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.
We studied the effect of platelet lysates from different donors on fibroblast growth in culture. In most samples (40 of 50), the growth-stimulating characteristics were greater than in 10% FCS, but every ninth sample exhibited low mitogenic activity. A weak dependence between platelet concentration and total protein content was noted, but no correlation was found between these parameters and fibroblast growth in culture.
Chronic graft versus host disease (cGVHD) remains a major complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT). It significantly decreases survival and quality of life. The present study demonstrates retrospective data on extracorporeal photopheresis (ECP) in children with cGVHD. A total of 42 children with steroid-refractory cGVHD were enrolled in the study. The majority of patients had acute leukemia (n = 32, 76%). All patients received ECP as second (n = 18, 43%) or third (n = 24, 57%) line of therapy. Initial ECP schedule consisted of bimonthly regimen for two consecutive days with possibility of further tapering according to response. Any concurrent treatment administered before ECP could be continued if considered necessary. Complete response to ECP was registered in seven (17%) patients and partial response in 24 (57%). Overall response according to organ involvement was as follows: skin (n = 24, 75%), mucous membranes (n = 16, 73%), liver (n = 8, 80%), gut (n = 4, 80%), lungs (n = 2, 22%) and joints (n = 2, 67%). Five-year overall, progression-free and failure-free survival was 57%, 56% and 30%, respectively. Non-relapse mortality at 5 years was 14%. We didn’t observe any clinically significant complications in children that could be attributed to the procedure. ECP remains important and safe treatment option in children with cGVHD.
Hematopoietic stem cell transplantation (HSCT) is a life-saving procedure for oncological, hematological and non-malignant disorders. Despite global trend for a decrease of transplantation activity in view of the COVID-19 pandemic, we tried to maintain it by taking preventive measures and optimizing infection control in our center. Patients and methodsThis is an observational study. We collected the performance data of our transplant center from April 2020 to July 2021, i.e., during two waves of the pandemic. The main objectives were to study the influence of COVID-19 pandemic on the workflow of the HSCT center, including morbidity among employees and HSCT recipients, as well as on the transplant activity. ResultsThe first case of COVID-19 infection in St. Petersburg was recorded on March 8, 2020. On March 30, 2020, a national lockdown had been imposed in the Russian Federation. The second wave of COVID-19 started in October 2020. Weekly screening of staff and patients was the main diagnostic tool, in addition to the governmental requirements. In sum, a total of 21702 PCR tests for SARS-CoV-2 were performed over the study period. As for July 1, 2021, 69.7% of employees became immune to the virus, due to previous COVID-19 disease, or by vaccination. In 2020, we managed to perform 419 HSCT, including 136 autologous and 283 allogeneic transplants. For comparison, 415 HSCTs were carried out in 2019, with 144 autologous and 271 allogeneic transplants. In 2020, the HSC donorship was shifted towards unrelated donors from the Russian Registry and haploidentical donors. Incidence of COVID-19 among HSCT recipients between April 2020 and July 2021 was 7.3% (n=39), being 8.6% (n=31) after allogeneic HSCT, and 4.5% (n=8) following auto-HSCT. The median age of patients with COVID-19 was 27 years (4-66). The median term for the COVID-19 onset was 68 days post-transplant (-1 to +2093). In most patients -29 (74.3%) the HCT CI comorbidity index at the time of transplantation was 0. The stem cell source were either peripheral blood stem cells (n=22, 56.4%), or bone marrow (n=17, 43.6%). Most of the patients achieved complete remission of the underlying disease at the time of HSCT (n=30, 76.9%). The overall 100-day survival rate among HSCT recipients since the diagnosis of the COVID-19 was 79.5% (95% CI 0.609 -0.884). The mortality rate was 20.5% (n=8). The causes of death were as follows: COVID-19 -50% (n=4); secondary infectious complications, 25% (n=2); relapse of the underlying disease, 12.5% (n=1);
