Assuntos
Leucemia Mieloide Aguda/tratamento farmacológico , Mutação , Recidiva Local de Neoplasia/diagnóstico , Proteínas Nucleares/genética , Transplante de Células-Tronco/mortalidade , Biomarcadores Tumorais/genética , Humanos , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/patologia , Recidiva Local de Neoplasia/etiologia , Nucleofosmina , Prognóstico , Transplante de Células-Tronco/efeitos adversos , Taxa de SobrevidaRESUMO
Background: The combination of intermediate-dose cytarabine plus mitoxantrone (IMA) can induce high complete remission rates with acceptable toxicity in elderly patients with acute myeloid leukemia (AML). We present the final results of a randomized-controlled trial comparing IMA with the standard 7 + 3 induction regimen consisting of continuous infusion cytarabine plus daunorubicin (DA). Patients and methods: Patients with newly diagnosed AML >60 years were randomized to receive either intermediate-dose cytarabine (1000 mg/m2 twice daily on days 1, 3, 5, 7) plus mitoxantrone (10 mg/m2 days 1-3) (IMA) or standard induction therapy with cytarabine (100 mg/m2 continuously days 1-7) plus daunorubicin (45 mg/m2 days 3-5) (DA). Patients in complete remission after DA received intermediate-dose cytarabine plus amsacrine as consolidation treatment, whereas patients after IMA were consolidated with standard-dose cytarabine plus mitoxantrone. Results: Between February 2005 and October 2009, 485 patients were randomized; 241 for treatment arm DA and 244 for IMA; 76% of patients were >65 years. The complete response rate after DA was 39% [95% confidence interval (95% CI): 33-45] versus 55% (95% CI: 49-61) after IMA (odds ratio 1.89, P = 0.001). The 6-week early-death rate was 14% in both arms. Relapse-free survival curves were superimposable in the first year, but separated afterwards, resulting in 3-year relapse-free survival rates of 29% versus 14% in the DA versus IMA arms, respectively (P = 0.042). The median overall survival was 10 months in both arms (P = 0.513). Conclusion: The dose escalation of cytarabine in induction therapy lead to improved remission rates in the elderly AML patients. This did not translate into a survival advantage, most likely due to differences in consolidation treatment. Thus, effective consolidation strategies need to be further explored. In combination with an effective consolidation strategy, the use of intermediate-dose cytarabine in induction may improve curative treatment for elderly AML patients.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Citarabina/administração & dosagem , Daunorrubicina/administração & dosagem , Leucemia Mieloide Aguda/tratamento farmacológico , Mitoxantrona/administração & dosagem , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Citarabina/efeitos adversos , Daunorrubicina/efeitos adversos , Relação Dose-Resposta a Droga , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mitoxantrona/efeitos adversos , Indução de Remissão , Análise de SobrevidaRESUMO
BACKGROUND: The value of allogeneic hematopoietic cell transplantation (alloHCT) as postremission treatment is not well defined for patients with intermediate-risk acute myeloid leukemia (AML) without FLT3-ITD, biallelic CEBPA-, or NPM1 mutations (here referred to as NPM1mut-neg/CEBPAdm-neg/FLT3-ITDneg AML) in first complete remission (CR1). PATIENTS AND METHODS: We addressed this question using data from two prospective randomized controlled trials on intensive induction- and risk-stratified postremission therapy. The NPM1mut-neg/CEBPAdm-neg/FLT3-ITDneg AML subgroup comprised 497 patients, aged 18-60 years. RESULTS: In donor versus no-donor analyses, patients with a matched related donor had a longer relapse-free survival (HR 0.5; 95% CI 0.3-0.9, P = 0.02) and a trend toward better overall survival (HR 0.6, 95% CI 0.3-1.1, P = 0.08) compared with patients who received postremission chemotherapy. Notably, only 58% of patients in the donor group were transplanted in CR1. We therefore complemented the donor versus no-donor analysis with multivariable Cox regression analyses, where alloHCT was tested as a time-dependent covariate: overall survival (HR 0.58, 95% CI 0.37-0.9, P = 0.02) and relapse-free survival (HR 0.51, 95% CI 0.34-0.76; P = 0.001) for patients who received alloHCT compared with chemotherapy in CR1 were significantly longer. CONCLUSION: Outside clinical trials, alloHCT should be the preferred postremission treatment of patients with intermediate risk NPM1mut-neg/CEBPAdm-neg/FLT3-ITDneg AML in CR1. CINICALTRIALS.GOV IDENTIFIER: NCT00180115, NCT00180102.
