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BACKGROUND: Despite frequent anemia and multiple transfusions in patients undergoing chemotherapy and allogeneic hematopoietic stem cell transplantation (allo-HSCT) for acute myeloid leukemia , recommendations for use of erythropoiesis-stimulating agents (ESAs) in these populations are still missing. The primary objective was the effect of ESA administration on patient's quality of life (QoL). Secondary objectives were hemoglobin (Hb) recovery, red blood cell (RBC) transfusions, overall survival, and event-free survival. METHODS: Adult patients with Hb ≤ 11 g/dL after consolidation chemotherapy for acute myeloid leukemia (group 1), or after allo-HSCT for any hematological diseases (group 2), were prospectively included. ESA was administered subcutaneously once per week during a maximum period of 6 months and was stopped when Hb level reached 12 g/dL. A paired-matched analysis using a historical control group was performed for secondary endpoints. Fifty-two patients were included in group 1, and 55 patients were in group 2. RESULTS: For the global population, a significant improvement of QoL was noticed with ESA use; 83% (group 1) and 71% (group 2) of patients achieved an Hb level ≥ 12 g/dL without transfusion requirement. The pair-matched analysis showed a reduction of 4 RBC units per patient in group 1 (P = .0002) and 3 RBC units per patient in group 2 (P = .04). No significant difference in terms of thromboembolic events, overall survival, and event-free survival was observed between ESA and control groups. A RBC transfusion median savings of 1712 per patient was estimated in each group. CONCLUSIONS: ESAs have a clinical and economic benefit on Hb recovery, could improve a patient's QoL, and lead to a significant reduction in number of RBC transfusions with no effect on survival.
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Eritropoyetina/uso terapéutico , Trasplante de Células Madre Hematopoyéticas , Leucemia Mieloide Aguda/tratamiento farmacológico , Leucemia Mieloide Aguda/psicología , Adulto , Anciano , Análisis Costo-Beneficio , Supervivencia sin Enfermedad , Femenino , Trasplante de Células Madre Hematopoyéticas/economía , Humanos , Leucemia Mieloide Aguda/economía , Leucemia Mieloide Aguda/mortalidad , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Calidad de Vida , Adulto JovenRESUMEN
To assess the value of administering timed-sequential chemotherapy (TSC; 2 therapeutic sequences separated by a 4-day interval-free chemotherapy) or high-dose cytarabine (HDAraC) cycles in consolidation therapy for acute myeloid leukemia (AML), 459 patients 15 to 50 years of age were enrolled in the prospective randomized Acute Leukemia French Association-9802 trial. Complete remission was achieved in 89%. A total of 237 patients were then randomized to either TSC consolidation (120 patients) or HDAraC consolidation cycles (117 patients). Overall, there was no significant difference between the 2 consolidation arms (5-year event-free survival [EFS]: 41% for HDAraC vs 35% for TSC), or cumulative incidence of relapse, or treatment-related mortality. Cytogenetically normal AML NPM1(+) or CEBPA(+) and FLT3-ITD(-) had the same outcome as those with favorable cytogenetics. When considering favorable and unfavorable risk groups, the trend was in favor of HDAraC. However, the difference became significant when considering intermediate cytogenetics (5-year EFS: 49% vs 29%; P = .02), especially cytogenetically normal AML (5-year EFS: 48% vs 31%; P = .04), which was related to lower relapse rate and less toxicity. This study demonstrates that TSC did not produce any benefit when used as consolidation therapy in younger adults compared with HDAraC. This trial was registered at www.clinicaltrials.gov as #NCT00880243.
