Growth and puberty after treatment for acute lymphoblastic leukemia

Abstract

Over the last 20 years, after combining treatment of chemotherapy and radiotherapy, there has been an improvement in the survival rate of acute lymphoblastic leukemia patients, with a current cure rate of around 70%. Children with the disease have been enrolled into international treatment protocols designed to improve survival and minimize the serious irreversible late effects. Our oncology unit uses the international protocol: GBTLI LLA-85 and 90, with the drugs methotrexate, cytosine, arabinoside, dexamethasone, and radiotherapy. However, these treatments can cause gonadal damage and growth impairment. PATIENTS AND METHOD:The authors analyzed 20 children off therapy in order to determine the role of the various doses of radiotherapy regarding endocrinological alterations. They were divided into 3 groups according to central nervous system prophylaxis: Group A underwent chemotherapy, group B underwent chemotherapy plus radiotherapy (18 Gy), and group C underwent chemotherapy plus radiotherapy (24 Gy). Serum concentrations of LH, FSH, GH, and testosterone were determined. Imaging studies included bone age, pelvic ultrasound and scrotum, and skull magnetic resonance imaging. RESULTS: Nine of the patients who received radiotherapy had decreased pituitary volume. There was a significant difference in the response to GH and loss of predicted final stature (Bayley-Pinneau) between the 2 irradiated groups and the group that was not irradiated, but there was no difference regarding the radiation doses used (18 or 24 Gy). The final predicted height (Bayley-Pinneau) was significantly less (P = 0.0071) in both groups treated with radiotherapy. Two girls had precocious puberty, and 1 boy with delayed puberty presented calcification of the epididymis. CONCLUSION: Radiotherapy was been responsible for late side effects, especially related to growth and puberty.KEY WORDS: Endocrine dysfunction in lymphoblastic leukemia. Growth and acute leukemia. Puberty in lymphoblastic leukemia.

Late Effects of Childhood Leukemia Therapy

“…High doses of prednisone or dexamethasone used during the leukemia treatment also affect growth, although most children demonstrate good catch-up growth in the first few years of follow-up after treatment [93]. Age less than 4 years at diagnosis and CRT are high-risk factors predicting deficiencies in adult height potential [94,95]. It is very important to closely follow growth in these children, with referral to an endocrinologist when indicated [96].…”

Avaliação dos principais efeitos endócrinos tardios em crianças e adolescentes sobreviventes ao tratamento de neoplasias malignas

“…Os tumores de SNC e a irradiação craniana podem desencadear puberdade precoce em alguns pacientes (3,4,6,8). Fatores como tipo e localização do tumor (gliomas ópticos, astrocitomas e hamartomas) e doses de irradiação podem influenciar no aparecimento desse quadro clínico (3).…”

“…Nos indivíduos que receberam radioterapia, especialmente de crânio e eixo, o risco de acometimento é aumentado, o que pode tornar vulnerável a região hipotálamo-hipofisária, levando a uma secreção deficiente de hormônio de crescimento, além de alterações da puberdade tanto precoce como tardia (3)(4)(5)(6)(7)(8).…”

Alteraciones puberales en adolescentes con leucemia en fase de vigilancia

“…Entre estas complicaciones se presentan disfunción gonadal, infertilidad y trastornos del desarrollo puberal 3,4 . Se ha reportado que la edad prepuberal al inicio del tratamiento no protege del daño gonadal; al contrario, los niños que recibieron radioterapia a temprana edad presentaron algún trastorno del crecimiento o del desarrollo de la pubertad, y hasta el momento no se ha identificado ningún marcador clínico, hormonal o ecográfico que sea suficiente para determinar si existe insuficiencia gonadal 5,6 . El objetivo de este estudio es evaluar qué factores se asocian a alteraciones en el desarrollo puberal en pacientes pediátricos con leucemia en fase de vigilancia.…”