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1.
Transfus Clin Biol ; 25(4): 242-248, 2018 Nov.
Artigo em Francês | MEDLINE | ID: mdl-30145111

RESUMO

OBJECTIVE: One of the tasks of haemovigilance correspondents in Health Institutions (HI) is to reduce the destruction of labile blood components (LBC). The objective of this study was to analyse in depth, five years after a first multicentric study, the causes of LBC destruction in order to assess the impact of measures taken and to define new ways of improvement. METHODS: Prospective analysis was carried out throughout 2016. For every LBC destroyed, the following elements were reported: type of LBC, transfusion department, cause of destruction analysed according to a decision tree, subsequently classed as avoidable or unavoidable. RESULTS: The study included 15 HI. A total 3058 LBC were destroyed, representing an average 0.90% of issued LBC, and this analysis concerned 2576 LBC. Sixty-seven percent of LBC were issued for surgery, intensive care or emergencies. Forty percent of the causes of destruction were patient-related (death, clinical worsening, adverse effects or abnormal constants prior to delivery). Thirty percent were prescription-related, mainly cases of excessive prescription for different reasons. Eleven percent were linked to organisational issues. The rate of destruction judged avoidable, all causes combined, was 36%. CONCLUSION: Comparison with the precedent study shows improvement, thus revealing the efficacy of implemented measures (single-dose distribution, return procedures back to the site of distribution, training of participants). In order to further reduce this rate of destruction, we suggest to promote storage procedures and, above all, to continue to raise awareness within healthcare teams.


Assuntos
Bancos de Sangue/estatística & dados numéricos , Segurança do Sangue , Transfusão de Sangue/estatística & dados numéricos , Bancos de Sangue/normas , Transfusão de Sangue/normas , Humanos , Estudos Prospectivos
2.
Transfus Clin Biol ; 25(1): 8-13, 2018 Feb.
Artigo em Francês | MEDLINE | ID: mdl-29273503

RESUMO

The decision of November 6th, 2006 defining the principles of best practices recommends that posttransfusional red cell alloantibodies research is performed after one to three months after. In the University hospital of Brest, the haemovigilance unit takes charge of sending the medical prescription within the required time and centralizing the results. We wished to estimate if the realization of this research still remains relevant. METHODS: A prospective analysis was performed in 2015. We evaluated the realization rate, the red cell alloantibodies rate and the recipient adverse reactions with the diagnostic category: alloimmunization (delayed serological transfusion reaction, DSTR). RESULTS: In 2015, 2162 prescriptions were sent to the 3271 transfused patients. One thousand and eighteen red cell alloantibodies research were done, i.e. a return rate of 61%. Among them, 12 alloantibodies appeared (0.9%) within an average of 56 days. Thirty-three other alloantibodies appeared and were discovered most frequently before a new transfusion. In 10 cases, a posttransfusional research was done that was negative. A survey was conducted among GHCOH members to describe the practices in these health institutions. Twelve questionnaires were analysed. Ten institutions performed a posttransfusional alloantibodies research by issuing a prescription at the patient's exit with a return rate between 0.14 and 16%; 1 institution has a centralized organization with a return rate of 68.3%; 1566 red cell alloantibodies research were performed and among them, 24 alloantibodies appeared (1.53%). CONCLUSION: These results indicate that to be effective, the management of this biological test must be centralized. Despite this, the red cell alloantibodies rate remains very low (0.9 and 1.53%) and raises the question of the relevance of this systematic testing after transfusion, which is in any case mandatory before a new transfusion of red blood cells.


Assuntos
Segurança do Sangue/métodos , Transfusão de Sangue/legislação & jurisprudência , Isoanticorpos/sangue , Antígenos de Grupos Sanguíneos/imunologia , Segurança do Sangue/economia , Segurança do Sangue/normas , Custos e Análise de Custo , Membrana Eritrocítica/imunologia , França , Hospitais Universitários , Humanos , Imunização , Isoanticorpos/biossíntese , Isoanticorpos/imunologia , Guias de Prática Clínica como Assunto , Prevalência , Estudos Prospectivos , Inquéritos e Questionários , Fatores de Tempo , Reação Transfusional/epidemiologia , Reação Transfusional/imunologia , Reação Transfusional/prevenção & controle
3.
Transfus Clin Biol ; 16(1): 21-9, 2009 Mar.
Artigo em Francês | MEDLINE | ID: mdl-19318287

