adversos
, Acondicionamiento Pretrasplante/métodos
, Disfunción Ventricular Izquierda/diagnóstico por imagen
, Disfunción Ventricular Izquierda/fisiopatología
, Función Ventricular Izquierda
Asunto(s)
Trasplante de Células Madre Hematopoyéticas/efectos adversos , Melfalán/farmacocinética , Antineoplásicos/uso terapéutico , Humanos , Melfalán/efectos adversos , Mieloma Múltiple/tratamiento farmacológico , Mieloma Múltiple/terapia , Agonistas Mieloablativos/efectos adversos , Agonistas Mieloablativos/farmacocinética , Trasplante AutólogoRESUMEN
Haemorrhagic cystitis (HC) is the syndrome of haematuria and symptoms of lower urinary tract irritability in the absence of bacterial infection. We report a low incidence of HC (18.2%) in 681 haemopoietic stem cell transplant patients, using a prophylactic regimen of hyperhydration and forced diuresis. The incidence of grade 3-4 disease is 3.4%. There was a marked difference in incidence between allogeneic and autologous transplant populations, 24.2% vs. 3.5% (P<0.0005). Busulphan conditioning, acute GVHD, interstitial pneumonitis and use of methotrexate and cyclosporin immune suppression were associated with significantly increased incidence of HC in the allogeneic population. This may reflect the numerous factors that contribute to the greater immunosuppression and consequent increased risk for HC in allogeneic transplantation.
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Cistitis/etiología , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Hematuria/etiología , Cistitis/epidemiología , Enfermedad Injerto contra Huésped/etiología , Hematuria/epidemiología , Humanos , Incidencia , Análisis Multivariante , Factores de Riesgo , Trasplante Autólogo , Trasplante HomólogoRESUMEN
This article is based upon an SCI Model Project, funded by the American Association of Spinal Cord Injury Nurses (AASCIN). The purpose of this project was to develop a model to validate theoretical and practical knowledge of Registered Nurses and Licensed Practical Nurses/Licensed Vocational Nurses in an SCI rehabilitation setting. The investigators were direct care providers in a 68 bed SCI rehabilitation service at the James A. Haley Veterans Hospital in Tampa, Florida. The theoretical framework was based upon three aspects: Competency Validation, Theoretical Knowledge, and Practical Knowledge. Competency Validation was directed towards incorporating the elements of assessment, maintenance, demonstration, and improvement of competencies on an ongoing basis. Theoretical knowledge encompassed the cognitive and psychomotor aspects of SCI nursing, and Practical Knowledge highlighted the application of principles of caregiving. Two instruments were developed to harmonize theoretical and practical dimensions for competency validation: SCI Knowledge/Skill Appraisal (SKA) and Expertise in SCI Nursing Practice (ESNP). The purpose of this project was to design a model for validating theoretical and practical knowledge of Registered Nurses (RN's) and Licensed Practical Nurses/Licensed Vocational Nurses (LPN/LVN's) in an SCI rehabilitation setting. The investigators were direct care Licensed Practical Nurses/Licensed Vocational Nurses (LPN/LVN's) in an SCI rehabilitation setting. The investigators were direct care providers in a 68 bed spinal cord injury (SCI) rehabilitation service at the James A. Haley Veterans Hospital in Tampa, Florida.