Growth Failure and Growth-Hormone Deficiency After Treatment for Acute Lymphoblastic Leukaemia

Kirk, J A; Stevens, Michael; Menser, Margaret A.; Tink, Arnold; Raghupathy, P.; Cowell, CT; Bergin, Mary; Vines, RobertH.; Silink, Martin

doi:10.1016/s0140-6736(87)90004-3

Cited by 189 publications

(105 citation statements)

References 19 publications

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“…Clinical studies usually attribute effects on growth and craniofacial development to cranial irradiation (5, 9-11), although corticosteroids and chemotherapy are thought to be contributory (I, 32, 33). Clearly, it is not understood how radiation schedules and chemotherapy protocols interact to cause growth failure and growth hormone deficiency (3,34). The growth hormone requirements of children treated for ALL are still controversial (12).…”

Section: Discussionmentioning

confidence: 99%

“…Lp., intraperitoneal(ly) P, treatment with prednisolone GRF, growth hormone-releasing factor M, treatment with methotrexate X. treatment with cranial irradiation CNS therapy for childhood ALL has welI-documented adverse effects on growth and cognition. The growth deficits include short stature, increased weight for height, microcephaly, midfacial hypoplasia, and mandibular retrognathia (1)(2)(3)(4)(5). The cognitive deficits do not include mental retardation or hyperactivity, but significant reductions in overall IQ scores develop, along with impaired verbal and visual-spatial memory abilities, attention, organization, and motor output (6)(7)(8) …”

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confidence: 99%

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Radiation Effects on Growth Are Altered in Rats by Prednisolone and Methotrexate

Schunior¹,

Mullenix

Zengel³

et al. 1994

Pediatr Res

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ABSTRACT. CNS therapy for childhood leukemia has adverse effects upon growth and cognition. The cause of these deficits is unknown. In a rat model, we determined which agent, or combination of agents, in CNS therapy affected growth. Young Sprague-Dawley rats were exposed to cranial irradiation (1000 cGy), methotrexate (2 or 4 mg[ kg, intraperitoneally), or prednisolone (18 or 36 mg[kg, intraperitoneally) alone or in two-or three-agent combinations. Matched control groups received appropriate sham radiation, intraperitoneal saline, or both. Body weight was recorded from 14 through 150 d of age. After the rats were killed at 150 d, body length was recorded and the head and left femur were removed to determine body and craniofacial proportions. Cranial irradiation alone, but not methotrexate or prednisolone alone, stunted growth permanently and altered craniofacial proportions. When these agents were combined, methotrexate and prednisolone modified the growth response to cranial irradiation. Methotrexate given before cranial irradiation prevented radiation stunting in males. This protection was lost when the dose of methotrexate was increased, when prednisolone was added to the combination, or when females were studied. The protection in males was effective against both growth and behavioral deficits. These results indicate that the physical and behavioral side effects of CNS therapy are better understood in the context of dose, sex, and interactions ofthe agents. (Pediatr Res 35: 416-423,1994) The cause of these adverse effects has been reported to be cranial irradiation alone (9-11), or cranial irradiation interacting with chemotherapy ( I, 4, 12).Cranial irradiation or methotrexate has been manipulated in CNS therapy in an attempt to prevent neurotoxic interactions (13-15). Yet, the impact of these manipulations is uncertain, considering that some cranial irradiation and methotrexate interactions may be protective rather than neurotoxic. Balsom et al. (16) found that preirradiation methotrexate protected against decreased intellectual function in ALL survivors, illustrating the importance of agent interactions and sequence of administration to long-term outcome.We developed an animal model to study growth and behavioral deficits associated with exposures to cranial irradiation, methotrexate, and prednisolone, either as single agents or as combinations (17,18). Cranial irradiation alone stunted growth without significantly altering behavior, whereas cranial irradiation combined with methotrexate and prednisolone disrupted behavior in addition to stunting growth. Further study of behavior (19) demonstrated how different agent interactions affected outcome: 1) behavioral "signatures" varied with the components of the agent combinations; 2) behavioral outcome was influenced by steroids as welI as by cranial irradiation and methotrexate; 3) behavioral outcome was sex dependent; and 4) behavioral outcome varied with dose, which determined whether agents interacted antagonistically or synergisticalIy. Therefore, not...

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Radiation Effects on Growth Are Altered in Rats by Prednisolone and Methotrexate

Schunior¹,

Mullenix

Zengel³

et al. 1994

Pediatr Res

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“…One cause of the growth retardation in patients with ALL is thought to be cranial irradiation, which affects growth hormone secretion, among other results. 32,33 Cranial irradiation, however, cannot be the only cause of growth retardation. Cytostatic treatment with drugs like 6-mercaptopurine, methotrexate and vincristine could decrease production of insulin-like growth factor (IGF-I), and high doses of steroids also affect growth rate.…”

Section: Height Heightmentioning

confidence: 99%

Nutritional assessment and serum zinc and copper concentration among children with acute lymphocytic leukemia: a longitudinal study

et al. 2006

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CONTEXT AND OBJECTIVE: When undergoing chemotherapy and/or radiotherapy, children with acute lymphocytic leukemia may present important nutritional disorders because of the gastrointestinal toxicity of most chemotherapy agents or the effects of radiation on the organism. These patients may also present changes in their serum concentrations of trace elements such as zinc and copper. The present study aimed to follow anthropometric parameters and serum levels of zinc and copper in a group of children under treatment for acute lymphocytic leukemia. DESIGN AND SETTING: Longitudinal study, at the Pediatric Section of Hospital das Clínicas, Ribeirão Preto, Brazil. METHODS: Forty-five children with acute lymphocytic leukemia were studied. Anthropometric parameters such as weight and height and the daily intakes and serum levels of copper and zinc were recorded at diagnosis and during the treatment. RESULTS: During the initial phase of the treatment, there was an increase in energy intake accompanied by weight gain. However, during the later phases of treatment there was a reduction in energy intake with accompanying weight loss. Decreased growth rate during treatment was more pronounced in children with high-risk acute lymphocytic leukemia, probably due to radiation therapy. Serum zinc levels remained basically unaltered during the treatment, whereas copper levels decreased dramatically with the beginning of treatment. CONCLUSIONS: The treatment given to children with acute lymphocytic leukemia has an important effect on their linear growth rate and nutritional status, and also on their serum copper levels.

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“…and the duration of the radiation therapy (16). In children treated with low range radiation doses the apparent frequency of GH deficiency may also depend on the type of stimulation testing: impairment of GH response to insulin-induced hypoglycemia but not to arginine stimulation was reported after 2400 cGy by some (1 7, 18) but not other investigators (19).…”

Section: Growth Hormone Deficiencymentioning

confidence: 99%

Growth and Endocrine Disorders Secondary to Cranial Irradiation

1989

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Growth Failure and Growth-Hormone Deficiency After Treatment for Acute Lymphoblastic Leukaemia

Cited by 189 publications

References 19 publications

Radiation Effects on Growth Are Altered in Rats by Prednisolone and Methotrexate

Radiation Effects on Growth Are Altered in Rats by Prednisolone and Methotrexate

Nutritional assessment and serum zinc and copper concentration among children with acute lymphocytic leukemia: a longitudinal study

Growth and Endocrine Disorders Secondary to Cranial Irradiation

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