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Background: We used the Therapy Preference Scale, a 30-item questionnaire, to determine cancer treatment preferences of adults with cancer. Methods: We used Wilcoxon's rank sum test and Fisher's exact test to compare the preferences of younger (<60 years) versus older adults (≥60 years). Results: While 56% of patients would accept treatment offering increased life expectancy at an expense of short-term side effects, 75% preferred maintenance of cognition, functional ability and quality of life to quantity of days. Oral instead of intravenous treatment (p = 0.003), shorter hospital stay (p = 0.03), preservation of cognitive function (p = 0.01) and avoidance of pain (p = 0.02) were more important to older patients compared with younger patients. Conclusion: Many patients prioritized maintenance of cognition, functional ability and quality of life; older patients valued oral treatment, shorter hospital stay, preservation of cognitive function and avoidance of pain.
Lay abstract Understanding the preferences of adults with cancer is important for physicians to develop personalized cancer treatment plans. We used a self-reported 30-item questionnaire, the Therapy Preference Scale, to help patients express their preferences with regard to safety, efficacy and other aspects of therapy. While 56% of the patients in our study would accept treatment offering increased life expectancy at an expense of short-term side effects, 75% preferred maintenance of cognition, functional ability and quality of life to quantity of days. Compared with younger patients, older patients preferred oral instead of intravenous treatment, shorter hospital stay, preservation of cognitive function and avoidance of pain.
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Antineoplásicos/administração & dosagem , Dor do Câncer/tratamento farmacológico , Neoplasias/tratamento farmacológico , Preferência do Paciente/estatística & dados numéricos , Administração Intravenosa , Administração Oral , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/efeitos adversos , Dor do Câncer/etiologia , Dor do Câncer/psicologia , Cognição/efeitos dos fármacos , Tomada de Decisões , Humanos , Expectativa de Vida , Masculino , Pessoa de Meia-Idade , Neoplasias/complicações , Neoplasias/psicologia , Preferência do Paciente/psicologia , Qualidade de Vida , Inquéritos e Questionários/estatística & dados numéricos , Adulto JovemRESUMO
New interventions are needed in advanced chronic graft-versus-host disease (GVHD). In a phase II, single-arm, multicenter trial, we examined the efficacy of ixazomib in patients with chronic GVHD who had progressed after at least 1 previous line of systemic immunosuppressive (IS) therapy. Ixazomib was given as a 4 mg oral dose weekly on days 1, 8, and 15 of a 28-day cycle for up to 6 total cycles. The primary endpoint was 6-month treatment failure, a composite endpoint including death, relapse, and requirement for an additional line of systemic IS therapy. A total of 50 subjects were enrolled at 6 institutions. The median time from the onset of chronic GVHD to enrollment was 2.8 years (interquartile range, 1.5 to 4.3 years). The degree of chronic GVHD at enrollment was National Institutes of Health (NIH)-defined moderate (16%) or severe (84%), predominantly classic (80% versus 20% overlap), with 52% of patients having involvement of 4 or more organs. The patients were heavily pretreated, with 39 (78%) receiving 3 or more previous lines of systemic therapy for chronic GVHD. Of the 50 patients treated, 26 completed 6 months of planned therapy. The 6-month treatment failure rate was significantly lower than the historical benchmark (28% versus 44%; Pâ¯=â¯.01) previously established in second-line therapy for chronic GVHD. No patient, transplantation, or chronic GVHD variables were significantly associated with 6-month treatment failure. NIH-defined overall response rate was 40% at 6 months. Overall survival was 92% at 6 months and 90% at 12 months. Ixazomib met the primary endpoint of low treatment failure at 6 months in the setting of advanced chronic GVHD. At 6 months, the NIH-defined rate of complete/partial response was 40%, and 52% of patients remained on ixazomib therapy, suggesting that the low treatment failure rate was due in part due to prevention of progressive disease that would have required additional treatment.
