Bone marrow toxicity in mice treated with indium-114m-labelled blood cells.

Clinical trials with autologous indium-114m-labelled lymphocytes have revealed significant anti-tumour effects in chronic lymphocytic leukaemia patients with highly resistant disease. Substitution of the lymphocyte vector with heat-damaged red blood cells (HDRBC) may make this treatment more universally applicable and reduce the dose-limiting myelosuppression encountered with labelled lymphocytes. Therefore, the bone marrow localization and toxicities of indium-labelled lymphocytes or HDRBC have been investigated in BDFI mice. At 24 hours approximately 4% and 1.2% of 114In(m) administered as labelled lymphocytes or HDRBC respectively was localized within the bone marrow and remained constant for 57 days thereafter. Toxicity towards bone marrow stem cells, measured as CFU-S, was equivalent for both cellular vectors. However, at clinically relevant activities, 114In(m) HDRBC were less toxic than labelled lymphocytes towards committed progenitors, assayed as in vitro-CFC and CFU-Meg. These data suggest that substitution of HDRBC for lymphocytes as the 114In(m) vector may be beneficial in reducing the myelosuppression associated with this technique.

Bone density in long term users of depot medroxyprogesterone acetate.

OBJECTIVE: To identify any adverse effect on bone density in long term users of depot medroxyprogesterone acetate (DMPA) for contraception. DESIGN: Cross-sectional measurement of bone density in users with amenorrhoea of more than one year or any woman using DMPA for more than five years. SETTING: Community Family Planning Clinics in Portsmouth and Manchester. POPULATION: One hundred and eighty-five women aged 17-52 years (mean 33.3 years) who had used DMPA for between 1 and 16 years and were attending the clinics for further injections, between August 1994 and August 1996. METHODS: Dual energy X-ray measurement of bone density of femoral neck and lumbar spine, and venous blood sample taken just prior to the next injection of DMPA. MAIN OUTCOME MEASURES: Bone density of femoral neck and lumbar spine and serum oestradiol in relationship to years of DMPA use and duration of amenorrhoea. RESULTS: Most women (n=153) had serum oestradiol levels < 150 pmol/l. Despite this, the mean bone density of the lumbar spine compared with the population mean for women aged 20-59 years gave a Z score (95% CI) of -0.332 (-0.510 to -0.154). There was no significant difference in the mean density of the femoral neck from the normal population mean. CONCLUSION: Despite amenorrhoea and low serum oestradiol, this sample of long term DMPA users had bone density only minimally below the normal population mean. We therefore found no clinically important adverse effect on bone density and therefore no reason to recommend bone conserving measures, such as add-back oestrogen.

PIP: The effects on bone density of long-term depot medroxyprogesterone acetate (DMPA) use were investigated in a cross-sectional study of 185 clients 17-52 years of age at family planning clinics in Portsmouth and Manchester, England, who had been receiving contraceptive injections for 1-16 years (median, 5 years). Dual energy x-ray measurements of bone density of the femoral neck and lumbar spine, as well as venous blood samples, were taken prior to the women's next DMPA injection (1994-96). 153 women had serum estradiol levels under 150 pmol/l--the value considered adequate to maintain bone density. The mean bone density of the lumbar spine compared with the population mean for women 20-59 years old yielded a Z score of minus 0.332 (95% confidence interval, -0.510 to -0.154; p 0.001). There was a weak, nonsignificant correlation between lumbar spine Z score and years of DMPA use. Mean density of the femoral neck did not differ significantly from the normal population mean. There was no significant correlation between serum estradiol level and either bone density score. Overall, these findings provide no evidence that DMPA-induced amenorrhea places women at significant risk of further bone loss or that supplemental estrogen is required.

Treatment of lymphoid cell malignancy with In-114m labelled autologous lymphocytes.

This paper is a preliminary report of a clinical trial for the treatment of patients with refractory chronic lymphocytic leukaemia, using autologous In-114m-labelled lymphocytes. Fourteen patients have been treated so far with doses ranging from 69 to 211 MBq. All patients had progressive low grade NHL, resistant to chemotherapy and conventional radiotherapy. Following the intravenous administration of radiolabelled autologous lymphocytes 53% (range 33-92%) of the activity accumulated in the spleen, 35% (21-64%) in the liver and 5% in the bone marrow. The initial response in all patients was a rapid decrease in lymphocyte count in peripheral blood. 10 of the 14 (72%) patients showed a response to the treatment. In 2 patients, there was a complete response which lasted 24 and 36 months respectively, 8 patients showed a partial response of 2 to 17 months duration. None of the patients experienced any subjective toxicity although myelosuppression was seen in all patients. This is a novel concept for the administration of therapeutic radiation in a selective way for the treatment of lymphoid cell malignancy and has produced significant antitumour effect in patients with highly resistant disease. The trial is ongoing and a full report will be published on its completion.