Assuntos
Biomarcadores Tumorais/genética , Proteínas Estimuladoras de Ligação a CCAAT/genética , Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda/terapia , Mutação , Proteínas Nucleares/genética , Tirosina Quinase 3 Semelhante a fms/genética , Adolescente , Adulto , Feminino , Seguimentos , Humanos , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/patologia , Masculino , Pessoa de Meia-Idade , Nucleofosmina , Prognóstico , Estudos Prospectivos , Indução de Remissão , Taxa de Sobrevida , Transplante Homólogo , Adulto JovemAssuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Mutação/genética , Síndromes Mielodisplásicas/tratamento farmacológico , Síndromes Mielodisplásicas/genética , Proteínas Nucleares/genética , Idoso , Antraciclinas/uso terapêutico , Citarabina/uso terapêutico , Feminino , Células-Tronco Hematopoéticas/efeitos dos fármacos , Humanos , Masculino , Pessoa de Meia-Idade , NucleofosminaAssuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Transplante de Células-Tronco Hematopoéticas , Quimioterapia de Indução , Mieloma Múltiplo/terapia , Adolescente , Adulto , Idoso , Terapia Combinada , Dexametasona/administração & dosagem , Doxorrubicina/administração & dosagem , Feminino , Humanos , Lenalidomida , Masculino , Pessoa de Meia-Idade , Análise de Sobrevida , Talidomida/administração & dosagem , Talidomida/análogos & derivados , Adulto JovemRESUMO
Therapy-related acute promyelocytic leukemia (t-APL) is relatively rare, with limited data on outcome after treatment with arsenic trioxide (ATO) compared to standard intensive chemotherapy (CTX). We evaluated 103 adult t-APL patients undergoing treatment with all-trans retinoic acid (ATRA) alone (n=7) or in combination with ATO (n=24), CTX (n=53), or both (n=19). Complete remissions were achieved after induction therapy in 57% with ATRA, 100% with ATO/ATRA, 78% with CTX/ATRA, and 95% with CTX/ATO/ATRA. Early death rates were 43% for ATRA, 0% for ATO/ATRA, 12% for CTX/ATRA and 5% for CTX/ATO/ATRA. Three patients relapsed, two developed therapy-related acute myeloid leukemia and 13 died in remission including seven patients with recurrence of the prior malignancy. Median follow-up for survival was 3.7 years. None of the patients treated with ATRA alone survived beyond one year. Event-free survival was significantly higher after ATO-based therapy (95%, 95% CI, 82-99%) as compared to CTX/ATRA (78%, 95% CI, 64-87%; P=0.042), if deaths due to recurrence of the prior malignancy were censored. The estimated 2-year overall survival in intensively treated patients was 88% (95% CI, 80-93%) without difference according to treatment (P=0.47). ATO when added to ATRA or CTX/ATRA is feasible and leads to better outcomes as compared to CTX/ATRA in t-APL.
Assuntos
Arsenicais/uso terapêutico , Leucemia Promielocítica Aguda/tratamento farmacológico , Segunda Neoplasia Primária/tratamento farmacológico , Óxidos/uso terapêutico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Trióxido de Arsênio , Feminino , Humanos , Leucemia Promielocítica Aguda/etiologia , Leucemia Promielocítica Aguda/genética , Masculino , Pessoa de Meia-Idade , Segunda Neoplasia Primária/etiologia , Segunda Neoplasia Primária/genética , Indução de Remissão , Análise de Sobrevida , Resultado do Tratamento , Adulto JovemAssuntos
Evolução Clonal , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Leucemia Mieloide Aguda/genética , Pré-Leucemia/genética , Adulto , Feminino , Humanos , Doadores Vivos , Masculino , Pessoa de Meia-Idade , Pré-Leucemia/tratamento farmacológico , Pré-Leucemia/terapia , Condicionamento Pré-Transplante , Sequenciamento do ExomaRESUMO
The objective was to evaluate the prognostic impact of pre-transplant minimal residual disease (MRD) as determined by real-time quantitative polymerase chain reaction in 67 adult NPM1-mutated acute myeloid leukemia patients receiving allogeneic hematopoietic stem cell transplantation (HSCT). Twenty-eight of the 67 patients had a FLT3-ITD (42%). Median age at transplantation was 54.7 years, median follow-up for survival from time of allografting was 4.9 years. At transplantation, 31 patients were in first, 20 in second complete remission (CR) and 16 had refractory disease (RD). Pre-transplant NPM1 MRD levels were measured in 39 CR patients. Overall survival (OS) for patients transplanted in CR was significantly longer as compared to patients with RD (P=0.004), irrespective of whether the patients were transplanted in first or second CR (P=0.74). There was a highly significant difference in OS after allogeneic HSCT between pre-transplant MRD-positive and MRD-negative patients (estimated 5-year OS rates of 40 vs 89%; P=0.007). Multivariable analyses on time to relapse and OS revealed pre-transplant NPM1 MRD levels >1% as an independent prognostic factor for poor survival after allogeneic HSCT, whereas FLT3-ITD had no impact. Notably, outcome of patients with pre-transplant NPM1 MRD positivity >1% was as poor as that of patients transplanted with RD.