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Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Compostos de Boro/uso terapêutico , Doença Crônica , Glicina/análogos & derivados , Glicina/uso terapêutico , Doença Enxerto-Hospedeiro/tratamento farmacológico , HumanosRESUMO
Patients with primary refractory or relapsed acute myeloid leukemia (RR-AML) have very poor prognosis. Due to limited treatment options, some patients are treated with hypomethylating agents (HMAs) due to their tolerability. Little is known about the role of allogeneic hematopoietic stem cell transplantation (HSCT) following HMA therapy in this setting. We retrospectively analyzed an international cohort of 655 RR-AML patients who received HMA therapy to study patterns and outcomes with HSCT. Only 37 patients (5.6%) patients underwent HSCT after HMA therapy. The conditioning regimen was myeloablative in 57% and nonmyeloablative in 43%. Patients received matched unrelated donor, matched sibling, haploidentical and mismatched unrelated HSCT in 56%, 24%, 16% and 4% of cases, respectively. Acute GvHD and chronic GvHD were observed in 40% and 17% of patients. While the median OS for the entire cohort of patients was 15.3 months (95% CI 9.5 - 21.7 months), OS reached 29.7 months (95% CI 7.01 - not-reached) for patients who achieved a complete remission (CR) to HMA and no intervening therapies between HMA therapy and HSCT. Our study suggests that HMA therapy can effectively bridge some patients with RR-AML to HSCT.
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Antimetabólitos Antineoplásicos/uso terapêutico , Transplante de Células-Tronco Hematopoéticas/métodos , Leucemia Mieloide Aguda/terapia , Terapia de Salvação/métodos , Condicionamento Pré-Transplante/métodos , Adulto , Idoso , Feminino , Doença Enxerto-Hospedeiro/etiologia , Transplante de Células-Tronco Hematopoéticas/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Terapia de Salvação/mortalidade , Análise de Sobrevida , Condicionamento Pré-Transplante/mortalidade , Transplante HomólogoRESUMO
AIM: To evaluate practice patterns of hematopoietic cell transplantation (HCT) for acute lymphoblastic leukemia. MATERIALS & METHODS: We utilized the National Cancer Database to extract patient-level data of adults (aged 18-80 years) diagnosed with acute lymbhoblastic leukemia between 2003 and 2012. We performed multivariable logistic regression to determine variables associated with the use of HCT. RESULTS: Out of a total of 11,871 patients, 12.7% received HCT. In a multivariate analysis, older age, male sex, higher Charlson co-morbidity score, nonacademic treatment center, poor education and Medicare/Medicaid or no insurance were associated with lower likelihood of receiving HCT. CONCLUSION: Our study demonstrates variations in the utilization of HCT based on socioeconomic and health system factors.
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Transplante de Células-Tronco Hematopoéticas/estatística & dados numéricos , Padrões de Prática Médica/estatística & dados numéricos , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Adulto , Fatores Etários , Idoso , Comorbidade , Escolaridade , Feminino , Humanos , Masculino , Medicaid/estatística & dados numéricos , Medicare/estatística & dados numéricos , Pessoa de Meia-Idade , Leucemia-Linfoma Linfoblástico de Células Precursoras/epidemiologia , Fatores Sexuais , Transplante Homólogo/estatística & dados numéricos , Estados Unidos , Adulto JovemRESUMO
The broad goal of this study is to measure remote effects of cancer on brain physiology and behaviors that underpin instrumental activities of daily living such as automobile driving. Studies of hematological malignancies (HM) have demonstrated impairments in multiple brain functions shown to be critical for safe automobile driving. In the current pilot study, brain physiology during driving simulation was examined in 14 HM patients and 13 healthy comparison drivers. Electroencephalography was used to measure the eye fixation-related potential (EFRP)-a positive amplitude deflection evoked approximately 100 milliseconds after eye movement termination. Previous studies have demonstrated sensitivity of EFRP activity to information-processing capacity. All drivers completed visual search tasks to evaluate the relationship between driving-related changes in performance and EFRP activity. Results showed smaller EFRP amplitudes in drivers who had: (1) greater driving-related changes in visual search performance (p = 0.03, Cohen's d = 0.91); and (2) HM diagnosis (p = 0.18, Cohen's d = 0.54). Extending previous studies, these results provide neural evidence of reduced information-processing capacity associated with cancer diagnosis. Future large-scale studies are needed to confirm these results, given the high level of uncertainty and small sample size. This study provides a novel platform for linking changes in brain physiology and safety-critical driving behaviors.
