RESUMO
It is common for visitors to have rich and varied experiences in the limited space of a classical Chinese garden. This leads to the sense that the garden's scale is much larger than it really is. A main reason for this perceptual bias is the gardener's manipulation of visual information. Most studies have discussed this phenomenon in terms of qualitative description with fragmented perspectives taken from static points, without considering ambient visual information or continuously changing observation points. A general question arises, then, on why depth perception can vary from one observation point to another along a garden path. To better understand the spatial experience in classical Chinese gardens, this study focused on variations in perceived depth among different observation points and aimed to identify influential visual information through psychophysical experimentation. As stimuli for the experiment, panoramic photos of Liu garden were taken from three positions at Lvyin Pavilion. Considering the effects of pictorial visual cues on depth perception, the photos were processed to create 18 kinds of stimuli (six image treatments * three positions). Two tasks were presented to the participants. In Task 1, 71 participants were asked to rate the depth value of the garden using the magnitude estimation method in a cave automatic virtual environment (CAVE). Statistical analysis of Task 1 revealed that depth values differed significantly among different viewpoints. In Task 2, participants were asked to compare 18 stimuli and 3D images presented on three connected monitors and to judge the depth of the garden using the adjustment method. The results of Task 2 again showed that depth values differed significantly among different viewpoints. In both tasks, ambient information (i.e., the perspective of interior space) significantly influenced depth perception.
RESUMO
A multicenter phase II study was conducted in 44 elderly (≥ 65 years) Japanese patients with newly diagnosed acute myeloid leukemia (AML) to evaluate whether azacitidine is also effective and feasible in Japanese AML patients. The 28 patients with AML with poor-risk cytogenetics and/or myelodysplasia-related changes (unfavorable AML) were randomly assigned to receive either azacitidine or conventional care regimens (CCR), and the other 16 patients without unfavorable AML received azacitidine alone. The primary endpoint was overall survival. At the median follow-up of 29 months, among the 26 evaluable patients with unfavorable AML, the median survival time (MST) of patients who received azacitidine (N = 14) was 9.6 months and that of patients who received CCR (N = 12) was 5.3 months (HR 0.73; 95% CI 0.31-1.69; log-rank P = 0.459). The MST of all 29 patients who received azacytidine, including the 15 evaluable patients without unfavorable AML, was 12.4 months. Adverse events of azacitidine were manageable and consistent with its established safety profile. Azacitidine tended to prolong survival in newly diagnosed elderly Japanese patients with AML, and was feasible as a front-line therapy for elderly AML patients.
Assuntos
Leucemia Mieloide Aguda , Síndromes Mielodisplásicas , Idoso , Antimetabólitos Antineoplásicos/efeitos adversos , Azacitidina/efeitos adversos , Humanos , Japão , Leucemia Mieloide Aguda/tratamento farmacológico , Síndromes Mielodisplásicas/tratamento farmacológico , Resultado do TratamentoRESUMO
As the main place of people's daily activities, indoor space (its size, shape, colors, material and textures, and so on) has important physical, emotional and health-based implications on people's behavior and quality of life. Material texture is an integral part of architectural environment perception and quality evaluation, but the effect of material texture on perceptual spaciousness lacks the support of experimental data. This research examined the effects between different wall textures on the observer's perception of spaciousness in indoor space, the influence of wall texture changes in different room sizes, and how the associational meaning of texture affects the degree of influence of wall texture on the spaciousness of indoor space. By using VR technology and the magnitude estimation (ME) analysis method, the authors found that the effect of wall texture on perceptual spaciousness varies depending on the wall material, and the textural effect is affected by room size. The perception of spaciousness is influenced by the observer's associational meaning of material texture, and the influence of associational meaning of material texture varies contingent on the room size. In relatively small rooms, the objective aspect (such as hardness, surface reflectivity, texture direction and texture depth) of the wall texture has a significant impact on perceived space. In contrast, the effects of subjective aspects (such as affinity and ecology) become more pronounced in relatively larger rooms. This research makes up for the lack of material texture research in perceptual spaciousness, and provides a new way for the designer to choose materials for the design of a spatial scale.
