14 results on '"Dreger, Peter"'
Search Results
2. Continuously improving outcome over time after second allogeneic stem cell transplantation in relapsed acute myeloid leukemia: an EBMT registry analysis of 1540 patients.
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Schmälter, Ann-Kristin, Ngoya, Maud, Galimard, Jacques-Emmanuel, Bazarbachi, Ali, Finke, Jürgen, Kröger, Nicolaus, Bornhäuser, Martin, Stelljes, Matthias, Stölzel, Friedrich, Tischer, Johanna, Schroeder, Thomas, Dreger, Peter, Blau, Igor-Wolfgang, Savani, Bipin, Giebel, Sebastian, Esteve, Jordi, Nagler, Arnon, Schmid, Christoph, Ciceri, Fabio, and Mohty, Mohamad
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STEM cell transplantation ,ACUTE myeloid leukemia ,GRAFT versus host disease - Abstract
Second allogeneic stem cell transplantation (alloSCT2) is among the most effective treatments for acute myeloid leukemia (AML) relapse after first alloSCT (alloSCT1). Long-term EBMT registry data were used to provide large scale, up-to-date outcome results and to identify factors for improved outcome. Among 1540 recipients of alloSCT2, increasing age, better disease control and performance status before alloSCT2, more use of alternative donors and higher conditioning intensity represented important trends over time. Between the first (2000–2004) and last (2015–2019) period, two-year overall and leukemia-free survival (OS/LFS) increased considerably (OS: 22.5–35%, LFS: 14.5–24.5%). Cumulative relapse incidence (RI) decreased from 64% to 50.7%, whereas graft-versus-host disease and non-relapse mortality (NRM) remained unchanged. In multivariable analysis, later period of alloSCT2 was associated with improved OS/LFS (HR = 0.47/0.53) and reduced RI (HR = 0.44). Beyond, remission duration, disease stage and patient performance score were factors for OS, LFS, RI, and NRM. Myeloablative conditioning for alloSCT2 decreased RI without increasing NRM, leading to improved OS/LFS. Haploidentical or unrelated donors and older age were associated with higher NRM and inferior OS. In summary, outcome after alloSCT2 has continuously improved over the last two decades despite increasing patient age. The identified factors provide clues for the optimized implementation of alloSCT2. [ABSTRACT FROM AUTHOR]
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- 2024
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3. Donor KIR genotype based outcome prediction after allogeneic stem cell transplantation: no land in sight.
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Schetelig, Johannes, Baldauf, Henning, Heidenreich, Falk, Hoogenboom, Jorinde D., Spellman, Stephen R., Kulagin, Alexander, Schroeder, Thomas, Sengeloev, Henrik, Dreger, Peter, Forcade, Edouard, Vydra, Jan, Wagner-Drouet, Eva Maria, Choi, Goda, Paneesha, Shankara, Miranda, Nuno A. A., Tanase, Alina, de Wreede, Liesbeth C., Lange, Vinzenz, Schmidt, Alexander H., and Sauter, Jürgen
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STEM cell transplantation ,NUCLEOTIDE sequencing ,HEMATOPOIETIC stem cell transplantation ,ACUTE myeloid leukemia ,GENOTYPES - Abstract
Optimizing natural killer (NK) cell alloreactivity could further improve outcome after allogeneic hematopoietic cell transplantation (alloHCT). The donor's Killercell Immunoglobulin-like Receptor (KIR) genotype may provide important information in this regard. In the past decade, different models have been proposed aiming at maximizing NK cell activation by activating KIR-ligand interactions or minimizing inhibitory KIR-ligand interactions. Alternative classifications intended predicting outcome after alloHCT by donor KIRhaplotypes. In the present study, we aimed at validating proposed models and exploring more classification approaches. To this end, we analyzed samples stored at the Collaborative Biobank from HLA-compatible