RESUMEN
Childhood acute myeloid leukaemia (AML) requires intensive therapy and is associated with survival rates that are substantially inferior to many other childhood malignancies. We undertook a retrospective analysis of Australian Paediatric Cancer Registry data from 1997 to 2008 together with a single-centre audit during the same period assessing burden on service delivery at a tertiary children's hospital (Royal Children's Hospital, Brisbane). Although survival improved from 54.3% (1997-2002) to 69.2% (2003-2008), childhood AML caused a disproportionate number of childhood cancer deaths, accounting for 5.5% of all childhood cancer diagnoses yet 7.9% of all childhood cancer mortality. Furthermore, treatment was associated with significant toxicity requiring intensive use of local health resources. Novel therapeutic strategies aimed at improving survival and reducing toxicity are urgently required.
Asunto(s)
Recursos en Salud/estadística & datos numéricos , Leucemia Mieloide Aguda/epidemiología , Adolescente , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Australia/epidemiología , Niño , Preescolar , Terapia Combinada , Costo de Enfermedad , Infección Hospitalaria/epidemiología , Femenino , Trasplante de Células Madre Hematopoyéticas , Hospitales Pediátricos/estadística & datos numéricos , Humanos , Lactante , Recién Nacido , Unidades de Cuidado Intensivo Pediátrico/estadística & datos numéricos , Tiempo de Internación/estadística & datos numéricos , Leucemia Mieloide Aguda/tratamiento farmacológico , Leucemia Mieloide Aguda/terapia , Leucemia Mielomonocítica Aguda/tratamiento farmacológico , Leucemia Mielomonocítica Aguda/epidemiología , Leucemia Mielomonocítica Aguda/terapia , Masculino , Infecciones Oportunistas/epidemiología , Sistema de Registros , Estudios Retrospectivos , Tasa de Supervivencia , Centros de Atención Terciaria/estadística & datos numéricos , Resultado del TratamientoRESUMEN
BACKGROUND/OBJECTIVE: Acute myeloid leukemia (AML) is the most common acute leukemia in adults. We documented the characteristics and results of treatment of patients with AML at a single reference center. METHODS: Patients diagnosed with AML between June 2003 and July 2011 at a university hospital in northeast Mexico were studied. Overall survival (OS) and event-free survival (EFS) were determined, and risk factors were analyzed with respect to their influence on prognosis. RESULTS: A total of 132 AML patients were included. Median age was 32 years. Complete remission (CR) was achieved by 55% of patients. CR was achieved by 65.1% of patients <60 years (n = 109), compared to 8.7% of those >60 years (n = 23; p < 0.001). In all, 39% of patients >60 years suffered an early death, compared to 14.7% of those <60 years (p < 0.001). OS for patients with AML was 35%, whereas EFS was 32%. On multivariate analysis, patients >60 years had a lower OS and EFS (p < 0.001). A total of 28% of patients received a transplant, and they had high er OS and EFS. Conclusions: Our patients were considerably younger and had remarkably lower survival rates than reported for other populations; those >60 years had a higher early death rate, and fewer of these patients achieved CR.
Asunto(s)
Leucemia Mieloide Aguda/epidemiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Antiinfecciosos/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Transfusión de Componentes Sanguíneos , Niño , Preescolar , Terapia Combinada , Citarabina/administración & dosificación , Dexametasona/administración & dosificación , Supervivencia sin Enfermedad , Doxorrubicina/administración & dosificación , Etopósido/administración & dosificación , Femenino , Trasplante de Células Madre Hematopoyéticas , Hospitales Universitarios , Humanos , Lactante , Infusiones Intravenosas , Inyecciones Espinales , Estimación de Kaplan-Meier , Leucemia Mieloide Aguda/terapia , Leucemia Mielomonocítica Aguda/epidemiología , Leucemia Mielomonocítica Aguda/terapia , Masculino , Metotrexato/administración & dosificación , México/epidemiología , Persona de Mediana Edad , Mitoxantrona/administración & dosificación , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Factores de Riesgo , Resultado del Tratamiento , Adulto JovenRESUMEN
Acute myeloid leukemia (AML) with inv(16)(p13q22) or the variant t(16;16)(p13;q22), is strongly associated with the FAB subtype M4Eo. A high incidence of CNS involvement was reported in the 1980s, but otherwise little is known about the pattern of extamedullary leukemia (EML) manifestations in this AML type. We have compiled clinical and cytogenetic data on 27 consecutive AML cases with inv(16)/t(16;16) from southern Sweden. In general, these AMLs displayed the clinical features that have previously been described as characteristic for this disease entity: low median age, hyperleukocytosis, M4Eo morphology, and a favorable prognosis. However, CNS leukemia was only seen in relapse in one patient diagnosed in 1980, whereas the most common EML manifestation in our series was lymphadenopathy (5/27, 19%), most often cervical with or without gross tonsillar enlargement. A review of previously published, clinically informative cases corroborates that lymphadenopathy, with preference for the cervical region, is the most common EML at diagnosis in inv(16)-positive AML (58/175, 33%). CNS leukemia, on the other hand, has been reported in only 17% of the cases, mostly in the relapse setting, with a diminishing frequency over time, possibly due to protective effects of high-dose cytarabine. Other reported EML sites include the scalp, ovaries, and the intestine. Cervicotonsillar EML was in our series associated with a shorter duration of first remission, (P < 0.05), and may hence prove to be an important clinical parameter when deciding treatment strategies in AML with inv(16)/t(16;16).
