RESUMO
The LAM2001 phase 3 trial, involving 832 patients with acute myeloid leukemia (AML; median: 46 years) proposed HLA-identical sibling allograft HSCT for all patients with an identified donor. The trial compared reduced-intensity conditioning (RIC) for patients older than 50 years of age (N = 47) and myeloablative conditioning for younger patients (N = 117). BM HSCT was performed in the younger patients, while the older ones received a consolidation course, followed by peripheral blood allo-HSCT using RIC. The incidence of grade II-IV acute GVHD, was 51.9% (95% confidence interval [CI]: 42.1-61.8) and 11.3% (1.6-21.2) after myeloablative or RIC, respectively (P < .0001) and that of chronic GVHD 45.8% (95% CI: 34.8-56.7) and 41.7% (24.7-58.6; NS). Cumulative incidence of nonrelapse mortality at 108 months was 15.8% (95% CI: 9.8-23.2) for myeloablative, and 6.5% (0.2-16.2) for RIC (NS). CI of relapse at 108 months was 21.7% (95% CI: 13.9-28.6) and 28.6% (16.5-43.4; NS). Overall survival at 108 months was 63.4% (95% CI: 54.6-72.2) and 65.8% (52.2-72.2), respectively, after myeloablative or RIC (NS). RIC peripheral blood stem cell allo-HSCT is prospectively feasible for patients between the ages of 51 and 60 years without excess of relapse or nonrelapse mortality, and compares favorably with myeloablative marrow allo-HSCT proposed to younger patients.
Assuntos
Doença Enxerto-Hospedeiro/epidemiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/métodos , Leucemia Mieloide Aguda/cirurgia , Condicionamento Pré-Transplante/métodos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Transplante de Medula Óssea/efeitos adversos , Transplante de Medula Óssea/métodos , Transplante de Medula Óssea/mortalidade , Feminino , Doença Enxerto-Hospedeiro/mortalidade , Transplante de Células-Tronco Hematopoéticas/mortalidade , Humanos , Incidência , Estimativa de Kaplan-Meier , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/mortalidade , Masculino , Pessoa de Meia-Idade , Transplante de Células-Tronco de Sangue Periférico/efeitos adversos , Transplante de Células-Tronco de Sangue Periférico/métodos , Transplante de Células-Tronco de Sangue Periférico/mortalidade , Modelos de Riscos Proporcionais , Indução de Remissão , Irmãos , Condicionamento Pré-Transplante/mortalidadeRESUMO
BACKGROUND: The short-term effects of granulocyte-colony-stimulating factor (G-CSF) have been extensively studied, but recent reports of G-CSF-induced genetic perturbations raised concerns regarding its long-term safety. In this respect, duration of G-CSF-induced perturbations has been less studied than short-term effects and needs to be evaluated. STUDY DESIGN AND METHODS: G-CSF mobilization-induced immunologic alterations were prospectively analyzed in a cohort of 24 healthy donors. Blood samples were taken before G-CSF administration; at the time of administration; and at 1, 3, 6, and 12 months and analyzed for blood cell counts and in vitro cytokines (interleukin [IL]-2, -8, and -10) and immunoglobulin production, quantified in the culture supernatant of peripheral blood mononuclear cells (PBMNCs) after, respectively, phytohemagglutinin and pokeweed mitogen stimulation. RESULTS: Platelet, granulocyte, monocyte, B, and dendritic blood cell counts as well as the IL-2, -8, and -10 secretion by PBMNCs, perturbed at the time of G-CSF mobilization, returned to baseline values at 1 month, with T-cell and natural killer cell counts recovering at 3 months. In vitro immunoglobulin production was increased up to 6 months after mobilization. CONCLUSION: Although assessment of the potential long-term risk of G-CSF administration will require prolonged observation of larger cohorts, our data show that the duration of immunologic perturbations may be more persistent than previously anticipated, especially for B-cell functional alterations. Most perturbations remain, however, transient with a return to baseline values within 1 year.
