FINAL HEIGHT AND PUBERTY IN 40 PATIENTS AFTER ANTILEUKEMIC TREATMENT DURING CHILDHOOD

Endocrine dysfunction and damage of the epiphysial growth plates have been reported as late effects of antileukaemic treatment during childh ood. It is a common opinion that cranial irradiation (CI) is the most important factor for blunted growth. Accordingly, recent therapeutic s trategies in acute lymphoblastic leukaemia (ALL) avoid cranial irradia tion. Here we analysed longitudinal data on growth and puberty of 54 c hildren in first complete remission, who were treated with 18 Gy CI or not submitted to radiotherapy. Two chemotherapeutic protocols were co mpared which were similar during the induction period but differed in the intensity of maintenance therapy. In cranial irradiated patients b oth in males and females the pubertal growth spurt started at a mean a ge of 1.2 years (SD: 0.93 years) earlier than controls. Age at diagnos is and age at pubertal growth spurt were significantly correlated (r = 0.35, P = 0.017). Similarly, menarche occurred at a mean age (n = 22) of 12.1 years and was correlated with the age at start of therapy in girls who were treated with 18 Gy CI (r = 0.61, P = 0.01). Adult heigh t was reached spontaneously in 30 patients treated during prepubertal age and in 10 treated shortly before or during puberty. In all prepube rtal patients treated for 2-3 years with intensive maintenance therapy blunted growth resulted in a significant loss of -1.85 H-SDS (median, P = 0.0051) compared to height at diagnosis. However, if continuation treatment used only methotrexate and 6-mercaptopurine (i.e. BFM proto col) final height equalled projected adult height, despite 18 Gy CI. C onclusions (1) multiagent chemotherapy is of major impact for growth a nd puberty; (2) 18 Gy cranial irradiation is below the critical dosage responsible for blunted growth; (3) loss in potential growth might be prevented by current CT strategies; (4) onset of puberty depends on a ge when antileukaemic therapy is applied.