Comparative analysis of three various chemotherapy protocols for acute lymphoblastic leukemia BFM-90m, MB-91 and PECO-92 in Moscow and St.-Petersburg

Comparative retrospective analysis of treatment results of three different chemotherapy protocols - ALL BFM 90m, ALL MB 91 and PECO 92 — in primary ALL patients aged before 18 years, registered in Moscow and St-Petersburg clinics from 01.01.1993 to 01.01.1999 is presented. It has been shown, that treatment results of PECO 92 protocol have appeared much worse, thus, any differences in treatment results for children with ALL between ALL BFM 90m and ALL MB 91 protocols were not revealed. Event-free survival (pEFS) of St-Petersburg' patients, received PECO 92 protocol (60±3%), was significantly worse, in comparison with patients treated according to ALL BFM 90m protocol (74±4%; р=0,0056) and ALL MB 91 protocol (73±4%; р=0,0239). The high incidence of relapses became a main cause of efficacy decreasing. Differences of induction and remission death incidences between three chemotherapy protocols were not revealed. Significant and most expressive EFS differences between PECO-92 and two other protocols were obtained in boys, in a 1—10 age group, and in patients with leukocytes count > 100 000/mm³, in patients with non-T-ALL and in patients with spleen size >4 cm.

1. Алексеев Н.А., Воронцов И.М. Лейкозы у детей. Л.: Медицина, 1988.

2. Riehm H., Gadner H., Henze G. et al. Results and significance of six randomized trials in four consecutive ALL-BFM studies. Hematol Blood Transfus 1990;33:439—50.

3. Janka-Schaub G.E., Winkler K., Gobel U. et al. Rapidly rotating combination chemotherapy in childhood acute lymphoblastic leukemia: preliminary results of a randomized comparison with conventional treatment. Leukemia 1988;2:73—8.

4. Schrappe M., Reiter A., Zimmermann M. et al. Long-term results of four consecutive trials in childhood ALL performed by the ALL-BFM study group from 1981 to 1995. Leukemia 2000;14:2205—22.

5. Harms D.O., Janka-Shaub G.E. Cooperative study group for childhood acute lymphoblastic leukemia (COALL): long-term follow-up of trials 82, 85, 89 and 92. Leukemia 2000;14(12):2234—9.

6. Rivera G., Raimondi S., Hancock M. et al. Improved outcome in childhood acute lymphoblastic leukaemia with reinforced early treatment and rotational combination chemotherapy. Lancet 1991;337(8733):61—6.

7. Tubergen D.G., Gilchrist G.S., O’Brien R.T. et al. Improved outcome with delayed intensification in children with acute lymphoblastic leukemia and intermediate presenting features: a Children’s Cancer Group phase III trial. J Clin Oncol 1993;11:527.

8. Neglia J.P., Meadows A.T., Robinson L.L. et al. Second neoplasms after acute lymphoblastic leukemiain childhood. N Engl J Med 1991;325:1330—6.

9. Meadows A.T., Baum E., Fossati-Bellani F. et al. Second malignant neoplasms in children: an update from the Late Effects Study Group. J Clin Oncol 1985;3:532—8.

10. Walter A.W., Hancock M.L., Pui C.-H. et al. Secondary brain tumors in children treated for acute lymphoblastic leukemia at St. Jude Children’s Research Hospital. J Clin Oncol 1998;16:3761—7.

11. Pui C.-H., Ribeiro R.C., Hancock M.L. et al. Acute myeloid leukemia in children treated with epipodophyllotoxins foracute lymphoblastic leukemia. N Engl J Med 1991;325:1682—7.

12. Kreissman S.G., Gelber R.D., Cohen H.J. et al. Incidence of secondary acute myelogenous leukemia after treatment of childhood acute lymphoblastic leukemia. Cancer 1992;70:2208—13.

13. Pui C.-H., Relling M.V., Rivera G.K. et al. Epipodophyllotoxin-related acute myeloid leukemia: a study of 35 cases. Leukemia 1995;9:1990—6.

14. Карачунский А.И., Штакельберг А., Мякова Н.В. и др. Сравнение протоколов ОЛЛ-БФМ-90М и ALL-MB-91 для лечения острого лимфобластного лейкоза у детей (предварительные результаты). Педиатрия 1995;(2):10—6.

15. Janka-Shaub G.E., Stuhrk H., Kortum B.U., Winkler K. Initial response to therapy as an important prognostic factor in acute lymphoblastic leukaemia in childhood COALL Study Group. Klin Padiatr 1991;203(4):231—5.

16. Eckhof-Donovan S., Schwamborn D., Korholz D. et al. Thrombosis in children with acute lymphoblastic leukaemia treated with the COALL-protocol. Klin Padiatr 1994;206(4):327—30.