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Antimetabolitos Antineoplásicos/administración & dosificación , Antimetabolitos Antineoplásicos/uso terapéutico , Citarabina/administración & dosificación , Citarabina/uso terapéutico , Leucemia Mieloide Aguda/tratamiento farmacológico , Adolescente , Adulto , Factores de Edad , Análisis Citogenético , Supervivencia sin Enfermedad , Quimioterapia/métodos , Humanos , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/terapia , Persona de Mediana Edad , Nucleofosmina , Estudios Prospectivos , Inducción de Remisión , Adulto JovenRESUMEN
Prognostic factors for response and survival in higher-risk myelodysplastic syndrome patients treated with azacitidine (AZA) remain largely unknown. Two hundred eighty-two consecutive high or intermediate-2 risk myelodysplastic syndrome patients received AZA in a compassionate, patient-named program. Diagnosis was RA/RARS/RCMD in 4%, RAEB-1 in 20%, RAEB-2 in 54%, and RAEB-t (AML with 21%-30% marrow blasts) in 22%. Cytogenetic risk was good in 31%, intermediate in 17%, and poor in 47%. Patients received AZA for a median of 6 cycles (1-52). Previous low-dose cytosine arabinoside treatment (P = .009), bone marrow blasts > 15% (P = .004), and abnormal karyotype (P = .03) independently predicted lower response rates. Complex karyotype predicted shorter responses (P = .0003). Performance status ≥ 2, intermediate- and poor-risk cytogenetics, presence of circulating blasts, and red blood cell transfusion dependency ≥ 4 units/8 weeks (all P < 10(-4)) independently predicted poorer overall survival (OS). A prognostic score based on those factors discriminated 3 risk groups with median OS not reached, 15.0 and 6.1 months, respectively (P < 10(-4)). This prognostic score was validated in an independent set of patients receiving AZA in the AZA-001 trial (P = .003). Achievement of hematological improvement in patients who did not obtain complete or partial remission was associated with improved OS (P < 10(-4)). In conclusion, routine tests can identify subgroups of patients with distinct prognosis with AZA treatment.
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Antimetabolitos Antineoplásicos/uso terapéutico , Azacitidina/uso terapéutico , Síndromes Mielodisplásicos/tratamiento farmacológico , Síndromes Mielodisplásicos/mortalidad , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Pronóstico , Adulto JovenRESUMEN
One hundred and fifty-four acute myeloid leukemia patients with trisomy 8 were studied for their clinical and biological characteristics, and treatment outcome. Forty-seven patients presented with trisomy 8 as the sole aberration, 107 with trisomy 8 associated with other cytogenetic abnormalities (13 with favorable, 54 with intermediate, and 40 with unfavorable risk cytogenetics). Overall complete remission (CR) proportion was 48%. Median disease-free survival (DFS) and overall survival (OS) were 7.8 and 8.3 months, respectively. In multivariate analysis, age >or=60 years (P<0.0001) and association with unfavorable karyotype (P=0.03) were of poor prognostic value for CR achievement. Age >or=60 years (P<0.0001) and antecedents of dysmyelopoiesis (P=0.02) were of poor prognostic value for OS. Patients with trisomy 8 alone did not show any difference in terms of outcome as compared with those in whom trisomy 8 was associated to intermediate risk cytogenetics (P=0.0002). Trisomy 8 in addition to favorable karyotype maintained a good clinical outcome, while trisomy 8 in addition to unfavorable cytogenetics showed the worst prognosis.