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Cancer health disparities may exist based on the facility type. We aimed to determine the association between the academic status of centers and outcomes of patients with acute myeloid leukemia (AML). Using the National Cancer Data Base, we compared 1-month mortality and long-term overall survival (OS) of 60 738 patients with AML, who received first course treatment between 2003 and 2011 at academic or nonacademic centers (community cancer program, comprehensive community cancer program, and others). Multivariate analysis was done using logistic regression for one-month mortality and Cox regression with backward elimination approach for OS. Patients treated at academic centers differed from those at nonacademic centers in that they were younger with a median age of 62 versus 70 years (P < .0001), more often an ethnic minority (P < .0001), had lower education level (P = .005), lower co-morbidity score (P < .0001), a different income (P < .0001), and insurance profile (P < .0001), and more often received chemotherapy (P < .0001) and transplant (P < .0001). Receipt of care at nonacademic centers was associated with worse 1-month mortality (29% vs. 16%, P < .0001) and 5-year OS (15% vs. 25%; P < .0001). After adjusting for prognostic covariates, the 1-month mortality (odds ratio, 1.52; 95% confidence interval, CI 1.46-1.59; P < .0001) and OS were significantly worse in nonacademic centers, compared to academic centers. Our large database study suggests that the receipt of initial therapy at academic centers is associated with lower 1-month mortality and higher long-term OS. Investigation of the underlying reasons may allow reducing this disparity.
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Institutos de Câncer , Leucemia Mieloide Aguda/mortalidade , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Bases de Dados Factuais , Análise Fatorial , Feminino , Humanos , Leucemia Mieloide Aguda/terapia , Masculino , Pessoa de Meia-Idade , Mortalidade , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco , Fatores Socioeconômicos , Análise de Sobrevida , Estados Unidos/epidemiologia , Adulto JovemRESUMO
The optimal management of hematologic malignancy-associated venous thromboembolism (VTE) in patients with moderate-to-severe thrombocytopenia is unclear. This is a retrospective study of 128 adult patients with hematologic malignancies who were diagnosed with VTE. The outcome of patients with significant thrombocytopenia (≤50,000/µL) was compared with those without. Forty-seven patients (36.7%) had a platelet count ≤50,000/µL during a period of time of perceived need for new or continued anticoagulation. The median nadir platelet count in those with significant thrombocytopenia was 10,000/µL (range 2,000-45,000/µL) versus 165,000/µL (50,000-429,000/µL) in those without (P < 0.001). The median duration of significant thrombocytopenia in the first group was 10 days (1-35 days). Therapy during the period of significant thrombocytopenia included prophylactic-dose low-molecular-weight heparin (LMWH) (47%), therapeutic-dose LMWH or heparin (30%), warfarin (2%), inferior vena cava filter (2%), and observation (17%). Patients without thrombocytopenia were managed with the standard of care therapy. At a median follow-up of more than 2 years, the risk of clinically significant bleeding (11% vs 6%, P = 0.22) including major bleeding (6% vs 2%) and clot progression or recurrence (21% vs 22%, P = 1.00) were similar in patients with or without significant thrombocytopenia. In a multivariate analysis, the risk of recurrence/progression (hazard ratio, HR 0.59, 95% CI 0.21-1.66, P = 0.31) and hemorrhage rate (HR 0.29, 95% CI 0.05-1.56, P = 0.15) did not differ based on the presence of significant thrombocytopenia. Within the limits of this retrospective study, cautious use of prophylactic-dose LMWH may be safe in thrombocytopenic patients with hematologic malignancy-associated VTE. Am. J. Hematol. 91:E468-E472, 2016. © 2016 Wiley Periodicals, Inc.