Фгбоу «первый санкт-петербургский государственный медицинский университет им. акад. и. п. павлова» минздрава россии, санктпетербург Цель: продемонстрировать редкий случай проявления посттрансфузионной реакции трансплантат против хозяина (ПТ-РТПХ) после трансфузии компонентов крови� Причина возникновения ПТ-РТПХ -приживление донорских лимфоцитов, содержащихся в компоненте крови, связанное с иммунологической HLA-гомологией между донором и реципиентом, и дефектом иммунной системы реципиента, которая не элиминирует донорские клетки� Летальность -90-100%� Больной 68 лет перенес плановую операцию -аортокоронарное шунтирование� В послеоперационном периоде на фоне анемии выполнены трансфузии трех доз необлученной эритроцитной массы� На 17-е сут после трансфузии у пациента развилась фебрильная температура, появилась сливная эритематозная сыпь на кожных покровах� На 24-е сут после трансфузии развилась нейтропения� По результатам оценки аллельной дискриминации высокополиморфных маркеров подтвержден диагноз ПТ-РТПХ� Ретроспективно выполнено HLA-типирование доноров крови и реципиента� Донор оказался гомозиготен в пяти локусах на низком разрешении и в локусах HLA-А*, HLA-В*, HLA-DRB1* имел общий ген с пациентом� На 34-й день после гемотрансфузии пациент умер от инфекционных осложнений� Единственным методом гарантированного предотвращения ПТ-РТПХ считается рентгеновское или гамма-облучение компонентов крови для инактивации жизнеспособных Т-лимфоцитов донора� Поскольку эффективная терапия ПТ-РТПХ отсутствует, предотвращение риска развития реакции, строгие показания к гемотрансфузиям и возможность ранней диагностики имеют решающее значение� Ключевые слова: посттрансфузионная реакция трансплантат против хозяина, аортокоронарное шунтирование, искусственное кровообращение, HLA-типирование, гамма-облучение, рентгеновское облучение компонентов крови, оценка аллельной дискриминации высокополиморфных маркеров� FATAL TRANSFUSION-ASSOCIATED GRAFT-VERSUS-HOST DISEASE IN THE PATIENT AFTER AORTOCORONARY BYPASS (ClINICAl CASE) o. V. GoloScHaPoV, m. А. EStrina, n. E. iVanoVa, i. m. barkHatoV, А. d. kulaGin, S. n. bondarEnko, i. S. moiSEEV, i. V. SHlyk, yu. S. PoluSHin, b. V. АFanaSiEV pavlov First saint petersburg state medical university, Russian ministry of health, st. petersburg, RussiaGoal: to demonstrate the rare case of transfusion-associated graft-versus-host disease (TA-GvHD) after transfusion of blood components� The cause of TA-GvHD is implantation of donor lymphocytes, contained in blood components, which is related to immunological HLA-homology between the donor and recipient, that does not eliminate the donor cells� Mortality makes 90-100%� 68 year old patient had planned surgery -aortocoronary bypass� In the post-operative period under pressure anemia three doses of unirradiated packed red blood cells were transfused� On the 17th day after transfusion the patient developed febrile fever and manifested erythematous cutaneous rush� On the 24th day after transfusion neutropenia developed� Evaluation results of allele discrimination ...
Influence of AB0 incompatibility on complications occur rence after allogeneic hematopoietic stem cell trans plantation Research objective: To assess the impact of AB0 erythrocyte antigens system incompatibility on complications incidence after allogeneic hematopoietic stem cell transplantation (alloHSCT). Patients and methods. The study included 240 patientsrecipients for alloHSCT with oncological and hematological diseases. The median age was 19.0 (1-66) years. The research revealed that overall incidence of acute graft versus host disease (aGVHD) was higher in the case of AB0 incompatibility (p <0.01), and the rate of aGVHD severe forms at AB0 incompatible alloHSCT were observed more often (p = 0.005). At AB0 inco mpatible unrelative alloHSCT risk of aGVHD was higher (81,3 %) compared to the relative alloHSCT (44 %) (p = 0.002). AB0 incompatibility between donor of HSC and the recipient may be a risk factor for aGVHD.
