Decreased spermatogonial numbers in boys with severe haematological diseases.

This study examines spermatogonial numbers in testicular samples from 43 prepubertal patients undergoing haematopoietic stem cell transplantation (HSCT). High-dose chemotherapy and/or radiation during HSCT can impact spermatogenesis requiring fertility preservation. Results show that 49% of patients have decreased and 19% severely depleted spermatogonial pool prior to HSCT.

[Transition in sickle cell disease - recommendations of the transition initiative sickle cell disease].

Sickle cell disease is a rare, but complex multi-systemic disorder with high need of interdisciplinary and specialized care and new structural requirements. Besides care of those chronically sick patients, transition process is a vulnerable phase which highly influences further treatment. To make matters worse, patients often have migration background with subsequent communication problems.

Finding a balance in reduced toxicity hematopoietic stem cell transplantation for thalassemia: role of infused CD3+ cell count and immunosuppression.

We performed a retrospective analysis on 124 patients with transfusion-dependent thalassemia who were registered in the German pediatric registry for stem cell transplantation. All patients underwent first allogeneic hematopoietic stem cell transplantation (HSCT) between 2011 and 2020 and belonged mainly to Pesaro risk class 1-2. Four-year overall (OS) and thalassemia-free survival (TFS) were 94.

Look at the future -perceptions of fertility counseling and decision-making among adolescents and their parents in the context of hematopoietic stem cell transplantation-experience of one major center for pediatric stem cell transplantation.

Introduction: Increasing survival rates after hematopoietic stem cell transplantation (HSCT) in childhood should put focus on improving the quality of life as adults. An essential aspect is fertility and its preservation. In order to take advantage of the possibility of fertility preservation, fertility counseling should be provided to patients and their parents prior to gonadotoxic therapies.

Donor-type red blood cell transfusion to deplete isoagglutinins prior to allogeneic stem cell transplantation from ABO major incompatible bone marrow donors.

ABO incompatibility affects approximately 40% of allogeneic stem cell transplants in Caucasian patient populations. Because bone marrow (BM), the preferred graft from paediatric sibling donors and for non-malignant diseases, has a red blood cell (RBC) content similar to blood, anti-donor isoagglutinins must either be depleted from the recipient or RBCs removed from the graft. To achieve tolerability of unmanipulated BM grafts, we used controlled infusions of donor ABO-type RBC units to deplete isoagglutinins before the transplant.

CD19 CAR T cells are an effective therapy for posttransplant relapse in patients with B-lineage ALL: real-world data from Germany.

Patients with precursor B-cell acute lymphoblastic leukemia (pB-ALL) who have relapsed after allogeneic hematopoietic stem cell transplantation (allo-HSCT), have relapsed more than once, or are resistant upfront have a dismal prognosis. CD19-targeted chimeric antigen receptor (CAR) T cells have evolved as potent immune therapies. Tisagenlecleucel (Tisa-cel) is a commercially available autologous CD19-directed CAR T-cell product.

Current German Guidelines on Diagnosis and Treatment of Secondary Hemochromatosis in Patients with Congenital Anemias.

Adequate diagnosis and treatment of secondary hemochromatosis in patients with congenital anemias is important for reducing long-term mortality and morbidity as for improving patients' quality of life. Due to the strong migration movements during recent years, the number of patients in Germany suffering from hemoglobinopathies as some of the most relevant disorders in the context of iron overload (IOL) has increased enormously. Many of these patients had received inadequate medical care in their countries of origin prior to migration, including diagnosis and treatment of IOL.

Treatment of inborn errors of immunity patients with inflammatory bowel disease phenotype by allogeneic stem cell transplantation.

Patients with inborn errors of immunity (IEI) can suffer from treatment-refractory inflammatory bowel disease (IBD) causing failure to thrive and consequences of long-term multiple immunosuppressive treatments. Allogeneic haematopoietic stem cell transplantation (alloHSCT) can serve as a curative treatment option. In this single-centre retrospective cohort study we report on 11 paediatric and young adult IEI patients with IBD and failure to thrive, who had exhausted symptomatic treatment options and received alloHSCT.

Transition in Sickle Cell Disease (SCD): A German Consensus Recommendation.

Sickle cell disease (SCD) is considered a rare disease in Germany. Due to the increasing prevalence, the acute and chronic morbidities associated with the disease and the sharp increase in the mortality rate of young adults, a need-based transition structure for patients with SCD in Germany is explicitly required. This is the first multicenter German consensus statement addressing the importance of implementing a standardized transition guideline that allows adolescents and young adults to safely transition from pediatric to adult care.

