Optimization of native E. coli-asparaginase therapy in standard risk-group children with acute lymphoblastic leukemia treated by the ALL-MB 2002 protocol
https://doi.org/10.17650/1818-8346-2008-0-3-25-33
Abstract
The paper presents the results of a multicenter randomized study of two-dose COLI-ASP regimens in therapy of consolidation of standard risk-group (SRG) children and adolescents with acute lymphoblastic leukemia (ALL) treated by the ALL-MB-2002 protocol. The principal aim of the study was to elucidate whether the dose of COLI-ASP might be reduced without losing the efficiency of therapy. The analysis covered primary ALL patients notified at 36 clinics of Russia and Belarus, enrolled for the study in the period of May 1, 2002, to October 10, 2006. Out of 819 patients to be examined, 414 received COLI-ASP in a dose of 10,000 U/m2 (a control group), and 405 children took it in a dose of 5,000 U/m2 (a study group). No statistically significant differences were found between the patients in gender, age, baseline leukocytosis, and spleen size. The study showed no statistically and clinically significant differences in event-free, overall, and relapse-free survival (EFS, OS, and RFS, respectively) and relapse rates with the use of two-dose COLI-ASP regimens. However, in the control group, the death rate in remission was twice greater than that in the study group (p = 0.02). Detailed analysis of the outcomes of therapy in some subgroups revealed no differences between the control and study groups. The Cox multiple regression analysis has indicated that the factors influencing EFS and RFS are the baseline sizes of the spleen, baseline leukocytosis, age, and a response to treatment in the period of induction, rather than the dose of E. coli asparaginase. The authors have also found that among the SRG patients, there is a subgroup of patients without risk factors, in whom the reduction in the COLI-ASP dose may substantially increase survival rates, by lowering toxicity and mortality in remission.
About the Authors
M. Yu. Goroshkova
Clinical Children Hospital №4
Russian Federation
Russian Federation
Novokuznetsk
Yu. V. Rumyantseva
Federal Research Centre of Pediatric Hematology, Oncology and Immunology
Russian Federation
Russian Federation
Moscow
O. V. Aleinikova
Republic Centre for Paediatric Oncology and Haematology
Belarus
Belarus
Minsk
S. A. Dudkin
Clinical Children Hospital №4
Russian Federation
Russian Federation
Novokuznetsk
L. G. Fechina
Regional Centre for Paediatric Oncology and Haematology
Russian Federation
Russian Federation
Yekaterinburg
A. V. Shamardina
Regional Clinical Children Hospital
Russian Federation
Russian Federation
N. Novgorod
O. V. Streneva
Regional Centre for Paediatric Oncology and Haematology
Russian Federation
Russian Federation
Yekaterinburg
K. L. Kondratchik
Morozov Children Clinical Hospital
Russian Federation
Russian Federation
Moscow
L. M. Minkina
Clinical Children Hospital
Russian Federation
Russian Federation
Vladivostok
E. S. Lapotentova
Republic Centre for Paediatric Oncology and Haematology
Belarus
Belarus
Minsk
E. V. Inyushkina
Moscow District Oncology Dispanser
Russian Federation
Russian Federation
Balaschicha
O. B. Kozlova
Regional Clinical Hospital
Russian Federation
Russian Federation
Ivanovo
E. V. Zhukovskaya
Regional Children Clinical Hospital
Russian Federation
Russian Federation
Chelyabinsk
O. P. Khlebnikova
Regional Centre for Paediatric Oncology and Haematology
Russian Federation
Russian Federation
Yekaterinburg
E. V. Basharova
Regional Children Clinical Hospital
Russian Federation
Russian Federation
Chelyabinsk
V. N. Timofeeva
Regional Children Clinical Hospital
Russian Federation
Russian Federation
Ulyanovsk
G. P. Pavlova
Republic Children Clinical Hospital
Russian Federation
Russian Federation
Cheboksary
V. D. Zlobina
Regional Clinical Hospital
Russian Federation
Russian Federation
Novosibirsk
O. A. Utrobina
Regional Clinical Hospital
Russian Federation
Russian Federation
Novosibirsk
E. S. Banshchikova
