Knee radiosynovectomy with 153Sm-hydroxyapatite compared to 90Y-hydroxyapatite: initial results of a prospective trial.

INTRODUCTION: Radiosynovectomy (RS) with 90Y-hydroxyapatite (90Y-HyA) aims to control knee hemarthrosis in hemophiliac patients to prevent secondary arthropathy. However, knee RS using 153Sm-hydroxyapatite (153Sm-HyA) is considered less suitable due to the lower average soft tissue range and energy of 153Sm for large joints, such as the knees. PURPOSE: The objective of this investigation was to assess the efficacy and safety of knee RS with 153Sm-HyA, compared to 90Y-HyA. METHODS: Forty patients were prospectively assigned to undergo knee RS with 153Sm-HyA (n = 19) or with 90Y-HyA (n = 21). The frequency of hemarthrosis episodes before and after treatment were compared. RESULTS: After six months of knee RS, 153Sm-HyA and 90Y-HyA promoted a similar reduction of hemarthrosis episodes (50% and 66.7%, respectively). However, after 12 months of knee RS, the reduction of hemarthrosis episodes was significantly (p = 0.037) higher using 153Sm-HyA (87.5%) compared to 90Y-HyA (50.0%). This discrepancy was more pronounced (p = 0.002) for 153Sm-HyA compared to 90Y-HyA in adults/adolescents. CONCLUSION: Knee radiosynovectomy with 153Sm-HyA is safe, reduces hemarthrosis episodes after 12 months of treatments, especially in adults/adolescents and even with grades III/IV arthropathy, similar to 90Y-HyA. 90Y-HyA seems to promote better hemarthrosis control in small children.

Treatment with radiosynoviorthesis in hemophilic patients with and without inhibitor.

BACKGROUND: Spontaneous bleedings occurring into joints (hemarthrosis) are the most common manifestations of hemophilia and causes severe joint damage ultimately resulting in joint disfunction known as hemophilic arthropathy. Among available therapeutic options for reducing recurrent hemarthrosis-associated damage, radiosynoviorthesis (RS) has proven effective in improving joint function. AIM: To assess the impact of RS with Yttrium(90) citrate (C-Y(90)) on frequency of hemarthroses and joint function in a group of pediatric patients. METHODS: Between November 1998 and February 2017, we evaluated 27 pediatric patients with mild, moderate or severe hemophilia with haemophilic arthropathy. Overall, RS was applied in 60 joints. Some patients received more than one single intra-articular injection with C-Y(90). RESULTS: During the follow-up, one patient showed joint bleeding 15 months after RS, one patient after 12 months and one patient after 45 days. The episodes of hemarthrosis were reduced and joint function significantly improved in all patients. CONCLUSION: RS with C-Y(90) is a simple and safe treatment for reducing the frequency of hemarthroses in patients with hemophilia. It decreases the use of factor VIII / IX and improves joint function.

The use of 185 MBq and 740 MBq of 153-samarium hydroxyapatite for knee synovectomy in haemophilia.

The penetration of beta energy of 153-samarium ((153) Sm) (0.8 MeV) is not only appropriate for synovectomy of median articulations but is possible to improve the radiobiological effect using increased activities. The aim of this study was to assess the effectiveness of 185 MBq and 740 MBq of 153-samarium hydroxyapatite ((153) Sm-HA) in knees of haemophilic patients. Thirty-one patients--36 knees, 30 males, were divided into two groups without coinjection of corticosteroid: A - 14 patients (17 knees) treated with intra-articular dose of 185 MBq of (153) Sm-HA, average age 23 years; B--17 patients (19 knees) with 740 MBq of (153) Sm-HA, average age 21.3 years. The evaluation before and after 1 year of synovectomy used the following criteria: reduction in the number of haemarthroses and use of the coagulation factor and improvement in articular motility. Adverse-effects occurrence was considered too. Early and late scintigraphic studies were performed after synoviorthesis and no joint immobilization was recommended. The reduction in haemarthrosis and use of coagulation factor were: group 1--31.3% and 25%; group 2--81.5% and 79% with P < 0.001 respectively; no significant improvement in knees motility was noted for both groups. Four cases of mild reactional synovitis were observed in each group. The scintigraphic control showed homogenous distribution of the radiopharmaceuticals with no articular escape; the material was considered safe by its permanence in the articulation. We have significant improvement in the synovectomy of haemophilic knees with 740 MBq of (153) Sm-HA; the less penetration of its beta radiation was compensated by the increased biological effect with the higher used activity.