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Neoplasias Hematológicas/complicações , Heparina de Baixo Peso Molecular/uso terapêutico , Trombocitopenia/etiologia , Tromboembolia Venosa/etiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticoagulantes/uso terapêutico , Feminino , Hemorragia/induzido quimicamente , Heparina/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Contagem de Plaquetas , Pré-Medicação , Recidiva , Estudos Retrospectivos , Trombocitopenia/tratamento farmacológico , Trombocitopenia/patologia , Tromboembolia Venosa/patologia , Varfarina/uso terapêutico , Adulto JovemAssuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Leucemia Mieloide Aguda/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Compostos Bicíclicos Heterocíclicos com Pontes/administração & dosagem , Metilação de DNA/efeitos dos fármacos , Decitabina/administração & dosagem , Avaliação de Medicamentos , Feminino , Humanos , Leucemia Mieloide Aguda/genética , Masculino , Pessoa de Meia-Idade , Mutação , Estudos Retrospectivos , Sulfonamidas/administração & dosagem , Resultado do TratamentoRESUMO
BACKGROUND: This large population-based study determined the epidemiology and outcomes of secondary acute myeloid leukemia (sAML) developing in Hodgkin lymphoma survivors. METHODS: We utilized the Surveillance Epidemiology and End Results (SEER) 9 database to identify 104 cases of sAML. RESULTS: Patients with sAML (median age: 47 years; 82% <60 years) were significantly younger than de novo AML cases (66 years; p < 0.01). sAML had worse overall survival (OS) than de novo AML (p < 0.01). OS was better in younger patients and in more recent years. CONCLUSION: Older patients with sAML have a dismal OS and should be enrolled in trials of novel therapies. Younger patients have improved OS and hence may benefit from curative intent intensive therapy and allogeneic transplant.
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Doença de Hodgkin , Leucemia Mieloide Aguda/epidemiologia , Segunda Neoplasia Primária/epidemiologia , Adolescente , Adulto , Fatores Etários , Idoso , Feminino , Doença de Hodgkin/terapia , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Programa de SEER , Sobreviventes/estatística & dados numéricos , Adulto JovemRESUMO
Atypical chronic myeloid leukemia is a rare entity that presents diagnostic and therapeutic challenges. Traditionally utilized therapeutic agents such as hydroxyurea or interferon result in a median survival of approximately two years, thus warranting identification of better options. We report a 49-year-old Caucasian female, who presented with extreme leukocytosis (white blood cells of 148,300/µL) with left shift, severe anemia, and thrombocytopenia. Following a diagnosis of atypical chronic myeloid leukemia, she was started on intravenous decitabine. She subsequently developed paraneoplastic vasculitis of large arteries, which responded to high-dose glucocorticoid. Decitabine therapy resulted in an excellent hematologic response, transfusion independence, and successful transition to an allogeneic peripheral stem cell transplantation. However, the patient subsequently succumbed to the complications of acute graft-versus-host-disease. This case illustrates an association between atypical chronic myeloid leukemia and steroid-responsive paraneoplastic vasculitis and highlights the single-agent disease activity of decitabine in atypical chronic myeloid leukemia, which may be utilized as a bridging therapy to allogeneic stem cell transplantation.
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Antimetabólitos Antineoplásicos/administração & dosagem , Azacitidina/análogos & derivados , Leucemia Mieloide Crônica Atípica BCR-ABL Negativa/diagnóstico , Leucemia Mieloide Crônica Atípica BCR-ABL Negativa/tratamento farmacológico , Administração Intravenosa , Azacitidina/administração & dosagem , Decitabina , Feminino , Doença Enxerto-Hospedeiro/diagnóstico , Doença Enxerto-Hospedeiro/prevenção & controle , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Pessoa de Meia-Idade , Transplante HomólogoAssuntos
Anticorpos Biespecíficos/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Fator VIIa/uso terapêutico , Hemofilia A/complicações , Hemofilia A/tratamento farmacológico , Embolia Pulmonar/etiologia , Infarto do Miocárdio com Supradesnível do Segmento ST/etiologia , Adulto , Anticorpos Biespecíficos/farmacologia , Anticorpos Monoclonais Humanizados/farmacologia , Fator VIIa/farmacologia , Humanos , MasculinoAssuntos
Antineoplásicos/efeitos adversos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/etiologia , Neoplasias/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/uso terapêutico , Antineoplásicos/toxicidade , Ensaios Clínicos como Assunto , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/prevenção & controle , Avaliação Geriátrica , Humanos , Fatores de Risco , Análise de SobrevidaRESUMO
Interferon has been widely used in the management of patients with hematological malignancies such as polycythemia vera, myelofibrosis, chronic myeloid leukemia and viral infections such as chronic hepatitis C. Hematological adverse effects such as cytopenias have been observed, particularly in patients who receive a combination of interferon-α-2a and ribavirin for hepatitis C. Mild myelosuppression can be seen with pegylated interferon; however, bone marrow aplasia in patients with myelofibrosis has not been reported. It is important to be aware of such a serious complication since persistent bone marrow aplasia can be fatal. We describe a case of pegylated interferon-induced reversible bone marrow aplasia in a patient with primary myelofibrosis.
