title: Peripheral blood cytogenetics allows treatment monitoring and early identification of treatment failure to lenalidomide in MDS patients: results of the LE-MON-5 trial.
abstract: 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.
  
  
  BACKGROUND
  EudraCT:2008-001866-10.
authors.affiliation: Department of Hematology and Medical Oncology, University Medicine of Goettingen, Robert-Koch-Str. 40, 37075, Goettingen, Germany. friederike.braulke@med.uni-goettingen.de.
authors.forename: Friederike
authors.initials: F
authors.lastname: Braulke
authors.affiliation: Department of Medical Statistics, University Medicine of Goettingen, Goettingen, Germany.
authors.forename: Xenia
authors.initials: X
authors.lastname: Schulz
authors.affiliation: Department of Hematology and Oncology, University of Duesseldorf, Duesseldorf, Germany.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Germing
authors.affiliation: Department of Hematology and Oncology, University of Duesseldorf, Duesseldorf, Germany.
authors.forename: Esther
authors.initials: E
authors.lastname: Schuler
authors.affiliation: Department of Hematology and Oncology, University of Dresden, Dresden, Germany.
authors.forename: Uwe
authors.initials: U
authors.lastname: Platzbecker
authors.affiliation: Department of Hematology and Oncology, Medical Faculty Mannheim of the University of Heidelberg, Mannheim, Germany.
authors.forename: Florian
authors.initials: F
authors.lastname: Nolte
authors.affiliation: Department of Hematology and Oncology, Medical Faculty Mannheim of the University of Heidelberg, Mannheim, Germany.
authors.forename: Wolf-Karsten
authors.initials: WK
authors.lastname: Hofmann
authors.affiliation: Department of Hematology and Oncology, Marienhospital, Duesseldorf, Germany.
authors.forename: Aristoteles
authors.initials: A
authors.lastname: Giagounidis
authors.affiliation: Department of Hematology and Oncology, Technical University of Munich, Munich, Germany.
authors.forename: Katharina
authors.initials: K
authors.lastname: Götze
authors.affiliation: Department of Hematology and Oncology, University of Freiburg Medical Center, Freiburg, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Lübbert
authors.affiliation: Department of Hematology and Oncology, University of Ulm, Germany, now National Center of Tumor Diseases, Heidelberg, Germany.
authors.forename: Richard F
authors.initials: RF
authors.lastname: Schlenk
authors.affiliation: Department of Hematology and Medical Oncology, University Medicine of Goettingen, Robert-Koch-Str. 40, 37075, Goettingen, Germany.
authors.forename: Julie
authors.initials: J
authors.lastname: Schanz
authors.affiliation: Department of Hematology and Medical Oncology, University Medicine of Goettingen, Robert-Koch-Str. 40, 37075, Goettingen, Germany.
authors.forename: Ulrike
authors.initials: U
authors.lastname: Bacher
authors.affiliation: Department of Hematology, Hemostaseology and Stem Cell Transplantation, Hannover Medical School (MHH), Hannover, Germany.
authors.forename: Arnold
authors.initials: A
authors.lastname: Ganser
authors.affiliation: Institute of Pathology, Hannover Medical School (MHH), Hannover, Germany.
authors.forename: Guntram
authors.initials: G
authors.lastname: Büsche
authors.affiliation: Departement of Hematology and Oncology, Charite University Medical Center Berlin, Berlin, Germany.
authors.forename: Anne
authors.initials: A
authors.lastname: Letsch
authors.affiliation: Department of Oncology, Hematology, BMT with section Pneumology, Hubertus Wald Cancer Center, Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Philippe
authors.initials: P
authors.lastname: Schafhausen
authors.affiliation: Department of Internal Medicine II, Hematology and Oncology, Johann Wolfgang Goethe University of Frankfurt, Frankfurt, Germany.
authors.forename: Gesine
authors.initials: G
authors.lastname: Bug
authors.affiliation: Department of Hematology and Oncology, Hemostaseology and SCT, University Hospital RWTH Aachen, Aachen, Germany.
authors.forename: Tim H
authors.initials: TH
authors.lastname: Brümmendorf
authors.affiliation: Department of Hematology and Oncology, University of Duesseldorf, Duesseldorf, Germany.
authors.forename: Rainer
authors.initials: R
authors.lastname: Haas
authors.affiliation: Department of Hematology and Medical Oncology, University Medicine of Goettingen, Robert-Koch-Str. 40, 37075, Goettingen, Germany.
authors.forename: Lorenz
authors.initials: L
authors.lastname: Trümper
authors.affiliation: Department of Hematology and Medical Oncology, University Medicine of Goettingen, Robert-Koch-Str. 40, 37075, Goettingen, Germany.
authors.forename: Katayoon
authors.initials: K
authors.lastname: Shirneshan
authors.affiliation: Department of Hematology and Medical Oncology, University Medicine of Goettingen, Robert-Koch-Str. 40, 37075, Goettingen, Germany.
authors.forename: Detlef
authors.initials: D
authors.lastname: Haase
mesh_terms: D000208:Acute Disease; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use; D018952:Antigens, CD34 / Q000097:blood; D002871:Chromosome Banding; D002872:Chromosome Deletion; D002895:Chromosomes, Human, Pair 5 / Q000235:genetics; D018572:Disease-Free Survival; D005260:Female; D005858:Germany; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007621:Karyotyping; D000077269:Lenalidomide; D007951:Leukemia, Myeloid / Q000175:diagnosis / Q000235:genetics; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000188:drug therapy* / Q000235:genetics; D011379:Prognosis; D013792:Thalidomide / Q000031:analogs & derivatives* / Q000627:therapeutic use; D017211:Treatment Failure
chemical_list: D020533:Angiogenesis Inhibitors; D018952:Antigens, CD34; D013792:Thalidomide; D000077269:Lenalidomide
keywords: 5q-deletion; CD34+ cells; Chromosome banding analysis; Clonal evolution; Fluorescence in situ hybridization (FISH); Myelodysplastic syndromes (MDS)