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Growth in children after bone marrow transplantation for acute leukemia
1Department of Pediatrics, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
Insights
Children undergoing bone marrow transplant (BMT) for acute leukemia, especially those receiving cranial radiation, experience significant growth failure. Growth hormone deficiency is common, but GH therapy improves growth velocity.
Area of Science:
- Pediatric Oncology
- Endocrinology
- Hematology
Background:
- Bone marrow transplantation (BMT) is a critical treatment for acute leukemia in children.
- Hyperfractionated total body irradiation (TBI) is used in BMT preparation.
- Cranial irradiation (RT) is sometimes administered before BMT.
Purpose of the Study:
- To evaluate the long-term growth outcomes in children with acute leukemia post-BMT.
- To identify factors influencing growth failure after BMT.
- To assess the prevalence of growth hormone deficiency and the efficacy of growth hormone (GH) therapy.
Main Methods:
- Studied 72 children (<14 years) with acute lymphoblastic leukemia (ALL) or acute myelogenous leukemia (AML) undergoing BMT.
- Analyzed height standard deviation scores (SDS) up to 4 years post-BMT.
- Compared growth outcomes based on prior cranial RT, leukemia type, and TBI dosage.
Main Results:
- Overall height SDS decreased significantly from -0.28 at BMT to -1.11 at 4 years (P < .0001).
- Patients receiving cranial RT showed a greater height SDS loss (-0.52 to -1.83) compared to those without (-0.11 to -0.73).
- ALL patients experienced greater height loss than AML patients (P = .033). Fifteen of 18 tested patients were GH deficient; GH therapy improved growth velocity in 9 patients.
Conclusions:
- Children with acute leukemia, particularly ALL patients receiving cranial RT before BMT, are at high risk for growth failure and GH deficiency.
- Fractionation of TBI may offer some growth sparing effect.
- GH therapy is effective in improving growth velocity in GH-deficient pediatric BMT patients.
Abstract:
We evaluated the growth of children with acute leukemia who received a bone marrow transplant (BMT) after preparation with hyperfractionated total body irradiation (TBI). Seventy-two patients (27 female and 45 male patients) with acute lymphoblastic leukemia (ALL; n = 39) or acute myelogenous leukemia (AML; n = 33) who were less than 14 years of age at BMT were studied. Before BMT all had received multiagent chemotherapy and 31 had received cranial irradiation (RT). Preparation for BMT included total body irradiation (1,375 cGy [n = 37] or 1,500 cGy [n = 35]). Heights, expressed as standard deviation scores (SDS), were studied up to 4 years post-BMT. The estimated height SDS for the entire group at the time of BMT was -0.28 +/- 0.05 and decreased to -1.11 +/- 0.22 at 4 years post-BMT (P < .0001). Using a growth curve model to compare covariate groups over the period of study, we found that the loss in height SDS was most significant in those patients who received cranial RT before BMT (P = .005). The estimated height SDS for patients treated with cranial RT went from -0.52 +/- 0.20 at transplantation to -1.83 +/- 0.23 4 years later. In contrast, patients who did not receive cranial RT before BMT showed a smaller decrease in height SDS over the 4-year observation period, ie, -0.11 +/- 0.20 decreasing to -0.73 +/- 0.21. Similarly, patients with a diagnosis of ALL had a greater loss of height SDS than those with AML (P = .033). Fifteen of 18 patients tested were found to be growth hormone (GH) deficient; 9 patients were treated with GH and all showed an improvement in growth velocity (P < .0001). We conclude that (1) children with acute leukemia who have received cranial RT and subsequently undergo BMT, primarily those with ALL, are at high risk for growth failure and GH deficiency, and (2) that fractionation of TBI may have a relative sparing effect on growth.