Influence of total genomic alteration and chromosomal fragmentation on response to a combination of azacitidine and lenalidomide in a cohort of patients with very high risk MDS.
We genetically analyzed a group of high risk MDS/AML patients treated by a combination of azacitidine and lenalidomide. In our cohort, the extent of genetic rearrangements was associated with outcome and response to treatment. The size of total genomic aberrations as defined by molecular karyotyping (SNP-array analysis) was a predictive marker for overall survival. TP53 mutations were associated with therapy refractoriness only if accompanied by heavily rearranged chromosomes. This study suggests a potential value of molecular karyotyping as a method to objectivate comprehensively the extent of genetic alterations in high risk patients with complex karyotypes, especially if the clinical value of the size of total genomic aberrations and the fragmentation status of single chromosomes could be evaluated in larger therapy trials.
Department of Hematology and Medical Oncology, University Hospital, University Göttingen, Göttingen, Germany. Electronic address: christina.ganster@med.uni-goettingen.de.
Christina
C
Ganster
Department of Hematology and Medical Oncology, University Hospital, University Göttingen, Göttingen, Germany.
Katayoon
K
Shirneshan
DNA Microarray Facility, Georg August University, Göttingen, Germany.
Gabriela
G
Salinas-Riester
Department of Hematology and Medical Oncology, University Hospital, University Göttingen, Göttingen, Germany.
Friederike
F
Braulke
Department of Hematology and Medical Oncology, University Hospital, University Göttingen, Göttingen, Germany.
Julie
J
Schanz
Medical Clinic and Polyclinic I, University Hospital, Technical University Dresden, Dresden, Germany.
Uwe
U
Platzbecker
Department of Hematology and Medical Oncology, University Hospital, University Göttingen, Göttingen, Germany.
Detlef
D
Haase
D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001374:Azacitidine / Q000008:administration & dosage; D002869:Chromosome Aberrations; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D007621:Karyotyping / Q000379:methods*; D000077269:Lenalidomide; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000188:drug therapy* / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D016016:Proportional Hazards Models; D013792:Thalidomide / Q000008:administration & dosage / Q000031:analogs & derivatives; D016159:Tumor Suppressor Protein p53 / Q000235:genetics
D016159:Tumor Suppressor Protein p53; D013792:Thalidomide; D000077269:Lenalidomide; D001374:Azacitidine
AML; Cytogenetics; FISH; MDS; SNP arrays