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      Leucemia mieloide aguda: Evaluación clínico terapéutica en niños del Hospital Universitario de Caracas (periodo 1995-2004)

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          Abstract

          Objetivo: Identificar las características clínico-hematológicas y la evolución terapéutica de niños con Leucemia Mieloide Aguda, no promielocitica de novo, en el Servicio de Hematología del HUC entre 1995-2004. Método: Estudio clínico-epidemiológico descriptivo y retrospectivo a través de la revisión de historias clínicas de pacientes menores de 18 años, tratados según el Protocolo P94 o el Protocolo modificado (PM), con sustitución de Idarubicina por Daunorubicina Resultados: Las características clínicas más frecuentes fueron fiebre, astenia, disnea, adenomegalias, palidez y hepatomegalia. La mayoría se presentó con anemia, leucocitosis y trombocitopenia. La incidencia de infiltración del SNC fue 5%. Cinco pacientes recibieron el P94 y 15 el PM. El P94 produjo 80% de remisión completa (RC) y el PM 73%(diferencia no significativa). La Sobrevida Libre de Eventos (SLEv), Sobrevida libre de enfermedad (SLE) y Sobrevida Total (ST) a los 26 meses de seguimiento fue 33.3%, 50% y 37,5% respectivamente para el P94 y de 14.3%, 20% y 18,7% para el PM (diferencias no significativas). Conclusiones: Los resultados son levemente superiores a los obtenidos en el HUC con el PN80 y el P86, e inferiores a los obtenidos por grupos internacionales.

          Translated abstract

          Objective: To identify clinical - hematological features and treatment results of 20 children with Acute Myeloid Leukemia, non promyelocytic diagnosed and treated in The Hematology Service of Caracas University Hospital between 1995 - 2004. Method: The study is of a retrospective, descriptive and clinical-epidemiologic type. Data was obtained by chart review of patients <18 years old treated by P94 regimen or Modified (MP) in which Idarubicin was changed by Daunorubicin. Results: Relevant clinical features were fever, fatigue, dispnea, lymph node enlargement, pallor and hepatomegaly. Most patients presented anemia, leukocytosis and thrombocytopenia. Central nervous system infiltration was present in 1 patient (5%). Five received P94 and 15 received MP. P94 produced 8o% and MP 73% complete remissions (non statiscal difference). The Event Free Survival (EFS), Disease Free Survival (DFS) and Total Survival (TS) at 26 monts with P94 were 33.3%, 50% y 37,5% and with the Modified Protocol 14.3%, 20% y 18,7% (non statistical difference). Conclusion: Results are slightly better than previously obtained at The University Hospital with PN80 and P86, but lower than those obtained by international groups.

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          Treatment strategies and long-term results in paediatric patients treated in four consecutive AML-BFM trials.

          A total of 1111 children with acute myeloblastic leukaemia (AML) were treated in four consecutive Berlin-Frankfurt-Münster (BFM) studies from 1978 to 1998. The first cooperative trial AML-BFM 78 established intensive chemotherapy with seven drugs, CNS irradiation and 2-year maintenance, achieving a long-term survival (overall survival (OS)) of 40%. Induction intensification in AML-BFM 83 resulted in significant improvement of disease-free survival (DFS). The risk of haemorrhage, especially in children with hyperleukocytosis, proved the high relevance of supportive care. In AML-BFM 87, the benefit of CNS irradiation in preventing CNS/systemic relapses was demonstrated. In AML-BFM 93, the introduction of idarubicin during first induction followed by intensification with HAM increased the 5-year EFS, DFS and OS to 50+/-2, 61+/-3 and 57+/-2%, respectively. Stem cell transplantation (SCT), as applied in high-risk patients with a matched related donor, did not significantly improve the outcome compared to chemotherapy alone. In spite of treatment intensification, the therapy-related death rate decreased from trial to trial, mainly during induction. The future aim is to reduce long-term sequelae, especially cardiotoxicity, by administration of less cardiotoxic drugs, and toxicity of SCT by risk-adapted indications. The AML-BFM studies performed in three European countries with >70 cooperating centres have significantly improved the outcome in AML children; nevertheless, increasing experience with these intensive treatment regimens is of fundamental importance to reduce fatal complications.
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            Long-term results of children with acute myeloid leukemia: a report of three consecutive Phase III trials by the Children's Cancer Group: CCG 251, CCG 213 and CCG 2891.