Assuntos
Arquitetura de Instituições de Saúde , Qualidade de Vida , Percepção Espacial , HumanosRESUMO
Recent studies have described various impacts of obesity and being overweight on acute myeloid leukemia (AML) outcomes in adult patients, but little is known about the impact of being underweight. We compared the outcomes of underweight patients to those of normal weight and overweight patients. Adult patients with AML who registered in the JALSG AML201 study (n = 1057) were classified into three groups: underweight (body mass index [BMI] < 18.5, n = 92), normal weight (BMI 18.5-25, n = 746), and overweight (BMI ≥ 25, n = 219). With the exception of age and male/female ratio, patient characteristics were comparable among the three groups. Rates of complete remission following induction chemotherapy were similar among the three groups (p = 0.68). We observed a significant difference in overall survival (OS), disease-free survival (DFS), and non-relapse mortality (NRM) between underweight and normal weight patients (3-year OS 34.8 vs. 47.7%, p = 0.01; DFS 28.6 vs. 39.8%, p = 0.02; 1-year NRM 6.2 vs. 2.6%, p = 0.05), but not between underweight and overweight patients. In multivariate analysis, underweight was an independent adverse prognostic factor for OS (p < 0.01), DFS (p = 0.01), and NRM (p = 0.04). During the first induction chemotherapy, the incidences of documented infection (DI) and severe adverse events (AEs) were higher in underweight patients than those in normal weight patients (DI 16 vs. 8.1%, p = 0.04; AE 36 vs. 24%, p = 0.05). In conclusion, underweight was an independent adverse prognostic factor for survival in adult AML patients.
Assuntos
Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/mortalidade , Magreza/complicações , Magreza/mortalidade , Adolescente , Adulto , Índice de Massa Corporal , Peso Corporal/fisiologia , Feminino , Humanos , Quimioterapia de Indução , Leucemia Mieloide Aguda/complicações , Leucemia Mieloide Aguda/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Prognóstico , Indução de Remissão , Estudos Retrospectivos , Análise de Sobrevida , Adulto JovemRESUMO
BACKGROUND: Contemporary treatment protocols for adult acute myeloid leukemia (AML) are age-specific, and older patients are generally treated less intensively than younger patients. However, it remains uncertain whether older but fit patients with AML really need to have their treatment attenuated. METHODS: To evaluate the contribution of age to outcome for patients with AML receiving intensive chemotherapy, data were analyzed for 2276 patients aged less than 65 years who were treated uniformly, regardless of age, in 3 consecutive prospective studies conducted by the Japan Adult Leukemia Study Group. RESULTS: A substantial drop in overall survival (OS) between patients aged 40 to 49 years and 50 to 64 years led to a focus on 2 comparisons: 1) age < 50 versus ≥ 50 years; and 2) age 50 to 54 versus 55 to 59 versus 60 to 64 years. OS was significantly better for patients aged < 50 years than that for those aged ≥ 50 years (49.6% and 37.0% at 5 years; P < .001); older patients were more susceptible to relapse, but not to early death or nonrelapse mortality. The significant differences in OS between these 2 age groups were equally seen for patients with favorable, intermediate, and adverse cytogenetics (P < .001 each). Outcomes for those aged 50 to 54, 55 to 59, and 60 to 64 years were similar, with 5-year OS rates of 38.2%, 35.1%, and 38.0%, respectively (P = .934), and no differences in early death or nonrelapse mortality were observed among these age groups. CONCLUSIONS: These findings justify the use of intensive chemotherapy without dose attenuation toward older but fit patients with AML, at least up to the age of 64 years.
Assuntos
Leucemia Mieloide Aguda/tratamento farmacológico , Adolescente , Adulto , Fatores Etários , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Análise de Sobrevida , Resultado do Tratamento , Adulto JovemRESUMO
The Science Council of Japan handed a proposal entitled "For the establishment of tobacco-free society" to the Japanese government in 2008, demanding stronger policy implementation. Among the 7 demands, top priority was placed on"education for improvement of knowledge on health risks of smoking". Ample scientific evidences have proven the health hazards that smoking causes directly and indirectly, which, however, are not well acknowledged among Japanese people, leaving Japan an underdeveloped country in terms of smoke-free society. More education is indispensable in schools and by mass media such as TV. The government must allocate more budgets for the education and advertisements, and, if unsuccessful, should request NHK, which collects mandatory TV reception fees akin to broadcast tax, to assume this task.