Assuntos
Biomarcadores Tumorais , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/mortalidade , Neoplasia Residual/genética , Proteínas Nucleares/genética , Adolescente , Adulto , Idoso , Biomarcadores , Medula Óssea/patologia , Feminino , Duplicação Gênica , Transplante de Células-Tronco Hematopoéticas , Humanos , Estimativa de Kaplan-Meier , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/terapia , Masculino , Pessoa de Meia-Idade , Mutação , Neoplasia Residual/diagnóstico , Nucleofosmina , Cuidados Pré-Operatórios , Prognóstico , Modelos de Riscos Proporcionais , Recidiva , Sequências Repetitivas de Ácido Nucleico , Transplante Homólogo , Resultado do Tratamento , Adulto Jovem , Tirosina Quinase 3 Semelhante a fms/genéticaRESUMO
A complex aberrant karyotype consisting of multiple unrelated cytogenetic abnormalities is associated with poor prognosis in patients with acute myeloid leukemia (AML). The European Leukemia Net classification and the UK Medical Research Council recommendation provide prognostic categories that differ in the definition of unbalanced aberrations as well as the number of single aberrations. The aim of this study on 3526 AML patients was to redefine and validate a cutoff for karyotype complexity in AML with regard to adverse prognosis. Our study demonstrated that (1) patients with a pure hyperdiploid karyotype have an adverse risk irrespective of the number of chromosomal gains, (2) patients with translocation t(9;11)(p21â¼22;q23) have an intermediate risk independent of the number of additional aberrations, (3) patients with ⩾4 abnormalities have an adverse risk per se and (4) patients with three aberrations in the absence of abnormalities of strong influence (hyperdiploid karyotype, t(9;11)(p21â¼22;q23), CBF-AML, unique adverse-risk aberrations) have borderline intermediate/adverse risk with a reduced overall survival compared with patients with a normal karyotype.
Assuntos
Aberrações Cromossômicas , Cariótipo , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/mortalidade , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Estimativa de Kaplan-Meier , Cariotipagem , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/terapia , Masculino , Pessoa de Meia-Idade , Poliploidia , Prognóstico , Ensaios Clínicos Controlados Aleatórios como Assunto , Adulto JovemRESUMO
In patients with relapsed or refractory (r/r) acute myeloid leukemia (AML), long-term disease control can only be achieved by allogeneic hematopoietic stem cell transplantation (HSCT). We studied the safety and efficacy of clofarabine-based salvage therapy. The study was designed as phase II, multicenter, intent-to-transplant (ITT) study. A total of 84 patients with r/r AML were enrolled. All patients received at least one cycle of CLARA (clofarabine 30 mg/m(2) and cytarabine 1 g/m(2), days 1-5). Chemo-responsive patients with a donor received HSCT in aplasia after first CLARA. Generally, HSCT was performed as soon as possible. The conditioning regimen consisted of clofarabine (4 × 30 mg/m(2)) and melphalan (140 mg/m(2)). The median patient age was 61 years (range 40-75). On day 15 after start of CLARA, 26% of patients were in a morphologically leukemia-free state and 79% exposed a reduction in bone marrow blasts. Overall, 67% of the patients received HSCT within the trial. The primary end point, defined as complete remission after HSCT, was achieved by 60% of the patients. According to the ITT, overall survival at 2 years was 43% (95% confidence interval (CI), 32-54%). The 2-year disease-free survival for transplanted patients was 52% (95% CI, 40-69%). Clofarabine-based salvage therapy combined with allogeneic HSCT in aplasia shows promising results in patients with r/r AML.
