Prognostic Significance of Cytogenetic Abnormalities for Patients with Acute Lymphoblastic Leukemia, a Region-Wide Retrospective Study

Background; Cytogenetic abnormalities (CA) have been reported as one of the independent prognostic factors for patients with acute lymphoblastic leukemia (ALL). The most common CA in ALL is the Philadelphia chromosome (Ph). Recently, by the introduction of tyrosine kinase inhibitors for Ph+ALL patients and pediatric-inspired protocol for adolescent/young-adult (AYA) patients, the management of ALL has progressed dramatically. We therefore retrospectively analyzed the impact of CA for patients with ALL in the era of TKIs and pediatric-inspired protocol for AYA.

Methods; Clinical data for 512 patients who were diagnosed as having ALL between 2007 and 2017 were collected from 21 centers in Hokkaido, Japan. Patients with lymphoblastic lymphoma and Burkitt leukemia were excluded from this study.

Results; The median age of the patients was 55 years (range: 15-84 years). Ninety-two of the patients were pediatric (0-14 years), 86 were AYA (15-35 years), 195 were adult (36-65 years) and 148 were elderly patients (66- years). Cytogenetic (G-banding) results were available in 486 patients. Three hundred forty-seven patients had abnormal karyotypes (AK), and 139 patients had normal karyotype (NK). BCR-ABL, including masked Ph, was positive in 193 patients, and 181 (93.8%) of them were more than 36 years. Abnormalities of -7/del (7), +8, +21, 11q32 (MLL), E2A/PBX1 or complex karyotype were seen in 38, 34, 46, 13, 10 and 94 of the patients, respectively. After a first remission induction therapy, 418 of 467 (89.5%) evaluable patients achieved complete remission (CR), and BCR-ABL+ patients showed better CR rate than those without BCR-ABL (93.7% vs. 87.4%, P=0.04).

At the median follow-up of 1180 days (9-4049 days), overall survival (OS) was superior in patients with NK than those with AK (P=0.01), and BCR-ABL+ patients showed poorer OS than those without BCR-ABL (P=0.01). However, by subgroup analyses of the age groups, there were no difference of OS between NK and AK (P=0.56 for pediatric, P=0.19 for AYA, P=0.32 for adult and P=0.98 for elderly). In adult and elderly patients, OS was not different between BCR-ABL+ and BCR-ABL-, though in patients over 70 years, BCR-ABL positivity was associated with superior OS (Hazard ratio, 3.2; 95% confidence intervals, 1.04-4.78, P=0.02). The abnormalities of +8 or +21 showed excellent OS in pediatric or AYA patients, however, they showed poor OS in adult or elderly patients. In adult or elderly BCR-ABL- patients, OS of patients with complex karyotype was inferior to those without complex karyotype.

Conclusion; BCR-ABL was not associated with poor outcome in the era of TKI. We need to evaluate the effect of CA on patients' outcome depending on age groups.