Final height and puberty in 40 patients after antileukaemic treatment during childhood.
Endocrine dysfunction and damage of the epiphysial growth plates have been reported as late effects of antileukaemic treatment during childhood. It is a common opinion that cranial irradiation (CI) is the most important factor for blunted growth. Accordingly, recent therapeutic strategies in acute lymphoblastic leukaemia (ALL) avoid cranial irradiation. Here we analysed longitudinal data on growth and puberty of 54 children in first complete remission, who were treated with 18 Gy CI or not submitted to radiotherapy. Two chemotherapeutic protocols were compared which were similar during the induction period but differed in the intensity of maintenance therapy. In cranial irradiated patients both in males and females the pubertal growth spurt started at a mean age of 1.2 years (SD: 0.93 years) earlier than controls. Age at diagnosis 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 height was reached spontaneously in 30 patients treated during prepubertal age and in 10 treated shortly before or during puberty. In all prepubertal 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 protocol) final height equalled projected adult height, despite 18 Gy CI.


CONCLUSIONS
(1) multiagent chemotherapy is of major impact for growth and 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 age when antileukaemic therapy is applied.
Mohnike
K
K
Otto-von-Guericke-Universität Magdeburg, Zentrum für Kinderheilkunde, Germany.
Dörffel
W
W
Timme
J
J
Kluba
U
U
Aumann
V
V
Vorwerk
P
P
Mittler
U
U
D000293:Adolescent; D000367:Age Factors; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology / Q000627:therapeutic use; D016022:Case-Control Studies; D003131:Combined Modality Therapy; D016371:Cranial Irradiation / Q000009:adverse effects; D004307:Dose-Response Relationship, Radiation; D005260:Female; D006128:Growth / Q000502:physiology; D006130:Growth Disorders / Q000209:etiology*; D006801:Humans; D008137:Longitudinal Studies; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy* / Q000532:radiotherapy*; D008297:Male; D015122:Mercaptopurine / Q000494:pharmacology / Q000627:therapeutic use; D008727:Methotrexate / Q000494:pharmacology / Q000627:therapeutic use; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000532:radiotherapy*; D011627:Puberty / Q000502:physiology
D000964:Antimetabolites, Antineoplastic; D015122:Mercaptopurine; D008727:Methotrexate