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Biomedical subjects

W Nürnberger

Publications and source records attributed to W Nürnberger.

At least 19 recordsLinked to original sources
PubMed2002

Serial evaluation of the oncological pediatric risk of mortality (O-PRISM) score following allogeneic bone marrow transplantation in children.

The O-PRISM score was introduced for risk assessment in children transferred to intensive care following BMT. The aim of this study is to determine the prognostic value of a serial evaluation of the O-PRISM score. Ninety-three children, 58 allogeneic-related and 35 unrelated BMT, were evaluated. At weekly intervals, the O-PRISM was calculated based on the standard PRISM score and the three additional variables CRP, GVHD and hemorrhage. Overall survival was 0.51 +/- 0.05 (48/93 patients). Seventeen children died of recurrent disease and 28 of BMT-related complications. High O-PRISM scores significantly correlated with adverse outcome. The relative risks of DOC of patients with scores > or =10 compared to patients with lower scores were: day 0: 3.9 (95% confidence-interval: 1.1-13.7, P = 0.02), day 7: 2.0 (0.7-6.2, P = 0.20), day 14: 5.2 (1.9-14.0, P = 0.001), day 21: 5.6 (1.9-16.5, P = 0.001), day 28: 11.5 (3.8-100.9, P < 0.001), day 35: 7.3 (1.9-27.7, P = 0.001). As early as day 0, children with scores > or =10 points showed a higher cumulative incidence of DOC than patients with lower scores (0.69 +/- 0.15 vs 0.27 +/- 0.05, P = 0.02). The O-PRISM score represents a useful clinical parameter for serial risk assessment following BMT. As it indicates fatal events early, it may be helpful for parent information and even more for the early establishment of intensified supportive treatment. The O-PRISM score may therefore be a valuable parameter for the evaluation of different strategies for BMT and supportive treatment.

Adolescent↗
PubMed2002

Bilateral exopthalmus due to retro-orbital chloromas in a boy with t(8;21)- positive acute myeloblastic acute leukemia.

Exophthalmus is an infrequent finding in pediatrics. The differential diagnoses include chloromas, tumors of immature hematopoietic precursor cells. The case of a child with acute myeloid leukemia is reported. The presenting signs had included exophthalmus and nasal speech due to retro-orbital and sinusoidal chloromas, respectively. As in most cases of pediatric acute myeloid leukemia with chloroma, the AML1/ETO fusion gene was found, which portended a not unfavorable prognosis. This child was treated according to the AML-BFM 98 protocol and achieved an ongoing remission. The exophthalmus resolved completely.

Antineoplastic Agents↗
PubMed2001

Thrombotic events revisited in children with acute lymphoblastic leukemia: impact of concomitant Escherichia coli asparaginase/prednisone administration.

Recently published data suggest that the prothrombin G20210A variant, the TT677 methylenetetrahydrofolate reductase genotype, the factor V G1691A mutation, deficiencies of protein C, protein S, antithrombin, and elevated lipoprotein (a) concentrations were associated with venous thromboembolism in childhood patients treated according to the BFM protocol. To unravel the role of these prothrombotic risk factors and different treatment modalities, the present comparative study was performed in childhood leukemia patients of the same living population. Four hundred and twenty consecutively recruited leukemic children (BFM n=300; COALL n=120) were enrolled in this study with respect to the presence of prothrombotic risk factors and the occurrence of symptomatic venous thrombosis. No significant difference was found in the prevalence rates of thrombotic risk factors in the Caucasian populations studied. Symptomatic venous thromboembolism occurred in 11.6% of BFM patients compared with 2.5% in the COALL treatment group [odds ratio (OR)/95% confidence intervals (CI): 7.7/1.8-32.6; P=.005]. Including age, prothrombotic risk factors, central venous lines, treatment protocols, and anti-leukemic drugs in a logistic regression model, only the concomitant Escherichia coli asparaginase/prednisone administration in leukemic children suffering from a prothrombotic risk factor was found to increase the rate of thrombotic manifestations during leukemia treatment in patients of the same Caucasian origin (OR/95% CI: 34.5/4.39-271.42; P=.0008). Based on the data presented here, we suggest the use of prednisone and E. coli asparaginase concomitantly administered in a leukemic patient suffering from a prothrombotic risk factor to be responsible for the onset of venous thrombosis in the majority of cases.

