New insights in the use of immunoglobulins for the management of immune deficiency (PID) patients

Immunoglobulin replacement therapy (IRT) is standard treatment for patients with primary immunodeficiency (PID). Because most of the patients with PID will require long life-time immunoglobulin replacement therapy, the quality of the prescribed products is of utmost importance. The IRT is generally administered either intravenously (abbreviated IVIG), or subcutaneously (abbreviated SCIG). Both routes have been demonstrated to be effective. The preferred route may vary at different times during a given patient’s life. Options are therefore not fixed and the choice of route for immunoglobulin therapy will depend on several factors, including patient characteristics, clinical indication, venous access, side effects, rural or remote location, treatment compliance and patient preference. Many years ago, immunoglobulin therapy was associated with side effects which may compromise patient’s compliance and quality of life of the patients. Most of the side effects were related to impurities. Recently, major advances in the manufacturing process have been made and new processes, such as the Quality by design (QbD) approach were added into the manufacturing steps to ensure patients tolerability and safety. Due to the improved purity of the immunoglobulin products obtained by these processes, the incidence of side effects is lower, while the ways of administration of Ig therapy and the choice of the regimen has widened to suit patient’s preference and needs

New insights in the use of immunoglobulins for the management of immune deficiency (PID) patients

Immunoglobulin replacement therapy (IRT) is standard treatment for patients with primary immunodeficiency (PID). Because most of the patients with PID will require long life-time immunoglobulin replacement therapy, the quality of the prescribed products is of utmost importance. The IRT is generally administered either intravenously (abbreviated IVIG), or subcutaneously (abbreviated SCIG). Both routes have been demonstrated to be effective. The preferred route may vary at different times during a given patient’s life. Options are therefore not fixed and the choice of route for immunoglobulin therapy will depend on several factors, including patient characteristics, clinical indication, venous access, side effects, rural or remote location, treatment compliance and patient preference. Many years ago, immunoglobulin therapy was associated with side effects which may compromise patient’s compliance and quality of life of the patients. Most of the side effects were related to impurities. Recently, major advances in the manufacturing process have been made and new processes, such as the Quality by design (QbD) approach were added into the manufacturing steps to ensure patients tolerability and safety. Due to the improved purity of the immunoglobulin products obtained by these processes, the incidence of side effects is lower, while the ways of administration of Ig therapy and the choice of the regimen has widened to suit patient’s preference and needs

Progress and trends in pediatric hematopoietic cell transplantation in Central-East European countries

Hematopoietic cell transplantation (HCT) is widely used as a treatment for acquired and congenital disorders. In recent years, a significant increase in transplant activity around the world has been observed, especially in Eastern European countries. This article aimed to assess progress and trends in pediatric HCT in Central-Eastern European countries between 2013 and 2018. Transplant activity survey in 2013 and 2018 in nine Central-Eastern European countries (Czech Republic, Croatia, Hungary, Lithuania, Poland, Romania, Slovakia, Slovenia, and Ukraine) was performed. The highest transplant rates in total were found in the Czech Republic and Hungary. When calculated per 10 million of the pediatric population, a 25.9% increase in the number of allo-HCT was observed with the highest in Croatia, Romania, Lithuania, and Poland; and a 12.2% increase in the number of auto-HCT was observed with the highest in Slovenia, Slovakia, Romania, Poland, Ukraine, and Croatia. We have shown, over the years 2013 and 2018, in some countries of Central-Eastern Europe that there was a significant increase in transplant activity, especially in those with the lower rates. This increase was observed mainly in centers already existing in 2013, especially in the allo-HCT setting. The rise of activity was significantly less influenced by the creation of new transplant centers or the increase in the number of pediatric transplant beds. In conclusion, our analysis indicates that in the Czech Republic, Hungary, Lithuania, and Slovenia, the actual infrastructure and the number of HCTs cover the needs, whereas in other countries, especially in Romania and Ukraine, the number of HCT needs to be increased

Supportive Care During Pediatric Hematopoietic Stem Cell Transplantation : Prevention of Infections. A Report From Workshops on Supportive Care of the Paediatric Diseases Working Party (PDWP) of the European Society for Blood and Marrow Transplantation (EBMT)

Specific protocols define eligibility, conditioning, donor selection, graft composition and prophylaxis of graft vs. host disease for children and young adults undergoing hematopoietic stem cell transplant (HSCT). However, international protocols rarely, if ever, detail supportive care, including pharmaceutical infection prophylaxis, physical protection with face masks and cohort isolation or food restrictions. Supportive care suffers from a lack of scientific evidence and implementation of practices in the transplant centers brings extensive restrictions to the child's and family's daily life after HSCT. Therefore, the Board of the Pediatric Diseases Working Party (PDWP) of the European Society for Blood and Marrow Transplantation (EBMT) held a series of dedicated workshops since 2017 with the aim of initiating the production of a set of minimal recommendations. The present paper describes the consensus reached within the field of infection prophylaxis.Peer reviewe

Stem cell transplantation for congenital dyserythropoietic anemia : an analysis from the European Society for Blood and Marrow Transplantation

Non peer reviewe

Treatment and Outcome Analysis of 639 Relapsed Non-Hodgkin Lymphomas in Children and Adolescents and Resulting Treatment Recommendations.

