14 results on '"Legdeur, Marie-Cecile J. C."'
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2. Phase I/II study of LDE225 in combination with gemcitabine and nab-paclitaxel in patients with metastatic pancreatic cancer.
- Author
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Pijnappel, Esther N., primary, Wassenaar, Nienke P.M., additional, Gurney-Champion, Oliver J., additional, Klaassen, Remy, additional, van der Lee, Koen S., additional, Pleunis- van Empel, Marjolein, additional, Richel, Dick J., additional, Legdeur, Marie-Cecile J C, additional, Nederveen, Aart J., additional, Van Laarhoven, Hanneke W.M., additional, and Wilmink, Johanna, additional
- Published
- 2021
- Full Text
- View/download PDF
3. Addition of lenalidomide to intensive treatment in younger and middle-aged adults with newly diagnosed AML: the HOVON-SAKK-132 trial.
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UCL - SSS/IREC/MONT - Pôle Mont Godinne, UCL - SSS/IREC/SLUC - Pôle St.-Luc, UCL - (MGD) Service d'hématologie, UCL - (SLuc) Service d'hématologie, Löwenberg, Bob, Pabst, Thomas, Maertens, Johan, Gradowska, Patrycja, Biemond, Bart J, Spertini, Olivier, Vellenga, Edo, Griskevicius, Laimonas, Tick, Lidwine W, Jongen-Lavrencic, Mojca, van Marwijk Kooy, Marinus, Vekemans, Marie-Christiane, van der Velden, Walter J F M, Beverloo, Berna, Michaux, Lucienne, Graux, Carlos, Deeren, Dries, de Weerdt, Okke, van Esser, Joost W J, Bargetzi, Mario, Klein, Saskia K, Gadisseur, Alain, Westerweel, Peter E, Veelken, Hendrik, Gregor, Michael, Silzle, Tobias, van Lammeren-Venema, Daniëlle, Moors, Ine, Breems, Dimitri A, Hoogendoorn, Mels, Legdeur, Marie-Cecile J C, Fischer, Thomas, Kuball, Juergen, Cornelissen, Jan, Porkka, Kimmo, Juliusson, Gunnar, Meyer, Peter, Höglund, Martin, Gjertsen, Bjorn T, Janssen, Jeroen J W M, Huls, Gerwin, Passweg, Jakob, Cloos, Jacqueline, Valk, Peter J M, van Elssen, Catharina H M J, Manz, Markus G, Floisand, Yngvar, Ossenkoppele, Gert J, UCL - SSS/IREC/MONT - Pôle Mont Godinne, UCL - SSS/IREC/SLUC - Pôle St.-Luc, UCL - (MGD) Service d'hématologie, UCL - (SLuc) Service d'hématologie, Löwenberg, Bob, Pabst, Thomas, Maertens, Johan, Gradowska, Patrycja, Biemond, Bart J, Spertini, Olivier, Vellenga, Edo, Griskevicius, Laimonas, Tick, Lidwine W, Jongen-Lavrencic, Mojca, van Marwijk Kooy, Marinus, Vekemans, Marie-Christiane, van der Velden, Walter J F M, Beverloo, Berna, Michaux, Lucienne, Graux, Carlos, Deeren, Dries, de Weerdt, Okke, van Esser, Joost W J, Bargetzi, Mario, Klein, Saskia K, Gadisseur, Alain, Westerweel, Peter E, Veelken, Hendrik, Gregor, Michael, Silzle, Tobias, van Lammeren-Venema, Daniëlle, Moors, Ine, Breems, Dimitri A, Hoogendoorn, Mels, Legdeur, Marie-Cecile J C, Fischer, Thomas, Kuball, Juergen, Cornelissen, Jan, Porkka, Kimmo, Juliusson, Gunnar, Meyer, Peter, Höglund, Martin, Gjertsen, Bjorn T, Janssen, Jeroen J W M, Huls, Gerwin, Passweg, Jakob, Cloos, Jacqueline, Valk, Peter J M, van Elssen, Catharina H M J, Manz, Markus G, Floisand, Yngvar, and Ossenkoppele, Gert J
- Abstract
Lenalidomide, an antineoplastic and immunomodulatory drug, has therapeutic activity in acute myeloid leukemia (AML), but definitive studies about its therapeutic utility have been lacking. In a phase 3 study, we compared 2 induction regimens in newly diagnosed patients age 18 to 65 years with AML: idarubicine-cytarabine (cycle 1) and daunorubicin and intermediate-dose cytarabine (cycle 2) without or with lenalidomide (15 mg orally on days 1-21). One final consolidation cycle of chemotherapy or autologous stem cell transplantation (auto-SCT) or allogeneic SCT (allo-SCT) was provided according to a prognostic risk and minimal residual disease (MRD)-adapted approach. Event-free survival (EFS; primary end point) and other clinical end points were assessed. A second random assignment in patients in complete response or in complete response with incomplete hematologic recovery after cycle 3 or auto-SCT involved 6 cycles of maintenance with lenalidomide (10 mg on days 1-21) or observation. In all, 392 patients were randomly assigned to the control group, and 388 patients were randomly assigned to lenalidomide induction. At a median follow-up of 41 months, the study revealed no differences in outcome between the treatments (EFS, 44% ± 2% standard error and overall survival, 54% ± 2% at 4 years for both arms) although in an exploratory post hoc analysis, a lenalidomide benefit was suggested in SRSF2-mutant AML. In relation to the previous Dutch-Belgian Hemato-Oncology Cooperative Group and Swiss Group for Clinical Cancer Research (HOVON-SAKK) studies that used a similar 3-cycle regimen but did not pursue an MRD-guided approach, these survival estimates compare markedly more favorably. MRD status after cycle 2 lost prognostic value in intermediate-risk AML in the risk-adjusted treatment context. Maintenance with lenalidomide showed no apparent effect on relapse probability in 88 patients randomly assigned for this part of the study.