RESUMO

During the years 1994-2001, a progressive decrease of the number of blood units transfused has been reported in France. In contrast, since 2002, there is an increasing number of blood units issuing (+7.6% between 2001 and 2006) and this must be investigated. On behalf of the French Society of Blood Transfusion, the "Recipients" working group promoted a nation wide survey with the support of the regional blood transfusion centres. This survey was aimed at describing the profiles of the transfused patients: socio-demographical patterns, and reasons of the blood transfusion (main and associated diagnoses). A cross-sectional survey was designed. All the patients who received a blood unit during a specific day were considered as the population of the study. They were identified by the regional transfusion centres by means of the "individual issuing form". Survey forms were fully filled for 90% of the patients. It has been considered as a good answer rate. Seven thousand four hundred and twenty-two blood units, delivered to 3450 patients were analyzed. Three groups of pathologies were found as a reason of transfusion: haematology-oncology (52.70% of the prescriptions) with 892 patients (27.8%) for haematological malignancies; surgical procedures (23.99%); intensive care and medicine procedures (21.92%). More than 50% of the recipients are 70 years old and more. This result is explained by the age distribution of inpatients. In a context of lack of donors and consequently difficulties to provide patients with optimal number of blood units, this study is helpful. Variability of blood unit issuings must be detected, analyzed and monitored in real time by the actors of the transfusion process, using computerized dashboards: the blood units provider (in order to adjust the strategy of blood units provision) and the health care establishment as well as care blood components prescribers (reasons of blood transfusion and evaluation of practices).


Assuntos
Bancos de Sangue/estatística & dados numéricos , Transfusão de Sangue/estatística & dados numéricos , Instalações de Saúde/estatística & dados numéricos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Estudos Transversais , Grupos Diagnósticos Relacionados , Feminino , França , Pesquisas sobre Atenção à Saúde , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Adulto Jovem
4.
Leukemia ; 12(9): 1447-56, 1998 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-9737695

RESUMO

The aim of the study was to analyze the factors influencing peripheral blood progenitor cell (PBPC) collection after high-dose cyclophosphamide (HDCYC) (7 g/m2) and hematopoietic recovery after autologous transplantation of HDCYC-mobilized PBPC (ABPCT) in 116 patients with aggressive multiple myeloma (MM). Following HDCYC 74 patients received hematopoietic growth factors (HGF), either G-CSF (n = 19) or GM-CSF (n = 55). All the patients were subsequently planned to undergo ABPCT. PBPC collection was possible for 106 patients. The most important prognostic factor for collection of more than 25 x 10(4) CFU-GM cells/kg and 2 x 10(6) CD34+ cells/kg was the use of HGF (P = 0.002 and 0.009, respectively). Previous use of an alkylating agent, response to treatment before HDCYC, and interval between diagnosis and HDCYC were also significant factors (P = 0.004, 0.025 and 0.001, respectively). The number of CFU-GM cells infused was the most important parameter for rapid and complete hematological recovery after ABPCT (P < 0.0001). Thus the use of HGF post-HDCYC is the major factor which, associated with reduced time between diagnosis and HDCYC and the use of an alkylating agent, could increase the numbers of hematopoietic progenitors collected, and subsequently improve hematopoietic recovery following ABPCT in MM patients.


Assuntos
Antineoplásicos/administração & dosagem , Ciclofosfamida/administração & dosagem , Mobilização de Células-Tronco Hematopoéticas , Transplante de Células-Tronco Hematopoéticas , Mieloma Múltiplo/sangue , Mieloma Múltiplo/terapia , Adulto , Idoso , Análise de Variância , Feminino , Humanos , Leucaférese , Masculino , Pessoa de Meia-Idade , Transplante Autólogo
5.
Bone Marrow Transplant ; 18(5): 955-9, 1996 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-8932851

RESUMO

Changes in endothelial cell activity are likely to play a role in the thrombotic complications of bone marrow transplantation (BMT) such as the development of veno-occlusive disease. Accordingly, we measured established plasma endothelial cell markers von Willebrand factor (vWf), soluble thrombomodulin (sTM), soluble ICAM-1 (sICAM-1), and possible inducers of these molecules, TNF alpha and elastase, in the plasma of 25 patients, 1 week before as well as 1 and 3 weeks after BMT. Compared to healthy age and sex-matched controls, patients exhibited increased vWf and sTM. One week after transplantation, there were significant increases in vWf and sICAM-1, with a significant fall in elastases. Three weeks after the transplantation, sICAM-1 and, to a lesser extent, vWf increased still further, whereas elastases were unchanged. There were no significant changes in sTM and in TNF alpha through the serial study. Our data suggest that before conditioning, vascular endothelium is damaged by both injury and activation, as seen by the variations of vWf and sTM. After transplantation, the enhancement of this damage seems to be more specifically related to activation, since we observed a strong subsequent increase in vWf and markedly in sICAM-1.