Assuntos
Educação em Saúde , Prevenção do Hábito de Fumar , Produtos do Tabaco/efeitos adversos , Promoção da Saúde , Humanos , Japão , Meios de Comunicação de Massa , Política Pública , Fumar/efeitos adversosRESUMO
Interdigitated electrodes (IDEs) that have a series of parallel microband electrodes with alternating microbands connected together were utilized in electrochemical impedance spectroscopy (EIS) to build a label-free human immunoglobulin A (IgA) immunosensor. Anti-human IgA (anti-IgA) was employed as an IgA receptor and was covalently immobilized on the IDE surface through a self-assembled monolayer, as confirmed by atomic force microscopy. EIS measurements revealed that the specific adsorption of IgA onto the immobilized anti-IgA gave rise to a clear increase in the value of interfacial charge transfer resistance (R(ct)). A linear relationship between ΔR(ct) and the logarithm of IgA concentration was found for the concentration range of 0.01-100 ng/mL. No modulation of R(ct) was detected by immersing the sensor in solutions of other proteins such as human immunoglobulin G or bovine serum albumin, which confirmed a high selectivity of this immunosensor for IgA. These results demonstrated that the anti-IgA receptor simply immobilized on the IDE surface can provide a sensitive biosensor.
Assuntos
Técnicas Biossensoriais/instrumentação , Condutometria/instrumentação , Espectroscopia Dielétrica/instrumentação , Eletrodos , Imunoensaio/instrumentação , Imunoglobulina G/sangue , Desenho de Equipamento , Análise de Falha de Equipamento , Humanos , Reprodutibilidade dos Testes , Sensibilidade e EspecificidadeRESUMO
We conducted a multicenter prospective randomized study to compare a fixed-scheduled induction therapy with a response-oriented individualized induction therapy for elderly patients with acute myeloid leukemia (AML). Newly diagnosed AML patients, aged between 65 and 80, were randomly assigned to receive fixed or individualized induction. Both groups received daunorubicin (DNR) 40 mg/m(2) for 3 days and behenoyl cytarabine (BHAC) 200 mg/m(2) for 8 days. In the individualized group, bone marrow biopsy was done on days 8 and 10, and according to the cellularity and blast ratio, the patients received additional DNR and BHAC for two to four more days. All patients achieving complete remission (CR) were randomized a second time to determine whether they would receive ubenimex. CR was obtained in 60.1 % of the fixed group and 63.6 % of the individualized group. Predicted 4-year relapse-free survival (RFS) was 9 % for the fixed group and 18 % for the individualized group. There were no statistically significant differences in CR and RFS between the fixed and individualized groups. In the ubenimex group, prolonged RFS was observed. Notably, gender was a prognostic factor in this study, as 102 female patients had a significantly higher CR rate (72.5 vs. 54.3 %, p = 0.0048) and better OS (24 vs. 14 % at 4 years, p = 0.018), compared with 140 male patients.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Quimioterapia de Consolidação , Quimioterapia de Indução , Leucemia Mieloide Aguda/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/administração & dosagem , Feminino , Humanos , Leucina/administração & dosagem , Leucina/análogos & derivados , Leucemia Mieloide Aguda/mortalidade , Masculino , Análise de Sobrevida , Resultado do TratamentoRESUMO
The safety, tolerability, pharmacokinetics and efficacy of nelarabine were evaluated in adult and pediatric patients with relapsed or refractory T-ALL/T-LBL. Adult patients received nelarabine i.v. over 2 hours on days 1, 3 and 5 in every 21 days, and pediatric patients received this regimen over 1 hour for 5 consecutive days in every 21 days. Safety was evaluated in 7 adult and 6 pediatric patients. Adverse events (AEs) were reported in all patients. Most frequently reported AEs included somnolence and nausea in adult patients and leukopenia and lymphocytopenia in pediatric patients. Five grade 3/4 AEs were reported in both adult and pediatric patients, most of which were hematologic events. There were no dose-limiting toxicities. Efficacy was evaluated in 7 adult and 4 pediatric patients. Complete response was noted in 1 adult and 2 pediatric patients. Higher intracellular ara-GTP concentrations were suggested to be associated with efficacy. Japanese adult and pediatric patients with T-ALL/T-LBL well tolerated nelarabine treatment, warranting further investigation.
