| Objective:This study aimed to explore the potential prognostic factors in adult patients with Ph chromosome positive acute lymphoblastic leukemia(Ph+ALL) in the new era with tyrosine kinase inhibitors (TKI) treatment, and the role of BCR-ABL isoforms in prognostic stratification, therefore provide an insight for improving the prognostic stratification and personalised treatment of the Ph+ ALL patients.Methods:We analysed the data of 79 patients retrospectively, who were diagnosed as Ph+ALL and administrated with conventional chemotherapy plus TKI treatment with or without hematopoietic stem cell transplantation (HSCT) from January 2005 to December 2015 in our hospital, then explore the potential prognostic factors in adult patients with Ph+ALL in the new era with TKI treatment, and compared the differences of clinical features and prognosis between the p190 group (n=41) and the p210 group (n=24).Results:Ph+ALL patients with initial white blood cell count(WBC)> 100× 109/ L had a worse 5-year overall survival (P=0.005) and 3-year event-free survival (P=0.025) compared with that WBC?100× 109/L; P190 group had a worse 5-year overall survival (P=0.043) and event-free survival (P=0.077) compared with p210 group; Ph+ALL patients who were not treated with HSCT had a worse 5-year overall survival (P=0.003) and event-free survival (P=0.002) than that who were treated with HSCT; Major molecular response (major molecular remission, MMR, BCR-ABL/ABL?1%) was not obtained before HSCT significantly correlated with a worse the overall survival (P=0.035) and event-free survival (P=0.042); While the mutations in ABL kinase domain were not seen significantly correlated with a poor prognosis, which may be related to that not all patients were detected about the mutation; Other clinical features such as initial BCR-ABL level, other chromosomal abnormalities were not seen significantly correlated with a poor prognosis, and application of TKI post-HSCT was not seen significantly correlated with prognosis as well.The p190 group had lower platelet count than the p210 group (46×109/L vs 65 ×109/L, P=0.085); The leukemic blast cells in the bone marrow at diagnosis was higher in p190 group than that in p210 group (90% vs 80%, P=0.015); Other clinical features such as gender, age, white blood cells, hemoglobin, leukemic blast cells in peripheral blood, BCR-ABL/ABL expression level showed no differences between the two groups. As to the response to treatment, the complete remission rate (CR) after induction therapy were 77%(36/47) and 87%(26/30) respectively in the p190 and p210 group, no significant difference was seen (P=0.277). The time period from induction to the first complete remission (CR1) showed no difference either (0.9 months vs 1 months, P=0.834). The time period from induction to the first complete molecular remission (CMR1) was shorter in p190 group than that in p210 group (3 months vs 7.9months, P=0.086); The level of BCR-ABL when achieved CR1 was lower in p190 group than that in p210 group (0.96% vs 5.96%, P=0.037); The duration of remission in p190 group was shorter than that in p210 group, from the time of CR1 to relapse (5.5 months vs 8.1 months, P=0.081). The interval of repeated recurrence was also shorter in p190 group than that in the p210 group (6.6 months vs 8.6 months, P=0.097). In the patients who obtained CR1 but did not underwent transplantation, p190 group relapsed earlier than that in p210 group (3.7 months vs 6.6 months, P=0.023), their relapse rates were not significantly different; In the patients who obtainedCR1 and then underwent transplantation, p190 group's duration from transplantation to relapse was not significantly different from that p210 group's (4.5 months vs 5.7 months, P=0.519), their relapse rates were not significantly different as well. Relapse rate in the patients who were not treated with HSCT after CR and MMR was 77%, p190 group had the trend of higher relapse rate (88% vs 60%, P=0.51) and earlier relapse (5.7 months vs 21.3 months, P=0.569); Relapse rate in the patients who were treated with HSCT after CR but non-MMR was 75%, p190 group also had the trend of higher relapse rate (83% vs 67%, P=1.000) and earlier relapse (3.65 months vs 5.6 months, P=0.556); In the patients who were treated with HSCT after CR and MMR,85% patients achieved long-lasting remission. The duration of remission from the time of CR to follow-up without relapse (25.79+months vs 25.3+ months, P=0.700), relapse rate (18% vs 11%, P=1.000) and the duration of remission from the time of CR to relapse (11.6 months vs 5.32 months, P=0.221) between pl90 and p210 had not significant difference trend. Conclusion:Ph+ALL patients whose initial WBC>100×109/L, with p190 positive, were not treated with HSCT, not obtained MMR before HSCT had poor prognosis; While the mutations in ABL kinase domain were not seen significantly correlated with a poor prognosis, which may be related to that not all patients were detected about the mutation; Other clinical features such as initial BCR-ABL level, other chromosomal abnormalities were not seen significantly correlated with a poor prognosis, and application of TKI post-HSCT was not seen significantly correlated with prognosis as well.The p190 group tended to have lower platelet count in peripheral blood and had higher percentage of leukemic blasts in bone marrow at diagnosis; while the CR rate and the time from induction to CR1 showed no differences; The time period from induction to CMR1 was shorter and the level of BCR-ABL when achieved CR1 was lower in p190 group; The duration of remission and the interval of repeated recurrence was also shorter in p190 group than that in the p210 group. HSCT after CR1 might improve the duration of remission in p190 group. Most of the patients who underwent HSCT after CR and MMR in the two groups could achieve long-lasting remission, indicating that MMR before HSCT is very important, p190 patients who underwent HSCT after CR and MMR may obtain as good survival as p210. |
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