22 results on '"Schetelig, Johannes"'
Search Results
2. Midostaurin in addition to intensive chemotherapy in acute myeloid leukemia with t(8;21) and KIT and/or FLT3-ITD mutations: results of the SAL MIDOKIT trial
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Ruhnke, Leo, primary, Röllig, Christoph, additional, Herold, Sylvia, additional, Sauer, Tim, additional, Brandts, Christian H, additional, Steffen, Björn, additional, Schäfer-Eckart, Kerstin, additional, Krause, Stefan W, additional, Hänel, Mathias, additional, Reichle, Albrecht, additional, Scholl, Sebastian, additional, Neubauer, Andreas, additional, Mikesch, Jan-Henrik, additional, Schetelig, Johannes, additional, Stölzel, Friedrich, additional, Kramer, Michael, additional, Haake, Annett, additional, Frimmel, Julia, additional, Krämer, Alwin, additional, Schlenk, Richard, additional, Platzbecker, Uwe, additional, Serve, Hubert, additional, Baldus, Claudia D, additional, Müller-Tidow, Carsten, additional, Aust, Daniela, additional, Bornhäuser, Martin, additional, Ehninger, Gerhard, additional, and Thiede, Christian, additional
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- 2023
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3. Prediction of complete remission and survival in acute myeloid leukemia using supervised machine learning
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Eckardt, Jan-Niklas, primary, Röllig, Christoph, additional, Metzeler, Klaus, additional, Kramer, Michael, additional, Stasik, Sebastian, additional, Georgi, Julia-Annabell, additional, Heisig, Peter, additional, Spiekermann, Karsten, additional, Krug, Utz, additional, Braess, Jan, additional, Görlich, Dennis, additional, Sauerland, Cristina M., additional, Woermann, Bernhard, additional, Herold, Tobias, additional, Berdel, Wolfgang E., additional, Hiddemann, Wolfgang, additional, Kroschinsky, Frank, additional, Schetelig, Johannes, additional, Platzbecker, Uwe, additional, Müller-Tidow, Carsten, additional, Sauer, Tim, additional, Serve, Hubert, additional, Baldus, Claudia, additional, Schäfer-Eckart, Kerstin, additional, Kaufmann, Martin, additional, Krause, Stefan, additional, Hänel, Mathias, additional, Schliemann, Christoph, additional, Hanoun, Maher, additional, Thiede, Christian, additional, Bornhäuser, Martin, additional, Wendt, Karsten, additional, and Middeke, Jan Moritz, additional
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- 2022
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4. The prevalence of extramedullary acute myeloid leukemia detected by 18FDG-PET/CT: final results from the prospective PETAML trial
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Stölzel, Friedrich, primary, Lüer, Tors, additional, Löck, Steffen, additional, Parmentier, Stefani, additional, Kuithan, Friederike, additional, Kramer, Michael, additional, Alakel, Nael S., additional, Sockel, Katja, additional, Taube, Franziska, additional, Middeke, Jan M., additional, Schetelig, Johannes, additional, Röllig, Christoph, additional, Paulus, Tobias, additional, Kotzerke, Jörg, additional, Ehninger, Gerhard, additional, Bornhäuser, Martin, additional, Schaich, Markus, additional, and Zoephel, Klaus, additional
- Published
- 2019
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5. EZH2 mutations and impact on clinical outcome: an analysis in 1,604 patients with newly diagnosed acute myeloid leukemia
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Stasik, Sebastian, primary, Middeke, Jan M., additional, Kramer, Michael, additional, Röllig, Christoph, additional, Krämer, Alwin, additional, Scholl, Sebastian, additional, Hochhaus, Andreas, additional, Crysandt, Martina, additional, Brümmendorf, Tim H., additional, Naumann, Ralph, additional, Steffen, Björn, additional, Kunzmann, Volker, additional, Einsele, Hermann, additional, Schaich, Markus, additional, Burchert, Andreas, additional, Neubauer, Andreas, additional, Schäfer-Eckart, Kerstin, additional, Schliemann, Christoph, additional, Krause, Stefan, additional, Herbst, Regina, additional, Hänel, Mathias, additional, Frickhofen, Norbert, additional, Noppeney, Richard, additional, Kaiser, Ulrich, additional, Baldus, Claudia D., additional, Kaufmann, Martin, additional, Rácil, Zdenek, additional, Platzbecker, Uwe, additional, Berdel, Wolfgang E., additional, Mayer, Jiri, additional, Serve, Hubert, additional, Müller-Tidow, Carsten, additional, Ehninger, Gerhard, additional, Bornhäuser, Martin, additional, Schetelig, Johannes, additional, and Thiede, Christian, additional
- Published
- 2019
