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Venous thromboembolism (VTE) affects 1.2 million people per year in the United States. With several clinical changes in diagnosis and treatment approaches in the past decade, we evaluated contemporary post-VTE mortality risk profiles and trends. Incident VTE cases were identified from the 2011-2019 Medicare 20% Sample, which is representative of nearly all Americans aged 65 and older. The social deprivation index was linked from public data; race/ethnicity and sex were self-reported. The all-cause mortality risk 30 days and 1 year after incident VTE was calculated in demographic subgroups and by prevalent cancer diagnosis status using model-based standardization. Risks for major cancer types, risk differences by age, sex, race/ethnicity, and socio-economic status (SES), and trends over time are also reported. The all-cause mortality risk among older US adults following incident VTE was 3.1% (95% CI 3.0-3.2) at 30 days and 19.6% (95% CI 19.2-20.1) at 1 year. For cancer-related VTE events, the age-sex-race-standardized risk was 6.0% at 30 days and 34.7% at 1 year. The standardized 30-day and 1-year risks were higher among non-White beneficiaries and among those with low SES. One-year mortality risk decreased 0.28 percentage points per year (95% CI 0.16-0.40) on average across the study period, with no trend observed for 30-day mortality risk. In sum, all-cause mortality risk following incident VTE has decreased slightly in the last decade, but racial and socio-economic disparities persist. Understanding patterns of mortality among demographic subgroups and in cancer-associated events is important for targeting efforts to improve VTE management.
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Neoplasias , Tromboembolia Venosa , Humanos , Anciano , Adulto , Estados Unidos/epidemiología , Persona de Mediana Edad , Tromboembolia Venosa/epidemiología , Medicare , Neoplasias/epidemiología , Factores de RiesgoRESUMEN
BACKGROUND: Globally, 5 million to 10 million people are infected with human T-cell leukemia virus type 1, which causes adult T-cell leukemia/lymphoma (ATLL) in 2% to 5% of the carriers. ATLL is a rare but extremely aggressive malignancy that can be challenging to diagnose. Very little data exist on the incidence patterns of ATLL in the United States. METHODS: ATLL cases reported to the National Program of Cancer Registries, the Surveillance, Epidemiology, and End Results (SEER) program, and the New York State Cancer Registry were used for the study. Age-adjusted incidence rates were calculated by age, race/ethnicity, sex, and year of diagnosis. The 5-year survival rate was compared among race/ethnicity groups with the SEER data. RESULTS: During 2001-2015, 2148 ATLL cases were diagnosed in the United States, 18% of which were in New York State. New York State had the highest incidence rate for ATLL, with a rising trend especially among non-Hispanic blacks (NHBs), whereas the incidence was stable across the remainder of the United States. NHBs were diagnosed at a younger median age (54 years) and had a shorter overall survival (6 months). In New York City, only 22.6% of the ATLL cases diagnosed were born in North America. CONCLUSIONS: This is the largest epidemiological study of ATLL in the United States and shows a rising incidence in New York City. NHBs have a younger age at presentation and poor overall survival. The rising incidence is largely due to NHBs originating from the Caribbean.
