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Article ; Online: Acute myeloid leukemia with monosomal karyotype at the far end of the unfavorable prognostic spectrum.

Breems, Dimitri A / Löwenberg, Bob

2011 Volume 96, Issue 4, Page(s) 491–493

MeSH term(s)	Humans ; Karyotyping ; Leukemia, Myeloid, Acute/diagnosis ; Leukemia, Myeloid, Acute/genetics ; Leukemia, Myeloid, Acute/mortality ; Leukemia, Myeloid, Acute/therapy ; Monosomy/genetics ; Prognosis
Language	English
Publishing date	2011-03-31
Publishing country	Italy
Document type	Comment ; Editorial
ZDB-ID	2333-4
ISSN	1592-8721 ; 0017-6567 ; 0390-6078
ISSN (online)	1592-8721
ISSN	0017-6567 ; 0390-6078
DOI	10.3324/haematol.2011.043208
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Article ; Online: Measurable residual disease-guided therapy in intermediate-risk acute myeloid leukemia patients is a valuable strategy in reducing allogeneic transplantation without negatively affecting survival.

Tettero, Jesse M / Ngai, Lok Lam / Bachas, Costa / Breems, Dimitri A / Fischer, Thomas / Gjertsen, Bjorn T / Gradowska, Patrycja / Griskevicius, Laimonas / Janssen, Jeroen J W M / Juliusson, Gunnar / Maertens, Johan / Manz, Markus G / Pabst, Thomas / Passweg, Jakob / Porkka, Kimmo / Valk, Peter J M / Löwenberg, Bob / Ossenkoppele, Gert J / Cloos, Jacqueline

Haematologica

2023 Volume 108, Issue 10, Page(s) 2794–2798

MeSH term(s)	Humans ; Transplantation, Homologous ; Hematopoietic Stem Cell Transplantation ; Leukemia, Myeloid, Acute/therapy ; Neoplasm, Residual ; Recurrence ; Transplantation Conditioning
Language	English
Publishing date	2023-10-01
Publishing country	Italy
Document type	Letter
ZDB-ID	2333-4
ISSN	1592-8721 ; 0017-6567 ; 0390-6078
ISSN (online)	1592-8721
ISSN	0017-6567 ; 0390-6078
DOI	10.3324/haematol.2022.282639
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Article: Acute myeloid leukemia and the position of autologous stem cell transplantation.

Breems, Dimitri A / Löwenberg, Bob

Seminars in hematology

2007 Volume 44, Issue 4, Page(s) 259–266

Abstract: Most adult patients with acute myeloid leukemia (AML) who reach a complete remission (CR) after induction chemotherapy will relapse if they do not receive further therapy. Autologous stem cell transplantation (SCT) represents one of the options of ... ...

Abstract	Most adult patients with acute myeloid leukemia (AML) who reach a complete remission (CR) after induction chemotherapy will relapse if they do not receive further therapy. Autologous stem cell transplantation (SCT) represents one of the options of postremission therapy in AML. Here we discuss the therapeutic impact of consolidation treatment with autologous SCT that has been studied extensively. Meta-analyses of published randomized trials using bone marrow as the source of stem cells show a modest improvement of disease-free survival as compared to nonmyeloablative chemotherapy. However, there is no apparent improvement of overall survival, probably due to the slightly increased mortality associated with autologous bone marrow transplantation (BMT). Subsequently, the value of autologous SCT in different prognostic subsets of AML is discussed. Autologous mobilized peripheral blood stem cell (PBSC) transplantation offers a much faster hematopoietic recovery and is associated with reduced morbidity and treatment-related mortality. To fully appreciate the role of autologous PBSC transplantation, the results of a recently closed randomized trial must be awaited.
MeSH term(s)	Adult ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Bone Marrow Transplantation ; Combined Modality Therapy ; Disease-Free Survival ; Evidence-Based Medicine ; Hematopoietic Stem Cell Transplantation ; Humans ; Leukemia, Myeloid, Acute/drug therapy ; Leukemia, Myeloid, Acute/mortality ; Leukemia, Myeloid, Acute/radiotherapy ; Leukemia, Myeloid, Acute/surgery ; Peripheral Blood Stem Cell Transplantation ; Randomized Controlled Trials as Topic ; Risk Assessment/methods ; Transplantation, Autologous ; Transplantation, Homologous
Language	English
Publishing date	2007-10
Publishing country	United States
Document type	Evaluation Studies ; Journal Article ; Review
ZDB-ID	206923-4
ISSN	1532-8686 ; 0037-1963
ISSN (online)	1532-8686
ISSN	0037-1963
DOI	10.1053/j.seminhematol.2007.08.002
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Article ; Online: The impact of abn(17p) and monosomy -5/del(5q) on the prognostic value of the monosomal karyotype in acute myeloid leukemia.