Assuntos
Transplante de Medula Óssea/efeitos adversos , Endotélio Vascular/patologia , Molécula 1 de Adesão Intercelular/análise , Trombomodulina/análise , Fator de von Willebrand/análise , Adolescente , Adulto , Biomarcadores , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Elastase Pancreática/análise , Fator de Necrose Tumoral alfa/análise
6.
Leuk Res ; 20(6): 481-9, 1996 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-8709620

RESUMO

Twenty-three patients with acute myelogenous leukemia (AML) in first relapse were treated with high-dose cytosine-arabinoside (Ara-C) and amsacrine or idarubicin. To prime the cells, the patients were given rhGM-CSF. We studied the influence of 48-h infusion of rhGM-CSF on proliferation and Ara-C sensitivity of leukemic cells both ex vivo and in vitro. We found that a 48-h infusion of rhGM-CSF increased both white blood cell counts and peripheral blood blast cell percentages. Using a Bromodeoxyuridine/DNA (BrdUrd/DNA) staining in flow cytometry, we found an non-constant increase in cells in the S-phase. Ex vivo 48-h culture of leukemic cells with or without rhGM-CSF, with or without other hematopoietic growth factors (HGFs), showed a greater increase of the cells in the S-phase with GF but no correlation with the ex vivo results. We used a method of quantitation of the DNA synthesis previously described (Lacombe F., et al. (1992) Cytometry 13, 730) to monitor the Ara-C sensitivity of the cells in S-phase before and after 48-h infusion with rhGM-CSF. We observed a great variation in the Ara-C sensitivity of the leukemic cells before and after infusion with rhGM-CSF from one patient to another. The BrdUrd/DNA method seems a convenient method to study the influence of HGFs on Ara-C sensitivity of the patients.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Leucemia Mieloide/tratamento farmacológico , Doença Aguda , Adolescente , Adulto , Idoso , Bromodesoxiuridina/análise , Ciclo Celular , Citarabina/administração & dosagem , DNA de Neoplasias/análise , Relação Dose-Resposta a Droga , Interações Medicamentosas , Resistencia a Medicamentos Antineoplásicos , Ensaios de Seleção de Medicamentos Antitumorais , Feminino , Citometria de Fluxo , Fator Estimulador de Colônias de Granulócitos e Macrófagos/administração & dosagem , Humanos , Leucemia Mieloide/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Proteínas Recombinantes/administração & dosagem , Fase S/efeitos dos fármacos
7.
J Clin Oncol ; 14(4): 1306-13, 1996 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-8648388

RESUMO

PURPOSE: The aims of the current study were to evaluate in patients with high-risk multiple myeloma (MM) the feasibility and usefulness of high-dose chemotherapy or chemoradiotherapy followed by hematopoietic stem-cell support with autologous peripheral-blood progenitor cells (PBPC) harvested after high-dose cyclophosphamide (HDCYC). PATIENTS AND METHODS: Seventy-three patients with high-risk MM were entered onto the study. Before the procedure, all patients had received HDCYC to collect PBPC by leukapheresis. One patient died of infection after HDCYC. All other patients subsequently received high-dose melphalan (HDM) (140 mg/m2) either alone (n = 1) or associated with either busulfan (16 mg/kg; n = 4) or total-body irradiation (TBI) (8 to 15 Gy; n= 67). In addition, three of the latter patients received cyclophosphamide (120 mg/kg). Thereafter, PBPC were reinfused either alone in 61 patients or together with back-up bone marrow cells in 11 patients in whom the granulocyte-macrophage colony-forming unit (CFU-GM) cell content of the leukapheresis was low. RESULTS: One patient died of acute cardiac failure after reinfusion of PBPC; three patients did not respond after autologous blood progenitor cell transplantation (ABPCT), while the other 68 patients achieved either a complete response (CR; n = 32) or partial response (PR; n = 36). Thirty-six patients relapsed or progressed after a median response duration of 14.5 months (range, 3 to 43) and 19 of these subsequently died. Four other patients died while still responsive of lung cancer (n = 1) or infection (n = 3). The remaining 28 patients are currently alive and still responding with a median follow-up duration of 27 months (range, 6 to 66). The 3-year probability of survival was 66% +/- 12% (95% confidence interval [CI] after ABPCT and 77% +/- 51% (95% CI) from diagnosis. CONCLUSION: High-dose chemotherapy or chemoradiotherapy followed by autologous PBPC support in MM is feasible and efficient. Further studies are needed to confirm these encouraging, although preliminary, results and to compare this technique with other therapeutic strategies.


