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2.
J Oncol Pharm Pract ; : 10781552241268429, 2024 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-39090994

RESUMEN

INTRODUCTION: Teclistamab, a bispecific T-cell engaging antibody targeting B-cell maturation antigen (BCMA), is indicated for the treatment of relapsed or refractory multiple myeloma after at least four lines of therapy. It has boxed warnings for life threatening cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). To mitigate these risks, teclistamab is initiated using step-up doses. This article examines safety event rates following the implementation of a 2-day separation between step-up doses at one institution to streamline patient care. METHODS: This was a retrospective, single-center study encompassing all patients who received teclistamab within a 1-year period. The primary endpoint was the overall incidence of CRS and ICANS. Secondary endpoints included hospital length of stay, hematological toxicities, infection rates, among other adverse events. RESULTS: A total of 27 patients were included in the analysis and stratified into accelerated (days 1,3,5) or standard (days 1,4,7) dosing groups. CRS occurred in 48% (11) of patients for the accelerated dosing and 50% (2) for the standard dosing group. ICANS was seen in 17% (4) of patients in the accelerated dosing group and none in the standard dosing group. Average length of stay in the accelerated dose was 7.6 days versus 9.2 days in the standard dose group. CONCLUSION: Accelerated dose escalation of teclistamab yielded safety event rates comparable to those in the literature. These findings may support outpatient administration for teclistamab. Accelerated dose escalation strategy allowed for the optimization of hospitalization and resources.

3.
J Natl Compr Canc Netw ; 21(1): 67-81, 2023 01.
Artículo en Inglés | MEDLINE | ID: mdl-36652935

RESUMEN

Primary systemic light chain amyloidosis (SLCA) is characterized by production of light chains that get converted to amyloid fibrils with an affinity for visceral organs and causing organ dysfunction. The therapy for SLCA is directed to recovering the function of the affected organs by targeting the abnormal plasma cell clone and slowing deposition of amyloid fibrils. The NCCN Guidelines for SLCA provide recommendations for workup, diagnosis, and treatment of primary as well as previously treated SLCA.


Asunto(s)
Amiloide , Amiloidosis , Humanos , Amiloidosis/diagnóstico , Amiloidosis/terapia , Amiloidosis/etiología , Células Plasmáticas
4.
J Natl Compr Canc Netw ; 21(12): 1281-1301, 2023 12.
Artículo en Inglés | MEDLINE | ID: mdl-38081133

RESUMEN

The treatment of relapsed/refractory multiple myeloma (MM) has evolved to include several new options. These include new combinations with second generation proteasome inhibitors (PI); second generation immunomodulators, monoclonal antibodies, CAR T cells, bispecific antibodies, selinexor, venetoclax, and many others. Most patients with MM undergo several cycles of remissions and relapse, and therefore need multiple lines of combination therapies. Selecting treatment options for relapsed/refractory MM requires consideration of resistance status to specific classes, and patient-specific factors such as age and other comorbidities should be considered. The NCCN Guidelines for MM provide a framework on which to base decisions regarding workup, treatment, and follow-up of newly diagnosed and previously treated MM. This manuscript outlines the recommendations from NCCN Guidelines for MM specific to relapsed/refractory disease.


Asunto(s)
Mieloma Múltiple , Humanos , Anticuerpos Monoclonales/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Oncología Médica , Mieloma Múltiple/terapia , Mieloma Múltiple/tratamiento farmacológico , Recurrencia Local de Neoplasia/tratamiento farmacológico
5.
J Oncol Pharm Pract ; 29(7): 1715-1724, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-36731514

RESUMEN

BACKGROUND: For patients with multiple myeloma (MM) who have undergone autologous stem cell transplant (auto-SCT), the immunomodulatory agent lenalidomide is a first-line option for maintenance therapy. Because longer durations of lenalidomide maintenance are associated with improved survival, identifying strategies to avoid premature cessation of maintenance is an important priority in the post-transplant setting. OBJECTIVES: The primary objective of this analysis was to identify specific clinical predictors of lenalidomide treatment duration that could guide optimal medication management. Key secondary objectives included predictors of intolerable toxicity, rationale for lenalidomide dose reduction/discontinuation, and characterization of dose adjustments. STUDY DESIGN: This retrospective, multi-center cohort study included adults with MM who underwent auto-SCT and initiated maintenance lenalidomide between 01/01/2012 and 02/28/2021. Variables assessed as potential predictors of maintenance duration or intolerable toxicity included age, body mass index (BMI), Eastern Cooperative Oncology Group (ECOG) performance status at time of auto-SCT, renal function, initial lenalidomide dose, use of combination maintenance therapy, and cytogenetic risk category. RESULTS: Among 299 patients included, the median age at time of auto-SCT was 62 years (range 30-77). The majority of patients had standard-risk cytogenetics (64%) and an ECOG performance status of 0 or 1 (72%). In the overall population, the median duration of maintenance was 1.3 years (range 0.3-8.6 years). The median initial dose of lenalidomide was 10 mg daily (range 2.5-25 mg). During the study period, 35% of patients had a dose reduction due to toxicity, 21% stopped lenalidomide due to disease progression, and 19% stopped due to toxicity. Multivariate linear regression analyses did not identify any significant predictors of lenalidomide duration or discontinuation due to intolerable toxicity. The most frequently reported toxicities leading to discontinuation were cytopenias, rash, and fatigue. CONCLUSION: This analysis did not identify any significant risk factors to predict the duration of lenalidomide maintenance or discontinuation for toxicity following auto-SCT in patients with MM. While limited by the retrospective design and relatively small sample size, our findings suggest that a priori lenalidomide dose reductions based on patient co-morbidities or performance status may not substantially affect the duration of lenalidomide maintenance.


Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Mieloma Múltiple , Adulto , Humanos , Persona de Mediana Edad , Anciano , Mieloma Múltiple/tratamiento farmacológico , Lenalidomida/uso terapéutico , Estudios Retrospectivos , Estudios de Cohortes , Supervivencia sin Enfermedad , Trasplante Autólogo , Trasplante de Células Madre , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico
6.
Lancet Oncol ; 21(10): 1317-1330, 2020 10.
Artículo en Inglés | MEDLINE | ID: mdl-32866432

RESUMEN

BACKGROUND: Bortezomib, lenalidomide, and dexamethasone (VRd) is a standard therapy for newly diagnosed multiple myeloma. Carfilzomib, a next-generation proteasome inhibitor, in combination with lenalidomide and dexamethasone (KRd), has shown promising efficacy in phase 2 trials and might improve outcomes compared with VRd. We aimed to assess whether the KRd regimen is superior to the VRd regimen in the treatment of newly diagnosed multiple myeloma in patients who were not being considered for immediate autologous stem-cell transplantation (ASCT). METHODS: In this multicentre, open-label, phase 3, randomised controlled trial (the ENDURANCE trial; E1A11), we recruited patients aged 18 years or older with newly diagnosed multiple myeloma who were ineligible for, or did not intend to have, immediate ASCT. Participants were recruited from 272 community oncology practices or academic medical centres in the USA. Key inclusion criteria were the absence of high-risk multiple myeloma and an Eastern Cooperative Oncology Group performance status of 0-2. Enrolled patients were randomly assigned (1:1) centrally by use of permuted blocks to receive induction therapy with either the VRd regimen or the KRd regimen for 36 weeks. Patients who completed induction therapy were then randomly assigned (1:1) a second time to either indefinite maintenance or 2 years of maintenance with lenalidomide. Randomisation was stratified by intent for ASCT at disease progression for the first randomisation and by the induction therapy received for the second randomisation. Allocation was not masked to investigators or patients. For 12 cycles of 3 weeks, patients in the VRd group received 1·3 mg/m2 of bortezomib subcutaneously or intravenously on days 1, 4, 8, and 11 of cycles 1-8, and day 1 and day 8 of cycles nine to twelve, 25 mg of oral lenalidomide on days 1-14, and 20 mg of oral dexamethasone on days 1, 2, 4, 5, 8, 9, 11, and 12. For nine cycles of 4 weeks, patients in the KRd group received 36 mg/m2 of intravenous carfilzomib on days 1, 2, 8, 9, 15, and 16, 25 mg of oral lenalidomide on days 1-21, and 40 mg of oral dexamethasone on days 1, 8, 15, and 22. The coprimary endpoints were progression-free survival in the induction phase, and overall survival in the maintenance phase. The primary analysis was done in the intention-to-treat population and safety was assessed in patients who received at least one dose of their assigned treatment. The trial is registered with ClinicalTrials.gov, NCT01863550. Study recruitment is complete, and follow-up of the maintenance phase is ongoing. FINDINGS: Between Dec 6, 2013, and Feb 6, 2019, 1087 patients were enrolled and randomly assigned to either the VRd regimen (n=542) or the KRd regimen (n=545). At a median follow-up of 9 months (IQR 5-23), at a second planned interim analysis, the median progression-free survival was 34·6 months (95% CI 28·8-37·8) in the KRd group and 34·4 months (30·1-not estimable) in the VRd group (hazard ratio [HR] 1·04, 95% CI 0·83-1·31; p=0·74). Median overall survival has not been reached in either group. The most common grade 3-4 treatment-related non-haematological adverse events included fatigue (34 [6%] of 527 patients in the VRd group vs 29 [6%] of 526 in the KRd group), hyperglycaemia (23 [4%] vs 34 [6%]), diarrhoea (23 [5%] vs 16 [3%]), peripheral neuropathy (44 [8%] vs four [<1%]), dyspnoea (nine [2%] vs 38 [7%]), and thromboembolic events (11 [2%] vs 26 [5%]). Treatment-related deaths occurred in two patients (<1%) in the VRd group (one cardiotoxicity and one secondary cancer) and 11 (2%) in the KRd group (four cardiotoxicity, two acute kidney failure, one liver toxicity, two respiratory failure, one thromboembolic event, and one sudden death). INTERPRETATION: The KRd regimen did not improve progression-free survival compared with the VRd regimen in patients with newly diagnosed multiple myeloma, and had more toxicity. The VRd triplet regimen remains the standard of care for induction therapy for patients with standard-risk and intermediate-risk newly diagnosed multiple myeloma, and is a suitable treatment backbone for the development of combinations of four drugs. FUNDING: US National Institutes of Health, National Cancer Institute, and Amgen.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Bortezomib/uso terapéutico , Mieloma Múltiple/tratamiento farmacológico , Oligopéptidos/uso terapéutico , Inhibidores de Proteasoma/uso terapéutico , Anciano , Dexametasona/uso terapéutico , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Femenino , Humanos , Análisis de Intención de Tratar , Lenalidomida/uso terapéutico , Masculino , Persona de Mediana Edad , Mieloma Múltiple/patología , Terapia Neoadyuvante , Resultado del Tratamiento
7.
Biochemistry ; 59(43): 4163-4175, 2020 11 03.
Artículo en Inglés | MEDLINE | ID: mdl-33074657