Assuntos
Nucleotídeos de Adenina/uso terapêutico , Antimetabólitos Antineoplásicos/uso terapêutico , Arabinonucleosídeos/uso terapêutico , Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda/terapia , Terapia de Salvação , Adulto , Idoso , Clofarabina , Feminino , Doença Enxerto-Hospedeiro/etiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Leucemia Mieloide Aguda/mortalidade , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Recidiva , Transplante HomólogoRESUMO
DNA methylation changes are a constant feature of acute myeloid leukemia. Hypomethylating drugs such as azacitidine are active in acute myeloid leukemia (AML) as monotherapy. Azacitidine monotherapy is not curative. The AML-AZA trial tested the hypothesis that DNA methyltransferase inhibitors such as azacitidine can improve chemotherapy outcome in AML. This randomized, controlled trial compared the efficacy of azacitidine applied before each cycle of intensive chemotherapy with chemotherapy alone in older patients with untreated AML. Event-free survival (EFS) was the primary end point. In total, 214 patients with a median age of 70 years were randomized to azacitidine/chemotherapy (arm-A) or chemotherapy (arm-B). More arm-A patients (39/105; 37%) than arm-B (25/109; 23%) showed adverse cytogenetics (P=0.057). Adverse events were more frequent in arm-A (15.44) versus 13.52 in arm-B, (P=0.26), but early death rates did not differ significantly (30-day mortality: 6% versus 5%, P=0.76). Median EFS was 6 months in both arms (P=0.96). Median overall survival was 15 months for patients in arm-A compared with 21 months in arm-B (P=0.35). Azacitidine added to standard chemotherapy increases toxicity in older patients with AML, but provides no additional benefit for unselected patients.
Assuntos
Antimetabólitos Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Azacitidina/uso terapêutico , Quimioterapia de Indução/métodos , Leucemia Mieloide Aguda/tratamento farmacológico , Idoso , Citarabina/uso terapêutico , Análise Citogenética , Daunorrubicina/uso terapêutico , Feminino , Humanos , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/mortalidade , Masculino , Pessoa de Meia-Idade , Indução de Remissão , Análise de SobrevidaRESUMO
The optimal timing of allogeneic hematopoietic stem cell transplantation (HCT) in acute myeloid leukemia (AML) is controversial. We report on 1179 patients with a median age of 48 years who were randomized upfront. In the control arm, sibling HCT was scheduled in the first complete remission for intermediate-risk or high-risk AML and matched unrelated HCT in complex karyotype AML. In the experimental arm, matched unrelated HCT in first remission was offered also to patients with an FLT3-ITD (FMS-like tyrosine kinase 3-internal tandem duplication) allelic ratio >0.8, poor day +15 marrow blast clearance and adverse karyotypes. Further, allogeneic HCT was recommended in high-risk AML to be performed in aplasia after induction chemotherapy. In the intent-to-treat (ITT) analysis, superiority of the experimental transplant strategy could not be shown with respect to overall survival (OS) or event-free survival. As-treated analyses suggest a profound effect of allogeneic HCT on OS (HR 0.73; P=0.002) and event-free survival (HR 0.67; P<0.001). In high-risk patients, OS was significantly improved after allogeneic HCT in aplasia (HR 0.64; P=0.046) and after HCT in remission (HR 0.74; P=0.03). Although superiority of one study arm could not be demonstrated in the ITT analysis, secondary analyses suggest that early allogeneic HCT is a promising strategy for patients with high-risk AML.
