Search

Aim. To determine predictors for decision-making on a differential approach to choosing glucocorticosteroids (GCS) for children and adolescents with acute lymphoblastic leukemia (ALL). Subjects and methods. The analysis covered 1064 primary patients aged to 1 to 18 years with ALL who had been registered at the clinics of Russia and Belorussia in April 2002 to November 2006. Before induction therapy, the patients were randomized into a dexamethasone (DEXA) 6 mg/m2 group (n=539) and a methylprednisolone (MePRED) 60 mg/m2 one (n=525). Results. The entire group showed no statistically significant differences in survival rates between the patients receiving DEXA or MePRED. However, an analysis of age groups revealed the benefits of DEXA in children younger than 14 years (the event-free survival (EFS) was 76±2 and 71±2%, respectively (p=0.048); the overall survival (OS) was 81±2 and 77±2%, respectively (р=0.046); therapy-induced mortality was 6.4% (DEXA) and11.1% (MePRED) (р=0.014); the rate of isolated extramedullary relapses was 1.5% (DEXA) and 4.4% (MePRED) ( р=0.009). At the same time, EFS and OS in 14-to-18-year-old adolescents were statistically significantly higher than in those who used MePRED (EFS, 65±6 and 52±6%, respectively (р=0.087); OS, 72±6 and 61±6%, respectively; (р=0.17). Conclusion. The findings suggest that it is possible that the choice of a GCS for ALL therapy must be also based on a patient’s age. There is a need for further studies of this matter in prospective randomized multicenter trials in children and adolescents.

Aim. To evaluate the efficiency of the original ALL-MB-2002 protocol within the multicenter study of treatment of acute lymphoblastic leukemia (ALL) in children. Subjects and methods. A total of 1873 primary patients with ALL aged 1 to 18 years, of whom 1544 patients were enrolled in this study, were notified at 36 clinics of Russia and Belarus from April 15, 2002, to January 1, 2008. Results. With the median observation of 4.12 years, 7-year event-free survival (EFS) was 73±13%; overall survival (OS) 78±2%; relapse-free survival 82±1%. The rates of EFS and OS were equal and amounted to 76±2 and 80±2% in the standard-risk group (SRG) and intermediate-risk group (ImRG), respectively. In the high-risk group (HRG) patients, EFS and OS were as high as 30±6 and 37±6%, respectively. The frequency of relapses with central nervous system lesion was as much as 4.7% in all the patients, 6-year cumulative risk for isolated neurorecurrences being 2.5% in the SRG patients. Adolescents, patients with the baseline leukocytosis (more than 100109/l), and those with a splenic size of over 4 cm or more from the costal arch margin had substantially worse survival rates. A poor early response to therapy (on induction days 8 and 15) was also associated with its lower efficiency. Conclusion. Despite a considerable rise in the number of centers and a slight increase in the intensity of therapy, the results of the new ALL-MB-2002 protocol are as minimum equivalents obtained in the use of the previous ALL-MB-91 protocol. A significant improvement in the overall results of therapy and a reduction in the cumulative risk for isolated neurorecurrences were noted in the ImRG patients.

Проанализирована значимость прогностических факторов эффективности терапии у детей с острым лимфобластным лейкозом (ОЛЛ), получающих терапию по протоколу ALL-MB-2002, в зависимости от группы риска. В исследование были включены 1544 первичных больных ОЛЛ в возрасте от 1 года до 18 лет, получавших лечение в 36 клиниках России и Беларуси в период с 15 апреля 2002 г. до 1 января 2008 г. Из 1544 больных, включенных в анализ, пациенты группы стандартного риска (SRG) составили 69,2 %, промежуточного риска (ImRG) — 24,5 % и 6,3 % пациентов были отнесены к группе высокого риска. Анализ, проведенный у пациентов SRG, продемонстрировал резкие различия в выживаемости между отдельными подгруппами больных. Выявлены достоверные различия в показателях выживаемости пациентов в зависимости от возраста (старше и младше 10 лет), инициального лейкоцитоза (более и менее 30 × 10 9 /л), инициального пальпаторного увеличения селезенки (более и менее 4 см из-под края реберной дуги) и параметров раннего ответа на терапию (8-й и 15-й день). При ретроспективном определении больных, относящихся к SRG, с использованием новых критериев (инициальный лейкоцитоз

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.

In present article comparative efficacy analysis of two conceptually various acute lymphoblastic leukemia (ALL) chemotherapy programs from 18. 04. 2002 till 01. 01. 2007 aimed at definition of optimum ALL chemotherapy strategy in children is presented. To obtain an ultimate correct analysis patients data bases from Moscow and St.-Petersburg oncohematology departments have been united to the subsequent carrying out of meta-analysis. 292 primary patients are included in this analysis from ALL-MB-2002 group and 126 patients from COALL-St.Petersburg-92 group aged from 4 months to 18 years. Analysis of treatment results dynamics in ALL patients received COALL-St.Petersburg-92 protocol for 2 periods: from 01. 01. 1999 till 18. 04. 2002 and from 18. 04. 2002 till 01. 01. 2007 is also presented. Detailed comparison of two chemotherapy programs efficacy has not found any statistically significant differences concerning such factors, as complete remission rate, early death rate and relapse rate, and as number of children who are in continuous complete remission. Event-free survival (EFS) in both groups was 78 ± 3 and 78 ± 4 %, respectively (р = 0.85). The overall survival (OS) was 80 ± 5 % for patients treated according to ALL-MB-2002 protocol, and 83 ± 4 % for patients receiving COALL-St.Petersburg-92 protocol (р = 0.65). Though comparison of ALL-MB-2002 and COALL-St.Petersburg-92 protocols has shown, that efficacy of both chemotherapy regimens is identical, however such advantages of ALL-MB-2002 protocol as reduced toxicity and greater simplicity in implementation could be crucial for the choice of optimal chemotherapy strategy for childhood ALL in Russia.