R Erttmann

University Medical Center Hamburg - Eppendorf, Hamburg, Hamburg, Germany

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Publications (112)488.35 Total impact

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    ABSTRACT: Patients with metastatic rhabdomyosarcoma (RMS) have a poor prognosis. The aim of this systematic review is to investigate whether high-dose chemotherapy (HDCT) followed by autologous hematopoietic stem cell transplantation (HSCT) in patients with metastatic RMS has additional benefit or harm compared to standard chemotherapy. Systematic literature searches were performed in MEDLINE, EMBASE, and The Cochrane Library. All databases were searched from inception to February 2010. PubMed was searched in June 2010 for a last update. In addition to randomized and non-randomized controlled trials, case series and case reports were included to complement results from scant data. The primary outcome was overall survival. A meta-analysis was performed using the hazard ratio as primary effect measure, which was estimated from Cox proportional hazard models or from summary statistics of Kaplan Meier product-limit estimations. A total of 40 studies with 287 transplant patients with metastatic RMS (age range 0 to 32 years) were included in the assessment. We identified 3 non-randomized controlled trials. The 3-year overall survival ranged from 22% to 53% in the transplant groups vs. 18% to 55% in the control groups. Meta-analysis on overall survival in controlled trials showed no difference between treatments. Result of meta-analysis of pooled individual survival data of case series and case reports, and results from uncontrolled studies with aggregate data were in the range of those from controlled data. The risk of bias was high in all studies due to methodological flaws. HDCT followed by autologous HSCT in patients with RMS remains an experimental treatment. At present, it does not appear justifiable to use this treatment except in appropriately designed controlled trials.
    PLoS ONE 02/2011; 6(2):e17127. DOI:10.1371/journal.pone.0017127 · 3.23 Impact Factor
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    ABSTRACT: For patients with myeloid malignancies who relapse after allogeneic stem cell transplantation (allo-SCT), one salvage option is a second SCT. We retrospectively analyzed outcomes of the second allo-SCT in 25 patients who received at least 2 allografts from related/unrelated donors due to relapse of acute myeloid leukemia, myelodysplastic syndrome or myelofibrosis after the first SCT. A minority of the acute myeloid leukemia/myelodysplastic syndrome patients had reached complete hematological remission before the second SCT (6/25, 24%). Reduced conditioning strategies were performed in the majority (n = 23). Complete remission was achieved in all 21 cases with available data after the second SCT, but relapse was seen in 11/25 patients (44%). After a median follow-up of 18 months (range 6-47), 8/25 patients (32%) were still alive, and of those, 6 (24%) were in stable remission. In 9 cases mortality was associated to relapse and in 8 cases to transplant-related causes (treatment-related mortality; 8/25, 32%). In conclusion, a second SCT offers the chance of stable remission for some patients relapsing with a myeloid malignancy after a first allo-SCT, although high treatment-related mortality and relapse rates remain a problem. Efforts should concentrate on an optimization of conditioning strategies, immunosuppression and post-transplant surveillance for this specific situation.
    Acta Haematologica 10/2009; 122(4):185-92. DOI:10.1159/000253025 · 1.12 Impact Factor

  • Acta Haematologica 01/2009; 122:185-192. · 1.12 Impact Factor
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    ABSTRACT: Neuroblastoma (NBL) is a tumor from neural crest cells, and is the most frequent solid tumor in children. Midkine (MK) is a pleiotropin analogon, which is frequently expressed in neuronal and epithelial tumors and is a marker for a poor clinical outcome. The aims of this study were to assess MK expression in NBL and investigate the correlation with clinical outcome. Fifty-six specimens of NBL were stained for MK on a tissue microarray by immunohistochemistry (IHC). Fresh frozen tumor tissues were used for RNA isolation, and RT-PCR analysis for MK-mRNA expression was performed. Survival data, risk factors and disease stages were correlated with MK status assessed by IHC and RT-PCR analysis. MK-mRNA expression was found in the majority of the tumor tissues (75%), whereas MK protein could be detected only in 46% of the NBL by IHC. No correlation of MK status with survival, risk factors or disease stage was observed. A majority of NBL express MK-mRNA, whereas not all MK mRNA positive tumors showed also a positive MK IHC staining. The high expression of MK-mRNA expression might present a promising target for new adenovirus-based gene therapeutic approaches for the treatment of NBL.