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Aberraciones Cromosómicas , Cromosomas Humanos Par 8 , Leucemia Mieloide Aguda/genética , Leucemia Mieloide/genética , Trisomía/genética , Adolescente , Adulto , Distribución por Edad , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Leucemia Mieloide/sangre , Leucemia Mieloide/mortalidad , Leucemia Mieloide Aguda/sangre , Leucemia Mieloide Aguda/mortalidad , Recuento de Leucocitos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Análisis de Supervivencia , Resultado del TratamientoRESUMEN
AIM: To evaluate the importance of the CD34+CD38- cell population when compared to the CD34+CD38+/low and CD34+CD38+/high leukemic cell sub-populations and to determine its correlations with leukemia characteristics and known prognostic factors, as well as with response to therapy and survival. METHODS: Two hundred bone marrow samples were obtained at diagnosis from 200 consecutive patients with newly diagnosed acute myeloid leukemia (AML) were studied between September 2008 and December 2010 at our Institution (Hematology Department, Lyon, France). The CD34/CD38 cell profile was analyzed by multiparameter flowcytometry approach using 8C panels and FACS CANTO and Diva software (BD Bioscience). RESULTS: We analyzed CD34 and CD38 expression in bone marrow samples of 200 AML patients at diagnosis, and investigated the prognostic value of the most immature CD34+CD38- population. Using a cut-off value of 1% of CD34+CD38- from total "bulk leukemic cells" we found that a high (> 1%) level of CD34+CD38- blasts at diagnosis was correlated with advanced age, adverse cytogenetics as well as with a lower rate of complete response after induction and shorter disease-free survival. In a multivariate analysis considering age, leukocytosis, the % of CD34+ blasts cells and the standardized cytogenetic and molecular risk subgroups, a percentage of CD34+CD38- leukemic cells > 1% was an independent predictor of DFS [HR = 2.8 (1.02-7.73), P = 0.04] and OS [HR = 2.65 (1.09-6.43), P = 0.03]. CONCLUSION: Taken together, these results show that a CD34/CD38 "backbone" for leukemic cell analysis by multicolour flowcytometry at diagnosis provides useful prognostic information.
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INTRODUCTION: All trans retinoic acid has shown a remarkable effectiveness in acute promyelocytic leukemia. These results have encouraged studies of treatment with ATRA in other acute myeloid leukemia subtypes. PATIENTS AND METHODS: In order to evaluate toxicity and antileukemic efficacy of all ATRA in patients with relapsed or refractory non promyelocytic AML, 95 patients (median age, 58 years; range, 20 to 80 years), with unclassified AML according to the FAB classification or secondary AML at diagnosis, or refractory or relapsing AML, received induction therapy with Idarubicin, 10 mg/m(2)/day, for 3 days and cytarabine, 1000 mg/m(2)/12 h, for 6 days, alone or combined, on a randomized basis, with ATRA, 45 mg/m(2)/day, from day 1 to complete remission. Patients in CR received maintenance therapy with 6 monthly courses combining Ida, 10 mg/m(2)/day, intravenously, on day 1 with Ara-C100 mg/m(2)/day, subcutaneously, from day 1 to day 5. RESULTS: Results were evaluated after one induction course. Overall 54 patients (57%, 26 with ATRA and 28 without ATRA) achieved CR including five patients treated at time of initial diagnosis, seven previously resistant, 38 in first relapse and four in further relapse. Thirty patients (31%) had resistant disease and 11 (12%) died from toxicity. Median time for neutrophil recovery to 0.5 x 10(9)/l and platelets to 20 x 10(9)/l was 31 and 21 days respectively. Severe toxicity (WHO grade >or=3) included infections (37%), diarrhea (9%), bleeding (3%), vomiting (16%), hyperbilirubinemia (5%), mucositis (6%) and hypercreatininemia (2%). No ATRA syndrome was noted in the ATRA arm. Median overall survival for the entire cohort was 6.3 months and median disease-free survival was 4.7 months. There were no statistical differences in terms of CR, DFS, and OS between the two arms. CONCLUSION: We conclude that ATRA in combination with Ida and Ara-C can be administered safely to high-risk AML patients. However, in this setting, ATRA did not offer any advantage when compared to chemotherapy alone.
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Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Leucemia Mieloide/tratamiento farmacológico , Tretinoina/administración & dosificación , Enfermedad Aguda , Adulto , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/toxicidad , Citarabina/administración & dosificación , Femenino , Humanos , Idarrubicina/administración & dosificación , Leucemia Mieloide/complicaciones , Leucemia Mieloide/mortalidad , Masculino , Persona de Mediana Edad , Inducción de Remisión , Terapia Recuperativa , Análisis de Supervivencia , Equivalencia Terapéutica , Resultado del Tratamiento , Tretinoina/toxicidadRESUMEN
Recent cohort and case-control studies have suggested that cigarette smoking may be involved in the etiology of leukemia. Rising trends have been observed for all leukemias when the amount of cigarettes smoked increased. However, the magnitude of the trend was strongest for myeloid leukemia. Although no detailed biological mechanism has been proposed, a causal link is made plausible by evidence of systemic effects of cigarette smoke and the presence in cigarette smoke of chemicals (benzene) and radioactive substances that have been associated with leukemia risk. Cigarette smoking has a deleterious effect on survival in leukemia by shortening complete remission duration and subsequent survival. The data reported in this review are derived from the medical literature and from the experience of the authors.
