Pierre Morel

Treatment of Acute Promyelocytic Leukemia: A Report of 70 Cases

Over a period of 14 years, we treated 70 cases of acute promyelocytic leukemia (APL) with 3 different chemotherapy protocols. In protocol 1, patients received high dose daunorubicin (DNR) alone for induction, followed by regular reinduction courses and continuous maintenance therapy with 6 mercaptopurine (6 MP) and methotrexate (MTX) during 3 years. In protocol 2, induction with high dose DNR and Ara C was also followed by regular reinduction courses, but without continuous maintenance therapy. Protocol 3 randomized high dose Amsacrine (AMSA) or Rubidazone in association with Ara C, for induction and consolidation, this was followed by reinduction courses and continuous maintenance therapy with 6 MP and MTX. During the induction all patients received, prophylactic heparinization and platelet transfusions. Fifty six patients (80%) achieved complete remission (CR), 13 patients (18.5%) had early death (ED) or hypoplastic death (HD), and 1 patient had true resistant leukemia. Only two patients died of hemorrhage. Median actuarial disease free survival (DFS) was 16.5 months and a plateau at 29.1% was reached after 29 months. Patients with fever at diagnosis had a significantly lower CR rate while age below 20 years and circulating blasts above 0.5 × 10(9)/1 were associated with shorter DFS. The CR rate did not significantly differ between protocols 1, 2 and 3 (87.5%, 80% and 60% respectively) but 9 of the 30 patients on protocols 2 or 3 had ED or HD, compared to 4 of the 40 treated with protocol 1 (p < 0.05). DFS was significantly shorter in protocol 2, which included no continuous maintenance chemotherapy, than in protocols 1 and 3. Median actuarial survival was significantly shorter in patients treated with protocols 2 or 3, compared to protocol 1. These results suggest that high dose DNR alone, associated with adequate prophylaxis of disseminated intravascular coagulation, gives very high CR rates in APL, with short periods of aplasia and limited toxicity. Combinations of an anthracycline or AMSA at the doses used with regular dose Ara C may be too toxic. Although this was not a randomized trial, our findings also suggest a possible benefit of prolonged continuous maintenance therapy with 6 MP and MTX in APL.

De novo myelodysplastic syndromes in adults aged 50 or less. A report on 37 cases

We report on 37 adults aged 50 years or less with de novo myelodysplastic syndrome (MDS) (excluding cases secondary to chemo or radiotherapy), who represented 6.7% of our total cases of adult MDS. Median age was 42 (range 18-50). At diagnosis, there were 9 RA, 6 RAEB, 13 RAEB-T, 9 CMML but no RARS. Five patients had a familial history of MDS, and 3 a history of occupational exposure to potential carcinogens. Twenty-one patients received intensive chemotherapy (at diagnosis or during the evolution) but only 8 (38%) achieved complete remission (CR), and median CR duration was 10 months. Five patients were allografted (3 of them as first line therapy): 2 remained disease free after 12 and 10 months, and 3 died of transplant related complications. Median actuarial survival of the 37 patients was 21 months. Significantly shorter survival was seen in patients who had circulating blasts, Bournemouth score greater than 1 or 2, abnormal karyotype (especially monosomy 7) and RAEB or CMML. When compared with our MDS aged more than 50, our MDS aged 50 or less were characterized by more familial cases, more cases of RAEB-T and less cases of RAEB and RARS, more frequent abnormal karyotype and monosomy 7, more frequent progression to AML, identical overall survival but longer survival in RAEB-T and shorter survival in CMML. MDS in younger adults seem relatively often familiar or associated to occupational exposure. They have a poor prognosis with conventional therapeutic approaches and therefore require allografting, whenever possible.