RESUMEN

T cell receptors (TCRs) orchestrate cellular immunity by recognizing peptides presented by a range of major histocompatibility complex (MHC) proteins. Naturally occurring TCRs bind the composite peptide/MHC surface, recognizing peptides that are structurally and chemically compatible with the TCR binding site. Here we describe a molecularly evolved TCR variant that binds the human class I MHC protein HLA-A2 independent of the bound peptide, achieved by a drastic perturbation of the TCR binding geometry that places the molecule far from the peptide binding groove. This unique geometry is unsupportive of normal T cell signaling. A substantial divergence between affinity measurements in solution and in two dimensions between proximal cell membranes leads us to attribute the lack of signaling to steric hindrance that limits binding in the confines of a cell-cell interface. Our results provide an example of how receptor binding geometry can impact T cell function and provide further support for the view that germline-encoded residues in TCR binding loops evolved to drive productive TCR recognition and signaling.


Asunto(s)
Receptores de Antígenos de Linfocitos T/metabolismo , Sitios de Unión , Antígenos HLA-A/metabolismo , Humanos , Complejo Mayor de Histocompatibilidad/genética , Complejo Mayor de Histocompatibilidad/fisiología , Unión Proteica , Conformación Proteica
8.
Pediatr Blood Cancer ; 66(4): e27559, 2019 04.
Artículo en Inglés | MEDLINE | ID: mdl-30511461

RESUMEN

BACKGROUND: This population-based study considered the influence of rituximab on the survival of children (0-19 years), adolescents, and young adults (AYAs, 20-39 years) with diffuse large B-cell lymphoma (DLBCL), including patients with human immunodeficiency virus (HIV) infection. METHODS: Data on 642 children and AYAs diagnosed with DLBCL during 2001-2014 were obtained from the Greater Bay Area Cancer Registry in California. Facility-level reports provided treatment details. The Kaplan-Meier method estimated survival and Cox regression models examined the association between survival and rituximab use, adjusting for sociodemographic and clinical factors. RESULTS: Rituximab use increased from 2001-2007 to 2008-2014 among children (from 32% to 48%), AYAs (from 68% to 84%), and HIV patients (from 57% to 67%). Five-year survival was higher among children (91%) than AYAs (82%). On multivariable analysis, the hazard of death was 44% lower among rituximab recipients, and higher among uninsured patients, those with HIV, and those with advanced stage at diagnosis. HIV patients who received rituximab were 60% less likely to die than nonrecipients. CONCLUSIONS: Our study suggests a benefit of rituximab on the treatment of AYAs and HIV patients with DLBCL. The worse survival observed among HIV-positive and uninsured patients is of concern and calls for further investigation. Careful consideration should be given on whether to recommend rituximab more often on the front-line treatment of children and HIV-positive patients with DLBCL.


Asunto(s)
Infecciones por VIH , VIH-1 , Linfoma de Células B Grandes Difuso , Rituximab/administración & dosificación , Adolescente , Adulto , Factores de Edad , California , Niño , Preescolar , Supervivencia sin Enfermedad , Femenino , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/mortalidad , Humanos , Lactante , Recién Nacido , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Linfoma de Células B Grandes Difuso/mortalidad , Masculino , Tasa de Supervivencia , Adulto Joven
9.
J Arthroplasty ; 34(10): 2392-2397, 2019 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-31178387

