Statement of current majority practices in graft-versus-host disease prophylaxis and treatment in children

Great variations exist in the prophylaxis and treatment of GVHD in children undergoing allogeneic stem cell transplantation (SCT). The EBMT Working Party Paediatric Diseases (EBMT-WP PD) and the International BFM Study Group--Subcommittee Bone Marrow Transplantation (IBFM-SG), aimed at evaluating current local standards in the prevention and treatment of GVHD and steps which can be taken to achieve a uniform policy for the individual methods. Several conferences with their members assessed practices which are mainly applied or under investigation in children and identified where additional information is needed. For prevention of GVHD, the majority of the paediatric centres prefer CsA +/- MTX. Addition of folinic acid to MTX was considered for reduction of side-effects. During treatment of acute GVHD most centres administer prednisolone and whole blood level-adjusted CsA as medications of first choice. In cases of poor or no response to this therapy, additional immunosuppressive agents such as ATG, mycophenolate-mofetile and tacrolimus are being increasingly used. The treatment of chronic GVHD usually consists of various combinations of prednisolone and CsA. In severe cases, extracorporeal photopheresis, psoralene-UVA (PUVA) and thalidomide are administered.     

Permanent tunneled silicone central venous catheters for autologous PBPC harvest in children and young adults

Children with high risk malignancies are usually given permanent (Hickman-type) tunneled silicone rubber central venous catheters (silicone CVCs) for the administration of chemotherapy. In the past, these children received an additional short-term polyurethane dialysis CVC for stem cell apheresis. To avoid placement of an additional short-term CVC, we started in 1995 to use pre-existing silicone CVCs for PBPC harvests. From May 1996 to February 1999 we evaluated 165 harvests in 37 children and 14 young adults (16-28 years) treated with high-dose chemotherapy and stem cell support, comparing CD34+ cell harvest efficiency, catheter tolerability, and complications in three different approaches to vascular access. Pre-existing silicone CVCs (64%) or peripheral venous cannulae (15%) were the first choice for venous access. Only when these failed were polyurethane CVCs (21%) used. No significant difference was seen between these three groups, even after dividing the silicone CVC group (105 harvests in 32 patients) into three subgroups according to weight and age. The most frequent problems were citrate toxicity (n = 33), mechanical obstruction inside (n = 9) and outside the cell separator (n = 2), decreased draw line flow in silicone CVCs (n = 7), decreased draw line flow in peripheral venous cannulae (n = 6), and one occlusion in a polyurethane CVC. Pre-existing CVCs and peripheral venous cannulae functioned efficiently when used as a draw line in 79% of the apheresis procedures without significantly reducing single harvest efficiency or catheter tolerability. Consequently, the risks and costs associated with the placement of a dialysis CVC could be avoided in the majority of cases. Bone Marrow Transplantation (2000) 26, 781-786.     

Autoantibodies in chronic GVHD: high prevalence of antinucleolar antibodies

Sera from 32 bone marrow allograft recipients were screened for the presence of autoantibodies 4-61 months post-graft. Sera from 12 of 19 patients with extensive chronic graft-versus-host disease (c-GVHD) stained the nucleolar region strongly in immunofluorescence, indicating the presence of specific antinucleolar antibodies. In contrast, none of three patients with limited and none of 10 patients without c-GVHD had antinucleolar antibodies. Antibodies reacting with nuclear constituents other than nucleoli were found in five of the 12 antinucleolar positive patients. The appearance of antinucleolar antibodies coincided with early clinical symptoms of c-GVHD. We conclude that the appearance of antinucleolar antibodies after bone marrow transplantation is specific for patients with extensive c-GVHD. Furthermore, the development of extensive c-GVHD is paralleled by the emergence of these antinucleolar antibodies.     

Akute PankreatitisSeltene Komplikation bei prim?rem Hyperparathyroidismus (pHPT) Seltene Komplikation bei prim?rem Hyperparathyroidismus (pHPT)

Fragestellung. Prim?rer Hyperparathyroidismus (pHPT) im Kindes- und Jugendalter ist eine ?u?erst seltene Erkrankung, weshalb die Diagnose h?ufig verz?gert gestellt wird.     

