title: Response to lenalidomide in myelodysplastic syndromes with del(5q): influence of cytogenetics and mutations.
abstract: Lenalidomide is an effective drug in low-risk myelodysplastic syndromes (MDS) with isolated del(5q), although not all patients respond. Studies have suggested a role for TP53 mutations and karyotype complexity in disease progression and outcome. In order to assess the impact of complex karyotypes on treatment response and disease progression in 52 lenalidomide-treated patients with del(5q) MDS, conventional G-banding cytogenetics (CC), single nucleotide polymorphism array (SNP-A), and genomic sequencing methods were used. SNP-A analysis (with control sample, lymphocytes CD3+, in 30 cases) revealed 5q losses in all cases. Other recurrent abnormalities were infrequent and were not associated with lenalidomide responsiveness. Low karyotype complexity (by CC) and a high baseline platelet count (>280 × 10(9) /l) were associated with the achievement of haematological response (P = 0·020, P = 0·013 respectively). Unmutated TP53 status showed a tendency for haematological response (P = 0·061). Complete cytogenetic response was not observed in any of the mutated TP53 cases. By multivariate analysis, the most important predictor for lenalidomide treatment failure was a platelet count <280 × 10(9) /l (Odds Ratio = 6·17, P = 0·040). This study reveals the importance of a low baseline platelet count, karyotypic complexity and TP53 mutational status for response to lenalidomide treatment. It supports the molecular study of TP53 in MDS patients treated with lenalidomide.
authors.affiliation: Laboratori de Citogenètica Molecular, Laboratori de Citologia Hematològica, Servei de Patologia, Hospital del Mar, Barcelona, Spain.
authors.forename: Mar
authors.initials: M
authors.lastname: Mallo
authors.forename: Mónica
authors.initials: M
authors.lastname: Del Rey
authors.forename: Mariam
authors.initials: M
authors.lastname: Ibáñez
authors.forename: M José
authors.initials: MJ
authors.lastname: Calasanz
authors.forename: Leonor
authors.initials: L
authors.lastname: Arenillas
authors.forename: M José
authors.initials: MJ
authors.lastname: Larráyoz
authors.forename: Carmen
authors.initials: C
authors.lastname: Pedro
authors.forename: Andrés
authors.initials: A
authors.lastname: Jerez
authors.forename: Jaroslaw
authors.initials: J
authors.lastname: Maciejewski
authors.forename: Dolors
authors.initials: D
authors.lastname: Costa
authors.forename: Meritxell
authors.initials: M
authors.lastname: Nomdedeu
authors.forename: María
authors.initials: M
authors.lastname: Diez-Campelo
authors.forename: Eva
authors.initials: E
authors.lastname: Lumbreras
authors.forename: Teresa
authors.initials: T
authors.lastname: González-Martínez
authors.forename: Isabel
authors.initials: I
authors.lastname: Marugán
authors.forename: Esperanza
authors.initials: E
authors.lastname: Such
authors.forename: José
authors.initials: J
authors.lastname: Cervera
authors.forename: Juan C
authors.initials: JC
authors.lastname: Cigudosa
authors.forename: Sara
authors.initials: S
authors.lastname: Alvarez
authors.forename: Lourdes
authors.initials: L
authors.lastname: Florensa
authors.forename: Jesús M
authors.initials: JM
authors.lastname: Hernández
authors.forename: Francesc
authors.initials: F
authors.lastname: Solé
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002871:Chromosome Banding; D002872:Chromosome Deletion; D002895:Chromosomes, Human, Pair 5; D018450:Disease Progression; D005260:Female; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use*; D017404:In Situ Hybridization, Fluorescence; D000077269:Lenalidomide; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009190:Myelodysplastic Syndromes / Q000188:drug therapy* / Q000235:genetics* / Q000401:mortality; D020641:Polymorphism, Single Nucleotide; D013792:Thalidomide / Q000031:analogs & derivatives* / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D007155:Immunologic Factors; D013792:Thalidomide; D000077269:Lenalidomide