Assuntos
Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/terapia , Adolescente , Adulto , Alelos , Intervalo Livre de Doença , Feminino , Regulação Leucêmica da Expressão Gênica , Humanos , Estimativa de Kaplan-Meier , Cariotipagem , Masculino , Pessoa de Meia-Idade , Recidiva , Indução de Remissão , Transplante Homólogo , Resultado do Tratamento , Adulto Jovem , Tirosina Quinase 3 Semelhante a fms/genética , Tirosina Quinase 3 Semelhante a fms/metabolismoRESUMO
Owing to the more recent positive results with the anti-CD33 immunotoxin gemtuzumab ozogamicin, therapy against acute myeloid leukemias (AMLs) targeting CD33 holds many promises. Here, CD33 and CD123 expression on AML blasts was studied by flow cytometry in a cohort of 319 patients with detailed information on French-American-British/World Health Organization (FAB/WHO) classification, cytogenetics and molecular aberrations. AMLs of 87.8% express CD33 and would therefore be targetable with anti-CD33 therapies. Additionally, 9.4% of AMLs express CD123 without concomitant CD33 expression. Thus, nearly all AMLs could be either targeted via CD33 or CD123. Simultaneous presence of both antigens was observed in 69.5% of patients. Most importantly, even AMLs with adverse cytogenetics express CD33 and CD123 levels comparable to those with favorable and intermediate subtypes. Some patient groups with unfavorable alterations, such as FMS-related tyrosine kinase 3-internal tandem duplication (FLT3-ITD) mutations, high FLT3-ITD mutant/wild-type ratios and monosomy 5 are even characterized by high expression of CD33 and CD123. In addition, blasts of patients with mutant nucleophosmin (NPM1) revealed significantly higher CD33 and CD123 expression pointing toward the possibility of minimal residual disease-guided interventions in mutated NPM1-positive AMLs. These results stimulate the development of novel concepts to redirect immune effector cells toward CD33- and CD123-expressing blasts using bi-specific antibodies or engineered T cells expressing chimeric antigen receptors.
Assuntos
Subunidade alfa de Receptor de Interleucina-3/biossíntese , Leucemia Mieloide Aguda/imunologia , Lectina 3 Semelhante a Ig de Ligação ao Ácido Siálico/biossíntese , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Citometria de Fluxo , Humanos , Leucemia Mieloide Aguda/sangue , Leucemia Mieloide Aguda/enzimologia , Leucemia Mieloide Aguda/genética , Masculino , Pessoa de Meia-Idade , Nucleofosmina , Fatores de Risco , Adulto Jovem , Tirosina Quinase 3 Semelhante a fms/sangue , Tirosina Quinase 3 Semelhante a fms/genéticaAssuntos
Anemia Aplástica/terapia , Antineoplásicos/efeitos adversos , Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda/terapia , Recidiva Local de Neoplasia/terapia , Adolescente , Adulto , Idoso , Anemia Aplástica/induzido quimicamente , Intervenção Educacional Precoce , Feminino , Seguimentos , Humanos , Leucemia Mieloide Aguda/mortalidade , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/mortalidade , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida , Transplante Homólogo , Adulto JovemAssuntos
Antimetabólitos Antineoplásicos/uso terapêutico , Azacitidina/uso terapêutico , Deleção Cromossômica , Cromossomos Humanos Par 5 , Leucemia Mieloide Aguda/tratamento farmacológico , Síndromes Mielodisplásicas/tratamento farmacológico , Talidomida/análogos & derivados , Idoso , Antimetabólitos Antineoplásicos/administração & dosagem , Azacitidina/administração & dosagem , Humanos , Lenalidomida , Leucemia Mieloide Aguda/genética , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/genética , Talidomida/administração & dosagem , Talidomida/uso terapêuticoRESUMO
This study evaluated azacitidine as treatment of minimal residual disease (MRD) determined by a sensitive donor chimerism analysis of CD34(+) blood cells to pre-empt relapse in patients with CD34(+) myelodysplastic syndromes (MDS) or acute myeloid leukemia (AML) after allogeneic hematopoietic stem cell transplantation (HSCT). At a median of 169 days after HSCT, 20/59 prospectively screened patients experienced a decrease of CD34(+) donor chimerism to <80% and received four azacitidine cycles (75 mg/m(2)/day for 7 days) while in complete hematologic remission. A total of 16 patients (80%) responded with either increasing CD34(+) donor chimerism to ≥80% (n=10; 50%) or stabilization (n=6; 30%) in the absence of relapse. Stabilized patients and those with a later drop of CD34(+) donor chimerism to <80% after initial response were eligible for subsequent azacitidine cycles. A total of 11 patients (55%) received a median of 4 (range, 1-11) additional cycles. Eventually, hematologic relapse occurred in 13 patients (65%), but was delayed until a median of 231 days (range, 56-558) after initial decrease of CD34(+) donor chimerism to <80%. In conclusion, pre-emptive azacitidine treatment has an acceptable safety profile and can substantially prevent or delay hematologic relapse in patients with MDS or AML and MRD after allogeneic HSCT.
