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Dive into the research topics where Stefanie Buchholz is active.

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Featured researches published by Stefanie Buchholz.


Lancet Oncology | 2012

Reduced-intensity conditioning versus standard conditioning before allogeneic haemopoietic cell transplantation in patients with acute myeloid leukaemia in first complete remission: a prospective, open-label randomised phase 3 trial

Martin Bornhäuser; Joachim Kienast; Rudolf Trenschel; Andreas Burchert; Ute Hegenbart; Michael E. Stadler; Herrad Baurmann; Kerstin Schäfer-Eckart; Ernst Holler; Nicolaus Kröger; Christoph Schmid; H. Einsele; Michael Kiehl; Wolfgang Hiddemann; Rainer Schwerdtfeger; Stefanie Buchholz; Peter Dreger; Andreas Neubauer; Wolfgang E. Berdel; Gerhard Ehninger; Dietrich W. Beelen; Johannes Schetelig; Matthias Stelljes

BACKGROUND Reduced-intensity conditioning regimens have been developed to minimise early toxic effects and deaths after allogeneic haemopoietic cell transplantation. However, the efficacy of these regimens before this procedure has not been investigated in a randomised trial. In this prospective, open-label randomised phase 3 trial we compared a reduced-intensity fludarabine-based conditioning regimen with a standard regimen in patients with acute myeloid leukaemia in first complete remission. METHODS Patients were aged 18-60 years and had intermediate-risk or high-risk acute myeloid leukaemia (defined by cytogenetics) in first complete remission; an available HLA-matched sibling donor or an unrelated donor with at least nine of ten HLA alleles; and adequate renal, cardiac, pulmonary, and neurological function. Between Nov 15, 2004, and Dec 31, 2009, patients were randomly assigned (1:1, by a computer-based minimisation procedure that balanced patients for age, cytogenetic risk, induction therapy, and donor type) to receive either reduced-intensity conditioning of four doses of 2 Gy of total-body irradiation and 150 mg/m(2) fludarabine or standard conditioning of six doses of 2 Gy of total-body irradiation and 120 mg/kg cyclophosphamide. All patients were given ciclosporin and methotrexate as prophylaxis against graft-versus-host disease. Neither investigators nor patients were blinded to study treatment. Our primary endpoint was the incidence of non-relapse mortality, analysed in the intention-to-treat population. The trial is registered with ClinicalTrials.gov, number NCT00150878. FINDINGS The trial was stopped early on Dec 31, 2009, because of slow accrual of patients. 99 patients were randomly assigned to receive reduced-intensity conditioning and 96 to receive standard conditioning. The incidence of non-relapse mortality did not differ between the reduced-intensity and standard conditioning groups (cumulative incidence at 3 years 13% [95% CI 6-21] vs 18% [10-26]; HR 0·62 [95% CI 0·30-1·31]). Relapse incidence (cumulative incidence 3 years 28% [95% CI 19-38] vs 26% [17-36]; HR 1·10 [95% CI 0·63-1·90]), disease-free survival (3 year disease-free survival 58% [95% CI 49-70] vs 56% [46-67]; HR 0·85 [95% CI 0·55-1·32]), and overall survival (3 year overall survival 61% [95% CI 50-74] vs 58% [47-70]; HR 0·77 [95% CI 0·48-1·25]) did not differ significantly between groups. Grade 3-4 of oral mucositis was less common in the reduced-intensity group than in the standard conditioning group (50 patients in the reduced-intensity conditioning group vs 73 patients in the standard conditioning group); the frequency of other side-effects such as graft-versus-host disease and increased concentrations of bilirubin and creatinine did not differ significantly between groups. INTERPRETATION Reduced-intensity conditioning results in a similar incidence of non-relapse mortality and reduced toxic effects compared with standard conditioning without affecting survival outcomes, and thus could be preferentially used in patients younger than 60 years with acute myeloid leukaemia transplanted in first complete remission.


Blood | 2011

Human regulatory T cells in allogeneic stem cell transplantation.