Adolescent↗
PubMed2001

Growth factors and hemostasis: differential effects of GM-CSF and G-CSF on coagulation activation--laboratory and clinical evidence.

Granulocyte-macrophage (GM-CSF) and granulocyte colony-stimulating factors (G-CSF) are equally effective hematopoietic growth factors in terms of their potential to shorten the period of neutropenia following high-dose chemotherapy or to mobilize hematopoietic stem cells. Thus the choice between the two preparations must be based on a comparison of adverse effects. Both GM-CSF and G-CSF have been implicated in disturbances of the hemostatic system, resulting in both hemorrhagic and thrombotic complications. We therefore studied the effects of GM-CSF and G-CSF therapy on hemostasis both ex vivo and clinically. In a prospective, non-randomized study 34 patients who were treated with a myeloablative regimen according to the hyper-ME+/-C protocol and stem cell or bone marrow transplantation received posttransplantation hematopoietic support with GM-CSF (n=15) or G-CSF (n=19). The patients were monitored for alterations in plasmatic coagulation parameters and clinical evidence of hemorrhagic or thrombotic events. GM-CSF, but not G-CSF, induced a significant, albeit usually mild activation of the coagulation cascade. We observed an increased frequency of veno-occlusive disease in the GM-CSF group (3/15 vs. 1/19 on G-CSF, n.s.). Other thrombotic events were rare. At the same time, hemorrhage was both more common and more severe in GM-CSF treated patients than in those on G-CSF (macroscopic hemorrhage 11/15 vs. 10/19, III hemorrhage 7/15 vs. 1/19 on GM-CSF or G-CSF, respectively). In conclusion, unlike G-CSF, if given after hyper-ME chemotherapy plus stem cell or bone marrow transplantation, at the dosage used here GM-CSF induced an activation of the coagulation system and was associated with an increased risk of hemostasis associated treatment complications.

Adolescent↗
PubMed2001

Glycosylated vs non-glycosylated granulocyte colony-stimulating factor (G-CSF)--results of a prospective randomised monocentre study.

The discovery of the haematopoietic growth factor granulocyte colony-stimulating factor (G-CSF) has reduced infection-related morbidity in cancer patients by alleviating post-chemotherapy neutropenia. Two formulations of recombinant human (rh) G-CSF, one glycosylated and one non-glycosylated, are available. The glycosylated form, lenograstim, possesses at least 25% greater bioactivity in vitro. Some comparative studies into the preparation's potential to mobilise haematopoietic stem cells suggest a similar advantage. In the light of the great clinical importance of G-CSF, we have performed the first prospective, randomised, crossover study on children with chemotherapy-induced neutropenia. G-CSF (250 microg/m(2)) was started 1 day after the chemotherapy block, and was administered until a WBC >1500/microl was achieved on 3 successive days. Thirty-three G-CSF cycles from 11 patients (16 lenograstim, 17 filgrastim) were studied. They were investigated for duration of very severe (WBC <500/microl, 9 vs 9.5 days, lenograstim vs filgrastim, median) and severe leukopenia (WBC <1000/microl, 11 vs 11 days), infections (CRP >5 mg/dl, 5 vs 5.5 days), infection-related hospital stay (11 vs 9 days) and antibiotic treatment (9 vs 9 days). Statistical evaluation by paired analysis could not detect any difference between treatment groups; the median difference for all end-points was zero. In summary, at least at 250 microg/m(2), in terms of their clinical effect on neutropenia, the two G-CSF preparations appear to have identical activity.

Adolescent↗
PubMed2000

Allogeneic and autologous stem-cell transplantation in advanced Ewing tumors. An update after long-term follow-up from two centers of the European Intergroup study EICESS. Stem-Cell Transplant Programs at Düsseldorf University Medical Center, Germany and St. Anna Kinderspital, Vienna, Austria.