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Leucemia-Linfoma de Células T del Adulto/epidemiología , Linfoma/epidemiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Leucemia-Linfoma de Células T del Adulto/patología , Leucemia-Linfoma de Células T del Adulto/terapia , Linfoma/patología , Linfoma/terapia , Masculino , Persona de Mediana Edad , Ciudad de Nueva York/epidemiología , América del Norte/epidemiología , Programa de VERF , Estados Unidos/epidemiología , Población Blanca , Adulto JovenRESUMEN
In the United States adult T cell lymphoma-leukemia (ATLL) carries a dismal prognosis and mainly affects immigrants from human T cell lymphotropic virus 1 endemic areas. Allogeneic hematopoietic stem cell transplant (alloHSCT) can be effective and is recommended as an upfront treatment in the National Comprehensive Cancer Network guidelines. We studied the barriers to alloHSCT in one of the largest ATLL populations in the United States. Comprehensive chart and donor registry reviews were conducted for 88 ATLL patients treated at Montefiore Medical Center from 2003 to 2018. Among 49 patients with acute and 32 with lymphomatous subtypes, 48 (59.5%) were ineligible for alloHSCT because of early mortality (52%), loss to follow-up (21%), uninsured status (15%), patient declination (10%), and frailty (2%). Among 28 HLA-typed eligible patients (34.6%), matched related donors were identified for 7 (25%). A matched unrelated donor (MUD) search yielded HLA-matched in 2 patients (9.5%), HLA mismatched in 6 (28.5%), and no options in 13 (62%). Haploidentical donors were identified for 6 patients (46%) with no unrelated options. There were no suitable donors for 7 (25%) alloHSCT-eligible patients. The main limitation for alloHSCT after donor identification was death from progressive disease (82%). AlloHSCT was performed in 10 patients (12.3%) and was associated with better relapse-free survival (26 versus 11 months, Pâ¯=â¯.04) and overall survival (47 versus 10 months, Pâ¯=â¯.03). Early mortality and progressive disease are the main barriers to alloHSCT, but poor follow-up, uninsured status, and lack of suitable donor, including haploidentical, are also substantial limitations that might disproportionally affect this vulnerable population. AlloHSCT can achieve long-term remissions, and strategies aiming to overcome these barriers are urgently needed to improve outcomes in ATLL.
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Trasplante de Células Madre Hematopoyéticas/métodos , Virus Linfotrópico T Tipo 1 Humano/patogenicidad , Leucemia-Linfoma de Células T del Adulto/terapia , Trasplante Homólogo/métodos , Adulto , Estudios de Cohortes , Femenino , Humanos , Masculino , Persona de Mediana Edad , Centros de Atención Terciaria , Estados UnidosRESUMEN
Factors that impact first-year morbidity and mortality in adults undergoing myeloablative allogeneic hematopoietic cell transplantation with ex vivo CD34+ selection have not been previously reported. We assessed all toxicities ≥ grade 3 from the start of conditioning to date of death, relapse, or last contact in 200 patients during the first year after transplantation, identifying 1885 individual toxicities among 17 organ-based toxicity groups. The most prevalent toxicities in the first year were of infectious, metabolic, hematologic, oral/gastrointestinal, hepatic, cardiac, and pulmonary etiologies. Renal complications were minimal. Grades II to IV and III and IV acute GVHD at day 100 were 11.5% and 3%, respectively. In separate multivariate models, cardiovascular, hematologic, hepatic, neurologic, pulmonary, and renal toxicities negatively impacted nonrelapse mortality (NRM) and overall survival during the first year. A higher-than-targeted busulfan level, patient cytomegalovirus seropositivity, and an Hematopoietic Cell Transplantation-Specific Comorbidity Index of ≥3 were associated with increased risk of NRM and all-cause death. Ex vivo CD34+ selection had a favorable 1-year OS of 75% and NRM of 17% and a low incidence of sinusoidal obstruction syndrome. These data establish a benchmark to focus efforts in reducing toxicity burden while improving patient outcomes.
