Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0018133 (graft-versus-host disease)
 18,032 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Radiographically detectable complications in 35 children after bone marrow transplant are reviewed. These complications are most frequently due to infection, chemoradiotherapeutic toxicity, and graft versus host disease (a transplant rejection phenomenon peculiar to bone marrow transplant patients). The pulmonary complications within the first 2 months are secondary to a form of interstitial lung disease. Interstitial lung disease has a strong correlation with graft versus host disease. Extrapulmonary visceral complications include hepatosplenomegaly, nephromegaly, and hemorrhagic cystitis. These are due to graft versus host disease, radiation, and chemotherapeutic toxicities, respectively. Sinusitis, cerebral atrophy, and intracerebral hematomas are less frequent complications. Osteoporosis due to steroids is the single most important osseous complication.
 ...
PMID:Radiographic manifestations of bone marrow transplantation in children. 3 66

Nine adult patients 31-47 (median 39) years of age treated with prednisone and cyclosporin A (CsA) for chronic graft-versus-host disease (GVHD) were evaluated for biochemical factors associated with skeletal turnover at initiation of immunosuppressive therapy (3 months after marrow transplant) and 9 months later (follow-up). Absorptiometry studies of the wrist and lumbar spine were also performed. Serum levels of 1,25-dihydroxycholecalciferol (1,25(OH)2D) were decreased at enrollment, particularly in the six males. Values for all nine patients remained low at follow-up. Levels of serum 25-hydroxycholecalciferol (25(OH)D), parathyroid hormone, and ionized calcium were normal at enrollment and follow-up. Mean urine hydroxyproline and calcium levels were elevated at enrollment, suggesting increased bone resorption; the mean values decreased to the high normal range at follow-up. Urine magnesium excretion was elevated in eight of nine patients at baseline and remained elevated at follow-up in three of eight evaluable patients. Single and dual photon absorptiometry of the wrist and spine, respectively, and dual energy X-ray absorptiometry of the spine, were utilized to evaluate bone mineral density over time. The precision of these tests was, respectively, +/- 3.5%, +/- 3.1% and +/- 1.0%. Results showed a significant ( > 2.5 times the precision) decrease over 9 months in bone mineral density in three of five evaluable males and all three females. The findings indicate increased collagen and bone turnover, increased urinary magnesium and calcium excretion and a significant risk of osteoporosis in patients receiving treatment for chronic GVHD. Preventive measures, including gonadal hormone replacement in females, should be initiated early after transplantation. Further studies are needed to identify patients at highest risk of bone loss and to monitor the effects of preventive therapy.
 ...
PMID:Bone density loss during treatment of chronic GVHD. 870 93

A significant proportion of patients will be long-term survivors of bone marrow transplantation (BMT) and little is known about their risk of late bony complications. We therefore evaluated bone mineral density (BMD) prior to BMT, post-transplantation changes in BMD, and mechanisms of bone loss in long-term survivors. We performed two analyses. The first was a cross-sectional study of 83 consecutive BMT patients (38 F, 45 M), examining the relationship between BMD and bone turnover, measured immediately prior to transplantation, and a number of disease and patient variables. The second was a prospective study of 39 patients (19F, 20 M) followed for a median of 30 months (range 5-64 months) following either allogeneic (allo, n = 29) or autologous (auto, n = 10) BMT to determine if bone loss was related to treatment of graft versus host disease (GVHD) with glucocorticoids and cyclosporine A, high bone turnover rates, or hypogonadism. Auto BMT recipients acted as a control group for effects of GVHD therapy on BMD. Prior to BMT, spinal and femoral neck (FN) BMDs were 8.6% and 14% lower in female auto BMT recipients than in female allo BMT recipients, respectively (p = 0.12 and p = 0. 003). Urinary bone resorption markers were higher than in normal gender- and age-matched control subjects. Patients treated previously with glucocorticoids also had 8% lower FN BMD. Glucocorticoid-pretreated women with amenorrhoea had lower lumbar spine (LS) and FN BMDs than eumenorrheic women and women receiving HRT. Post-allo BMT, patients lost 11.7% of FN BMD compared with a nonsignificant decrease of 1.1% post-auto BMT (p < 0.001). Spinal BMD and total body bone mineral content (TBBMC) decreased by 3.9% and 3.5%, respectively, post-allo, compared with an increase (1.5%, p = 0.03) or nonsignificant decrease (-3.7%, p = NS), respectively, post-auto BMT. Post-allo BMT bone loss correlated best with the cumulative prednisolone dose at the LS and FN, and with average daily prednisolone dose for TBBMC. At the spine, the rate of bone loss was 4%/10 g of prednisolone, while the rate of bone loss at the FN was greater (9%/10 g of prednisolone). Bone loss was also negatively related to the duration of cyclosporine therapy for GVHD and baseline deoxypyridinoline concentrations. Avascular necrosis of the femoral head occurred in four, and vertebral and rib fractures occurred in one of the allo BMT patients, but in no auto BMT patients. In conclusion, BMT recipients are at risk of osteoporosis secondary to bone loss associated with their underlying illness and/or chemotherapy, particularly in female autograft recipients, and in allograft recipients secondary to GVHD and its treatment.
 ...
PMID:Mechanisms of bone loss following allogeneic and autologous hemopoietic stem cell transplantation. 1002 99