17. Jurgens H., Janka-Shaub G., Ibrahim M. et al. Prognostic significance of exposure to intermediate-dose methotrexate in children with standard risk ALL: The COALL 82/85 Experience. Haematol Blood Transfus 1992;34:338—42.

18. Gobrecht O., Gobel U., Graubner U. et al. Effect of dose intensity and therapy-included leukocytopenia in childhood. Results in 213 patients of the COALL-85 study. Klin Padiatr 1992;204(4):230—5.

19. Janka-Shaub G., Harms D., Goebel U. et al. for the Coall Study Group. Randomized comparison of rational chemotherapy in high-risk acute lymphoblastic leukaemia of childhood — follow up after 9 years. Eur J Pediatr 1996;155:640—8.

20. Janka G., Harms D., Escherich G. et al. Thioguanine offers no advantage over mercaptopurine in maintenance therapy of childhood ALL. Med Pediatr Oncol 1999;33:217.

21. Harms D., Schwamborn D., Winkler K. et al. Daunorubicin-induced cell kill in 1-hour vs. 24-hour infusions: randomized comparison in newly diagnosed children with acute lymphoblastic leukemia. Med Pediatr Oncol 1994;23:197.

22. Ritter J., Creutzig V., Reiter A. et al. Childhood leukemia: Cooperative Berlin—Frankfurt—Munster trails in the Federal Republic of Germany. J Cancer Res Clin Oncol 1990;116:100.

23. Карачунский А.И., Штакельберг А., Мякова Н.В. и др. Лечение острого лимфобластного лейкоза у детей: 6-летние результаты нерандомизированного моноцентрового исследования с минимальным сроком наблюдения 2 года. Гематол трансфузиол 1997;(5):14—8.

24. Мякова Н.В., Карачунский А.И. Штакельберг А. и др. Сравнительный анализ токсичности полихимиотерапии острого лимфобластного лейкоза у детей по протоколам ALL-BFM-90m и ALL-MB-91. Педиатрия 1997;(4): 29—33.

25. Von Stackelberg A., Karachunsky A., Miakova N. et al. Toxicity, supportive care and costs of two chemotherapy protocols for treatment of childhood ALL in Russia: BFM-90m and MB-91. Eur J Cancer 1999;35:1349—55.

26. Карачунский А.И. Стратегия терапии острого лимфобластного лейкоза у детей. Автореф. докт. … мед. наук. М., 1999.

27. Bleyer W.A. Biology and pathogenesis of CNS leukemia. Am J Pediatr Hem Oncol 1989;11(1):57—63.

28. Henze G., Langermann H.-J., Braemswig J. et al. Ergebnisse der Studie BFM 76/79 zur Behandlung der akuten lymphoblastischen Leukämie bei Kindern und Jugendlichen. Klin Pädiatrie 1981;193:145—54.

29. Reiter A., Schrappe M., Ludwig W. et al. Chemotherapy in 998 unselected childhood acute lymphoblastic leukemia patients. Results and conclusions of the multicenter trial ALL-BFM 86. Blood 1994;84:3122—33.

30. Veerman A.J.P., Hahlen K., Kamps W.A. et al. Dutch Childhood Leukemia Study Group: Early results of study ALL VI (1984—1988). Haematol Blood Transfus 1990;33:473—7.

31. Veerman A.J.P., Hahlen K., Kamps W.A. et al. High cure rate with a moderately intensive treatment regimen in non-highrisk childhood acute lymphoblastic leukemia: Results of protocol ALL-VI from the Dutch Leukemia Study Group. J Clin Oncol 1996;14:911—8.

32. Clavell L.A., Gelber R.D., Cohen H.J. et al. Four-agent induction and intensive asparaginase therapy for childhood acute lymphoblastic leukemia. N Engl J Med 1986;315:657—63.

33. Barr R.D., DeVeber L.L., Pai K.M. et al. Management of children with acute lymphoblastic leukemia by the Dana-Farber Cancer Institute Protocols. Am J Pediatr Hem Oncol 1992;14:136—9.

34. Schorin M.A., Blattner S., Gelber R. et al. Treatment of childhood acute lymphoblastic leukemia: Results of Dana-Farber Institute/Children’s Hospital Acute Lymphoblastic Leukemia Consortium Protocol 85-01. J Clin Oncol 1994;12:740—7.

35. Карачунский А.И., Мякова Н.В., Тимаков А.М. и др. Результаты мультицентрового исследования лечения острого лимфобластного лейкоза у детей — ALL-MB-91/ALL-BFM-90m: анализ эффективности и токсичности. Тер арх 2007;79(7):19—26.