Summary. Streptococcus pneumoniae (S. pneumoniae) may cause severe and lethal infections months and years following stem cell transplantation (SCT). In a prospective survey over a 3AE5-year period, we assessed the incidence, risk factors and outcome for invasive pneumococcal infection (IPI) following SCT. Fifty-one episodes of IPI were reported: 43 episodes after bone marrow transplantation (BMT) and 8 after peripheral blood stem cell transplantation (PBSCT); 35 after allogeneic SCT and 16 after autologous SCT. Seven IPI episodes, all bacteraemias, were defined as early, occurring 1-35 d (median 3 d) post transplantation. Forty-four episodes were defined as late ( ‡ 100 d post SCT), occurring 4 months to 10 years (median 17 months) post transplantation. The incidences of early and late IPI were 2AE03/1000 and 8AE63/1000 transplantations respectively (P ¼ 0AE001). A higher incidence of late IPI was observed after BMT than after PBSCT (10AE99 versus 3AE23/1000; P < 0AE01) and after allogeneic versus autologous SCT (12AE20 versus 4AE60/1000; P < 0AE01). There was a higher estimated incidence of IPI in allogeneic patients with than in those without graft-versus-host disease (GVHD) (18AE85 versus 8AE25/1000; P ¼ 0AE015). The mortality rate was 20%, including 2/7 of early and 8/44 of late IPI. S. pneumoniae is a rare but important complication during the aplastic phase after SCT. In conclusion, S. pneumoniae is a significant cause of morbidity late post-transplantation, especially in allogeneic patients, and particularly those with GVHD. The high IPI mortality rate, both early and late posttransplantation, requires preventive approaches, mainly effective immunization.

Myeloblative therapy with hyper-ME +/- C radiochemotherapy can improve the prognosis of multifocal primary and early or multiple relapsing Ewing's sarcoma.

Summary:Prognostic scoring systems based on physiological parameters have been established in order to predict the outcome of ICU patients. It has been demonstrated that the predictive value of these scores is limited in patients following hematopoietic stem cell transplantation (HSCT). Therefore, we evaluated patients from the Dü sseldorf pediatric stem cell transplantation center with regard to predisposing factors and prognostic variables for ICU treatment and outcome. Between January 1989 and December 1998, 180 HSCT have been performed. The clinical, laboratory and HSCT-related parameters such as conditioning treatment, engraftment, GVHD, infections and HSCT toxicity were prospectively recorded and retrospectively analyzed. Established pediatric scoring systems (PRISM, TISS, P-TISS) were applied. Twenty-eight patients required intensive care (16 male, 12 female, median age: 10.9 years (range: 0.4 to 18.9 years), five autologous, 13 allogeneic-related and 10 unrelated transplanted patients). Ventilator-dependent respiratory failure was the most frequent cause of admission to the ICU (n ‫؍‬ 23). Fourteen of 28 patients were discharged from ICU, and six of 28 patients achieved a long-term survival (110 to 396 weeks). At admission to the ICU, impaired cardiovascular status, high CRP levels and presence of macroscopic bleeding were each associated with fatal outcome (P Ͻ 0.05). The Pediatric Risk of Mortality (PRISM) score was not prognostically significant at the 0.

Multiple transplant-related complications (MTRC) represent a severe condition after bone marrow transplantation (BMT) and are supposed to reflect systemic endothelial damage. Soluble thrombomodulin (sTM) and plasminogen activator inhibitor type-1 (PAI-1) were investigated as markers of endothelial dysfunction in 35 patients after autologous or allogeneic BMT and compared with the occurrence of the typical complications sepsis, veno-occlusive disease of the liver (VOD), graft-versus-host disease (GVHD), and capillary leakage syndrome (CLS). PAI-1 was assessed by an assay of functional activity and sTM by antigenic determination. In patients who had undergone allogeneic BMT and had no transplant-related complications (TRC), PAI-1 peaked on day +14 (20 +/- 5 units/ml), and sTM doubled in comparison to the starting range, to 60-80 ng/ml between days +14 and +49. In contrast, PAI-1 and sTM were unchanged following autologous BMT. PAI-1 was increased in sepsis, CLS, and VOD to 39-49 units/ml (p < 0.05, compared with patients without TRC), and in GVHD to 16-47 units/ml (not significant). Soluble TM increased to 63-309 ng/ml in patients with sepsis, VOD, or CLS (p < 0.05, compared with patients without TRC) and to 79-224 ng/ml in GVHD (not significant). The increase of sTM and PAI-1 was also positively correlated to the number of complications, so that in patients with three complications PAI-1 was increased 2.8-fold and sTM 3.5-fold over patients with no complications at all. We conclude that endothelial dysfunction is a feature of VOD, sepsis, CLS, and to lesser extent of GVHD and is worse in patients with multiple complications.