Bone marrow transplantation is now an established successful treatment for several hematologic malignancies. Bone loss is among the long-term adverse effects of this procedure. The underlying pathophysiology is believed to be multifactorial. We report a case of osteoporosis in a young patient who underwent allogenic bone marrow transplantation for acute lymphoblastic leukemia that was complicated by intestinal graft-versus- host disease. Her bone density measurement showed T-scores of -3.46 and -2.47 in the lumbar spine and femoral neck respectively. On evaluation, she had low normal serum calcium, low urine calcium, low 25- hydroxyvitamin D, elevated total and bone specific alkaline phosphatases, and elevated parathyroid hormone. Following treatment with calcifediol, the biochemical markers normalized and the bone mineral density increased by 88% in the lumbar spine and almost 60% in the femoral neck, both of which were above the mean for her age group. We believe that the graft-versus-host disease caused a malabsorptive state that led to vitamin D deficiency and possible resistance and consequent osteomalacia.
 ...
PMID:Dramatic improvement of BMD following vitamin D therapy in a bone marrow transplant recipient. 1235 64

In mice, interleukin-7 (IL-7) hastens T-cell reconstitution and might cause autoimmune diseases, lymphoma, and osteoporosis. We assessed the effect of IL-7 on T-cell reconstitution and toxicity in baboons that underwent total body irradiation followed by autologous transplantation of marrow CD34 cells. Three baboons received placebo and 3 baboons received recombinant human IL-7 (rhIL-7, 75 microg/kg twice a day subcutaneously) between 6 and 10 weeks after transplantation. The mean increase in blood absolute CD4 T-cell counts was 0.9-fold in the placebo-treated animals versus 9.0-fold in those treated with IL-7 (P =.02). The increase observed in the IL-7-treated animals appeared attributable to peripheral expansion rather than de novo generation. The IL-7-treated animals had greater mean increases in the volumes of the spleen (2.0-fold with placebo versus 4.5-fold with IL-7, P =.02) and lymph nodes (1.8-fold with placebo versus 4.1-fold with IL-7, P =.10) but not the thymus (3.4-fold with placebo versus 1.1-fold with IL-7, P =.18). Side effects of IL-7 included thrombocytopenia and possibly neutropenia and hemolytic anemia. One IL-7-treated animal failed to thrive due to a disease resembling graft-versus-host disease. No animals developed lymphoma. Bone density was not decreased. In conclusion, IL-7 raises CD4 T-cell counts in irradiated primates. It remains to be determined whether this is associated with clinical benefit.
 ...
PMID:Interleukin-7 improves CD4 T-cell reconstitution after autologous CD34 cell transplantation in monkeys. 1254 64

Cytokines including IL-6 and TNF-alpha play an important role in the pathogenesis of postmenopausal osteoporosis. However, the relationship between changes in the cytokine levels and subsequent bone loss in patients undergoing a bone marrow transplantation (BMT) is unclear. A total of 46 patients undergoing an allogeneic BMT were prospectively investigated. The bone turnover markers and the serum cytokines were measured before BMT and serially after BMT. Bone mineral density (BMD) was measured before and 1 year after BMT. At 1 year after BMT, the lumbar spine BMD had decreased by 4.8%, and the total proximal femoral BMD had decreased by 12.3%. The serum IL-6 and TNF-alpha levels increased until 2 and 3 weeks after BMT, respectively. The lumbar BMD was significantly decreased as the serum IL-6 and TNF-alpha levels increased by post-BMT 3 weeks. The lumbar BMD decreased significantly as the cumulative prednisolone and cyclosporine dose increased. Patients with GVHD > or =grade II had higher lumbar bone loss than patients with GVHD <grade I. In conclusion, immunosuppressants, GVHD occurrence and increase in bone-resorbing cytokines in the early post-BMT period were associated with later bone loss after BMT. Further studies are needed to elucidate the precise mechanism.
 ...
PMID:Impact of circulating bone-resorbing cytokines on the subsequent bone loss following bone marrow transplantation. 1517 Jan 75