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6. Long-term outcome after allogeneic hematopoietic cell transplantation for myelofibrosis
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Robin, Marie, primary, de Wreede, Liesbeth C., additional, Wolschke, Christine, additional, Schetelig, Johannes, additional, Eikema, Diderik-Jan, additional, Van Lint, Maria Teresa, additional, Knelange, Nina Simone, additional, Beelen, Dietrich, additional, Brecht, Arne, additional, Niederwieser, Dietger, additional, Vitek, Antonin, additional, Bethge, Wolfgang, additional, Arnold, Renate, additional, Finke, Jürgen, additional, Volin, Liisa, additional, Yakoub-Agha, Ibrahim, additional, Nagler, Arnon, additional, Poiré, Xavier, additional, Einsele, Hermann, additional, Chevallier, Patrice, additional, Holler, Ernst, additional, Ljungman, Per, additional, Robinson, Stephen, additional, Radujkovic, Alekxandar, additional, McLornan, Donal, additional, Chalandon, Yves, additional, and Kröger, Nicolaus, additional
- Published
- 2019
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7. T-cell receptor-α repertoire of CD8+ T cells following allogeneic stem cell transplantation using next-generation sequencing
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Link-Rachner, Cornelia S., primary, Eugster, Anne, additional, Rücker-Braun, Elke, additional, Heidenreich, Falk, additional, Oelschlägel, Uta, additional, Dahl, Andreas, additional, Klesse, Christian, additional, Kuhn, Matthias, additional, Middeke, Jan Moritz, additional, Bornhäuser, Martin, additional, Bonifacio, Ezio, additional, and Schetelig, Johannes, additional
- Published
- 2018
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8. Competing-risk outcomes after hematopoietic stem cell transplantation from the perspective of time-dependent effects
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Fuerst, Daniel, primary, Frank, Sandra, additional, Mueller, Carlheinz, additional, Beelen, Dietrich W, additional, Schetelig, Johannes, additional, Niederwieser, Dietger, additional, Finke, Jürgen, additional, Bunjes, Donald, additional, Kröger, Nicolaus, additional, Neuchel, Christine, additional, Tsamadou, Chrysanthi, additional, Schrezenmeier, Hubert, additional, Beyersmann, Jan, additional, and Mytilineos, Joannis, additional
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- 2018
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9. Mass spectrometry-based identification of a naturally presented receptor tyrosine kinase-like orphan receptor 1-derived epitope recognized by CD8 + cytotoxic T cells
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Heidenreich, Falk, primary, Rücker-Braun, Elke, additional, Walz, Juliane S., additional, Eugster, Anne, additional, Kühn, Denise, additional, Dietz, Sevina, additional, Nelde, Annika, additional, Tunger, Antje, additional, Wehner, Rebekka, additional, Link, Cornelia S., additional, Middeke, Jan M., additional, Stölzel, Friedrich, additional, Tonn, Torsten, additional, Stevanovic, Stefan, additional, Rammensee, Hans-Georg, additional, Bonifacio, Ezio, additional, Bachmann, Michael, additional, Zeis, Matthias, additional, Ehninger, Gerhard, additional, Bornhäuser, Martin, additional, Schetelig, Johannes, additional, and Schmitz, Marc, additional
- Published
- 2017
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10. Dynamics of epigenetic age following hematopoietic stem cell transplantation
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Stölzel, Friedrich, primary, Brosch, Mario, additional, Horvath, Steve, additional, Kramer, Michael, additional, Thiede, Christian, additional, von Bonin, Malte, additional, Ammerpohl, Ole, additional, Middeke, Moritz, additional, Schetelig, Johannes, additional, Ehninger, Gerhard, additional, Hampe, Jochen, additional, and Bornhäuser, Martin, additional
- Published
- 2017
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11. Multi-state analysis illustrates treatment success after stem cell transplantation for acute myeloid leukemia followed by donor lymphocyte infusion
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Eefting, Matthias, primary, de Wreede, Liesbeth C., additional, Halkes, Constantijn J.M., additional, von dem Borne, Peter A., additional, Kersting, Sabina, additional, Marijt, Erik W.A., additional, Veelken, Hendrik, additional, Putter, Hein, additional, Schetelig, Johannes, additional, and Falkenburg, J.H. Frederik, additional
- Published
- 2016
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12. Hematopoietic cell transplantation for older acute myeloid leukemia patients in first complete remission: results of a randomized phase III study.