Age, hematopoietic growth factors, cyclosporin A, mode of bone marrow transplantation (BMT) (autologous, allogeneic-related, unrelated), and underlying disease were assessed as potential risk factors for capillary leakage syndrome (CLS) in 96 patients after BMT. CLS was defined as unexplained weight gain of > 3% within 24 h and nonresponsiveness to furosemide. CLS occurred in 9/21 patients after unrelated compared with 2/33 after allogeneic-related BMT (p = 0.0017) for hematopoietic disorders (n = 54) and in 6/7 patients after allogeneic-related compared with 3/35 after autologous BMT (p = 0.001) for solid tumors (n = 42). Hematopoietic growth factors and cyclosporin A were no significant risk factors on their own. We conclude that unrelated BMTs or high-intensity conditioning regimens used in combination with allogeneic-related BMT are the main risk factors for CLS.

Summary:In the absence of a donor alternative a stem cell transplantation consisting of two cord blood components originating from the haploidentical brother was performed in a 2-year-old girl with c-ALL, early CNS relapse and 7% of blast cells in the BM 14 days before transplantation. Because of various ongoing infectious complications at that time, 1/8 of the immunogenetically acceptable sibling cord blood was ex vivo expanded 10 days before the transplantation date. The total CB consisting of 1.17 ؋ 10 9 NC was cryopreserved in four separate bags. The one containing 1/8 of the total CB with 1.4 ؋ 10 8 NC CliniMACS selected CD34 ؉ cells was expanded in the presence of 100 ng/ml G-CSF, 100 ng/ml TPO and 100 ng/ml flt3-L in 10% autologous CB plasma and X-VIVO 10 medium at day ؊10 before transplantation. This expanded cell population was sterile and consisted of about 60% granulocytic cells (CD13 ؉ Cord blood (CB) has clearly become an alternative and even a promising source of marrow repopulating cells for the treatment of pediatric patients over the past 10 years. Hitherto, over 1000 unrelated and related cord blood transplants have been performed, mostly in pediatric patients. [1][2][3][4][5] In spite of one or two HLA-antigen mismatches these patients have engrafted with no or only moderate acute or chronic GVHD. [1][2][3][4][5] Due to the relatively low numbers of cells in the primary residual cord blood including colony-forming units and CD34 ϩ cells, presently there are certain limitations for the widespread use of CB as a source of hematopoietic cells for transplantation, particularly in adults or overweight patients. Delays in engraftment for neutrophils and platelets have been observed when lower cell numbers were transplanted, resulting in more frequent infectious complications after transplantation. With about 40% frequency the latter were the major cause of death in the most recent analysis published.,5 Therefore, ex vivo expanded CB infused into the patient at the time of transplantation as the nonexpanded cord blood from the same donor could increase the number of immediately available progenitor cells responsible for short-term engraftment. While expansion with recombinant hematopoietic growth factors has been shown to increase the number of multipotent colony-

We report the long-term follow-up of children transplanted with Treosulfan (TREO)-based conditioning in Germany and Austria. Nine centres reported a total of 109 transplantations. Patients were stratified according to the paediatric TRM risk score derived from the paediatric BMT registry (PRST) and compared with the historical transplant population of this registry. Underlying diseases were malignancies, immunodeficiencies, and haematologic and metabolic disorders. TREO total dose ranged from 21-42 g/m 2 . Additional conditioning drugs included fludarabine, thiotepa, melphalan, CY and/or TBI. EFS at 3 years for non-malignant and malignant diseases was 88% and 49%, respectively. Leukaemia patients in remission had a survival of 51% at 3 years; nonremission patients relapsed and died within 18 months. TRM and OS in the low-risk groups 0 and 1 were similar to PRST controls. TRM in the high-risk groups 2 and 3 was markedly lower (9% vs 28% and 13% vs 53%, respectively) than in the PRST group, but OS was similar.In conclusion, TREO-based conditioning regimens in children resulted in excellent engraftment and long-term survival in nonmalignant disease. In high-risk malignancy, low acute toxicity was followed by low TRM but it did not translate into increased survival.

Because of the rather short observation period. secondary malignant neoplasms (SMN) may complicate the future clinical course of some of our patients who are currently viewed as event-free survivors. EFS in AET is not improved by allogeneic SCT due to a higher complication rate. The patient group was to small to analyze for a possible graft-versus-tumor effect.