unrelated stem cell donors who had donated for patients with acute myeloid leukemia (AML) or myelodysplastic neoplasm (MDS) and whose outcome data had been reported to EBMT or CIBMTR. The donor KIR genotype was determined by high resolution amplicon-based next generation sequencing. We analyzed data from 5,017 transplants. The median patient age at alloHCT was 56 years. Patients were transplanted for AML between 2013 and 2018. Donor-recipient pairs were matched for HLA-A, -B, -C, -DRB1, and -DQB1 (79%) or had single HLA mismatches. Myeloablative conditioning was given to 56% of patients. Fiftytwo percent of patients received anti-thymocyte-globulin-based graft-versushost disease prophylaxis, 32% calcineurin-inhibitor-based prophylaxis, and 7% post-transplant cyclophosphamide-based prophylaxis. We tested several previously reported classifications in multivariable regression analyses but could not confirm outcome associations. Exploratory analyses in 1,939 patients (39%) who were transplanted from donors with homozygous centromeric (cen) or telomeric (tel) A or B motifs, showed that the donor cen B/B-tel A/A diplotype was associated with a trend to better event-free survival (HR 0.84, p=.08) and reduced risk of non-relapse mortality (NRM) (HR 0.65, p=.01). When we further dissected the contribution of B subtypes, we found that only the cen B01/B01- telA/A diplotype was associated with a reduced risk of relapse (HR 0.40, p=.04) while all subtype combinations contributed to a reduced risk of NRM. This exploratory finding has to be validated in an independent data set. In summary, the existing body of evidence is not (yet) consistent enough to recommend use of donor KIR genotype information for donor selection in routine clinical practice. [ABSTRACT FROM AUTHOR]
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- 2024
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4. Evaluation of six different types of sequential conditioning regimens for allogeneic stem cell transplantation in relapsed/refractory acute myelogenous leukemia – a study of the Acute Leukemia Working Party of the EBMT.
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Heinicke, Thomas, Labopin, Myriam, Polge, Emmanuelle, Stelljes, Matthias, Ganser, Arnold, Tischer, Johanna, Brecht, Arne, Kröger, Nicolaus, Beelen, Dietrich W., Scheid, Christof, Bethge, Wolfgang, Dreger, Peter, Bunjes, Donald, Wagner, Eva, Platzbecker, Uwe, Savani, Bipin N., Nagler, Arnon, and Mohty, Mohamad
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ACUTE myeloid leukemia ,STEM cell transplantation ,ACUTE leukemia - Abstract
The Acute Leukemia Working Party (ALWP) of the EBMT assessed the outcome of allogeneic stem cell transplantation (alloSCT) in patients with relapsed/refractory AML (r/rAML) evaluating six sequential conditioning regimens (SR) groups. A total of 2132 patients were included. LFS at 2 years was 28.9%, 33.6%, 35.3%, 20.6%, 24.4%, and 27% for the FLAMSA-TBI4, FLAMSA-Chemo, Mel-Flu-TBI8, Mel-Treo-Flu, Thio-ETO-Cy-Bu2-Flu, and Clo-ARAC-(Bu2/TBI4)-Cy groups, respectively. In patients <55 years of age Mel-Flu-TBI8 had the best LFS, which was statistically significant only in comparison to the Mel-Treo-Flu group, while in patients ≥55 years LFS was best with FLAMSA-Chemo without significant differences compared to FLAMSA-TBI4 and Mel-Flu-TBI8. Furthermore, best NRM rates were obtained with the two FLAMSA regimens groups. Our study suggests that in younger (<55 years) patients a more intense regimen might be used whereas in older (≥55 years) patients the focus might be more on tolerability. [ABSTRACT FROM AUTHOR]
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- 2021
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5. The impact of SAMHD1 expression and mutation status in mantle cell lymphoma: An analysis of the MCL Younger and Elderly trial.