Assuntos
Antineoplásicos Alquilantes/uso terapêutico , Transplante de Células-Tronco Hematopoéticas , Mieloma Múltiplo/cirurgia , Adulto , Idoso , Análise de Variância , Bussulfano/administração & dosagem , Quimioterapia Adjuvante , Ciclofosfamida/administração & dosagem , Estudos de Viabilidade , Feminino , Humanos , Masculino , Melfalan/administração & dosagem , Pessoa de Meia-Idade , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/radioterapia , Prognóstico , Modelos de Riscos Proporcionais , Dosagem Radioterapêutica , Radioterapia Adjuvante , Fatores de Risco , Análise de Sobrevida , Transplante Autólogo , Resultado do Tratamento
8.
Rev Prat ; 46(1): 62-8, 1996 Jan 01.
Artigo em Francês | MEDLINE | ID: mdl-8596894

RESUMO

The treatment of acute myeloid leukaemia in adults is based on chemotherapy which is divided in two phases: induction (to achieve a complete remission) and post-induction treatment (to maintain the complete remission). Induction chemotherapy usually combines cytosine arabinoside and one anthracycline. The complete remission rate which varies from 50 to 90% is mainly influenced by the age of patients, the presence of certain cytogenetic abnormalities or the presence of a preleukaemic phase. The efficacy of post-induction treatments remains controversial. Maintenance treatment (with low-dose chemotherapy) has probably a marginal efficacy. More intensive (as intensive as induction chemotherapy) chemotherapies seems capable to prolong survival but can only be applied to the youngest patients. The rate of 5-years survivors is about 30-45% and influenced by a very low numbers of factors. The treatment of relapses is very difficult and seems to prolong survival only when the duration of the first remission has been longer than 18 months. In other cases, it can be justified to restrict the treatment to transfusions and oral chemotherapy.


Assuntos
Leucemia Mieloide/tratamento farmacológico , Doença Aguda , Adulto , Fatores Etários , Humanos , Pessoa de Meia-Idade , Prognóstico , Recidiva , Indução de Remissão
9.
Ann Fr Anesth Reanim ; 15(8): 1219-29, 1996.
Artigo em Francês | MEDLINE | ID: mdl-9636798

RESUMO

New agents such as recombinant human erythropoietin (rHu EPO) modify conventional transfusionnal strategies. For accurate indications, such as, anaemia associated with chronic renal failure, cancer or cardiac disease, the preoperative prescription of rHu EPO may reduce transfusion requirements. rHu EPO may also be associated with pre-deposit transfusion in patients with anaemia before blood donation, when the transfusion needs are high, or the period for blood pre-deposit donation shortened. Postoperatively rHu EPO is only efficient if it is administered for a prolonged period; this condition limits its indications and value because of its high cost.


Assuntos
Transfusão de Sangue/métodos , Procedimentos Cirúrgicos Eletivos , Eritropoetina/uso terapêutico , Aprotinina/administração & dosagem , Transfusão de Sangue/economia , Hemostáticos/administração & dosagem , Humanos , Substitutos do Plasma/administração & dosagem , Guias de Prática Clínica como Assunto , Cuidados Pré-Operatórios/métodos , Proteínas Recombinantes
10.
Leukemia ; 9(12): 1997-2002, 1995 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-8609708