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Antineoplásicos/efeitos adversos , Doenças da Medula Óssea/induzido quimicamente , Medula Óssea/efeitos dos fármacos , Interferon-alfa/efeitos adversos , Polietilenoglicóis/efeitos adversos , Mielofibrose Primária/tratamento farmacológico , Biópsia , Medula Óssea/patologia , Doenças da Medula Óssea/diagnóstico , Exame de Medula Óssea , Feminino , Humanos , Pessoa de Meia-Idade , Mielofibrose Primária/diagnóstico , Proteínas Recombinantes/efeitos adversos , Resultado do TratamentoRESUMO
INTRODUCTION: Many older adults with acute myeloid leukemia (AML) do not receive chemotherapy because of physicians' and patients' concern for toxicities and functional decline. This highlights the critical and urgent need to generate knowledge of functional changes following new treatments. MATERIALS AND METHODS: As a part of a pragmatic single-center trial, 59 older adults ≥60 years with AML completed geriatric assessment and health-related quality of life measures before treatment and at one month and three months after chemotherapy initiation. Changes in scores of various geriatric assessment measures were computed by subtracting the baseline score from the one-month and three-month scores for each patient. Established cut-offs were used to determine a clinically meaningful change (improvement or worsening). This study provides results of descriptive exploratory analyses. RESULTS: Patients experienced significant comorbidity burden and a high prevalence of functional impairments before treatment, with 56% of patients having ≥2 comorbid conditions, 69% having abnormal cognitive function (using Montreal Cognitive Assessment), 69% having impaired objective physical function (using Short Physical Performance Battery), and 64% having a positive depression screen (Patient Health Questionnaire-9). Patients (n = 53) received treatment with predominantly low-intensity chemotherapy; six patients received intensive chemotherapy. Among those who completed some or all of the three-month evaluation (N = 43), from baseline before treatment to three months later, cognitive function improved (38.7%) or remained stable (38.7%), objective physical function improved (51.6%) or remained stable (22.6%), and depression scores improved (9.4%) or remained stable (53.1%). Global health status score and role functioning moderately improved by a score of >16. DISCUSSION: An exploratory analysis of our phase 2 trial demonstrated improvement or stabilization of cognitive and physical function and depression score at three months in a high proportion of older survivors of AML, despite a high prevalence of frailty and significant comorbidity burden at baseline. These results demonstrate success of treatment in improving cognitive and physical function and depression score, and, if confirmed in larger studies, should encourage oncologists to offer chemotherapy to older adults with AML. CLINICAL TRIAL REGISTRATION: The study is registered in the ClinicalTrials.gov ID: NCT03226418.
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Leucemia Mieloide Aguda , Qualidade de Vida , Humanos , Idoso , Leucemia Mieloide Aguda/tratamento farmacológico , Nível de Saúde , Comorbidade , CogniçãoRESUMO
The study aimed to determine the association of chronic graft-versus-host disease (cGVHD) diagnosis and severity with the development of subsequent neoplasms (SN) and nonmalignant late effects (NM-LE) in 2-year disease-free adult survivors following hematopoietic cell transplantation (HCT) for a hematologic malignancy. To do so, we conducted a retrospective analysis of 3884 survivors of HCT for hematologic malignancy in the Center of International Blood and Marrow Transplant Research database. We conducted a landmark analysis at the 2-year post-transplantation date, comparing first SN and NM-LE in survivors with and without cGVHD. The cumulative incidence (CuI) of SN and NM-LE were estimated through 10 years post-HCT in both groups, with death or disease relapse as a competing risk. Cox proportional hazards models were used to evaluate the associations of cGVHD and its related characteristics with the development of SN and NM-LE. The estimated 10-year CuI of SN in patients with GVHD (n = 2669) and patients without cGVHD (n = 1215) was 15% (95% confidence interval [CI], 14% to 17%) versus 9% (7.2% to 11%) (P < .001). cGVHD by 2 years post-HCT was independently associated with SN (hazard ratio [HR], 1.94; 95% CI, 1.53 to 2.46; P < .0001) with a standardized incidence ratio of 3.2 (95% CI, 2.9 to 3.5; P < .0001). Increasing severity of cGVHD was associated with an increased risk of SN. The estimated 10-year CuI of first NM-LE in patients with and without cGVHD was 28 (95% CI, 26% to 30%) versus 13% (95% CI, 11% to 15%) (P < .001). cGVHD by 2 years post-HCT was independently associated with NM-LE (HR, 2.23; 95% CI, 1.81 to 2.76; P < .0001). Multivariate analysis of cGVHD-related factors showed that increasing severity of cGVHD, extensive grade, having both mucocutaneous and visceral involvement, and receiving cGVHD treatment for >12 months were associated with the greatest magnitude of risk for NM-LE. cGVHD was closely associated with both SN and NM-LE in adult survivors of HCT for hematologic malignancy. Patients identified as having more severe involvement and both mucocutaneous and visceral organ involvement may warrant enhanced monitoring and screening for SNs and NM-LEs. However, caution is warranted when interpreting these results, as patients with cGVHD may have more vigilant post-transplantation health care and surveillance for late effects.