    Pediatric Surgery International 01/2009; 24(12):1355-9. DOI:10.1007/s00383-008-2263-0 · 1.00 Impact Factor
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    ABSTRACT: For patients lacking an HLA-identical sibling, more than ten million unrelated donor (UD) are available for donation of hematopoietic stem cells. Despite this increasing number of UD, up to 30 % of the patients will not find a completely-HLA-matched donor. HLAmismatched unrelated stem cell transplantation (SCT) is associated with an increased risk of acute and chronic graft-versus-host disease and a higher transplant-related mortality resulting in a lower survival after allogeneic SCT. We analyzed on outcome of allele- and antigen-mismatch SCT from UD using pre-transplantation anti-thymocyte globulin (ATGFresenius ®) at a median dose of 60 mg/kg as part of the conditioning regimen. Between 08/1996 and 12/2004, 369 patients received SCT from UD in our institution. In 268, complete molecular typing (4-digit) of HLA-A, -B, -C, and DRB1, and DQB1 was available for donor as well as for recipient. According to high-resolution HLA-typing, 110 of the patients were completely matched for 10 alleles, whereas 91 patients had at least one allele-mismatch (9/10), 67 patients were mismatched for 2–4 alleles (6–8/10). The median age of patients was 41 years (range, 1–68). Diagnoses were acute leukemia or MDS in 135, chronic myeloproliferative disease (CML or PMF) (n=53), lymphoid malignancy (CLL, NHL, Hodgkin’s disease, MM) (n=60), or others (n=20). Stem cell source was either bone marrow (n=103) or peripheral blood stem cells (n=165). The matched and the mismatched group did not differ significantly between age, sex, risk category, graft source, CMV-status, conditioning, or CD34+ transplanted cells. Two patients (1 %) experienced primary graft-failure and were transplanted from 10/10-matched donors while in none of the mismatch-transplanted patients primary graftfailure occurred. The incidence of grade II–IV acute GvHD was 33 % in the 10/10-matched group, 41 % in the 9/10-mismatch-group, and 40 % in the 6–8/10-mismatch-group (p=0.1). The overall rate of chronic GvHD was 42 % in the 10/10-matched group, 46 % in the 9/10-mismatch group, and 46 % in the 6–8/10-mismatch group (p=0.8). Non-relapse mortality (NRM) in the 10/10-matched group was 27 %, in the 9/10-mismatch group 31 %, and in the 6–8/10-mismatch group 32 % (p=0.2). In a multivariate analysis, only age as continuous variable (HR 1.023) (p<0.001) influenced NRM. There was no difference in the cumulative incidence of relapse between the 10/10-matched, the 9/10-mismatch, and the 6–8/10-mismatch group (28 % vs. 27 % vs. 26 %) (p=0.9). After a median follow-up of 35 months (range, 3–120), the estimated 5-year disease-free survival (DFS) was 42 % and did not differ between the 10/10-matched, the 9/10-mismatch, and the 6–8/10-mismatch group (45 % vs. 42 % vs. 39 %) (p=0.5). In the multivariate analysis, only age (HR 1.013) (p=0.004) and bad-risk disease (HR 1,975) (p<0.001) were independent risk factors for DFS. The estimated 5-year overall survival (OS) at five years was 41 % (95 % CI: 45–57 %) with no difference between the 10/10-matched, the 9/10-mismatch, and the 6–8/10-mismatch group (53 % vs. 55 % vs. 41 %) (p=0.3). In a multivariate analysis, age as con tinuous variable (HR 1.017) (p=0.001), and bad-risk disease (HR 1.920) (p=0.01) were significant factors for OS. The negative impact of HLA-disparity in allogeneic SCT from UD can be overcome by using ATG to prevent GvHD and primary graft failure.
    The American Society of Hematology (ASH), 50th Annual Meeting and Exposition, San Francisco, California, USA; 12/2008
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    ABSTRACT: Hurler's syndrome is an inborn error of mucopolysaccharide metabolism leading to premature death in childhood. Allogeneic hematopoietic SCT can achieve long-term survival by correcting the enzymatic deficiency. In an attempt to improve long-term engraftment and to reduce regimen-related toxicity (RRT), a prospective multicenter approach was initiated in Germany using a fludarabine-based radiation-free preparative regimen. Between 2001 and 2008, 12 children were enrolled. Median age at SCT was 14 months (range, 4-31 months). The conditioning regimen contained fludarabine, BU, melphalan and antithymocyte globulin. CD34 positively selected PBSC were used in 10 children with a matched unrelated donor. Median cell dose was 24.6 x 10(6) CD34+ cells per kg (range 10.0-54.8). Two children with a matched sibling donor received non-manipulated BM. Donor lymphocyte infusions were given in 6/12 children for mixed hematopoietic chimerism. At a median follow-up of 29 months (range 2-85 months), all children engrafted and have either stabilized or improved neurological function. In total, 12/12 patients showed donor-derived engraftment with 9/12 having full and 3/12 having mixed hematopoiesis. One developed acute GVHD >or=grade II. RRT >or=grade II was observed in two patients.