Assuntos
Arabinonucleosídeos/administração & dosagem , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células T Precursoras/tratamento farmacológico , Adolescente , Adulto , Arabinonucleosídeos/efeitos adversos , Arabinonucleosídeos/farmacocinética , Arabinonucleotídeos/metabolismo , Criança , Esquema de Medicação , Feminino , Guanosina Trifosfato/análogos & derivados , Guanosina Trifosfato/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva , Linfócitos T/metabolismo , Resultado do Tratamento , Adulto JovemRESUMO
The aim of this retrospective study was to evaluate the toxicity profiles of dasatinib in patients with Philadelphia chromosome positive chronic myeloid leukemia (CML) or acute lymphatic leukemia (ALL) who were intolerant to imatinib, and who had been enrolled in our previous clinical trials to evaluate efficacy of dasatinib in patients resistant or tolerant to imatinib therapy. Twenty-four patients with CML and four with ALL were enrolled in the clinical studies to evaluate the efficacy according to the eligibility criteria related to intolerance to imatinib therapy. The toxicities reported during imatinib therapy were non-hematological toxicities in 23 patients and hematological toxicities in six patients. Patients were administered dasatinib 50-70 mg BID or 100 mg QD. Cross intolerance was observed in four patients who showed hematological toxicity after dasatinib treatment. However, it was possible to successfully continue therapy with only temporary interruption. No cross intolerance in non-hematological toxicity was found with the exception of one patient who showed cross intolerance, which did not result in treatment interruption. Dasatinib can be safely administered to imatinib-intolerant CML or Ph-positive ALL patients.
Assuntos
Antineoplásicos , Leucemia Mielogênica Crônica BCR-ABL Positiva , Piperazinas/uso terapêutico , Leucemia-Linfoma Linfoblástico de Células Precursoras , Inibidores de Proteínas Quinases , Pirimidinas/efeitos adversos , Pirimidinas/uso terapêutico , Tiazóis/efeitos adversos , Tiazóis/uso terapêutico , Adulto , Idoso , Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêutico , Benzamidas , Dasatinibe , Doenças Hematológicas/etiologia , Humanos , Mesilato de Imatinib , Leucemia Mielogênica Crônica BCR-ABL Positiva/complicações , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Pessoa de Meia-Idade , Piperazinas/administração & dosagem , Piperazinas/efeitos adversos , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicações , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Inibidores de Proteínas Quinases/efeitos adversos , Inibidores de Proteínas Quinases/uso terapêutico , Pirimidinas/administração & dosagem , Estudos Retrospectivos , Tiazóis/administração & dosagemRESUMO
We analyzed the incidence and prognosis of bacteremia/fungemia and pneumonia during remission induction therapy of a newly diagnosed acute myelogenous leukemia (AML) in the Japan Adult Leukemia Study Group treated with individual protocols of AML-87/-89 (1987-1991), AML-92 (1992-1995), AML-95 (1995-1997), and AML-97 (1997-2001). Bacteremia/fungemia was present in 251 of 2585 cases (9.7%); the causative microorganism was gram-positive bacteria (GPB) in 122 cases (49%), gram-negative bacteria (GNB) in 90 cases (36%), fungi (F) in 31 cases (12%), and polymicrobes (P) in 8 cases (3%). Particularly prevalent were Pseudomonas aeruginosa in 49 cases (20%), Staphylococcus epidermidis in 29 cases (12%), and Staphylococcus aureus in 25 cases (10%). With AML-87/-89, incidence of bacteremia/fungemia was 11.8% while it was 9.4% with AML-92, 8.7% with AML-95, and 9.2% with AML-97. The proportion of GPB, GNB, F, and P was 40, 41, 16, and 3% in AML-87/-89, 46, 40, 11, and 3% in AML-92, 48, 39, 11, and 2% in AML-95, and 59, 26, 11, and 4% in AML-97. The mortality rate by period was 26.5, 16.4, 14.0, and 6.8%, respectively. Pneumonia was found in 433 cases (16.8%); microbiological research covered 359 cases of AML-87/-89, AML-92, AML-97 