RESUMO

To improve the management of chronic myeloid leukemia (CML) in a single center, we used interferon alpha (IFN alpha) to treat newly diagnosed CML patients and investigated the factors predictive of a major cytogenetic response. Fifty-two patients (pts) with a median age of 51.5 years (16-68), were given interferon alpha (IFN alpha) (5 millions/m2/day, subcutaneously). The median interval between diagnosis and IFN alpha was 41.5 days (0-160). The doses of INF alpha were adjusted to maintain the white blood cell (WBC) count between 1.5 and 5 x 10(9)/l and the platelet count between 50 and 100 x 10(9)/l. At diagnosis, Sokal's criteria were used to classify patients into three groups: low (n = 24), intermediate (n = 19) and high risk (n = 9). A complete hematological response (CHR) was achieved in 42 cases (80.7%). A partial response was present in nine; only one patient did not respond. By multivariate logistic regression analysis, only the age at diagnosis was found to influence the CHR rate (P = 0.06). Cytogenetic response was evaluated in 46 responder patients. Twenty-three patients achieved a major cytogenetic response (MCR) which was either partial ( > or = 65% pH negative cells) (n = 3) or complete (CCR) (n = 20). By univariate analysis, two disease-related variables were found to influence the MCR rate in 40 evaluable CHR patients: spleen size at diagnosis and peripheral blood blast percentage. However, using either univariate or multivariate analysis, the most significant factor was the achievement of CHR within 3 months (P < 0.0004 and P < 0.0002, respectively). These results show that IFN alpha can induce high rates of hematological and cytogenetic responses when administered in doses leading to myelosuppression. The achievement of CHR within 3 months could be useful to identify early, those patients who will not respond to IFN alpha and who need alternative treatments such as allogeneic or autologous stem cell transplantation.


Assuntos
Interferon Tipo I/administração & dosagem , Leucemia Mielogênica Crônica BCR-ABL Positiva/terapia , Adolescente , Adulto , Idoso , Feminino , Humanos , Injeções Subcutâneas , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Leucemia Mielogênica Crônica BCR-ABL Positiva/mortalidade , Masculino , Pessoa de Meia-Idade , Cromossomo Filadélfia , Valor Preditivo dos Testes , Proteínas Recombinantes , Análise de Regressão , Análise de Sobrevida
11.
Am J Clin Pathol ; 104(5): 495-502, 1995 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-7572808

RESUMO

To evaluate the leukocyte differential flags of the Cobas Argos 5 Diff., the authors performed a comparative study between their current analyzer, the Technicon H2, and the manual leukocyte differential. Samples (n = 1,600) were collected from the Blood Disease Department of their hospital and were tested on both Cobas Argos 5 Diff. (ABX/Roche Hematology Division, Montpellier, France) and Technicon H2. Abnormalities of the manual leukocyte differential (immature granulocytes, blast cells, atypical lymphocytes, hyperbasophil cells, erythroblasts, and hairy cells) were found in 597 samples. The authors determined the best cut-off of the quantitative flags--atypical lymphocytes (ALYs) and large immature cells (LICs)--using the likelihood ratio method, and the capability of the 5 Diff. qualitative flags to determine abnormal subpopulations by the predictive value of a positive result. The presence of particular combinations of flags was associated with band cells and blast cells of acute lymphoblastic leukemia (ALL) or acute myeloblastic leukemia (AML). The sensitivity, specificity, and efficiency of the two analyzers were 92.1, 53.9, and 68.2, respectively, for the Argos 5 Diff., and 93.5, 36.7 and 57.9, respectively, for Technicon H2. In conclusion, the Cobas Argos 5 Diff. is well adapted for detecting leukocyte abnormalities.


Assuntos
Contagem de Leucócitos/instrumentação , Contagem de Leucócitos/métodos , Interpretação Estatística de Dados , Estudos de Avaliação como Assunto , Humanos , Valor Preditivo dos Testes , Sensibilidade e Especificidade
12.
Stem Cells ; 13 Suppl 2: 160-3, 1995 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-8520506

RESUMO

The aim of the study was to evaluate the feasibility and the efficacy of high-dose chemoradiotherapy followed by autologous hematopoietic stem cell support with peripheral blood progenitor cells (PBPC) harvested after high-dose cyclophosphamide (HDCYC) treatment in patients with high-risk multiple myeloma (MM). Inclusion criteria were: age less than 65 years and high-risk MM defined as stage II MM, stage III MM, refractory or relapsed MM. The design of the study was: 1) HDCYC +/- hematopoietic growth factors followed by PBPC collection, and 2) high-dose melphalan combined with total body irradiation (or busulfan for previously irradiated patients) followed by PBPC reinfusion (ABPCT). All 60 patients completed the procedure except two who died from infection after HDCYC and another of acute cardiac failure after reinfusion of PBPC. Out of the 60 evaluable patients, three failed to respond while the other 57 achieved either a partial (n = 33) or complete (n = 24) response. Thirty-one patients progressed or relapsed after a median duration of response of 15 months (range: 3-43). The median follow-up for the other 26 responder patients was 24 months (range: 2-66). Twenty-one patients died, 18 of MM (2 after failure, 16 after relapse) and three responders of lung cancer (n = 1) and infection (n = 2). In conclusion, this study shows that this therapeutic approach is feasible and efficient.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Mieloma Múltiplo/terapia , Adulto , Idoso , Terapia Combinada , Ciclofosfamida/administração & dosagem , Feminino , Fatores de Crescimento de Células Hematopoéticas/administração & dosagem , Humanos , Masculino , Melfalan/administração & dosagem , Pessoa de Meia-Idade , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/radioterapia , Fatores de Risco , Análise de Sobrevida , Transplante Autólogo , Irradiação Corporal Total
13.
Bone Marrow Transplant ; 16(1): 69-70, 1995 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-7581131