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Niederwieser D, Hasenclever D, Berdel WE, Biemond BJ, Al-Ali H, Chalandon Y, Van Gelder M, Junghanß C, Gahrton G, Hänel M, Hehlmann R, Heinicke T, Hochhaus A, Iacobelli S, Kooy RVM, Kröger N, Janssen J, Jentzsch M, Breywisch F, Mohty M, Masouridi-Levrat S, Ossenkoppele G, Passweg J, Pönisch W, Schetelig J, Schliemann C, Schwind S, Stelljes M, Verdonck LF, Vucinic V, Löwenberg B, and Cornelissen J
- Abstract
Given the selection of elderly patients with AML in first complete remission (CR1) the advantage of consolidation with allogeneic hematopoietic cell transplantation (HCT) over chemotherapy is still unclear. Newly diagnosed AML patients in CR1 aged 60-75 years were registered and a donor search initiated. After one consolidation cycle, patients with a matched donor were randomized to HCT with fludarabine/lowdose total body irradiation and cyclosporine/mycophenolate mofetil immunosuppression or conventional non-HCT. Primary outcome was restricted mean leukemia-free survival (RM-LFS) up to five years. Between 2010 and 2017, 245 patients (median age 67 years) were registered at CR1. After one consolidation, 26.9% of patients failed inclusion criteria. Of the 179 (73%) patients still on study, 75.4% had an HLA identical donor. Ten ineligible patients were excluded, and 125 randomized to HCT (n=83) or non-HCT (n=42). The primary outcome RM-LFS up to 5 years was 24.5 months (95%CI:18.9-30.1) in the HCT and 15.6 months (95%CI:10.4-20.8) in the non-HCT arm (p=0.022) due to a decrease in cumulative relapse incidence from 91.1 (95%CI:80.7-100.0) after non-HCT to 37.8 (95%CI:27.2-48.4)% after HCT (p.
- Published
- 2024
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13. Allogeneic hematopoietic stem cell transplantation in patients aged 60-79 years in Germany (1998-2018): a registry study.
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Weller JF, Lengerke C, Finke J, Schetelig J, Platzbecker U, Einsele H, Schroeder T, Faul C, Stelljes M, Dreger P, Blau IW, Wulf G, Tischer J, Scheid C, Elmaagacli A, Neidlinger H, Flossdorf S, Bornhäuser M, Bethge W, Fleischhauer K, Kröger N, De Wreede LC, and Christopeit M
- Subjects
- Humans, Transplantation, Homologous adverse effects, Germany epidemiology, Chronic Disease, Transplantation Conditioning adverse effects, Recurrence, Retrospective Studies, Hematopoietic Stem Cell Transplantation adverse effects, Graft vs Host Disease epidemiology, Graft vs Host Disease etiology
- Abstract
Incidences of diseases treated with transplantation frequently peak at higher age. The contribution of age to total risk of transplantation has not been estimated amidst an aging society. We compare outcomes of 1,547 patients aged 70-79 years and 9,422 patients aged 60-69 years transplanted 1998-2018 for myeloid, lymphoid and further neoplasia in Germany. To quantify the contribution of population mortality to survival, we derive excess mortality based on a sex-, year- and agematched German population in a multistate model that incorporates relapse and graft-versus-host-disease (GvHD). Overall survival, relapse-free survival (RFS) and GvHD-free-relapse-free survival (GRFS) is inferior in patients aged 70-79 years, compared to patients aged 60-69 years, with 36% (95% Confidence Interval [CI]: 34-39%) versus 43% (41-44%), 32% (30- 35%) versus 36% (35-37%) and 23% (21-26%) versus 27% (26-28%) three years post-transplant (P<0.001). Cumulative incidences of relapse at three years are 27% (25-30%) for patients aged 70-79 versus 29% (29-30%) (60-69 years) (P=0.71), yet the difference in non-relapse mortality (NRM) (40% [38-43%] vs. 35% [34-36%] in patients aged 