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Roider, Tobias, Wang, Xi, Hüttl, Katrin, Müller‐Tidow, Carsten, Klapper, Wolfram, Rosenwald, Andreas, Stewart, James Peter, Castro, David Gonzalez, Dreger, Peter, Hermine, Olivier, Kluin‐Nelemans, Hanneke C., Grabe, Niels, Dreyling, Martin, Pott, Christiane, Ott, German, Hoster, Eva, and Dietrich, Sascha
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MANTLE cell lymphoma ,ACUTE myeloid leukemia ,CYTARABINE ,B cells ,ENZYME metabolism ,HIV status - Abstract
The sterile alpha motif and histidine‐aspartic domain‐containing protein 1 (SAMHD1) has been demonstrated to predict the response to high‐dose cytarabine consolidation treatment in acute myeloid leukemia patients. Here, we evaluated SAMHD1 as potential biomarker for the response to high‐dose cytarabine in mantle cell lymphoma (MCL) patients. We quantified SAMHD1 protein expression and determined the mutation status in patients of the MCL Younger and Elderly trials (n = 189), who had received high‐dose cytarabine‐ or fludarabine‐based polychemotherapy. Additionally, we quantified SAMHD1 expression in B cell lymphoma cell lines and exposed them to cytarabine, fludarabine, and clinically relevant combinations. Across both trials investigated, SAMHD1 mutations had a frequency of 7.1% (n = 13) and did not significantly affect the failure‐free survival (FFS, P =.47). In patients treated with high‐dose cytarabine‐ or fludarabine‐containing regimes, SAMHD1 expression was not significantly associated with FFS or complete remission rate. SAMHD1 expression in B cell lymphoma cell lines, however, inversely correlated with their in vitro response to cytarabine as single agent (R =.65, P =.0065). This correlation could be reversed by combining cytarabine with other chemotherapeutics, such as oxaliplatin and vincristine, similar to the treatment regime of the MCL Younger trial. We conclude that this might explain why we did not observe a significant association between SAMHD1 protein expression and the outcome of MCL patients upon cytarabine‐based treatment. What's new? While mantle cell lymphoma (MCL) treatment has improved, relapse and unfavorable outcome remain problematic. Here, to better predict therapeutic response in MCL, the authors assessed the biomarker potential of the nucleotide metabolism enzyme SAMHD1. Analyses of patients in the MCL Younger and Elderly trial show that neither SAMHD1 protein expression nor mutation status are associated with failure‐free survival or complete remission rate upon cytarabine‐based treatment in MCL patients. Drug perturbation assays in B cell lymphoma cell lines suggest that high SAMHD1 expression mediates cytarabine resistance as monotherapy but not when combined with other chemotherapeutics, similar to MCL treatment in vivo. [ABSTRACT FROM AUTHOR]
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- 2021
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6. High leukemia-free survival after TBI-based conditioning and mycophenolate mofetil-containing immunosuppression in patients allografted for chronic myelomonocytic leukemia: a single-center experience.
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Radujkovic, Aleksandar, Hegenbart, Ute, Müller-Tidow, Carsten, Herfarth, Klaus, Dreger, Peter, and Luft, Thomas
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CHRONIC leukemia ,TOTAL body irradiation ,ACUTE myeloid leukemia ,GRAFT versus host disease ,IMMUNOSUPPRESSION ,THERAPEUTIC use of antimetabolites ,TREATMENT of chronic myeloid leukemia ,ACUTE myeloid leukemia treatment ,HOMOGRAFTS ,MELPHALAN ,MYCOPHENOLIC acid ,ANTIVIRAL agents ,RETROSPECTIVE studies ,ANTILYMPHOCYTIC serum ,PROGNOSIS ,METHOTREXATE ,ANTIMETABOLITES ,KAPLAN-Meier estimator ,SECONDARY primary cancer ,HEMATOPOIETIC stem cell transplantation ,IMMUNOSUPPRESSIVE agents ,RADIOTHERAPY ,BUSULFAN ,T cells ,PROPORTIONAL hazards models ,THERAPEUTICS - Abstract
This retrospective single-center analysis studied the impact of the conditioning and the graft-versus-host disease (GVHD) prophylaxis on outcome in unselected patients allografted for chronic myelomonocytic leukemia (CMML) and acute myeloid leukemia (AML) secondary to documented prior CMML. A total of 44 patients (median age 61 years) allografted between 2002 and 2019 in our institution were analyzed. Fifteen patients had secondary AML. The conditioning regimen was fractionated 6-8 Gy total body irradiation (TBI) in combination with fludarabine in 33 (75%) patients. Eleven patients (25%) received alkylator-based conditioning therapy without TBI. For GVHD prophylaxis, a calcineurin inhibitor (CNI) backbone in combination with methotrexate (MTX) or mycophenolate mofetil (MMF) was applied in 21 and 23 patients, respectively. All patients allografted from an unrelated donor (UD) received antithymocyte globuline. In univariate analysis of the entire cohort, TBI-based conditioning and MMF-containing immunosuppression were associated with improved leukemia-free survival (LFS, HR 0.16, P < 0.001 and HR 0.41, P = 0.030, respectively). After stratification according to conditioning and GVHD prophylaxis into four groups (TBI-MMF [n = 17], TBI-MTX [n = 16], alkylator-MMF [n = 6], alkylator-MTX [n = 5]), TBI-MMF was associated with improved overall survival (OS) and LFS (P = 0.001 and P < 0.001, respectively). Patient and disease characteristics did not differ between the groups. The associations of TBI-based conditioning and MMF with prolonged LFS were observed across the CMML (n = 29), secondary AML (n = 15), and UD allograft (n = 34) subgroups. In summary, our study suggests that allografting based on intermediate-dose TBI conditioning and MMF-containing GVHD prophylaxis is associated with increased disease control in CMML. Larger (registry-based) studies are warranted to confirm our findings. [ABSTRACT FROM AUTHOR]
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- 2020
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7. Azacitidine and low-dose cytarabine in palliative patients with acute myeloid leukemia and high bone marrow blast counts - a retrospective single-center experience.