Asunto(s)
Inversión Cromosómica , Cromosomas Humanos Par 16/genética , Leucemia Mielomonocítica Aguda/epidemiología , Infiltración Leucémica , Ganglios Linfáticos/patología , Tonsila Palatina/patología , Adulto , Anciano , Sistema Nervioso Central/patología , Niño , Preescolar , Cromosomas Humanos Par 16/ultraestructura , Femenino , Humanos , Leucemia Mielomonocítica Aguda/genética , Leucemia Mielomonocítica Aguda/patología , Masculino , Pronóstico , Estudios Retrospectivos , Resultado del TratamientoAsunto(s)
Leucemia Mielomonocítica Aguda/epidemiología , Factores de Edad , Causas de Muerte , Femenino , Humanos , Japón/epidemiología , Leucemia Mielomonocítica Aguda/clasificación , Leucemia Mielomonocítica Aguda/diagnóstico , Masculino , Pronóstico , Estándares de Referencia , Factores Sexuales , Tasa de Supervivencia , Factores de TiempoRESUMEN
Conventional-dose Ara-C (200 mg/m2 d 1-5) combined with idarubicin (12 mg/m2 d 1-3) was employed as remission induction and consolidation therapy in 23 elderly AML patients with a median age of 66 years (range, 60-75) with AML according to the FAB criteria (M1 n = 3, M2 n = 10, M4 n = 6, M5 n = 2, M6 n = 2), eligible for the study. In seven patients earlier MDS had been documented by previous bone marrow aspirates. The CR rate after one induction course was 65% (15/23). Toxicity was acceptable, with four patients dying during the chemotherapy-induced hypoplasia (4/23). Although 80% of the CR patients received two additional cycles of Ara-C and idarubicin as consolidation therapy, only two patients are still in continuous complete remission more than 12 months after achieving CR. The median disease-free survival of the CR patients was 11.5 months and the median survival of the entire group was 10 months. We conclude that conventional dose Ara-C/idarubicin is an effective protocol for inducing complete remission in elderly patients with AML, but that consolidation therapy consisting of two courses of the same regimen does not produce a relevant rate of long-term disease-free survival.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Citarabina/administración & dosificación , Idarrubicina/administración & dosificación , Leucemia Mieloide/tratamiento farmacológico , Enfermedad Aguda , Anciano , Relación Dosis-Respuesta a Droga , Humanos , Leucemia Eritroblástica Aguda/tratamiento farmacológico , Leucemia Eritroblástica Aguda/epidemiología , Leucemia Monocítica Aguda/tratamiento farmacológico , Leucemia Monocítica Aguda/epidemiología , Leucemia Mieloide/epidemiología , Leucemia Mieloide Aguda/tratamiento farmacológico , Leucemia Mieloide Aguda/epidemiología , Leucemia Mielomonocítica Aguda/tratamiento farmacológico , Leucemia Mielomonocítica Aguda/epidemiología , Persona de Mediana Edad , Análisis de SupervivenciaRESUMEN
Morphological pattern of 234 consecutive cases of various types of leukemias is presented. Acute leukemias (62.8%) were commoner than chronic (37.2%). Amongst acute leukemias, myeloid leukemias (AML) were more frequent as compared to lymphoblastic (ALL). AML:ALL ratio was 2.57:1 in adults and 1:3 in children. Amongst AML cases, M4 was the commonest, followed by M2, M1, M3 and M4 and M6 and M7 respectively. In ALL patients, L1 was the commonest, followed by L2 and L3 respectively. Amongst chronic leukemias, myelocytic leukemia (CML) was more common than lymphocytic leukemia (CLL) with a CML:CLL ratio of 3.1:1. In a total of 60 CML cases, two had juvenile CML, four were between 10 and 15 years of age and the remaining 54 were adults. Hairy cell leukemia (2 cases) and lymphoma/leukemia syndrome (5 cases) were uncommon.