Republic Hospital №1 — National Medicine Centre
Russian Federation
Russian Federation
Yakutsk
K. S. Aslanyan
Regional Children Clinical Hospital
Russian Federation
Russian Federation
Rostov-on-Don
E. V. Kondakova
Regional Children Clinical Hospital
Russian Federation
Russian Federation
Surgut
E. V. Tselousova
Kirov Research Centre of Hematology and Transfusiology
Russian Federation
Russian Federation
Kirov
N. V. Myakova
Federal Research Centre of Pediatric Hematology; Russian Children Clinical Hospital
Russian Federation
Russian Federation
Moscow
T. V. Turobova
Regional Children Clinical Hospital
Russian Federation
Russian Federation
Archangelsk
O. V. Ryskal
Regional Children Clinical Hospital
Russian Federation
Russian Federation
Perm
O. Yu. Fuks
Federal Research Centre of Pediatric Hematology, Oncology and Immunology; Morozov Children Clinical Hospital
Russian Federation
Russian Federation
Moscow
V. V. Lebedev
Regional Children Clinical Hospital
Russian Federation
Russian Federation
Krasnodar
N. F. Chipsanova
Regional cardiological dispanser
Russian Federation
Russian Federation
Syktyvkar
S. R. Varfolomeeva
Federal Research Centre of Pediatric Hematology, Oncology and Immunology
Russian Federation
Russian Federation
Moscow
A. I. Karachunsky
Federal Research Centre of Pediatric Hematology, Oncology and Immunology
Russian Federation
Russian Federation
Moscow
References
1. Riehm H., Gadner H., Henre G. et al. The Berlin childhood acute lymphoblastic leukemia study. Am J Pediatr Hematol 1980;2:229—35.
2. Sallan S.E., HitchcocK-Bryan S., Gelber R. et al. Influence of intensive asparaginase in the treatment of childhood non-T-cell acute lymphoblastic leukemia. Can Res 1983;43:5601—7.
3. Broome J.D. Evidence that the COLIASParaginase of guinea pig serum is responsible for its antilymphoma effects. J Exp Med 1963;118:99—120.
4. Kidd J.G. Regression of transplanted lymphomas induced in vivo by means of normal guinea pig serum. J Exp Med 1953;98(6):565—82.
5. Jones B., Holland J.F., Glidewell O. et al. Optimal use of COLI-ASParaginase (NSE-109229) in acute lymphoblastic leukemia. Med Ped Oncol 1977;3:387—400.
6. Oettgen H.F., Stephenson P.A., Schwartz M.K. et al. Toxicity of E. coli COLI-ASParaginase in man. Cancer 1970;25(2):253—78.
7. Pui C.H., Evans W.E., Frankel L.S. et al. Treatment of acute lymphoblastic leukemia. N Engl J Med 2006;354: 166—78.
8. 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.
9. Silverman L.B., Gelber R.D., Declerck L. et al. Results of Dana-Farber Cancer Institute Consortium protocols for children with newly diagnosed acute lymphoblastic leukemia (1981—1995). Leukemia 2000;14:2247—56.
10. Ahlke E., Nowak-Gottl U., Schulze-Westhoff P. et al. Dose reduction of asparaginase under pharmacokinetic and pharmacodynamic control during induction therapy in children with acute lymphoblastic leukaemia. Br J Hematol 1997;96:675—81.
11. 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.
12. 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—34.
13. Румянцева Ю.В., Карачунский А.И. Оптимизация терапии острого лимфобластного лейкоза у детей в России и Белоруссии: стратегия Москва-Берлин. Вопр гематол онкол иммунол педиатр 2007;6(4):13—21.
Review
For citations:
Goroshkova M.Yu., Rumyantseva Yu.V., Aleinikova O.V., Dudkin S.A., Fechina L.G., Shamardina A.V., Streneva O.V., Kondratchik K.L., Minkina L.M., Lapotentova E.S., Inyushkina E.V., Kozlova O.B., Zhukovskaya E.V., Khlebnikova O.P., Basharova E.V., Timofeeva V.N., Pavlova G.P., Zlobina V.D., Utrobina O.A., Banshchikova E.S., Aslanyan K.S., Kondakova E.V., Tselousova E.V., Myakova N.V., Turobova T.V., Ryskal O.V., Fuks O.Yu., Lebedev V.V., Chipsanova N.F., Varfolomeeva S.R., Karachunsky A.I. Optimization of native E. coli-asparaginase therapy in standard risk-group children with acute lymphoblastic leukemia treated by the ALL-MB 2002 protocol. Oncohematology. 2008;(3):25-33. (In Russ.) https://doi.org/10.17650/1818-8346-2008-0-3-25-33
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