Risk of Leukaemia, Carcinoma, and Myelofibrosis in³²P- or Chemotherapy-Treated Patients with Polycythaemia Vera: a Prospective Analysis of 682 Cases

Abstract

An analysis of the risk of progression towards leukemia, carcinoma and myelofibrosis was performed in 93 patients treated by 32P alone (PVSG protocols) since 1970-1979, 395 patients over the age of 65 years treated by 32P with or without maintenance therapy using hydroxyurea (French protocol) since 1980-1994, and 202 patients under the age of 65 treated by either hydroxyurea or pipobroman since 1980. The risk of leukemia, or myelodysplasia, or lymphoma in the 32P-treated patients was 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 not dose-related. Despite a marked reduction of the cumulative 32P dose in the patients maintained by hydroxyurea, the actuarial risk was 19% at the 10th year. In the patients treated exclusively by non radio-mimetic agents (hydroxyurea or pipobroman) a risk of 10% at the 10th year was observed. The risk of carcinoma (excluding skin cancers) was about 15% at the 10th year in the 32P-treated cases, a value similar to that generally reported by the French statistics. There was no prevalence of digestive carcinomas. In contrast, the patients receiving 32P and hydroxyurea as maintenance had an excess risk: 29% at the 10th year. 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 myeloid metaplasia was still relatively low at the 10th year, about 15% in all 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 cases with long-term following, no myelo-fibrosis with splenic metaplasia has been observed in the pipobroman-treated cases. The present results, 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 32P increases the risk of both leukemia and carcinoma,-and hydroxyurea does not delay the risk of developing myelo-fibrosis, in comparison with 32P alone.

Polycythemia vera: myths, mechanisms, and management

“…In contrast to the well-established body of data on treatmentinduced acute leukemia in polycythemia vera, 163,180,197,200,207,[212][213][214] few data exist other than anecdotal case reports with respect to the spontaneous occurrence of acute leukemia. As mentioned above, up to 1950, Schwartz and Ehrlich accepted as valid only one published report describing such an event.…”

Polycythemia Vera era 1939-1998 from Berkeley to Rotterdam and Change of PVSG into ECP Criteria of Myeloproliferative Disorders ET, PV and PMGM: Proceedings of the First Rotterdam MPD Workshop 1998 and beyond

“…I look forward to the ECLAP study to answer the question can aspirin lower the hemorrhagic and thrombotic complications [21]. As I read and re-read some of the recent literature [22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40][41], I must say that I do not come before you today with original ideas of what should be done. I can only add my choice to that of others and last for the sin of omission in failing to recognize many of the contributions of those here today I apologize and ask forgiveness and for not mentioning only the senior authors in this talk I apologize.…”

“…Leukemia & Lymphoma volume 1996 Guest Edited by Jan Jacques Michiels [19]. From these publications, we got the very strong feeling to refrain from all old PVSG studies including the old studies of Najean from Paris, which all are extensively reviewed in the Leukemia & Lymphoma issue of 1996 [35]. The main conclusion from the PVSG is that Hydroxyurea (HU) is currently recommended as the least leukemogenic approach and supplement to aspirin/phlebotomy for newly diagnosed patients, who are at risk for thrombosis and for PV patients with progressed myeloproliferative disease at presentation or during follow-up.…”

Diagnosis and treatment of polycythemia vera: Brazilian experience from a single institution

“…Concerning the evolution to myelofibrosis, some studies from other countries have shown sMF rates of about 10 to 30% over 10 years of cohort follow-up. 14,15 Since treatment with hydroxyurea has not been shown to reduce the sMF rate, its occurrence in only five of our patients is probably a reflection of our stringent definition of sMF, since the detection of SMF was based on nonstandardized criteria in the trials performed before 2001. 14,15 Treatment with hydroxyurea and phlebotomy gave rise to good hematological control in our population.…”

“…14,15 Since treatment with hydroxyurea has not been shown to reduce the sMF rate, its occurrence in only five of our patients is probably a reflection of our stringent definition of sMF, since the detection of SMF was based on nonstandardized criteria in the trials performed before 2001. 14,15 Treatment with hydroxyurea and phlebotomy gave rise to good hematological control in our population. The Hb levels were brought under control within the first three months of therapy, with Hb levels ranging from 13.0 to 15.5 g/dl.…”