RESUMO
BACKGROUND: Endocrine complications after acute lymphoblastic leukemia (ALL) are common. METHODS: Final height, GH/IGF-1 axis, and body mass index were analyzed after 13.7 (7.0-20.7) years from diagnosis in 34 boys aged <12 years at diagnosis and 41 girls <10 years at diagnosis. A modified German BFM-83 ALL protocol included (n = 42) or did not include (n = 33) prophylactic cranial irradiation. In 27 patients, GH after insulin tolerance test, IGF-1, cortisol, free T(4) and estradiol/testosterone were determined. RESULTS: Final height was significantly reduced (mean Z-score for height between final height and diagnosis, ΔHAZ = -0.61, p = 0.0001). At that point, 3 patients were obese (4%) and 17 were overweight (22.7%). Patients aged ≤ 4 years at diagnosis and those irradiated had a greater loss in final height (p = 0.001 and p = 0.008, respectively). Abnormalities in GH/IGF-1 axis were observed in 4 patients: 3 had a GH peak <6 ng/ml and 1 had a serum IGF-1 concentration <25 ng/ml. Growth deficit was significantly higher in patients with hormonal deficiency (p = 0.006). CONCLUSIONS: Treatment of ALL during childhood is associated with final height deficit. Young age at diagnosis and radiotherapy were the major risk factors. GH/IGF-1 deficiency was found particularly in irradiated patients, even though it was detected in 1 non-irradiated patient.
Assuntos
Transtornos do Crescimento/etiologia , Hormônio do Crescimento/fisiologia , Fator de Crescimento Insulin-Like I/fisiologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/fisiopatologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Radioterapia/efeitos adversos , Transdução de Sinais/fisiologia , Fatores Etários , Estatura/fisiologia , Índice de Massa Corporal , Pré-Escolar , Terapia Combinada , Irradiação Craniana/efeitos adversos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Feminino , Seguimentos , Transtornos do Crescimento/epidemiologia , Humanos , Masculino , Estudos Retrospectivos , Fatores de Risco , Adulto JovemRESUMO
There are conflicting data on the incidence and severity of height deficits in children with acute lymphoblastic leukemia (ALL). This is probably due to: (1) collection of data in different phases of treatment; (2) differences in chemotherapeutic regimens; (3) inclusion or not of children who had received cranial irradiation (CRT); (4) limited numbers of patients; (5) relative numbers of prepubertal and pubertal children; (6) different ways of measuring growth deficits. Twenty-five papers published between 1987 and 2006 were reviewed. These reveal that (1) chemotherapy always causes some height reduction during treatment regardless of whether additional CRT is given; (2) catch-up growth occurs immediately after cessation of treatment; (3) intensive chemotherapy alone significantly decreases height in the long-term but to a lesser extent than with additional CRT; (4) young children develop more severe height loss; (5) girls are reported to have greater height deficits but confounding factors have not been adequately considered; (6) late growth hormone (GH) deficiency has been detected in many children, mostly in those who had CRT; (7) GH replacement therapy seems to be effective. ALL relapse in GH-treated children is not more common than in those not treated with GH.
Assuntos
Estatura , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Criança , Seguimentos , Hormônio do Crescimento/deficiência , Hormônio do Crescimento/metabolismo , Humanos , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/epidemiologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/metabolismo , Puberdade , Fatores de TempoRESUMO
BACKGROUND: Growth deficit has been reported as a frequent complication of the treatment of acute lymphoblastic leukemia (ALL). PROCEDURE: Longitudinal analysis of the growth of 129 children, from a total of 351 cases diagnosed between 1987 and 1994 in Brazil, was determined. Height data were converted into standard deviation Z scores. Only girls younger than 10 and boys younger than 12 years old at diagnosis were included. Patients were treated according to a German BFM-83 based protocol. Fifty-eight children received 18 Gy cranial irradiation, four 12 Gy, and two 24 Gy. Patients were aggregated into five non-excluding groups according to availability of height data at diagnosis, during the treatment, at the end of it, and several years after; 35 children reached their final height. RESULTS: Height deficit at the end of the therapeutic treatment was evident (P < 0.0001). Catch-up occurred 1 year after stopping treatment (P = 0.016). At the last follow-up, over 5 years after the end of treatment (n = 83) or at final height (n = 35), impressive height deficits were recorded (P < 0.0001 for both end points). Multivariate analysis demonstrated that growth impairment was more severe in children younger than 4 years at diagnosis and in those who received cranial irradiation. No significant effect of gender was observed. Children who were treated solely with chemotherapy also had significant height loss. CONCLUSIONS: Treatment of ALL in children is associated with growth deficit during the treatment and several years after it, affecting the final height negatively, particularly in patients younger than 4 and in those who received cranial irradiation.