70-79 vs. 60-69 years) (P<0.001) translates into survival differences. Median OS of patients surviving >1 year relapse-free is 6.7 (median, 95% CI: 4.5-9.4, 70-79 years) versus 9 (8.4-10.1, 60-69 years) years since landmark. Three years after RFS of one year, excess NRM is 14% (95% CI: 12-18%) in patients aged 70-79 versus 12% [11-13%] in patients aged 60-69, while population NRM is 7% (6-7%) versus 3% (3-3%). Mortality for reasons other than relapse, GvHD, or age is as high as 27% (24-29%) and 22% (22-23%) four years after transplantation. In conclusion, survival amongst older patients is adequate after allogeneic stem cell transplantation.
- Published
- 2024
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14. Prediction of complete remission and survival in acute myeloid leukemia using supervised machine learning.
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Eckardt JN, Röllig C, Metzeler K, Kramer M, Stasik S, Georgi JA, Heisig P, Spiekermann K, Krug U, Braess J, Görlich D, Sauerland CM, Woermann B, Herold T, Berdel WE, Hiddemann W, Kroschinsky F, Schetelig J, Platzbecker U, Müller-Tidow C, Sauer T, Serve H, Baldus C, Schäfer-Eckart K, Kaufmann M, Krause S, Hänel M, Schliemann C, Hanoun M, Thiede C, Bornhäuser M, Wendt K, and Middeke JM
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- Humans, Prognosis, Splicing Factor U2AF genetics, Mutation, Supervised Machine Learning, Hemoglobins genetics, fms-Like Tyrosine Kinase 3 genetics, Nucleophosmin, Leukemia, Myeloid, Acute diagnosis, Leukemia, Myeloid, Acute genetics, Leukemia, Myeloid, Acute therapy
- Abstract
Achievement of complete remission signifies a crucial milestone in the therapy of acute myeloid leukemia (AML) while refractory disease is associated with dismal outcomes. Hence, accurately identifying patients at risk is essential to tailor treatment concepts individually to disease biology. We used nine machine learning (ML) models to predict complete remission and 2-year overall survival in a large multicenter cohort of 1,383 AML patients who received intensive induction therapy. Clinical, laboratory, cytogenetic and molecular genetic data were incorporated and our results were validated on an external multicenter cohort. Our ML models autonomously selected predictive features including established markers of favorable or adverse risk as well as identifying markers of so-far controversial relevance. De novo AML, extramedullary AML, double-mutated CEBPA, mutations of CEBPA-bZIP, NPM1, FLT3-ITD, ASXL1, RUNX1, SF3B1, IKZF1, TP53, and U2AF1, t(8;21), inv(16)/t(16;16), del(5)/del(5q), del(17)/del(17p), normal or complex karyotypes, age and hemoglobin concentration at initial diagnosis were statistically significant markers predictive of complete remission, while t(8;21), del(5)/del(5q), inv(16)/t(16;16), del(17)/del(17p), double-mutated CEBPA, CEBPA-bZIP, NPM1, FLT3-ITD, DNMT3A, SF3B1, U2AF1, and TP53 mutations, age, white blood cell count, peripheral blast count, serum lactate dehydrogenase level and hemoglobin concentration at initial diagnosis as well as extramedullary manifestations were predictive for 2-year overall survival. For prediction of complete remission and 2-year overall survival areas under the receiver operating characteristic curves ranged between 0.77-0.86 and between 0.63-0.74, respectively in our test set, and between 0.71-0.80 and 0.65-0.75 in the external validation cohort. We demonstrated the feasibility of ML for risk stratification in AML as a model disease for hematologic neoplasms, using a scalable and reusable ML framework. Our study illustrates the clinical applicability of ML as a decision support system in hematology.