Asunto(s)
Leucemia/epidemiología , Leucemia/patología , Enfermedad Aguda , Adolescente , Adulto , Anciano , Niño , Preescolar , Enfermedad Crónica , Femenino , Humanos , Lactante , Leucemia Linfocítica Crónica de Células B/epidemiología , Leucemia Linfocítica Crónica de Células B/patología , Leucemia Mielógena Crónica BCR-ABL Positiva/epidemiología , Leucemia Mielógena Crónica BCR-ABL Positiva/patología , Leucemia Mieloide/epidemiología , Leucemia Mieloide/patología , Leucemia Mieloide Aguda/epidemiología , Leucemia Mieloide Aguda/patología , Leucemia Mielomonocítica Aguda/epidemiología , Leucemia Mielomonocítica Aguda/patología , Masculino , Persona de Mediana Edad , Pakistán/epidemiología , Leucemia-Linfoma Linfoblástico de Células Precursoras/epidemiología , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologíaRESUMEN
BACKGROUND AND METHODS: Consistent and specific chromosomal aberrations have been observed in an increasing number of neoplasias. In the present report, we describe the cytogenetic findings from 50 cases of de novo ANLL in Argentina, South America, studied at diagnosis. In addition, their relation with the FAB classification is analyzed. Children with Down's syndrome and secondary ANLL were excluded from this analysis. RESULTS AND CONCLUSIONS: Out of 50 banded cases studied, 11 (22%) had normal karyotype, while the remaining 39 (78%) presented abnormal metaphases with structural alterations in the majority of them. Chromosomes 7 and 22 were most frequently involved in numerical alterations in children, while chromosomes 6, 8, 14 and 16 were the ones most often involved in adults. Consistent chromosome rearrangements were observed and they were linked to specific cytomorphologic subsets. The translocations t(8;21) and t(15;17) were seen only in M2 and M3, respectively. The inversion of chromosome 16, inv(16), was a typical finding in M4, but was not restricted to this subtype. Translocation t(2;3) was observed in three cases, all M4, each with a variable chromosome pattern. These results are in accordance with cytogenetic findings in Western Europe and the USA.
Asunto(s)
Aberraciones Cromosómicas , Leucemia Mieloide Aguda/genética , Leucemia Mielomonocítica Aguda/genética , Adolescente , Adulto , Anciano , Aneuploidia , Argentina/epidemiología , Niño , Preescolar , Bandeo Cromosómico , Femenino , Humanos , Lactante , Cariotipificación , Leucemia Mieloide Aguda/epidemiología , Leucemia Mieloide Aguda/patología , Leucemia Mielomonocítica Aguda/epidemiología , Leucemia Mielomonocítica Aguda/patología , Masculino , Persona de Mediana Edad , Translocación GenéticaRESUMEN
BACKGROUND: Epidemiologic studies of acute myeloid leukemias (AMLs) show small increases in risk of disease associated with certain occupations and chemical exposures. PURPOSE: This study was designed to determine whether the presence of mutationally activated ras oncogenes in AML are associated with occupational and chemical exposures. METHODS: We interviewed 62 patients with newly diagnosed AML (or their next-of-kin), all of whom were enrolled in a national multicenter clinical trial, and 630 healthy control subjects. DNA extracted from patients' pretreatment bone marrow samples was amplified by using the polymerase chain reaction and probed with allele-specific oligonucleotides for activating point mutations at the 12th, 13th, and 61st codons of three protooncogenes: H-ras (also known as HRAS), K-ras (also known as KRAS2), and N-ras (also known as NRAS). RESULTS: Patients with ras mutation-positive AML had a higher frequency (six of 10 patients) of working 5 or more years in an a priori high-risk occupation than did patients with ras mutation-negative AML (eight of 52; odds ratio [OR] = 6.8; 95% confidence interval [CI] = 1.3-36). Patients with ras mutation-positive AML were more likely than patients with ras mutation-negative AML to have breathed chemical vapor on the job (OR = 9.1; 95% CI = 1.3-64) or to have had skin contact with chemicals (OR = 6.9; 95% CI = 1.3-37). When ras-positive patients were compared with healthy control subjects, the ORs for occupation and occupational exposures remained elevated, while patients with ras mutation-negative AML showed no increased risk when compared with control subjects. CONCLUSION: Activation of ras proto-oncogenes may identify an etiologic subgroup of AML caused by occupation and chemical exposure. IMPLICATION: Disease etiology may be better understood if epidemiologic measures of exposure are integrated with molecular assays of the genetic defects responsible for cancer initiation and promotion.