Growth impairment is a common late effect of childhood stem cell transplantation. A Japan-wide study found that growth hormone therapy improves adult height, but prior radiation therapy and transplant-related complications negatively affect how much children benefit.
Hematopoietic stem cell transplantation (HCT) is a treatment for some life-threatening cancers and nonmalignant disorders. As HCT is a curative treatment, it is used to treat children where necessary. It is historically a dangerous procedure, but advances in medicine have led to increases in the number of long-term survivors. This increase has also revealed late effects in childhood survivors, most notably growth impairment and short stature, which are common after HCT.
A multi-institute research team of the Japanese Children's Cancer Group, led by Hiroshima University, studied the long-term effectiveness and response patterns to growth hormone therapy in children who underwent HCT, and were thereafter diagnosed with short stature.
Their findings were published in the journal Frontiers in Endocrinology on May 20, 2026.
"Growth impairment is one of the most common long-term complications in children who undergo HCT," said Maiko Shimomura , assistant professor at Hiroshima University Hospital , and first and corresponding author of the study. "We aimed to determine whether GH therapy improves final height outcomes in childhood HCT survivors and to identify clinical factors associated with treatment response. This is important because the number of childhood transplant survivors is increasing, and improving long-term health and quality of life has become a major goal of survivorship care."
The researchers conducted a nationwide, multicenter retrospective cohort study of childhood HCT survivors with post-transplant short stature. Height outcomes were evaluated using final adult height standard deviation scores (SDS).
Of the 268 patients enrolled in the study, 171 had available final height data. Of these, 58 had received GH therapy, while the remaining 113 had not. Other patient characteristics such as age at diagnosis, age at HCT, sex, diagnosis, types of HCT, comorbidities and others were also collected, and all data was statistically analyzed.
"GH therapy was associated with improved final height outcomes in childhood HCT survivors with short statures," Shimomura said. "However, treatment responses were highly variable. Growth outcomes were strongly influenced by transplant-related factors such as total body irradiation (TBI) and chronic graft-versus-host disease (GVHD). Our findings suggest that GH therapy is beneficial, but individualized long-term management is essential."
One particularly interesting finding was that growth improvement often continued for many years after GH therapy was started, and height gains continued to increase at 5 years and even at final adult height in some patients. This is a marked difference from the pattern typically observed in children with classical GH deficiency.
The strongest negative predictor of height was total body irradiation (TBI), a form of radiotherapy that serves to destroy or suppress the recipient's immune system. TBI is often used prior to HCT to eradicate all cancer cells and increase the success of HCT. The researchers also observed differences in response to GH therapy depending on whether the transplant was allogenic—stem cells taken from a donor—or autologous—stem cells taken from the patient themself prior to HCT. This suggests that there are distinct biological mechanisms that underlie growth impairment.
"Our next goal is to better understand why some patients respond well to GH therapy while others show limited benefit," Shimomura concludes. "We hope to identify patients at risk for poor growth outcomes and develop more personalized treatment strategies. Ultimately, our goal is not only to help children survive transplantation, but also to help them achieve their full growth potential and enjoy a better quality of life throughout adulthood."
This study was carried out by the Transplantation and Cellular Therapy Committee and the Long-term Follow-up Committee of the Japanese Children's Cancer Group.
This study was supported by the Hiroshima University Hospital Research Support Grant.