RESUMEN

BACKGROUND: Patients between 45 and 54 years old will be the fastest-growing cohort seeking total knee arthroplasty (TKA) over the next 15 years. The purpose of this investigation is to determine the clinical outcomes of TKA in patients less than 50 years old at a minimum of 10 years. We hypothesized that this patient population would have a high rate of survivorship that is similar to that of older patients. METHODS: We reviewed 298 consecutive TKAs on 242 patients at a minimum of 10 years postoperatively. Twenty patients died and 30 TKAs were lost to follow-up leaving 248 TKAs in 202 patients (91 male, 111 female) with a mean age of 45.7 years (range, 26-49) at the time of surgery. Patient-reported outcomes, survivorship, causes of reoperation, and initial postoperative radiographic parameters were collected. RESULTS: At a mean of 13.0 years, there were 9 revisions for tibial loosening (3.6%), 8 for deep infection (3.2%), 7 for polyethylene wear (2.8%), and 3 for failed ingrowth of a cementless femoral component (1.2%). Kaplan-Meier analysis demonstrated 92.0% survivorship with failures defined as aseptic component revision and 83.9% survivorship for all-cause reoperation at 13 years. Patients with tibial alignment of 4° or more of varus or 10° or more of posterior slope were found to have increased rate of failure. CONCLUSION: While overall durability was good in this young patient population, tibial fixation and deep infection were relatively common causes of failure. In addition, increased tibial varus and slope were found to increase the rate of failure. Furthermore, the nearly 3% risk of revision for wear suggests that the use of more wear-resistant bearing surfaces may reduce the risk of failure in this patient population.


Asunto(s)
Artroplastia de Reemplazo de Rodilla/efectos adversos , Prótesis de la Rodilla/efectos adversos , Adulto , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Medición de Resultados Informados por el Paciente , Polietileno , Periodo Posoperatorio , Diseño de Prótesis , Falla de Prótesis , Reoperación/efectos adversos , Estudios Retrospectivos , Riesgo , Tibia/fisiología , Tibia/cirugía
10.
Cancer ; 124(6): 1260-1268, 2018 03 15.
Artículo en Inglés | MEDLINE | ID: mdl-29205296

RESUMEN

BACKGROUND: The adverse impact of second primary malignancies (SPMs) on survival is substantial for adolescents and young adults (AYAs; ie, those 15-39 years old). No studies have evaluated whether the latency time between the first malignancy (the primary malignancy [PM]) and the SPM affects cancer-specific survival (CSS). METHODS: A multivariate Cox proportional hazards regression with Surveillance, Epidemiology, and End Results data for 13 regions from 1992 to 2008 was used to ascertain whether the latency time (1-5 vs ≥ 6 years) to the development of an SPM affected the CSS and overall survival with respect to either the PM or SPM for AYAs with common SPMs. RESULTS: The majority of 1515 AYAs with an SPM had their PM diagnosed between the ages of 26 and 39 years (74.2%) and an SPM diagnosed within 1 to 5 years (72.9%) of the PM's diagnosis. Overall, AYAs that developed an SPM 1 to 5 years after the diagnosis (vs ≥ 6 years) had an increased risk of death from cancer (hazard ratio [HR], 2.52; 95% confidence interval [CI], 1.92-3.29) as well as any cause (HR, 2.60; 95% CI, 2.04-3.32). Specifically, for AYAs with an SPM that was leukemia or a colorectal, breast, or central nervous system malignancy, a shorter latency time (1-5 years) from their PM diagnosis was associated with an overall significantly increased risk of death (2.6-fold) from either their PM or that particular SPM. However, latency did not appear to affect the CSS with respect to either the PM or SPM for AYA patients with a lymphoma or sarcoma SPM. CONCLUSIONS: Most AYAs who develop an SPM do so within 1 to 5 years of their primary cancer diagnosis, and they have an increased risk of death from cancer in comparison with AYAs with an SPM developing after longer survivorship intervals. Cancer 2018;124:1260-8. © 2017 American Cancer Society.


Asunto(s)
Neoplasias Primarias Secundarias/epidemiología , Neoplasias Primarias Secundarias/mortalidad , Neoplasias/mortalidad , Adolescente , Adulto , Factores de Edad , California/epidemiología , Terapia Combinada , Femenino , Estudios de Seguimiento , Humanos , Incidencia , Masculino , Neoplasias/patología , Neoplasias/terapia , Neoplasias Primarias Secundarias/diagnóstico , Pronóstico , Factores de Riesgo , Programa de VERF , Tasa de Supervivencia , Factores de Tiempo , Adulto Joven
11.
Cancer ; 124(9): 1938-1945, 2018 05 01.
Artículo en Inglés | MEDLINE | ID: mdl-29451695