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Radujkovic, Aleksandar, Dietrich, Sascha, Bochtler, Tilmann, Krämer, Alwin, Schöning, Tilman, Ho, Anthony D., Dreger, Peter, and Luft, Thomas
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ACUTE myeloid leukemia ,AZACITIDINE ,CYTARABINE ,BONE marrow ,FEBRILE neutropenia ,MULTIVARIATE analysis ,PATIENTS ,THERAPEUTICS - Abstract
We retrospectively analyzed and compared the efficacy and toxicity of azacitidine ( AZA) and low-dose cytarabine ( LD- Ara- C) in 65 palliative patients with acute myeloid leukemia ( AML) showing high bone marrow blast counts (≥30%) before start of treatment. Twenty-seven and 38 patients received AZA and LD- Ara- C, respectively. The median patient age was 71 yr. Patient and disease characteristics did not differ between the treatment groups, except for BM blast counts, and peripheral leukocyte and blast counts which were significantly higher in the LD- Ara- C group. AZA and LD- Ara- C were first-line treatment in 12 (44%) and 17 patients (45%), respectively. Response and hematologic improvement rates were low and similar in both treatment groups. In both treatment groups, most common non-hematologic toxicities included febrile neutropenia, pneumonia, and bleedings without significant differences regarding frequencies. Estimated 1-yr survival rates were 15% (95% CI 8-22) and 13% (95% CI 7-19) in the AZA and LD- Ara- C groups, respectively, without statistically significant difference. In multivariate analysis ( n = 65), previous treatment ( HR 2.27, 95% CI 1.00-5.22, P = 0.05) and adverse cytogenetics ( HR 2.50, 95% CI 1.20-5.22, P = 0.02) were independent predictors of poor survival. In our center and within the limitations of a retrospective study, both treatment regimens showed similar but limited efficacy in palliative patients with AML and high BM blast counts. [ABSTRACT FROM AUTHOR]
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- 2014
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8. Pre-Transplant Serum Leptin Levels and Relapse of Acute Myeloid Leukemia after Allogeneic Transplantation.
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Schwarzbich, Mark-Alexander, Dai, Hao, Kordelas, Lambros, Beelen, Dietrich W., Radujkovic, Aleksandar, Müller-Tidow, Carsten, Dreger, Peter, and Luft, Thomas
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ACUTE myeloid leukemia ,LEPTIN ,PEPTIDE hormones ,STEM cell transplantation ,ACUTE leukemia - Abstract
Weight loss and metabolic activity influence outcome after allogeneic stem cell transplantation (alloSCT). This study evaluates pre-conditioning Leptin, a peptide hormone involved in metabolism and immune homeostasis, as a prognostic factor for survival, relapse and non-relapse mortality (NRM) following alloSCT. Leptin serum levels prior to conditioning were determined in a cohort of patients transplanted for various hematologic malignancies (n = 524) and correlated retrospectively with clinical outcome. Findings related to patients with acute leukemia (AL) from this sample were validated in an independent cohort. Low pre-conditioning serum Leptin was an independent prognostic marker for increased risk of relapse (but not of NRM and overall mortality) following alloSCT for AL of intermediate and advanced stage (beyond first complete remission). Multivariate analysis revealed a hazard ratio (HR) for relapse of 0.75 per log2 increase (0.59–0.96, p = 0.020). This effect was similar in an independent validation cohort. Pre-conditioning serum Leptin was validated as a prognostic marker for early relapse by fitting the multivariate Cox model to the validation data. Pre-conditioning serum Leptin levels may serve as an independent prognostic marker for relapse following alloSCT in intermediate and advanced stage AL patients. Prospective studies are required to prove whether serum Leptin could be used for guiding nutritional intervention in patients with AL undergoing alloSCT. [ABSTRACT FROM AUTHOR]
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- 2022
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9. Chimeric Antigen Receptor (CAR) T Cell Therapy in Acute Myeloid Leukemia (AML).