- Published
- 2021
4. Addition of lenalidomide to intensive treatment in younger and middle-aged adults with newly diagnosed AML : the HOVON-SAKK-132 trial
- Author
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Löwenberg, Bob, Pabst, Thomas, Maertens, Johan, Gradowska, Patrycja, Biemond, Bart J., Spertini, Olivier, Vellenga, Edo, Griskevicius, Laimonas, Tick, Lidwine W., Jongen-Lavrencic, Mojca, Kooy, Marinus van Marwijk, Vekemans, Marie-Christiane, van der Velden, Walter J. F. M., Beverloo, Berna, Michaux, Lucienne, Graux, Carlos, Deeren, Dries, de Weerdt, Okke, van Esser, Joost W. J., Bargetzi, Mario, Klein, Saskia K., Gadisseur, Alain, Westerweel, Peter E., Veelken, Hendrik, Gregor, Michael, Silzle, Tobias, Van Lammeren-Venema, Danielle, Moors, Ine, Breems, Dimitri A., Hoogendoorn, Mels, Legdeur, Marie-Cecile J. C., Fischer, Thomas, Kuball, Juergen, Cornelissen, Jan, Porkka, Kimmo, Juliusson, Gunnar, Meyer, Peter, Höglund, Martin, Gjertsen, Bjorn T., Janssen, Jeroen J. W. M., Huls, Gerwin, Passweg, Jakob, Cloos, Jacqueline, Valk, Peter J. M., van Elssen, Catharina H. M. J., Manz, Markus G., Floisand, Yngvar, Ossenkoppele, Gert J., Löwenberg, Bob, Pabst, Thomas, Maertens, Johan, Gradowska, Patrycja, Biemond, Bart J., Spertini, Olivier, Vellenga, Edo, Griskevicius, Laimonas, Tick, Lidwine W., Jongen-Lavrencic, Mojca, Kooy, Marinus van Marwijk, Vekemans, Marie-Christiane, van der Velden, Walter J. F. M., Beverloo, Berna, Michaux, Lucienne, Graux, Carlos, Deeren, Dries, de Weerdt, Okke, van Esser, Joost W. J., Bargetzi, Mario, Klein, Saskia K., Gadisseur, Alain, Westerweel, Peter E., Veelken, Hendrik, Gregor, Michael, Silzle, Tobias, Van Lammeren-Venema, Danielle, Moors, Ine, Breems, Dimitri A., Hoogendoorn, Mels, Legdeur, Marie-Cecile J. C., Fischer, Thomas, Kuball, Juergen, Cornelissen, Jan, Porkka, Kimmo, Juliusson, Gunnar, Meyer, Peter, Höglund, Martin, Gjertsen, Bjorn T., Janssen, Jeroen J. W. M., Huls, Gerwin, Passweg, Jakob, Cloos, Jacqueline, Valk, Peter J. M., van Elssen, Catharina H. M. J., Manz, Markus G., Floisand, Yngvar, and Ossenkoppele, Gert J.
- Abstract
Lenalidomide, an antineoplastic and immunomodulatory drug, has therapeutic activity in acute myeloid leukemia (AML), but definitive studies about its therapeutic utility have been lacking. In a phase 3 study, we compared 2 induction regimens in newly diagnosed patients age 18 to 65 years with AML: idarubicine-cytarabine (cycle 1) and daunorubicin and intermediate-dose cytarabine (cycle 2) without or with lenalidomide (15 mg orally on days 1-21). One final consolidation cycle of chemotherapy or autologous stem cell transplantation (auto-SCT) or allogeneic SCT (allo-SCT) was provided according to a prognostic risk and minimal residual disease (MRD)-adapted approach. Event-free survival (EFS; primary end point) and other clinical end points were assessed. A second random assignment in patients in complete response or in complete response with incomplete hematologic recovery after cycle 3 or auto-SCT involved 6 cycles of maintenance with lenalidomide (10 mg on days 1-21) or observation. In all, 392 patients were randomly assigned to the control group, and 388 patients were randomly assigned to lenalidomide induction. At a median follow-up of 41 months, the study revealed no differences in outcome between the treatments (EFS, 44% +/- 2% standard error and overall survival, 54% = 2% at 4 years for both arms) although in an exploratory post hoc analysis, a lenalidomide benefit was suggested in SRSF2-mutant AML. In relation to the previous Dutch-Belgian Hemato-Oncology Cooperative Group and Swiss Group for Clinical Cancer Research (HOVON-SAKK) studies that used a similar 3-cycle regimen but did not pursue an MRD-guided approach, these survival estimates compare markedly more favorably. MRD status after cycle 2 lost prognostic value in intermediate-risk AML in the risk-adjusted treatment context. Maintenance with lenalidomide showed no apparent effect on relapse probability in 88 patients randomly assigned for this part of the study.
