Height Deficit and Impairment of the GH/IGF-1 Axis in Patients Treated for Acute Lymphoblastic Leukemia during Childhood

Abstract

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 T₄ 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.

Protocolo de seguimento e revisão da literatura: sequelas endócrinas em longo prazo após tratamento de doença oncológica na idade pediátrica

“…8 No entanto, o déficit de GH não é a única causa implicada nas alteraç ões do crescimento: a má nutriç ão tão comum nesses doentes, as lesões da coluna vertebral (por RT à espinal medula em tumores como meduloblastomas e ependimomas), a corticoterapia e períodos de imobilizaç ão prolongada, disfunç ão tiroidea associada e eventualmente a presenç a de puberdade precoce são todos fatores que influenciam a estatura final da crianç a. 9 Os efeitos da quimioterapia são controversos: alguns estudos demonstraram que a QT associada à RT espinal agrava as expectativas de estatura na idade adulta. 10,11 A RT espinal provoca muitas vezes uma diminuiç ão irreversí-vel do crescimento vertebral, o que poderá alterar as proporç ões corporais 12 -alteraç ões no quociente entre a estatura em ortostatismo e na posiç ão de sentado.…”

Final height and body mass index in adult survivors of childhood acute lymphoblastic leukemia treated without cranial radiotherapy: a retrospective longitudinal multicenter Italian study

“…Treatment of ALL during childhood is associated with final height deficit. Young age at diagnosis and radiotherapy are considered the major risk factors [ 6 ]. Moreover, adult survivors of childhood ALL have a four-fold excess risk of mortality from cardiovascular disease.…”

Impact of treatment on the growth of children treated for acute lymphoblastic leukemia

“…The increased risk of impaired linear growth and obesity/overweight has been largely studied over the past decades to determine whether these adverse outcomes are predictable and potentially reversible. [5][6][7][8][9][10][11][12][14][15][16][17][18][19][20][21][22][23][24] Published results are conflicting and, in some cases, difficult to interpret considering the heterogeneity of therapeutic protocols in use. In recent decades, cranial radiotherapy (CRT) has mostly been replaced by intrathecal chemotherapy as the standard central nervous system prophylaxis and treatment, resulting in less sequelae related to this treatment modality.…”

“…Height deficit during treatment is a common finding in children treated for ALL. 5 Many studies further suggest that adult survivors of ALL have long-term impaired growth and decreased final height (FH) [5][6][7] , while others find that FH is not significantly affected by treatment. [8][9][10] Different studies found this effect on linear growth to be more pronounced or only significantly seen in some subgroups such as patients treated with CRT, 7,8,11 females 12 or younger children.…”

“…[8][9][10] Different studies found this effect on linear growth to be more pronounced or only significantly seen in some subgroups such as patients treated with CRT, 7,8,11 females 12 or younger children. 7 When addressing height after treatment, most published studies compare height percentiles (HP) or standard deviation-scores (SD) with general population height patterns and with patient's height at the time of diagnosis. This approach does not take into account the so-called "genetic potentiality", usually evaluated by the target height (TH), which can be estimated from parent's height.…”