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Hofmann, Susanne, Schubert, Maria-Luisa, Wang, Lei, He, Bailin, Neuber, Brigitte, Dreger, Peter, Müller-Tidow, Carsten, and Schmitt, Michael
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CHIMERIC antigen receptors ,ACUTE myeloid leukemia ,T cells ,CELLULAR therapy ,STEM cell transplantation - Abstract
Despite high response rates after initial chemotherapy in patients with acute myeloid leukemia (AML), relapses occur frequently, resulting in a five-year-survival by <30% of the patients. Hitherto, allogeneic hemotopoietic stem cell transplantation (allo-HSCT) is the best curative treatment option in intermediate and high risk AML. It is the proof-of-concept for T cell-based immunotherapies in AML based on the graft-versus-leukemia (GvL)-effect, but it also bears the risk of graft-versus-host disease. CD19-targeting therapies employing chimeric antigen receptor (CAR) T cells are a breakthrough in cancer therapy. A similar approach for myeloid malignancies is highly desirable. This article gives an overview on the state-of-the art of preclinical and clinical studies on suitable target antigens for CAR T cell therapy in AML patients. [ABSTRACT FROM AUTHOR]
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- 2019
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10. Transplant Outcomes for Secondary Acute Myeloid Leukemia: Acute Leukemia Working Party of the European Society for Blood and Bone Marrow Transplantation Study.
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Sengsayadeth, Salyka, Gatwood, Katie S., Savani, Bipin N., Blaise, Didier, Dreger, Peter, Mufti, Ghulam, Chevallier, Patrice, Gorin, Norbert, Esteve, Jordi, Ciceri, Fabio, Baron, Frederic, Schmid, Christoph, Giebel, Sebastian, Boumendil, Ariane, Mailhol, Audrey, Nagler, Arnon, Labopin, Myriam, Mohty, Mohamad, Finke, Jürgen, and Ganser, Arnold
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ACUTE myeloid leukemia treatment , *HEMATOPOIETIC stem cell transplantation , *HEALTH outcome assessment , *MULTIVARIATE analysis , *UNIVARIATE analysis - Abstract
Secondary acute myeloid leukemia (sAML) has been associated with inferior outcomes compared with de novo AML. Little is known about patient risk factors and outcomes in sAML after allogeneic hematopoietic stem cell transplantation (HCT); thus, this large systemic analysis of the European Society for Blood and Bone Marrow Transplantation registry was performed. This study included 4997 patients with sAML who received HCT from 2000 to 2016. In univariate analysis the 2-year cumulative incidence of chronic graft-versus-host disease (GVHD), relapse, and nonrelapse mortality (NRM) were 33.5% (95% confidence interval [CI], 32% to 34.9%), 33.7% (95% CI, 32.3% to 35.1%), and 27.5% (95% CI, 26.1% to 28.7%), respectively. Overall survival (OS), leukemia-free survival (LFS), and GVHD-free, relapse-free survival (GRFS) at 2 years were 44.5% (95% CI, 43% to 46%), 38.8% (95% CI, 37.4% to 40.3%), and 27.2% (95% CI, 25.9% to 28.6%), respectively. In multivariate analysis, patients receiving myeloablative regimens had decreased relapse (hazard ratio, .859; 95% CI, .761 to .97; P = .01), higher NRM (hazard ratio, 1.175; 95% CI, 1.03 to 1.341; P = .02), and no differences in OS, LFS, and GRFS compared with patients receiving reduced-intensity conditioning regimens. Active disease, adverse cytogenetics, older age, Karnofsky performance status (≤80%), ex vivo T cell depletion, other malignant hematologic diseases, and patient cytomegalovirus seropositivity were associated with inferior OS and LFS. These variables should be considered in patients with sAML in need of HCT, and further study regarding the impact of conditioning regimens on relapse is needed. [ABSTRACT FROM AUTHOR]