BACKGROUND: An update of results from the High Risk Protocol of the Meta-EICESS Study, conducted at the Pediatric Stem-Cell Transplant Centers of Düsseldorf and Vienna. In order to evaluate a possible therapeutic benefit after allogeneic SCT in patients with advanced Ewing tumors (AET), we compared outcome after autologous and allogeneic stem-cell transplantation (SCT). PATIENTS AND METHODS: We analyzed 36 patients treated with the myeloablative Hyper-ME protocol (hyperfractionated total body irradiation, melphalan, etoposide +/- carboplatin) between November 1986 and December 1994. Minimal follow-up for all patients was five years. All patients underwent remission induction chemotherapy and local treatment before myeloablative therapy. Seventeen of thirty-six patients had multifocal primary Ewing's tumor, eighteen of thirty-six had early, multiple or multifocal relapse, one of thirty-six patients had unifocal late relapse. Twenty-six of thirty-six were treated with autologous and ten of thirty-six with allogeneic hematopoietic stem cells. We analyzed the following risk factors, that could possibly influence the event-free survival (EFS): number of involved bones, degree of remission at time of SCT, type of graft, indication for SCT, bone marrow infiltration, bone with concomitant lung disease, age at time of diagnosis, pelvic involvement, involved compartment radiation, histopathological diagnosis. RESULTS: EFS for the 36 patients was 0.24 (0.21) +/- 0.07. Eighteen of thirty-six patients suffered relapse or died of disease, nine of thirty-six died of treatment related toxicity (DOC). Nine of thirty-six patients are alive in CR. Age > or = 17 years at initial diagnosis (P < 0.005) significantly deteriorated outcome. According to the type of graft, EFS was 0.25 +/- 0.08 after autologous and 0.20 +/- 0.13 after allogeneic SCT. Incidence of DOC was more than twice as high after allogeneic (40%) compared to autologous (19%) SCT, even though the difference did not reach significance (P = 0.08, Fisher's exact test). CONCLUSIONS: 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.

Adolescent↗
PubMed2000

Successful treatment of relapsed CML after cord blood transplantation with donor leukocyte infusion IL-2 and IFNalpha.

A 3-year-old girl with BCR/ABL-positive CML relapsed after related HLA-identical cord blood transplantation. She was treated with three cycles of donor lymphocyte (DLI) infusion from her 15-month-old brother. Interferon alpha was added after the second DLI, whereas a trial of IL-2 had to be discontinued because of increasing immature myeloid cells in the blood smear. No signs of GVHD were observed, but she developed myelosuppression and needed one platelet and one red blood cell transfusion. She achieved a molecular remission after 6 months with transient molecular relapse followed by sustained remission for 15 months. Thus, DLI with or without interferon alpha might prove to be a promising treatment option with tolerable side-effects in relapsed CML after cord blood transplantation. Bone Marrow Transplantation (2000) 25, 219-222.

Blood Component Transfusion↗
PubMed2000

'Sepsis' and multi-organ failure: predictors of poor outcome after hematopoietic stem cell transplantation in children.

Prognostic scores, such as the PRISM and APACHE II, have been established, predicting with reasonable accuracy the outcome of patients admitted to intensive care units (ICU). In keeping with previous reports, we found, however, that these scores failed to perform in a series of 28 recipients of hematopoietic auto- or allografts (BMT) who required ICU admission for reasons including respiratory (82%) and multi-organ (36%) failure. We therefore retrospectively analyzed the charts of these patients, evaluating predisposing factors and prognostic variables which might confound the validity of these ICU tools which in other clinical scenarios have proven so valuable. Of all the parameters tested, logistic analysis established the following as predictors for poor outcome: increased C-reactive protein (CRP) to > 10 mg/dl (P = 0.04), macroscopic hemorrhage (P = 0.04), hypotension (mean arterial pressure < normal) (P = 0.04) and GVHD > or = III (P = 0.002). Most of these factors are not accounted for by the standard prognostic questionnaires. The development of an 'oncological' or 'post-BMT' risk of mortality score, taking into account these patients' specific clinical problems, might improve the risk assessment for this patient group, and might thus facilitate the timely recognition of those patients most in need of more intensive therapeutic measures.

