Allogenic bone marrow transplantation in adults: endocrine sequelae after 1–6 years

Benker, G.; Schäfer, U.; Hermanns, U.; Mohammadi, Mahmoud; Olbricht, Th.; Schulte, H. M.; Windeck, R.; Reinwein, D.

doi:10.1530/acta.0.1200037

Cited by 25 publications

(26 citation statements)

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“…7 Furthermore, the sex hormone deficiency induced by high-dose chemotherapy and total-body irradiation increases bone loss and commonly occurs in women after BMT. 8 Bone resorption markers are increased while bone formation markers are reduced or within normal limits after BMT. [9][10][11] The amount of bone loss within 1 year after transplantation varied between 2% for the lumbar spine 12 and 12% for the femoral neck.…”

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confidence: 99%

Bone metabolism in patients more than five years after bone marrow transplantation

Kerschan‐Schindl

Mitterbauer

Füreder

et al. 2004

Bone Marrow Transplant

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Summary:We investigated the bone metabolism of 22 patients (median age 38 years) over 6 years after allogeneic bone marrow transplantation (BMT). Biplanar roentgenograms of the thoracic and lumbar spine were used to diagnose vertebral deformities caused by fractures. The actual bone mineral density (BMD) of the lumbar spine and the femoral neck were measured. Laboratory tests included calcium, phosphate, parathyroid hormone, a marker of bone resorption (beta-crosslaps, CTX), markers of bone formation (osteocalcin, bone-specific alkaline phosphatase), osteoprotegerin (OPG) -an antagonist of the osteoclast differentiation factor RANKL, and sex hormone status. One patient had a vertebral fracture. Seven patients (28%) had osteopenia in the lumbar spine while 12 patients (48%) had osteopenia in the femoral neck. Bone resorption was increased in nine patients (43%) and bone formation was increased in four patients (20%). BMT recipients had significantly increased serum levels of OPG (P ¼ 0.029). Three women (75%) and four men (25%) were hypogonadal. The data showed that BMD is reduced and bone metabolism is still disturbed more than 6 years after BMT. The RANKL/osteoprotegerin system appears to play an important role in the pathophysiology of late post transplantation osteoporosis.

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confidence: 99%

Bone metabolism in patients more than five years after bone marrow transplantation

Kerschan‐Schindl

Mitterbauer

Füreder

et al. 2004

Bone Marrow Transplant

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“…[5][6][7] Much less is known about the effects of high-dose chemotherapy on ovarian function in children. 2,8,9 We report an analysis of ovarian function in long-term survivors following myeloablative chemotherapy and bone marrow transplantation.…”

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confidence: 99%

Ovarian function after autologous bone marrow transplantation in childhood: high-dose busulfan is a major cause of ovarian failure