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Leucemia/etiología , Fumar/efectos adversos , Enfermedad Aguda , Humanos , Leucemia/patología , Factores de RiesgoRESUMEN
AIM: To evaluate quantitatively and qualitatively the different CD34(+) cell subsets after priming by chemotherapy granulocyte colony-stimulating factor (± G-CSF) in patients with acute myeloid leukemia. METHODS: Peripheral blood and bone marrow samples were harvested in 8 acute myeloid leukemia patients during and after induction chemotherapy. The CD34/CD38 cell profile was analyzed by multi-parameter flow cytometry. Adhesion profile was made using CXC chemokine receptor 4 (CXCR4) (CD184), VLA-4 (CD49d/CD29) and CD47. RESULTS: Chemotherapy ± G-CSF mobilized immature cells (CD34(+)CD38(-) population), while the more mature cells (CD34(+)CD38(low) and CD34(+)CD38(+) populations) decreased progressively after treatment. Circulating CD34(+) cells tended to be more sensitive to chemotherapy after priming with G-CSF. CD34(+) cell mobilization was correlated with a gradual increase in CXCR4 and CD47 expression, suggesting a role in cell protection and the capacity of homing back to the marrow. CONCLUSION: Chemotherapy ± G-CSF mobilizes into the circulation CD34(+) bone marrow cells, of which, the immature CD34(+)CD38(-) cell population. Further manipulations of these interactions may be a means with which to control the trafficking of leukemia stem cells to improve patients' outcomes.
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Forty-seven percent of adults with acute myeloid leukemia (AML) who entered the ALFA-9802 trial and achieved a first complete remission (CR) experienced a first relapse. We examined the outcome of these 190 adult patients. Eighty-four patients (44%) achieved a second CR. The median overall survival (OS) after relapse was 8.9 months with a 2-year OS at 25%. Factors predicting a better outcome after relapse were stem cell transplant (SCT) performed in second CR and a first CR duration >1 year. Risk groups defined at the time of diagnosis and treatment received in first CR also influenced the outcome after relapse. The best results were obtained in patients with core binding factor (CBF)-AML, while patients initially defined as favorable intermediate risk showed a similar outcome after relapse than those initially entering the poor risk group. We conclude that most adult patients with recurring AML could not be rescued using current available therapies, although allogeneic SCT remains the best therapeutic option at this stage of the disease.
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Ensayos Clínicos como Asunto , Leucemia Mieloide Aguda/terapia , Terapia Recuperativa , Adolescente , Adulto , Algoritmos , Femenino , Francia/epidemiología , Humanos , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/mortalidad , Masculino , Persona de Mediana Edad , Pronóstico , Recurrencia , Inducción de Remisión , Terapia Recuperativa/métodos , Análisis de Supervivencia , Resultado del Tratamiento , Adulto JovenRESUMEN
This study reports a case of promyelocytic sarcoma that developed as a solitary sternal mass without any clinical evidence of acute promyelocytic leukemia. The case presented the diagnostic difficulties common to all aleukemic granulocytic sarcomas, and diagnosis was made possible by local identification of the PML/RARα fusion gene by fluorescent in situ hybridization. The patient was treated by surgery followed by chemotherapy plus all-trans retinoic acid therapy and local radiotherapy.