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- 2018
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11. 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
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Bornhäuser, Martin, Kienast, Joachim, Trenschel, Rudolf, Burchert, Andreas, Hegenbart, Ute, Stadler, Michael, Baurmann, Herrad, Schäfer-Eckart, Kerstin, Holler, Ernst, Kröger, Nicolaus, Schmid, Christoph, Einsele, Herrmann, Kiehl, Michael G, Hiddemann, Wolfgang, Schwerdtfeger, Rainer, Buchholz, Stefanie, Dreger, Peter, Neubauer, Andreas, Berdel, Wolfgang E, and Ehninger, Gerhard
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ACUTE myeloid leukemia , *CELL transplantation , *CLINICAL trials , *FLUDARABINE , *CYCLOPHOSPHAMIDE , *GRAFT versus host disease - Abstract
Summary: 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/m2 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. Funding: Medical Faculty of Dresden University. [Copyright &y& Elsevier]
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- 2012
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12. Transplant Outcomes for Secondary Acute Myeloid Leukemia: Acute Leukemia Working Party of the European Society for Blood and Bone Marrow Transplantation Study
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Katie S. Gatwood, Jordi Esteve, Patrice Chevallier, Peter Dreger, Matthias Stelljes, Myriam Labopin, Bipin N. Savani, Norbert Claude Gorin, Arnold Ganser, Audrey Mailhol, Juergen Finke, Dietrich W. Beelen, Sebastian Giebel, Ghulam J. Mufti, Gerhard Ehninger, Arnon Nagler, Christoph Schmid, Frédéric Baron, Didier Blaise, Ariane Boumendil, Dietger Niederwieser, Mohamad Mohty, Fabio Ciceri, Salyka Sengsayadeth, Service d'hématologie clinique et de thérapie cellulaire [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Centre de Recherche Saint-Antoine (CR Saint-Antoine), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de Réanimation Médicale [CHU Saint-Antoine], Hannover Medical School [Hannover] (MHH), Westfälische Wilhelms-Universität Münster (WWU), University of Münster, Technische Universität Dresden = Dresden University of Technology (TU Dresden), Dept. of Bone Marrow Transplantation, University Hospital, Essen, University Hospital Essen, Division Hematology, Oncology and Hemostasiology [Leipzig, Germany], University Hospital in Leipzig [Germany], Service d’Hématologie [Institut Paoli Calmettes, Marseille], Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Centre de Recherche en Cancérologie de Marseille (CRCM), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Aix Marseille Université (AMU), Department of Medicine V, Universität Heidelberg [Heidelberg], King's College Hospital (KCH), Département d'Hématologie [CHU Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), Laboratoire de Thérapie Cellulaire et de Radioprotection Accidentelle (DRPH/SRBE/LTCRA), Institut de Radioprotection et de Sûreté Nucléaire (IRSN), Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona (UB), IRCCS Ospedale San Raffaele [Milan, Italy], Université de Liège, Ludwig Maximilian University [Munich] (LMU), Cancer Center Gliwice, Université Pierre et Marie Curie - Paris 6 - UFR de Médecine Pierre et Marie