Adolescent↗
PubMed2000

Introduction of the oncological pediatric risk of mortality score (O-PRISM) for ICU support following stem cell transplantation in children.

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 Düsseldorf 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 < 0.05). The Pediatric Risk of Mortality (PRISM) score was not prognostically significant at the 0.05 level. Long-term survival after discharge from the ICU correlated with HSCT-related parameters such as the type of transplant and severity of GVHD (P = 0.002). By introduction of HSCT related parameters such as severity of GVHD (grade 2: 2 points; grade >2: 4 points), CRP-level (>10 mg/dl: 4 points), and presence of macroscopic bleeding (4 points) into the PRISM score a new oncological PRISM ('O-PRISM') score was established. This score significantly correlated with the risk of mortality in the ICU (P = 0.01). In conclusion, the new O-PRISM score accurately characterizes the clinical situation of children requiring ICU treatment following HSCT. It distinguishes more appropriately between success and failure of ICU treatment following HSCT than the standard prognostic scores. It needs to be evaluated in future prospective studies of critically ill children after HSCT. Bone Marrow Transplantation (2000).

Adolescent↗
PubMed2000

In vivo cytokine responses to interleukin-2 immunotherapy after autologous stem cell transplantation in children with solid tumors.

The potent immunostimulatory cytokine interleukin-2 (IL-2) has been extensively investigated for its potential to induce anti-tumor immunity in a number of tumor models. Only recently the complex interplay of mutually suppressive or supportive cytokines of the IL-2-induced network of cytokines has been better characterized. The aim of this study was to assess which of these in vitro findings are reproducible in vivo in recipients of stem cell transplants (SCT), since in these patients long- lasting impairments in cytokine inducibility have been described. We have therefore studied the kinetics of putative modulators and mediators of IL-2-induced immune activation, namely IL-1beta, IL-4, IL-5, IL-10, IL-12, soluble Fas ligand (sFasL), and GM-CSF during IL-2 therapy. All patients were children or adolescents suffering from solid tumors with poor prognosis who received three 5-day courses of high-dose intravenous IL-2 as an adjuvant to their radio-chemotherapy and autologous SCT. While IL-1beta, IL-4 and IL-12 were not, and sFasL was only mildly affected by the IL-2 therapy, we observed a consistent and early rise of IL-10, IL-5, and GM-CSF. These increases were rapidly reversible after discontinuation of IL-2 therapy. The inducibility of IL-10, IL-5 and GM-CSF was more pronounced with increasing time from the SCT, and in the third cycle reached an order of magnitude as in high-dose IL-2 patients without SCT. Together with the abundant in vitro data, these findings may help devise a combination immunotherapy permitting stronger anti-tumor effects, but lesser adverse effects.

Adolescent↗
PubMed1999

Additive effects of infection and neutropenia on the induction of granulocytopoietic activity in vivo.

BACKGROUND: Granulocyte-colony stimulating factor (G-CSF) is a potent stimulator of granulocytopoiesis and granulocyte function. It has been used in the treatment of children with neutropenic infection; in this context, it was expected to shorten aplasia and limit the severity of infection. Clinical trials, however, have demonstrated conflicting results as to whether these aims can be met. Recently, the use of other, less lineage specific growth factors, such as interleukin (IL)-11 and stem cell factor (SCF), has also been discussed. The dynamics of growth factors and growth factor-regulating proteins during neutropenic infection, particularly in youngsters, are not well understood. METHODS: Serial blood samples from children and adolescents with infection during chemotherapy-induced neutropenia were assayed for C-reactive protein, white blood cell count, IL-11, SCF, G-CSF, IL-10, IL-4, IL-lalpha, and IL-1beta. RESULTS: Although no correlation could be demonstrated between endogenous IL-11 or SCF levels, infection, and leukocyte counts, endogenous G-CSF levels were increased during both aplasia and infection. However, only the additive effects of infection and neutropenia led to maximally stimulated endogenous G-CSF levels. CONCLUSIONS: The elevated G-CSF levels in a majority of patients during severe neutropenic infection may explain why a therapeutic benefit of G-CSF treatment cannot be demonstrated in all cases. There remains, however, a subgroup of patients in whom infection and cytopenia do not yield a good G-CSF response. This latter group should be identified, because they might derive some benefit from adjuvant growth factor therapy. The authors predict that the efficacy of G-CSF in the treatment of patients with neutropenic fever might depend on each individual's ability to initiate the necessary cytokine production.

