Verena Wiegering

Haemophiliacs and extremely premature infants are both at an increased risk for intracranial haemorrhage; both conditions might be further elevating the risk. We report a case of a very immature preterm-infant of 26 gestational weeks (birth weight 635 g) with severe haemophilia A. Furthermore, we provide an overview of the published literature on this subject matter. Until now, deficiency of factor VIII or IX as a potential risk factor for ICH in preterm infants remains controversial. However, prophylactic substitution of factor VIII or IX in preterm infants with haemophilia may minimize the risk of bleeding complications and neurologic sequelae.

Summary: Glanzmann’s thrombasthenia (GT) is an autosomal recessive disorder characterized by a lack of thrombocyte aggregation due to the absence of thrombocyte glycoproteins IIb and αIIbβ3. The role of haematopoietic stem cell transplantation (HSCT) in GT remains controversial. However, HSCT offers the only curative approach for patients with a severe clinical phenotype.In this review, we will discuss the limitation of current status evidence and the specific risk of GT, in particular the alloimmunization and refractoriness to thrombocyte infusions. 19 successful HSCT in 18 GT type I patients have been reported. Mean age at transplantation was 5 years. All patients are still alive. The majority received sibling bone marrow transplant with busulfan and cyclophosphamid conditioning. GvHD incidence was within the normal range, but 10 patients showed alloimmunization of thrombocytes. Median follow up is 25 months.

Background: Tumor genesis of many pediatric malignancies remains unclear. Data of immune function are lacking at diagnosis. We prospectively analyzed 109 pediatric patients with malignancy at diagnosis. Methods: Lymphocyte subpopulations were characterized by FACS, TREC-assay, and Immunoscope, cytokines by FACS and ELISA. Observations: We detected higher values of CD4⁺ T cells and consecutively shifted CD4⁺/CD8⁺ ratio in all patients compared with the control group. In patients with lymphoma, interleukin-2 was upregulated in all subpopulations. Conclusions: On the basis of these findings an altered immune function could be found in children with different malignancies at diagnosis. Further investigations are necessary to identify tumor-related immune deficiency for novel therapeutic approaches.

Background: For Thrombasthenia Glanzmann (GT) patients presenting with a severe clinical phenotype due to complete lack of thrombocyte function or increased titres of anti-platelet antibodies hematopoietic stem cell transplantation (SCT) is the only curative therapy. Case report: We report the case of a 13-month-old boy, presenting with a severe course of GT, who was successfully treated with an HLA-identical sibling bone marrow transplant. SCT was complicated by anti-platelet alloimmunization after platelet transfusion successfully treated with high dosage immunoglobulins (2 g/kg) and partial plasma exchange. Conclusion: SCT may be a viable option for selected patients with GT. However, SCT in GT carries its own significant risks, resulting from the development of anti-platelet antibodies. A critical risk-benefit analysis is mandatory prior to SCT. Hintergrund: Die Thrombasthenia Glanzmann (GT) ist eine autosomal rezessive Erkrankung, bei der die Thrombozytenaggregation durch einen fehlenden/funktionslosen Glykoprotein-IIb/IIIa-Komplex stark vermindert ist. Die allogene Stammzelltransplantation (SCT) stellt bei Patienten mit einem schweren Phänotyp die einzige kurative Therapieoption dar. Fallbericht: Ein 13-monatiger Knabe mit GT wurde erfolgreich mit Knochenmark seines HLA-identischen Bruders transplantiert. Als Komplikation trat eine antithrombozytäre Alloimmunsierung auf, die durch eine hochdosierte Immunglobulintherapie (2 g/kg) und partiellen Plasmaaustausch behandelt werden konnte. Schlussfolgerung: Die allogene SCT ist eine geeignete Therapie für Patienten mit GT. Als besonderes Risiko sind bei einem Kind antithrombozytäre Antikörper aufgetreten. Deshalb ist bei dieser Diagnose jeder Einzelfall einer kritischen Risiko-Nutzen-Analyse zu unterziehen.

Background: Infection with varicella-zoster virus (VZV) contemporaneously with malignant disease or immunosuppression represents a particular challenge and requires individualized decisions and treatment. Although the increasing use of varicella-vaccines in the general population and rapid initiation of VZV-immunoglobulins and acyclovir in case of exposure has been beneficial for some patients, immunocompromised individuals are still at risk for unfavourable courses.Methods: In this single center, 6-year analysis we review incidence, hospitalization and complication rates of VZV-infections in our center and compare them to published data. Furthermore, we report three instructive cases.Results: Hospitalization rate of referred children with VZV-infections was 45%, among these 17% with malignancies and 9% under immunosuppressive therapy. Rate of complications was not elevated in these two high-risk cohorts, but one ALL-patient died due to VZV-related complications. We report one 4-year old boy with initial diagnosis of acute lymphoblastic leukemia who showed a rapidly fatal outcome of his simultaneous varicella-infection, one 1.8-year old boy with an identical situation but a mild course of his disease, and an 8.5-year old boy with a steroid-dependent nephrotic syndrome. This boy developed severe hepatic involvement during his varicella-infection but responded to immediate withdrawl of steroids and administration of acyclovir plus single-dose cidofovir after nonresponse to acyclovir after 48 h.Conclusion: Our data show that patients with malignant diseases or immunosuppressive therapy should be hospitalized and treated immediately with antiviral agents. Despite these measures the course of VZV-infections can be highly variable in these patients. We discuss aids to individual decision-making for these difficult situations.

Cytokine production by human lymphocytes from healthy children (ages 0-18 years) was assessed using a flow cytometric procedure involving staining of intracellular cytokines by the paraformaldehyde-saponin procedure. To establish valid cytokine values for intracellular cytokine expression in healthy children in the different age groups, we measured 117 samples after 24 h in vitro stimulation with PMA, ionomycin and brefeldin followed by staining with intracellular anti-cytokine and surface antibodies. We found decreasing IL-2 expression, increasing IFN-gamma and TNF-alpha production and stable IL-4, Ki67 and TGFb levels with advancing age. The cytokines were mainly produced by memory T-cells. Apart from age, there was a differential expression in boys and girls: boys (< 6 years) produce significantly more IL-2 (p < 0,04), while girls > 12 years produce more IFNg than boys of the same age (p < 0.05). This systematic analysis of cytokine profiles during childhood allows a better understanding of immune maturation and will contribute significantly to the interpretation of cytokine data from children with pathological conditions.