Tehran University Medical Journal

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Background: Graft-versus-host disease is one of the major complications after allogenic bone marrow transplantation, but it is not easy to anticipate the onset. Cytokines released by type 1 T-helper cells are thought to play a pivotal role in acute graft-versus-host disease (aGVHD). The ability to predict the likely occurrence of graft-versus-host-disease (GVHD) after BMT would be extremely valuable. By serially measuring serum levels of soluble IL-2 receptor (sIL-2R), IL-18 and following allogeneic bone marrow transplantation (BMT), we tried to define their relationship to aGVHD as complication of the transplantation and determine useful markers for aGVHD predictors.

Materials and Methods: Serum sIL-2R, IL-18, and levels were measured by sandwich ELISA in 219 sera samples from 39 patients (with hematological disorders before and after allogeneic BMT) and 28 controls. All patients received BMT from HLA-identical siblings.

Results: 25 patients developed aGVHD and serum levels of sIL-2 R and IL-18 , in sera drawn before transplantation , in patients with acute graft-versus-host disease (aGVHD +) , were increased in comparison of patients without acute graft-versus-host disease (aGVHD ¯) and control group and there wasn’t any significant differences in serum levels of sIL-2 R and IL-18 in aGVHD ¯ patients and controls. Serum level of IL-18, in aGVHD+ patients, was increased during day 3 - 24 after BMT, and there was a significant difference in patients with GVHD 0 – GVHD III. In majority of patients with acute GVHD (60 %) , the peak levels of IL-18 and IL-2R was achieved on day 10 after BMT and the rise in sIL-2R and IL-18 preceded of clinical signs of GVHD (mean day 15 after BMT). Level of IL-18 in patients with aGVHD had strongly correlated with the severity of aGVHD on Day 10 after BMT. IL-18 level mean (before BMT), in patients who received Busulfan and Fludarabin to treat aGVHD, was lower than in patients who received Busulfan - Endoxan, or Cyclophosphamide.

Conclusion: Our data concluded that IL-18 plays an important role in the development of aGVHD and IL-18 level might be an indicator for aGVHD, reflecting the severity of the disease. These findings suggest that IL-18 may play important roles in the pathogenesis of aGVHD and that measurement of serum IL-18 levels can be useful predictor of aGVHD.

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Background: Bone marrow transplantation (BMT) is the treatment of choice for many patients with malignant and nonmalignant diseases. Long-term complications such as osteoporosis should be considered, because it is directly associated with the morbidity and mortality. The purpose of this study is to assess the bone mineral density after allogenic or autologous bone marrow transplantation in patients with leukemia or lymphoma.
Methods: We prospectively investigated 63 patients undergoing BMT for acute and chronic leukemia and lymphoma. At the end of the study, a total of 28 patients were assessed. Bone mineral density (BMD) was measured prior BMT, and 6 and 12 months after BMT. Osteocalcin, bone alkaline phosphatase and C-terminal telopeptides of type 1 collagen (ICTP) were assessed. Serum concentration of calcium, phosphorous, vitamin D, PTH and sex hormones (FSH, LH, testosterone and estradiol) were also measured.
Results: There was a significant decrease in the bone mineral density of the femoral neck six months after BMT (p<0.001), 1.01±0.13g/cm² prior to BMT and 0.96±0.13 g/cm² at six months, but no considerable changes were seen in lumbar vertebrae. Bone loss between the 6th and 12th months was not observed. The levels of ICTP and phosphorus increased significantly by the 12th month (p=0.04). The level of calcium was higher at the 6th month (p=0.002) but the level of vitamin D and PTH decreased by the end of the study (p=0.04 and p=0.01, respectively) and the average of osteocalcin did not increase significantly. In women, the level of estradiol decreased by the 6th month (p=0.01), but the testosterone changes were not significant.
Conclusion: The risk of bone loss in both allogeneic and autologous BMT is higher in the femoral neck than the lumbar vertebrae, occurring mainly in the first six months after BMT. Preventive and clinical procedures should be considered.