- Published
- 2021
- Full Text
- View/download PDF
5. Addition of lenalidomide to intensive treatment in younger and middle-aged adults with newly diagnosed AML: the HOVON-SAKK-132 trial
- Author
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CTI Kuball, MS Hematologie, Infection & Immunity, Regenerative Medicine and Stem Cells, Cancer, Löwenberg, Bob, Pabst, Thomas, Maertens, Johan, Gradowska, Patrycja, Biemond, Bart J, Spertini, Olivier, Vellenga, Edo, Griskevicius, Laimonas, Tick, Lidwine W, Jongen-Lavrencic, Mojca, van Marwijk Kooy, Marinus, Vekemans, Marie-Christiane, van der Velden, Walter J F M, Beverloo, Berna, Michaux, Lucienne, Graux, Carlos, Deeren, Dries, de Weerdt, Okke, van Esser, Joost W J, Bargetzi, Mario, Klein, Saskia K, Gadisseur, Alain, Westerweel, Peter E, Veelken, Hendrik, Gregor, Michael, Silzle, Tobias, van Lammeren-Venema, Daniëlle, Moors, Ine, Breems, Dimitri A, Hoogendoorn, Mels, Legdeur, Marie-Cecile J C, Fischer, Thomas, Kuball, Juergen, Cornelissen, Jan, Porkka, Kimmo, Juliusson, Gunnar, Meyer, Peter, Höglund, Martin, Gjertsen, Bjorn T, Janssen, Jeroen J W M, Huls, Gerwin, Passweg, Jakob, Cloos, Jacqueline, Valk, Peter J M, van Elssen, Catharina H M J, Manz, Markus G, Floisand, Yngvar, Ossenkoppele, Gert J, CTI Kuball, MS Hematologie, Infection & Immunity, Regenerative Medicine and Stem Cells, Cancer, Löwenberg, Bob, Pabst, Thomas, Maertens, Johan, Gradowska, Patrycja, Biemond, Bart J, Spertini, Olivier, Vellenga, Edo, Griskevicius, Laimonas, Tick, Lidwine W, Jongen-Lavrencic, Mojca, van Marwijk Kooy, Marinus, Vekemans, Marie-Christiane, van der Velden, Walter J F M, Beverloo, Berna, Michaux, Lucienne, Graux, Carlos, Deeren, Dries, de Weerdt, Okke, van Esser, Joost W J, Bargetzi, Mario, Klein, Saskia K, Gadisseur, Alain, Westerweel, Peter E, Veelken, Hendrik, Gregor, Michael, Silzle, Tobias, van Lammeren-Venema, Daniëlle, Moors, Ine, Breems, Dimitri A, Hoogendoorn, Mels, Legdeur, Marie-Cecile J C, Fischer, Thomas, Kuball, Juergen, Cornelissen, Jan, Porkka, Kimmo, Juliusson, Gunnar, Meyer, Peter, Höglund, Martin, Gjertsen, Bjorn T, Janssen, Jeroen J W M, Huls, Gerwin, Passweg, Jakob, Cloos, Jacqueline, Valk, Peter J M, van Elssen, Catharina H M J, Manz, Markus G, Floisand, Yngvar, and Ossenkoppele, Gert J
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- 2021
6. Addition of lenalidomide to intensive treatment in younger and middle-aged adults with newly diagnosed AML: the HOVON-SAKK-132 trial
- Author
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Löwenberg, Bob, primary, Pabst, Thomas, additional, Maertens, Johan, additional, Gradowska, Patrycja, additional, Biemond, Bart J., additional, Spertini, Olivier, additional, Vellenga, Edo, additional, Griskevicius, Laimonas, additional, Tick, Lidwine W., additional, Jongen-Lavrencic, Mojca, additional, van Marwijk Kooy, Marinus, additional, Vekemans, Marie-Christiane, additional, van der Velden, Walter J. F. M., additional, Beverloo, Berna, additional, Michaux, Lucienne, additional, Graux, Carlos, additional, Deeren, Dries, additional, de Weerdt, Okke, additional, van Esser, Joost W. J., additional, Bargetzi, Mario, additional, Klein, Saskia K., additional, Gadisseur, Alain, additional, Westerweel, Peter E., additional, Veelken, Hendrik, additional, Gregor, Michael, additional, Silzle, Tobias, additional, van Lammeren-Venema, Daniëlle, additional, Moors, Ine, additional, Breems, Dimitri A., additional, Hoogendoorn, Mels, additional, Legdeur, Marie-Cecile J. C., additional, Fischer, Thomas, additional, Kuball, Juergen, additional, Cornelissen, Jan, additional, Porkka, Kimmo, additional, Juliusson, Gunnar, additional, Meyer, Peter, additional, Höglund, Martin, additional, Gjertsen, Bjorn T., additional, Janssen, Jeroen J. W. M., additional, Huls, Gerwin, additional, Passweg, Jakob, additional, Cloos, Jacqueline, additional, Valk, Peter J. M., additional, van Elssen, Catharina H. M. J., additional, Manz, Markus G., additional, Floisand, Yngvar, additional, and Ossenkoppele, Gert J., additional