RESUMO

We report our experience with 67 patients with myeloid malignancies (acute myeloid leukaemia (AML) or chronic myelogenous leukaemia (CML) conditioned with busulphan and melphalan as preparation for autologous haemopoietic cell transplantation. The major non-haematological toxicities were severe mucositis, nausea and vomiting, but the marrow aplasia was delayed and of short duration. The anti-tumor effect was appreciable with subsequent chronic phase (CP) obtained in 30/31 CML in transformation and complete remission (CR) obtained in 2/3 refractory AML. Among 32 patients treated while they had no evidence of active disease, 12 remained in CR or CP with a median follow-up of 54.7 months.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Transplante de Medula Óssea , Leucemia Mielogênica Crônica BCR-ABL Positiva/terapia , Leucemia Mieloide/terapia , Adolescente , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Bussulfano/administração & dosagem , Bussulfano/efeitos adversos , Terapia Combinada , Feminino , Humanos , Masculino , Melfalan/administração & dosagem , Melfalan/efeitos adversos , Pessoa de Meia-Idade
14.
Presse Med ; 24(17): 822-6, 1995.
Artigo em Francês | MEDLINE | ID: mdl-7543203

RESUMO

Haematopoietic colony-stimulating factors are a group of molecules that can stimulate haemopoiesis. With the advent of recombinant DNA technology and the cloning of their genes, they can be utilized against malignant blood diseases. They might be useful in therapy of acute myelogenous leukaemia either by increasing the efficacy of antileukaemic drugs or by shortening the duration of granulocytopoenia following chemotherapy or bone marrow transplantation. Encouraging results have been obtained, but stimulation of leukaemic cells is not ruled out. Further clinical and biological investigations are required to provide insight into the role of cytokines in treatment of acute myelogenous leukaemia.


Assuntos
Citarabina/uso terapêutico , Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Fator Estimulador de Colônias de Granulócitos e Macrófagos/uso terapêutico , Interleucina-3/uso terapêutico , Leucemia Mieloide Aguda/tratamento farmacológico , Amsacrina/uso terapêutico , Quimioterapia Combinada , Feminino , Humanos , Idarubicina/uso terapêutico , Masculino
15.
Bull Cancer ; 82(5): 349-56, 1995.
Artigo em Francês | MEDLINE | ID: mdl-7626842

RESUMO

Ara-C is currently used in the treatment of adult acute myeloid leukemia (AML). The cytotoxicity of Ara-C derives from an inhibition of DNA synthesis which can be determined using flow cytometry from the amount of bromodeoxyuridine (BrdUrd) incorporated into cells after a short exposure to BrdUrd. We developed a computer program to quantify inhibition of the rate of DNA synthesis by analysis of the distribution of BrdUrd/DNA. A resistance index (RI) was expressed as the ratio of the amount of BrdUrd incorporated into S phase cells incubated with Ara-C to that incorporated in the absence of Ara-C. In Ara-C sensitive and resistant HL60 cell lines, a linear relationship between RI and log Ara-C concentration was observed. This technique was applied to 96 bone marrow samples from patients with de novo AML treated by a regimen containing Ara-C. A first group of nine patients with high RI values included only drug resistant (DR) patients; a second group of 63 patients with low RI values included 62 patients who achieved a complete remission (CR); a third group of 24 patients with intermediate RI values included 19 CR and five DR patients. In view of these results, we think that it is possible to detect a majority of DR patients treated by Ara-C.