RESUMEN

BACKGROUND: To the authors' knowledge, few population-based studies to date have evaluated the association between location of care, complications with induction therapy, and early mortality in patients with acute myeloid leukemia (AML). METHODS: Using linked data from the California Cancer Registry and Patient Discharge Dataset (1999-2014), the authors identified adult (aged ≥18 years) patients with AML who received inpatient treatment within 30 days of diagnosis. A propensity score was created for treatment at a National Cancer Institute-designated cancer center (NCI-CC). Inverse probability-weighted, multivariable logistic regression models were used to determine associations between location of care, complications, and early mortality (death ≤60 days from diagnosis). RESULTS: Of the 7007 patients with AML, 1762 (25%) were treated at an NCI-CC. Patients with AML who were treated at NCI-CCs were more likely to be aged ≤65 years, live in higher socioeconomic status neighborhoods, have fewer comorbidities, and have public health insurance. Patients treated at NCI-CCs had higher rates of renal failure (23% vs 20%; P = .010) and lower rates of respiratory failure (11% vs 14%; P = .003) and cardiac arrest (1% vs 2%; P = .014). After adjustment for baseline characteristics, treatment at an NCI-CC was associated with lower early mortality (odds ratio, 0.46; 95% confidence interval, 0.38-0.57). The impact of complications on early mortality did not differ by location of care except for higher early mortality noted among patients with respiratory failure treated at non-NCI-CCs. CONCLUSIONS: The initial treatment of adult patients with AML at NCI-CCs is associated with a 53% reduction in the odds of early mortality compared with treatment at non-NCI-CCs. Lower early mortality may result from differences in hospital or provider experience and supportive care. Cancer 2018;124:1938-45. © 2018 American Cancer Society.


Asunto(s)
Antineoplásicos/efectos adversos , Instituciones Oncológicas/estadística & datos numéricos , Paro Cardíaco/mortalidad , Leucemia Mieloide Aguda/mortalidad , Insuficiencia Renal/mortalidad , Insuficiencia Respiratoria/mortalidad , Adulto , Anciano , Antineoplásicos/administración & dosificación , California/epidemiología , Femenino , Paro Cardíaco/etiología , Humanos , Leucemia Mieloide Aguda/complicaciones , Leucemia Mieloide Aguda/terapia , Masculino , Persona de Mediana Edad , National Cancer Institute (U.S.)/estadística & datos numéricos , Sistema de Registros/estadística & datos numéricos , Inducción de Remisión/métodos , Insuficiencia Renal/etiología , Insuficiencia Respiratoria/etiología , Clase Social , Análisis de Supervivencia , Factores de Tiempo , Resultado del Tratamiento , Estados Unidos , United States Department of Veterans Affairs/estadística & datos numéricos , Adulto Joven
12.
J Thromb Thrombolysis ; 45(4): 536-542, 2018 May.
Artículo en Inglés | MEDLINE | ID: mdl-29574610

RESUMEN

Making a definitive diagnosis of heparin-induced thrombocytopenia (HIT) can be problematic. A prompt platelet rise following treatment has been proposed as a "post-test" criterion for diagnosis. However, the platelet response following discontinuation of heparin and initiation of a recommended alternative anticoagulant remains largely undefined and unstudied. This study aimed to characterize platelet response to initial treatment in patients with a low, intermediate, or high likelihood of having HIT. This was a multicenter retrospective cohort study. Patients were over 18 years in age, underwent serologic testing for HIT, and received alternative anticoagulation treatment for HIT. Classification of each patient's likelihood of having HIT was based on an empiric, pre-hoc combination of the 4T score and serology results. The primary outcome for this study was a platelet count response after initiation of direct thrombin inhibitor (DTI) or fondaparinux therapy within 48 h. 124 patients were analyzed. The sensitivity and specificity of having an immediate platelet rise of at least 10,000/µL by day 2 after starting treatment among high-likelihood for HIT patients were 0.71 (95% CI 0.55-0.84) and 0.64 (95% CI 0.5-0.76), respectively. The negative predictive value of no platelet rise was 75.5% (95% CI 0.61-0.86). A prompt platelet count rise may be appropriate to consider along with other known criteria for the clinical diagnosis of HIT. The rise should be immediate following discontinuation of heparin and initiation of recommended treatment, with an upward rise within 48 h.


Asunto(s)
Antitrombinas/uso terapéutico , Plaquetas/efectos de los fármacos , Heparina/efectos adversos , Trombocitopenia/inducido químicamente , Adulto , Anciano , Antitrombinas/farmacología , Plaquetas/citología , Inhibidores del Factor Xa/farmacología , Fondaparinux , Humanos , Persona de Mediana Edad , Recuento de Plaquetas , Polisacáridos/farmacología , Valor Predictivo de las Pruebas , Estudios Retrospectivos , Trombocitopenia/diagnóstico , Adulto Joven
13.
Br J Haematol ; 178(2): 319-326, 2017 07.
Artículo en Inglés | MEDLINE | ID: mdl-28369826