and excluded AML-95 as there was no listing for the causative microorganism on questionnaires. Microbiologically documented pneumonia was found in 123 cases (34.3%), with GPB in 33 cases (27%), GNB in 28 cases (23%), F in 44 cases (36%), and P in 18 cases (15%); particularly prevalent were Aspergillus in 23 cases (19%), Staphylococcus aureus in 16 cases (13%), and Pseudomonas aeruginosa in 15 cases (12%). The incidence of pneumonia overall was 24.6% with AML-87/-89, 16.9% with AML-92, 13.9% with AML-95, and 12.9% with AML-97, with a mortality rate of 28.9, 33.3, 16.7, and 16.7%, respectively. Incidence of bacteremia/fungemia and pneumonia complicating AML has tended to decline in recent years, and mortality has also tended to improve.
Assuntos
Bacteriemia/epidemiologia , Fungemia/epidemiologia , Leucemia Mieloide Aguda/epidemiologia , Pneumonia/epidemiologia , Adulto , Bacteriemia/microbiologia , Feminino , Fungemia/microbiologia , Humanos , Japão , Leucemia Mieloide Aguda/microbiologia , Masculino , Pneumonia/microbiologia , Estudos RetrospectivosRESUMO
BCR-ABL1 kinase domain mutations were evaluated in 60 imatinib-resistant patients with Philadelphia-positive (Ph(+)) leukemia using PCR-Invader assay and direct sequencing. In chronic myelogenous leukemia (CML)--chronic phase (CP), 5 had P-loop mutations and 3 had T315I mutations. CML-CP patients with high Sokal score showed significantly higher incidence of mutations. P-loop mutations were associated with higher risk of disease progression. In CML-advanced phase, P-loop mutations and T315I mutation were associated with significantly shorter survival. In Ph(+) acute lymphoblastic leukemia, overall survival was poor irrespective of mutational status. The PCR-Invader assay is useful for screening of mutations and prediction of prognosis.
Assuntos
Resistencia a Medicamentos Antineoplásicos/genética , Proteínas de Fusão bcr-abl/genética , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Mutação , Piperazinas/uso terapêutico , Reação em Cadeia da Polimerase/métodos , Pirimidinas/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/uso terapêutico , Benzamidas , Análise Mutacional de DNA/métodos , Feminino , Proteínas de Fusão bcr-abl/análise , Proteínas de Fusão bcr-abl/química , Testes Genéticos/métodos , Humanos , Mesilato de Imatinib , Leucemia Mielogênica Crônica BCR-ABL Positiva/diagnóstico , Masculino , Pessoa de Meia-Idade , Mutação/fisiologia , Fosfotransferases/química , Fosfotransferases/genética , Prognóstico , Estrutura Terciária de Proteína/genética , Análise de Sobrevida , Adulto JovemRESUMO
To investigate treatment effects of thrombomodulin alfa (TM-α) in patients with disseminated intravascular coagulation (DIC) having infection as the underlying disease, retrospective subanalysis of a double-blind, randomized controlled phase 3 trial was conducted. In the phase 3 trial, 227 DIC patients (full-analysis set) having infection and/or hematologic malignancy as the underlying disease received either TM-α (0.06 mg·kg for 30 min once daily) or heparin (8 U·kg·h for 24 h) for 6 days using the double-dummy method. Among these patients, 147 patients with noninfectious comorbidity leading to severe thrombocytopenia (e.g., hematologic malignancy, or aplastic anemia) were excluded from the present analysis, and 80 patients with infectious disease and DIC were extracted and subjected to the present retrospective subanalysis. Disseminated intravascular coagulation resolution rates were determined using the DIC diagnostic criteria for critically ill patients at 7 days, and mortality rates were evaluated at 28 days. In the TM-α and heparin groups, DIC resolution rates were 67.5% (27/40) and 55.6% (20/36), and 28-day mortality rates were 21.4% (9/42) and 31.6% (12/38), respectively. Mortality rates of patients who recovered from DIC were 3.7% (1/27) in the TM-α group and 15% (3/20) in the heparin group. These results suggest TM-α may be valuable in the treatment of DIC associated with infection.