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Antígenos CD34/metabolismo , Neoplasias Hematológicas/terapia , Trasplante de Células Madre Hematopoyéticas/métodos , Acondicionamiento Pretrasplante/métodos , Trasplante Homólogo/métodos , Adulto , Anciano , Femenino , Neoplasias Hematológicas/patología , Humanos , Masculino , Persona de Mediana Edad , Resultado del Tratamiento , Adulto JovenRESUMEN
Nivolumab is a treatment option for patients with metastatic renal cell carcinoma (RCC) previously treated with targeted antiangiogenic therapy. Papillary renal cell carcinoma (PRCC) comprises 10-15% of RCC cases but non-clear cell subtypes were excluded from the immunotherapy trials. We report the case of a woman with recurrent metastatic PRCC who had an impressive therapeutic response to nivolumab with no significant adverse events. She had previously been treated with sunitinib and pazopanib with no response. She showed a remarkable clinical improvement after only the first 2 immunotherapy cycles and subsequent radiographic studies demonstrated a marked decrease in tumor burden. At present, she continues to show a durable benefit after 8 months of treatment. Her tumor had <1% positivity for PD-L1 staining and a low tumor mutational burden with no actionable mutations on genomic sequencing. Considering its high genetic variation, checkpoint blockade immunotherapies (CBIs) are attractive treatment options in PRCC. This is the third case that reports objective responses of nivolumab in PRCC. We believe our patient's experience supports the inclusion of non-clear cell RCC on clinical trials using CBIs. PD-L1 status and TMB may not serve as predictive biomarkers for response.
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Anticuerpos Monoclonales/uso terapéutico , Antineoplásicos/uso terapéutico , Carcinoma de Células Renales/tratamiento farmacológico , Neoplasias Renales/tratamiento farmacológico , Adulto , Femenino , Humanos , Inmunoterapia/métodos , NivolumabRESUMEN
Background: Multiple myeloma (MM) is associated with high risk of venous thromboembolism (VTE). Anticoagulant prophylaxis is frequently recommended but underutilized partly due to the absence of studies assessing bleeding risk. Objectives: To determine the rate of severe (hospitalized) bleeding from thromboprophylaxis in patients treated for MM and identify clinical risk factors for bleeding in this population. Methods: Using the MarketScan database, we analyzed 6656 patients treated for MM between 2013 and 2021. Concomitant thromboprophylaxis was defined using prescription claims. Hospitalized bleeding was identified through the Cunningham algorithm. Bleeding rates were compared by thromboprophylaxis status, and Cox regression identified risk factors for bleeding. Results: Anticoagulant thromboprophylaxis was used in 6.6% (436) patients treated for MM. Patients on thromboprophylaxis had a higher rate of immunomodulatory-based therapy (63.8% vs 46.7%; P < .01) and lower rate of antiplatelet use (2.1% vs 4.7%; P < .01). Bleeding occurred in 1.4% of them during median follow-up of 1.3 years. Rate of severe bleeding was not different between those on prophylaxis (7.8 per 1000 person-years) and those not on prophylaxis (10.1 per 1000 person-years). No association was identified between thromboprophylaxis and bleeding. Factors associated with increased bleeding included age (hazard ratio [HR], 1.38 per 10 years increase in age), comorbidity index (HR, 1.18 per SD increase), history of bleeding (HR, 1.54), hypertension (HR, 1.87), and renal disease (HR, 1.56). Conclusion: Risk of serious bleeding from thromboprophylaxis in patients treated for MM was low, and concomitant anticoagulant therapy did not result in increased bleeding risk. Clinical risk factors for bleeding included age, comorbidity index, bleeding history, hypertension, and renal disease.
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BACKGROUND: Cytopenia is associated with cancer through mechanisms including clonal hematopoiesis and chronic inflammation. Cytopenia is more prevalent in Black people but its relationship with racial disparities in cancer mortality is unknown. METHODS: Cytopenia was defined in 19,028 Black and White participants recruited between 2003 and 2007 for the REasons for Geographic and Racial Differences in Stroke cohort, based on age-, sex-, and race-adjusted ranges for blood counts. Cancer death was ascertained from Social Security Death and National Death Indexes. Multivariable Cox models estimated the risk of cancer mortality associated with cytopenia, adjusting for demographics (model1), anemia and cancer risk factors (model2), and socioeconomics (model3). Racial differences in the cytopenia-cancer death association were tested by cross-product interaction terms. RESULTS: Cytopenia was identified in 383 (2%) participants, 250 (65%) White, and 113 (35%) Black people. With median follow-up 11.3 years, 1,224 (6.4%) cancer deaths occurred. Cytopenia was associated with increased risk of cancer mortality in model1 (HR = 1.57, 95%CI 1.15-2.24), model2 (HR = 1.67, 95%CI 1.22-2.30), and model3 (HR = 1.59, 95%CI 1.17-2.17). Participants with cytopenia had twofold increased cumulative incidence of cancer death (13% vs. 6.5%, p < 0.01). Race by cytopenia interaction terms showed higher HR for cancer death in Black compared to White participants: 2.01 versus 1.41 (pinteraction = 0.016, model1), 2.12 versus 1.45 (pinteraction = 0.009, model2), and 1.82 versus 1.44 (pinteraction = 0.04, model3). CONCLUSION: In this large, observational biracial prospective study, cytopenia was a risk factor for cancer death, with stronger association in Black than White people. Though race impacted the association of cytopenia with cancer mortality, cytopenia was not a mediator of the racial disparity in cancer mortality.