    Bone marrow transplantation 10/2008; 43(5):375-81. DOI:10.1038/bmt.2008.328 · 3.57 Impact Factor
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    ABSTRACT: About one third of patients requiring allogeneic hematopoetic stem cell transplantation (HSCT) would not find a matched sibling or alternative donor. Allogeneic HSCT from matched unrelated and mismatched donors carries an increased risk of graft-vs-host disease (GVHD) and transplant-related mortality (TRM). We used anti-thymocyte globulin (ATG-Fresenius) at a median dose of 90 mg/kg body weight as part of a total body irradiation or busulfan-based conditioning regimen for prevention of serious GVHD. All patients received cyclosporine A and short-course methotrexate. We compared outcomes of 65 recipients of human leukocyte antigen (HLA)-mismatched unrelated grafts and 194 recipients of HLA-matched unrelated grafts. Mismatches involved one or two loci. Both groups were comparable in age, graft source, diagnosis, stage of disease, and conditioning regimen, and differed only in dose of ATG administered. For matched and mismatched transplants, respectively, there was no significant difference in graft failure (0.5% vs 3%; p = 0.16), in the cumulative incidence of grade II to IV acute GVHD (45% vs 35%; p = 0.14) and no difference in overall chronic GVHD (42% vs 40%; p = 0.68). Estimated overall survival (OS) and disease-free survival (DFS) at 5 years were 55% vs 50% (p = 0.99) and 47% vs 47% (p = 1.0), respectively. The cumulative incidence of relapse and TRM at 5 years were 24% vs 25% (p = 0.63), and 29% vs 27% (p = 0.59), respectively. Inclusion of ATG-Fresenius in the conditioning regimen permits HSCT from mismatched unrelated donors without excess TRM and GVHD, resulting in identical OS and DFS of recipients of HLA-matched and HLA-mismatched grafts.
    Experimental Hematology 09/2008; 36(8):1047-54. DOI:10.1016/j.exphem.2008.03.011 · 2.48 Impact Factor
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    ABSTRACT: Antithymocyte globulin (ATG) as part of conditioning regimens is known to reduce the incidence and severity of acute and chronic graft-versus-host disease (aGVHD, cGVHD). The influence of ATG on transplant-related mortality (TRM) and disease-free survival (DFS) is controversial, and may depend on the dose and timing of ATG. We retrospectively compared 2 doses of ATG-Fresenius (ATG-F) in patients undergoing matched unrelated donor allogeneic hematopoetic stem cell transplantation (HSCT) for hematologic malignancies. A dose of 60 mg/kg body weight has previously been recommended for ATG-F. All patients received cyclosporine A and short course methotrexate. ATG-F was administered at a dose of 30 mg/kg on day -1 (ATG-30 group, n = 34) or 20 mg/kg/day on days -3 to -1 (ATG-60 group, n = 49). There was no difference in time to leukocyte and platelet engraftment in the 2 groups. The incidence of aGVHD grade II-IV (50% versus 53%, P = .83) and grade III-IV (27 versus 20%, P = .60) was similar in the ATG-30 versus ATG-60 groups, respectively. There was a trend to a higher incidence of cGVHD in the ATG-30 group (59% versus 40%, P = .14). The estimated 3-year incidence of relapse was similar in the ATG-30 and ATG-60 groups (15% versus 16%, P = .84) whereas the 2-year TRM was lower for the ATG-30 group (12% versus 33%, P = 0.02), mainly because of a higher incidence of fatal infections in the ATG-60 group. This resulted in a better DFS (73% versus 51%, P = .07) for the ATG-30 group. ATG-F (30 mg/kg) administered as a single dose on day -1 may lead to better outcome in patients undergoing unrelated donor allogeneic HSCT compared to 60 mg/kg given in 3 equivalent doses. A prospective randomized study comparing these 2 doses of ATG-F is warranted.
    Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation 08/2008; 14(8):913-9. DOI:10.1016/j.bbmt.2008.05.023 · 3.40 Impact Factor
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    Rudolf Erttmann ·
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    ABSTRACT: Serum of healthy individuals may contain natural antibodies which are able to induce complement dependent cytotoxicity against neuroblastoma. The prevalence of cytotoxic activity in serum of neuroblastoma patients is low compared with age matched healthy children which indicates a role of natural cytotoxic antibodies in immunosurveillance of neuroblastoma. Based on these findings we selected plasma of blood donors with a high in-vitro cytotoxic activity against LA-N-1 neuroblastoma cells. Using these plasma preparations a phase I/II therapy study in children with relapsed neuroblastoma based on a complete plasma exchange has been instituted. 34 plasma exchange cycles have been performed in nine patients. This therapy has been found to be feasible in all patients. In three patients a transient minor tumor response has been observed. In one patient stable disease could be established for 3 years. In another patient, who has got ten therapy cycles, disease-free survival is maintained for 8 years without any further therapy. Conclusion: The response data in patients with relapsed high-risk neuroblastoma justify the further evaluation of this immunotherapeutic approach. For this purpose a standardized pharmaceutical product generated by screening and pooling the plasma of selected blood donors would be of benefit.
    Autoimmunity Reviews 07/2008; 7(6):496-500. DOI:10.1016/j.autrev.2008.03.014 · 7.93 Impact Factor
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    ABSTRACT: Fatal problems encountered in allogeneic stem cell transplantation include EBV reactivation and post transplant lymphoproliferative disorders (PTLDs) with high mortality rates. We performed a retrospective analysis in all consecutive adult and pediatric EBV reactivations and PTLD during a period of 8.5 years. There were 26 patients with EBV reactivation/PTLD out of a total of 854 transplantations giving an overall incidence of 3.0%. Specifically, the incidence of EBV-PTLD was 1.3%, whereas that of EBV reactivation was 1.8%. Median age was 46.0 and 11.0 years in the adult and pediatric patients, respectively. There were high rates (54%) of concomitant bacterial, viral, fungal and parasitic infections at the time of EBV manifestation. Variable treatment regimens were applied including in most cases an anti-CD20 regimen often in combination with virustatic compounds, polychemotherapy or donor lymphocytes. The mortality rates were 9 of 11 (82%) in patients with EBV-PTLD and 10 of 15 (67%) in patients with reactivation. Only 7 of 26 patients (27%) are alive after a median follow-up of 758 days (range 24-2751). The high mortality rates of EBV reactivation and of EBV-PTLD irrespective of multimodal treatment approaches emphasize standardization and optimization of post transplant surveillance and treatment strategies to improve control of these often fatal complications.
    Bone Marrow Transplantation 07/2008; 42(3):181-6. DOI:10.1038/bmt.2008.150 · 3.57 Impact Factor
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    ABSTRACT: Background: Patients with a history of or ongoing invasive fungal infection (IFI) who undergo allogeneic stem cell transplantation (SCT) have a high risk of reactivation or progression.In a prospective study we evaluated the efficacy and safety of caspofungin as secondary prophylaxis or as therapy for persistent disease.Methods: Twenty-eight adult patients were included in this study, all of whom had acute leukemia. At the time of SCT 16 patients had no signs of infection, while in 12 cases radiographic signs (CT scan) of florid fungal infections were noted. Caspofungin 50 mg intravenously was given daily from start of conditioning until stable engraftment.Results: No patient experienced side effects leading to the discontinuation of caspofungin. In 14 out of 16 patients (88 %) without active signs of infection at start of transplantation, no fungal disease was observed after prophylaxis with caspofungin. In 10 out of 12 cases (83 %) with radiographic signs of florid fungal infection pre-transplantation, complete (n=4) or partial (n=6) responses after caspofungin treatment were achieved.Conclusions: The use of caspofungin is safe and effective in high-risk patients with a history of IFI when undergoing allogeneic SCT.