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- 2021
- Full Text
- View/download PDF
7. Therapeutic value of clofarabine in younger and middle-aged (18-65 years) adults with newly diagnosed AML
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Löwenberg, Bob, Pabst, Thomas, Maertens, Johan, van Norden, Yvette, Biemond, Bart J, Schouten, Harry C, Spertini, Olivier, Vellenga, Edo, Graux, Carlos, Havelange, Violaine, de Greef, Georgine E, de Weerdt, Okke, Legdeur, Marie-Cecile J C, Kuball, Juergen, Kooy, Marinus van Marwijk, Gjertsen, Bjorn T, Jongen-Lavrencic, Mojca, van de Loosdrecht, Arjan A, van Lammeren-Venema, Daniëlle, Hodossy, Beata, Breems, Dimitri A, Chalandon, Yves, Passweg, Jakob, Valk, Peter J M, Manz, Markus G, Ossenkoppele, Gert J, Dutch-Belgian Hemato-Oncology Cooperative Group (HOVON), Swiss Group for Clinical Cancer Research (SAKK), MUMC+: MA Hematologie (9), RS: GROW - R3 - Innovative Cancer Diagnostics & Therapy, Interne Geneeskunde, CCA - Cancer Treatment and quality of life, Hematology, University of Zurich, Löwenberg, Bob, Guided Treatment in Optimal Selected Cancer Patients (GUTS), Stem Cell Aging Leukemia and Lymphoma (SALL), CCA - Cancer Treatment and Quality of Life, and Clinical Haematology
- Subjects
1303 Biochemistry ,PROGNOSIS ,medicine.medical_treatment ,2720 Hematology ,Hematopoietic stem cell transplantation ,Gastroenterology ,Biochemistry ,RECOMMENDATIONS ,1307 Cell Biology ,0302 clinical medicine ,Clofarabine ,610 Medicine & health ,ddc:616 ,Adenine Nucleotides ,Remission Induction ,Induction Chemotherapy ,Hematology ,Middle Aged ,CHEMOTHERAPY ,Chemotherapy regimen ,CYTARABINE ,Survival Rate ,Leukemia, Myeloid, Acute ,030220 oncology & carcinogenesis ,SURVIVAL ,Nucleophosmin ,medicine.drug ,Adult ,Risk ,medicine.medical_specialty ,Antimetabolites, Antineoplastic ,Adolescent ,Gemtuzumab ozogamicin ,Immunology ,ACUTE MYELOID-LEUKEMIA ,03 medical and health sciences ,Young Adult ,Internal medicine ,medicine ,Journal Article ,Humans ,Survival rate ,Aged ,Chemotherapy ,2403 Immunology ,OLDER PATIENTS ,business.industry ,Myelodysplastic syndromes ,Cell Biology ,medicine.disease ,GEMTUZUMAB OZOGAMICIN ,Surgery ,Consolidation Chemotherapy ,10032 Clinic for Oncology and Hematology ,Cytarabine ,Arabinonucleosides ,business ,030215 immunology - Abstract
Clofarabine has demonstrated antileukemic activity in acute myeloid leukemia (AML) but has yet to be critically evaluated in younger adults in the frontline with standard chemotherapy. We compared 2 induction regimens in newly diagnosed patients ages 18 to 65 with acute myeloid leukemia (AML)/high-risk myelodysplastic syndromes, that is, idarubicine-cytarabine (cycle I) and amsacrine-cytarabine (cycle II) without or with clofarabine (10 mg/m 2 on days 1-5 of each of both cycles). Consolidation involved chemotherapy with or without hematopoietic stem cell transplantation. Event-free survival (EFS, primary endpoint) and other clinical endpoints and toxicities were assessed. We randomized 402 and 393 evaluable patients to the control or clofarabine induction treatment arms. Complete remission rates (89%) did not differ but were attained faster with clofarabine (66% vs 75% after cycle I). Clofarabine added grades 3 to 4 toxicities and delayed hematological recovery. At a median follow-up of 36 months, the study revealsnodifferences in overall survival and EFS between the control (EFS, 35% 63 [ standard error] at 4 years) and clofarabine treatments (38% +/- 3) but a markedly reduced relapse rate (44% +/- 3 vs 35% +/- 3) in favor of clofarabine and an increased death probability in remission (15% +/- 2 vs 22% +/- 3). In the subgroup analyses, clofarabine improved overall survival and EFS for European Leukemia Net (ELN) 2010 intermediate I prognostic riskAML(EFS, 26% +/- 4 vs40% +/- 5 at 4 years; CoxP5.002) and for the intermediate risk genotype NPM1 wild-type/FLT3 without internal-tandem duplications (EFS, 18% +/- 5 vs 40% +/- 7; Cox P