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- 2023
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15. The prevalence of extramedullary acute myeloid leukemia detected by 18 FDG-PET/CT: final results from the prospective PETAML trial.
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Stölzel F, Lüer T, Löck S, Parmentier S, Kuithan F, Kramer M, Alakel NS, Sockel K, Taube F, Middeke JM, Schetelig J, Röllig C, Paulus T, Kotzerke J, Ehninger G, Bornhäuser M, Schaich M, and Zoephel K
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- Humans, Positron Emission Tomography Computed Tomography, Positron-Emission Tomography, Prevalence, Prospective Studies, Radiopharmaceuticals, Sensitivity and Specificity, Fluorodeoxyglucose F18, Leukemia, Myeloid, Acute diagnostic imaging, Leukemia, Myeloid, Acute epidemiology
- Abstract
Extramedullary (EM) disease in patients with acute myeloid leukemia (AML) is a known phenomenon. Since the prevalence of EM AML has so far only been clinically determined on examination, we performed a prospective study in patients with AML. The aim of the study was to determine the prevalence of metabolically active EM AML using total body
18 Fluorodesoxy-glucose positron emission tomography/computed tomography (18 FDG-PET/CT) imaging at diagnosis prior to initiation of therapy. In order to define the dynamics of EM AML throughout treatment, PET-positive patients underwent a second18 FDG-PET/CT imaging series during follow up by the time of remission assessment. A total of 93 patients with AML underwent18 FDG-PET/CT scans at diagnosis. The prevalence of PET-positive EM AML was 19% with a total of 65 EM AML manifestations and a median number of two EM manifestations per patient (range, 1-12), with a median maximum standardized uptake value of 6.1 (range, 2-51.4). When adding those three patients with histologically confirmed EM AML who were18 FDG-PET/CT negative in the18 FDG-PET/CT at diagnosis, the combined prevalence for EM AML was 22%, resulting in 77% sensitivity and 97% specificity. Importantly, 60% (6 of 10) patients with histologically confirmed EM AML still had active EM disease in their follow up18 FDG-PET/CT.18 FDG-PET/CT reveals a high prevalence of metabolically active EM disease in AML patients. Metabolic activity in EM AML may persist even beyond the time point of hematologic remission, a finding that merits further prospective investigation to explore its prognostic relevance. (Trial registered at clinicaltrials.gov identifier: 01278069 )., (Copyright© 2020 Ferrata Storti Foundation.)- Published
- 2020
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16. EZH2 mutations and impact on clinical outcome: an analysis in 1,604 patients with newly diagnosed acute myeloid leukemia.
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Stasik S, Middeke JM, Kramer M, Röllig C, Krämer A, Scholl S, Hochhaus A, Crysandt M, Brümmendorf TH, Naumann R, Steffen B, Kunzmann V, Einsele H, Schaich M, Burchert A, Neubauer A, Schäfer-Eckart K, Schliemann C, Krause S, Herbst R, Hänel M, Frickhofen N, Noppeney R, Kaiser U, Baldus CD, Kaufmann M, Rácil Z, Platzbecker U, Berdel WE, Mayer J, Serve H, Müller-Tidow C, Ehninger G, Bornhäuser M, Schetelig J, and Thiede C
- Subjects
- Enhancer of Zeste Homolog 2 Protein genetics, Humans, Mutation, Leukemia, Myeloid, Acute diagnosis, Leukemia, Myeloid, Acute genetics
- Published
- 2020
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17. T-cell receptor-α repertoire of CD8+ T cells following allogeneic stem cell transplantation using next-generation sequencing.