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Anemia , Neoplasias , Humanos , Estados Unidos , Estudios Prospectivos , Factores Raciales , Factores de Riesgo , BlancoRESUMEN
Background: Multiple myeloma (MM) is associated with high risk of venous thromboembolism (VTE). Thromboprophylaxis is thoroughly studied in MM. Contrarily, studies assessing the risk of bleeding in people with MM on anticoagulation are lacking. Objectives: To determine the rate of serious bleeding in patients with MM receiving anticoagulation for VTE and the clinical factors associated with bleeding risk. Methods: Using the MarketScan commercial database, we identified 1298 people with MM treated with anticoagulation for incident VTE events between 2011 and 2019. Hospitalized bleeding was identified using the Cunningham algorithm. Rates of bleeding were calculated and Cox regression identified risk factors for bleeding. Results: Bleeding occurred in 51 (3.9%) cases during median follow-up of 1.13 years. Rate of bleeding among patients with MM on anticoagulation was 24.0 per 1000 person-years. In adjusted regression, factors associated with increased bleeding included age (HR, 1.31 per 10-year increase; 95% CI, 1.03-1.65), Charlson comorbidity index (HR, 1.29 per SD increase; 95% CI, 1.02-1.58), use of antiplatelet agents (HR, 2.4; 95% CI, 1.03-5.68), diabetes (HR, 1.85; 95% CI, 1.06-3.26), and renal disease (HR, 1.80; 95% CI, 1.05-3.16). Cumulative incidence of bleeding was 4.7%, 3.2%, and 3.4% for warfarin, low molecular weight heparin, and direct oral anticoagulants, respectively. Conclusion: In this real-world analysis, the rate of bleeding in people with MM on anticoagulation was comparable to those in other subsets of cancer-related VTE. Bleeding rate was lower with low molecular weight heparin and direct oral anticoagulants than warfarin. Higher comorbidity index, diabetes, antiplatelet agent use, and renal disease were risk factors for serious bleeding.
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Preexisting autoimmune disease affects between 10% and 30% of patients with myelodysplastic syndromes (MDS). Studies comparing outcomes in patients with MDS with and without autoimmune disease show discordant results. Using the Surveillance, Epidemiology, and End Results Medicare database, we conducted a population analysis to define the impact of autoimmunity on MDS outcomes. Cases were ascertained between 2007 and 2017 and claim algorithms used to identify autoimmune disease, demographic characteristics, comorbidity scores, MDS histology, transfusion burden, treatment with hypomethylating agents, and hematopoietic stem cell transplantation. Cox regression models estimated the impact on survival, and competing-risk regression models defined the effect on leukemic transformation. We analyzed 15 277 patients with MDS, including 2442 (16%) with preexisting autoimmune disease. The epidemiologic profile was distinctive in cases with preexisting autoimmunity, who were younger, were predominantly female, and had higher transfusion burden without difference in MDS histologic distribution. Autoimmune disease was associated with 11% decreased risk of death (hazard ratio [HR], 0.89; 95% confidence interval [CI], 0.85-0.94; P < .001). The effect on risk of leukemic transformation differed based on MDS histology. In low-risk MDS histologies, autoimmunity was associated with a 1.9-fold increased risk of leukemia (HR, 1.87; 95% CI, 1.17-2.99; P = .008), whereas no significant effect was seen in other groups. These results suggest that autoimmune disease affects survival in MDS and is associated with decreased mortality. The survival effect was evident in low-risk histologies despite higher risk of progression to leukemia. This could represent inflammation-driven hematopoiesis, simultaneously favoring less aggressive phenotypes and clonal expansion, which warrants further investigation.
