PS1022 PREFERENTIAL TRANSCRIPTION OF THE MUTATED ALLELE IN NPM1 MUTATED ACUTE MYELOID LEUKAEMIA

Abstract

Background: Early studies in the 1980 s concentrated on defining AMLs poorly responding/resistant to SICT as cases of AMLs with trilineage (TLD) or multilineage dysplasia (MLD). These AMLs with MLD were supplemented with AMLs exhibiting cytogenetic findings typical for myelodysplastic syndromes (MDS) and with AMLs arising from previous MDS into the category of AML with MDS-related changes (AML-MRC) in the WHO 2016 classification. AML with MLD have to exhibit erythroblastic and/or megakaryocytic dysplasia (EMD) and originate from myeloid pluripotent progenitors. However, AML M0-M5 with granulocyte-monocyte blasts exhibiting a single line dysplastic features of EMD (not MLD by definition but two lines involved) belong to EMD-AML and not to single-line GM-AMLs which responded well to SICT (Lemez et al., Leuk Res 2000;24:207). Aims: The aim of this study was to review our published and unpublished de novo AML patients examined for dysplastic features and treated with SICT as well as similar de novo AML cases from the literature and their response to SICT. Methods: We have analyzed our cases examined for dysplastic bone marrow features treated with SICT or high-dose cytarabine with daunorubicin cycle 10/2. A literature review of reported AML cases examined for dysplasia and treated with SICT was also analyzed. Results: Our single-institution study on consecutive adult de novo AML cases <65 years of age showed that those with GM-AML reached complete remission (CR) in 78% after SICT but cases with EMD-AML in 29% (p = 0.02). However, 7/10 EMD-AML cases reached CR after the cycle with high-dose cytarabine and daunorubicin 10/2 (Lemez et al., 2000). Coasguen et al. (Leukemia 1992;6:520) reported 74.4% CR after SICT in 156 cases without dysplastic features (GM-AML), but 56% CR in 39 cases with TLD AMLs. Brito-Babapulle et al. (Br J Haematol 1987;66:445), Estienne et al. (Clin Lab Haematol 1990;12:57), and Kuriyama et al. (Br J Haematol 1994;86:767) reported post SICT 86%, 79%, and 81% CR in 136, 118, and 190 selected non-TLD cases, but CR 50%, 43%, and 63% in TLD AML cases, respectively. Patients’ selection of cases suitable for SICT with median age below 50 years probably increased the CR rates in non-TLD and TLD AML categories. Papers with high or intermediate doses of cytarabine during induction were not included in this literature review. Our 6 of 12 consecutive cases with de novo AML over 80 years of age opted for SICT administration. Three cases with GM-AML reached CR after one cycle of SICT and survived 16.5–28 months on maintenance therapy while none of the three octogenarians with EMD-AML reached CR and all died within 0.4–2.7 months. A 79-year old man with GM-AML reached CR post 2 cycles of low-dose cytarabine (LDAC) and survived on 53 repeated cycles LDAC 84 months. Another 67-year old man with GM-AML and near-tetraploid karyotype reached CR post SICT and after two further same cycles he survived in CR 51 months and with further treatment altogether 80 months. Summary/Conclusion: Our results and the literature review showed that GM-AML cases achieve CR after SICT in 74–85% of patients <60/65 years of age. Five older patients > 65 years including three > 80 years of age reached CR after SICT in spite of poor performance status 3 in two and had survival 16.5–28 months on maintenance therapy. We estimate that de novo GM-AML cases constitute about 20% of all cases 80+ years old with newly diagnosed AML. GM-AML cases > 65 years exhibit a good sensitivity to SICT. Further reports and studies are needed to enlarge the number of older GM-AML cases treated with SICT.