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- 2017
8. Therapeutic value of clofarabine in younger and middle aged (18 - 65 yrs) adults with newly diagnosed AML.
- Author
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UCL - SSS/IREC/MONT-Pôle Mont Godinne, UCL - SSS/DDUV - Institut de Duve, UCL - SSS/DDUV/MEXP - Médecine expérimentale, UCL - (MGD) Service d'hématologie, UCL - (SLuc) Service d'hématologie, Löwenberg, Bob, Pabst, Thomas, Maertens, Johan, van Norden, Yvette, Biemond, Bart J, Schouten, Harry C, Spertini, Olivier, Vellenga, Edo, Graux, Carlos, Havelange, Violaine, de Greef, Georgine E, de Weerdt, Okke, Legdeur, Marie-Cecile J C, Kuball, Juergen, van Marwijk Kooy, Marinus, Gjertsen, Bjorn T, Jongen-Lavrencic, Mojca, van de Loosdrecht, Arjan A, van Lammeren-Venema, Daniëlle, Hodossy, Beata, Breems, Dimitri A, Chalandon, Yves, Passweg, Jakob, Valk, Peter J M, Manz, Markus G, Ossenkoppele, Gert J, Dutch-Belgian Hemato-Oncology Cooperative Group (HOVON), Swiss Group for Clinical Cancer Research (SAKK), UCL - SSS/IREC/MONT-Pôle Mont Godinne, UCL - SSS/DDUV - Institut de Duve, UCL - SSS/DDUV/MEXP - Médecine expérimentale, UCL - (MGD) Service d'hématologie, UCL - (SLuc) Service d'hématologie, Löwenberg, Bob, Pabst, Thomas, Maertens, Johan, van Norden, Yvette, Biemond, Bart J, Schouten, Harry C, Spertini, Olivier, Vellenga, Edo, Graux, Carlos, Havelange, Violaine, de Greef, Georgine E, de Weerdt, Okke, Legdeur, Marie-Cecile J C, Kuball, Juergen, van Marwijk Kooy, Marinus, Gjertsen, Bjorn T, Jongen-Lavrencic, Mojca, van de Loosdrecht, Arjan A, van Lammeren-Venema, Daniëlle, Hodossy, Beata, Breems, Dimitri A, Chalandon, Yves, Passweg, Jakob, Valk, Peter J M, Manz, Markus G, Ossenkoppele, Gert J, Dutch-Belgian Hemato-Oncology Cooperative Group (HOVON), and Swiss Group for Clinical Cancer Research (SAKK)
- Abstract
Clofarabine has demonstrated antileukemic activity in acute myeloid leukemia (AML) but has yet to be critically evaluated in younger adults in the frontline with standard chemotherapy. We compared two induction regimens in newly diagnosed patients aged 18-65 with AML/high risk MDS, i.e., idarubicine-cytarabine (cycle I) and amsacrine-cytarabine (cycle II) without or with clofarabine (10 mg/m(2) on days 1-5 of each of both cycles). Consolidation involved chemotherapy with or without hematopoietic stem cell transplantation. Event free survival (EFS, primary endpoint) and other clinical endpoints and toxicities were assessed. 402 and 393 evaluable patients were randomized to the control or clofarabine induction treatment arms. Complete remission rates (89%) did not differ but were attained faster with clofarabine (66% versus 75% after cycle I). Clofarabine added grade III-IV toxicities, and delayed hematological recovery. At a median follow up of 36 months, the study reveals no differences in overall survival and EFS between the control (EFS 35% ±3 (SE) at 4 years) and clofarabine treatments (38% ±3) but a markedly reduced relapse rate (44% ± 3 versus 35% ± 3) in favor of clofarabine and an increased death probability in remission (15% ±2 versus 22% ±3). In the subgroup analyses, clofarabine improved OS and EFS for European-Leukemia-Net ELN 2010 Intermediate-I prognostic risk AML (EFS 26 % ±4 versus 40% ±5 at 4 years, Cox-P=0.002) and for the intermediate risk genotype NPM1wild type/FLT3 without internal-tandem-duplications (EFS 18% ±5 versus 40% ±7, Cox- P<0.001). Clofarabine improves survival in subsets of intermediate-risk AML only.
- Published
- 2017
9. Graft-Versus-Leukemia Effect of Allogeneic Stem-Cell Transplantation and Minimal Residual Disease in Patients With Acute Myeloid Leukemia in First Complete Remission.
