Imatinib-induced CML remission as evidenced by automated FISH analysis predicts good outcome but is not achieved in patients with der(9) deletion within 30-month follow up.

Program Nr: 292 for the 2006 ASHG Annual Meeting

Imatinib-induced CML remission as evidenced by automated FISH analysis predicts good outcome but is not achieved in patients with der(9) deletion within 30-month follow up. G. Calabrese^1,2,3, D. Fantasia², P. Guanciali Franchi^1,2, R. DiGianfilippo², E. Morizio², M. Alfonsi^1,2, A. Di Tecco², A. Marzoli², L. Stuppia^1,3, R. DiLorenzo⁴, G. Palka^1,2,3. 1) Scienze Biomed/Genetica Medica, Univ G D'Annunzio, Chieti, Italy; 2) U.O. Genetica Umana, Pescara Hospital, Pescara, Italy; 3) CESI, Center for Aging, D'Annunzio Foundation, Chieti, Italy; 4) Dept. Hematology, Pescara Hospital, Pescara, Italy.
Seventy patients with CML, 63 in chronic phase (CP), 1 in accelerate phase (AP), and 6 in blastic crisis (BC), were treated with imatinib mesylate (IM). The patients were studied for a 18-61 months follow up period using clinical and haematological features, cytogenetics and FISH analysis with a dual-fusion BCR-ABL probe, and an automated FISH imaging system for rare cell events (BioView-Duet). Before IM treatment 51 patients showed Ph chromosome in all examined cells while in the remaining 19 patients a normal clone was also found. FISH analysis showed BCR-ABL fusion gene in >95% of cells in 49 patients including 9 with a partial deletion on der(9) at band q34. In 18 patients BCR-ABL rearrangement was observed in 5-95% of cells while in 3 it was present in <5% of nuclei. Complete or partial cytogenetic remission rate [CCR or PCR: t(9;22) absent or <35% of cells, respectively] overlapped complete or partial FISH remission rate (CFR or PFR: BCR-ABL absent or <35% of cells, respectively) along all the follow up period being observed in 72% of patients. However, CFR achievement within 12 months of treatment resulted in a disease-free second year of treatment in 94% of patients, while 33% of samples with a CCR actually showed >1% leukaemic cells at FISH analysis. Moreover, FISH unravelled leukaemic cells in 21% of samples unsuitable for cytogenetic investigation from 9 patients who subsequently developed haematological relapse. In patients with partial deletion on der(9), no CCR/CFR was achieved. Clinical and haematological relapse was observed in 4 cases, while in the remaining 5 a PCR/PFR was observed only after 30 months of treatment supporting a negative role of der(9) deletion on IM effect in CML patients as previously reported with other therapy protocols.