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It has been proposed that Vitamin D has a significant influence on disease progression in malignancy. This study aims to investigate whether serum levels of 25-hydroxyvitamin D [25(OH)D] are associated with prognosis in patients with hematological malignancies. This study is based on 105 patients with hematological disease (acute and chronic leukemias, myelodysplastic syndromes, monoclonal gammapathies, and chronic lymphoid disorders), seen over a 6-months period. 25(OH)D deficiency (<20 ng/ml) appeared very common and an inverse relationship was observed between 25(OH)D levels and the response to therapy: lower levels being related to poorer response. In acute leukemias, a significant difference was noted between patients with long-term disease-free survival in those tested at diagnosis (P=0·001) or in those tested at the time of relapse (P=0·05). Similarly in patients with Philadelphia-positive leukemias, there was a correlation between molecular response and levels of 25(OH)D (P=0·01). Previously identified factors, such as age, season, gender, or nutritional index, were not related to circulating 25(OH)D levels. Lower levels of circulating 25(OH)D appeared related to a progressive stage of the disease and poor response to therapy, and, therefore, to the aggressiveness of the disease. It is a potential marker of prognosis in patients with leukemia.
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Neoplasias Hematológicas/diagnóstico , Vitamina D/análogos & derivados , Adulto , Anciano , Anciano de 80 o más Años , Progresión de la Enfermedad , Femenino , Neoplasias Hematológicas/mortalidad , Neoplasias Hematológicas/patología , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Recurrencia , Estaciones del Año , Análisis de Supervivencia , Carga Tumoral , Vitamina D/sangre , Adulto JovenRESUMEN
BACKGROUND: The treatment of older adults with acute myeloid leukemia (AML) is associated with unsatisfactory rates of response and overall survival. Identification of valuable factors that can facilitate therapeutic decision-making between intensive chemotherapy and investigational treatment strategies is warranted. METHODS: Analysis of proliferative (white blood cell [WBC] count) and invasive (percentage of blast cells in peripheral blood) characteristics of leukemic blasts at diagnosis is presented in a population of 432 promyelocytic leukemia AML patients who are older than than 60 years and have been selected for entering onto five successive clinical trials combining an anthracycline and cytarabine. RESULTS: Five groups of patients were defined according to these two relevant parameters used in clinical practice. Response rates were lower for the hyperproliferative groups (47% and 46%, respectively) and the nonproliferative groups displaying circulating blasts (56% and 59%, respectively) compared with those for the nonproliferative and noninvasive group (77%) (P = .0003). Median overall survivals were shorter for the hyperproliferative groups (5.7 and 5.8 months, respectively) compared with those observed for the nonproliferative groups (8.9 and12.6 months, respectively). CONCLUSIONS: This combination of basic characteristics helps estimate the outcome of elderly AML patients who are usually selected for intensive chemotherapy. Although these factors remain valuable for identifying leukemia behavior, our study demonstrated that results of intensive chemotherapy in elderly patients remained poor, whatever the prognostic group. Comparison with recent data from the literature requires investigators to study results differently and to consider investigational therapy as being the most appropriate treatment even for this highly selected population.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Leucemia Mieloide Aguda/sangre , Leucemia Mieloide Aguda/tratamiento farmacológico , Leucocitosis/tratamiento farmacológico , Factores de Edad , Anciano , Anciano de 80 o más Años , Antraciclinas/uso terapéutico , Comorbilidad , Citarabina/uso terapéutico , Análisis Citogenético , Femenino , Humanos , Leucemia Mieloide Aguda/epidemiología , Leucocitos/metabolismo , Leucocitosis/epidemiología , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