Assuntos
Doadores de Sangue , Fator Estimulador de Colônias de Granulócitos/farmacologia , Mobilização de Células-Tronco Hematopoéticas/métodos , Doenças do Sistema Imunitário/fisiopatologia , Leucaférese/métodos , Linfócitos/fisiologia , Adulto , Movimento Celular/efeitos dos fármacos , Movimento Celular/imunologia , Feminino , Seguimentos , Fator Estimulador de Colônias de Granulócitos/efeitos adversos , Mobilização de Células-Tronco Hematopoéticas/efeitos adversos , Células-Tronco Hematopoéticas/efeitos dos fármacos , Células-Tronco Hematopoéticas/fisiologia , Humanos , Doenças do Sistema Imunitário/sangue , Doenças do Sistema Imunitário/induzido quimicamente , Doenças do Sistema Imunitário/imunologia , Linfócitos/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Proteínas Recombinantes , Recuperação de Função Fisiológica/imunologia , Fatores de Tempo , Adulto JovemAssuntos
Aneuploidia , Fator Estimulador de Colônias de Granulócitos/efeitos adversos , Mobilização de Células-Tronco Hematopoéticas/métodos , Células-Tronco Hematopoéticas/efeitos dos fármacos , Leucemia/patologia , Adulto , Antígenos CD34/metabolismo , Divisão Celular , Feminino , Fator Estimulador de Colônias de Granulócitos/administração & dosagem , Células-Tronco Hematopoéticas/citologia , Células-Tronco Hematopoéticas/fisiologia , Humanos , Hibridização in Situ Fluorescente , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
BACKGROUND AND OBJECTIVES: The aim of this study was first, to analyze the post-thaw progenitor assays usually performed on peripheral blood stem cell autografts and second, to achieve standardization with improved flow cytometric and CFU-GM assays. MATERIALS AND METHODS: In the first part of the study (n=79), recovery and Intraclass Correlation Coefficient (ICC) of total nucleated cells, CD34 and CFU-GM were analyzed before and after cryopreservation. In the second part (n=20), evaluation methods were modified : the washing step was suppressed in the flow cytometric method and 500 CD34 were plated compared to 4×10(4) total nucleated cells in the CFU-GM assay. The recovery rates were analyzed and the CFU-GM results were regarded as reliable when 30-100 colonies were observed, according to the manufacturer recommendation. RESULTS: The analysis of the first part showed an ICC that was perfect for total nucleated cells (0.93), substantial for CD34 (0.67) and fair for CFU-GM (0.25). Median CD34 recovery was 112.6% (29.9-222%). The CFU-GM median recovery was 31.7% (0.19-142%) leading to reliable results for 27 grafts. In the second part, the median CD34 recovery was 85.75% (54-99%). No recovery over 100% was observed. The CFU-GM assay led to 18 out of 20 evaluable autografts when 500 CD34 were seeded, compared to 10 out of 20 when total nucleated cell were seeded. CONCLUSION: Avoiding cell washing in the flow cytometric method limited the overestimate of the CD34 percentage. Plating 500 thawed CD34 improved reliability of the results and allowed a better standardization of the assay.