Despite poor survival, controversies remain in the treatment for refractory or relapsed pediatric non-Hodgkin lymphoma (r/r NHL). The current project aimed to collect international experience on the re-induction treatment of r/r NHL, hematopoietic stem cell transplantation (HSCT), risk factors associated with outcome, and to suggest treatment recommendations. Inclusion criteria were (i) refractory disease, disease progression or relapse of any NHL subtype except anaplastic large cell lymphoma, (ii) age < 18 years at initial diagnosis, (iii) diagnosis in/after January 2000. Data from 639 eligible patients were evaluable. The eight-year probability of overall survival was 34 ± 2% with highly significant differences according to NHL subtypes: 28 ± 3% for 254 Burkitt lymphoma/leukemia, 50 ± 6% for 98 diffuse large B-cell lymphomas, 57 ± 8% for 41 primary mediastinal large B-cell lymphomas, 27 ± 3% for 177 T-lymphoblastic lymphomas, 52 ± 10% for 34 precursor-B-cell lymphoblastic lymphomas and 30 ± 9% for 35 patients with rare NHL subtypes. Subtype-specific factors associated with survival and treatment recommendations are suggested. There were no survivors without HSCT, except in few very small subgroups. Conclusions: There is an urgent need to further improve survival in r/r NHL. The current study provides the largest real-world series, which underlines the role of HSCT and suggests treatment recommendations

Low rate of nonrelapse mortality in under-4-year-olds with ALL given chemotherapeutic conditioning for HSCT: a phase 3 FORUM study

Allogeneic hematopoietic stem cell transplantation (HSCT) is highly effective for treating pediatric high-risk or relapsed acute lymphoblastic leukemia (ALL). For young children, total body irradiation (TBI) is associated with severe late sequelae. In the FORUM study (NCT01949129), we assessed safety, event-free survival (EFS), and overall survival (OS) of 2 TBI-free conditioning regimens in children aged &lt;4 years with ALL. Patients received fludarabine (Flu), thiotepa (Thio), and either busulfan (Bu) or treosulfan (Treo) before HSCT. From 2013 to 2021, 191 children received transplantation and were observed for ≥6 months (median follow-up: 3 years). The 3-year OS was 0.63 (95% confidence interval [95% CI], 0.52-0.72) and 0.76 (95% CI, 0.64-0.84) for Flu/Thio/Bu and Flu/Thio/Treo (P = .075), respectively. Three-year EFS was 0.52 (95% CI, 0.41-0.61) and 0.51 (95% CI, 0.39-0.62), respectively (P = .794). Cumulative incidence of nonrelapse mortality (NRM) and relapse at 3 years were 0.06 (95% CI, 0.02-0.12) vs 0.03 (95% CI: &lt;0.01-0.09) (P = .406) and 0.42 (95% CI, 0.31-0.52) vs 0.45 (95% CI, 0.34-0.56) (P = .920), respectively. Grade &gt;1 acute graft-versus-host disease (GVHD) occurred in 29% of patients receiving Flu/Thio/Bu and 17% of those receiving Flu/Thio/Treo (P = .049), whereas grade 3/4 occurred in 10% and 9%, respectively (P = .813). The 3-year incidence of chronic GVHD was 0.07 (95% CI, 0.03-0.13) vs 0.05 (95% CI, 0.02-0.11), respectively (P = .518). In conclusion, both chemotherapeutic conditioning regimens were well tolerated and NRM was low. However, relapse was the major cause of treatment failure. This trial was registered at www.clinicaltrials.gov as #NCT01949129

Progress and trends in pediatric hematopoietic cell transplantation in Central-East European countries

Hematopoietic cell transplantation (HCT) is widely used as a treatment for acquired and congenital disorders. In recent years, a significant increase in transplant activity around the world has been observed, especially in Eastern European countries. This article aimed to assess progress and trends in pediatric HCT in Central-Eastern European countries between 2013 and 2018. Transplant activity survey in 2013 and 2018 in nine Central-Eastern European countries (Czech Republic, Croatia, Hungary, Lithuania, Poland, Romania, Slovakia, Slovenia, and Ukraine) was performed. The highest transplant rates in total were found in the Czech Republic and Hungary. When calculated per 10 million of the pediatric population, a 25.9% increase in the number of allo-HCT was observed with the highest in Croatia, Romania, Lithuania, and Poland ; and a 12.2% increase in the number of auto-HCT was observed with the highest in Slovenia, Slovakia, Romania, Poland, Ukraine, and Croatia. We have shown, over the years 2013 and 2018, in some countries of Central-Eastern Europe that there was a significant increase in transplant activity, especially in those with the lower rates. This increase was observed mainly in centers already existing in 2013, especially in the allo-HCT setting. The rise of activity was significantly less influenced by the creation of new transplant centers or the increase in the number of pediatric transplant beds. In conclusion, our analysis indicates that in the Czech Republic, Hungary, Lithuania, and Slovenia, the actual infrastructure and the number of HCTs cover the needs, whereas in other countries, especially in Romania and Ukraine, the number of HCT needs to be increase