Data from 42 adult patients with newly diagnosed minimally differentiated (M0) acute myeloid leukemia (AML) were reported. Clinical and biological characteristics at diagnosis were heterogenous. All patients received induction chemotherapy combining an anthracycline with cytarabine. Complete remission (CR) was achieved in 22 cases (52%). Most patients received continuation chemotherapy. Median disease-free survival (DFS) was 13.6 months with a 2-year survival rate of 28%. As post-remission therapy, 7 patients could be allografted and showed an encouraging outcome. Overall, 14 patients have relapsed (63%) after a median time of 10.2 months. Median overall survival (OS) was 20.5 months with a 5-year survival rate of 18%. This retrospective analysis points to a somewhat heterogenous group of AML in terms of biological features and outcome, and warrants a larger multicenter study with study in molecular biology to clarify treatment effects further.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Diferenciación Celular , Leucemia Mieloide Aguda/mortalidad , Leucemia Mieloide Aguda/patología , Adulto , Anciano , Antraciclinas/administración & dosificación , Citarabina/administración & dosificación , Femenino , Estudios de Seguimiento , Humanos , Inmunofenotipificación , Cariotipificación , Leucemia Mieloide Aguda/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Tasa de Supervivencia , Resultado del Tratamiento , Adulto JovenRESUMEN
Dose intensity has been demonstrated to be one determinant for treatment efficacy in younger adults with high-risk (relapsed and refractory) acute myelogenous leukemia. Between 2000 and 2006, 56 patients entered the EMA 2000 study and received timed sequential reinduction chemotherapy. From 2004, chemotherapy was also followed by one subcutaneous dose of pegfilgrastim. Thirty-six patients reached a complete remission, while nine obtained a partial remission. Median time to granulocyte and platelet recovery was 34 and 38 days respectively. The major non-hematologic toxicities were severe infections but despite this 23 remitters could proceed to their post-remission treatment, although 13 did not because of severe toxicity or early relapse. The median overall survival was 9.3 months. The EMA 2000 regimen is a highly effective treatment with a response rate of 64% and a low early death rate. The period of critical neutropenia was relatively short in both phases and the supportive use of pegfilgrastim, although showing a trend toward reduced neutropenic period, did not appear to reduce the risk of infection in this group and may not be a critical requirement for reducing the risk of treatment-related toxicity.
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Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Factor Estimulante de Colonias de Granulocitos/administración & dosificación , Leucemia Mieloide Aguda/sangre , Leucemia Mieloide Aguda/tratamiento farmacológico , Neutropenia/tratamiento farmacológico , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Citarabina/administración & dosificación , Citarabina/efectos adversos , Esquema de Medicación , Etopósido/administración & dosificación , Etopósido/efectos adversos , Femenino , Filgrastim , Humanos , Masculino , Persona de Mediana Edad , Mitoxantrona/administración & dosificación , Mitoxantrona/efectos adversos , Neutropenia/inducido químicamente , Polietilenglicoles , Pronóstico , Proteínas Recombinantes , Inducción de Remisión , Análisis de Supervivencia , Resultado del Tratamiento , Adulto JovenRESUMEN
BACKGROUND: Epigenetic deregulation of gene expression is a newly recognized mechanism that leads to hematologic malignancies such as leukemia and myelodysplastic syndromes. DNA methylation is one of the most commonly occurring epigenetic events. OBJECTIVE/METHODS: The rationale and use of hypomethylation agents in adult acute myeloid leukemia are discussed. Data in this review came from the published literature. RESULTS/CONCLUSION: In leukemias, alterations in DNA methylation are characterized by the hypermethylation of several genes. Hypermethylation represses transcription of the promoter regions of tumor suppressor genes leading to gene silencing. This change is reversible making it an important therapeutic target. Drugs such as methyltranferase inhibitors including 5-azacytidine and 5-aza-2'-deoxycytidine, and histone deacetylase inhibitors are being used in the treatment of these hematological malignancies.