RESUMEN

Previous reports show increased incidence of venous thromboembolism [VTE, deep-vein thrombosis (DVT) and pulmonary embolus (PE)] in sickle cell disease (SCD) patients but did not account for frequency of hospitalization. We determined the incidence of VTE in a SCD cohort versus matched controls. For SCD patients, risk factors for incident VTE, recurrence and the impact on mortality were also determined. Among 6237 patients with SCD, 696 patients (11·2%) developed incident-VTE: 358 (51·6%) had PE (±DVT); 179 (25·7%) had lower-extremity DVT only and 158 (22·7%) had upper-extremity DVT. By 40 years of age, the cumulative incidence of VTE was 17·1% for severe SCD patients (hospitalized ≥3 times a year) versus 8·0% for the matched asthma controls. Amongst SCD patients, women (Hazard ratio [HR] = 1·22; 95% confidence interval [CI]: 1·05-1·43) and those with severe disease (HR = 2·86; 95% CI: 2·42-3·37) had an increased risk of VTE. Five-year recurrence was 36·8% in patients with severe SCD. VTE was associated with increased risk of death (HR = 2·88, 95% CI: 2·35-3·52). In this population-based study, the incidence of VTE was higher in SCD patients than matched controls and was associated with increased mortality. The high incidence of recurrent VTE in patients with severe SCD suggests that extended anticoagulation may be indicated.


Asunto(s)
Anemia de Células Falciformes/complicaciones , Tromboembolia Venosa/etiología , Adolescente , Adulto , Anciano , Anemia de Células Falciformes/mortalidad , California/epidemiología , Niño , Preescolar , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Recurrencia , Estudios Retrospectivos , Factores de Riesgo , Tromboembolia Venosa/mortalidad , Adulto Joven
14.
Br J Haematol ; 178(1): 72-80, 2017 07.
Artículo en Inglés | MEDLINE | ID: mdl-28542862

RESUMEN

With the addition of rituximab and other treatment advances, survival after diffuse large B-cell lymphoma (DLBCL) has improved, but subsequent primary malignancies (SPMs) have emerged as an important challenge for DLBCL survivorship. We calculated standardized incidence ratios (SIRs) and 95% confidence intervals (CIs) for SPMs among 23 879 patients who survived at least 1 year after a first primary DLBCL diagnosed during 1989-2012, compared to the general population in California. Cumulative incidence (CMI) of SPMs, accounting for the competing risk of death, also was calculated. We found that the incidence of acute myeloid leukaemia (AML) nearly doubled in the post-rituximab era [SIR (95% CI) 4·39 (2·51-7·13) pre- (1989-2000) and 8·70 (6·62-11·22) post-rituximab (2001-2012)]. Subsequent thyroid cancer was rare pre-rituximab, but increased substantially after 2001 [0·66 (0·08-2·37) vs. 2·27(1·44-3·41)]. The 5-year CMI for all SPMs (4·77% pre- vs. 5·41% post-rituximab, P = 0·047), AML (0·15% vs. 0·41%, P = 0·003), thyroid cancer (0·03% vs. 0·15%, P = 0·003) and melanoma (0·25% vs. 0·42%, P = 0·020) were greater in DLBCL patients diagnosed in the post- versus pre-rituximab period. This study provides insight into the changing pattern of SPM occurrence after the introduction of rituximab, which may elucidate the aetiology of SPMs and should guide future cancer surveillance efforts among DLBCL patients.


Asunto(s)
Linfoma de Células B Grandes Difuso/epidemiología , Neoplasias Primarias Secundarias/epidemiología , Adolescente , Adulto , Anciano , Antineoplásicos/efectos adversos , Antineoplásicos/uso terapéutico , California/epidemiología , Femenino , Estudios de Seguimiento , Humanos , Incidencia , Leucemia Mieloide Aguda/inducido químicamente , Leucemia Mieloide Aguda/epidemiología , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Masculino , Melanoma/inducido químicamente , Melanoma/epidemiología , Persona de Mediana Edad , Neoplasias Primarias Secundarias/inducido químicamente , Sistema de Registros , Rituximab/efectos adversos , Rituximab/uso terapéutico , Neoplasias de la Tiroides/inducido químicamente , Neoplasias de la Tiroides/epidemiología , Adulto Joven
15.
J Arthroplasty ; 32(4): 1328-1334, 2017 04.
Artículo en Inglés | MEDLINE | ID: mdl-27884418

RESUMEN

BACKGROUND: Heterotopic ossification (HO) is a known complication following total hip arthroplasty. Radiation is an effective prophylaxis, but an optimal protocol has yet to be determined. We performed a randomized, double-blinded clinical trial in high-risk patients to determine the efficacy of 400 vs 700 cGy doses of radiation. METHODS: One hundred forty-seven patients undergoing total hip arthroplasty and at high risk for HO at an urban medical center were randomized to receive either a single 400 or 700 cGy dose of radiation postoperatively. High risk was defined as a diagnosis of diffuse idiopathic skeletal hyperostosis, hypertrophic osteoarthritis, ankylosing spondylitis, or history of previous HO. Radiation was administered on the first or second postoperative day. A single blinded reviewer graded radiographs taken immediately postoperatively and at a minimum of 6 months postoperatively using the Brooker classification. Progression was defined as an increase in Brooker classification. Operative data including surgical approach, implant fixation, revision surgery, and postoperative range of motion data were also collected. RESULTS: A significantly greater portion of patients who received the 400 cGy dose demonstrated progression of HO than patients who received the 700 cGy dose. There were no wound complications. No preoperative factors were associated with a higher rate of progression. Patients who progressed had less flexion on physical examination than patients who did not progress, but this was not clinically significant. CONCLUSION: Seven hundred centigray was superior to 400 cGy in preventing HO formation following total hip arthroplasty in high-risk patients and may be the more effective treatment in this population. Further studies comparing 700 cGy to dosages between 400 and 700 cGy may help to clarify if a more optimal dose can be identified.


