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Randomized Controlled Trial
. 2019 Apr;145(4):1001-1012.
doi: 10.1007/s00432-019-02854-x. Epub 2019 Mar 6.

Reduced vs. standard dose native E. coli-asparaginase therapy in childhood acute lymphoblastic leukemia: long-term results of the randomized trial Moscow-Berlin 2002

Alexander Karachunskiy  1   2   3 , Gesche Tallen  4   5   6 , Julia Roumiantseva  7   8 , Svetlana Lagoiko  7 , Almira Chervova  7 , Arend von Stackelberg  4 , Olga Aleinikova  9 , Oleg Bydanov  9 , Lyudmila Bajdun  10 , Tatiana Nasedkina  7 , Natalia Korepanova  11 , Sergei Kuznetsov  11 , Galina Novichkova  7   8 , Marina Goroshkova  12 , Dmitry Litvinov  7   8 , Natalia Myakova  7 , Natalia Ponomareva  10 , Evgeniya Inyushkina  13 , Konstantin Kondratchik  8   14 , Julia Abugova  7 , Larisa Fechina  15 , Oleg Arakaev  15 , Alexander Karelin  7 , Vladimir Lebedev  16 , Natalia Judina  17 , Gusel Scharapova  18 , Irina Spichak  19 , Anastasia Shamardina  20 , Olga Ryskal  21 , Alexander Shapochnik  22 , Alexander Rumjanzew  7   8 , Joachim Boos  23 , Günter Henze  8   4 ; ALL-MB study group
Affiliations
Randomized Controlled Trial

Reduced vs. standard dose native E. coli-asparaginase therapy in childhood acute lymphoblastic leukemia: long-term results of the randomized trial Moscow-Berlin 2002

Alexander Karachunskiy et al. J Cancer Res Clin Oncol. 2019 Apr.

Abstract

Purpose: Favorable outcomes were achieved for children with acute lymphoblastic leukemia (ALL) with the first Russian multicenter trial Moscow-Berlin (ALL-MB) 91. One major component of this regimen included a total of 18 doses of weekly intramuscular (IM) native Escherichia coli-derived asparaginase (E. coli-ASP) at 10000 U/m2 during three consolidation courses. ASP was initially available from Latvia, but had to be purchased from abroad at substantial costs after the collapse of Soviet Union. Therefore, the subsequent trial ALL-MB 2002 aimed at limiting costs to a reasonable extent and also at reducing toxicity by lowering the dose for standard risk (SR-) patients to 5000 U/m2 without jeopardizing efficacy.

Methods: Between April 2002 and November 2006, 774 SR patients were registered in 34 centers across Russia and Belarus, 688 of whom were randomized. In arm ASP-5000 (n = 334), patients received 5000 U/m2 and in arm ASP-10000 (n = 354) 10 000 U/m2 IM.

Results: Probabilities of disease-free survival, overall survival and cumulative incidence of relapse at 10 years were comparable: 79 ± 2%, 86 ± 2% and 17.4 ± 2.1% (ASP-5000) vs. 75 ± 2% and 82 ± 2%, and 17.9 ± 2.0% (ASP-10000), while death in complete remission was significantly lower in arm ASP-5000 (2.7% vs. 6.5%; p = 0.029).

Conclusion: Our findings suggest that weekly 5000 U/m2E. coli-ASP IM during consolidation therapy are equally effective, more cost-efficient and less toxic than 10000 U/m2 for SR patients with childhood ALL.

Keywords: Acute lymphoblastic leukemia; Children; Multicenter trial; Native Escherichia coli-derived asparaginase.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Fig. 1
Fig. 1
a Consort diagram showing recruitment, eligibility, and randomization of standard risk group patients for treatment with 5000 vs. 10,000 U/m2 of E. coli-asparaginase (E. coli-ASP) given intramuscularly during consolidation therapy in trial ALL-Moscow–Berlin 2002 (for details, see main text). b Treatment overview: randomization arms ASP-5000 and ASP-10000 in trial ALL-MB 2002
Fig. 2
Fig. 2
Treatment results (“intent-to-treat-analysis”) for standard risk group patients after consolidation therapy with 5000 vs. 10,000 U/m2 of E. coli-ASP IM in trial ALL-Moscow–Berlin 2002 by randomization arm (for details, see main text). a Disease-free survival (DFS) at 10 years, b probability of overall survival (pOS) at 10 years, c cumulative incidence (CI) of relapses and deaths in CR at 10 years. d Disease-free survival (DFS) at 10 years only patients randomized to DEXA during induction, e disease-free survival (DFS) at 10 years only patients randomized to MePRED during induction. ASP asparaginase, CI cumulative incidence, CR complete remission, CCR continuous CR, DFS disease-free survival, IM intramuscular, pOS probability of overall survival
See this image and copyright information in PMC

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