PMID- 28374162 OWN - NLM STAT- MEDLINE DCOM- 20170815 LR - 20181202 IS - 1432-0584 (Electronic) IS - 0939-5555 (Linking) VI - 96 IP - 6 DP - 2017 Jun TI - Peripheral blood cytogenetics allows treatment monitoring and early identification of treatment failure to lenalidomide in MDS patients: results of the LE-MON-5 trial. PG - 887-894 LID - 10.1007/s00277-017-2983-0 [doi] AB - Transfusion-dependent patients with low- or intermediate-1-risk myelodysplastic syndrome, <5% bone marrow (BM) blasts and isolated 5q-deletion received lenalidomide within the German MDS study group phase-II clinical trial LE-MON-5 (EudraCT:2008-001866-10) of the University of Duesseldorf, Germany. Cytogenetic monitoring was performed by chromosome banding analyses (CBA) of BM cells and fluorescence in situ hybridization (FISH) analyses of peripheral blood (PB) mononuclear CD34+ cells using extended probe panels. Out of 144 patients screened for study enrollment, 24% failed to meet inclusion criteria due to cytogenetic findings. Eighty-seven patients were followed with a median observation time of 30 months. Cytogenetic response detected by FISH and CBA in 74 and 66% of patients, respectively, was predictive for hematologic response as well as of high prognostic relevance. After 2 years, AML rate was 8% for all patients. Karyotype evolution was detected in 21 (FISH)-34% (CBA) of patients associated with significantly shorter AML-free survival. Disease progression was first detectable on the cytogenetic level on average 5-6 months before recurrence of transfusion dependence. Our data show for the first time in a prospective setting that a cytogenetic monitoring from the PB helps to early identify treatment failure and progressive disease in lenalidomide-treated patients to improve clinical management. TRIAL REGISTRATION: EudraCT:2008-001866-10. FAU - Braulke, Friederike AU - Braulke F AD - Department of Hematology and Medical Oncology, University Medicine of Goettingen, Robert-Koch-Str. 40, 37075, Goettingen, Germany. friederike.braulke@med.uni-goettingen.de. FAU - Schulz, Xenia AU - Schulz X AD - Department of Medical Statistics, University Medicine of Goettingen, Goettingen, Germany. FAU - Germing, Ulrich AU - Germing U AD - Department of Hematology and Oncology, University of Duesseldorf, Duesseldorf, Germany. FAU - Schuler, Esther AU - Schuler E AD - Department of Hematology and Oncology, University of Duesseldorf, Duesseldorf, Germany. FAU - Platzbecker, Uwe AU - Platzbecker U AD - Department of Hematology and Oncology, University of Dresden, Dresden, Germany. FAU - Nolte, Florian AU - Nolte F AD - Department of Hematology and Oncology, Medical Faculty Mannheim of the University of Heidelberg, Mannheim, Germany. FAU - Hofmann, Wolf-Karsten AU - Hofmann WK AD - Department of Hematology and Oncology, Medical Faculty Mannheim of the University of Heidelberg, Mannheim, Germany. FAU - Giagounidis, Aristoteles AU - Giagounidis A AD - Department of Hematology and Oncology, Marienhospital, Duesseldorf, Germany. FAU - Gotze, Katharina AU - Gotze K AD - Department of Hematology and Oncology, Technical University of Munich, Munich, Germany. FAU - Lubbert, Michael AU - Lubbert M AD - Department of Hematology and Oncology, University of Freiburg Medical Center, Freiburg, Germany. FAU - Schlenk, Richard F AU - Schlenk RF AD - Department of Hematology and Oncology, University of Ulm, Germany, now National Center of Tumor