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BACKGROUND: The poor prognosis for elderly patients with acute myeloid leukemia (AML) raises questions regarding the benefit of treating them with intensive chemotherapy. The impact of initial characteristics on prognosis has been addressed previously in elderly patients; however, very few data are available regarding the prognostic value of immunophenotypic characteristics in this setting. METHODS: The authors investigated expression of the membrane antigens CD13, CD15, CD33, and CD34 by flow cytometry in elderly patients with newly diagnosed AML and analyzed whether these parameters had clinical or prognostic relevance to help physicians in their choice of therapy. RESULTS: Immunophenotyping was performed in 273 patients aged > or =60 years (median age, 69 years). CD13 was expressed in 73% of patients, CD15 was expressed in 43% of patients, CD33 was expressed in 64% of patients, and CD34 was expressed in 66% of patients. Complete remission was obtained in 157 patients (58%). The median overall survival was 8.1 months, and the 3-year survival rate was 14%. Three risk groups were defined based on CD34 and CD33 antigen expression: The poor-risk group included patients with CD34-positive/CD33-positive or CD34-negative/CD33-negative disease, the intermediate-risk group included patients with CD34-positive/CD33-negative disease, and the favorable-risk group included patients with CD34-negative/CD33-positive disease. After cytogenetic analyses, immunophenotype was the most significant prognostic factor in terms of survival in a multivariate analysis (P = .03 and P < .0001, respectively). When immunophenotypic and cytogenetic parameters were combined, patients were classified into 4 prognostic groups: Group A (3-year survival rate, 33%) included patients with favorable and normal karyotypes who had a favorable immunophenotype, Group B (3-year survival rte, 28%) included patients with normal karyotypes who had an intermediate immunophenotype, Group C (3-year survival rate, 8%) included patients with intermediate or normal karyotypes who had an unfavorable immunophenotype, and Group D (3-year survival rate, 2%) included all patients who had unfavorable cytogenetics. CONCLUSIONS: Immunophenotypic characteristics appeared to be a major prognostic factor in this population of elderly patients with AML. By using 2 simple parameters assessed at the time of diagnosis, the authors devised a prognostic system of immediate clinical utility for prognostic stratification and risk-adapted therapeutic choices.
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Antígenos CD34/metabolismo , Antígenos CD/metabolismo , Antígenos de Diferenciación Mielomonocítica/metabolismo , Antígenos CD13/metabolismo , Inmunofenotipificación/métodos , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/inmunología , Antígeno Lewis X/metabolismo , Anciano , Anciano de 80 o más Años , Antineoplásicos/uso terapéutico , Médula Ósea/inmunología , Médula Ósea/patología , Quimioterapia , Femenino , Estudios de Seguimiento , Humanos , Cariotipificación , Leucemia Mieloide Aguda/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Análisis Multivariante , Pronóstico , Lectina 3 Similar a Ig de Unión al Ácido Siálico , Análisis de Supervivencia , Resultado del TratamientoRESUMEN
We retrospectively assess the long-term outcome and determined prognostic factors correlated with outcomes in adults with acute myeloid leukemia (AML) undergoing autologous hematopoietic stem cell transplantation (HSCT) in our institution over a 19-year period. A total of 78 adults who received autologous HSCT for AML in first complete remission (CR) and of 21 adults in further CR were included in the study. Bone marrow (n = 14) or peripheral blood stem cells (PBSC) (n = 85) transplantation was performed at a median of 2.9 months from CR. Hematologic recovery was significantly reduced in the PBSC group. Five-year cumulative incidences of relapse were 56 and 49%, respectively. Corresponding 5-year probabilities of event-free survival (EFS) were 33 and 35%, while those of overall survival (OS) were 38 and 49%, respectively. In multivariate analyses, cytogenetics was the main prognostic factor for outcome. Treatment-related mortality (TRM) was of 15% at 5 years, but higher in females as compared to males (p = 0.04). We confirmed that long-term EFS can be achieved after autologous HSCT in adult patients with AML. Results in adults who experience a relapse after conventional chemotherapy support the use of autologous HSCT as salvage therapy if such patients achieve a subsequent CR.