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    ABSTRACT: Neuroblastoma (NBL) is the most common solid tumor in children. Tumors in advanced stage or with positive risk factors still have a poor prognosis. Thy1 (CD90) is a membrane glycoprotein expressed in thymus, retinal ganglionic cells, and several types of stem cells. The aim of this study was to assess Thy1 expression in NBL and analyze the correlation with clinical outcome. Sixty-three specimens of NBL were stained for Thy1 on a tissue microarray by immunohistochemistry. Fresh frozen tumor tissues were used for RNA isolation, and RT-PCR analysis for Thy1-mRNA expression was performed. Patients' survival data were correlated with Thy1 status using a log rank test and a Cox regression multivariate analysis. Thy1 was expressed on 51 (81%) of the tumors. Kaplan-Meier survival analysis showed a significantly impaired survival in patients with NBL missing Thy1 (P < 0.005 by log-rank test). A multivariate Cox regression showed an independent prognostic value of Thy1 status for overall survival (P < 0.05). In addition, the frequency of events and deaths was significantly higher in the group of patients with Thy1 negative tumors, as assessed by ANOVA analysis (P < 0.05 by F-test). The data showed that Thy1-negative NBL patients have a significantly impaired overall survival compared with Thy1-positive NBL patients. Thus, Thy1 seemed to be a marker with a specific prognostic value in NBL patients. Future studies are aiming at the biological role of this marker in the tumor cell differentiation.
    Pediatric Surgery International 01/2008; 24(1):101-5. DOI:10.1007/s00383-007-2033-4 · 1.00 Impact Factor
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    ABSTRACT: Neuroblastoma is the most common solid tumor in childhood with unconventional clinical behavior. L1, a neuronal cell adhesion molecule, is associated with poor survival in malignant adult tumors. The aim of the current study was to determine expression of L1 in pediatric neuroblastoma. L1 expression was assessed on a tissue microarray with 66 surgically resected neuroblastoma samples by immunohistochemistry with a monoclonal antibody and peroxidase method. Additionally, mRNA expression was analyzed by reverse transcriptase-polymerase chain reaction with L1-specific primers. Data were correlated survival data by log rank test and Cox regression multivariate analysis. L1 was detected in 57 (86%) of 66 neuroblastomas, whereas 9 (14%) were L1 negative. Median survival of all children was 72 months. Analysis with Kaplan-Meier method revealed a surprising and contrary finding to adult tumor entities: an association of L1 positivity with better event-free and overall survival (P < .001 and P < .01 by log rank test). Multivariate Cox regression analysis showed an independent prognostic impact of L1 negativity for event-free and overall survival of the children (P < .05). In contrast to adult tumor entities, where L1 is associated with aggressive clinical behavior, our data show that L1 predicts good outcome in children with neuroblastoma. This novel finding suggests an inverse role of L1 in neuroblastoma. Future studies might focus on the molecular basis of the varying effect of L1 in different tumors.
    Annals of Surgical Oncology 12/2007; 14(12):3575-80. DOI:10.1245/s10434-007-9608-0 · 3.93 Impact Factor
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    ABSTRACT: Allogeneic hemopoietic stem cell transplantation of matched unrelated donors carries an increased risk of graft versus host disease (GvHD) and transplant related mortality (TRM). We introduced ATG Fresenius at median dose of 90 mg/kg body weight as part of the conditioning regimen for prevention of serious GvHD. We compared 48 recipients of mismatched transplants with 170 recipients of an HLA-matched transplant. The mismatches involved one or two loci. The groups differed in age [HLA-matched: 33 years (0,9–61) HLA-mismatched: 21 years (0,9–51)] and graft source, bone marrow versus peripheral blood stem cell (matched 67% bone marrow, mismatched 83% bone marrow). They were comparable in diagnosis, stage of disease and conditioning. Key words: Mismatched unrelated donor, anti-thymocyte-globuline, stem cell transplantation
    10/2007: pages 263-274;
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    ABSTRACT: We report the results of 84 patients with ALL after related (n = 46) or unrelated (n = 38) allogeneic SCT. Mean recipient age was 23 years (range: 1-60) and median follow-up was 18 months (range: 1-133). Forty-three patients were transplanted in CR1; 25 in CR2 or CR3; four were primary refractory; four in PR; eight in relapse. The conditioning regimen consisted of TBI/VP16/CY (n = 76), TBI/VP16 (n = 2), TBI/CY (n = 2), Bu/VP16/CY (n = 4). The OS at 3 years was 45% (44% unrelated, 46% related). Univariate analysis showed a significantly better OS for patients <18 years (P=0.03), mismatched sex-combination (P = 0.03), both with a stronger effect on increasing OS after unrelated SCT. Factors decreasing TRM were patient age <18 years (P = 0.004), patient CMV-seronegativity (P = 0.014), female recipient (P = 0.04). There was no significant difference in TRM and the relapse rate was similar in both donor type groups. Multivariate analysis showed that factors for increased OS which remained significant were mismatched sex-combination (RR: 0.70,95% CI: 0.51-0.93, P = 0.015), patient age < 18 years (RR: 0.66, 95% CI: 0.47-0.93, P = 0.016). A decreased TRM was found for female patients (RR: 0.56, 95% CI: 0.33-0.98, P=0.042), negative CMV status of the patient (RR: 0.57, 95% CI: 0.36-0.90, P = 0.015). Unrelated stem cell transplantation for high-risk ALL patients with no HLA-compatible family donor is justifiable.