Breems, Dimitri A / Van Putten, Wim L J / Löwenberg, Bob

Blood

2013 Volume 121, Issue 15, Page(s) 3056–3057

MeSH term(s)	Acute Disease ; Chromosome Aberrations ; Chromosome Deletion ; Chromosomes, Human, Pair 17/genetics ; Chromosomes, Human, Pair 5/genetics ; Disease-Free Survival ; Humans ; Karyotype ; Leukemia, Myeloid/genetics ; Leukemia, Myeloid/surgery ; Monosomy ; Multivariate Analysis ; Prognosis ; Regression Analysis ; Stem Cell Transplantation/methods ; Time Factors ; Transplantation, Homologous
Language	English
Publishing date	2013-04-11
Publishing country	United States
Document type	Letter
ZDB-ID	80069-7
ISSN	1528-0020 ; 0006-4971
ISSN (online)	1528-0020
ISSN	0006-4971
DOI	10.1182/blood-2013-01-475012
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Uh III Zs.140: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular ab Jg. 2022: Lesesaal (EG)
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Article ; Online: The added value of multi-state modelling in a randomized controlled trial: The HOVON 102 study re-analyzed.

Bakunina, Katerina / Putter, Hein / Versluis, Jurjen / Koster, Eva A S / van der Holt, Bronno / Manz, Markus G / Breems, Dimitri A / Gjertsen, Bjorn T / Cloos, Jacqueline / Valk, Peter J M / Passweg, Jakob / Pabst, Thomas / Ossenkoppele, Gert J / Löwenberg, Bob / Cornelissen, Jan J / de Wreede, Liesbeth C

Cancer medicine

2021 Volume 11, Issue 3, Page(s) 630–640

Abstract: Clofarabine is an active antileukemic drug for subgroups of patients with acute myeloid leukemia (AML). Multi-state models can provide additional insights to supplement the original intention-to-treat analysis of randomized controlled trials (RCT). We re- ...

Abstract	Clofarabine is an active antileukemic drug for subgroups of patients with acute myeloid leukemia (AML). Multi-state models can provide additional insights to supplement the original intention-to-treat analysis of randomized controlled trials (RCT). We re-analyzed the HOVON102/SAKK30/09 phase III RCT for newly diagnosed AML patients, which randomized between standard induction chemotherapy with or without clofarabine. Using multi-state models, we evaluated the effects of induction chemotherapy outcomes (complete remission [CR], measurable residual disease [MRD]), and post-remission therapy with allogeneic stem cell transplantation [alloSCT] on relapse and death. Through the latter a consistent reduction in the hazard of relapse in the clofarabine arm compared to the standard arm was found, which occurred irrespective of MRD status or post-remission treatment with alloSCT, demonstrating a strong and persistent antileukemic effect of clofarabine. During the time period between achieving CR and possible post-remission treatment with alloSCT, non-relapse mortality was higher in patients receiving clofarabine. An overall net benefit of treatment with clofarabine was identified using the composite endpoint current leukemia-free survival (CLFS). In conclusion, these results enforce and extend the earlier reported beneficial effect of clofarabine in AML and show that multi-state models further detail the effect of treatment on competing and series of events.
MeSH term(s)	Clofarabine/therapeutic use ; Hematopoietic Stem Cell Transplantation ; Humans ; Leukemia, Myeloid, Acute/drug therapy ; Recurrence ; Remission Induction ; Treatment Outcome
Chemical Substances	Clofarabine (762RDY0Y2H)
Language	English
Publishing date	2021-12-24
Publishing country	United States
Document type	Journal Article ; Randomized Controlled Trial
ZDB-ID	2659751-2
ISSN	2045-7634 ; 2045-7634
ISSN (online)	2045-7634
ISSN	2045-7634
DOI	10.1002/cam4.4392
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Article: Concordance in measurable residual disease result after first and second induction cycle in acute myeloid leukemia: An outcome- and cost-analysis.

