Allogeneic haematopoietic stem-cell transplantation for children with refractory systemic juvenile idiopathic arthritis and associated lung disease: outcomes from an international, retrospective cohort study.

Background: Systemic juvenile idiopathic arthritis-related lung disease (sJIA-LD) is a severe complication in patients with treatment-refractory systemic juvenile idiopathic arthritis (sJIA). The objective of this study was to evaluate the effect of allogeneic haematopoietic stem-cell transplantation (HSCT) in a cohort of children with sJIA-LD.

Methods: This international, retrospective cohort study was performed in nine hospitals across the USA and Europe in children with sJIA-LD who had received allogeneic HSCT.

Late effects following HSCT for childhood ALL: A national single-center study using three different modalities of delivery of total body irradiation.

Background: Total body irradiation (TBI) is a pivotal part of conditioning prior to hematopoietic stem cell transplantation (HSCT) for childhood acute lymphoblastic leukemia (ALL), yet evidence is sparse regarding the effect of TBI delivery techniques on acute and late toxicities.

Design: In a national cohort of pediatric HSCT-recipients, we compared three TBI schedules; 12 Gray (Gy) delivered as (i) 4 Gy daily fractions from 2008 to 2011 (n = 12); (ii) 2 Gy fractions twice daily with two-dimensional (2D) planning technology from 2012 to 2015 (n = 16); and (iii) 2 Gy twice daily with three-dimensional (3D) planning intensity-modulated radiotherapy (IMRT) from 2016 to 2020 (n = 14).

Results: The 5-year event-free survival was 75.

Genetic polymorphisms in IL-2, IL-10 and FOXP3 are associated with autoimmune neutropenia in early childhood and autoantibody specificity in a Danish cohort.

Autoimmune neutropenia (AIN) in early childhood is characterized by chronic neutropenia and positivity for human neutrophil antibodies (HNA), resulting in the excessive destruction of neutrophils. The association between regulatory T cells (Tregs) and AIN has been described, and in this study, we investigated three Treg-associated genes, IL-2, IL-10 and FOXP3. The frequencies of three single nucleotide polymorphisms (SNPs) in IL-2 -330T>G (rs2069762), +114G>T (rs2069763) and IVS3-116 A>G (rs2069772), four SNPs in IL-10 -3575T>A (rs1800890), -1082G>A (rs1800896), -819 C>T (rs1800871) and -592 C>A (rs1800872) and three SNPs in FOXP3 -3499 A>G (rs3761547), -3279 C>A (rs3761548) and -924 A>G (rs2232365) were compared between 166 Danish AIN patients and 358 healthy controls.

High-resolution HLA genotyping identifies risk alleles in both class I and II for primary autoimmune neutropenia in early childhood in a Danish cohort.

HLA studies in patients with autoimmune neutropenia (AIN) have shown very consistent results for the association with HLA class II alleles at low resolution. This study aimed to examine the association of both HLA class I and class II at high resolution to clarify the contribution of risk alleles to the disease. A total of 107 AIN patients were genotyped for six loci of HLA class I (HLA-A, -B and -C) and class II (HLA-DRB1, -DQB1, and -DPB1) genes by a high-resolution (3-field, 6-digit) analysis and compared with HLA typing of 1000 healthy controls.

HAX1-related congenital neutropenia: Long-term observation in paediatric and adult patients enrolled in the European branch of the Severe Chronic Neutropenia International Registry (SCNIR).

HAX1-related congenital neutropenia (HAX1-CN) is a rare autosomal recessive disorder caused by pathogenic variants in the HAX1 gene. HAX1-CN patients suffer from bone marrow failure as assessed by a maturation arrest of the myelopoiesis revealing persistent severe neutropenia from birth. The disorder is strongly associated with severe bacterial infections and a high risk of developing myelodysplastic syndrome or acute myeloid leukaemia.

Genetic variations in low-to-medium-affinity Fcγ receptors and autoimmune neutropenia in early childhood in a Danish cohort.

Autoimmune neutropenia (AIN) in early childhood is caused by autoantibodies directed against antigens on the neutrophil membrane and is a frequent cause of neutropenia in children. Association of AIN with Fcγ receptor (FCGR) 3B variants is well described. In this study, we investigate genetic variations in the FCGR locus and copy number variation of FCGR3B.

Added Value of Reanalysis of Whole Exome- and Whole Genome Sequencing Data From Patients Suspected of Primary Immune Deficiency Using an Extended Gene Panel and Structural Variation Calling.

Background: Knowledge of the genetic variation underlying Primary Immune Deficiency (PID) is increasing. Reanalysis of genome-wide sequencing data from undiagnosed patients with suspected PID may improve the diagnostic rate.

Methods: We included patients monitored at the Department of Infectious Diseases or the Child and Adolescent Department, Rigshospitalet, Denmark, for a suspected PID, who had been analysed previously using a targeted PID gene panel (457 PID-related genes) on whole exome- (WES) or whole genome sequencing (WGS) data.

ABO, secretor, and Lewis carbohydrate histo-blood groups are associated with autoimmune neutropenia of early childhood in Danish patients.

Background: Autoimmune neutropenia of early childhood (AIN) is caused by autoantibodies directed against antigens on the neutrophil membrane. The ABO, secretor, and Lewis histo-blood group systems control the expression of carbohydrate antigens and have previously been linked to autoimmune diseases. We aimed to investigate the association between genotypes and the risk of AIN in Danish patients.

