Changes of Bone Density in Pediatric Patients with β-thalassemia Major after Allogenic Hematopoietic Stem Cell Transplantation.
Hematology-Oncology and Stem Cell Transplantation Research Center, Tehran University of Medical Sciences, Tehran, Iran. . Archives of Iranian medicine
(Impact Factor: 1.11).
Thalassemia major and its treatment by stem cell transplantation can have deleterious effects on bone integrity. This study assesses the adverse effects of transplantation on growing bones of pediatric thalassemic patients.
Bone mineral density (BMD) of 20 patients from three thalassemia classes whose mean (SD) age was 7.4 (3.8) years were tested with a Norland XR-46 device at baseline (before transplantation), 6 and 12 months after transplantation.
At 6 and 12 months after transplantation we observed no significant changes in mean BMD. There were no Z-scores less than -2 among patients. Class 3 thalassemia did not negatively impact BMD. Calcium (Ca), phosphorous (P) and ferritin levels were not significantly related to patients' BMD scores. Transfusion duration and chelation therapy showed positive significant relationships to BMD (g/cm2), but no significant relation with the BMD Z-score. The deleterious relation between corticosteroid use and changes in BMD was not significant. In contrast, patients who developed acute graft versus host disease (aGVHD) after transplantation showed significant adverse effects on BMD of their femur (P = 0.020) and spine (P = 0.027).
Stem cell transplantation in pediatric thalassemic patients who do not develop aGVHD does not appear to have any significant positive or negative effects on BMD.
Available from: Amir Ali Hamidieh
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Beta thalassemia major is a genetic hemoglobin disorder that affects bone density. The disease leads to deteriorating bone structure but can be treated with hematopoietic stem cell transplant. We aimed to assess bone mineral density changes in pediatric beta thalassemia major patients who had undergone a hematopoietic stem cell transplant compared with similarly affected patients who had not undergone a hematopoietic stem cell transplant.
Materials and methods:
Forty beta thalassemia major patients, 20 transplant and 20 nontransplant, younger than 16 years of age were enrolled. The mean age of transplant patients was 8.15 years and nontransplant patients was 9.5 years (P = .242). The female:male ratio was 1:1 in both groups. None of the patients reached puberty during this study. Bone mineral density was evaluated in transplant patients before and 1 year after hematopoietic stem cell transplant. Bone mineral density of nontransplant patients also was evaluated 1 year after their initial bone mineral density test. A Norland XR-46 densitometer was used to make all bone mineral density measurements. None of the patients had a z score < -2.
Mean bone mineral density changes in the femur and spine during this study were 0.008 ± 0.075 g/cm2 and 0.048 ± 0.045 g/cm2 in transplant patients and 0.045 ± 0.072 g/cm2 and 0.036 ± 0.058 g/cm2 in nontransplant patients. No significant differences between bone mineral density changes in transplant and nontransplant patients were detected during the study.
No significant effects on bone mineral density were detected in hematopoietic stem cell transplant pediatric beta thalassemia major patients compared with similarly affected nontransplant patients. Studies of longer duration may be required to identify significant changes in bone mineral density in hematopoietic stem cell transplant patients.
Experimental and clinical transplantation: official journal of the Middle East Society for Organ Transplantation 11/2014; 13(2). DOI:10.6002/ect.2014.0178 · 0.62 Impact Factor
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ABSTRACT: Low BMDs, short stature, hypogonadism, subclinical hypothyroidism, and IFG are found in 3.3, 10, 33, 16.6, 6.6, and 26.6 % of 30 pediatric β thalassemia major patients, respectively. Age is related with low Z-scores. Short stature and hypogonadism patients were older. These patients’ monitoring in late childhood and early teenage for these complications is recommended.
Beta-thalassemia major patients frequently have low BMD and increased fracture risk. We tried to determine the relation between BMD and biochemical, transfusion, and endocrinological parameters in pediatric patients.
Thirty beta-thalassemia major patients entered the study. Male to female ratio was 14/16. Physicians collected demographic; anthropometric; menstrual; transfusion and treatments histories; and serum levels of calcium, phosphorus, alkalin phosphatase, FBS, Hb, Ferritin, T3, T4, TSH, LH, FSH, testosterone (for boys), and estradiol (for girls). BMD of the spine and femur was measured using a DXA Norland XR-46 device.
Prevalence of “low bone density” (Z-score
Archives of Osteoporosis 12/2014; 9(1):174. DOI:10.1007/s11657-014-0174-3
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ABSTRACT: Bone marrow transplants (BMTs) are mainly limited by a low number of CD34(+) cells. The transforming growth factor-beta (TGF-β) pathway downregulation is a key factor that increases cell self-renewal. In nature, hematopoietic stem cells (HSCs) are in a microenvironment, surrounded by cells in a three-dimensional (3D) configuration. The aim of this study is to investigate the association between a 3D culture and the delivery ratio of downregulation. Demineralized bone matrix (DBM) and mineralized bone allograft (MBA) scaffolds were coated using unrestricted somatic stem cells (USSCs) as the feeder layer. Umbilical cord blood (UCB)-CD34(+) cells were then ex vivo expanded in them and transfected by small interfering RNA (siRNA) against TGFbR2, a type 2 receptor in the TGF-β pathway. Finally, quantitative real-time PCR, flow cytometry, and clonogenic assay were performed. In a global comparison, we observed that the highest expansion ratio, lowest expression level, and the highest CD34 marker belonged to the simple 2D culture transfected group. This suggests that TGFbR2 downregulation in a 2D culture can be done more effectively. The siRNA delivery system and the transfection ratio in an ex vivo environment, which mimicks in vivo conditions, have low efficiency. Genetic modification of the cells needs free 3D spaces to enable better transfection.
In Vitro Cellular & Developmental Biology - Animal 12/2014; 51(5). DOI:10.1007/s11626-014-9854-y · 1.15 Impact Factor
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