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Link-Rachner CS, Eugster A, Rücker-Braun E, Heidenreich F, Oelschlägel U, Dahl A, Klesse C, Kuhn M, Middeke JM, Bornhäuser M, Bonifacio E, and Schetelig J
- Subjects
- CD8-Positive T-Lymphocytes immunology, Female, Graft vs Host Disease etiology, Hematopoietic Stem Cell Transplantation, High-Throughput Nucleotide Sequencing, Humans, Immunologic Memory, Lymphocyte Depletion, Male, T-Lymphocyte Subsets immunology, T-Lymphocyte Subsets metabolism, Transplantation, Homologous, CD8-Positive T-Lymphocytes metabolism, Receptors, Antigen, T-Cell, alpha-beta genetics, Receptors, Antigen, T-Cell, alpha-beta metabolism
- Abstract
Alloreactivity or opportunistic infections following allogeneic stem cell transplantation are difficult to predict and contribute to post-transplantation mortality. How these immune reactions result in changes to the T-cell receptor repertoire remains largely unknown. Using next-generation sequencing, the T-cell receptor alpha (TRα) repertoire of naïve and memory CD8
+ T cells from 25 patients who had received different forms of allogeneic transplantation was analyzed. In parallel, reconstitution of the CD8+ /CD4+ T-cell subsets was mapped using flow cytometry. When comparing the influence of anti-T-cell therapy, a delay in the reconstitution of the naïve CD8+ T-cell repertoire was observed in patients who received in vivo T-cell depletion using antithymocyte globulin or post-transplantation cyclophosphamide in case of haploidentical transplantation. Sequencing of the TRα identified a repertoire consisting of more dominant clonotypes (>1% of reads) in these patients at 6 and 18 months post transplantation. When comparing donor and recipient, approximately 50% and approximately 80% of the donors' memory repertoire were later retrieved in the naïve and memory CD8+ T-cell receptor repertoire of the recipients, respectively. Although there was a remarkable expansion of single clones observed in the recipients' memory CD8+ TRα repertoire, no clear association between graft- versus -host disease or cytomegalovirus infection and T-cell receptor diversity was identified. A lower TRα diversity was observed in recipients of a cytomegalovirus-seropositive donor ( P =0.014). These findings suggest that CD8+ T-cell reconstitution in transplanted patients is influenced by the use of T-cell depletion or immunosuppression and the donor repertoire., (Copyright© 2019 Ferrata Storti Foundation.)- Published
- 2019
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18. Proinflammatory human 6-sulfo LacNAc-positive dendritic cells accumulate in intestinal acute graft-versus-host disease.
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Sommer U, Larsson B, Tuve S, Wehner R, Zimmermann N, Kramer M, Kloβ A, Günther C, Babatz J, Schmelz R, Brückner S, Schetelig J, Bornhäuser M, Schäkel K, Bachmann MP, Aust D, Baretton G, and Schmitz M
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- Graft vs Host Disease etiology, Hematopoietic Stem Cell Transplantation adverse effects, Humans, Intestines pathology, Transplantation, Homologous, Amino Sugars metabolism, Dendritic Cells immunology, Dendritic Cells metabolism, Graft vs Host Disease immunology, Graft vs Host Disease metabolism, Intestinal Mucosa metabolism, Intestines immunology
- Published
- 2014
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19. Assessment of dysplastic hematopoiesis: lessons from healthy bone marrow donors.
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Parmentier S, Schetelig J, Lorenz K, Kramer M, Ireland R, Schuler U, Ordemann R, Rall G, Schaich M, Bornhäuser M, Ehninger G, and Kroschinsky F
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- Adolescent, Adult, Cell Lineage, Cohort Studies, Female, Humans, Male, Middle Aged, Observer Variation, Prognosis, Young Adult, Bone Marrow pathology, Erythropoiesis physiology, Granulocytes pathology, Hematopoiesis physiology, Megakaryocytes pathology, Tissue Donors
- Abstract
Background: According to WHO 2008 guidelines, the required percentage of cells manifesting dysplasia in the bone marrow to qualify as significant is 10% or over in one or more hematopoietic cell lineages, but this threshold is controversial. No 'normal' values have been established. Therefore, we investigated dyshematopoiesis in bone marrow aspirate squash preparations of 120 healthy bone marrow donors., Design and Methods: Bone marrow squash slides of 120 healthy unrelated bone marrow donors were examined independently by 4 experienced morphologists. Samples were taken from the first aspiration during the harvest. Bone marrow preparation and assessment were performed according to WHO recommendations and ICSH guidelines., Results: More than 10% dysmyelopoiesis could be detected in 46% of bone marrow aspirate squash preparations with 26% in 2 or more cell lineages and 7% in 3 cell lineages in healthy bone marrow donors. Donors under the age of 30 years exhibited more dysgranulopoietic changes and dysmegakaryopoietic changes (P<0.001) compared to the older donors. Female donors showed more dysgranulopoietic changes than male donors (P = 0.025). The concordance rate between the 4 investigators was modest in dysgranulopoiesis but poor in dyserythropoiesis and dysmegakaryopoiesis., Conclusions: The poor reliability of the 10% cut off was partly related to the proximity of the current criteria to the observed cut-off mean values of the normal population. These findings question the current WHO threshold of the 10% or over necessary for the percentage of cells manifesting dysplasia to be considered significant, and suggest that either a higher threshold would be more appropriate or different thresholds should be set for each lineage.