    Bone Marrow Transplantation 01/2006; 37(2):155-63. DOI:10.1038/sj.bmt.1705221 · 3.57 Impact Factor
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    ABSTRACT: The thiazolidinedione (TZD) or glitazone class of peroxisome proliferator-activated-gamma (PPAR-gamma) ligands not only induce adipocyte differentiation and increase insulin sensitivity, but also exert growth inhibitory effects on several carcinoma cell lines in vitro as well as in vivo. In the current study the in vitro effect of four PPAR-gamma agonists (ciglitazone, pioglitazone, troglitazone, rosiglitazone) on the cell growth of seven human neuroblastoma cell lines (Kelly, LAN-1, LAN-5, LS, IMR-32, SK-N-SH, SH-SY5Y) was investigated. Growth rates were assessed by a colorimetric XTT-based assay kit. Expression of PPAR-gamma protein was examined by immunohistochemistry and Western blot analysis. All glitazones inhibited in vitro growth and viability of the human neuroblastoma cell lines in a dose-dependent manner showing considerable effects only at high concentrations (10 microM and 100 microM). Effectiveness of the glitazones on neuroblastoma cell growth differed depending on the cell line and the agent. The presence of PPAR-gamma protein was demonstrated in all cell lines. Our findings indicate that ligands for PPAR-gamma may be useful therapeutic agents for the treatment of neuroblastoma. Thus the effect of glitazones on the growth of neuroblastoma should now be investigated in an in vivo animal model.
    Toxicology 10/2005; 213(1-2):157-68. DOI:10.1016/j.tox.2005.05.024 · 3.62 Impact Factor
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    ABSTRACT: Myeloablative megatherapy is commonly used to improve the poor outlook of children with high-risk neuroblastoma, yet its role is poorly defined. We aimed to assess whether megatherapy with autologous stem-cell transplantation could increase event-free survival and overall survival compared with maintenance chemotherapy. 295 patients with high-risk neuroblastoma (ie, patients with stage 4 disease aged older than 1 year or those with MYCN-amplified tumours and stage 1, 2, 3, or 4S disease or stage 4 disease and <1 year old) were randomly assigned to myeloablative megatherapy (melphalan, etoposide, and carboplatin) with autologous stem-cell transplantation (n=149) or to oral maintenance chemotherapy with cyclophosphamide (n=146). The primary endpoint was event-free survival. Secondary endpoints were overall survival and the number of treatment-related deaths. Analyses were done by intent to treat, as treated, and treated as randomised. Intention-to-treat analysis showed that patients allocated megatherapy had increased 3-year event-free survival compared with those allocated maintenance therapy (47% [95% CI 38-55] vs 31% [95% CI 23-39]; hazard ratio 1.404 [95% CI 1.048-1.881], p=0.0221), but did not have significantly increased 3-year overall survival (62% [95% CI 54-70] vs 53% [95% CI 45-62]; 1.329 [0.958-1.843], p=0.0875). Improved 3-year event-free survival and 3-year overall survival were also recorded for patients given megatherapy in the as-treated group (n=212) and in the treated-as-randomised group (n=145). Two patients died from therapy-related complications during induction treatment. No patients given maintenance therapy died from acute treatment-related toxic effects. Five patients given megatherapy died from acute complications related to megatherapy. Myeloablative chemotherapy with autologous stem-cell transplantation improves the outcome for children with high-risk neuroblastoma despite the raised risk of treatment-associated death.
