Kinya Hattori

The Kinetics of Immune Reconstitution after Cord Blood Transplantation and Selected cd34+ Stem Cell Transplantation in Children: Comparison with Bone Marrow Transplantation

The present study compares immune reconstitution after allogeneic cord blood transplantation (CBT) and CD34+ stem cell transplantation (CD34-SCT) with that after bone marrow transplantation (BMT). Eighty-eight children who underwent CBT (20 patients), BMT (58), and CD34-SCT (10) were enrolled, and lymphocytes and T-, B-, and natural killer—lymphocyte subsets were monitored for more than 5 years after transplantation. CBT recipients showed significant increases in (1) total lymphocyte counts (P < .001), (2) CD4+/CD8+ cell ratios (P < .01), (3) CD4+ and CD4+CD45RA+ cells (P < .001), (4) CD8+CD11b+ cells (P < .001), and (5) CD19+ and CD19+CD5+ cells (P < .0001) and marked decreases in the frequencies of CD8+ and CD8+CD11b- cells (P < .0001). CD34-SCT recipients showed lower lymphocyte counts in the first 6 months and an emergence of lymphocyte and CD4+CD45RA+ cells at approximately 9 months and 1 year. Both CBT and CD34-SCT recipients showed increased frequencies of CD56+ cells at 1 month (CD34-SCT versus BMT, P < .001) but decreased frequencies after 6 months (CBT versus BMT, P < .001). Lymphoproliferative responses to exogenous interleukin 2 were constantly lower in CBT and CD34-SCT recipients than in BMT recipients.These results suggest that the delay in immune reconstitution after CBT in the early phase was mainly qualitative and related to the immaturity of cells, whereas the delay in CD34-SCT was mainly quantitative in the first several months. Int J Hematol. 2003;77:399-407.

Changes in thyroid function after bone marrow transplant in young patients.

Abstract Background : Changes in thyroid function among young patients who received bone marrow transplantation (BMT) were evaluated.

Changes in hypothalamic-pituitary function following bone marrow transplantation in children

Patients who undergo bone marrow transplantation (BMT) frequently experience impaired pituitary function, but precise assessment using repeated provocative tests has not been described. We studied 32 children (16 boys) who had BMT after receiving preparative irradiation. Assessment of pituitary function was performed by infusing insulin, luteinizing hormone‐releasing hormone (LHRH), and thyrotropin‐releasing hormone (TRH) on several occasions at various intervals during the follow‐up period.

Growth and growth hormone secretion in children after bone marrow transplantation.

Long‐term sequelae of bone marrow transplantation (BMT) are a major concern among long‐term survivors since the procedure has been considerably developed over the past decade. In this study, linear growth and growth hormone (GH) secretion were evaluated in 25 children (14 males and 11 females) with various neoplastic or non‐neoplastic hematological disorders who had survived for more than 3 years after BMT. Impaired linear growth after BMT, as defined by a change in height standard deviation score (SDS) by more than − 1.0 SD, was observed in 14 patients (56%). Four children showed severe growth suppression with a decrease in SD score by more than 2.0, and 10 exhibited a moderate reduction by between 1.0 and 2.0 SD. A recovery of normal height velocity was observed in those who had received BMT at a younger age. The type of disease, a difference in preconditioning regimen, the presence of chronic graft‐versus‐host disease or a GH secretory capacity 1 year after BMT were not contributing factors for impaired growth. A serial examination of GH secretion with insulin‐induced hypoglycemia demonstrated that poor GH secretion was not necessarily a prerequisite for impaired growth. These results indicate that the secretory status of GH does not predict the future growth pattern of children who received BMT.

Growth and Endocrine Function in Long-term Adult Survivors of Childhood Stem Cell Transplant

The number of long-term surviving stem cell transplant (SCT) recipients has increased steadily, and attention has now extended to the late complications of this procedure. The objective of this study was to investigate relationship among growth and endocrine functions in long-term adult survivors of childhood SCT. The inclusion criteria of this study were survival at least 5 yr after SCT and achievement of adult height. Fifty-four patients (39 males) fulfilled these criteria and were included in this study. Growth was mainly evaluated by height standard deviation score (SDS) and individual longitudinal growth curves. Among the 54 patients, those that received SCT before 10 yr of age showed significantly greater reductions in changes in height SDS (mean –1.75, range –4.80 to –0.10) compared with those that received SCT at or after 10 yr of age (mean –0.50, range –1.74 to 1.20; P<0.001). The mean loss of height for all patients who received SCT during childhood was estimated to be approximately 1 SDS/6.5 yr (r=0.517). Individual longitudinal growth curves indicated that a significant growth spurt was absent in severe short stature patients during the pubertal period without severe endocrine dysfunctions including GH deficiency. The incidence of growth disorder in long-term adult survivors depends on the age at SCT and whether they received radiation therapy. Life-long follow-up is necessary for survivors to detect, prevent and treat the late endocrine complications in SCT survivors.

Allogeneic bone marrow transplantation in childhood leukemia.

Allogeneic bone marrow transplantation was performed in 94 patients with hematologic malignancies or other various diseases during the period between March 1982 and November 1990 at Tokai University Hospital. Projected disease‐free survival rates of HLA genotypically identical marrow recipients were 88.9% for chronic myeloid leukemia transplanted in the first chronic phase (N = 9), 90.9% for acute leukemia in the first complete remission (N = 15), 54.5% for acute leukemia in later remissions (N = 14), 62.5% for solid tumors (N = 8) and 0% for patients transplanted in relapse (N = 7). The rate for HI A‐mismatched marrow recipients with leukemia was 27.8% (N = 16). For patients with non‐neoplastic diseases it was 100% regardless of HLA‐compatibility (N = 26). The quality of life in long‐term surviving pediatric marrow recipients has been acceptable. Common abnormalities among survivors are long‐lasting hypogonadism due to radiation and subclinical impairment of lung function in the first year post‐BMT. About two‐thirds of children experienced a transient decrease in growth velocity in the immediate posttransplant period.