            The Children's Cancer Group (CCG) conducted three Phase III prospective clinical trials for children with de novo acute myeloid leukemia between the years 1979 and 1995. A total of 1903 eligible children ages birth to 21 years of age were enrolled on CCG 251 (n=485), CCG 213 (n=532) and CCG 2891 (n=886). Follow-up is ongoing, with medians of 7.9, 10.9 and 8.6 years, respectively. These three clinical trials developed dose- and time-intensive induction regimens based upon high-dose cytarabine and daunomycin and randomly assigned patients to allogeneic bone marrow transplantation in first remission if an HLA-matched related donor was identified. Despite dose- and time-intensive induction regimens, remission induction rates remained relatively stable at 77-78%. However, overall survival, event-free survival and disease-free survival (DFS) increased for patients receiving intensive-timing induction therapy in comparison to patients who received standard-timing induction, regardless of the type of postremission therapy. Outcomes were best for patients receiving intensive-timing induction followed by matched related donor allogeneic transplantation with DFS of 65+/-9% at 6 years. These three clinical trials have established a strong foundation for the development of future studies focusing on further risk group stratification and the development of novel, molecularly-targeted therapies.
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              Treatment of childhood acute myeloblastic leukemia: dose intensification improves outcome and maintenance therapy is of no benefit--multicenter studies of the French LAME (Leucémie Aiguë Myéloblastique Enfant) Cooperative Group.

              From 1989 to 1998, 341 children were included in the French multicentric LAME (Leucémie Aiguë Myéloblastique Enfant) trials. A total of 309 children were registered in the LAME 89/91 protocol. This intensive regimen included an induction phase (mitoxantrone plus cytarabine), two consolidation courses, one containing timed-sequential high-dose cytarabine, asparaginase and amsacrine; 276 (90%) achieved a CR. The 5-year overall survival (OS) and event-free survival (EFS) were 60+/-4 and 48+/-4%, respectively. From 1997, timed-sequencing of the LAME SP induction chemotherapy led to an unacceptable frequency of consolidation delay; future improvements are unlikely to come from further increases in intensity. The role of allogenic bone-marrow transplantation from an HLA-identical sibling in CR1 was examined. The disease-free survival (DFS) was 52+/-4% for non-allografted patients and 57+/-7% for allografted patients (P=NS); a better OS for allografted patients was shown and could be related either to allo-BMT early in CR1 or to a second allo-BMT in CR2. For the complete responders after consolidation therapy, the 5-year OS was significantly better in patients randomized for no maintenance therapy (MT-) than in patients randomized for MT (77.6+/-8 vs 59+/-8%; P=0.05), while the 5-year DFS was not significantly different. Exposure to low-dose MT might contribute to clinical drug resistance and treatment failure in relapsing patients.
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                Author and article information

                Contributors
                Role: ND
                Role: ND
                Role: ND
                Journal
                avpp
                Archivos Venezolanos de Puericultura y Pediatría
                Arch Venez Puer Ped
                Sociedad Venezolana de Puericultura y Pediatría (Caracas )
                0004-0649
                March 2007
                : 70
                : 1
                : 7-15
                Affiliations
                [1 ] Hospital Universitario de Caracas Venezuela
                [2 ] Hospital Universitario de Caracas Venezuela
                [3 ] Hospital Universitario de Caracas Venezuela
                Article
                S0004-06492007000100003
                b42e7b8c-187d-44bc-9a9b-025557619dc1

                http://creativecommons.org/licenses/by/4.0/

                History
                Product

                SciELO Venezuela

                Self URI (journal page): http://www.scielo.org.ve/scielo.php?script=sci_serial&pid=0004-0649&lng=en
                Categories
                HEALTH CARE SCIENCES & SERVICES
                HEALTH POLICY & SERVICES
                PEDIATRICS

                Pediatrics,Health & Social care,Public health
                Acute Myeloid Leukemia,Leucemia Mieloide Aguda,Tratamiento,Quimioterapia,treatment,Chemotherapy

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