Long‐term evaluation of chromosomal breakages after radioisotope synovectomy for treatment of target joints in patients with haemophilia

Abstract

Radioisotope synovectomy (RS) is defined as the intra-articular injection of radioisotopic agents with the aim of fibrosis on hypertrophic synovium in the target joint. The aim of this study was to investigate genotoxic effects on lymphocytes and malign transformation induced by Yttrium(90) (Y(90)) and Rhenium(186) (Re(186)) in children with haemophilia undergone RS. Forty haemophilia patients were enrolled. The mean age was 16.4 +/- 6.2 years (range: 8-40). Y(90) was used for knees, Re(186) was used for other joints. For safety, cytogenetic analysis was performed to determine potential chromosomal changes after RS procedure at three different time points as prior to procedure, 3rd day and 90th day. For the stimulation of chromosomal breakages, diepoxybutane was used (DEB test). Chromosomal breakages (CBs) were found in 23 patients (67.6%) prior to RS. We have found CBs additionally in nine of 11 patients who had no CBs prior to RS after 3 days of radioisotope exposure. At that time, the patients who had CBs were 29 (85.2%). At day 90, only 21 patients revealed (61.7%) CBs. The mean frequency of CBs slightly but not significantly increased in the 3rd day. However, there was a significant decreasing trend between 3rd and 90th days. Radioisotope synovectomy with Y(90) and Re(186) does not seem to induce the genotoxic effects significantly on peripheral blood lymphocytes. However, CBs even after one year in the re-evaluation of four patients, significant decrease in the number of CBs between the 3rd and 90th days and de novo CBs after exposure may be accepted as warning signals for young population. It should also be pointed out that families and patients be informed properly related with historical and potential dangers of radioisotopic agents.

Progress in intra-articular therapy

“…138 Radiation synovectomy is complicated by rare cutaneous radiation necrosis 67 and concerns about genotoxic effects. 68 …”

Micronucleus evaluation for determining the chromosomal breakages after radionuclide synovectomy in patients with hemophilia

“…32 P has not been approved by European Medicine Agency (EMA) for European countries yet. In our country, due to unavailability of 32 P in the market, we have never used this agent for Turkish patients just like other European centers [8].…”

“…Recently, we have studied the effect of RS procedure in patients with hemophilia before and after the therapy [8].…”

“…Genotoxic effects of RS with 90 Y and 186 Re in hemophilic children have been evaluated using diepoxybutane (DEB) test in a recent study [8] and have not seemed to induce a significant genotoxic effect on peripheral blood lymphocytes. However, chromosomal breakages which were detected even after 1 year of radioisotope synovectomy and de novo chromosomal changes after radioisotopic exposure might be warning signs for young patients.…”

Radiosynovectomy in Hemophilic Synovitis

“…Regarding the chromosomal changes after RS, several authors have shown that genotoxic radiation doses delivered to the peripheral lymphocytes are not statistically significant (17,18,19,20,21). However, transient increase in micronuclei of peripheral lymphocytes may be expected soon after Y-90 therapy which disappeared at 90 th .…”