Immune Responses to SARS-CoV-2 Vaccination in Young Patients with Anti-CD19 Chimeric Antigen Receptor T Cell-Induced B Cell Aplasia.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines are capable of inducing combined humoral and cellular immunity. Which effect is more relevant for their potent protective effects is unclear, but isolated T cell responses without seroconversion in healthy household members of individuals with Coronavirus disease 19 (COVID-19) suggest that T cell responses effectively protect against clinical infection. Oncologic patients have an outsize risk of unfavorable outcomes after SARS-CoV-2 infection and therefore were prioritized when vaccines first became available, although the quality of their immune response to vaccination was expected to be suboptimal, as has been confirmed in subsequent studies.

SARS-CoV-2-specific T cells are generated in less than half of allogeneic HSCT recipients failing to seroconvert after COVID-19 vaccination.

Little is known about the cellular immune response to SARS-CoV-2 vaccination in patients after HSCT and B-NHL with iatrogenic B-cell aplasia. In nonseroconverted HSCT patients, induction of specific T-cell responses was assessed. The majority of allogeneic HSCT patients not showing humoral responses to vaccination also fail to mount antigen-specific T-cell responses.

Monitoring of Circulating CAR T Cells: Validation of a Flow Cytometric Assay, Cellular Kinetics, and Phenotype Analysis Following Tisagenlecleucel.

Chimeric antigen receptor (CAR) T cell therapy is a potent new treatment option for relapsed or refractory hematologic malignancies. As the monitoring of CAR T cell kinetics can provide insights into the activity of the therapy, appropriate CAR T cell detection methods are essential. Here, we report on the comprehensive validation of a flow cytometric assay for peripheral blood CD19 CAR T cell detection.

Benefits of a Disease Management Program for Sickle Cell Disease in Germany 2011-2019: The Increased Use of Hydroxyurea Correlates with a Reduced Frequency of Acute Chest Syndrome.

Sickle Cell Disease (SCD) is the most common monogenic disorder globally but qualifies as a rare disease in Germany. In 2012, the German Society for Paediatric Oncology and Haematology (GPOH) mandated a consortium of five university hospitals to develop a disease management program for patients with SCD. Besides other activities, this consortium issued treatment guidelines for SCD that strongly favour the use of hydroxyurea and propagated these guidelines in physician and patient education events.

How can fertility counseling be implemented for every newly diagnosed pediatric patient facing gonadotoxic treatment?-A single-center experience.

Since the survival rates of pediatric patients undergoing cancer treatment or hematopoietic stem cell transplantation (HSCT) have increased rapidly in recent decades, the late effects of treatment are now an important focus of patient care. Access to fertility preservation (FP) procedures as well as their financing differs considerably across Europe. However, some countries in Europe have recently changed the legal basis for financing FP procedures; therefore, the implementation of structures is mandatory to give patients access to FP.

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.

Unstimulated apheresis for chimeric antigen receptor manufacturing in pediatric/adolescent acute lymphoblastic leukemia patients.

Autologous unstimulated leukapheresis product serves as starting material for a variety of innovative cell therapy products, including chimeric antigen receptor (CAR)-modified T-cells. Although it may be reasonable to assume feasibility and efficiency of apheresis for CAR-T cell manufacture, several idiosyncrasies of these patients warrant their separate analysis: target cells (mononuclear cells [MNC] and T-cells) are relatively few which may instruct the selection of apheresis technology, low body weight, and, hence, low total blood volume (TBV) can restrict process and product volume, and patients may be in compromised health. We here report outcome data from 46 consecutive leukaphereses in 33 unique pediatric patients performed for the purpose of CD19-CAR-T-cell manufacturing.

Long-term pulmonary function testing in pediatric bronchiolitis obliterans syndrome after hematopoietic stem cell transplantation.

Rationale: Bronchiolitis obliterans syndrome (BOS) is a severe, chronic inflammation of the airways leading to an obstruction of the bronchioles. So far, there are only a few studies looking at the long-term development of pulmonary impairment in children with BOS.

Objective: The objective of this study was to investigate the incidence and long-term outcome of BOS in children who underwent allogeneic hematopoietic stem cell transplantation (HSCT).

Correction: Supportive care during pediatric hematopoietic stem cell transplantation: beyond infectious diseases. A report from workshops on supportive care of the Pediatric Diseases Working Party (PDWP) of the European Society for Blood and Marrow Transplantation (EBMT).

An amendment to this paper has been published and can be accessed via a link at the top of the paper.