Introduction.Neuroblastoma (NB) is the most common extracranial pediatric solid tumor. The high-risk group patients are characterized by adverse prognosis and require intensive complex therapy including high-dose chemotherapy (HDCT) with hematopoietic stem cell transplantation (auto-HSCT). The current study presents a single center experience of HSCT with auto-HSCT for high-risk NB performed in Raisa Gorbacheva Memorial Research Institute of Children Oncology, Hematology and Transplantation, First Pavlov State Medical University of St. Petersburg, Ministry of Health of Russia.Patients and methods.A cohort of 72 consecutive high-risk NB patients was included in the study. Among them 69 patients received Bu-Mel conditioning regimen (busulfan 16 mg/kg, melphalan 140 mg/m2 ), in 3 patients the 5D/5D regimen was used (carboplatin 1000 mg/m2 , irinotecan 150 mg/m2 , temozolomide 750 mg/m2 , etoposide 400 mg/m2 , cyclophosphamide 140 mg/kg). In most cases the autologous hematopoietic stem cells source was bone marrow (BM) (n = 59; 82 %), peripheral blood stem cells (PBSC) (n = 11; 15 %), or BM and PBSC (n = 2; 3 %). In 52/66 (79 %) patients with initial bone marrow involvement the potential transplant contamination was assessed by flow cytometry.Results.The 2-year and 5-year overall (OS) and event-free (EFS) survival was 61 % and 48 %, 41 % and 35 % accordingly. The main adverse factors for OS and EFS were age of more than 18 months at diagnosis, combined bone marrow and bones involvement, MYCN amplification, initial neuron-specific enolase level of more than 100 ng/ml, primary resistance or relapse, and metaiodobenzylguanidinepositive lesions persistence prior to or after HSCT with auto-HSCT.Conclusions.The results achieved are comparable to those described for similar cohorts. Some patient subgroups are unlikely to achieve response after HSCT with auto-HSCT. Therefore, additional stratification methods and treatment modalities are needed.Conflict of interest. The authors declare no conflict of interest.Funding. The study was performed without external funding.

Background. In the expanding population of immunocompromised patients rare fungi have emerged as important pathogens, causing invasive infections associated with high morbidity and mortality. The number of publications on the invasive fungal diseases caused by rare pathogens (rare IFD) after hematopoietic stem cell transplantation (HSCT) and chemotherapy is limited. Patients and methods. We design the retrospective study in order to investigate the epidemiology of rare IFD in large cohort of patients after HSCT and chemotherapy for 11-year period. From 2008 to 2018 in R. Gorbacheva Memorial Institute of Children Oncology, Hematology and Transplantation (CIC725) were performed 3209 HSCT including 2118 allogeneic (allo-HSCT) and 1037 autologous HSCT (auto-HSCT). During the observation period 41 probable and proven rare IFD (EORTC/MSG 2008 criteria) cases were diagnosed in children and adults with hematological malignances and non-malignant hematological diseases after allo-HSCT (n=30), auto-HSCT (n=2), and chemotherapy (n=9). The median age was 24 (2-59) y.o., males - 61%(n=25). The median follow up time for rare IFD cases was 3 months; for survivors - 30 months. Results. Incidence of rare IFD in HSCT recipients was 1,3%, it was higher after allo-HSCT (1,4%) than auto-HSCT (0,2%) (p<0,002). In nine patients, this complication developed after CT and four of them proceed to allo-HSCT. The most frequent underlying diseases were acute lymphoblastic leukemia (32%) and acute myeloid leukemia (29%). The median time of onset of rare IFD after allo-HSCT was 104 (21-1057) days, auto-HSCT - 138 (60-216), after start of CT - 161 (79-189). Etiology of rare IFD was identified by culture in 61% cases: Rhizopus spp. - 44%, Paecilomyces spp. - 16%, Fuzarium spp. - 8%, Malassezia furfur - 8%, Trichosporon asahii - 4%, Scedosporium apiosperium - 4%, Scopulariopsis gracilis - 4%, Rhizomucor pusillus - 4%, mix rare IFD with Rhizopus spp. + Paecilomyces spp. - 4%, Paecilomyces spp. + Fuzarium spp. - 4%. 35% cases (mucormycosis) were diagnosed with microscopy. In 44% cases rare IFD developed after or in combination with invasive aspergillosis, and 2 patients had both preexisting invasive aspergillosis and co-infection with mucormycosis. The main site of infection were lungs (82%), the main clinical symptom - fever (95%). All patients were treated with antifungals: lipid amphotericin B - 32%, lipid amphotericin B + caspofungin - 23%, voriconazole - 15%, posaconazole - 12,5%, lipid amphotericin B + posaconazole - 10%, and echinocandins - 7,5%. Surgery was used in 10% patients. Overall survival at 12 weeks from the diagnosis of rare IFD was 51,2%. The 12-weeks overall survival was better in patients after CT and auto-HSCT (81%) than allo-HSCT (40%), p=0,025. Conclusions. The incidence of rare IFD in HSCT recipients was 1,3% and depends on type of transplantation. Rare IFD was a late complication after chemotherapy and HSCT and usually developed after or in combination with invasive aspergillosis. Higher incidence and worst prognosis of rare IFD was observed in allo-HSCT recipients. Disclosures Moiseev: MSD: Other: Travel grants; Pfizer: Other: Travel grants; Celgene: Consultancy, Other: Travel grants; BMS: Other: Travel grants; Novartis: Consultancy, Honoraria, Other: Travel grants, Speakers Bureau; Takeda: Other: Travel grants.