Sya N. Ukena; Sarvari Velaga; Robert Geffers; Jens Grosse; Udo Baron; Stefanie Buchholz; Michael Stadler; Dunja Bruder; Arnold Ganser; Anke Franzke

GVHD is still one of the major complications after allogeneic stem cell transplantation. Whereas murine data have clearly shown the beneficial effects of regulatory T cells (Tregs) on the prevention of GVHD, data from the human system are rare. Here, we present a comparative dynamic analysis of CD4(+)CD25(hi)CD127(lo/-) Tregs from patients with and without GVHD analyzing the whole genome profile over the first 6 months after stem cell transplantation, representing the most sensitive time window for tolerance induction. The Treg transcriptome showed a high stability. However, the comparison of Treg transcriptomes from patients with and without GVHD uncovered regulated gene transcripts highly relevant for Treg cell function. The confirmative protein analyses demonstrated a significantly higher expression of granzyme A, CXCR3, and CCR5 in Tregs of immune tolerant patients. These results point to a reduced suppressive function of Tregs from GVHD patients with diminished migration capacity to the target organs.


Blood | 2009

Limited efficacy of imatinib in severe pulmonary chronic graft-versus-host disease

Michael Stadler; Renate Ahlborn; Haytham Kamal; Helmut Diedrich; Stefanie Buchholz; Matthias Eder; Arnold Ganser

To the editor: We read with interest that Olivieri et al[1][1] observed complete or partial responses to imatinib 100 or 200 mg daily with improvement of lung function in 7 of 11 patients (64%) with pulmonary chronic graft-versus-host disease (cGVHD) of mild severity (lung function score [LFS] of


European Journal of Haematology | 2012

Cytoreductive treatment with clofarabine/ara‐C combined with reduced‐intensity conditioning and allogeneic stem cell transplantation in patients with high‐risk, relapsed, or refractory acute myeloid leukemia and advanced myelodysplastic syndrome

Stefanie Buchholz; Elke Dammann; Michael Stadler; Juergen Krauter; Gernot Beutel; Arne Trummer; Matthias Eder; Arnold Ganser

The combination of cytoreductive chemotherapy with reduced‐intensity conditioning (RIC) is a highly effective antileukemic therapy. Purpose of this retrospective analysis was to evaluate the antileukemic efficacy and toxicity of clofarabine‐based chemotherapy followed by RIC and allogeneic stem cell transplantation (SCT) for high‐risk, relapsed, or refractory acute myeloid leukemia (AML) or myelodysplastic syndromes (MDS). From May 2007 until October 2009, a total of 27 patients underwent allogeneic SCT after treatment with clofarabine and ara‐C for 5 d and RIC (4 Gy TBI/cyclophosphamide/ATG). Prophylaxis of graft‐versus‐host disease (GvHD) consisted of cyclosporine and mycophenolate mofetil. Unmanipulated G‐CSF mobilized PBSC (n = 26) or bone marrow cells (n = 1) were transplanted from unrelated (n = 21) or matched related (n = 6) donors. Non‐hematological toxicities of this regimen mainly affected liver and skin and were all reversible. Seven patients relapsed within a median time of 5.7 months. The overall survival (OS) and relapse‐free survival rates were 56% and 52% at 2 yr, respectively. In this cohort of patients, cytoreduction with clofarabine/ara‐C (ClAraC) followed by RIC allogeneic SCT was well tolerated and showed good antileukemic efficacy even in patients with high‐risk AML or MDS, with engraftment and GvHD‐incidence comparable to other RIC regimens.


Blood | 2008

Angiopoietin-2 predicts disease-free survival after allogeneic stem cell transplantation in patients with high-risk myeloid malignancies

Philipp Kümpers; Christian Koenecke; Hartmut Hecker; Julian Hellpap; Rüdiger Horn; Willem Verhagen; Stefanie Buchholz; Bernd Hertenstein; Jürgen Krauter; Matthias Eder; Sascha David; Gudrun Göhring; Hermann Haller; Arnold Ganser

Emerging data suggest a critical role for bone marrow angiogenesis in hematologic malignancies. The angiopoietin/Tie ligand-receptor system is an essential regulator of this process. We evaluated whether circulating angiopoietin-2 (Ang-2) is a predictor for the probability of disease-free survival (DFS) in allogeneic hematopoietic stem cell transplantation (allo-HSCT) for high-risk acute myeloid leukemia or myelodysplastic syndrome. Ang-2 was measured by enzyme-linked immunosorbent assay in serum from 20 healthy controls and 90 patients with acute myeloid leukemia or myelodysplastic syndrome before conditioning for HSCT. Circulating Ang-2 was elevated in patients (median, 2.21 ng/mL; range, 0.18-48.84 ng/mL) compared with controls (median, 0.87 ng/mL; range, 0.27-4.51 ng/mL; P < .001). Multivariate analyses confirmed the independent prognostic impact of Ang-2 (hazard ratio [HR] = 2.46; 95% confidence interval [CI], 1.27-4.76, P = .005), percentage of bone marrow infiltration (HR = 1.14; 95% CI, 1.01-1.29, P = .033), and chemotherapy cycles before HSCT (HR = 1.38; 95% CI, 1.01-1.08, P = .048). Regression tree analysis detected optimal cutoff values for Ang-2 and recursively identified bone marrow blasts and Ang-2 as the best predictors for DFS. Because few predictors for DFS exist in the setting of allo-HSCT, Ang-2 may be used as a readily available powerful biomarker to pre-estimate DFS and may open new perspectives for risk-adapted treatment of high-risk myeloid malignancies.