Radiosynoviorthesis in haemophilia: how safe?

One of the best procedures to prevent haemarthrosis in haemophilia has been radioactive synovectomy (radiosynoviorthesis). Since 1976 we have performed 119 radiosynoviortheses in 110 patients, aged from 3 to 40 years (mean 10), and of whom 71 were under 12 years of age. The knees were injected in 71, elbow in 29, ankles in 16, and shoulders in 3 cases. Clinical results of the procedure gave excellent results 80% of patients with no further bleeding. In the case of failure a reinjection can be given in the same joint at a 6 month interval. One of the criticisms against this method is possible chromosomal damage. In our centre, 4 studies have been made in order to see whether these changes are permanent, but all have demonstrated that chromosomal changes are reversible. Radioactive material used in 2 studies was Au-189. In 1978, 354 metaphases were studied with 61 ruptures, with 17.23% non-premalignant and 6 structural changes considered premalignant (1.69%). Further study was done in 1982, in the same group of patients with the result of 21 ruptures (3.34%) and no structural changes. The third study was performed in 13 patients that sustained radiosynoviorthesis with Re-186 in 1991. We compared the chromosomal study before and 6 months after the radioactive material injection and the results confirmed that changes appeared equally in non-irradiated and radiated patients and disappeared with time, never reaching the dangerous zone of 2%. In the group treated with Re-186 we studied an additional number of 130 metaphases with identical results and no structural changes. A study performed before and after radiosynoviorthesis with Y-90 revealed no premalignant changes. It seems than radiosynoviorthesis is safe and highly beneficial to haemophilic patients.

Cytogenetic studies in patients with hemophilic hemarthrosis treated by 198Au, 186Rh, and 90Y radioactive synoviorthesis.

This study assesses chromosomal structural changes (CSCs) studied by conventional lymphocyte cultures and banding techniques in 79 hemophilic patients with hemarthrosis treated with radioactive synoviorthesis, 31 hemophilic patients with hemarthrosis not treated by this procedure, and 110 nonhemophilic patients matched by age and sex (control group). In 14 patients treated with 198Au (group A), premalignant CSCs and nonspecific CSCs were found, respectively, in 1.69% and 17.23% of metaphases. The former disappeared, but 1.7% of the nonspecific changes persisted 2 years after injection. In 31 patients treated with 186Rh (group B), CSCs were not found previous to radioactive synoviorthesis but were present as nonspecific changes in 1.25% of metaphases 6 months later; they disappeared 1 year after injection. In 34 patients treated with 90Y (group C), CSCs were not found previous to radioactive synoviorthesis but were present as nonspecific changes in 0.89% of metaphases 6 months later; they disappeared 1 year after injection. Only nonspecific CSCs were found in 0.79% of metaphases in patients not treated with radioactive synoviorthesis (group D). CSCs were not present in control subjects. The authors conclude that in some hemophilic patients with hemarthosis treated with radioactive synoviorthesis using 198Au, 186Rh, or 90Y, reversible premalignant or nonspecific CSCs could be present; nonspecific CSCs may persist in a low proportion of metaphases up to 2 years after injection when 198Au is used as the radioactive agent. Radioactive synoviorthesis seems to be from a cytogenetic point of view a safe alternative for these patients.

Radioactive synoviorthesis in hemophilic hemarthrosis: materials, techniques, and dangers.

Radioactive synoviorthesis with 198Au, 90Y, 186Re, and 31P would seem to be the treatment of choice for recurrent hemarthroses in hemophilia. The clinical results, obtained by different centers, show a definite diminution of hemarthroses in 88% of cases. The advantages of radioactive synoviorthesis compared with surgical synovectomy are: better results, the requirement of substantially reduced antihemophilic factor, the possibility of performing the procedure on multiple cases concurrently on an ambulatory basis, no interference with articular range of movement, and the low cost of the procedure. In cases of failure, the procedure can be repeated after 6 months, and on as many as 3 occasions. Studies performed on the chromosomal changes that could be attributed to the radioactive material show the disappearance of these alterations a few years after treatment. No physical changes have been found that could be attributed to cytogenic alteration (hematologic or other) in any reported patients.