About 20% of initially high-risk patients with neuroblastoma (NB) develop primary resistant to chemotherapy and more than 50% of them subsequently have a relapse. There is currently no uniform approach to therapy in this group and long-term outcomes are dismal. The study was approved by the Independent Ethics Committee and the Scientific Council of the I.P. Pavlov First Saint Petersburg State Medical University. A total of 78 patients with a median age of 5 (1–20) years with primary resistant (n = 33) or (n = 45) relapsed NB receiving treatment in R.M. Gorbacheva Memorial Center were included in this study. In 20 cases the 2nd-line therapy including topotecan (n = 10) or irinotecan (n = 10) was used, 58 patients received combined chemo- and targeted therapy (RIST regimen: rapamycin, irinotecan, sirolimus, temozolomide). Nineteen patients with primary resistant disease (n = 4) or systemic relapse (n = 15) subsequently underwent an allogeneic hemopoietic stem cell transplantation from haploidentical donor (haplo-HSCT). In all cases fludarabin-based reduced intensity conditioning (RIC) regimens were used. Ten patents received modified graft (immunomagnetic selection or depletion), in 9 unmodified graft with subsequent post-transplant cyclophosphamide (PTCM) was used. Also, 16 of 19 haplo-HSCT recipients had post-transplant therapy. The clinical effect was seen in 79% of patients. The median event-free survival (EFS) in 2nd-line therapy and RIST recipients was 2.5 (1–11) and 8 (1–76) months, accordingly. The complete of good partial response in 2nd-line therapy or RIST recipients was seen in 5% and 15%, 14% and 31% of cases accordingly. The therapy toxicity was comparable in both groups. The median EFS for haplo-HSCT recipients was 15 months with 2-year OS and EFS in this group bring 44% and 21% accordingly. Seven of 19 (37%) patients are currently alive and 4 (21%) of 19 maintain response. All long-term responders have history of posttransplant therapy. There was no statistically significant difference based on graft-versus-host disease prophylaxis used (graft modification or PTCM) or KIR compatibility. Combined chemo- and targeted therapy (RIST) is characterized by acceptable toxicity and effective even in some previously resistant cases. In 20% of responders a long-term effect may be achieved by subsequent haplo-HSCT and post-transplant therapy.

К л и н и ч е с к и е н а б л ю д е н и я Длительная стабилизация заболевания после аллогенной трансплантации гемопоэтических стволовых клеток у пациента с рецидивом нейробластомы. Клиническое наблюдение и обзор литературы

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