Journal of Clinical Virology | 2011

High lethality of human adenovirus disease in adult allogeneic stem cell transplant recipients with high adenoviral blood load

Tina Ganzenmueller; Stefanie Buchholz; Gabi Harste; Elke Dammann; Rudolf Trenschel; Albert Heim

BACKGROUND Human adenoviruses (HAdV) can cause disseminated disease as a severe complication after haematopoietic stem cell transplantation (SCT) and may originate from the reactivation of latent infections. However, data about the clinical relevance of HAdV DNAaemia and disease in adults are scarce. OBJECTIVES To retrospectively analyse the outcome of adult allogeneic SCT recipients with high HAdV loads in peripheral blood. STUDY DESIGN Our diagnostic database was screened for allogeneic SCT recipients with peak HAdV DNAaemia above 1.0×10(4)copies/ml (tested by quantitative real-time PCR) and medical records were reviewed retrospectively. RESULTS From 1674 adult allogeneic SCT recipients 539 (32.2%) received HAdV DNAaemia testing. In twenty-seven of these HAdV blood loads above 1.0×10(4) (range: 1.6×10(4)-1.8×10(9))copies/ml were observed. Seven of these 27 succumbed to HAdV disease and their median peak HAdV DNAaemia was significantly higher than in patients without HAdV-associated death (1.0×10(8) vs. 3×10(5)copies/ml, p<0.001). T-cell depletion was a risk factor for fatal HAdV disease. HAdV of species C predominated (66.7%) and were of high virulence (6 of 7 fatal cases). HAdV of species B were observed more frequently (n=6) in our study than reported for paediatrics, indicating a different pattern of HAdV reactivation in adults. CONCLUSIONS The presence of several HAdV-associated deaths in adult SCT recipients with high-level HAdV DNAaemia confirmed the clinical relevance of HAdV DNAaemia testing in adults. Quantitative HAdV DNAaemia testing is a promising tool to predict the outcome of HAdV disease.


Transplant Infectious Disease | 2011

Tetramer monitoring to assess risk factors for recurrent cytomegalovirus reactivation and reconstitution of antiviral immunity post allogeneic hematopoietic stem cell transplantation

Sylvia Borchers; Susanne Luther; U. Lips; Norbert Hahn; Julia Kontsendorn; Michael Stadler; Stefanie Buchholz; Helmut Diedrich; Matthias Eder; Ulrike Koehl; Arnold Ganser; Eva Mischak-Weissinger

S. Borchers, S. Luther, U. Lips, N. Hahn, J. Kontsendorn, M. Stadler, S. Buchholz, H. Diedrich, M. Eder, U. Koehl, A. Ganser, E. Mischak‐ Weissinger. Tetramer monitoring to assess risk factors for recurrent cytomegalovirus reactivation and reconstitution of antiviral immunity post allogeneic hematopoietic stem cell transplantation.
Transpl Infect Dis 2011: 13: 222–236. All rights reserved


Transplant Infectious Disease | 2012

Chronic hepatitis E in hematopoietic stem cell transplant patients in a low-endemic country?

Christian Koenecke; Sven Pischke; Albert Heim; L. Raggub; B. Bremer; R. Raupach; Stefanie Buchholz; Thomas F. Schulz; Michael P. Manns; Arnold Ganser; Heiner Wedemeyer

Cases of chronic hepatitis E have been described in patients after kidney and liver transplantation. In addition, hepatitis E virus (HEV) reactivation was reported after hematopoietic stem cell transplantation (HSCT). We here evaluated if HEV infection might explain elevated liver enzymes in a well selected cohort of allogeneic HSCT patients with biochemical evidence of hepatitis (n = 52). Of note, none of the subjects tested positive for HEV RNA, including 2 HSCT patients who had been infected with HEV already before transplantation. Thus, both chronic courses of HEV infections and HEV reactivations seem to be rather rare events in HSCT patients in a non‐endemic country.


