PurposeFavorable 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.MethodsBetween 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.ResultsProbabilities 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).ConclusionOur 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.Electronic supplementary materialThe online version of this article (10.1007/s00432-019-02854-x) contains supplementary material, which is available to authorized users.
Serious side effects occur during therapy for childhood acute lymphoblastic leukemia (ALL), and survivors can experience long-term consequences. This study aimed at identifying patients who can be successfully treated with low treatment intensity combining clinical parameters and minimal residual disease (MRD) measurements. The study was approved by the Independent Ethics Committee and the Scientific Council of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology. ALL-MB studies used reduced-intensity therapy from the beginning, for standard risk (SR) patients no cyclophosphamide, a very low daunorubicin dose, no high dose of methotrexate, no cranial irradiation. In the ALL-MB 2008 study, 1702 children (49.1 % of all patients) were classified as SR due to favorable initial characteristics. These included 295 patients treated in institutions who took part in a pilot study on MRD measurement using flow cytometry on day 15 and/or at the end of induction (EOI). The most suitable time point for MRD measurement was EOI with threshold 0.1% in 90.5 % of the patients with excellent results: event-free survival of 95 % and overall survival of 97 %, that identified the large proportion of patients (more than 40 % of all ALL patients). The outcome of children with slower MRD response was significantly worse. Initial SR characteristics plus one single MRD measurement at EOI identify more than 40 % of all children with ALL who can be successfully treated with low-intensity regimens as used in the MB protocols.
Introduction. Neuroblastoma (NB) in children is a rare disease, accounting for 7 % of all cases of oncological diseases in childhood. In this regard, epidemiological analysis requires the accumulation of data over a long period of time. The purpose of the study is to study the morbidity, mortality and survival rate of children 0–14 years old with NB in the Republic of Belarus (RB).Materials and methods. Based on the data from the children’s cancer subregister, morbidity, mortality and survival rates in child population were calculated from 1997 to 2017. A comparative epidemiological analysis was carried out in 2 time periods (1997–2007, 2008–2017).Results and discussion. The incidence rate of NB in the RB, standardized for age, was 1.142 ± 0.062 per 100 000 child population with an average annual growth rate of 3.2 % per year. The mortality rate for this period was 0.32 ± 0.03 per 100 000 child population, an increase of 0.51 % per year. The main cause of death in patients with NB is the recurrence of the underlying disease. In 2008, a single protocol was used to treat all risk groups, which led to a significant increase in the observed population survival rate from 56 % (1997–2007) to 72 % (2008–2017) (p = 0.0041). Comparing the age structure of morbidity in Germany and the RB, it is noted that we have a reliably later diagnosis of the disease in the age categories from 0 to 1 year, from 1 to 4 years, from 5 to 9 years. The median age of the patient at the time of diagnosis in Germany is 1 year and 2 months, in our country 1 year and 6 months.Conclusion. Indicators of standardized morbidity and mortality from NB in the RB correspond to the indicators of cancer registries in Western Europe and the USA. However, analyzing the age of the specific incidence of the disease, insufficient diagnosis of the disease is noted in the periods from 0 to 1 year, from 1 to 4 years and from 5 to 9 years compared to the data in Germany. This requires further improvement of the pediatric oncology service in the country.
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