Life-threatening viral disease in a novel form of autosomal recessive IFNAR2 deficiency in the Arctic.

Type I interferons (IFN-I) play a critical role in human antiviral immunity, as demonstrated by the exceptionally rare deleterious variants of IFNAR1 or IFNAR2. We investigated five children from Greenland, Canada, and Alaska presenting with viral diseases, including life-threatening COVID-19 or influenza, in addition to meningoencephalitis and/or hemophagocytic lymphohistiocytosis following live-attenuated viral vaccination. The affected individuals bore the same homozygous IFNAR2 c.

International retrospective study of allogeneic hematopoietic cell transplantation for activated PI3K-delta syndrome.

Background: Activated phosphoinositide 3-kinase delta syndrome (APDS) is a combined immunodeficiency with a heterogeneous phenotype considered reversible by allogeneic hematopoietic cell transplantation (HCT).

Objectives: This study sought to characterize HCT outcomes in APDS.

Methods: Retrospective data were collected on 57 patients with APDS1/2 (median age, 13 years; range, 2-66 years) who underwent HCT.

Association between human leukocyte antigens (HLAs) and human neutrophil antigens (HNAs) and autoimmune neutropenia of infancy in Danish patients.

Background: Autoimmune neutropenia of infancy (AIN) is a frequent cause of neutropenia in children. The disease is caused by antibodies against epitopes on the immunoglobulin G (IgG) Fc receptor type 3b (FcγIIIb). We investigated the possible association of human neutrophil antigens (HNA), human leukocyte antigen (HLA)-DR, and HLA-DQ alleles with AIN and the association of these genotypes with the presence of autoantibodies.

[Treatment of monogenic disorders with viral transduced haematopoietic stem cells].

Infusion of ex vivo transduced haematopoietic stem cells (HSC) has emerged as a promising new treatment of certain monogenetic disorders. Since early clinical studies on patients with severe combined immune deficiency were halted due to de novo leukaemia, the technology has matured. Thus, treatment of transfusion-dependent thalassaemia and adenosine deaminase deficient severe combined immunodeficiency by using lentiviral vectors for gene correction of autologous HSC can induce expression of the deficient protein and thus potentially cure the patients.

Is microchimerism a sign of imminent disease recurrence after allogeneic hematopoietic stem cell transplantation? A systematic review of the literature.

Chimerism analysis following hematopoietic stem cell transplantation (HSCT) for leukemia is routinely applied in parallel with quantification of minimal residual disease (MRD) to identify imminent relapse. In the past decades, new methods with a lower limit of detection compared to standard methods have been developed, so-called microchimerism analysis. Microchimerism analysis is fast, simple, applicable across pre-HSCT disease-type and can be applied on peripheral blood allowing frequent testing during follow-up.

Highly sensitive chimerism detection in blood is associated with increased risk of relapse after allogeneic hematopoietic cell transplantation in childhood leukemia.

Analysis of chimerism in blood post-HCT using STR-PCR is routinely applied in parallel with quantification of MRD to predict relapse of leukemia. RQ-PCR chimerism is 10- to 100-fold more sensitive, but clinical studies in children are sparse. We analyzed IMC in blood samples following transplantation for acute lymphoblastic or myeloid leukemia in 56 children.

Feasibility of extracorporeal photopheresis in pediatric patients with graft-versus-host disease after hematopoietic stem cell transplantation.

Graft-versus-host disease (GVHD) is a main cause of morbidity and mortality following hematopoietic stem cell transplantation. The cumulative incidence of acute and chronic GVHD (aGVHD, cGVHD) reaches 30%-50% and 20% in pediatric populations, respectively. Prednisolone and/or calcineurin inhibitors (CNI) are first-line treatments, but no superior second-line treatment has yet been established.

The prognostic value of YKL-40 concentrations in nonmyeloablative conditioning allogeneic hematopoietic cell transplantation.

Increased plasma concentrations of YKL-40, also called chitinase-3-like-1 protein (CHI3L1), have been correlated with disease severity in a variety of malignant and inflammatory diseases. The objective of the current study was to assess pretransplant recipient and donor CHI3L1 polymorphisms and plasma YKL-40 concentrations as prognostic biomarkers in a cohort of 149 patients treated with hematopoietic cell transplantation (HCT) after nonmyeloablative conditioning for hematologic malignancies. Recipients with pretransplant YKL-40 concentrations above the age-adjusted 95th percentile (high) had higher relapse-related mortality (33% versus 18%, P = .

Allogeneic haematopoietic cell transplantation with nonmyeloablative conditioning in Denmark.

Introduction: Haematopoietic cell transplantation with nonmyeloablative conditioning (NMC-HCT) is used in the treatment of haematological malignancies.

Material And Methods: Use of NMC-HCT in Denmark from 2000-07 was examined.

Results: Unrelated donor searches resulted in a suitable donor in 75% of cases of which 36% were transplanted.

[Health status and degree of traumatisation among newly arrived asylum seeker--secondary publication].

An unknown number of asylum seekers arriving in Denmark have been exposed to torture. Amnesty International's Danish Medical Group examined 142 asylum seekers, of whom 45% had been exposed to torture. Physical and psychological symptoms were 2-3 times as frequent among torture survivors as among non-tortured asylum seekers.