Adolescent↗
PubMed1999

Systemic meningococcal infection: which children may benefit from adjuvant haemostatic therapy? Results from an observational study.

UNLABELLED: The potential benefits of haemostatic therapy (heparin, antithrombin (AT) concentrate, fresh frozen plasma (FFP)) in severe systemic meningococcal infections (SMI) are controversial. A reduction of the still high case fatality rate would be an important indicator for potential benefits of adjuvant haemostatic therapy in children with SMI. Observational data from nationwide, active surveillance for SMI in children under 16 years in all German paediatric hospitals over a one-year period were used to assess whether potentially beneficial effects of haemostatic therapy are related to the severity of disease. The Neisseria sepsis index (NESI), which grades the severity of SMI from 0 to 8 and has proven to be a reliable tool for predicting the outcome of children with SMI, was used as an indicator of the severity of SMI. During the study period from July 1994 to June 1995, 305 children met the case definition; for 176 of these, complete data sets providing information on parameters underlying the NESI index and regarding the specific haemostatic therapy were available. As all recorded children with NESI 0-2 (n = 129; 73%) survived, a potential impact of haemostatic therapy (given to 45 of them) on survival would be undetectable in this group. A NESI between 3 and 8 was found in 47/176 patients (24%), 35 of whom received some kind of haemostatic therapy. The survival rates were 80% in children with haemostatic therapy (n = 35) and 50% in those without (n = 12) (odds ratio 0.25; 95% confidence interval 0.06-0.98). A subgroup analysis of patients with NESI 3-5 versus those with NESI scores above 5 showed that the beneficial effect of haemostatic therapy was almost confined to children in the NESI 3-5 subgroup. In this subgroup there were 28/31 (90%) survivors with, and 6/11 (55%) survivors without adjuvant haemostatic therapy, whereas none of the patients (n = 5) with a NESI of 6-8 survived, although 4 had received adjuvant haemostatic therapy. CONCLUSION: Studies on the impact of adjuvant haemostatic therapy on survival in children with SMI should focus on those with NESI scores 3-5. The data from this population-based, observational study suggests that haemostatic therapy might reduce the case fatality rate in these children. The optimal dosage and choice of preparations remains to be established. Alternative adjuvant therapeutic strategies may be required in children with SMI and NESI scores > 5.

Anticoagulants↗
PubMed1999

Simultaneous cord blood transplantation of ex vivo expanded together with non-expanded cells for high risk leukemia.