Assuntos
Anticoagulantes/uso terapêutico , Coagulação Intravascular Disseminada/diagnóstico , Coagulação Intravascular Disseminada/tratamento farmacológico , Infecções/tratamento farmacológico , Trombomodulina/uso terapêutico , Coagulação Intravascular Disseminada/metabolismo , Coagulação Intravascular Disseminada/mortalidade , Fibrinogênio/metabolismo , Humanos , Infecções/complicações , Infecções/mortalidadeRESUMO
We conducted a multi-institutional randomized study to determine whether high-dose daunorubicin would be as effective as standard-dose idarubicin in remission-induction therapy for newly diagnosed adult patients younger than 65 years of age with acute myeloid leukemia. Of 1064 patients registered, 1057 were evaluable. They were randomly assigned to receive either daunorubicin (50 mg/m(2) daily for 5 days) or idarubicin (12 mg/m(2) daily for 3 days) in combination with 100 mg/m(2) of cytarabine by continuous infusion daily for 7 days as induction therapy. Complete remission was achieved in 407 (77.5%) of 525 patients in the daunorubicin group and 416 (78.2%) of 532 in the idarubicin group (P = .79). Patients achieving complete remission received intensive postremission therapy that consisted of either 3 courses of high-dose cytarabine or 4 courses of standard-dose therapy. Overall survival rates at 5 years were 48% for the daunorubicin group and 48% for the idarubicin group (P = .54), and relapse-free survival rates at 5 years were 41% and 41% (P = .97), respectively. Thus, high-dose daunorubicin and standard-dose idarubicin were equally effective for the treatment of adult acute myeloid leukemia, achieving a high rate of complete remission and good long-term efficacy. This study is registered at http://www.umin.ac.jp/ctrj/ as C000000157.
Assuntos
Daunorrubicina/administração & dosagem , Idarubicina/administração & dosagem , Leucemia Mieloide Aguda/tratamento farmacológico , Adolescente , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Citarabina/administração & dosagem , Citarabina/uso terapêutico , Daunorrubicina/uso terapêutico , Relação Dose-Resposta a Droga , Humanos , Idarubicina/uso terapêutico , Leucemia Mieloide Aguda/mortalidade , Pessoa de Meia-Idade , Indução de Remissão/métodos , Análise de Sobrevida , Adulto JovemAssuntos
Aberrações Cromossômicas , Leucemia Promielocítica Aguda/tratamento farmacológico , Leucemia Promielocítica Aguda/genética , Adolescente , Adulto , Idoso , Antineoplásicos/uso terapêutico , Cromossomos Humanos Par 15/genética , Cromossomos Humanos Par 17/genética , Feminino , Seguimentos , Humanos , Japão , Leucemia Promielocítica Aguda/patologia , Masculino , Pessoa de Meia-Idade , Indução de Remissão , Taxa de Sobrevida , Fatores de Tempo , Translocação Genética/genética , Tretinoína/uso terapêutico , Adulto JovemRESUMO
We conducted a prospective randomized study to assess the optimal postremission therapy for adult acute myeloid leukemia in patients younger than 65 years in the first complete remission. A total of 781 patients in complete remission were randomly assigned to receive consolidation chemotherapy of either 3 courses of high-dose cytarabine (HiDAC, 2 g/m(2) twice daily for 5 days) alone or 4 courses of conventional standard-dose multiagent chemotherapy (CT) established in the previous JALSG AML97 study. Five-year disease-free survival was 43% for the HiDAC group and 39% for the multiagent CT group (P = .724), and 5-year overall survival was 58% and 56%, respectively (P = .954). Among the favorable cytogenetic risk group (n = 218), 5-year disease-free survival was 57% for HiDAC and 39% for multiagent CT (P = .050), and 5-year overall survival was 75% and 66%, respectively (P = .174). In the HiDAC group, the nadir of leukocyte counts was lower, and the duration of leukocyte less than 1.0 × 10(9)/L longer, and the frequency of documented infections higher. The present study demonstrated that the multiagent CT regimen is as effective as our HiDAC regimen for consolidation. Our HiDAC regimen resulted in a beneficial effect on disease-free survival only in the favorable cytogenetic leukemia group. This trial was registered at www.umin.ac.jp/ctr/ as #C000000157.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Citarabina/administração & dosagem , Leucemia Mieloide Aguda/tratamento farmacológico , Adolescente , Adulto , Antimetabólitos Antineoplásicos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Citarabina/uso terapêutico , Relação Dose-Resposta a Droga , Humanos , Leucemia Mieloide Aguda/mortalidade , Contagem de Leucócitos , Pessoa de Meia-Idade , Indução de Remissão , Análise de Sobrevida , Resultado do Tratamento , Adulto JovemRESUMO