Curie (UPMC), Université Pierre et Marie Curie - Paris 6 (UPMC), Sengsayadeth, Salyka, Labopin, Myriam, Boumendil, Ariane, Finke, Jürgen, Ganser, Arnold, Stelljes, Matthia, Ehninger, Gerhard, Beelen, Dietrich, Niederwieser, Dietger, Blaise, Didier, Dreger, Peter, Mufti, Ghulam, Chevallier, Patrice, Mailhol, Audrey, Gatwood, Katie S., Gorin, Norbert, Esteve, Jordi, Ciceri, Fabio, Baron, Frederic, Schmid, Christoph, Giebel, Sebastian, Mohty, Mohamad, Savani, Bipin N., Nagler, Arnon, CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Westfälische Wilhelms-Universität Münster = University of Münster (WWU), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Universität Heidelberg [Heidelberg] = Heidelberg University, Laboratoire de Thérapie Cellulaire et de Radioprotection Accidentelle (IRSN/DRPH/SRBE/LTCRA), Service de RadioBiologie et d'Epidémiologie (IRSN/DRPH/SRBE), and Institut de Radioprotection et de Sûreté Nucléaire (IRSN)-Institut de Radioprotection et de Sûreté Nucléaire (IRSN)
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Adult ,Male ,medicine.medical_specialty ,Secondary ,Transplantation Conditioning ,Adolescent ,medicine.medical_treatment ,[SDV]Life Sciences [q-bio] ,Medizin ,Hematopoietic stem cell transplantation ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,medicine ,Humans ,Secondary Acute Myeloid Leukemia ,Cumulative incidence ,ddc:610 ,Aged ,Bone Marrow Transplantation ,Aged, 80 and over ,Acute leukemia ,Univariate analysis ,Transplantation ,Acute myeloid leukemia ,Toxicity ,business.industry ,Hazard ratio ,Hematopoietic Stem Cell Transplantation ,Hematology ,Middle Aged ,Confidence interval ,3. Good health ,Allogeneic stem cell transplantation ,Europe ,Antileukemic effect ,Leukemia, Myeloid, Acute ,Treatment Outcome ,030220 oncology & carcinogenesis ,Female ,business ,030215 immunology ,Conditioning - Abstract
International audience; Secondary acute myeloid leukemia (sAML) has been associated with inferior outcomes compared with de novo AML. Little is known about patient risk factors and outcomes in sAML after allogeneic hematopoietic stem cell transplantation (HCT); thus, this large systemic analysis of the European Society for Blood and Bone Marrow Transplantation registry was performed. This study included 4997 patients with sAML who received HCT from 2000 to 2016. In univariate analysis the 2-year cumulative incidence of chronic graft-versus-host disease (GVHD), relapse, and nonrelapse mortality (NRM) were 33.5% (95% confidence interval [Cl], 32% to 34.9%), 33.7% (95% CI, 32.3% to 35.1%), and 27.5% (95% CI, 26.1% to 28.7%), respectively. Overall survival (OS), leukemia-free survival (LFS), and GVHD-free, relapse-free survival (GRFS) at 2 years were 44.5% (95% CI, 43% to 46%), 38.8% (95% CI, 37.4% to 40.3%), and 27.2% (95% Cl, 25.9% to 28.6%), respectively. In multivariate analysis, patients receiving myeloablative regimens had decreased relapse (hazard ratio, .859; 95% CI, .761 to .97; P = .01), higher NRM (hazard ratio, 1.175; 95% CI, 1.03 to 1341; P = .02), and no differences in OS, LFS, and GRFS compared with patients receiving reduced-intensity conditioning regimens. Active disease, adverse cytogenetics, older age, Karnofsky performance status (
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- 2018
13. Allogeneic Stem Cell Transplantation for Myelofibrosis with Leukemic Transformation: A Study from the Myeloproliferative Neoplasm Subcommittee of the CMWP of the European Group for Blood and Marrow Transplantation.