Frontiers in oncology

2022 Volume 12, Page(s) 999822

Abstract: Measurable residual disease (MRD) measured using multiparameter flow-cytometry (MFC) has proven to be an important prognostic biomarker in acute myeloid leukemia (AML). In addition, MRD is increasingly used to guide consolidation treatment towards a non- ... ...

Abstract	Measurable residual disease (MRD) measured using multiparameter flow-cytometry (MFC) has proven to be an important prognostic biomarker in acute myeloid leukemia (AML). In addition, MRD is increasingly used to guide consolidation treatment towards a non-allogenic stem cell transplantation treatment for MRD-negative patients in the ELN-2017 intermediate risk group. Currently, measurement of MFC-MRD in bone marrow is used for clinical decision making after 2 cycles of induction chemotherapy. However, measurement after 1 cycle has also been shown to have prognostic value, so the optimal time point remains a question of debate. We assessed the independent prognostic value of MRD results at either time point and concordance between these for 273 AML patients treated within and according to the HOVON-SAKK 92, 102, 103 and 132 trials. Cumulative incidence of relapse, event free survival and overall survival were significantly better for MRD-negative (<0.1%) patients compared to MRD-positive patients after cycle 1 and cycle 2 (
Language	English
Publishing date	2022-10-10
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2649216-7
ISSN	2234-943X
ISSN	2234-943X
DOI	10.3389/fonc.2022.999822
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Article ; Online: Molecular characterization of mutant TP53 acute myeloid leukemia and high-risk myelodysplastic syndrome.

Blood

2022 Volume 139, Issue 15, Page(s) 2347–2354

Abstract: Substantial heterogeneity within mutant TP53 acute myeloid leukemia (AML) and myelodysplastic syndrome with excess of blast (MDS-EB) precludes the exact assessment of prognostic impact for individual patients. We performed in-depth clinical and molecular ...

Abstract	Substantial heterogeneity within mutant TP53 acute myeloid leukemia (AML) and myelodysplastic syndrome with excess of blast (MDS-EB) precludes the exact assessment of prognostic impact for individual patients. We performed in-depth clinical and molecular analysis of mutant TP53 AML and MDS-EB to dissect the molecular characteristics in detail and determine its impact on survival. We performed next-generation sequencing on 2200 AML/MDS-EB specimens and assessed the TP53 mutant allelic status (mono- or bi-allelic), the number of TP53 mutations, mutant TP53 clone size, concurrent mutations, cytogenetics, and mutant TP53 molecular minimal residual disease and studied the associations of these characteristics with overall survival. TP53 mutations were detected in 230 (10.5%) patients with AML/MDS-EB with a median variant allele frequency of 47%. Bi-allelic mutant TP53 status was observed in 174 (76%) patients. Multiple TP53 mutations were found in 49 (21%) patients. Concurrent mutations were detected in 113 (49%) patients. No significant difference in any of the aforementioned molecular characteristics of mutant TP53 was detected between AML and MDS-EB. Patients with mutant TP53 have a poor outcome (2-year overall survival, 12.8%); however, no survival difference between AML and MDS-EB was observed. Importantly, none of the molecular characteristics were significantly associated with survival in mutant TP53 AML/MDS-EB. In most patients, TP53 mutations remained detectable in complete remission by deep sequencing (73%). Detection of residual mutant TP53 was not associated with survival. Mutant TP53 AML and MDS-EB do not differ with respect to molecular characteristics and survival. Therefore, mutant TP53 AML/MDS-EB should be considered a distinct molecular disease entity.
MeSH term(s)	Cytogenetics ; Humans ; Leukemia, Myeloid, Acute/diagnosis ; Mutation ; Myelodysplastic Syndromes/diagnosis ; Tumor Suppressor Protein p53/genetics
Chemical Substances	TP53 protein, human ; Tumor Suppressor Protein p53
Language	English
Publishing date	2022-02-19
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	80069-7
ISSN	1528-0020 ; 0006-4971
ISSN (online)	1528-0020
ISSN	0006-4971
DOI	10.1182/blood.2021014472
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Article: Autologous stem cell transplantation in the treatment of adults with acute myeloid leukaemia.