Assuntos
Antígenos CD34/análise , Ensaio de Unidades Formadoras de Colônias/métodos , Criopreservação , Citometria de Fluxo/métodos , Células-Tronco Hematopoéticas/citologia , Adolescente , Adulto , Idoso , Criança , Feminino , Transplante de Células-Tronco Hematopoéticas , Humanos , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
OBJECTIVE: The economic profile of acute myeloid leukaemia (AML) is badly known. The few studies published on this disease are now relatively old and include small numbers of patients. The purpose of this retrospective study was to evaluate the induction-related cost of 500 patients included in the AML 2001 trial, and to determine the explanatory factors of cost. SETTING: "Induction" patient's hospital stay from admission for "induction" to discharge after induction. METHOD: The study was performed from the French Public Health insurance perspective, restrictive to hospital institution costs. The average management of a hospital stay for "induction" was evaluated according to the analytical accounting of Besançon University Teaching Hospital and the French public Diagnosis-Related Group database. Multiple linear regression was used to search for explanatory factors. MAIN OUTCOME MEASURE: Only direct medical costs were included: treatment and hospitalisation. RESULTS: Mean induction-related direct medical cost was estimated at 41,852 ± 6,037, with a mean length of hospital stay estimated at 36.2 ± 10.7 days. After adjustment for age, sex and performance status, only two explanatory factors were found: an additional induction course and salvage course increased induction-related cost by 38% (± 4) and 15% (± 1) respectively, in comparison to one induction. These explanatory factors were associated with a significant increase in the mean length of hospital stay: 45.8 ± 11.6 days for 2 inductions and 38.5 ± 15.5 if the patient had a salvage course, in comparison to 32.9 ± 7.7 for one induction (P < 10â»4). This result is robust and was confirmed by sensitivity analysis. CONCLUSION: Consideration of economic constraints in health care is now a reality. Only the control of length of hospital stay may lead to a decrease in induction-related cost for patients with AML.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/economia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Custos Hospitalares , Hospitalização/economia , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/economia , Adolescente , Adulto , Distribuição de Qui-Quadrado , Ensaios Clínicos como Assunto/economia , Ensaios Clínicos Fase III como Assunto/economia , Custos e Análise de Custo , Custos de Medicamentos , Feminino , França , Humanos , Tempo de Internação/economia , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Modelos Econômicos , Estudos Multicêntricos como Assunto/economia , Programas Nacionais de Saúde/economia , Admissão do Paciente/economia , Alta do Paciente/economia , Estudos Retrospectivos , Terapia de Salvação/economia , Fatores de Tempo , Resultado do Tratamento , Adulto JovemRESUMO
A 26-year-old woman presented with a painful skin eruption which led to the diagnosis of acute myeloid leukemia. During chemotherapy, she developed an unusual orbital inflammation. Careful observation of the clinical course, computed tomography, and orbital biopsy were necessary to establish the diagnosis of dacryoadenitis associated with subcutaneous Sweet's syndrome. The skin eruption and the dacryoadenitis resolved rapidly with corticosteroid therapy. This is the first report of dacryoadenitis in the course of subcutaneous Sweet's syndrome.
Assuntos
Dacriocistite/diagnóstico , Leucemia Mieloide Aguda/diagnóstico , Síndrome de Sweet/diagnóstico , Corticosteroides/uso terapêutico , Adulto , Biópsia por Agulha , Dacriocistite/complicações , Dacriocistite/tratamento farmacológico , Feminino , Seguimentos , Humanos , Imuno-Histoquímica , Leucemia Mieloide Aguda/complicações , Leucemia Mieloide Aguda/terapia , Medição de Risco , Índice de Gravidade de Doença , Tela Subcutânea/patologia , Síndrome de Sweet/complicações , Síndrome de Sweet/tratamento farmacológico , Resultado do TratamentoRESUMO
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.
Assuntos
Leucemia/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Complicações Neoplásicas na Gravidez , Doença Aguda , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Feminino , Humanos , Leucemia Mieloide/tratamento farmacológico , Gravidez , Resultado da Gravidez , Trimestres da Gravidez , Indução de RemissãoRESUMO
The phosphoinositide 3-kinase (PI3K)/Akt signaling pathway has been shown to be frequently activated in blast cells from patients with acute myeloid leukemia (AML) and to contribute to survival and proliferation of these cells. Of the 8 distinct mammalian isoforms of PI3K, it is the class I PI3Ks (p110alpha, p110beta, p110gamma, and p110delta) that are responsible for Akt activation. It is not known which PI3K isoform is critical in AML. Here we show that the p110delta isoform of PI3K is consistently expressed at a high level in blast cells from AML, in contrast to the other class I isoforms, the expression of which was very variable among patients. IC87114, a p110delta-selective inhibitor, suppressed both constitutive and Flt-3-stimulated Akt activation in blasts to the same extent as Ly294002, an inhibitor of all PI3K isoforms. Moreover, IC87114 inhibited AML cell proliferation without affecting the proliferation of normal hematopoietic progenitor cells. These observations identify p110delta as a potential therapeutic target in AML.
