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 ¼ 358) vs 68 ± 3% on ALL-BFM 90m (N ¼ 355). The overall survival (OS) was 71±3% vs 74±2%, respectively. Anaemia, thrombocytopenia, agranulocytosis 410 days and hospitalization (median 35 vs 68 days) were lower on ALL-MB 91 (Po0.01, N ¼ 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.
Background
Inflammatory myofibroblastic tumors (IMTs) are exceptionally rare neoplasms, which are often driven by rearranged tyrosine kinases.
Methods
This study considered 33 consecutive patients with IMT (median age, 6.6; age range, 0.6‐15.8 years). RNA and cDNA were successfully obtained in 29 cases. The molecular analysis included sequential tests for 5′/3′‐end unbalanced gene expression, variant‐specific PCR, and next‐generation sequencing (NGS).
Results
5′/3′‐end unbalanced ALK expression was revealed in 15/29 (52%) IMTs. Strikingly, all these tumors demonstrated high amount of ALK protein detected by immunohistochemistry. Variant‐specific PCR was capable of identifying the type of ALK rearrangement in 11/15 IMTs with 5′/3′‐end unbalanced ALK expression. The remaining four tumors were analyzed by NGS; two known and two novel (CLTC‐ins6del84‐ALK and EEF1G‐ALK) ALK rearrangements were detected. Five IMTs demonstrated 5′/3′‐end unbalanced ROS1 expression, and all these tumors carried TFG‐ROS1 fusion. Nine tumors, which were negative for 5′/3′‐end unbalanced ALK/ROS1 expression, were subjected to further analysis. Variant‐specific PCR revealed two additional tumors with gene rearrangements (TFG‐ROS1 and ETV6‐NTRK3). The remaining seven IMTs were tested by NGS; single instances of TFG‐ROS1 and novel SRF‐PDGFRb translocations were detected.
Conclusions
Twenty‐four of 29 IMTs (83%) were shown to have druggable rearrangements involving tyrosine kinases, 20 of these 24 gene fusions were detectable by simple and inexpensive PCR assay, which is based on the detection 5′/3′‐end unbalanced gene expression.
The favorable mortality trends highlight the progress in Southern-Eastern European countries along their trajectory to converge with Northern-Western EU counterpart states. Socioeconomic status may act as a multipotent factor underlying the study findings.
Solid tumours represent about 50% of all malignant neoplasms in children aged less than 15 years. 1,2 The incidence and histological type of solid tumours is age-dependent. They make up more than 80% of all malignancies in infants. 3 The solid tumours to leukemias ratio is 2:1 in children aged 1-14 but 5:1 in infants less than 1 year. The Radiol Oncol 2008; 42(1): 39-44. doi:10.2478/v10019-007-0037-2
Dysregulation of the immune system undoubtedly plays an important and, perhaps, determining role in the COVID-19 pathogenesis. While the main treatment of the COVID-19 intoxication is focused on neutralizing the excessive inflammatory response, it is worth considering an equally significant problem of the immunosuppressive conditions including immuno-paralysis, which lead to the secondary infection. Therefore, choosing a treatment strategy for the immune-mediated complications of coronavirus infection, one has to pass between Scylla and Charybdis, so that, in the fight against the “cytokine storm,” it is vital not to miss the point of the immune silence that turns into immuno-paralysis.
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