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Alchalby, Haefaa, Zabelina, Tatjana, Stübig, Thomas, van Biezen, Anja, Bornhäuser, Martin, Di Bartolomeo, Paolo, Beelen, Dietrich, Cahn, Jean Yves, Dreger, Peter, Schroyens, William, de Witte, Theo, Olavarria, Eduardo, and Kröger, Nicolaus
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STEM cell transplantation , *MYELOFIBROSIS , *ACUTE myeloid leukemia , *MORTALITY , *MYELOPROLIFERATIVE neoplasms , *BONE marrow transplantation , *CONFIDENCE intervals , *THERAPEUTICS - Abstract
Abstract: Transformed acute myeloid leukemia in myelofibrosis results in a median survival of less than 5 months. We identified 46 of 1048 myelofibrosis patients in the European Group for Blood and Marrow Transplantation registry who received allogeneic stem cell transplantation for acute leukemia evolving from myelofibrosis. The cumulative incidence of treatment-related mortality at 1 year was 28% (95% confidence interval, 14 to 42) and of relapse at 3 years was 47% (95% confidence interval, 31 to 63). The 3-year progression-free (PFS) and overall survival (OS) rates were 26% and 33%, respectively. The only significant factor for survival was complete remission versus no complete remission before transplantation (69% versus 22%, P = .008); however, complete remission was achieved only in 8 patients. Allogeneic stem cell transplantation can cure myelofibrosis patients transformed to leukemia. [Copyright &y& Elsevier]
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- 2014
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14. Final Evaluation of a Clinical Phase III Trial Comparing Treosulfan to Busulfan-Based Conditioning Therapy Prior to Allogeneic Hematopoietic Stem Cell Transplantation of Adult Acute Myeloid Leukemia and Myelodysplastic Syndrome Patients Ineligible to Standard Myeloablative Regimens
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Beelen, Dietrich, Markiewicz, Miroslaw, Stelljes, Matthias, Remenyi, Peter, Wagner-Drouet, Eva-Maria, Dreger, Peter, Bethge, Wolfgang, Ciceri, Fabio, Stölzel, Friedrich, Junghanß, Christian, Michallet, Mauricette, Schaefer-Eckart, Kerstin, Grigoleit, Goetz, Scheid, Christof, Patriarca, Francesca, Mico, Maria Caterina, Niederwieser, Dietger, Hilgendorf, Inken, Russo, Domenico, and Socié, Gerard
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CLINICAL trials , *BUSULFAN , *HEMATOPOIETIC stem cell transplantation , *GRAFT versus host disease , *MYELODYSPLASTIC syndromes , *ACUTE myeloid leukemia - Abstract
Background Allogeneic hematopoietic stem cell transplantation (HCT) remains a challenge in elderly and comorbid AML and MDS patients. This patient population is at increased risk for non-relapse mortality (NRM) when treated with standard myeloablative conditioning and was selected to compare a newly developed treosulfan-based with a well-established reduced intensity busulfan-based preparative regimen in a prospective randomized clinical phase III trial. Methods Adult patients with AML in remission or MDS scheduled for HCT from matched related or unrelated donors, aged ≥50 years or with a comorbidity index (HCT-CI) of >2 were enrolled by a central stratified randomization procedure. Treatment arms consisted of intravenous (IV) treosulfan (10 g/m²/day [d-4 to d-2]) or IV busulfan (3.2 mg/kg/day [d-4 to d-3]), both combined with IV fludarabine (30 mg/m²/day [d-6 to d-2]). The primary objective was to compare event-free survival (EFS) at two years with relapse/progression of disease, graft failure, or death reported as events. Secondary endpoints were safety evaluation (according to CTCAE v4.03), engraftment, chimerism, overall survival (OS), relapse/progression incidence (RI), NRM and acute or chronic GvHD. After a previously conducted confirmatory interim analysis (based on 476 patients), which resulted in early termination of patient accrual due to significant non-inferiority of treosulfan treatment with improved EFS, NRM and OS (Beelen et al., ASH 2017), results of the final analysis of all 570 randomized patients including post surveillance data are provided here. Results Median age of the 551 patients (352 AML; 199 MDS) included in the full analysis set (268 treosulfan; 283 busulfan) was 60 years (range: 31, 70). Frequencies of early adverse events (d-6 to d+28) and incidences of acute and chronic GvHD were largely comparable between the two regimens, while extensive chronic GvHD was numerically in favor of treosulfan (19.7% vs. 26.7%; p=0.0750). Primary neutrophil recovery at day +28 was comparable, while the rate of complete donor-type chimerism (day +28) was higher after treosulfan (93.2% vs. 83.3%; p<0.0001). After a median follow-up of 29 months (range: 3.0, 54.3) the 2-year EFS was significantly higher in the treosulfan arm (65.7% vs. 51.2%; hazard ratio [HR] 0.64; p=0.0012) as was OS (72.7% vs. 60.2%; HR 0.64; p=0.0037) and NRM (12.0% vs. 20.4%; HR 0.63; p=0.0343). RI was comparable between both regimens (22.0% vs. 25.2%; HR 0.82; p=0.2631). Results were consistent within all pre-defined major prognostic subgroups of patients. Conclusions Final evaluation of this phase III trial substantiates the previous confirmatory analysis resulting in significantly improved survival after treosulfan-based conditioning. Due to the reduction of NRM a major clinical benefit of the new treosulfan conditioning regimen was demonstrated in the selected AML/MDS patient population. [ABSTRACT FROM AUTHOR]
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- 2019
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