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Síndrome de Bronquiolite Obliterante , Doença Enxerto-Hospedeiro , Neoplasias Hematológicas , Transplante de Células-Tronco Hematopoéticas , Adulto , Humanos , Estudos Retrospectivos , Doença Enxerto-Hospedeiro/epidemiologia , Doença Enxerto-Hospedeiro/etiologia , Aloenxertos/patologia , Recidiva Local de Neoplasia/complicações , Neoplasias Hematológicas/complicações , Neoplasias Hematológicas/epidemiologia , Neoplasias Hematológicas/terapia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/métodos , Progressão da DoençaRESUMO
Socioeconomic status (SES) and race/ethnicity have been associated with outcomes of allogeneic hematopoietic cell transplantation (allo-HCT). Certain aspects of GVHD management such as the need for long term care, prolonged immunosuppressive treatment, and need for close follow up for complications may exacerbate disparities. Adults (≥ 18 years) reported to the Center for International Blood and Marrow Transplant Research (CIBMTR) who underwent a first alloHCT for acute leukemia, myelodysplastic syndrome, or myeloproliferative neoplasm between 2008 - 2018 were included. Endpoints for those developing GVHD included overall survival (OS), transplant related mortality (TRM), and disease relapse. Models were adjusted for patient and transplant related variables. A two-sided p-value < 0.01 was considered significant. Among the 14,825 allo-HCT recipients, 6,259 (42.2%) and 6,675 (45.0%) patients developed aGVHD and cGVHD, respectively. In patients with aGVHD, non-Hispanic Blacks had increased TRM (HR 1.50, 95% CI 1.24-1.83, p=0.0001) and overall mortality (HR 1.31, 1.14-1.50, p=0.0002) compared with non-Hispanic Whites, an association that disappeared when severity of aGVHD was included in the model. Lower SES was associated with increased risk of disease relapse (p=0.0016) but not OS or TRM. In patients who developed cGVHD, race and ethnicity were not associated with OS, TRM and disease relapse. However, the highest quartile of annual household income (≥ $80,000) had improved OS (HR 0.77, 0.69-0.85, p<0.0001) and reduced TRM (HR 0.86, 0.67-0.87, p<0.0001) compared with lowest quartile, adjusting for race and ethnicity. Race/ethnicity and SES are associated with outcomes after GVHD. Optimizing health care resources available to low SES patients and strategies to minimize the risk of severe GVHD in non-Hispanic Blacks may improve long-term outcomes.
