RESUMEN
BACKGROUND: Five Asociación de Hemato-Oncología de Centroamérica (AHOPCA) countries have used an adapted BFM-based protocol for childhood acute lymphoblastic leukemia (ALL). PROCEDURE: In the AHOPCA-ALL 2008 protocol, patients were stratified by age, white blood cell count, immunophenotype, central nervous system involvement, day 8 prednisone response, and morphologic bone marrow response to induction therapy. Patients at Standard Risk (SR) received a three-drug induction regimen, a reinduction phase, and maintenance with protracted intrathecal therapy. Those at Intermediate (IR) and High Risk (HR) received, in addition, daunorubicin during induction therapy, a consolidation phase and two or three reinduction phases respectively. RESULTS: From August 2008 through July 2012, 1,313 patients were enrolled: 353 in SR, 548 in IR, 412 in HR. During induction therapy, 3.0% of patients died, 2.7% abandoned treatment, 1.1% had resistant ALL, and 93.2% achieved morphological complete remission (CR). Deaths and abandonment in first CR occurred in 2.7% and in 7.0% of patients, respectively. The relapse rate at a median observation time of 2.1 years was 15.0%. At 3 years, the event-free survival (EFS) and overall survival (OS), with abandonment considered as an event, were 59.4% (SE 1.7) and 68.2% (SE 1.6). Three-year EFS was 68.5% (SE 3.0), 62.1% (SE 2.6), and 47.8% (SE 3.2) for SR, IR, and HR groups. Adolescents had a significantly higher relapse rate (P = 0.001). CONCLUSIONS: This experience shows that common international studies are feasible in lower-middle income countries. Toxic deaths, abandonment of treatment, and relapses remain major obstacles to the successful treatment. Alternative treatment strategies may be beneficial.
Asunto(s)
Países en Desarrollo , Recurrencia Local de Neoplasia/terapia , Neoplasias Primarias Secundarias/terapia , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Privación de Tratamiento/estadística & datos numéricos , Adolescente , América Central , Niño , Preescolar , Terapia Combinada , Femenino , Estudios de Seguimiento , Humanos , Inmunofenotipificación , Renta , Lactante , Recién Nacido , Masculino , Recurrencia Local de Neoplasia/etiología , Recurrencia Local de Neoplasia/mortalidad , Neoplasias Primarias Secundarias/etiología , Neoplasias Primarias Secundarias/mortalidad , Pobreza , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicaciones , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidad , Pronóstico , Inducción de Remisión , Tasa de Supervivencia , Privación de Tratamiento/economíaRESUMEN
Survival rates among children with leukaemia in low-income countries are lower than those in high-income countries. This has been attributed in part to higher treatment-related mortality (TRM). We examined the demographics, treatment, and outcomes of paediatric patients in El Salvador with acute lymphoblastic leukaemia (ALL) or acute myeloid leukaemia (AML) to determine the incidence, causes, and risk factors for TRM. Two trained data managers collected data prospectively; no patients were excluded. Biological, socioeconomic and nutritional predictors were examined. A total of 469 patients with ALL and 78 patients with AML were included. The 2-year cumulative incidence of TRM was significantly higher among children with AML (35.4+/-6.4%) than those with ALL (12.5+/-1.7%; P<0.0001). However, the proportion of deaths attributable to the toxicity of treatment did not differ significantly between AML (25/47, 53.2%) and ALL (55/107, 51.4%; P=0.98). Among children with ALL, low monthly income (P=0.04) and low parental education (P=0.02) significantly increased the risk of TRM. Among children with AML, biological, socioeconomic, and nutritional variables were not associated with TRM. In this low-income country, toxic death significantly contributes to mortality in both ALL and AML. A better understanding of the effect of socioeconomic status on TRM may suggest specific strategies for patients with ALL.
Asunto(s)
Leucemia Mieloide Aguda/mortalidad , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidad , Adolescente , Niño , Preescolar , Escolaridad , El Salvador/epidemiología , Femenino , Humanos , Incidencia , Renta , Lactante , Recién Nacido , Leucemia Mieloide Aguda/epidemiología , Leucemia Mieloide Aguda/terapia , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras/epidemiología , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Factores SocioeconómicosAsunto(s)
Citometría de Flujo/estadística & datos numéricos , Leucemia/diagnóstico , Programas Médicos Regionales/organización & administración , América Central , Niño , Citometría de Flujo/economía , Citometría de Flujo/métodos , Humanos , Inmunofenotipificación , Leucemia/clasificación , Leucemia/patología , Desarrollo de Programa , Derivación y Consulta/estadística & datos numéricos , Programas Médicos Regionales/economía , Medición de RiesgoRESUMEN
Airborne infection with Venezuelan equine encephalitis virus (VEEV) is a significant hazard for laboratory workers, who may not be immunised against VEEV infection as there is no vaccine currently available suitable for human use. We describe a potential alternative strategy that could protect workers exposed to VEEV or similar viruses. VEEV-specific murine monoclonal antibodies (MAB), given by intraperitoneal (i.p.) injection to mice as a single dose of 100 microg, have a half-life of 6-10 days in serum and spread by transudation to respiratory secretions. Administration of MAB (approximately 4 mg/kg) to mice 24h before challenge with approximately 100LD50 of virulent VEEV protected up to 100% animals. The same dose of MAB delivered up to 24h after challenge protected approximately 50%. Two MAB that were synergistic in vitro in plaque reduction neutralisation tests were not synergistic in vivo in protection assays. An examination of virus multiplication, in the blood and internal organs (brain, spleen, lung) of MAB-treated mice infected by the airborne route with VEEV, suggested that therapeutic activity depended both upon the prevention of virus infection of the brain, and the rapid clearance of virus from the periphery. Antiviral therapy with VEEV-specific human or "humanised" MAB, providing that they are administered early, may offer an alternative means of specific medical intervention for those with a known exposure to VEEV.