Assuntos
Antimetabólitos Antineoplásicos/uso terapêutico , Azacitidina/uso terapêutico , Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda/terapia , Síndromes Mielodisplásicas/terapia , Adulto , Idoso , Antimetabólitos Antineoplásicos/efeitos adversos , Azacitidina/efeitos adversos , Quimerismo , Feminino , Seguimentos , Humanos , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/mortalidade , Masculino , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/tratamento farmacológico , Síndromes Mielodisplásicas/mortalidade , Neoplasia Residual/terapia , Recidiva , Fatores de Tempo , Transplante Homólogo , Resultado do Tratamento , Adulto JovemRESUMO
Current limitations in health services research (HRS) in Germany are caused by issues of research funding, interest-driven commissioning, and restricted research conditions due to the structural and organizational context of the German health system. Methodological challenges arise in the validation and generalizability of routine data. There are substantial risks of bias in non-controlled interventional studies. In order to overcome these limitations and to improve the standing and quality of HRS in Germany, political opinion leaders and stakeholders need to be provided with continuous information on the need and potential of HRS. Methodological standards are needed for the evaluation of routine data, and principles of evidence-based medicine must be applied in all research addressing the effectiveness of health care interventions.
Assuntos
Pesquisa sobre Serviços de Saúde/economia , Pesquisa sobre Serviços de Saúde/organização & administração , Programas Nacionais de Saúde/economia , Programas Nacionais de Saúde/organização & administração , Apoio à Pesquisa como Assunto/economia , Apoio à Pesquisa como Assunto/organização & administração , Viés , Terapia Combinada , Análise Custo-Benefício , Coleta de Dados , Alemanha , Necessidades e Demandas de Serviços de Saúde/economia , Necessidades e Demandas de Serviços de Saúde/organização & administração , Humanos , Masculino , Política , Prostatectomia , Neoplasias da Próstata/patologia , Neoplasias da Próstata/terapia , Ensaios Clínicos Controlados Aleatórios como Assunto/economia , Ensaios Clínicos Controlados Aleatórios como Assunto/estatística & dados numéricos , Projetos de PesquisaRESUMO
Patients with secondary acute myeloid leukemia (sAML) are generally thought to have a poor prognosis. As there are no prognostic risk stratification models for patients with sAML available, the aim of this study was to obtain a scoring system. Prognostic factors influencing overall survival (OS) and event-free survival (EFS) were analyzed in 305 sAML patients treated in the prospective AML96 trial. The obtained prognostic scoring system was then validated in an independent patient cohort included in the AML2003 and AML60+ trials. In addition to the known risk factors for AML, age and karyotype, we identified the absolute platelet count and the Nucleophosmin 1 mutational status at diagnosis as prognostic factors of sAML patients. A pronounced distribution of sAML patients into three score groups was achieved showing a 2-year OS/EFS of 52/44% for patients in the low-risk group, 21/12% in the intermediate-risk group and 7/3% in the high-risk group (both P<0.001). Validation of this scoring system in a second independent set of sAML patients revealed similar significantly different survival results. In conclusion, for the first time, a prognostic scoring system is provided for sAML patients, allowing differential treatment strategies in the future.
Assuntos
Leucemia Mieloide Aguda/mortalidade , Segunda Neoplasia Primária/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Ensaios Clínicos como Assunto , Feminino , Humanos , Leucemia Mieloide Aguda/genética , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Mutação , Segunda Neoplasia Primária/genética , Proteínas Nucleares/genética , Nucleofosmina , Contagem de Plaquetas , Prognóstico , Estudos Prospectivos , Risco , Resultado do TratamentoRESUMO
Despite the high incidence of prostate cancer and a variability of care due to different options for primary therapy, a comprehensive German clinical guideline has been missing up to now. Therefore, in 2005 the German Society for Urology initiated the development of a multidisciplinary and evidence-based S3 guideline for the early detection, diagnosis, and treatment of the different clinical manifestations of prostate cancer. There were 76 experts from 10 different medical societies and organizations including a patient organization involved in the development process. A total of 42 key questions were addressed. As a result of systematic literature searches and formal consensus processes, 170 recommendations and 42 statements were made. This article describes the objectives and the process of development of the guideline focusing on the cooperation between clinical and methodological experts as well as on the evidence and consensus basis of the recommendations.