Protocol AML-MM-2000 treatment results of unfavorable prognostic group in children with acute myeloid leukemia

Protocol AML-MM-2000 treatment results of unfavorable prognostic group in children with primary acute myeloid leukemia (AML) in Russia and Belarus are presented. 105 children at the age from 2 weeks till 18 years (a median age — 10.8 years) are included in the study. In 91 patients (86.7%) hematological remission have reached, from them 34 patients (37.4%) are in the first continuous complete remission (CCR). 6-years overall survival (OS), event-free survival (EFS) and relapse-free survival (RFS) rate for all group of patients was 0.35 ±} 0.05; 0.32 ±} 0.04 and 0.43 ±} 0.05, respectively. Survival analysis of children with different cytogenetic anomalies has allowed to define two prognostic groups of patients: the intermediate prognosis, including patients with normal kariotype and t(9;11) which EFS and RFS rate was 40—50%, and unfavorable prognosis with EFS and RFS rate less than 40%. The efficiency analysis of three postremission therapy type (allogeneic and autological hematopoietic stem cells transplantation (HSCT) and chemotherapy (HT)) in intermediate and unfavorable prognostis groups was carried out. High efficiency of related HLA-identical HSCT in patients both intermediate and unfavorable prognostis groups have been shown. Autological HSCT is possible in intermediate prognosis patients with absence of HLA-identical siblings and in unfavorable prognosis patients with absence of HLA-identical unrelated donor.

1. Kaspers G.J.L., Zwaan C.M. Pediatric acute myeloid leukemia: towards highquality cure of all patients. Haematologica 2007;92(11):1519—32.

2. Kaspers G.J.L., Creutzig U. Pediatric acute myeloid leukemia: international progress and future directions. Leukemia 2005;19:2025—9.

3. Meshinchi S., Arceci R.J. Prognostic factors and risk-based therapy in pediatric acute myeloid leukemia. The Oncologist 2007;12:341—55.

4. Creutzig U., Zimmermann M., Ritter J. et al. Treatment strategies and long-term results in paediatric patients treated in four consecutive AML-BFM trials. Leukemia 2005;19:2030—42.

5. Pession A., Rondelli R., Basso G. et al. Treatment and long-term results in children with acute myeloid leukemia treated according to the AIEOP AML protocols. Leukemia 2005;19:2043—53.

6. Gibson B.E.S., Wheatley K., Hann I.M. et al. Treatment strategy and long-term results in pediatric patients treated in consecutive UK AML trials. Leukemia 2005;19:2130—8.

7. Lie S.O., Abrahamsson J., Clausen N. et al. Long-term results in children with AML: NOPHO-AML Study Group report of three consecutive trials. Leukemia 2005;19:2090—100.

8. Rubnitz J.E., Raimondi S.C., Tong X. et al. Favorable impact of the t(9;11) in childhood acute myeloid leukemia. J Clin Oncol 2002;20:2302—9.

9. Ravindranath Y., Chang M., Steuber C.P. et al. Pediatric Oncology Group (POG) studies acute myeloid leukemia (AML): a review of four consecutive childhood AML trials conducted between 1981 and 2000. Leukemia 2005;19:2101—16.

10. Lange B.J., Smith F.O., Feusner J. et al. Outcomes in CCG-2961, a children's oncology group phase 3 trial for untreated pediatric acute myeloid leukemia: a report from the children's oncology group. Blood 2008;111:1044—53.

11. Woods W.G., Kobrinsky N., Buckley J.D. et al. Timed-sequential induction therapy improves postremission outcome in acute myeloid leukemia: a report from the Children's Cancer Group. Blood 1996;87(12):4979—89.

12. Woods W.G., Neudorf S., Gold S. et al. A comparison of allogeneic bone marrow transplantation, autologous bone marrow transplantation, and aggressive chemotherapy in children with acute myeloid leukemia in remission. Blood 2001;97:56—62.

