RISK OF LEUKEMIA, CARCINOMA, AND MYELOFIBROSIS IN P-32-TREATED OR CHEMOTHERAPY-TREATED PATIENTS WITH POLYCYTHEMIA-VERA - A PROSPECTIVE ANALYSIS OF 682 CASES

An analysis of the risk of progression towards leukemia, carcinoma and myelofibrosis was performed in 93 patients treated by P-32 alone (PVS G protocols) since 1970-1979, 395 patients over the age of 65 years tr eated by P-32 with or without maintenance therapy using hydroxyurea (F rench protocol) since 1980-1994, and 202 patients under the age of 65 treated by either hydroxyurea or pipobroman since 1980. The risk of le ukemia, or myelodysplasia, or lymphoma in the P-32-treated patients wa s 10% at the 10th year, but increase after that time to reach a value of about 30% at the 20th year, in the surviving case. This risk was no t dose-related. Despite a marked reduction of the cumulative P-32 dose in the patients maintained by hydroxyurea, the actuarial risk was 19% at the 10th year. In the patients treated exclusively by non radio-mi metic agents (hydroxyurea or pipobroman) a risk of 10% at the 10th yea r was observed. The risk of carcinoma (excluding skin cancers) was abo ut 15% at the 10th year in the P-32-treated cases, a value similar to that generally reported by the French statistics. There was no prevale nce of digestive carcinomas. In contrast, the patients receiving P-32 and hydroxyurea as maintenance had an excess risk: 29% at the 10th yea r. In the relatively young cases treated by non radio-mimetic agents, the risk was similar in both arms: 9% at the 10th year, similar to the expected incidence at this age. The risk of myelofibrosis with myeloi d metaplasia was still relatively low at the 10th year, about 15% in a ll arms, but increased towards a value higher than 30% in the patients surviving at the 20th year. At the present time, but in only a few ca ses with long-term following, no myelo-fibrosis with splenic metaplasi a has been observed in the pipobroman-treated cases. The present resul ts, which need to be confirmed (the present analysis has been done in spring 95) suggest that:-the use of non radio-mimetic agents does not protect against leukemic transformation, which may be a consequence of the disease, rather than of the treatment,-maintenance therapy after initial use of P-32 increases the risk of both leukemia and carcinoma- and hydroxyurea does not delay the risk of developing myelo-fibrosis, in comparison with P-32 alone.