- Author
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UCL - (SLuc) Centre du cancer, UCL - SSS/IREC/SLUC - Pôle St.-Luc, UCL - (SLuc) Service d'hématologie, Versluis, Jurjen, Kalin, Burak, Zeijlemaker, Wendelien, Passweg, Jakob, Graux, Carlos, Manz, Markus G, Vekemans, Marie-Christiane, Biemond, Bart J, Legdeur, Marie-Cecile J C, Kooy, Marinus van Marwijk, de Weerdt, Okke, Wijermans, Pierre W, Hoogendoorn, Mels, Bargetzi, Mario J, Kuball, Juergen, Schouten, Harry C, van der Velden, Vincent H J, Janssen, Jeroen J W M, Pabst, Thomas, Lowenberg, Bob, Jongen-Lavrencic, Mojca, Schuurhuis, Gerrit Jan, Ossenkoppele, Gert, Cornelissen, Jan J, UCL - (SLuc) Centre du cancer, UCL - SSS/IREC/SLUC - Pôle St.-Luc, UCL - (SLuc) Service d'hématologie, Versluis, Jurjen, Kalin, Burak, Zeijlemaker, Wendelien, Passweg, Jakob, Graux, Carlos, Manz, Markus G, Vekemans, Marie-Christiane, Biemond, Bart J, Legdeur, Marie-Cecile J C, Kooy, Marinus van Marwijk, de Weerdt, Okke, Wijermans, Pierre W, Hoogendoorn, Mels, Bargetzi, Mario J, Kuball, Juergen, Schouten, Harry C, van der Velden, Vincent H J, Janssen, Jeroen J W M, Pabst, Thomas, Lowenberg, Bob, Jongen-Lavrencic, Mojca, Schuurhuis, Gerrit Jan, Ossenkoppele, Gert, and Cornelissen, Jan J
- Abstract
The detection of minimal residual disease (MRD) in patients with acute myeloid leukemia (AML) may improve future risk-adapted treatment strategies. We assessed whether MRD-positive and MRD-negative patients with AML benefit differently from the graft-versus-leukemia effect of allogeneic hematopoietic stem-cell transplantation (alloHSCT). A total of 1,511 patients were treated in subsequent Dutch-Belgian Hemato-Oncology Cooperative Group and the Swiss Group for Clinical Cancer Research AML trials, of whom 547 obtained a first complete remission, received postremission treatment (PRT), and had available flow cytometric MRD before PRT. MRD positivity was defined as more than 0.1% cells with a leukemia-associated immunophenotype within the WBC compartment. PRT consisted of alloHSCT (n = 282), conventional PRT by a third cycle of chemotherapy (n = 160), or autologous hematopoietic stem-cell transplantation (n = 105). MRD was positive in 129 patients (24%) after induction chemotherapy before proceeding to PRT. Overall survival and relapse-free survival were significantly better in patients without MRD before PRT compared with MRD-positive patients (65% ± 2% 50% ± 5% at 4 years; = .002; and 58% ± 3% 38% ± 4%; < .001, respectively), which was mainly because of a lower cumulative incidence of relapse (32% ± 2% compared with 54% ± 4%; < .001, respectively). Multivariable analysis with adjustment for covariables showed that the incidence of relapse was significantly reduced after alloHSCT compared with chemotherapy or autologous hematopoietic stem cell transplantation (hazard ratio [HR], 0.36; < .001), which was similarly exerted in both MRD-negative and MRD-positive patients (HR, 0.38; < .001; and HR, 0.35; < .001, respectively). The graft-versus-leukemia effect of alloHSCT is equally present in MRD-positive and MRD-negative patients, which advocates a personalized application of alloHSCT, taking into account the risk of relapse determined by AML risk group and MRD status, as
- Published
- 2017
10. Therapeutic value of clofarabine in younger and middle-aged (18-65 years) adults with newly diagnosed AML
- Author
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Stamceltransplantatieteam, CTI Kuball, MS Hematologie, Infection & Immunity, Regenerative Medicine and Stem Cells, Cancer, Löwenberg, Bob, Pabst, Thomas, Maertens, Johan, van Norden, Yvette, Biemond, Bart J., Schouten, Harry C., Spertini, Olivier, Vellenga, Edo, Graux, Carlos, Havelange, Violaine, de Greef, Georgine E, De Weerdt, Okke, Legdeur, Marie-Cecile J C, Kuball, Juergen, van Marwijk Kooy, Marinus, Gjertsen, Bjorn T, Jongen-Lavrencic, Mojca, van de Loosdrecht, Arjan A, van Lammeren-Venema, Daniëlle, Hodossy, Beata, Breems, Dimitri A, Chalandon, Yves, Passweg, Jakob, Valk, Peter J M, Manz, Markus G, Ossenkoppele, Gert J, Stamceltransplantatieteam, CTI Kuball, MS Hematologie, Infection & Immunity, Regenerative Medicine and Stem Cells, Cancer, Löwenberg, Bob, Pabst, Thomas, Maertens, Johan, van Norden, Yvette, Biemond, Bart J., Schouten, Harry C., Spertini, Olivier, Vellenga, Edo, Graux, Carlos, Havelange, Violaine, de Greef, Georgine E, De Weerdt, Okke, Legdeur, Marie-Cecile J C, Kuball, Juergen, van Marwijk Kooy, Marinus, Gjertsen, Bjorn T, Jongen-Lavrencic, Mojca, van de Loosdrecht, Arjan A, van Lammeren-Venema, Daniëlle, Hodossy, Beata, Breems, Dimitri A, Chalandon, Yves, Passweg, Jakob, Valk, Peter J M, Manz, Markus G, and Ossenkoppele, Gert J