We designed a treatment protocol for newly diagnosed adult acute lymphoblastic leukemia (ALL) in the pre-imatinib era, employing intensified consolidation therapy with a total of 330 mg/m² doxorubicin and adopting slightly modified induction and maintenance regimen of the CALGB 8811 study. Of 404 eligible patients (median age 38 years, range 15-64 years), 298 (74%) achieved complete remission (CR). The 5-year overall survival (OS) rate was 32%, and the 5-year disease-free survival (DFS) rate was 33%. Of 256 Philadelphia chromosome (Ph)-negative patients, 208 (81%) achieved CR and the 5-year OS rate was 39%, and 60 of them underwent allogeneic-hematopoietic stem cell transplantation (allo-HSCT) from related or unrelated donors during the first CR, resulting in 63% 5-year OS. Of 116 Ph-positive patients, 65 (56%) achieved CR and the 5-year OS rate was 15%, and 22 of them underwent allo-HSCT from related or unrelated donors during the first CR, resulting in 47% 5-year OS. In Ph-negative patients, multivariate analysis showed that older age, advanced performance status and unfavorable karyotypes were significant poor prognostic factors for OS and higher WBC counts for DFS. The present treatment regimen could not show a better outcome than that of our previous JALSG-ALL93 study for adult ALL.
Assuntos
Antibióticos Antineoplásicos/administração & dosagem , Antibióticos Antineoplásicos/uso terapêutico , Doxorrubicina/administração & dosagem , Doxorrubicina/uso terapêutico , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Adolescente , Adulto , Feminino , Transplante de Células-Tronco Hematopoéticas , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Cromossomo Filadélfia , Leucemia-Linfoma Linfoblástico de Células Precursoras/cirurgia , Prognóstico , Indução de Remissão , Análise de Sobrevida , Adulto JovemRESUMO
In the pre-imatinib era, the treatment outcome of patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph(+) ALL) was dismal. Complete remission was generally achieved only in about 50% to 60% of patients, and allogeneic hematopoietic stem cell transplantation (allo-HSCT), when feasible in younger patients, was virtually the sole curative modality. Imatinib has changed the situation dramatically, however, in combination with conventional chemotherapy or with corticosteroid alone, producing about 95% complete remission and thus increasing the number of patients undergoing allo-HSCT. Currently, the overall survival of patients who have undergone allo-HSCT exceeds 50%, and a considerable proportion of patients for whom allo-HSCT is not feasible are predictably curable. The next question is how to prevent relapse, which is observed not only in more than half of patients for whom allo-HSCT is not feasible but also in a considerable number of patients after allo-HSCT. Thus, improvement of postremission therapy is crucial. Whether intensive chemotherapy with currently available cytotoxic drugs contributes to the prevention of relapse is questionable, because intensive chemotherapy alone in the pre-imatinib era nearly always failed to cure this disease. Promising partners to be combined with imatinib or with a second-generation tyrosine kinase inhibitor (TKI) will be corticosteroids and vincristine. New TKIs such as dasatinib should be incorporated into the early phase of postremission therapy. Recognizing the small number of patients with Ph(+) ALL, intergroup or international studies are necessary to develop the best postremission therapy. In the near future, it is hoped that Ph(+) ALL will become one of the leukemias for which allo-HSCT is offered only for relapsed or extremely high-risk patients.