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Enfermedades Autoinmunes , Leucemia Mieloide Aguda , Síndromes Mielodisplásicos , Humanos , Femenino , Anciano , Estados Unidos , Masculino , Medicare , Síndromes Mielodisplásicos/complicaciones , Síndromes Mielodisplásicos/epidemiología , Síndromes Mielodisplásicos/terapia , Leucemia Mieloide Aguda/etiología , Modelos de Riesgos Proporcionales , Enfermedades Autoinmunes/complicaciones , Enfermedades Autoinmunes/epidemiologíaRESUMEN
Adult T-cell leukemia/lymphoma (ATLL) remains challenging to treat and has dismal outcome. Allogeneic stem-cell transplantation (allo-SCT) has promising results, but data remain scarce. In this single-center retrospective analysis of 100 patients with ATLL from north America (67 acute, 22 lymphomatous), 17 underwent allo-SCT and 5 autologous SCT (ASCT), with a median follow-up of 65 months. Post-transplant 3-years relapse incidence (RI) and non-relapse mortality (NRM) were 51% and 37%, respectively, and 3-year progression-free survival (PFS) and overall survival (OS) were 31% and 35%, respectively. ASCT 1-year RI was 80% compared to 30% in allo-SCT (p = 0.03). After adjusting for immortal-time bias, allo-SCT had significantly improved OS (HR = 0.4, p = 0.01). In exploratory multivariate analysis, patients achieving first complete response and Karnofsky score ≥ 90 had significantly better outcomes, as did Black patients, compared to Hispanics, who had worse outcome. In transplanted patients, 14 died within 2 years, 4 of which ASCT recipients. Our data are the largest ATLL transplant cohort presented to date outside of Japan and Europe. We show that allo-SCT, but not ASCT, is a valid option in select ATLL patients, and can induce long term survival, with 40% of patients alive after more than 5 years.
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A sizable proportion of patients with acute myeloid leukemia (AML) fail to achieve remission. Hematopoietic stem cell transplantation (HSCT) is the only intervention with potential of long-term survival. A recent Acute Leukemia Working Party (ALWP)/European Society for Blood and Marrow Transplantation (EBMT) analysis reports substantial posttransplant survival gains for patients with active disease who received transplants. Decreased relapse was the largest contributor to survival, a cause for optimism in this challenging population. See related article by Nagler et al., p. 4258.
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Trasplante de Células Madre Hematopoyéticas , Leucemia Mieloide Aguda , Enfermedad Aguda , Humanos , Leucemia Mieloide Aguda/mortalidad , Recurrencia , Estudios RetrospectivosRESUMEN
INTRODUCTION: Clonal hematopoiesis, a precursor to myelodysplastic syndromes (MDS), constitutes a novel cardiovascular disease (CVD) risk factor, causing growing interest in cardiovascular outcomes in MDS. Rurality is associated with increased CVD but studies on cardiovascular geographic disparities in MDS are lacking. METHODS: Using the U.S. Surveillance, Epidemiology, and End Results (SEER) registry, we identified 52,750 MDS patients between 2001 and 2016. Rurality was defined using Rural-Urban Continuum Codes. Cox regression estimated the association of rurality and cardiovascular death. RESULTS: MDS incidence was equal in urban and rural populations (6.7 per 100,000). Crude probability of cardiovascular death was higher among rural MDS patients. Adjusting for age, sex, race/ethnicity, marital status, insurance, and MDS risk (defined from histology), rural patients had 12% increased risk of CVD death compared to urban patients (HR=1.12, 95%CI 1.03-1.21). HR for CVD death was 1.22 (95%CI 1.01-1.5) in patients from the most rural areas (less than 2500 urban population). Among MDS patients younger than 65 years, rurality was associated with 25% increased risk of CVD death (HR=1.25, 95%CI 1.01-1.59). DISCUSSION: This population-based analysis suggests that rural residence is linked to higher burden of cardiovascular death in patients with MDS. The disparity is not explained by demographic factors or MDS risk. Interventions targeting CVD may improve outcomes in rural MDS patients.