Cooperative studies in the treatment of acute lymphoblastic leukemia in children in Austria--report of 10 years' experience

437 children with acute lymphoblastic leukaemia (ALL) have been treated at 9 different institutions in Austria utilizing common protocols and central registration between 1974 and 1984. 227 patients (132 boys and 95 girls, group I) were treated between 1974 and 1980 using 3 consecutive protocols (KMK, O 76, A 78), which were essentially derived from the Memphis studies VII and VIII. Patients with a high risk of relapse were treated according to the LSA 2-L2 protocol. 210 patients (112 boys and 98 girls, group II) were consecutively treated following the BFM protocols 76/79 and 81/83. In this group, treatment intensity was adjusted to the initially determined individual risk of relapse (BFM risk score or risk factor). To date, the life table analysis demonstrates that the probability of continuous complete remission for patients in group II is 60% after 5 and 3 years (BFM 76/79 and BFM 81/83, respectively), whereas group I reaches a level of 37.3%. The prognostic difference between risk and non-risk patients in both studies of group II was eliminated. Despite a higher morbidity and non-leukaemia-related mortality in group II, the therapeutic success can be attributed to the intensification of induction therapy.     

Surface glycoproteins (S-GP) on normal and malignant human leukocytes

Summary This study aimed to investigate high molecular weight surface glycoprotein (S-GP) patterns on various types of human leukocytes. S-GP were externally labelled by the Galactose-oxidase-NaB³H₄ technique. Results based on the analysis of 120 samples derived from different types of normal and malignant leukocytes indicate that (i) the relative expression of high molecular weight S-GPs changes during haemopoietic cell differentiation and (ii) to some extent these changes enable the classification of human leukocytes.     

Leukemia-associated antigenic isoforms induce a specific immune response in children with T-ALL

The potential immunogenicity of acute lymphoblastic leukemia of the T cell (T-ALL), a small subgroup of childhood leukemia with increased risk for treatment failure and early relapse, was addressed by serological identification of leukemia-derived antigens by recombinant expression cloning (SEREX). Thirteen antigens with homology to known genes that are involved in critical cellular processes were detected. Further characterization of the 4 novel isoforms revealed that 3 (HECTD1Delta, CX-ORF-15Delta and hCAP-EDelta) had restricted mRNA expression in more than 70% of T-ALLs (n = 22) and that specific antibodies against these isoforms were detected in up to 30% of patients (n = 16), with the highest frequency for HECTD1Delta. The latter protein was present at high abundance in T-ALLs but not in normal hematopoietic tissues. Given that the leukemia-associated antigens detected in this study have an intracellular localization, the generation of immune effector responses most likely requires antigen presentation. To test this assumption, dendritic cells were loaded with HECTD1Delta protein and used for T cell stimulation. A specific T cell response was induced in vitro in all 3 healthy donors studied, including a former T-ALL patient. These data suggest that T-ALL may induce a specific cellular and humoral antileukemia immune response in children, thereby supporting new approaches for immunotherapy.     

Thrombozytenfunktionsstörung während der hochdosierten Substitutionstherapie bei Hämophilie A

Zusammenfassung Es wird über 2 Patienten mit Hämophilie A berichtet, bei denen sich während einer operationsbedingten hochdosierten Substitutionstherapie mit antihämophilem Globulin vorübergehend eine Thrombozytenfunktionsstörung mit manifester hämorrhagischer Diathese einstellte. Zum Zeitpunkt der Blutung waren bei ausreichend hoher Faktor VIII-Aktivität der Fibrinogenwert im Plasma auf 1700 mg-% und der Gehalt an Faktor VIII-assoziiertem Antigen auf über 600% der Norm angestiegen. Da es während der Substitution zu keiner Zeit gelang, Fibrinogenspaltprodukte oder Komponenten des antihämophilen Globulins mit üblichen Methoden nachzuweisen, wird — unterstützt durch in vitro-Untersuchungen der Thrombozytenaggregation — die Ansicht vertreten, daß die Beladung der Plättchenoberfläche mit überschüssig zugeführten Proteinen ursächlich mit der thrombozytären Funktionsstörung zusammenhängt. Die Bedeutung kleinmolekularer und dialysierbarer Faktor VIII-Komponenten wird ebenso wie die Möglichkeit immunpathologischer Vorgänge diskutiert.