Assuntos
Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Corticosteroides/uso terapêutico , Antineoplásicos/uso terapêutico , Benzamidas , Terapia Combinada , Transplante de Células-Tronco Hematopoéticas , Humanos , Mesilato de Imatinib , Piperazinas/uso terapêutico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Inibidores de Proteínas Quinases/uso terapêutico , Pirimidinas/uso terapêutico , Vincristina/uso terapêuticoRESUMO
Although imatinib has become the current standard treatment for chronic myeloid leukemia (CML), there is limited information regarding its efficacy and safety among Japanese patients. We therefore conducted a prospective multi-center open-label study of imatinib for Japanese patients with newly diagnosed chronic-phase CML (CP-CML). A total of 107 patients were enrolled and treated with imatinib at an initial daily dose of 400 mg. Eighty-three patients completed 3 years of study treatment. The cumulative rates of major cytogenetic response and complete cytogenetic response (CCyR) were 90.9 and 90.2% at 3 years, respectively. The safety profile was not very different from that reported in the IRIS study, although grade > or =3 neutropenia occurred relatively frequently (31.8 vs. 14.3%). Only seven patients discontinued the study due to adverse events, as did four patients due to insufficient efficacy. The 3-year probabilities of overall survival and progression-free survival were 93.2 and 91.4%, respectively. Higher average daily doses (i.e., > or =350 mg) were significantly associated not only with higher rates of achieving CCyR, but also with longer duration of CCyR. These findings confirm the clinical utility of imatinib in Japanese patients with newly diagnosed CP-CML, and suggest detrimental effect of low average daily dose on treatment results.
Assuntos
Leucemia Mieloide de Fase Crônica/tratamento farmacológico , Piperazinas/administração & dosagem , Pirimidinas/administração & dosagem , Adolescente , Adulto , Idoso , Benzamidas , Criança , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Feminino , Humanos , Mesilato de Imatinib , Japão , Leucemia Mieloide de Fase Crônica/complicações , Masculino , Pessoa de Meia-Idade , Piperazinas/efeitos adversos , Estudos Prospectivos , Pirimidinas/efeitos adversos , Indução de Remissão , Taxa de Sobrevida , Resultado do Tratamento , Adulto JovemRESUMO
A total of 120 patients with high-risk myelodysplastic syndrome (MDS) and AML progressed from MDS (MDS-AML) were registered in a randomized controlled study of the Japan Adult Leukemia Study Group (JALSG). Untreated adult patients with high-risk MDS and MDS-AML were randomly assigned to receive either idarubicin and cytosine arabinoside (IDR/Ara-C) (Group A) or low-dose cytosine arabinoside and aclarubicin (CA) (Group B). The remission rates were 64.7% for Group A (33 of 51 evaluable cases) and 43.9% for Group B (29 out of 66 evaluable cases). The 2-year overall survival rates and disease-free survival rates were 28.1 and 26.0% for Group A, and 32.1 and 24.8% for Group B, respectively. The duration of CR was 320.6 days for Group A and 378.7 days for Group B. There were 15 patients who lived longer than 1,000 days after diagnosis: 6 and 9 patients in Groups A and B, respectively. However, among patients enrolled in this trial, intensive chemotherapy did not produce better survival than low-dose chemotherapy. In conclusion, it is necessary to introduce the first line therapy excluding the chemotherapy that can prolong survival in patients with high-risk MDS and MDS-AML.