There is no doubt that autologous hematopoietic stem cell transplantation (auto-HSCT) with high-dose polychemotherapy (PCT) is a standard method for the second remission consolidation in case of relapse or for the fist remission consolidation in refractory disease in adult patients with non-Hodgkin lymphomas (NHL) (with the exception of lymphoblastic lymphoma in which allogeneic transplantation is preferable). Similar to patients older than 18 years of age, an identical algorithm is applied in pediatric patients, however in the absence of randomized clinical trials and due to a small number of patients, the evidence base in children is weaker compared to adults, which complicates the analysis. Due to a signifiant number of nonrandomized studies confiming the benefis of transplantation, it is impossible to plan and make a direct comparison of auto-HSCT and standard chemotherapy in pediatric patients within a randomized study primarily because of ethical reasons. Although transplantation is not able to fundamentally change the prognosis in all children with relapsed or refractory (R/R) NHL, a cure cannot be achieved without this method. Taking into account that most of the works devoted to auto-HSCT in children with R/R NHL were published more than 10 years ago, current data on this issue are of great interest due to the large-scale implementation of the effective methods of targeted and immunotherapy over the past decade. This study was approved by the Independent Ethics Committee and the Scientifi Council of the I.P. Pavlov First Saint-Petersburg State Medical University, Ministry of Healthcare of the Russian Federation. At the R.M. Gorbacheva Research Institute of Pediatric Oncology, Hematology and Transplantation, 31 children with R/R NHL underwent auto-HSCT from 2008 to 2020. The median age at the time of transplantation was 14 (2–18) years. At the onset of the disease, most patients were diagnosed with stage III or IV cancer (n = 30, 97%), the CNS involvement was registered in 4 patients (13%), the bone marrow involvement was registered in 2 patients (6%). The histological variants were as follows: primary mediastinal large B-cell lymphoma (n = 11, 35%), anaplastic large cell lymphoma (n = 6, 9%), Burkitt's lymphoma (n = 5, 16%), diffse large B-cell lymphoma (n = 5, 16%), peripheral T-cell lymphoma (n = 2, 7%), unspecifid B-NHL (n = 1, 3%) and lymphoblastic lymphoma (n = 1, 3%). The Karnofsky performance status prior to transplantation was ≥ 90% in all patients. The median time from diagnosis to auto-HSCT was 304 (122–3888) days. The median number of prior lines of therapy was 2 (1–4). In the majority of the patients (n = 27, 87%), a fist-line treatment was carried out according to the principles developed by the BFM group and in 4 older children (13%), we used regimens based on CHOP. As a second-line treatment, 18 (58%) patients received R-ICE (rituximab, ifosfamide, carboplatin, etoposide); the rest of the patients were treated with other regimens. NHL was relapsed (n = 14, 45%) or refractory (n = 17, 55%). A histological confimation of R/R NHL was carried out in 11 (35%) patients; in the rest of the cases, the diagnosis was made based on the imaging results and their correlation with the clinical presentation. Remission prior to auto-HSCT was achieved in 90% (n = 28) of cases: complete remission was observed in 39% (n = 8) of cases, and partial remission was observed in 51% (n = 16) of cases. In addition, transplantation was carried out in three patients (10%) who did not achieve remission. The graft sources were peripheral hematopoietic stem cells (n = 19, 61%) and bone marrow (n = 12, 39%). The median CD34+cells/kg was 3.85 (2–7.6). As conditioning regimens we used BEAM (n = 13, 42%) and BeEAM (n = 18, 58%). Both regimens consisted of etoposide 200 mg/m2/day from D5 to D2, cytarabine 400 mg/m2/day from D5 to D2, melphalan 140 mg/m2/day on D1. The regimens diffred in the following: we used carmustine 300 mg/m2/day on D6 in BEAM or bendamustine 160 mg/m2/day on D7 and D6 in BeEAM. Immunotherapy or targeted therapy prior to