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Hematologic malignancies disproportionately affect older adults. Hematopoietic cell transplantation (HCT) is potentially curative, but poor overall survival (OS) has limited its use in older adults. Fried's frailty phenotype (FFP) is a geriatric assessment tool that combines objective and subjective performance measures: gait speed, grip strength, activity level, exhaustion, and weight loss. People meeting ≥3 criteria are classified as frail; 1 or 2 criteria, as pre-frail; and 0 criteria, as fit. To evaluate the association of pre-HCT FFP with post-HCT outcomes, we assessed FFP prior to conditioning for 280 HCT recipients age ≥60 years with acute leukemia or a myeloid neoplasm at 3 institutions. When analyzing survival by age group, patients age ≥70 years had inferior OS compared to patients age 60 to 69 years (P = .002), with corresponding OS estimates of 38.9% (95% confidence interval [CI], 27.8% to 49.9%) and 59.3% (95% CI, 51.9% to 65.9%). Nonrelapse mortality (NRM) also was significantly higher in the older patients (P = .0005); the 2-year cumulative incidences of NRM were 38.5% (95% CI, 27.5% to 49.2%) and 17.2% (95% CI, 12.3% to 22.8%), for older and younger recipients, respectively. The cumulative incidences of relapse did not differ by age group (P = .3435). Roughly one-third (35.5%) of the patients were fit, 57.5% were pre-frail, and 7.5% were frail, with corresponding 2-year OS estimates of 68.4% (95% CI, 57.9% to 76.8%), 45.5% (95% CI, 37.4% to 53.2%), and 45.8% (95% CI, 23.4% to 65.8%) (P = .013). FFP was not significantly associated with NRM, but being frail or pre-frail was associated with a higher rate of disease-related deaths (33.3% and 27.3%, respectively, compared with 17.4% for fit patients; P = .043). In univariate modeling of restricted mean survival time with a 3-year horizon (RMST_3y), the factors that were significantly associated were FFP, age, Karnofsky Performance Status (KPS), Disease Risk Index (DRI), and HCT-specific Comorbidity Index (HCT-CI). Of those factors, only FFP (P = .006), age (P = .006), KPS (P = .004), and DRI (P = .005) were significantly associated in multivariate modeling of RMST_3y. Estimates of RMST_3y were computed and 5 risk-groups were created with survival ranging from 31.4 months for those who were age 60 to 69 years, fit, had KPS 90 to 100, and low/intermediate-risk DRI compared to 10.5 months for those who had high-risk features for all the evaluated factors. In univariate and multivariate analyses for restricted mean time to relapse with a 3-year horizon (RMRT_3y), FFP (pre-frail versus fit, P = .007; frail versus fit, P = .061) and DRI (P = .001) were the only significant factors. Predicted RMRT_3y was longest (30.6 months) for those who were fit and had low/intermediate-risk DRI scores and shortest (19.1 months) for those who were frail and had high-risk or very high-risk DRI scores. Both age and FFP impact survival after HCT. Incorporation of FFP into pre-HCT evaluations may improve decision-making and counseling regarding HCT risk for older adults. Our findings support future trials designed to reverse frailty, such as pre-HCT supervised exercise programs, and correlative analyses to unravel the connection of frailty and relapse to generate future targets for intervention. Finally, exploration of novel HCT platforms to reduce relapse in pre-frail and frail patients, as well as reduce NRM in adults age >70 years, are warranted.
Assuntos
Fragilidade , Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda , Humanos , Idoso , Pessoa de Meia-Idade , Recidiva , Transplante HomólogoRESUMO
OBJECTIVES: Large licensing trials did not find any association between the use of fondaparinux and the development of heparin-induced thrombocytopenia (HIT). Fondaparinux is in fact recommended as an option for the management of HIT. Since the first report of fondaparinux-associated HIT in 2007, additional reports have been published. However, the rarity of these cases, differences in case definition, and lack of larger case series have prevented better understanding of this disease. The objective of this study was to determine the clinical manifestations of fondaparinux-associated HIT, the predictive value of pretest probability (4Ts) scoring system, and the outcomes associated with current management. METHODS: Using several search terms, we reviewed all cases of fondaparinux-associated HIT reported and indexed in PubMed till May 2013. All references were also checked for additional reports. We categorized the cases of fondaparinux-associated HIT as confirmed, probable, and possible based on our case definition. RESULTS: A total of eight cases of fondaparinux-associated HIT were identified. Fondaparinux-associated HIT occurred in the setting of pro-inflammatory state, prior HIT, or exposure to heparin products. Bilateral adrenal hemorrhage or infarct, reflecting hypercoagulability or disseminated intravascular coagulation, was seen in 25% of patients. The pretest probability (4Ts) scoring system used for HIT appears to correctly risk stratify all the cases. Although functional assays can be used for the diagnosis, in the presence of recent exposure to heparin products, only the demonstration of fondaparinux-dependent platelet activation should be considered confirmatory. Non-heparin anticoagulants are effective therapy; however, one-third of the patients had poor outcomes. CONCLUSION: The risk of fondaparinux-associated HIT, although low is real, which along with documented cases of fondaparinux failure mandate its cautious use in the management of HIT.