title: Clinical effect of increasing doses of lenalidomide in high-risk myelodysplastic syndrome and acute myeloid leukemia with chromosome 5 abnormalities.
abstract: BACKGROUND
  Patients with chromosome 5 abnormalities and high-risk myelodysplastic syndromes or acute myeloid leukemia have a poor outcome. We hypothesized that increasing doses of lenalidomide may benefit this group of patients by inhibiting the tumor clone, as assessed by fluorescence in situ hybridization for del(5q31).
  
  
  METHODS
  Twenty-eight patients at diagnosis or with relapsed disease and not eligible for standard therapy (16 with acute myeloid leukemia, 12 with intermediate-risk 2 or high-risk myelodysplastic syndrome) were enrolled in this prospective phase II multicenter trial and treated with lenalidomide up to 30 mg daily for 16 weeks. Three patients had isolated del(5q), six had del(5q) plus one additional aberration, 14 had del(5q) and a complex karyotype, four had monosomy 5, and one had del(5q) identified by fluorescence in situ hybridization only.
  
  
  RESULTS
  Major and minor cytogenetic responses, assessed by fluorescence in situ hybridization, were achieved in 5/26 (19%) and 2/26 (8%) patients, respectively, who received one or more dose of lenalidomide, while two patients achieved only a bone marrow response. Nine of all 26 patients (35%) and nine of the ten who completed the 16 weeks of trial responded to treatment. Using the International Working Group criteria for acute myeloid leukemia and myelodysplastic syndrome the overall response rate in treated patients with acute myeloid leukemia was 20% (3/15), while that for patients with myelodysplastic syndrome was 36% (4/11). Seven patients stopped therapy due to progressive disease and nine because of complications, most of which were disease-related. Response rates were similar in patients with isolated del(5q) and in those with additional aberrations. Interestingly, patients with TP53 mutations responded less well than those without mutations (2/13 versus 5/9, respectively; P=0.047). No responses were observed among 11 cases with deleterious TP53 mutations.
  
  
  CONCLUSIONS
  Our data support a role for higher doses of lenalidomide in poor prognosis patients with myelodysplastic syndrome and acute myeloid leukemia with deletion 5q. (Clinicaltrials.gov identifier NCT00761449).
authors: Hematology Center, Karolinska University Hopsital Huddinge, 14186 Stockholm, Sweden. lars.mollgard@karolinska.se
authors: Lars
authors: L
authors: Möllgård
authors: Leonie
authors: L
authors: Saft
authors: Marianne Bach
authors: MB
authors: Treppendahl
authors: Ingunn
authors: I
authors: Dybedal
authors: Jan Maxwell
authors: JM
authors: Nørgaard
authors: Jan
authors: J
authors: Astermark
authors: Elisabeth
authors: E
authors: Ejerblad
authors: Hege
authors: H
authors: Garelius
authors: Inge Høgh
authors: IH
authors: Dufva
authors: Monika
authors: M
authors: Jansson
authors: Martin
authors: M
authors: Jädersten
authors: Lars
authors: L
authors: Kjeldsen
authors: Olle
authors: O
authors: Linder
authors: Lars
authors: L
authors: Nilsson
authors: Hanne
authors: H
authors: Vestergaard
authors: Anna
authors: A
authors: Porwit
authors: Kirsten
authors: K
authors: Grønbæk
authors: Eva
authors: E
authors: Hellström-Lindberg
authors: Eva Hellström
authors: EH
authors: Lindberg
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D001483:Base Sequence; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D002869:Chromosome Aberrations; D002895:Chromosomes, Human, Pair 5 / Q000235:genetics*; D005260:Female; D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D000077269:Lenalidomide; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D009190:Myelodysplastic Syndromes / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D015689:Oncogene Protein p21(ras) / Q000235:genetics / Q000378:metabolism; D013792:Thalidomide / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D016896:Treatment Outcome; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism; D025721:WT1 Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D016159:Tumor Suppressor Protein p53; D025721:WT1 Proteins; D013792:Thalidomide; D015689:Oncogene Protein p21(ras); D000077269:Lenalidomide