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Trasplante de Médula Ósea/estadística & datos numéricos , Leucemia Mieloide/cirugía , Trasplante de Células Madre de Sangre Periférica/estadística & datos numéricos , Terapia Recuperativa , Enfermedad Aguda , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Trasplante de Médula Ósea/mortalidad , Terapia Combinada , Supervivencia sin Enfermedad , Femenino , Humanos , Incidencia , Estimación de Kaplan-Meier , Leucemia Mieloide/tratamiento farmacológico , Leucemia Mieloide/epidemiología , Leucemia Mieloide/mortalidad , Masculino , Persona de Mediana Edad , Trasplante de Células Madre de Sangre Periférica/mortalidad , Recurrencia , Inducción de Remisión , Estudios Retrospectivos , Acondicionamiento Pretrasplante/efectos adversos , Trasplante Autólogo , Resultado del TratamientoRESUMEN
Following a dose-escalation study performed to assess the maximally tolerated dose of high-dose mitoxantrone in a single injection combined with chemotherapy, a phase II trial (EMA 2000 regimen) was performed in patients with refractory or relapsed acute myelogenous leukemia (AML) between October 2000 and December 2003. Sixty-two patients entered the study and received mitoxantrone 45 mg/m(2) on day 1 in combination with cytarabine and etoposide. Overall, 39 patients (63%) achieved complete remission (CR). Four patients died during remission induction, and 19 patients had resistant disease. Median time to granulocyte and platelet recovery was 34 and 39 days, respectively. The predominant non-hematologic toxicity was infection, with 53% severe infections. Thirty-three of the 39 remitters received subsequent treatment consisting of maintenance chemotherapy courses in 17 patients, allogeneic stem cell transplantation (SCT) in 7 patients, and autologous SCT in 9 patients. The median overall survival of the entire cohort was 8.1 months, with 18% at 2.5 years. EMA chemotherapy using a single injection of mitoxantrone is effective in the treatment of high-risk AML. CR proportion was significantly higher in patients with a first CR duration > or =6 months when compared with those from a control trial using standard-dose mitoxantrone (90 vs 70%, p=0.03).
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Leucemia Mieloide/tratamiento farmacológico , Enfermedad Aguda , Adolescente , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Trasplante de Médula Ósea , Terapia Combinada , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Femenino , Estudios de Seguimiento , Enfermedades Gastrointestinales/inducido químicamente , Enfermedades Hematológicas/inducido químicamente , Humanos , Infecciones/etiología , Infusiones Intravenosas , Leucemia Mieloide/mortalidad , Leucemia Mieloide/terapia , Tablas de Vida , Masculino , Persona de Mediana Edad , Mitoxantrona/administración & dosificación , Pronóstico , Inducción de Remisión , Riesgo , Estomatitis/inducido químicamente , Análisis de Supervivencia , Resultado del TratamientoRESUMEN
BACKGROUND: Acute leukemia (AL) requiring cytotoxic treatment occurring during pregnancy poses a very difficult therapeutic dilemma. METHODS: By means of a mail questionnaire, information on a series of 37 patients with a diagnosis of AL during pregnancy was collected from 13 French centers between December, 1988 and November, 2003. RESULTS: Thirty-one patients had acute myeloid leukemia (AML), and 6 patients had acute lymphoblastic leukemia (ALL). Nine patients were diagnosed during the first trimester, 10 patients were diagnosed during the second trimester, and 18 patients were diagnosed during the third trimester. Fifteen pregnancies ended with therapeutic or spontaneous abortion. There were 13 normal deliveries, including 1 gemellary pregnancy, and 9 Cesarean sections. Twenty-three healthy babies survived from the 37 pregnancies, of whom 15 babies had been exposed to chemotherapeutic agents. A complete remission was achieved in 34 patients. Eleven women had severe extrahematologic complications during the induction remission course. The median disease-free survival (DFS) was not reached, with a 5-year DFS of 54%. Ten patients developed recurrent disease. Overall, 12 of 37 pregnant women died from leukemia. CONCLUSIONS: Pregnancy does not affect the course of AL. In the first trimester, termination of pregnancy should be discussed because of the potential fetal consequences of chemotherapy. Chemotherapy treatment during the second or third trimester may not require termination of pregnancy, because as remission of AL and delivery of a normal infant are likely to be obtained.