Teinturier

Hartmann

Valteau‐Couanet

et al. 1998

Bone Marrow Transplant

192

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Summary:We studied pubertal status and ovarian function in 21 girls aged 11-21 years who had earlier received 1.2-13 years (median 7 years) high-dose chemotherapy and autologous BMT without TBI for malignant tumors. Ten of them were given busulfan (600 mg/m 2 ) and melphalan (140 mg/m 2 ) with or without cyclophosphamide (3.6 g/m 2 ). Eleven others did not receive busulfan. Twelve girls (57%) had clinical and hormonal evidence of ovarian failure. Among nine others who had completed normal puberty, six had normal gonadotropin levels, one had elevated gonadotropin levels and two had gonadotropin levels at the upper limit of normal. The 10 girls who received busulfan all developed severe and persistent ovarian failure. High-dose busulfan is therefore a major cause of ovarian failure even when given in the prepubertal period. These findings emphasize the need for long-term endocrine follow-up of these patients in order to initiate estrogen replacement therapy. Keywords: ovarian function; high-dose chemotherapy; bone marrow transplantation; busulfan; childhood Increasing numbers of children who receive hematopoietic stem cell transplants (HSCT) for malignancies now survive. It is therefore important to evaluate ovarian toxicity secondary to the therapeutic regimens. New chemotherapy protocols will have to aim towards effecting long-term survival with minimal late morbidity. Chemotherapy is used alone or in combination with total body irradiation. Total body irradiation, used in the preparative regimens for hematologic malignancies, is deleterious to gonadal function. 1,2 Myeloablative therapy consisting of cyclophosphamide, busulfan or melphalan, has been used as an alternative to avoid the side-effects of irradiation on endocrine functions and growth. 1,3,4 Cytotoxics are known to induce ovarian toxicity in adults, dependent upon type of agent, dosage, administration schedule and patient age. 5-7 Much less is known about the effects of high-dose chemotherapy on ovarian function in children. 2,8,9 We report an analysis of ovarian function in long-term survivors following myeloablative chemotherapy and bone marrow transplantation. Patients and methodsWe screened all long-term female survivors older than 11 years who had received high-dose chemotherapy and autologous bone marrow transplantation without abdominal or pelvic radiation for malignant tumors at Institut Gustave Roussy. Twenty-one girls fulfilled these criteria.At time of transplantation, they were aged 2-17 years (median 9 years). Pubertal development was evaluated clinically according to Tanner. 10 Fourteen girls were prepubertal (stage 1), two were undergoing puberty (stage 3) and five had regular menses (stage 5). No hormonal evaluation was carried out before chemotherapy, but pubertal stages of all the patients were appropriate for their age.The study took place 1.2-13 years (median 7 years) after bone marrow transplantation and discontinuation of chemotherapy. At time of study, girls were aged 11.5-21 years (median 14.5 years).Serum concentrations of 17...

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“…This may be explained by the influence of primary ovarian failure following total body irradiation, whereas in men only a moderate elevation of gonadotropins and testosterone within the reference interval were observed (2,11). Cyclosporirji A may enhance the deleterious effect of oestrogen deficiency, since in oophorectomised rats bone mass loss is accelerated by the application of cyclosporin A (12).…”

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confidence: 99%

Relationship between Bone Metabolism and Plasma Cytokine Levels in Patients at Risk of Post-Transplantation Bone Disease after Bone Marrow Transplantation

Withold

Wolf²,

Kollbach³

et al. 1996

CCLM

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Summary:Bone marrow transplant recipients may carry an increased risk of bone diseases, involving numerous factors that affect bone mineral metabolism. Interleukin-6 is a potent stimulator of bone resorption in vivo. The soluble fraction of interleukin-6 receptor is reported to trigger osteoclast formation by interleukin-6 in vitro.In a cross-sectional study we measured serum bone alkaline phosphatase concentrations and the urinary excretion of pyridinium cross-links in 21 patients after bone marrow transplantation, and investigated the relationship between these values and those for the plasma levels of interleukin-6 and soluble interleukin-6 receptor.Following bone marrow transplantation female -but not male -patients showed higher serum bone alkaline phosphatase values than age-and sex-adjusted controls (p < 0.05). Both female and male patients were characterized by increased urinary excretion values of pyridinium cross-links (p < 0.05). In contrast to a marked increase of interleukin-6 plasma levels (p < 0.001) no significant difference in the soluble interleukin-6 receptor levels was found between patients and apparently healthy persons (p = 0.838). Multiple regression analysis (taking into account different variables of the immunosuppressive regimen applied) revealed the plasma concentration of interleukin-6 as an independent predictor of the urinary excretion of pyridinium cross-links (p < 0.05).In conclusion, in patients following bone marrow transplantation, these findings indicate (a) an increase of bone formation in female -but not in male -patients possibly reflecting primary ovarian failure and (b) an enhancement of bone resorption possibly mediated by circulating interleukin-6.

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Allogenic bone marrow transplantation in adults: endocrine sequelae after 1–6 years

Cited by 25 publications

References 0 publications

Bone metabolism in patients more than five years after bone marrow transplantation

Bone metabolism in patients more than five years after bone marrow transplantation

Ovarian function after autologous bone marrow transplantation in childhood: high-dose busulfan is a major cause of ovarian failure

Relationship between Bone Metabolism and Plasma Cytokine Levels in Patients at Risk of Post-Transplantation Bone Disease after Bone Marrow Transplantation

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