    The Lancet Oncology 09/2005; 6(9):649-58. DOI:10.1016/S1470-2045(05)70291-6 · 24.69 Impact Factor
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    ABSTRACT: Current matching procedures neglect HLA-DPB1 as a relevant transplantation antigen, because the stimulatory effect of HLA-DPB1 on the mixed lymphocyte reaction is secondary to HLA-DRB1. Due to a hot spot of recombination matching for DRB1 did not result in matching for DPB1 in the majority of unrelated stem cell transplants. Whether prospective matching for HLA-DPB1 would be worthwhile is a matter of debate. We studied therefore the impact of DPB1 matching in 205 recipients who were treated with an unrelated stem cell transplant with a conditioning regimen including ATG to prevent GVHD. HLA-DPB1 identity was observed in 11%. Overall survival was 63±19% in the HLA-DPB1 identical and 43±11% in HLA-DPB1 different transplant group, which was not signifi cant in the log rank test. Results were similar when differences in Host-versus-Graft direction were counted only. But when differences in the Graft-versus-Host vector were counted, the overall survival was 78±22% in the DP compatible group compared to 41±11 in the DPB1 mismatched group. This result is at the edge of signifi cance with a log rank P=0.07 and a hazard ratio of 0.4 (0.2-1.1). In conclusion, if multivariate analysis confi rms this observation, prospective matching for HLA-DPB1 would be the next step to improve donor selection for unrelated stem cell transplantation.
    19th European Histocompatibility Conference of the European Federation for Immunogenetics (EFI), Istanbul, Turkey.; 04/2005
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    ABSTRACT: In Germany, neuroblastoma is the most frequent extracranial solid childhood tumour. Its properties made it seem an ideal candidate for screening. A German trial assessed the effect of screening at one year of age from 1995-2001 in a nationwide project. We present here the methods developed for the estimation of lead-time and overdiagnosis in this project. Follow up on 1.5 million screened children and 2.1 million control children is currently available until June 2002. Ascertainment of control cohort cases and false negative cases is complete up to this date. A method for determining an empirical lead-time distribution and overdiagnosis estimate from comparing the age specific incidences in the control group and the study group is presented. Lead-time leads to an excess of cases in the screening group at the screening age and cases missing at higher age. If more cases are observed at the screening age than can be explained by lead-time, the difference is attributed to overdiagnosis. The width of the screening age window and the empirical maximum lead-time have to be chosen from graphs. About 1.0/100000 cases (20 per cent of the possible cases) experienced lead-time while 6.8/100000 cases were overdiagnosed. The mean lead-time was estimated to be about 15 months. The number of cases who might benefit is much smaller than was expected before the study while the overdiagnosed group is much larger. The method is robust against the choices that have to be made in the estimation process.
    Statistics in Medicine 10/2003; 22(18):2877-92. DOI:10.1002/sim.1533 · 1.83 Impact Factor
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    ABSTRACT: Neuroblastoma is the second most frequent malignancy in childhood. We investigated whether screening for neuroblastoma at 1 year of age reduces the incidence of metastatic disease or mortality. Screening was offered in 6 of the 16 German states from 1995 to 2000 with the remaining states serving as controls. We studied 2,581,188 children in the screening area born between 1994 and 1999 and 2,117,600 in the control area. We compared mortality from neuroblastoma and the incidence of disseminated disease in the two groups. The screened group and the control group had similar rates of stage 4 neuroblastoma and mortality due to neuroblastoma. Comparison of the screened group and the control area revealed substantial over diagnosis in the screened participants. The present findings provide no support for mass screening for neuroblastoma at 1 year of age.
    Cancer Letters 08/2003; 197(1-2):19-28. DOI:10.1016/S0304-3835(03)00077-6 · 5.62 Impact Factor

Publication Stats

3k Citations
488.35 Total Impact Points


  • 1986-2011
    • University Medical Center Hamburg - Eppendorf
      • • Department of Paediatric Haematology and Oncology
      • • Bone Marrow Transplantation Unit
      Hamburg, Hamburg, Germany
  • 1985-2009
    • University of Hamburg
      • Department of Paediatric Haematology and Oncology
      Hamburg, Hamburg, Germany
  • 1999
    • Gesellschaft für Pädiatrische Onkologie und Hämatologie
      Hamburg, Hamburg, Germany
  • 1997-1999
    • Hannover Medical School
      • Clinic for Paediatric Surgery
      Hanover, Lower Saxony, Germany
  • 1994
    • St Anna's Kinderspital
      Wien, Vienna, Austria
  • 1991
    • University of Iowa Children's Hospital
      Iowa City, Iowa, United States