Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.1.1.69 (BMT)
 2,655 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Previously, we reported that 26 children with stage III or IV neuroblastoma (NBL) treated with BMT grew poorly post-BMT and significantly worse than a comparison group of hematologic BMT patients. Furthermore, unlike the hematologic patients, there was no apparent catch-up growth. Six of these previously reported long-term (> 2 years) NBL patients surviving BMT were evaluated with growth hormone (GH) provocative testing, frequent (every 20 min) overnight GH sampling and IGF-1 determinations. Three of 6 patients were GH deficient based on subnormal responses to provocative stimuli and subnormal pooled 12 h GH values. Only one child had completely normal GH testing and his growth was normal. Four patients were tested with recombinant GH for a period of 12-21 months. Three patients demonstrated an improvement in their growth velocity on therapy. However, the overall response to GH treatment was significantly less than the growth response in children who are GH-deficient due to causes other than BMT. In summary, GH deficiency may be a frequent complication of BMT treatment of NBL. It also appears that the BMT treatment protocol employing total body irradiation and high-dose melphalan may induce GH resistance.
 ...
PMID:Growth hormone function and treatment following bone marrow transplant for neuroblastoma. 827 38

The aim of the present study was to assess growth, final height, growth hormone (GH) secretion and growth factors after BMT including TBI in childhood. The median age of the 25 participants was 11.3 years at BMT, and a median of 7.5 years had elapsed since BMT. The median height standard deviation score (SDS) declined significantly from diagnosis until 4 years after BMT (n = 25, P = 0.015), and decreased 1.08 SDS from diagnosis until final height (n = 14, P = 0.030). Sitting height to standing height ratio was impaired, -0.64 SDS, P < 0.05. GH insufficiency was found in 32% at follow-up. Repeated assessments of GH production over the years indicated improvement in GH secretion in nine individuals. Evaluation of spontaneous 24-h GH secretion indicated a secretory pattern similar to controls, although the total amount of GH secreted was lower. Neither insulin-like growth factor-1 (IGF-1) nor IGF binding protein-3 (IGFBP-3) alone could be used as a marker of GH insufficiency. IGF-1 was low: -1.18 SDS; (P < 0.001). In conclusion, our study demonstrated the impact on growth, final height, body proportions, GH secretion and growth factors after BMT including TBI. We hypothesize that children who receive BMT at a younger age are more at risk of loss of final height and abnormal body proportions. Our data indicate that some improvement in GH production may occur over the years.
 ...
PMID:Growth, growth hormone and final height after BMT. Possible recovery of irradiation-induced growth hormone insufficiency. 883 10

The aim of this study was to evaluate the treatment effects with recombinant human growth hormone (rhGH) in a group of patients after bone marrow transplantation for thalassemia major. At the end of treatment we divided the subjects into two groups according to the outcome of the therapy: responder and nonresponder. Responder group: after 24 months of rhGH administration, growth rate was still significantly higher in respect to start of treatment (P < 0.0001). Plasma levels of IGF-I rose significantly (P < 0.003). The serum levels of serum asparate aminotransferase (SGOT) and alanine aminotransferase (SGPT) were higher compared to normal values but improved in non-responder patients. There was no difference in the mean concentration of these parameters before and after treatment (P = NS). Non-responder group: these patients had a worsening of the growth rate during rhGH administration. There was no increase of the IGF-I levels. Single values of transaminase and ferritin levels were higher than in responder patients before and after treatment. There was a significant correlation between IGF-I, SGOT, SGPT and ferritin in all patients before and after therapy. It appears from these data that rhGH administration is worth serious consideration in patients after BMT for thalassemia major presenting impaired growth hormone secretion. This treatment can offer good results only in cases where the normal hepatic synthesis of IGF-I is conserved and where liver damage has not reached irreversible conditions, as we have seen in the responder group.
 ...
PMID:Growth after recombinant human growth hormone (rhGH) treatment in transplanted thalassemic patients. 933 58

