Subnormal androgen levels in young female bone marrow transplant recipients with ovarian dysfunction, chronic GVHD and receiving glucocorticoid therapy.

Ovarian function and sex hormone production with special focus on androgens (testosterone, androstenedione, dehydroepiandrosterone and its sulfate, DHEAS) was followed up during 1.5-20 (mean 9) years after bone marrow transplantation (BMT) in 24 female subjects aged 16-33 (mean 21) years at the last follow-up. All patients had received TBI and high-dose chemotherapy as the preparative regimen. A total of 24 female patients with conventionally treated pediatric hematologic malignancies served as controls. Four of 24 transplanted patients had spontaneous menstruation several years post transplantation, but in only one of them were serum FSH levels normal. Androgen levels of the BMT patients were lower than those of the conventionally treated patients. Subnormal testosterone levels were observed in 43% of BMT patients and subnormal DHEAS levels in 34% of BMT patients, the latter being a constant finding during glucocorticoid therapy for chronic GVHD (cGVHD). These results indicate that ovarian damage is a common late effect in patients transplanted at a young age, still having a seemingly normal pubertal development. Ovarian damage and cGVHD with glucocorticoid therapy are strongly associated with subnormal androgen levels. The clinical consequences of these changes and possible benefits of putative androgen replacement therapy remain to be elucidated.

Prevention of acute adverse events related to infliximab infusions in pediatric patients.

OBJECTIVE: To study whether premedication with an oral antifebrile agent (acetaminophen) and antihistamine (cetirizine) could decrease the frequency of acute infusion reactions in pediatric patients. METHODS: All pediatric patients scheduled for infliximab infusions at the Helsinki University Central Hospital, a tertiary care center, were prospectively introduced to a standard oral premedication of acetaminophen (20 mg/kg) and cetirizine (10 mg) prior to infliximab infusions for a period of 1 year. All acute adverse events related to infliximab infusions given according to the guidelines of pediatric rheumatologists or gastroenterologists were registered for this time period and retrospectively during the preceding year. RESULTS: During the study period, infliximab infusions with premedication were given to 64 pediatric patients (48 with rheumatic disease and l6 with inflammatory bowel disease, mean age 13 years, n = 34 boys, and n = 30 girls). Infliximab was introduced to 14 children; the rest were on maintenance therapy. Twelve infusion reactions, 4 mild and 8 severe, were observed in 8 (12.5%) of the 64 subjects, and in 1 subject 4 times. During the preceding year, 60 pediatric patients had received infliximab infusions without premedication. In this latter group, infusion reactions occurred in 5 children (8.3%; P > 0.05). The presentation of an acute infusion reaction was not related to the sex or diagnosis of the patient. CONCLUSION: In pediatric patients, acute infusion reactions related to infliximab could not be prevented with premedication with oral acetaminophen and cetirizine.

Restoration of ovarian function after chemotherapy for osteosarcoma.

AIM: To evaluate ovarian function after modern intensive multi-agent chemotherapy for osteosarcoma given during childhood or adolescence. METHODS: After discontinuation of treatment, 10 female osteosarcoma survivors were followed up for 1.5-14 (median 4.6) years. Their age at diagnosis was a median of 12.9 (range 6-15) years and at the last follow up 18.6 (range 16-22). The main follow up included recording of their pubertal and menstrual status and of sex hormone determinations. RESULTS: Prior to diagnosis, 5/10 had had their menarche, and one had it while on therapy. At discontinuation of chemotherapy, ovarian function had severely deteriorated; none of the girls experienced regular menstrual cycles. However, during follow up, significant restoration of ovarian function was evident. At the last follow up, 9/10 patients were menstruating spontaneously. During follow up, four patients, three of whom had received high doses of alkylating agents, presented with clear hypergonadotrophism with high FSH levels (14.4-132 IU/l). Three of these four patients initiated menstruation after their gonadotrophin levels normalised. CONCLUSIONS: The modern multi-agent chemotherapy applied for osteosarcoma impairs ovarian function. Normalisation of ovarian function is common, even in cases with severe hypergonadotrophic hypogonadism, but may only occur after several years off chemotherapy. Regular assessment of ovarian function and cautious use of hormone replacement therapy are important in patients with chemotherapy induced gonadal damage.