auto-HSCT was carried out in the majority of the patients (n = 25, 80%). The following medications were used: rituximab (n = 20, 65%), brentuximab vedotin (n = 6, 19%), nivolumab (n = 3, 10%), crizotinib (n = 2, 6%). Temporary three-lineage grade IV cytopenia was observed in all patients after auto-HSCT. Grade III–IV mucositis was registered in 10 (30%) patients, and 3 (10%) children developed grade III–IV infectious complications. Transplant-related mortality was not registered. During the follow-up period, six (19%) patients died due to the underlying disease progression. At the median follow-up of 888 (66–3375) days, the 5-year overall (OS) and event-free (EFS) survival rates were 70% (95% CI: 43–86) and 62% (95% CI: 41–80), respectively. The cumulative incidence of relapse was 38% (95% CI: 20–58). Based on the data obtained in our work, we can conclude that the use of targeted or immunotherapy provides a statistically signifiant improvement in overall survival (OS) (p = 0.013). This is associated with both factors: a more sustained remission prior to auto-HSCT and the availability of effctive treatment for some patients (mainly for the patients with anaplastic large cell lymphoma) in case of relapse after auto-HSCT. The achieved long-term survival rate is comparable or even slightly superior to the data previously obtained by other researchers. Almost one third of the patients suffred from primary mediastinal large B-cell lymphoma, and this is one of the possible reasons for higher long-term OS and EFS rates compared to the previously published results. Moreover, the presence of 6 patients with R/R anaplastic large cell lymphoma with a more favorable prognosis, and, probably, the absence of the morphological confimation of R/R NHL (“second look”) in some patients (n = 20, 65%) could have inflenced the survival rates, which does not exclude the possible inclusion of a number of cured patients in the work. The importance of our work lies in the fact that a signifiant part of the patients (n = 25, 80%) underwent targeted or immunotherapy. This allowed us to show the effctiveness of transplantation in different types of NHL in children in the so-called era of immunotherapy. Auto-HSCT is an effctive and relatively safe treatment strategy for children with R/R NHL which makes it possible to achieve a cure in a signifiant number of patients. The use of targeted and immunotherapy improves the prognosis in transplanted patients. A second biopsy is recommended to confim R/R NHL.
Allogeneic hematopoietic stem cell transplantation (allo-SCT) is used widely in the management of children with hematological, oncological and inherited diseases. Study to compare efficiency of steroid-refractory acute graft versus host disease treatment (extracorporeal photopheresis (ECP) vs anticytokine therapy) was conducted in Raisa Gorbacheva Memorial Institute of Children Oncology, Hematology and Transplantation, First Pavlov State Medical University of Saint Petersburg. Sixty four children were included in the analysis. Patients were divided into two groups: first “group with ECP” (n = 31; 50,5 %) ("ECP group") and second - "group without ECP" (n = 33; 49,5 %). Treatment in the second group consisted of anticytokine therapy (etanercept (n = 12), infliximab (n = 9), daclizumab (n = 8)) and alemtuzumab (n = 4). Ten-year overall survival (OS) of children with steroid-refractory acute graft versus host disease was 39 % without difference in OS between ECP and anticytokine therapy (5-year OS 40 % vs 35 %, p = 0,34). Response rate to the therapy was also the same in both groups (68 % after ECP and 70 % after anticytokine therapy, p = 0,77). Difference in cumulative incidence of relapse in "ECP group" and "group without ECP" was not statistically significant (18 % and 7 %, respectively, p = 0,2). In conclusion, ECP and anticytokine therapy are equally effective in the treatment of children with steroid-refractory acute graft versus host disease and are associated with the same cumulative incidence of relapse.
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