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- 2012
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20. Monitoring of donor chimerism in sorted CD34+ peripheral blood cells allows the sensitive detection of imminent relapse after allogeneic stem cell transplantation.
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Bornhäuser M, Oelschlaegel U, Platzbecker U, Bug G, Lutterbeck K, Kiehl MG, Schetelig J, Kiani A, Illmer T, Schaich M, Theuser C, Mohr B, Brendel C, Fauser AA, Klein S, Martin H, Ehninger G, and Thiede C
- Subjects
- Antigens, CD34, Hematopoietic Stem Cell Transplantation adverse effects, Hematopoietic Stem Cell Transplantation mortality, Humans, Leukemia diagnosis, Leukemia mortality, Molecular Diagnostic Techniques, Prospective Studies, Recurrence, Survival Analysis, Transplantation, Homologous, Hematopoietic Stem Cell Transplantation methods, Neoplasm, Residual diagnosis, Transplantation Chimera
- Abstract
Analysis of donor chimerism is an important diagnostic tool to assess the risk of relapse after allogeneic stem cell transplantation, especially in patients lacking a specific marker suitable for monitoring of minimal residual disease. We prospectively investigated the predictive value of donor chimerism analyses in sorted CD34(+) peripheral blood cells in 90 patients with acute leukemia and myelodysplastic syndrome. The cumulative incidence of relapse after four years was significantly increased in cases with decreasing or incomplete CD34(+) donor chimerism (57% vs. 18%, p=0.0001). Multivariate analysis confirmed decreasing CD34(+) donor chimerism as an independent predictor of relapse and inferior survival. The interval between a decrease of CD34(+) chimerism of less than 80% and hematologic relapse was 61 days (range 0-567). Monitoring of CD34(+) donor chimerism in the peripheral blood allows prediction of imminent relapse after allogeneic stem cell transplantation even when a disease-specific marker is lacking.
- Published
- 2009
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21. Long-term disease-free survival in patients with angioimmunoblastic T-cell lymphoma after high-dose chemotherapy and autologous stem cell transplantation.
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Schetelig J, Fetscher S, Reichle A, Berdel WE, Beguin Y, Brunet S, Caballero D, Majolino I, Hagberg H, Johnsen HE, Kimby E, Montserrat E, Stewart D, Copplestone A, Rösler W, Pavel J, Kingreen D, and Siegert W
- Subjects
- Adult, Combined Modality Therapy, Disease Progression, Disease-Free Survival, Female, Health Surveys, Humans, Immunoblastic Lymphadenopathy mortality, Immunoblastic Lymphadenopathy therapy, Life Tables, Lymphoma, T-Cell mortality, Lymphoma, T-Cell therapy, Male, Middle Aged, Remission Induction, Retrospective Studies, Salvage Therapy, Survival Analysis, Transplantation Conditioning, Transplantation, Autologous, Treatment Outcome, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Immunoblastic Lymphadenopathy drug therapy, Lymphoma, T-Cell drug therapy, Peripheral Blood Stem Cell Transplantation
- Abstract
Background and Objectives: Patients with angioimmunoblastic T-cell lymphoma (AIL) have a poor prognosis with conventional treatment., Design and Methods: We initiated an EBMT-based survey studying the impact of high-dose chemotherapy (HDCT) and autologous hematopoietic stem cell transplantation in patients with AIL. Data on 29 patients, who were transplanted between 1992 and 1998 in 16 transplant centers, were collected on standardized documentation forms., Results: The median age at transplantation was 53 years. HDCT was given as part of 1st-line therapy (N=14; 48%) or 2nd/3rd-line therapy (N=15; 52%). Regimens for the mobilization of peripheral blood stem cells (PBSC) included VIPE (N=7; 26%), DexaBEAM (N=6; 22%), CHOP-like regimens (N=6; 22%), other regimens (N=5; 