Assuntos
Citarabina/uso terapêutico , Citometria de Fluxo , Leucemia Mieloide Aguda/tratamento farmacológico , Adolescente , Adulto , Idoso , Ciclo Celular/efeitos dos fármacos , Células Clonais , Citarabina/farmacologia , DNA de Neoplasias/efeitos dos fármacos , Resistência a Medicamentos , Feminino , Humanos , Técnicas In Vitro , Leucemia Mieloide Aguda/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Indução de Remissão , Fase S , Células Tumorais Cultivadas/efeitos dos fármacos
16.
Blood Rev ; 8(4): 234-40, 1994 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-7888830

RESUMO

The rate of relapse after allogeneic bone marrow transplantation (BMT) varies between 15 and 60%. New therapeutic strategies are required urgently as no significant results have been obtained with standard chemotherapy. The best results of second allogeneic BMT have been obtained when the interval between the first and the second transplant was more than 6 to 20 months, depending on the study. Veno-occlusive disease was an important cause of non-leukemic death (13-65%). As the toxicity of second BMT is very high, other treatments have been considered: complete remissions were reported after sudden discontinuation of the immunosuppressive therapy. Interferon-alpha has been used for chronic myeloid leukemia patients and may achieve hematological and cytogenetic complete remission. More recently, donor leucocytes transfusions have been proposed and at least in some cases, have led to molecular complete remission (polymerase chain reaction with double amplification) in chronic myeloid leukemia patients. However, non predictable marrow aplasias and graft-versus-host reactions hamper the efficacy of this strategy. Finally, hemopoietic growth factors used to promote donor cell growth produce interesting results which deserve further studies.


Assuntos
Transplante de Medula Óssea , Leucemia/terapia , Linfoma/terapia , Terapia de Salvação , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Terapia Combinada , Intervalo Livre de Doença , Doença Enxerto-Hospedeiro , Fatores de Crescimento de Células Hematopoéticas/uso terapêutico , Humanos , Fatores Imunológicos/uso terapêutico , Interferon-alfa/uso terapêutico , Leucemia/mortalidade , Transfusão de Leucócitos , Linfoma/mortalidade , Prognóstico , Indução de Remissão , Reoperação , Falha de Tratamento
17.
Blood ; 84(3): 716-23, 1994 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-8043860

RESUMO

Cytarabine (Ara-C) is currently used in the treatment of adult acute myeloid leukemia (AML). To predict the results of induction chemotherapy, it could be useful to detect leukemic cells that are resistant to Ara-C in patients with AML. Using a bromodeoxyuridine/DNA (BrdUrd/DNA) staining method in flow cytometry (FCM), we have developed a cell resistance index to Ara-C (RI). The technique has been applied to 121 bone marrow (BM) samples from patients with de novo AML treated by a regimen containing Ara-C and daunorubicin (DNR). Ninety-seven patients achieved a complete remission (CR), and 24 patients did not and were considered drug-resistant (DR). The BM cells collected at diagnosis were cultured for 48 hours and underwent BrdUrd/DNA analysis. Among 25 patients with no or very low proliferative activity (<3% of cells in S-phase), the proportion of DR patients (nine of 25) was significantly higher than in a second group of 96 patients with detectable proliferative activity (15 of 96) (P < .025). Within this second group, there was a first group of nine patients with high RI values, which included only DR patients; a second group of 63 patients with low RI values, which included 62 CR patients; and a third group of 24 patients with intermediate RI values, which included 19 CR and five DR patients. In view of this series, our results show that it is possible to detect a majority of DR patients treated by Ara-C.


Assuntos
Citarabina/uso terapêutico , Leucemia Mieloide/tratamento farmacológico , Doença Aguda , Adolescente , Adulto , Idoso , Divisão Celular/efeitos dos fármacos , Células Clonais , Citarabina/farmacologia , Resistência a Medicamentos , Feminino , Citometria de Fluxo , Humanos , Leucemia Mieloide/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico
18.
Leuk Res ; 18(5): 313-8, 1994 May.
Artigo em Inglês | MEDLINE | ID: mdl-8182921

RESUMO

By using flow cytometry, the intracellular accumulation (Acc) of idarubicin (IDA) and daunorubicin (DNR) and the effect of verapamil (VRP) on both anthracycline accumulation (VRP index) were studied in leukemic cell lines (K562 and HL60 and their two DNR-resistant subclones) and fresh leukemic cells. IDA accumulated more than DNR in both parental (K562: p < 0.03 and HL60: 0.09) and resistant cell lines (p < 0.01 for both cell lines) irrespective of whether or not they were treated with VRP. VRP index was higher for DNR than for IDA (p < 0.05). Similar results were observed in fresh leukemic blasts from 25 patients with ANLL (IDA Acc superior to DNR Acc: p < 0.0001; higher VRP index for DNR than for IDA: p < 0.01). The higher Acc of IDA than DNR seen in fresh leukemic cells could explain the better clinical efficacy of IDA reported in patients with ANLL.


