Chronic myeloid leukemia (CML) with e1a2 BCR-ABL fusion transcript type: Analysis of characteristics, outcomes, and prognostic significance

Abstract

7030 Background: The most common BCR-ABL fusion transcripts in CML are e13a2 (b2a2) and e14a2 (b3a2). Rarely, other transcripts like e1a2 are seen. Currently, there is no published series of data on efficacy of imatinib or other tyrosine kinase inhibitors (TKIs) in CML with e1a2. Methods: We analyzed records of 1,292 CML patients treated with TKI at our institution between January 2000 and November 2008. Results: 14 CML patients with e1a2 transcripts were identified, 9 in chronic phase (CP), 1 in accelerated phase (AP), and 4 in blast phase (BP). Median age at diagnosis was 60 (range 28–86) years, median follow-up 39.5 (range 2–109) months. Of the 9 in CP, 3 received interferon and then imatinib after interferon failure, 6 received TKI as first-line therapy (5 imatinib, 1 nilotinib): 5 achieved CHR only, 1 CCyR, 1 MCyR, 1 PCyR, and 1 did not respond to imatinib. 5 patients (2 post-interferon failure - 1 in CHR, 1 in PCyR; 3 frontline imatinib - 1 in CHR, 1 in CCyR, 1 non-responder) progressed to advanced phases (3 myeloid BP, 1 lymphoid BP, 1 AP) at a median 48 (range 4–92) months after CML diagnosis; with only 1 alive and in CMR after allogeneic SCT. AP patient received various TKIs sequentially and achieved only CHR with disappearance of clonal evolution. BP patients received Hyper-CVAD+imatinib/dasatinib or idarubicin+Ara-C; 2 did not respond, 1 had CCyR lasting 12 months with Hyper-CVAD+Imatinib and 1 had CMR after allogeneic SCT lasting 2 months. In all 14 patients, cytogenetic responses lasted 1–9 months before being lost and none (except 2) achieved MMR or CMR on imatinib or other TKI therapy. Six patients (5 CP, 1 AP) were alive at a median 39 (range 2–85) months after initial diagnosis: 4 with CHR (2 on imatinib, 1 nilotinib, 1 bosutinib), 1 with MCyR on imatinib, and 1 with CMR after allogeneic SCT. Conclusions: CML with e1a2 BCR-ABL fusion transcripts is rare and is associated with an inferior outcome to therapy with TKI, with responses being usually short-lived. These patients need to be identified as high-risk patients and monitored closely for efficacy during therapy with TKI. No significant financial relationships to disclose.