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Enfermedades Cardiovasculares , Síndromes Mielodisplásicos , Humanos , Incidencia , Síndromes Mielodisplásicos/epidemiología , Población Rural , Población UrbanaRESUMEN
Alternative statistical designs cannot fully mitigate the limitations of traditional clinical trials in rare cancers. Creative study designs that integrate early clinical data and correlative outcomes from concomitant translational and laboratory models to evaluate the efficacy of druggable targets can potentially expedite access to novel therapies for these patients.See related article by Hunter et al., p. 6095.
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Neoplasias , Pirimidinas , Humanos , Nitrilos , Pirazoles , Pirimidinas/uso terapéutico , Proyectos de InvestigaciónRESUMEN
Thrombocytopenia remains a challenge in myeloid malignancies, needing safer and more effective therapies. JNJ-26366821, a pegylated synthetic peptide thrombopoietin (TPO) mimetic not homologous to endogenous TPO, has an in-vitro EC50 of 0.2 ng/mL for the TPO receptor and dose dependently elevates platelets in volunteers. We demonstrate that JNJ-26366821 increases megakaryocytic differentiation and megakaryocytic colony formation in healthy controls and samples from myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). JNJ-26366821 had no effect on proliferation of malignant myeloid cell lines at doses up to 1000 ng/mL and malignant patient-derived mononuclear cells showed no increased cell growth or leukemic colony formation capacity at concentrations between 0.2 ng/mL and 10 ng/mL. Furthermore, JNJ-26366821 did not enhance in-vivo engraftment of leukemic cells in an AML xenotransplantation murine model. Our results show that JNJ-26366821 stimulates megakaryopoiesis without causing proliferation of the malignant myeloid clones in MDS/AML and provides the rationale for clinical testing of JNJ-26366821 in myeloid malignancies.
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Leucemia Mieloide Aguda , Síndromes Mielodisplásicos , Animales , Proliferación Celular , Humanos , Leucemia Mieloide Aguda/tratamiento farmacológico , Ratones , Síndromes Mielodisplásicos/tratamiento farmacológico , Receptores de Trombopoyetina , Trombopoyetina/farmacologíaRESUMEN
INTRODUCTION: Nanoparticle albumin-bound paclitaxel (nab-paclitaxel), a microtubule inhibitor, has demonstrated clinical efficacy in the treatment of advanced non-small cell lung cancer (NSCLC) either as monotherapy or in combination. Nab-paclitaxel was developed to reduce the toxicities associated with solvent-bound paclitaxel (sb-paclitaxel). Areas covered: This review first focuses on the clinical trials evaluating the efficacy and tolerability of nab-paclitaxel in NSCLC at different settings. The approval of nab-paclitaxel in combination with carboplatin at the front-line setting for advanced NSCLC was based on the key phase III study, which showed that nab-paclitaxel/carboplatin was associated with superior overall response rate and favorable toxicity profile compared to sb-paclitaxel/carboplatin. The review also addresses the nab-paclitaxel pharmacology, other combinations (e.g. immunotherapy with PD-1/PD-L1 inhibitors), potential biomarkers (e.g. caveolin-1), and special subgroups (e.g. the elderly, squamous histology). Expert opinion: Existing data has established the role of nab-paclitaxel in the management of advanced NSCLC. Emerging evidence, such as preliminary results from Keynote-407 and IMpower 131 studies, indicates that novel combinations of nab-paclitaxel/carboplatin and PD-1/PD-L1 inhibitors could further improve clinical benefits with manageable toxicity. Nevertheless, in order to better position nab-paclitaxel and to improve patient selection, future studies are warranted to further understand its mechanism of action, predictive biomarkers, and potential synergism with other agents.
