Improvement of the Treatment Results in Childhood Acute Myeloid Leukemia in Poland from 1983 to 2017

Introduction: Acute myeloid leukemia (AML), heterogeneous group of malignant neoplasm of hematopoietic system, comprises of 15% of all leukemias in children. Standardized AML-BFM based protocols of the treatment of AML introduced in Poland from 1983 enabled successive improvement of survival rates. Before 1983 only 10% of children with AML in our country had chance to survive.

The aim of the study was analysis of the treatment results in five consecutive periods: AML-PGPLBC83 (1983-1993, group I), AML-PGPLBC94 (1994 -1997, group II), AML-PGPLBC98 (1998-2004, group III), AML-BFM2004 Interim (2005-2014, group IV ) and AML-BFM 2012 (2015-2017, group V).

Patients: Eight hundred and two patients diagnosed with AML from 1983 to 2016 in Poland were eligible for evaluation (187, 74, 149, 351 and 41 respectively in group I, II, III, IV and V). Patients with acute promyelocytic leukemia, AML in Down syndrome and secondary AML were excluded from analysis. Median observation time was 128, 73, 119, 65 and 12 months in consecutive groups respectively.

Results: Complete remission rate in the groups I to V was: 72%, 66%, 84%, 87% and 83%, respectively. Percentage of early deaths (before 42. day of the treatment) was 22%, 14%, 5% , 4%, and 7% respectively. Non-responders comprised of 6% of all patients in the first group, 18% in the second, 10% in the third, 8% in the fourth and 9% in the last group. Among patients who achieved remission in the group I 16% died in remission and 42% relapsed, in the group II 16% died in remission and 33% relapsed, in the group III 11% died in remission and 40% relapsed, in the group IV 7% died in remission and 34% relapsed, in the last group 3% died in remission and 9% relapsed. Probability of the 5-years overall survival (OS) was 33%, 38%, 53% and 63% in four consecutive periods, respectively. Probability of the 5-years event free survival (EFS) was 32%, 36%, 46% and 49%, respectively in groups I-IV. Probability of relapse free survival (RFS) in patients who achieved remission was 51%, 62%, 55%, 62% respectively in groups I-IV. Because of too short observation time in the last group (V), 12-months survival rates were counted: OS - 74% (compared to 50%, 52%, 68% and 80% in groups I-IV), EFS - 70% (compared to 34%, 44%, 58%, 66% in the groups I-IV) and RFS - 89% (67%, 74%, 72%, 78% in the groups I-IV).

Discussion: Systematic improvement of the treatment results, increase in proportion of achieved remission and reduction of early deaths and deaths in remission in the four consecutive groups treated from 1983 to 2015 was observed. The progress was achieved by modification of protocols with more accurate stratification to the risk groups, development of supportive care and gaining experience in reducing number of toxic deaths. Unfortunately proportion of relapses was still high. Therefore in 2015 new treatment protocol AML-BFM 2012 with stratification to the risk group based on cytogenetic and molecular genetics changes, as well as treatment responses was introduced. Number of patients in the group V treated with that protocol is low with short observations time however preliminary results seem to be encouraging. Further progress in AML therapy seems to be possible due to further oncology centers' cooperation within large international study groups.