- Published
- 2017
11. Phase 1a/1b and pharmacogenetic study of docetaxel, oxaliplatin and capecitabine in patients with advanced cancer of the stomach or the gastroesophageal junction
- Author
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Deenen, MJ, Meulendijks, Didier, Boot, Henk, Legdeur, Marie Cecile J C, Beijnen, Jos H., Schellens, Jan H M, Cats, Annemieke, Pharmacoepidemiology and Clinical Pharmacology, and Sub Clinical Pharmacology
- Subjects
Oxaliplatin ,Pharmacology ,Cancer Research ,Oncology ,Pharmacogenetics ,Pharmacokinetics ,Pharmacology (medical) ,Docetaxel ,Gastric cancer ,Toxicology ,Capecitabine - Abstract
Purpose: The prognosis of gastroesophageal cancer is poor, and current regimens are associated with limited efficacy. The purpose of this study was to explore the safety and preliminary efficacy of docetaxel, oxaliplatin plus capecitabine for advanced cancer of the stomach or the gastroesophageal junction (GEJ). Secondary objectives included pharmacokinetic and pharmacogenetic analyses. Methods: Patients were treated in escalating dose levels with docetaxel and oxaliplatin (both on day 1), plus capecitabine b.i.d. on days 1-14 every 3 weeks, to determine the dose-limiting toxicity and maximum tolerated dose (MTD). An expansion cohort was treated at the MTD. A total of ten polymorphisms in pharmacokinetic and pharmacodynamic candidate genes were analyzed and tested for association with treatment outcome. Results: A total of 34 evaluable patients were enrolled. The MTD was docetaxel 50 mg/m2, oxaliplatin 100 mg/m2 plus capecitabine 850 mg/m2 b.i.d. The median number of treatment cycles was 6 (range 2-8). Grade ≤ 3 toxicities included neutropenia (24 %), leukocytopenia (15 %), febrile neutropenia (12 %), fatigue (9 %) and diarrhea (6 %). The overall response rate was 45 %; two patients achieved a complete response. Median progression-free survival and overall survival were 6.5 months (95 % CI 5.4-7.6) and 11.0 months (95 % CI 7.9-14.1), respectively. The polymorphisms ERCC1 354C>T, TYMS 1053C>T and rs2612091 in ENOSF1 were associated with severe toxicity; ERCC1 354C>T and ERCC2 2251A>C were associated with poor progression-free survival. Conclusion: Docetaxel, oxaliplatin plus capecitabine are a well-tolerable, safe and effective treatment regimen for patients with advanced cancer of the stomach or GEJ. Pharmacogenetic markers in pharmacokinetic and pharmacodynamic candidate genes may be predictive for treatment outcome.
- Published
- 2015
12. Phase 1a/1b and pharmacogenetic study of docetaxel, oxaliplatin and capecitabine in patients with advanced cancer of the stomach or the gastroesophageal junction
- Author
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Pharmacoepidemiology and Clinical Pharmacology, Sub Clinical Pharmacology, Deenen, MJ, Meulendijks, Didier, Boot, Henk, Legdeur, Marie Cecile J C, Beijnen, Jos H., Schellens, Jan H M, Cats, Annemieke, Pharmacoepidemiology and Clinical Pharmacology, Sub Clinical Pharmacology, Deenen, MJ, Meulendijks, Didier, Boot, Henk, Legdeur, Marie Cecile J C, Beijnen, Jos H., Schellens, Jan H M, and Cats, Annemieke
- Published
- 2015
13. Addition of lenalidomide to intensive treatment in younger and middle-aged adults with newly diagnosed AML: the HOVON-SAKK-132 trial
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Löwenberg, Bob, Pabst, Thomas, Maertens, Johan, Gradowska, Patrycja, Biemond, Bart J, Spertini, Olivier, Vellenga, Edo, Griskevicius, Laimonas, Tick, Lidwine W, Jongen-Lavrencic, Mojca, van Marwijk Kooy, Marinus, Vekemans, Marie-Christiane, van der Velden, Walter J F M, Beverloo, Berna, Michaux, Lucienne, Graux, Carlos, Deeren, Dries, de Weerdt, Okke, van Esser, Joost W J, Bargetzi, Mario, Klein, Saskia K, Gadisseur, Alain, Westerweel, Peter E, Veelken, Hendrik, Gregor, Michael, Silzle, Tobias, van Lammeren-Venema, Daniëlle, Moors, Ine, Breems, Dimitri A, Hoogendoorn, Mels, Legdeur, Marie-Cecile J C, Fischer, Thomas, Kuball, Juergen, Cornelissen, Jan, Porkka, Kimmo, Juliusson, Gunnar, Meyer, Peter, Höglund, Martin, Gjertsen, Bjorn T, Janssen, Jeroen J W M, Huls, Gerwin, Passweg, Jakob, Cloos, Jacqueline, Valk, Peter J M, van Elssen, Catharina H M J, Manz, Markus G, Floisand, Yngvar, and Ossenkoppele, Gert J
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hemic and lymphatic diseases ,610 Medizin und Gesundheit ,3. Good health - Abstract
