Incidence, Clinical Characteristics, and Prognostic Significance Of Chromosome 3q Abnormalities In Patients With CML Blast Phase

Abstract Abnormalities involving the long arm of chromosome 3 (3q) have been associated with aberrant expression of the EVI1 oncoprotein and portend adverse prognosis in myeloid malignancies. Chromosome 3 abnormalities are relatively common in CML blast phase and may also be associated with treatment resistance and an unfavorable outcome. We sought to further characterize the frequency, clinical characteristics, and outcomes associated with 3q abnormalities in cases of CML in blastic phase (BP). We retrospectively reviewed cases of CML BP seen at our institution between 2000 and 2012 and analyzed their clinico-pathologic characteristics, response to therapy, and outcome. We then compared patients with BP and chromosome 3q abnormality (3q-POS) to patients with BP but without involvement of chromosome 3q (3q-NEG). A total of 320 patients with CML BP were analyzed. Among those, 38 pts (12%) had abnormalities of chromosome 3q. Abnormalities involving 3q were represented as follows: t(3;21) in 33%; inv(3), 24%; del 3q, 12%; t(3;4), 6%; t(3;7), 6%; t(3;8), 6%; t(3;6;7), 3%; t(3;11), 3%; t(2;3), 3%; and 3q+ in 3%. The characteristics of the two cohorts: 3q-POS vs. 3q-NEG are outlined in Table 1. The clinical characteristics were similar between the 2 cohorts. However, there were trends for older age and higher peripheral blast percentage in patients with 3q-POS. A similar percentage of pts received chemotherapy, stem cell transplant (SCT), and tyrosine kinase inhibitor (TKI, alone or combined with chemotherapy) among the 2 groups as their initial therapy for BP. Likewise, there was no significant difference in the percentage of pts eventually going for SCT. Patients with BP and 3q-POS had a significantly lower rate of complete hematologic response (CR, 22% vs. 45%), complete cytogenetic response (CCyR, 0% vs. 24%), and a higher rate of resistance (74% vs. 45%) to their first BP therapy compared to those with 3q-NEG. This translated into a trend towards lower median overall survival (OS) (7.5 vs. 9.9m, p=0.157) in pts with 3q-POS. Figure 1. Table 1 . Patient Characteristics Chrom Abnl involving 3q (3q-POS) All other Blast Phase (3q-NEG) p-value Number of Patients (%) 38 (12) 282 (88) Median age (range) 56 (29-79) 52 (17-81) 0.102 Sex Male, N (%) 23 (61) 174 (62) 0.849 Median WBC (range) 30.2 (0.5-347.0) 25.7 (0.5-768.0) 0.738 Median Periph blast % (range) 35 (0-95) 30 (0-96) 0.095 Median BM blast % (range) 38 (6-96) 40 (0-99) 0.457 Median Platelets (range) 146 (6-1009) 80 (2-2750) 0.248 BCR-ABL transcript, N (%) b2a2 9 (47) 60 (42) 0.138 b3a2 4 (21) 55 (39) both 4 (21) 24 (17) other 2 (11) 3 (2) Median number of previous TKIs 1 (0-4) 1 (0-3) 0.49 Extramedullary disease (yes, N (%)) 7 (26) 52 (25) 0.92 Therapy for BP, N (%) Chemo 8 (32) 56 (28) 0.166 SCT 0 (0) 2 (1) TKI 13 (52) 69 (34) TKI+Chemo 4 (16) 74 (37) Response to 1st BP Rx, N (%) CR 5 (22) 77 (45) 0.029* Died 1 (4) 19 (11) Refractory 17 (74) 77 (45) Rate of CCyR after 1st BP Rx, N (%) 0(0) 42(24) 0.008* Median OS in months 7.5 9.9 0.157 Pts going to transplant, N (%) 6 (16) 38 (13) 0.697 Median Months from Dx to BP (range) 25.2 (0-173) 35.8 (0-1240) 0.378 Download : Download high-res image (92KB) Download : Download full-size image Figure 1 . Chromosome 3q abnormalities are not uncommon in patients with CML BP and may occur with numerous translocation partners. The presence of 3q abnormalities is associated with resistance to therapy for BP and portends an unfavorable outcome. Understanding the role of EVI1 in the biology of these diseases will be important in developing more effective therapies to improve outcome. Disclosures: No relevant conflicts of interest to declare.