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 x 10(9) NC was cryopreserved in four separate bags. The one containing 1/8 of the total CB with 1.4 x 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+, CD15+), about 30% myelomonocytic cells (CD14, HLA-DR+), 5.2% megakaryocytes (CD61+) and 1.2% CD34+ cells. The proportion of T (CD3+), NK cells (CD56+) as well as dendritic cells (CD83+) was below 0.2%. The unseparated CB infused at day 0 and +1 consisted of a total of thawed 4.4 x 10(7) NC/kg BW, 5.8 x 10(4) CFU-GM/kg BW, 1.54 x 10(5) CD34+cells/kg BW and 7. 73 x 10(2) LTC-IC/kg BW. In addition, the 1 x 10(7) NC/kg BW ex vivo expanded cells representing 1.9 x 10(4) CFU-GM/kg BW, 1.13 x 10(5) CD34 cells/kg BW and 4.37 x 10(2) LTC-IC/kg BW, were infused at day +1. At day +2 after transplantation the patient revealed a focal pneumonia on X-ray with generalized sepsis and became catecholamine dependent. From day +4 the patient received 280 microg/m2 G-CSF. At day +5 she developed an erythroderma, which could not be identified as acute GVHD by biopsy. Early engraftment with leukocyte counts at days 8 and 14 were 350 and 700/microl, ANC 310 and 410/microl, respectively. Donor cells determined by chimerism analysis were 97% and 98% in the periphery at this early time. Most importantly, the pneumonia as well as the septicemia subsided within a few days. Notably, as well is the clearly shortened aplastic phase observed after this simultaneous CB cell component transplantation. The patients T cell and NK cell reconstitution could be detected at day +37 with 330 CD3+ cells/microl and 40 CD56+ cells/microl, respectively. The time to reach an absolute platelet count of 20 000 (50 000)/microl was 75 (103) days. The disease-free survival now exceeds 1 year in complete remission without chronic GVHD or any other health problems. These data show that the applicability of ex vivo expanded committed progenitors and LTC-IC, even in high risk leukemia at the time of transplantation, is feasible and can provide sufficient myeloid progenitors resulting in rapid engraftment able to clear bacterial pneumonia and sepsis. In addition, accelerated hematopoietic reconstitution apparently served as a well functioning platform for definitive graft-versus-leukemia activity. This transplantation of defined ex vivo generated components presents a feasible and generally applicable approach and may open a promising new avenue for cell therapy in malignant diseases.

Cell Culture Techniques↗
PubMed1999

Adjuvant treatment of severe acute pancreatitis with C1 esterase inhibitor concentrate after haematopoietic stem cell transplantation.

BACKGROUND: With an incidence of 4%, acute pancreatitis is a common complication of bone marrow or peripheral haematopoietic stem cell transplantation, which contributes significantly to morbidity and mortality in these patients. In most cases, the pathogenesis of acute pancreatitis cannot be attributed to a single pathogenetic factor, as treatment toxicity, acute graft versus host disease, infection, and cholestasis may all contribute. Acute pancreatitis is characterised by inflammation and activation of digestive proenzymes leading to autodigestive destruction of the pancreas and systemic activation of protease cascades including the complement system. AIM: To describe the effects of human C1 esterase inhibitor in two children, who developed severe acute pancreatitis with considerable complement activation after allogeneic haematopoietic stem cell transplantation. METHODS: Both children showed clinical features resembling those observed in capillary leakage syndrome. In both patients, treatment with C1 esterase inhibitor concentrate contributed to a rapid clinical stabilisation. CONCLUSIONS: These observations strongly support the proposed pathophysiological concept that early treatment with C1 esterase inhibitor interferes with the activation of the complement system in acute pancreatitis. Inhibition of complement activation prevents its adverse effects on vascular function and permeability, and thus stabilises intravascular fluid status and prevents multiorgan failure in acute pancreatitis.

Acute Disease↗
PubMed1998

Endothelial dysfunction after bone marrow transplantation: increase of soluble thrombomodulin and PAI-1 in patients with multiple transplant-related complications.

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.

Adolescent↗
PubMed1998

Hepatic veno-occlusive disease with severe capillary leakage after peripheral stem cell transplantation: treatment with recombinant plasminogen activator and C1-esterase inhibitor concentrate.

Severe veno-occlusive disease (VOD), characterised by elevated serum bilirubin levels, is a known complication in the first 3 weeks after peripheral blood stem cell transplantation (PBSCT). Severe VOD is associated with capillary leakage and multiple organ dysfunction and leads to high mortality. We report a 17-year-old male, who developed VOD with capillary leakage (CL) after allogeneic PBSCT. The patient presented with a maximum serum bilirubin of 25.4 mg/dl, weight gain (10% of baseline weight), generalized edema, cardiovascular insufficiency, complement activation, jaundice and a decreased AT and protein C functional activity. After VOD and CL were diagnosed the patient was treated with recombinant human plasminogen activator (rt-PA) and C1 esterase-inhibitor concentrate (C1-INH-C). The clinical symptoms resolved and the patient's status stabilized. The patient was in an adequate clinical state 5 months after transplantation. We noted that the combined therapy with rt-PA and C1-INH-C in this high-risk situation led to a resolution of VOD with CL.

Adolescent↗