Lenalidomide, an antineoplastic and immunomodulatory drug, has therapeutic activity in acute myeloid leukemia (AML), but definitive studies about its therapeutic utility have been lacking. In a phase 3 study, we compared 2 induction regimens in newly diagnosed patients age 18 to 65 years with AML: idarubicine-cytarabine (cycle 1) and daunorubicin and intermediate-dose cytarabine (cycle 2) without or with lenalidomide (15 mg orally on days 1-21). One final consolidation cycle of chemotherapy or autologous stem cell transplantation (auto-SCT) or allogeneic SCT (allo-SCT) was provided according to a prognostic risk and minimal residual disease (MRD)-adapted approach. Event-free survival (EFS; primary end point) and other clinical end points were assessed. A second random assignment in patients in complete response or in complete response with incomplete hematologic recovery after cycle 3 or auto-SCT involved 6 cycles of maintenance with lenalidomide (10 mg on days 1-21) or observation. In all, 392 patients were randomly assigned to the control group, and 388 patients were randomly assigned to lenalidomide induction. At a median follow-up of 41 months, the study revealed no differences in outcome between the treatments (EFS, 44% ± 2% standard error and overall survival, 54% ± 2% at 4 years for both arms) although in an exploratory post hoc analysis, a lenalidomide benefit was suggested in SRSF2-mutant AML. In relation to the previous Dutch-Belgian Hemato-Oncology Cooperative Group and Swiss Group for Clinical Cancer Research (HOVON-SAKK) studies that used a similar 3-cycle regimen but did not pursue an MRD-guided approach, these survival estimates compare markedly more favorably. MRD status after cycle 2 lost prognostic value in intermediate-risk AML in the risk-adjusted treatment context. Maintenance with lenalidomide showed no apparent effect on relapse probability in 88 patients randomly assigned for this part of the study.
14. Graft-Versus-Leukemia Effect of Allogeneic Stem-Cell Transplantation and Minimal Residual Disease in Patients With Acute Myeloid Leukemia in First Complete Remission.
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Versluis J, Kalin B, Zeijlemaker W, Passweg J, Graux C, Manz MG, Vekemans MC, Biemond BJ, Legdeur MJC, Kooy MVM, de Weerdt O, Wijermans PW, Hoogendoorn M, Bargetzi MJ, Kuball J, Schouten HC, van der Velden VHJ, Janssen JJWM, Pabst T, Lowenberg B, Jongen-Lavrencic M, Schuurhuis GJ, Ossenkoppele G, and Cornelissen JJ
- Abstract
Purpose: The detection of minimal residual disease (MRD) in patients with acute myeloid leukemia (AML) may improve future risk-adapted treatment strategies. We assessed whether MRD-positive and MRD-negative patients with AML benefit differently from the graft-versus-leukemia effect of allogeneic hematopoietic stem-cell transplantation (alloHSCT)., Methods: A total of 1,511 patients were treated in subsequent Dutch-Belgian Hemato-Oncology Cooperative Group and the Swiss Group for Clinical Cancer Research AML trials, of whom 547 obtained a first complete remission, received postremission treatment (PRT), and had available flow cytometric MRD before PRT. MRD positivity was defined as more than 0.1% cells with a leukemia-associated immunophenotype within the WBC compartment. PRT consisted of alloHSCT (n = 282), conventional PRT by a third cycle of chemotherapy (n = 160), or autologous hematopoietic stem-cell transplantation (n = 105)., Results: MRD was positive in 129 patients (24%) after induction chemotherapy before proceeding to PRT. Overall survival and relapse-free survival were significantly better in patients without MRD before PRT compared with MRD-positive patients (65% ± 2% v 50% ± 5% at 4 years; P = .002; and 58% ± 3% v 38% ± 4%; P < .001, respectively), which was mainly because of a lower cumulative incidence of relapse (32% ± 2% compared with 54% ± 4%; P < .001, respectively). Multivariable analysis with adjustment for covariables showed that the incidence of relapse was significantly reduced after alloHSCT compared with chemotherapy or autologous hematopoietic stem cell transplantation (hazard ratio [HR], 0.36; P < .001), which was similarly exerted in both MRD-negative and MRD-positive patients (HR, 0.38; P < .001; and HR, 0.35; P < .001, respectively)., Conclusion: The graft-versus-leukemia effect of alloHSCT is equally present in MRD-positive and MRD-negative patients, which advocates a personalized application of alloHSCT, taking into account the risk of relapse determined by AML risk group and MRD status, as well as the counterbalancing risk of nonrelapse mortality.
- Published
- 2017
- Full Text
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