Breems, Dimitri A / Löwenberg, Bob

British journal of haematology

2005 Volume 130, Issue 6, Page(s) 825–833

Abstract: Most adult patients under 60 years with acute myeloid leukaemia (AML) who achieve a complete remission after induction chemotherapy will relapse if they do not receive further therapy. Consolidation treatment with autologous stem cell transplantation ( ... ...

Abstract	Most adult patients under 60 years with acute myeloid leukaemia (AML) who achieve a complete remission after induction chemotherapy will relapse if they do not receive further therapy. Consolidation treatment with autologous stem cell transplantation (SCT) is one option that has been studied extensively. High-dose cytotoxic therapy followed by autologous SCT or intensive cycles of chemotherapy furnish overall approximately similar probabilities of survival when applied in first remission. Here, we present a concise update regarding the place of autologous SCT in the treatment of AML. Particular issues discussed are the value of autologous SCT in different prognostic subsets of AML and the value of autologous mobilised peripheral blood stem cell transplants, which offer a much faster haematopoietic recovery.
MeSH term(s)	Acute Disease ; Adult ; Hematopoietic Stem Cell Mobilization ; Humans ; Leukemia, Myeloid/therapy ; Peripheral Blood Stem Cell Transplantation/methods ; Prognosis ; Stem Cell Transplantation/methods
Language	English
Publishing date	2005-09
Publishing country	England
Document type	Journal Article ; Meta-Analysis ; Review
ZDB-ID	80077-6
ISSN	1365-2141 ; 0007-1048
ISSN (online)	1365-2141
ISSN	0007-1048
DOI	10.1111/j.1365-2141.2005.05628.x
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Article ; Online: Prospective validation of the prognostic relevance of CD34+CD38- AML stem cell frequency in the HOVON-SAKK132 trial.

Ngai, Lok Lam / Hanekamp, Diana / Janssen, Fleur / Carbaat-Ham, Jannemieke / Hofland, Maaike A M A / Fayed, Mona M H E / Kelder, Angèle / Oudshoorn-van Marsbergen, Laura / Scholten, Willemijn J / Snel, Alexander N / Bachas, Costa / Tettero, Jesse M / Breems, Dimitri A / Fischer, Thomas / Gjertsen, Bjørn T / Griškevičius, Laimonas / Juliusson, Gunnar / van de Loosdrecht, Arjan A / Maertens, Johan A /

Manz, Markus G / Pabst, Thomas / Passweg, Jakob R / Porkka, Kimmo / Valk, Peter J M / Gradowska, Patrycja / Löwenberg, Bob / de Leeuw, David C / Janssen, Jeroen J W M / Ossenkoppele, Gert J / Cloos, Jacqueline

Blood

2023 Volume 141, Issue 21, Page(s) 2657–2661

MeSH term(s)	Humans ; Prognosis ; Antigens, CD34 ; ADP-ribosyl Cyclase 1 ; Leukemia, Myeloid, Acute ; Stem Cells ; Neoplastic Stem Cells ; Flow Cytometry
Chemical Substances	Antigens, CD34 ; ADP-ribosyl Cyclase 1 (EC 3.2.2.6)
Language	English
Publishing date	2023-03-09
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	80069-7
ISSN	1528-0020 ; 0006-4971
ISSN (online)	1528-0020
ISSN	0006-4971
DOI	10.1182/blood.2022019160
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Article ; Online: A phase 2, randomized, double-blind, multicenter study comparing siltuximab plus best supportive care (BSC) with placebo plus BSC in anemic patients with International Prognostic Scoring System low- or intermediate-1-risk myelodysplastic syndrome.