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Albúminas/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Neoplasias Pulmonares/tratamiento farmacológico , Paclitaxel/uso terapéutico , Anciano , Albúminas/farmacocinética , Albúminas/farmacología , Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Humanos , Paclitaxel/farmacocinética , Paclitaxel/farmacologíaRESUMEN
Progressive multifocal leukoencephalopathy (PML) is a life-threatening opportunistic infection of immunomodulatory therapies. PML cases reported in PubMed (1995-2017) following stem-cell transplantation (HSCT) or chemoimmunotherapy (CIT) for hematologic malignancies were reviewed. We found 107 cases, 40% were HSCT recipients (32 allogeneic, 11 autologous) and 40% indolent lymphomas receiving monoclonal antibodies (mAbs). HSCT cases had longer time to PML diagnosis (10.8 vs. 4 months, p < .001), higher proportion of PML therapy response (58% vs. 25%, p = .019), lower mortality rate (56% vs. 88%, p < .001), and longer median survival (8 vs. 2 months, p < .001). Outcome differences might be caused by selection bias as HSCT patients are most likely treated aggressively; however, time-dependent immune reconstitution might also contribute to their better prognosis. Increased use of mAbs and HSCT are associated with rising PML incidence in hematological malignancies, currently constituting the second largest vulnerable population after HIV-infected patients; further research is needed for its optimal treatment.
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Neoplasias Hematológicas/complicaciones , Trasplante de Células Madre Hematopoyéticas , Leucoencefalopatía Multifocal Progresiva/diagnóstico , Leucoencefalopatía Multifocal Progresiva/mortalidad , Anciano , Femenino , Neoplasias Hematológicas/terapia , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Trasplante de Células Madre Hematopoyéticas/métodos , Humanos , Leucoencefalopatía Multifocal Progresiva/etiología , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , PronósticoRESUMEN
INTRODUCTION: In the United States, autologous hematopoietic cell transplantation (autoHCT) has fallen out of favor over chemotherapy consolidation for non-high-risk acute myeloid leukemia (AML) when allogeneic hematopoietic cell transplantation (alloHCT) is unfeasible, which is common in racial minorities because of donor registry under-representation and socioeconomic challenges. We compared autoHCT consolidation outcomes with chemotherapy alone in a minority-rich cohort in the Bronx. PATIENTS AND METHODS: We identified adults with favorable or intermediate cytogenetic risk AML in first complete remission after induction at Montefiore Medical Center from 1999 to 2015, and analyzed 81 patients who received consolidation with ≥2 cycles of chemotherapy, of whom 28 received autoHCT. RESULTS: The cohort predominantly consisted of ethnic/racial minorities (69%). Age, sex, race, presenting white cell count, and cytogenetic risk were similar between groups. The autoHCT group had longer relapse-free (RFS; 43 vs. 11 months; P = .003) and overall (OS) survival (not reached vs. 36 months; P = .043). Adjusted multivariable analysis showed significant benefit of autoHCT over chemotherapy alone for RFS (hazard ratio [HR], 0.53; 95% confidence interval [CI], 0.37-0.75; P < .001) and OS (HR, 0.61; 95% CI, 0.40-0.95; P = .027). CONCLUSION: In this inner-city non-high-risk AML cohort, autoHCT provided OS and RFS benefit compared with chemotherapy alone. AutoHCT might constitute a valuable option for ethnic/racial minorities affected by significant barriers to alloHCT, whereas integration of measurable residual disease can help select patients more likely to benefit.