Diseases, Heidelberg, Germany. FAU - Schanz, Julie AU - Schanz J AD - Department of Hematology and Medical Oncology, University Medicine of Goettingen, Robert-Koch-Str. 40, 37075, Goettingen, Germany. FAU - Bacher, Ulrike AU - Bacher U AD - Department of Hematology and Medical Oncology, University Medicine of Goettingen, Robert-Koch-Str. 40, 37075, Goettingen, Germany. FAU - Ganser, Arnold AU - Ganser A AD - Department of Hematology, Hemostaseology and Stem Cell Transplantation, Hannover Medical School (MHH), Hannover, Germany. FAU - Busche, Guntram AU - Busche G AD - Institute of Pathology, Hannover Medical School (MHH), Hannover, Germany. FAU - Letsch, Anne AU - Letsch A AD - Departement of Hematology and Oncology, Charite University Medical Center Berlin, Berlin, Germany. FAU - Schafhausen, Philippe AU - Schafhausen P AD - Department of Oncology, Hematology, BMT with section Pneumology, Hubertus Wald Cancer Center, Medical Center Hamburg-Eppendorf, Hamburg, Germany. FAU - Bug, Gesine AU - Bug G AD - Department of Internal Medicine II, Hematology and Oncology, Johann Wolfgang Goethe University of Frankfurt, Frankfurt, Germany. FAU - Brummendorf, Tim H AU - Brummendorf TH AD - Department of Hematology and Oncology, Hemostaseology and SCT, University Hospital RWTH Aachen, Aachen, Germany. FAU - Haas, Rainer AU - Haas R AD - Department of Hematology and Oncology, University of Duesseldorf, Duesseldorf, Germany. FAU - Trumper, Lorenz AU - Trumper L AD - Department of Hematology and Medical Oncology, University Medicine of Goettingen, Robert-Koch-Str. 40, 37075, Goettingen, Germany. FAU - Shirneshan, Katayoon AU - Shirneshan K AD - Department of Hematology and Medical Oncology, University Medicine of Goettingen, Robert-Koch-Str. 40, 37075, Goettingen, Germany. FAU - Haase, Detlef AU - Haase D AD - Department of Hematology and Medical Oncology, University Medicine of Goettingen, Robert-Koch-Str. 40, 37075, Goettingen, Germany. LA - eng PT - Clinical Trial, Phase II PT - Journal Article PT - Multicenter Study DEP - 20170403 PL - Germany TA - Ann Hematol JT - Annals of hematology JID - 9107334 RN - 0 (Angiogenesis Inhibitors) RN - 0 (Antigens, CD34) RN - 4Z8R6ORS6L (Thalidomide) RN - F0P408N6V4 (Lenalidomide) SB - IM MH - Acute Disease MH - Adult MH - Aged MH - Aged, 80 and over MH - Angiogenesis Inhibitors/therapeutic use MH - Antigens, CD34/blood MH - Chromosome Banding MH - Chromosome Deletion MH - Chromosomes, Human, Pair 5/genetics MH - Disease-Free Survival MH - Female MH - Germany MH - Humans MH - In Situ Hybridization, Fluorescence MH - Karyotyping MH - Lenalidomide MH - Leukemia, Myeloid/diagnosis/genetics MH - Leukocytes, Mononuclear/metabolism MH - Male MH - Middle Aged MH - Myelodysplastic Syndromes/*drug therapy/genetics MH - Prognosis MH - Thalidomide/*analogs & derivatives/therapeutic use MH - Treatment Failure OTO - NOTNLM OT - 5q-deletion OT - CD34+ cells OT - Chromosome banding analysis OT - Clonal evolution OT - Fluorescence in situ hybridization (FISH) OT - Myelodysplastic syndromes (MDS) EDAT- 2017/04/05 06:00 MHDA- 2017/08/16 06:00 CRDT- 2017/04/05 06:00 PHST- 2017/01/24 00:00 [received] PHST- 2017/03/22 00:00 [accepted] PHST- 2017/04/05 06:00 [pubmed] PHST- 2017/08/16 06:00 [medline] PHST- 2017/04/05 06:00 [entrez] AID - 10.1007/s00277-017-2983-0 [pii] AID - 10.1007/s00277-017-2983-0 [doi] PST - ppublish SO - Ann Hematol. 2017 Jun;96(6):887-894. doi: 10.1007/s00277-017-2983-0. Epub 2017 Apr 3.