Assuntos
Proliferação de Células , Leucemia Mieloide/enzimologia , Leucemia Mieloide/patologia , Fosfatidilinositol 3-Quinases/metabolismo , Doença Aguda , Adulto , Idoso , Classe I de Fosfatidilinositol 3-Quinases , Ativação Enzimática , Feminino , Humanos , Isoenzimas , Leucemia Mieloide/etiologia , Masculino , Pessoa de Meia-Idade , Fosfatidilinositol 3-Quinases/fisiologia , Fosforilação , Isoformas de Proteínas/fisiologia , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Proto-Oncogênicas/metabolismo , Proteínas Proto-Oncogênicas c-akt , Células Tumorais CultivadasRESUMO
BACKGROUND: The implementation of a quality-assurance program is a major requirement to ensure quality and safety of the final PBPC components intended for clinical use. It is not clear whether the quantification of CFU-GM and CD34+ cells should be done on fresh components and after cryopreservation, which better represents the actual composition of the graft. STUDY DESIGN AND METHODS: Correlation between prefreeze and postthaw MNCs, CD34+ cells, and CFU-GM collected from 126 patients undergoing BMT (n=43) or PBPC (n =83) transplantation were evaluated. The statistical incidence of prefreeze and postthaw parameters as well as patient characteristics and conditioning regimens on hematologic recovery were analyzed. RESULTS: By multivariate analysis, prefreeze and postthaw CD34+ cells were the only two variables significantly and independently correlated to hematologic recovery. Low prefreeze and postthaw CD34+ cell numbers associated to a low CD34+ yield characterize PBPC grafts from patients who have the slowest hematologic recovery. The postthaw PBPC CD34+ cell number can be estimated before conditioning regimen by thawing a small aliquot of the graft. CONCLUSION: In association to prefreeze CD34+ cell number and to CD34+ yield, postthaw CD34+ cell number may be useful in monitoring cell loss during processing and identifying patients at risk of slow PBPC engraftment.
Assuntos
Antígenos CD34/análise , Contagem de Células , Criopreservação , Células-Tronco Hematopoéticas/citologia , Transplante de Células-Tronco de Sangue Periférico , Adulto , Plaquetas/citologia , Transplante de Medula Óssea , Feminino , Citometria de Fluxo , Sobrevivência de Enxerto , Granulócitos/citologia , Hematopoese , Temperatura Alta , Humanos , Masculino , Transfusão de Plaquetas , Transplante Autólogo , Resultado do TratamentoRESUMO
Based on our previous demonstration that quinine could be used clinically to reverse P-glycoprotein-mediated resistance, we designed a multicenter, randomized trial aiming to determine whether quinine would improve the survival of adult patients (15-60 years old) with de novo acute myelogenous leukemia (AML). These patients randomly received (n = 213) or did not receive (n = 212) a 30 mg/kg/day continuous intravenous infusion of quinine in combination with induction chemotherapy combining idarubicine and cytarabine and, depending on bone marrow examination at day 20, an additional course of cytarabine and mitoxantrone. The mean steady-state quinine concentration was 7.8 mg/L and the mean multidrug resistance reversing activity of serum was 1.96. Complete remission (CR) was obtained in 344 patients (80.9%) without significant influence of quinine. Of the patients in complete remission, 82 were assigned to receive HLA-matched bone marrow transplants, whereas 262 were assigned to 2 courses of intensive consolidation chemotherapy, with or without quinine, depending on initial randomization. The 4-year actuarial overall survival (OS) of the 425 eligible patients was 42.0% +/- 2.5%, without significant influence of quinine. Of 160 patients who could be studied, 54 demonstrated rhodamine 123 efflux. In these patients, quinine significantly improved the CR rate from 12 of 25 (48.0%) to 24 of 29 (82.8%) (P =.01). However, there was no significant difference in OS. Neither mdr1 gene nor P-glycoprotein expression influenced the outcome. We conclude that quinine does not improve the survival of adult patients with de novo AML, even though it improves CR rate in a small subgroup of patients defined by rhodamine 123 efflux.