Non-anaplastic peripheral T cell lymphoma in children and adolescents-an international review of 143 cases.

Peripheral T cell lymphomas (PTCL) are rare in children and adolescents, and data about outcome and treatment results are scarce. The present study is a joint, international, retrospective analysis of 143 reported cases of non-anaplastic PTCL in patients <19 years of age, with a focus on treatment and outcome features. One hundred forty-three patients, between 0.3 and 18.7 years old, diagnosed between 2000 and 2015 were included in the study. PTCL not otherwise specified was the largest subgroup, followed by extranodal NK/T cell lymphoma, hepatosplenic T cell lymphoma (HS TCL), and subcutaneous panniculitis-like T cell lymphoma (SP TCL). Probability of overall survival (pOS) at 5 years for the whole group was 0.56 ± 0.05, and probability of event-free survival was (pEFS) 0.45 ± 0.05. Patients with SP TCL had a good outcome with 5-year pOS of 0.78 ± 0.1 while patients with HS TCL were reported with 5-year pOS of only 0.13 ± 0.12. Twenty-five percent of the patients were reported to have a pre-existing condition, and this group had a dismal outcome with 5-year pOS of 0.29 ± 0.09. The distribution of non-anaplastic PTCL subtypes in pediatric and adolescent patients differs from what is reported in adult patients. Overall outcome depends on the subtype with some doing better than others. Pre-existing conditions are frequent and associated with poor outcomes. There is a clear need for subtype-based treatment recommendations for children and adolescents with PTCL.

[Efficiency of the ALL-MB-2002 protocol in children with acute lymphoblastic leukemia].

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 100 x 10(9)/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.

Results of the first randomized multicentre trial on childhood acute lymphoblastic leukaemia in Russia.

Until 1990, the survival of children with acute lymphoblastic leukaemia (ALL) in Russia was below 10%. To establish a protocol feasible under conditions there, ALL-MB 91 was designed to avoid prolonged bone marrow aplasia, thereby reducing needs for extensive supportive care, blood transfusions, long-lasting hospitalization and costs. High-dose therapies were avoided, anthracycline use was limited and CNS radiation therapy only foreseen in high-risk patients (about 30%). This was randomized against a modified BFM protocol. From 1995 to 2002, 834 patients of age up to 18 years were registered in 10 centres and 713 received after central randomization the allocated risk-stratified treatment. After a median follow-up of 7 years, the event-free survival (EFS) was 67+/-3% on ALL-MB 91 (N=358) vs 68+/-3% on ALL-BFM 90m (N=355). The overall survival (OS) was 71+/-3% vs 74+/-2%, respectively. Anaemia, thrombocytopenia, agranulocytosis >10 days and hospitalization (median 35 vs 68 days) were lower on ALL-MB 91 (P<0.01, N=197). While EFS and OS were similar with both protocols, ALL-MB 91 significantly incurred fewer toxicity and resource requirements and, therefore, has been increasingly used across Russia.

[The results of a multicenter trial of acute lymphoblastic leukemia treatment on ALL-MB 91/ALL-BFM 90m in children: analysis of efficacy and toxicity].

AIM: A comparative analysis of efficacy and toxicity of two chemotherapy regimens: standard German protocol ALL-BFM 90m and less intensive original test protocol ALL-MB 91 in a multicenter trial of acute lymphoblastic leukemia (ALL) in children. MATERIAL AND METHODS: In 1995-2002 a total of 834 patients with newly diagnosed ALL aged 0-18 years were admitted to 10 clinics of Russia. Of them, 713 were randomized in two groups: treatment program ALL-BFM 90m (n = 355) and ALL-MB 91 program (n = 358). RESULTS: In 7-year follow-up median, 10-year event-free survival (EFS) and overall survival (OS) did not differ significantly between the groups and was 67 +/- 3 and 68 +/- 3% (ALL-MB 91) and 74 +/- 2, 71 +/- 3% (ALL-BFM 90m), respectively. Though the rate of isolated recurrences in CNS in patients on the protocol ALL-MB 91 was 2.8%, they developed only in 0.8% patients of the standard risk group. Anemia, thrombocytopenia and agranulocytosis developed less frequently, hospital stay was significantly shorter on the test protocol vs the control one (p < 0.01). CONCLUSION: EFS and OS on the test (ALL-MB 91) and control (ALL-BFM 90m) protocols were equivalent in lower toxicity and cost of therapy.