Garcia-Manero, Guillermo / Gartenberg, Gary / Steensma, David P / Schipperus, Martin R / Breems, Dimitri A / de Paz, Raquel / Valcárcel, David / Kranenburg, Britte / Reddy, Manjula / Komrokji, Rami S

American journal of hematology

2014 Volume 89, Issue 9, Page(s) E156–62

Abstract: Interleukin-6 (IL-6) may play an important role in the pathophysiology of anemia of inflammation associated with myelodysplastic syndrome (MDS). This double-blind, placebo-controlled, phase 2 study assessed the efficacy and safety of siltuximab, a ... ...

Abstract	Interleukin-6 (IL-6) may play an important role in the pathophysiology of anemia of inflammation associated with myelodysplastic syndrome (MDS). This double-blind, placebo-controlled, phase 2 study assessed the efficacy and safety of siltuximab, a chimeric anti-IL-6 monoclonal antibody, in patients with low- and intermediate-1-risk MDS who require transfusions for MDS anemia. Patients were randomized in a 2:1 ratio to siltuximab 15 mg kg(-1) every 4 weeks + best supportive care (BSC) or placebo + BSC for 12 weeks. The primary endpoint was reduction in red blood cell (RBC) transfusions to treat MDS anemia, defined as ≥50% relative decrease and ≥2-unit absolute decrease in RBC transfusions. Fifty and 26 patients were randomized to the siltuximab and placebo groups, respectively. The study did not meet its prespecified hypothesis, with six (12%) patients in the siltuximab group and one (3.8%) in the placebo group having reductions in RBC transfusions (P = 0.271). At the time of the planned futility analysis, the prespecified cutoff criteria were not met, and the study was terminated early due to lack of efficacy. No unexpected safety findings were observed. In conclusion, compared to placebo, treatment with siltuximab did not reduce RBC transfusions in transfusion-dependent patients with low- and intermediate-1-risk MDS. Future studies might explore siltuximab in patients with less iron overload and with elevated IL-6 levels and/or using higher doses for MDS.
MeSH term(s)	Aged ; Aged, 80 and over ; Anemia, Refractory/drug therapy ; Anemia, Refractory/etiology ; Anemia, Refractory/immunology ; Antibodies, Monoclonal/administration & dosage ; Antibodies, Monoclonal/adverse effects ; Antibodies, Monoclonal/blood ; Antibodies, Monoclonal/therapeutic use ; Combined Modality Therapy ; Double-Blind Method ; Early Termination of Clinical Trials ; Erythrocyte Transfusion/statistics & numerical data ; Female ; Hemoglobins/analysis ; Humans ; Interleukin-6/immunology ; Male ; Medical Futility ; Middle Aged ; Myelodysplastic Syndromes/complications ; Myelodysplastic Syndromes/drug therapy ; Myelodysplastic Syndromes/immunology ; Patient Care/methods
Chemical Substances	Antibodies, Monoclonal ; Hemoglobins ; IL6 protein, human ; Interleukin-6 ; siltuximab (T4H8FMA7IM)
Language	English
Publishing date	2014-06-23
Publishing country	United States
Document type	Clinical Trial, Phase II ; Journal Article ; Multicenter Study ; Randomized Controlled Trial
ZDB-ID	196767-8
ISSN	1096-8652 ; 0361-8609
ISSN (online)	1096-8652
ISSN	0361-8609
DOI	10.1002/ajh.23780
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