Conventional and Molecular Cytogenetic Responses in Patients with Myelodysplastic Syndrome (MDS) with Deletion 5q Treated with Lenalidomide.

Interstitial deletions of the long arm of chromosome 5 - del (5q) - are the most common chromosomal abnormalities in MDS. Del (5q) is detected in 14 % of the patients. Lenalidomide induces complete cytogenetic remissions and abolishes transfusion dependence in a significant proportion of these patients, apparently correlated with the malignant clone suppression. The objectives of this study were to assess clinical and cytogenetic responses to Lenalidomide and to establish the relationship between the number of 5q deleted cells detected by conventional cytogenetics (CG) and by fluorescence in situ hybridization (FISH) previously and after treatment. Due to its larger sensitivity, the FISH technique might be able to predict an eventual loss of response to treatment.

Bone marrow samples were collected at diagnosis and every 6 months from the beginning of treatment with lenalidomide. CG and FISH (with LSI EGR1 (5q31)SO/D5S23, D5S721 (5p15.2) probe, from Vysis) studies were performed in all samples, even in the cases that a complete cytogenetic remission was confirmed by karyotype during the treatment follow-up.

We have treated 9 transfusion dependent MDS patients with lenalidomide, with a median age of 76 years (45-92). Four of the patients had one additional cytogenetic anomaly besides 5q deletion. Due to high clinical and cytological suspicion, one of the patients had a trisomy 9 by karyotype (2/20 metaphase) and was diagnosed of del (5q) by FISH, with a low clonal load (9,4% of deleted nuclei). Six patients were low IPSS risk, while 2 were Int-1 and one was Int-2 risk IPSS. All patients achieved complete erythroid response and transfusion independence (in a median of 8 weeks of treatment) and are still in response. Treatment was stopped in two patients after achieving complete hematologic response, maintaining normal hemoglobine levels for > 24 months. Five patients achieved cytogenetic remission, but 2 of them relapsed in a latter phase of the treatment (25 and 30 months). FISH analysis could not predict cytogenetic relapse in these two cases.

Our results support the established high efficacy of lenalidomide in MDS with del (5q). In our experience a single additional cytogenetic anomaly did not compromise hematologic response. Moreover, in our study FISH analysis did not bring additional information to CG analysis in prediction of response and follow-up in the majority of the cases.

No relevant conflicts of interest to declare.