Therapy-Related Myelodysplastic Syndrome (sMDS) /Acute Myelogenous Leukemia (sAML) in Acute Promyelocytic Leukemia (APL) Patients with Long-Lasting Molecular Remission: The GIMEMA Experience.

The occurrence of a sMDS in patients potentially cured from a previous APL has been recently reported. To evaluate the real incidence and the clinical characteristics of sMDS/sAML post APL, the follow-up of 336 patients with newly diagnosed APL enrolled by 22 GIMEMA Centers in the LAP AIDA 0493 protocol has been revised. After the induction, 314 patients (93.4%) achieved complete remission (CR): of them, 225 (71.6%) are still alive in 1st CR, 12 (3.8%) died in CR and 71 (22.7%) relapsed. The remaining 6 patients (1.9%) developed a sMDS while in 1st morphological CR, after a median time from CR achievement of 42 months (range 27 - 75). Among the 71 relapsed patients, 15 had no further data and 41/56 (73.2%) achieved a 2nd CR after salvage treatments: 2 of them (4.8%) developed a sMDS while in 2nd morphological CR, after 48 and 27 months from 1st CR, respectively. Furthermore, another patient showed a sMDS while in 3rd CR. As to clinical and biological characteristics of these 9 sMDS patients, there were 3 male and 6 female with a median age at sMDS diagnosis of 57 years (range 31 – 71): cytogenetic analysis failed in 2 patients, was normal in 1 patient and revealed abnormalities of chromosomes 5 or 7 in the remaining 6 patients, with a complex karyotype in 4 of them. One patient underwent allogeneic BMT soon after sMDS and is still alive after 57 months, 2 patients are in stable myelodysplastic phase after 25 and 63 months respectively. An evolution in sAML occurred in the remaining 6 patients, after a median sMDS duration of 7.6 months (range 2 – 45): 5 sAML patients received only supportive care +/− palliative chemotherapy, 1 patient underwent intensive chemotherapy but was resistant. All sAML patients died after a median time from AML evolution of 4 months (range 0.8 – 5) In conclusion, the incidence of sMDS post APL seems low in 1^st molecular CR, but increases in patients achieving 2^nd or subsequent CR: clinical characteristics and prognosis are similar to those observed in other sMDS. A longer follow-up will help us to define the late occurrence (> 5 years from CR) of this severe complication. In addition, the availability of prognostic score systems at initial diagnosis and residual disease monitoring by PCR might allow better tailoring of treatment intensity in APL, in an attempt to spare unnecessary toxicity and minimise the risk of sMDS/sAML development for patients who have low risk disease.