Assuntos
Daunorrubicina/farmacocinética , Idarubicina/farmacocinética , Leucemia Mieloide Aguda/metabolismo , Verapamil/farmacologia , Adolescente , Adulto , Resistência a Medicamentos , Feminino , Citometria de Fluxo , Humanos , Leucemia Mieloide Aguda/patologia , Masculino , Pessoa de Meia-Idade , Fatores de Tempo , Células Tumorais Cultivadas
19.
Leuk Lymphoma ; 13(3-4): 291-6, 1994 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-8049651

RESUMO

The DNR accumulation (DNR Acc) and the verapamil (VRP) index (percent increase of VRP on DNR accumulation) was studied by using flow cytometry. Fresh leukemic mononuclear bone marrow blasts from 80 unselected ANLL patients' samples were incubated with DNR in the presence or absence of VRP. The DNR accumulation was determined by flow cytometry. The median DNR Acc was 28 (range: 4-101) and the median VRP index was 4% (range 0-53). VRP significantly enhanced DNR Acc in 42 of the ANLL samples (52.5%). DNR Acc or VRP index were not influenced by age, sex, or WBC counts. Only the FAB subclassification and the blast immunophenotyping were found to influence the parameters studied here. The lowest DNR Acc was found in M0 and M6 blast cells (15 range 0-46 and 10.5 range 8-13 respectively). M4 and M5 ANLL samples accumulated significantly more DNR than M0 and M6 blast cells. The VRP index was significantly higher in M0 compared with M1 and M2 samples, as well as in M4 compared with M1 samples. A slightly positive correlation was found between the percentage of CD34-positive cells in the CD34-positive samples and DNR Acc. In this study, DNR Acc and the VRP index were not significantly correlated with the response to chemotherapy or survival. In conclusion, this study shows that ANLL leukemic cells differ in anthracyclin accumulation and response to VRP in vitro.


Assuntos
Daunorrubicina/metabolismo , Leucemia Mieloide/patologia , Células-Tronco Neoplásicas/metabolismo , Verapamil/farmacologia , Doença Aguda , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Transporte Biológico/efeitos dos fármacos , Medula Óssea/patologia , Transplante de Medula Óssea , Citarabina/administração & dosagem , Daunorrubicina/administração & dosagem , Feminino , Citometria de Fluxo , Humanos , Idarubicina/administração & dosagem , Leucemia Mieloide/tratamento farmacológico , Leucemia Mieloide/terapia , Masculino , Pessoa de Meia-Idade , Células-Tronco Neoplásicas/efeitos dos fármacos , Estimulação Química , Falha de Tratamento
20.
J Hematother ; 3(3): 185-91, 1994.
Artigo em Inglês | MEDLINE | ID: mdl-7530133

RESUMO

We retrospectively studied the factors affecting the rate of hematopoietic reconstitution (HR) in 118 patients with hematological malignancies who underwent peripheral blood progenitor cell (PBPC) transplantation at a single institution. The patients received a median number of 6.6 x 10(8) nucleated cells/kg corresponding to 9.5 x 10(4) (0.5-578) CFU-GM/kg and 6.8 x 10(6) (0.2-161) CD34-positive cells/kg. The median number of days to reach 500 polymorphonuclear cells/mm3 and 50,000 platelets/mm3 was 12.5 (6-93) and 14.5 (6-440) days, respectively. No patient died from infection during the aplastic phase. By multivariate analysis, we found that the dose of CFU-GM infused was the only factor that significantly affects the HR rate (p < 0.0001). Moreover, patients with acute myelogenous leukemia or those transplanted after busulfan or total-body irradiation conditioning regimens had a slower engraftment (p < 0.08). These results could lead to identifying patients who need growth factors posttransplantation and/or the reinfusion of "back-up" marrow together with PBPC.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Leucemia/terapia , Linfoma/terapia , Mieloma Múltiplo/terapia , Análise Atuarial , Adolescente , Adulto , Idoso , Antígenos CD , Antígenos CD34 , Criança , Ensaio de Unidades Formadoras de Colônias , Feminino , Sobrevivência de Enxerto , Humanos , Leucemia/mortalidade , Linfoma/mortalidade , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/mortalidade , Contagem de Plaquetas , Estudos Retrospectivos , Taxa de Sobrevida , Fatores de Tempo
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