Prophylactic cranial irradiation of acute lymphoblastic leukemia in childhood: outcomes of late effects on pituitary function and growth in long-term survivors.

Abstract

It is well known that prophylactic cranial irradiation is highly effective in preventing central nervous system (CNS) relapse of acute lymphoblastic leukemia (ALL). Nevertheless, there have been very few reports on the late effects, especially pituitary function and growth, in long-term survivors who were treated with 18 Gy cranial irradiation in childhood. The subjects consisted of 35 children with ALL who were treated with prophylactic 18 Gy cranial irradiation at Kanagawa Children's Medical Center between October 1981 and February 1995. All patients received cranial irradiation after first attaining complete remission with induction chemotherapy, according to the treatment protocols prescribed by the Tokyo Children's Leukemia Study Group (TCLSG) and Tokyo Children's Cancer Study Group (TCCSG). Their ages at the time of cranial irradiation ranged from 2.2-15.0 years (mean 6.8). We evaluated their pituitary functions by measuring their pituitary hormone values 0.7-11.3 years (mean 6.0) after cranial irradiation and their growth by analyzing their height standard deviation score (SDS) at diagnosis of ALL and their final height SDS at the mean follow-up period of 8.2 years after cranial irradiation. Height SDS is defined as the difference between the patient's height and the mean height of their age and sex, divided by the standard deviation of their age and sex. Eight of 35 patients had ALL relapse, involving the bone marrow in seven patients and the CNS in only one. Six of the eight patients with relapse died 1.5-6.6 years after cranial irradiation and the other two patients were salvaged by further intensive therapies. The remaining 27 relapse-free patients have survived for 1.4-15.8 years (mean 10.1) after cranial irradiation. Twenty-six of the 29 survivors are long-term survivors of more than 5 years. Although there was one patient with an abnormal result in each value of growth hormone (GH), adrenocorticotropic hormone (ACTH), and prolactin (PRL), and two patients with abnormal results in thyroid-stimulating hormone (TSH) values, none of the patients had clinical symptoms of pituitary hormone abnormality and none required hormone supplements. The final height SDS decreased significantly compared with the height SDS at diagnosis of ALL in the long-term survivors (P = 0.001) and the height SDS of the patients who had received cranial irradiation at a young age tended to decrease gradually (P = 0.019). However, no patient showed severe growth failure. It is considered that prophylactic 18 Gy cranial irradiation plus chemotherapy for ALL in childhood can effectively prevent CNS relapse and is unlikely to produce clinically significant late effects, although it may cause slight pituitary hormone abnormality.