19%) or alternatively growth factor alone (N=3; 11%). The median yield of PBSC was 3.8x106 CD34+cells/kg. Two patients received autologous bone marrow. The HDCT consisted of BEAM-type regimens in 16 patients, ICE-type regimens in 7, and other regimens in 6 patients. There was one treatment-related death. The rate of complete remissions increased from 45% before HDCT to 76% after HDCT. As of January 2003, after a median observation time of living patients of 5 years (range 2.5 to 10 years), 14 patients have died (13 from progressive disease), and 15 patients are alive. The probability of 5-year overall and event-free survival was 44% (95% CI, 22% to 66%) and 37% (95% CI, 17% to 57%), respectively. Long-term disease-free survival was observed in patients transplanted during 1st-line treatment as well as in the context of 2nd/3rd-line therapy., Interpretation and Conclusions: There is evidence that AIL is susceptible to high-dose chemotherapy. HDCT and autologous stem cell transplantation should be considered in selected patients with AIL.
- Published
- 2003
22. Allogeneic transplantation after reduced conditioning in high risk patients is complicated by a high incidence of acute and chronic graft-versus-host disease.
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Schetelig J, Kröger N, Held TK, Thiede C, Krusch A, Zabelina T, Dubiel M, Rick O, Bornhäuser M, Ehninger G, Zander AR, and Siegert W
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- Acute Disease, Adult, Antineoplastic Combined Chemotherapy Protocols administration & dosage, Antineoplastic Combined Chemotherapy Protocols toxicity, Chronic Disease, Contraindications, Female, Graft vs Host Disease mortality, Humans, Incidence, Male, Middle Aged, Neoplasms complications, Neoplasms mortality, Neoplasms therapy, Risk, Transplantation Conditioning mortality, Transplantation Conditioning standards, Transplantation, Homologous, Treatment Outcome, Graft vs Host Disease chemically induced, Hematopoietic Stem Cell Transplantation adverse effects, Transplantation Conditioning methods
- Abstract
Background and Objectives. We studied the toxicity and efficacy of reduced intensity conditioning followed by allogeneic stem cell transplantation in 50 patients over 50 years old or with relative contraindications against myeloablative regimens. Diagnoses were chronic myeloid leukemia (n=15), acute myeloid leukemia (n=9), myelodysplastic syndromes (n=9), lymphoma (n=11) and refractory solid tumors (n=6). Design and Methods. Donors were identical siblings (n=25), non-identical family members (n=6) and unrelated volunteers (n=19). Peripheral blood stem cells (n=36) or bone marrow (n=14) were transplanted. The conditioning regimen consisted of fludarabine 180 mg/m(2), busulphan 8 mg/kg and rabbit antithymocyte globulin 40 mg/kg (Fresenius). Graft-versus-host disease (GVHD) prophylaxis was carried out with cyclosporin A (CSA) alone (n=17) or in combination with methotrexate (n=18) or mycophenolate mofetil (n=15). Results. Neutrophil counts >0.5/nL and platelet counts > 20/nL were reached after 17 (range 0-66) and 19 days (range 0-111), respectively. Three graft failures occurred. Fever lasted for a median of 2 days (range 0-15). Six patients developed veno-occlusive disease of the liver. Acute GVHD grade II-IV occurred in 47% of the patients and chronic GVHD in 46%. The 1-year overall survival probability was 44% (95% CI: 30-58%). GVHD-related complications were a major cause of the probability of 1-year non-relapse mortality of 31% (95% CI: 16-46%). Interpretation and Conclusions. In conclusion, the regimen itself can be carried out safely in patients with relative contraindications against myeloablative conditioning. However, GVHD causes significant non-relapse mortality in high risk patients.
- Published
- 2002
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