The purpose of this study was to analyze medical late effects among patients with chronic myeloid leukemia (CML) treated with hematopoietic cell transplantation (HCT). Subjects included 248 CML survivors who received an HC transplant (related donors [RDs], n = 150; unrelated donors [URDs], n = 70; or autologous, n = 28) and had survived at least 2 years, and a comparison group of 317 siblings. Subjects completed a 238-item survey on medical late effects. Compared with siblings, survivors were at a higher risk of developing ocular, oral health, endocrine, gastrointestinal, musculoskeletal, neurosensory, and neuromotor impairments. Multivariate analysis limited to RD and URD recipients found that chronic graft-versus-host disease (cGVHD) was associated with a higher risk of hypothyroidism, osteoporosis, cardiopulmonary, neurosensory, and neuromotor impairments. Overall health was reported as excellent, very good, or good in 78% of subjects, although those with cGVHD were more likely to report poor overall health. URD survivors were more likely to report a need for assistance with routine activities and that their current health prevented work or school attendance. This study demonstrates that HCT survivors, regardless of donor type, have a high prevalence of long-term health-related complications. However, adverse medical late effects with significant morbidity were uncommon. Chronic GVHD is the most important predictor of adverse medical late effects and poor overall health.
 ...
PMID:Late effects in survivors of chronic myeloid leukemia treated with hematopoietic cell transplantation: results from the Bone Marrow Transplant Survivor Study. 1517 72

We have established new bone marrow transplantation (BMT) methods for the treatment of stem cell disorders such as autoimmune diseases. The methods include the perfusion method (PM) and intra-bone marrow (IBM)-BMT. PM, in comparison with the conventional aspiration method, can minimize the contamination of bone marrow cells (BMCs) with T cells from the peripheral blood. Therefore, without removing T cells, no graft-versus-host disease develops in the case of PM. Because BMCs collected using the PM contain not only hemopoietic stem cells (HSCs) but also mesenchymal stem cells (MSCs), the injection of both cells directly into the bone marrow cavity (IBM-BMT) facilitates the engraftment of donor hemopoietic cells. With IBM-BMT, no graft failure therefore occurs even if the radiation dose is reduced. IBM-BMT is applicable to regeneration therapy and various age-associated diseases such as osteoporosis, because it can efficiently recruit donor-derived normal MSCs into the bone marrow. We believe that this strategy heralds a revolution in the field of transplantation and regenerative therapy.
 ...
PMID:Intra-bone marrow-bone marrow transplantation: a new strategy for treatment of stem cell disorders. 1612 3

The Ancillary Therapy and Supportive Care Working Group had 3 goals: (1) to establish guidelines for ancillary therapy and supportive care in chronic graft-versus-host disease (GVHD), including treatment for symptoms and recommendations for patient education, preventive measures, and appropriate follow-up; (2) to provide guidelines for the prevention and management of infections and other common complications of treatment for chronic GVHD; and (3) to highlight the areas with the greatest need for clinical research. The definition of "ancillary therapy and supportive care" embraces the most frequent immunosuppressive or anti-inflammatory interventions used with topical intent and any other interventions directed at organ-specific control of symptoms or complications resulting from GVHD and its therapy. Also included in the definition are educational, preventive, and psychosocial interventions with this same objective. Recommendations are organized according to the strength and quality of evidence supporting them and cover the most commonly involved organs, including the skin, mouth, female genital tract, eyes, gastrointestinal tract, and lungs. Recommendations are provided for prevention of infections, osteoporosis, and steroid myopathy and management of neurocognitive and psychosocial adverse effects related to chronic GVHD. Optimal care of patients with chronic GVHD often requires a multidisciplinary approach.
 ...
PMID:Ancillary therapy and supportive care of chronic graft-versus-host disease: national institutes of health consensus development project on criteria for clinical trials in chronic Graft-versus-host disease: V. Ancillary Therapy and Supportive Care Working Group Report. 1654 22

We studied bone mineral density (BMD) in 79 long-term survivors of allogeneic stem cell transplantation (SCT) (median follow-up: 78 months; range: 38-160). Seventy patients received a total body irradiation (TBI)-based myeloablative SCT and 9 patients received a non-TBI, reduced-intensity SCT. Fourteen (18%) patients were receiving immunosuppressive therapy (IST) for chronic graft-versus-host disease (cGVHD) beyond 3 years from SCT. Fifty-eight (73.4%) of patients had bone loss (BL): 33 (41.8%) with osteopenia and 25 (31.6%) with osteoporosis. Factors associated with a significantly increased risk of osteoporosis were age and prolonged IST and for overall BL prolonged IST. However, BL was not associated with an increased fracture risk, despite the fact that most patients had not received prophylactic biphosphonates. Our data shows that BL is a long-term posttransplant complication, and emphasize the importance of serial BMD scans, and the treatment of BL with biphosphonates reserved for worsening BL or additional risk factors.
 ...
PMID:Increased risk of bone loss without fracture risk in long-term survivors after allogeneic stem cell transplantation. 1744 10


1 2 3 Next >>