Asunto(s)
Artroplastia de Reemplazo de Cadera/efectos adversos , Osificación Heterotópica/etiología , Osificación Heterotópica/prevención & control , Radioterapia , Adulto , Anciano , Artroplastia de Reemplazo de Cadera/estadística & datos numéricos , Progresión de la Enfermedad , Método Doble Ciego , Femenino , Articulación de la Cadera/cirugía , Humanos , Masculino , Persona de Mediana Edad , Osteoartritis/complicaciones , Examen Físico , Periodo Posoperatorio , Radiografía , Dosificación Radioterapéutica , Rango del Movimiento Articular , Reoperación/estadística & datos numéricos , Espondilitis Anquilosante/complicaciones , Resultado del Tratamiento
16.
Am J Hematol ; 91(6): 560-5, 2016 06.
Artículo en Inglés | MEDLINE | ID: mdl-26928381

RESUMEN

Hodgkin lymphoma post-transplant lymphoproliferative disorder (HL-PTLD) is an uncommon PTLD with unclear prognosis and differences between HL-PTLD and immunocompetent HL are not well defined. Patient characteristics were compared among 192 patients with HL-PTLD from the Scientific Registry of Transplant Recipients and 13,847 HL patients in SEER (HL-SEER). Overall survival (OS) and disease-specific survival (DSS) were compared after exact matching. Additionally, multivariable analyses were used to identify prognostic markers of survival and associations between treatment and survival. Median time from transplant to HL-PTLD diagnosis was 88 months. When compared with HL-SEER, patients with HL-PTLD were older (median age, 52 vs. 36 years, P = 0.001), more likely male (73% vs. 54%, P < 0.001), Caucasian (81% vs. 70%, P = 0.02), and had extranodal disease (42% vs. 3%, P < 0.001). Five-year OS for patients with HL-PTLD was 57% versus 80% for HL-SEER (P < 0.001); DSS was also inferior (P < 0.001). For patients with HL-PTLD, the use of any chemotherapy was associated with decreased hazard of death (HR = 0.36, P < 0.001). Furthermore, patients who received no chemotherapy or nontraditional HL regimens had increased hazard of death (aHR = 2.94, P = 0.001 and 2.01, P = 0.04) versus HL-specific chemotherapy regimens. In multivariable analysis, advanced age and elevated creatinine were associated with inferior OS (aHR = 1.26/decade P < 0.001 and 1.64/0.1 mg/dL increase P = 0.02). A prognostic score based on the number of these adverse factors (0, 1, 2) was associated with 10-year OS rates of 79%, 53%, and 11%, respectively (P < 0.001). Altogether, HL-PTLD patients have inferior survival when compared with HL-SEER. Furthermore, treatment with HL-specific chemotherapy was associated with improved OS, whereas age and creatinine identified patients with markedly divergent survival. Am. J. Hematol. 91:560-565, 2016. © 2016 Wiley Periodicals, Inc.


Asunto(s)
Enfermedad de Hodgkin/mortalidad , Enfermedad de Hodgkin/terapia , Trastornos Linfoproliferativos/mortalidad , Trastornos Linfoproliferativos/terapia , Adulto , Factores de Edad , Antineoplásicos/uso terapéutico , Creatina/sangre , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Sistema de Registros , Análisis de Supervivencia , Tasa de Supervivencia , Resultado del Tratamiento , Adulto Joven
17.
Am J Hematol ; 96(4): E114-E117, 2021 04 01.
Artículo en Inglés | MEDLINE | ID: mdl-33476436
18.
Instr Course Lect ; 65: 225-41, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-27049193

RESUMEN

Restoration of equal leg lengths and dynamic hip stability are essential elements of a successful total hip arthroplasty. A careful clinical examination, a preoperative plan, and appropriate intraoperative techniques are necessary to achieve these goals. Preoperative identification of patients at risk for residual leg length discrepancy allows surgeons to adjust the surgical approach and/or the type of implant and provide better preoperative patient education. The use of larger femoral heads, high-offset stem options, and enhanced soft-tissue repairs have improved impingement-free range of motion as well as dynamic hip stability and have contributed to an overall reduction in dislocation. Methods for accurate leg length restoration and component positioning include anatomic landmarks, intraoperative radiographs, intraoperative calipers, stability testing, and computer-assisted surgery. If recurrent instability occurs after total hip arthroplasty, the underlying cause for dislocation should be identified and treated; this may include the use of semiconstrained dual-mobility or fully constrained liners, depending on abductor function. Surgeons should be aware of the clinical and surgical techniques for achieving leg length equalization and dynamic hip stability in total hip arthroplasty.


