In 2017 the organization of the children’s hematology service celebrated the 50th jubilee in St. Petersburg. The first specialized children’s hematology department in Leningrad (now St. Petersburg) was opened in 1967. Over the years, a strong network of institutions that allowed to provide highly qualified assistance to all children in need with hematological diseases has been formed in the city with the population greater than 5 million: the number of divisions reached seven and its curative capacity is more than 180 beds. The article describes the main phase of the development of the hematological service in St. Petersburg.
One of the main risk-factors of acute lymphoblastic leukemia (ALL) is age. The most favorable age group is children from 2 to 9 years old, and the adolescents and young adults have the worst prognosis. Treatment of ALL at adolescents and young adults is a unique problem of modern hematology now. This work presents the analysis of 368 cases of patients with primary ALL 15–18 years old, which were registered in the database of Russian-Belarussian group from April 2002 to November 2014. The aim of the analysis was the estimation of effectiveness of different generations of protocol for adolescents and prognostic significance of different factors to reveal the ways of future therapy optimizing in this age group. Event-free survival of adolescents 15–18 years old according our study was 56 ± 5 % in ALL-MB-2002 study and 57 ± 6 % in ALL-MB-2008 study. We did not received any differences in survival based on immunophenotype of blast cells. But the risk group analysis showed the worst results at patients with ALL from pre-B-precursor cells of high risk. No difference was revealed according the gender. One of the general problems remains high toxicity of therapy at patients of this age group. Treatment related mortality (TRM) was 13.2 and 12 % at ALL-MB-2002 and ALL-MB-2008 accordingly. Main cause of deaths remains infection.
Children with acute lymphoblastic leukemia (ALL) and slow clearance of minimal residual disease (MRD) demonstrate a significantly worse outcome as compared to those with fast response to chemotherapy. Bispecific monoclonal antibody blinatumomab is the key drug for CD19-directed immunotherapy which opens wide opportunities for the elimination of MRD in patients with B-cell precursor ALL (BCP-ALL). Aim of the study – to evaluate the effectiveness of blinatumomab for MRD elimination in children with BCP-ALL and slow MRD clearance treated by the “ALL-MB 2015” protocol. 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. Patients from the “ALL-MB 2015” trial who demonstrated slow MRD clearance at the end of induction were included in the current study. MRD monitoring was performed by multicolor flow cytometry modified with respect to possible CD19 loss during targeted treatment. Threshold of 0.001% was used for MRD positivity definition. Between February 2020 and August 2023, 228 children with de novo Ph-negative KMT2A-negative BCP-ALL were defined as slow MRD responders according to the criteria of the “Moscow-Berlin” group. Fifty of them were treated with blinatumomab because of slow MRD clearance. Blinatumomab course was given immediately after induction in 23 children, after Consolidation I – in 14 patients, after Consolidation II – in 11 patients, while two children received immunotherapy prior to maintenance. After completion of blinatumomab course, 23 patients continued protocol treatment, 21 received maintenance only, two were treated with high-risk blocks and four received hematopoietic stem cell transplantation. Only 2 of 50 (4.0 %) patients remained MRD-positive after completion of blinatumomab course. By the end of December 2023, only two adverse events were registered: one relapse and one remission death. Two-year event-free survival was 94.7 % (standard error 3.6 %), while cumulative incidence of relapse was 2.6 % (standard error 2.7 %). Outcome in these 50 patients was much better in comparison with 178 children with a slow MRD response who did not receive blinatumomab. The use of blinatumomab in children with de novo Ph-negative BCP-ALL with slow MRD clearance allows achieving MRD-negative remission in nearly all cases. Although a longer follow-up is necessary for the reliable conclusion of CD19-directed therapy effectiveness, the promising results are obtained in the current study in this unfavorable patient group.
We observed 567 patients with invasive aspergillosis in 19 hospitals of St.-Petersburg from 1998 to 2012 years. It is known that invasive aspergillosis is a severe opportunistic infection with high mortality. The most severe invasive aspergillosis we observed in children. We analyzed the risk factors, etiology, basic clinical signs and treatment of invasive aspergillosis in children.
We present the results of a multicenter study of 445 patients with “proven” and “probable” invasive aspergillosis (EORTC/MSG, 2008). Invasive aspergillosis usually occurs in patients with hematological malignancies (88 %), main underlying diseases were acute myeloid and acute lymphoblastic leukemia. The risk factors: prolonged agranulocytosis (64 %), cytostatic chemotherapy (57 %), corticosteroid treatment (45 %), and allogeneic hematopoietic stem cells transplantation (29 %). The pathogens – A. fumigatus (42 %), A. niger (33 %), and A. flavus (21 %). The main site of infection were lungs (86 %). 12 week overall survival was 83 %. Bronchoscopy use for the early diagnosis (p = 0.01), adequate therapy with voriconazole (p = 0.002) and secondary antifungal prophylaxis (p = 0.0003) were positive prognostic factors for survival of patients with invasive aspergillosis.
