[Patients older than 80 years with de novo acute myeloid leukemias without erythroblastic and/or megakaryocytic dysplasia achieve complete remission and longer survival after classical chemotherapy 3 + 7]. / Nemocní starsí 80 let s de novo akutními myeloidními leukemiemi bez dysplazie v erytroblastické 8/nebo megakaryocytární rade dosahují kompletní remise a delsího prezlití po klasické chemoterapii 3+7.

Chemotherapy in most patients with AML over 80 years of age is not recommended because their median survival is about 1 month. The aim of our study was to identify patients in this age group who might achieve complete remission with standard dose chemotherapy. We report 9 consecutive patients with de novo AML diagnosed and treated in 1992-2008. All bone marrow samples were hypercellular, classified as FAB types M2 in 2 cases, M4 in 6, and M5 in one case. Three patients opted for supportive or palliative therapy and survived 1-4 months. Six patients received standard dose chemotherapy. Two patients with a normal karyotype had resistant AML and survived 1.0 and 2.7 months; one patient with a complex karyotype died of septic shock on the 10th day of therapy. All these three patients exhibited erythroblastic and/or megakaryocytic dysplasia (EMD) at presentation (two in more than 26% erythroblasts, all three in a half or more of megakaryocytes). Three remaining patients with AML M4, a normal karyotype but without EMD, achieved complete remission in spite of co-morbidities and a poor performance status. Two of them survived 18.6 and 28 months on maintenance therapy, the third 16.5 months without it. Very elderly AML patients without EMD appear to represent a favorable prognostic biological category (single-lineage AML) that show a good response to standard dose chemotherapy.

Do de novo acute myeloid leukemias with normal cytogenetics involve two main prognostic categories distinguished by the presence of erythroblastic and/or megakaryocytic dysplasia?

De novo acute myeloid leukemias (AML) patients with normal cytogenetics represent a standard risk cytogenetic group. Erythroblastic and/or megakaryocytic dysplasia (EMD) in diagnostic bone marrow smears of 28 consecutive AML patients with a normal karyotype was studied. Twelve patients 21-85 (median 48) years old were categorized without EMD, 14 patients 34-90 (median 58) years old with EMD, and 2 patients were not evaluable for EMD. One cycle of induction therapy 4 + 7, with 4 doses of daunorubicin 45 mg/m2/d and standard doses of cytosine arabinoside for 7 days induced 10 complete and 2 partial remissions in 12 cases without EMD but lead to only one complete remission, 6 non-responses and 3 induction deaths in 10 cases with EMD (p = 0.002). However, high doses of cytosine arabinoside plus daunorubicin induced complete remission in 6 of 7 patients with EMD. In patients under 66 years treated by intensive consolidations the estimate of median survival was 50.6 months in 10 cases without EMD, significantly higher than 8.0 months in 11 cases with EMD (p = 0.043). De novo AML with normal cytogenetics might be divided into two biological categories, the first favorable-risk category without EMD and the second poor-risk category with EMD.

Erythroblastic and/or megakaryocytic dysplasia in de novo acute myeloid leukemias M0-M5 show relation to myelodysplastic syndromes and delimit two main categories.

Erythroblastic and/or megakaryocytic dysplasia (EMD) was evaluated in diagnostic bone marrow smears of 43 consecutively treated patients under 65 years with de novo acute myeloid leukemia (AML) M0-M5 according to FAB criteria. The evaluation was possible in 39 (91%) patients, i.e. in 32 of 34 patients with non-M3 AML treated in the study UHKT-911 and seven of nine cases with AML M3 treated in other studies. Among non-M3 AML 15 patients were categorized without EMD and 17 cases with EMD. Cytogenetic abnormalities of chromosome 5, 7, 3 or a complex karyotype were found in eight of 17 patients with EMD and in one of 15 cases without EMD (P = 0.018). Seven patients in each category exhibited a normal karyotype. Classical induction therapy with three to four doses of daunorubicin 45 mg/m2 and standard doses of cytosine arabinoside (AraC) for 7 days lead to complete remission in 11 of 14 (78.6%) cases without EMD but only in four of 14 (28.6%) cases with EMD (P = 0.021). High doses (2000 mg/m2 per 12-h x 10) of AraC plus daunorubicin induced complete remission in seven of 10 patients with EMD. Patients with EMD showed significantly worse overall survival (P = 0.03) with a median 13.5 months, while the median survival was estimated to 68.7 months in cases without EMD. The dysplastic features of EMD, karyotypes typical for myelodysplastic syndromes (MDS), poor response to classical therapy and survival show a relation of AML with EMD to MDS. AML without EMD may represent a different biological favorable category.

[Poor response in patients with de novo acute myeloid leukemia and erythroblastic or megakaryocytic dysplasia to treatment with standard doses of cytosine arabinoside and daunorubicin]. / Spatná odpoved nemocných s de novo akutními myeloidními leukémiemi s erytroblastickou ci megakaryocytární dysplazií na lécbu standardními dávkami cytosin-arabinosidu a daunorubicinu.

Erythroid and/or megakaryocytic dysplasia (EMD) was evaluated in diagnostic bone marrow smears of 37 consecutively treated cases with de novo acute myeloid leukemia (AML) M0-M2 and M4-M5 types and three newly diagnosed cases of refractory anaemia with excess of blasts in transformation. This evaluation was possible in 38 of 40 (95%) patients and 17 cases were categorized without EMD and 21 cases with EMD. One or two cycles with 3-4 doses of daunorubicin 45 mg/m2/d and cytosine arabinoside 200 mg/m2/12 h x 14 lead to complete remission in 13 of 16 cases without EMD but only in 4 of 16 cases with EMD (p = 0.004). However, 10 of 13 patients with EMD reached complete remission with 2000 mg/m2/12 h x 10 of cytosine arabinoside plus daunorubicin. After intensive consolidations 20 patients under 65 years with EMD showed significantly worse overall survival (p = 0.017) with a median 11.5 months, while the median survival was estimated 66.8 months in 15 cases under 65 years without EMD. The proposed categorization of de novo AML patients according to the EMD seems to be useful for selection of optimal induction therapy, clinically relevant for survival and might reflect two biologic groups of AML arising in two different stages of differentiation.