Asunto(s)
Artroplastia de Reemplazo de Cadera , Luxación de la Cadera , Articulación de la Cadera , Prótesis de Cadera , Inestabilidad de la Articulación , Diferencia de Longitud de las Piernas , Osteoartritis de la Cadera/cirugía , Complicaciones Posoperatorias/prevención & control , Artroplastia de Reemplazo de Cadera/efectos adversos , Artroplastia de Reemplazo de Cadera/instrumentación , Artroplastia de Reemplazo de Cadera/métodos , Luxación de la Cadera/etiología , Luxación de la Cadera/prevención & control , Articulación de la Cadera/fisiopatología , Articulación de la Cadera/cirugía , Humanos , Cuidados Intraoperatorios/métodos , Inestabilidad de la Articulación/etiología , Inestabilidad de la Articulación/prevención & control , Diferencia de Longitud de las Piernas/etiología , Diferencia de Longitud de las Piernas/prevención & control , Cuidados Preoperatorios/métodos , Ajuste de Prótesis/métodos , Ajuste de Riesgo/métodos , Cirugía Asistida por Computador/métodos
19.
J Arthroplasty ; 31(7): 1516-8, 2016 07.
Artículo en Inglés | MEDLINE | ID: mdl-26860964

RESUMEN

BACKGROUND: Hip arthroscopy utilization is on the rise in the United States. Thus, determining the impact of prior hip arthroscopy on subsequent total hip arthroplasty (THA) is important to understand. METHODS: A retrospective review of a high-volume orthopedic surgery practice's billing database yielded 42 hip arthroscopies that underwent subsequent THA. An age-, sex-, and body mass index (2:1)-matched cohort of primary THAs was used for comparison. RESULTS: No difference was observed in the postoperative Harris Hip Score between groups (92.1 ± 10.9 vs 90.1 ± 6.6, P = .20); however, there was greater overall improvement in Harris Hip Score in the control group (40.4 ± 18.4 vs 45.1 ± 8.7, P = .05). There were no differences observed in the complication (P = .5) or revision rates (P = .4). CONCLUSION: With the numbers available, prior hip arthroscopy does not appear to have an impact on the functional outcomes of a subsequent THA.


Asunto(s)
Artroplastia de Reemplazo de Cadera/efectos adversos , Artroscopía/efectos adversos , Articulación de la Cadera/cirugía , Artropatías/cirugía , Reoperación/efectos adversos , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Resultado del Tratamiento
20.
Knee Surg Sports Traumatol Arthrosc ; 22(12): 2931-40, 2014 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-25026932

RESUMEN

PURPOSE: Contemporary total knee arthroplasty femoral component designs offer various degrees of fit amongst the global population. The purpose of this study was to assess component fit of contemporary femoral component design families against multiple ethnicities. METHODS: Using a multi-ethnic dataset including Caucasian, Indian, and Korean subjects, this study investigated component fit in six contemporary femoral component design families (A: Persona™, B: NexGen (®), C: Sigma (®), D: GENESIS™ II, E: Triathlon (®), F: Vanguard (®)). Component overhang/underhang was measured between the resected distal femur and its corresponding component size and compared across design families and ethnicities. The severity of overhang/underhang and propensity of downsizing due to clinically significant overhang were quantified for the overall dataset and each ethnicity. RESULTS: In all the overhang cases, Designs A and B had significantly lower component overhang than the other designs (p < 0.02). In all the underhang cases, Designs C and E had significantly greater underhang than the other designs (p < 0.01). Component design influenced the occurrence (% bones) of component downsizing due to clinically significant overhang (>3 mm), with the highest incidence observed in Designs D (20.5%) and F (17.7%), and the lowest incidence observed in Designs A (0%) and B (0.4%). Variation in component fit was significantly impacted by designs (p < 0.01) but not ethnicities (n.s.). CONCLUSIONS: The inclusion of multiple ML/AP shape offerings and the increased number of available sizes in Design A, as compared to other contemporary femoral component design families studied, result in improved femoral component fit across various ethnicities.


Asunto(s)
Artroplastia de Reemplazo de Rodilla/instrumentación , Fémur/cirugía , Articulación de la Rodilla/cirugía , Prótesis de la Rodilla , Diseño de Prótesis , Adulto , Anciano , Pueblo Asiatico , Pesos y Medidas Corporales , Bases de Datos Factuales , Femenino , Fémur/anatomía & histología , Humanos , Articulación de la Rodilla/anatomía & histología , Masculino , Persona de Mediana Edad , Población Blanca
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