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Quimioterapia de Consolidación/mortalidad , Accesibilidad a los Servicios de Salud/estadística & datos numéricos , Trasplante de Células Madre Hematopoyéticas/mortalidad , Leucemia Mieloide Aguda/mortalidad , Grupos Minoritarios/estadística & datos numéricos , Recurrencia Local de Neoplasia/mortalidad , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Terapia Combinada , Femenino , Estudios de Seguimiento , Humanos , Leucemia Mieloide Aguda/patología , Leucemia Mieloide Aguda/terapia , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/patología , Recurrencia Local de Neoplasia/terapia , Pronóstico , Inducción de Remisión , Estudios Retrospectivos , Tasa de Supervivencia , Trasplante Autólogo , Adulto JovenRESUMEN
Lung involvement has been reported in HTLV-1 carriers and in patients with ATLL. Whether there are differences in the pattern of lung involvement between ATLL and HTLV carriers in North American patients is unknown. We aimed to compare CT pulmonary findings among patients with HTLV-1 infection with and without ATLL. Among 140 patients with HTLV-1 diagnosis, 97 had CT chest available. Of these, 72 (74.2%) had ATLL and 25 (25.8%) did not have ATLL. CT chest abnormalities were present in 90 (92.8%) participants (94.4% in ATLL; 88% in non-ATLL). Higher rates of lymphadenopathy (69.4% versus 24%, p < .01) and lower rates of bronchiectasis (25% versus 48%, p = .04) were seen in ATLL compared to non-ATLL. Our study supports that staging of lung involvement in ATLL should consider HTLV-associated pulmonary findings as not all CT chest abnormalities necessarily represent malignant infiltration.
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Bronquiectasia/epidemiología , Infecciones por HTLV-I/patología , Virus Linfotrópico T Tipo 1 Humano/aislamiento & purificación , Leucemia-Linfoma de Células T del Adulto/patología , Neoplasias Pulmonares/epidemiología , Linfadenopatía/epidemiología , Adulto , Anciano , Anciano de 80 o más Años , Bronquiectasia/diagnóstico , Bronquiectasia/virología , Región del Caribe/epidemiología , Femenino , Infecciones por HTLV-I/virología , Humanos , Leucemia-Linfoma de Células T del Adulto/virología , Pulmón/diagnóstico por imagen , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/secundario , Neoplasias Pulmonares/virología , Linfadenopatía/diagnóstico , Linfadenopatía/virología , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Prevalencia , Estudios Retrospectivos , Tomografía Computarizada por Rayos XRESUMEN
INTRODUCTION: Squamous cell lung cancer (SQCLC) is the second most common subtype of non-small cell lung cancer (NSCLC) and has limited therapeutic options. Its development is likely a result of a multistep process in response to chronic tobacco exposure, involving sequential metaplasia, dysplasia and invasive carcinoma. Its complex genomic landscape has recently been revealed but no driver mutations have been validated that could lead to molecularly targeted therapy as have emerged in lung adenocarcinoma. Few preclinical murine models exist for testing and developing novel therapeutics in SQCLC. Areas covered: This review discusses the pathophysiology and molecular underpinnings of SQCLC that have limited the development of animal models. It then explores the advantages and limitations of a variety of existing mouse models and illustrates their potential application in drug discovery and chemoprevention. Expert opinion: There are several challenges in the development of mouse models for SQCLC, such as lack of validated driver genetic alterations, unclear cell of origin, and difficulty in reproducing the sophisticated tumor microenvironment of human disease. Nevertheless, several successful SQCLC murine models have emerged, especially Patient Derived Xenografts (PDXs) and Genetically Engineered Mouse Models (GEMMs). Continued efforts are needed to generate more SQCLC animal models to better understand its carcinogenesis and metastasis and to further test novel therapeutic strategies.