With the increasing use and success of BMT, larger numbers of children survive transplantation. Still, cancer treatment in children causes damage to the endocrine glands, often inducing growth deficiency, pubertal delay and thyroid dysfunction. This paper will deal with some of the most common endocrine disorders related to BMT in the pediatric population. Irradiation is the major contributor for growth impairment after BMT, acting through lesion to epiphyseal growth-plate, gonadal damage with delayed or precocious puberty, hypothyroidism, and growth hormone insufficiency. Gonadal dysfunction can be induced both by a direct injury to the gonads (irradiation, gonadotoxic agents) causing primary hypergonadotropic-hypogonadism, and with less frequency, by neuroendocrine injury to the hypothalamo-pituitary axis causing hypogonadotropic-hypogonadism. It seems that both doses of chemotherapy and of irradiation used by different regimens, fractionation of irradiation, and age at the time of BMT are the most important factors when we deal with toxic endocrine late-effects in long term survivors. In order to improve the quality of life of each single patient who receive BMT, and without inflicting the success-rate of this procedure, we recommend a life-long surveillance to prevent or to treat symptoms and disorders caused by hormone deficiencies, and we also advocate for a multidisciplinary team-approach that includes an endocrinologist consultant.
 ...
PMID:Endocrine late effects in children who underwent bone marrow transplantation: review. 963 Mar 30

Impaired growth after TBI prior to BMT has been a constant finding in children with leukemia. The growth of poor-risk neuroblastoma (NBL) survivors treated with myeloablative preparative regimens and ABMT at the Hospital for Children and Adolescents, University of Helsinki, since 1982 is reported. Two separate groups were analyzed: (1) The TBI- patients (n = 15) were conditioned with high-dose chemotherapy only. They had been treated at the age of 1.0-6.3 (mean 3.0) years and the post-ABMT follow-up time was 1.5-14.5 (mean 7.7) years. (2) The TBI+ patients (n = 16) had received TBI in addition to high-dose chemotherapy. They had been treated at the age of 1.3-4. 8 (mean 3.0) years, and the post-ABMT follow-up time was 1.5-8.0 (mean 4.7) years. The height standard deviation score (SDS) was similar for the two groups at the time of diagnosis, -0.3 +/- 1.2 (mean +/- s.d.), and at the time of ABMT, -0.7 +/- 1.1. After transplantation, the height SDS continued to decrease in the TBI+ group, the mean being -2.0 SDS at 5 years after ABMT. In the TBI-group, the mean height SDS remained within -0.7 to -0.9 to the 10 years of follow-up. Five patients received growth hormone (GH) therapy starting 2-6 years after ABMT. They all had low GH secretion in provocative tests. All showed some response to GH therapy. The mean height SDS increased 0.4 SDS during the 3 years following the start of GH therapy, while in the untreated patients a decrease of 0. 8 SDS during the corresponding time (P = 0.009) was observed. We conclude that NBL patients grow poorly following ABMT when TBI is included in the conditioning regimen, but close to normally when treated without TBI. The need for GH therapy should be evaluated early to avoid an unnecessary decrease in final height.
 ...
PMID:Growth in children with poor-risk neuroblastoma after regimens with or without total body irradiation in preparation for autologous bone marrow transplantation. 1057 63

Transplantation of whole bone marrow (BMT) leads to engraftment of both osteoprogenitor cells and hematopoietic cells; however, the robust osteopoietic chimerism seen early after BMT decreases with time. Using our established murine model, we demonstrate that a post-BMT regimen of either granulocyte-colony stimulating factor, growth hormone, parathyroid hormone, or stem cell factor each stimulates greater donor osteoblast chimerism at 4 months posttransplantation than saline-treated controls and approximates the robust osteopoietic chimerism seen early after BMT; however, only growth hormone led to significantly more donor-derived osteocytes than controls. Importantly, there were no adverse hematologic consequences of the different treatments. Our data demonstrate that these cytokines can stimulate the differentiation of transplanted donor marrow cells into the osteopoietic lineage after BMT. Post-BMT cytokine therapy may generate durable osteopoietic engraftment, which should lead to sustained clinical benefit and render BMT more applicable to bone disorders.
 ...
PMID:Cytokine-induced osteopoietic differentiation of transplanted marrow cells. 2171 5