13. Lowenthal R.M., Bradstock K.F., Matthews J.P. et al. A phase I/II study of intensive dose escalation of cytarabine in combination with idarubicin and etoposide in induction and consolidation treatment of adult acute myeloid leukemia. Australian Leukemia Study Group (ALSG). Leukemia and Lymphoma 1999;34(5—6):501—10.

14. Weick J.K., Kopecky K.J., Appelbaum F.R. et al. A randomized investigation of high-dose versus standarddose cytosine arabinoside with daunorubicin in patients with previously untreated acute myeloid leukemia: a Southwest Oncology Group study. Blood 1996;88:2841—51.

15. Creutzig U., Zimmermann M., Lehrnbecher T. et al. Less toxicity by optimizing chemotherapy, but not by additionof granulocyte colony-stimulating factor in children and adolescents with acute myeloid leukemia: results of AML-BFM 98. J Clin Oncol 2006;24:4499—506.

16. Burnett A.K., Wheatley K., Goldstone A.H. et al. The value of allogeneic bone marrow transplant in patients with acute myeloid leukemia at differing risk of relapse: results of the UK MRC AML 10 trial. Br J Haematol 2002;118:385—400.

17. Creutzig U., Reinhardt D. Currant controversies: which patients with acute myeloid leukemia should receive a bone marrow transplantation? A European view. Br J Hematol 2002;118:365—77.

18. Klingebiel T., Reinhardt D., Bader P. et al. Place of HSCT in treatment of childhood AML. Bone Marr Transplant 2008;42(Suppl 2):7—9.

19. Литвинко Н.П., Шнейдер М.М., Савва Н.Н. и др. Лечение острого миелобластного лейкоза у детей по протоколу ОМЛ-ММ-2000: предварительные результаты исследования кооперативной группы Россия—Беларусь. Вопр гематол онкол иммунопатол педиатр 2006;5(3):23—31.

20. Chen A.R., Alonzo T.A., Woods W.G., Arceci R.J. Currant controversies: which patients with acute myeloid leukemia should receive a bone marrow transplantation? An American view. Br J Hematol 2002;118:378—84.

21. Whealthy K. Currant controversies: which patients with acute myeloid leukemia should receive a bone marrow transplantation? A statistician view. Br J Hematol 2002;118:351—6.

22. Reinhardt D., Kremens B., Zimmermann M. et al. No improvement of overall-survival in children with highrisk acute myeloid leukemia by stem cell transplantation in 1st complete remission. Blood 2006;108:abstr 320.

23. Smith F.O., Alonzo T.A., Gerbing R.B. et al. Long-term results of children with acute myeloid leukemia: a report of three consecutive phase III trials by the Children's Cancer Group: CCG 251, CCG 213 and CCG 2891. Leukemia 2005;19:2054—62.

24. Ravindranath Y., Yeager A.M., Chang M.N. et al. Autologous bone marrow transplantation versus intensive consolidation chemotherapy for acute myeloid leukemia in childhood. Pediatric Oncology Group. N Engl J Med 1996;334(22):1428—34.

25. Stevens R.F., Hann I.M., Wheatley K., Gray R.G. Marked improvement in outcome with chemotherapy alone in pediatric acute myeloid leukemia: results of the United Kingdom Medical research Council's 10 AML trial. MRC Childhood Leukemia Working Party. Br J Haematol 1998;101(1):130—40.

26. Ortega J.J., Diaz de Heredia C., Olive T. et al. Allogeneic and autologous bone marrow transplantation after consolidation therapy in high-risk acute myeloid leukemia in children. Towards a risk oriented therapy. Haematologica 2003;88(3):290—9.

27. Klingebiel T., Pession A., Paolucci P., Rondelli R. Autologous versus allogeneic BMT in AML: the European experience. Report of EBMT- Pediatric disease Working party. Bone Marr Transplant 1996;18(Suppl 2):49—52.