[Results of the treatment of childhood acute lymphoblastic leukemia according to the Berlin-Moscow-91 protocol in 1991-2000]. / Rezul'taty lecheniia ostrogo limfoblastnogo leikoza u detei po protokolu Moskva-Berlin-91 v 1991-2000 gg.

The report deals with the results of application of an original protocol--the Berlin-Moscow-91 (BM-91)--for the treatment of acute lymphoblastic leukemia (ALL) in children. The researchers' major concern was to improve survival and cut down side-effects incidence as well as to prevent and successfully manage occult neuroleukemia as a potential source of relapse. Patients aged 5 months-15 years received the BM-91 and ALL BFM-90m treatment first at one clinic and later at several centers. Out of 852 children with primary diagnosis of ALL admitted to Russian hematological hospitals (March 2, 1991-November 3, 2000), 687 were included into the study; 329 received the MB-91 protocol. Nine-year recurrence-free survival was 73% while overall survival--80%. Toxic side-effects after L-asparaginase were reported in 27 (7.9%). It is concluded that good results in childhood ALL treatment can be achieved without resorting to high-dosage chemotherapy and radiation in most cases.

[Treatment of acute lymphoblastic leukemia in children according to the ALL-BFM-90m protocol in the Russian Federation and the Republic of Belarus]. / Lechenie ostrogo limfoblastnogo leikoza u detei po protokolu OLL-BFM-90m v Rossiiskoi Federatsii i Respublike Belarus'.

Prognosis for children treated according to the BFM-90m protocol (Berlin-Frankfurt-Munster Group) for acute lymphoblastic leukemia (ALL) improved significantly as compared with previous modalities. Methotrexate was used in the dose of 1,000 mg/m2, 36 h. The paper presents the 10-year results for this modification. Patients aged 0-15 years were treated at hematological hospitals of Moscow, other Russian towns and in Minsk, Belarus, (July 5, 1990-November 11, 2000). BFM-90m treatment was given to 682 children out of 1,326 with primary diagnosis of ALL; a comparative trial of the MB-91 protocol hed been carried out at the same clinics since 1991. During 10 years, recurrence-free survival was 72% while overall survival--77%. Toxicity of side-effects was tolerable. The BFM-90m treatment showed significantly better results in both countries.

Toxicity, supportive care and costs of two chemotherapy protocols for treatment of childhood ALL in Russia: BFM 90m and MB 91.

Since the late 1980s, polychemotherapy protocols for the treatment of childhood acute lymphoblastic leukaemia (ALL) derived from Western European and American regimens have been introduced in Russian paediatric oncology centres. Whereas treatment results were significantly improved compared with the results of former non-standard treatment strategies, the substantial toxicity of these protocols required a high standard of supportive care, and the high costs of treatment became a major problem. In 1991, a new protocol was developed with the aim of reducing toxicity and costs without affecting efficacy of the treatment. Since 1991, a single-centre study comparing the new Russian Protocol, Moscow-Berlin 91 (MB), with a modified version of the protocol ALL BFM 90 (BFM) of the Berlin-Frankfurt-Münster group was performed in Moscow to evaluate possible advantages of the new protocol under Russian conditions. The aim of the present analysis was to compare toxicity, need of supportive care and expense of both regimens (BFM, 25 pts; MB, 32 pts). Hepatotoxicity (liver enzymes), nephrotoxicity (creatinine), duration of neutropenia, and platelet transfusions were similar in both protocols. The median erythrocyte transfusion level was greater in the BFM (1000 ml/m2) than the MB patients (505 ml/m2, P < 0.01), as was the length of intravenous (i.v.) antibiotic therapy (22 days BFM versus 9 days MB, P < 0.01), treatment delays (39 days BFM versus 21 days MB, P < 0.001), and duration of in-patient treatment (47 days BFM versus 18 days MB, P < 0.001). Side-effects of the MB protocol occurred mainly during induction therapy. Total costs (mean cost/person/m2 body surface) of treatment including supportive care were 1.73-fold higher for the BFM protocol than MB, whereas costs of cytostatic drugs were comparable in both groups. In Russia both protocols were feasible. During consolidation therapy tolerance to treatment was better in MB 91 compared with BFM 90m, whereas toxicity during induction therapy was similar in both protocols. With respect to costs and side-effects, the MB 91 protocol appears to be an alternative to established protocols for countries with limited financial and clinical resources.