European Journal of Haematology | 2012

Clofarabine-containing conditioning regimen for allo-SCT in AML/ALL patients: a survey from the Acute Leukemia Working Party of EBMT.

Patrice Chevallier; Myriam Labopin; Stefanie Buchholz; Arnold Ganser; Fabio Ciceri; Bruno Lioure; Chistoph Faul; Gaelle Guillerm; J Finke; Anne Huynh; Joerg Schubert; Hans Jochem Kolb; Emmanuelle Polge; Arnon Nagler; Mohamad Mohty

Clofarabine (CLO), a second‐generation purine analogue, has demonstrated an efficient anti‐leukemia activity while showing a favorable toxicity profile. This retrospective multicenter report assessed the outcome of 90 patients who received a CLO‐containing conditioning regimen before allo‐SCT for AML (n = 69) or ALL (n = 21). Median age was 42 yr at transplant. The majority of cases (n = 66) presented with an active disease at transplant while 38 patients had received previous transplantation(s). A total of 88 and two patients received a reduced‐intensity conditioning or a myeloablative regimen, respectively. Engraftment was achieved in 97% of evaluable patients. With a median follow‐up of 14 months (range, 1–45), the 2‐year OS, LFS, relapse, and NRM rates were 28 ± 5%, 23 ± 5%, 41 ± 6%, and 35 ± 5%, respectively. When comparing AML and ALL patients, OS and LFS were significantly higher for AML (OS, 35 ± 6% vs. 0%, P < 0.0001); LFS: 30 ± 6% vs. 0%, P < 0.0001). In a Cox multivariate analysis, an AML diagnosis was the only factor associated with a better LFS (HR = 0.37; 95%CI, 0.21–0.66; P = 0.001). We conclude that a CLO‐containing conditioning regimen prior to allo‐SCT might be an effective treatment. Prospective studies are needed to evaluate the potential role of CLO as part of conditioning regimens in acute leukemias.


Haematologica | 2013

Influence of molecular subgroups on outcome of acute myeloid leukemia with normal karyotype in 141 patients undergoing salvage allogeneic stem cell transplantation in primary induction failure or beyond first relapse

Tim Pfeiffer; Michael Schleuning; Jiří Mayer; Karl Heinz Haude; Johanna Tischer; Stefanie Buchholz; Donald Bunjes; Gesine Bug; Ernst Holler; Ralf G. Meyer; Hildegard Greinix; Christof Scheid; Maximilian Christopeit; Susanne Schnittger; Jan Braess; Günter Schlimok; Karsten Spiekermann; Arnold Ganser; Hans Jochem Kolb; Çhristof C. Schmid

Based on molecular aberrations, in particular the NPM1 mutation (NPM1mut) and the FLT3 internal tandem duplication (Flt3-ITD), prognostic subgroups have been defined among patients with acute myeloid leukemia with normal karyotype. Whereas these subgroups are known to play an important role in outcome in first complete remission, and also in the indication for allogeneic stem cell transplantation, data are limited on their role after transplantation in advanced disease. To evaluate the role of molecular subgroups of acute myeloid leukemia with normal karyotype after allogeneic stem cell transplantation beyond first complete remission, we analyzed the data from 141 consecutive adults (median age: 51.0 years, range 18.4-69.3 years) who had received an allogeneic transplant either in primary induction failure or beyond first complete remission. A sequential regimen of cytoreductive chemotherapy (fludarabine, high-dose AraC, amsacrine) followed by reduced intensity conditioning (FLAMSA-RIC), was uniformly used for conditioning. After a median follow up of three years, overall survival from transplantation was 64±4%, 53±4% and 44±5% at one, two and four years, respectively. Forty patients transplanted in primary induction failure achieved an encouraging 2-year survival of 69%. Among 101 patients transplanted beyond first complete remission, 2-year survival was 81% among patients with the NPM1mut/FLT3wt genotype in contrast to 43% in other genotypes. Higher numbers of transfused CD34+ cells (hazard ratio 2.155, 95% confidence interval 0.263-0.964, P=0.039) and favorable genotype (hazard ratio 0.142, 95% confidence interval: 0.19-0.898, P=0.048) were associated with superior overall survival in multivariate analysis. In conclusion, patients with acute myeloid leukemia with normal karyotype can frequently be rescued after primary induction failure by allogeneic transplantation following FLAMSA-RIC. The prognostic role of NPM1mut/FLT3-ITD based subgroups was carried through after allogeneic stem cell transplantation beyond first complete remission.

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Elke Dammann

Hannover Medical School

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