Which Patients with Ph+ Acute Lymphoblastic Leukemia Should Undergo Autologous Hematopoietic Stem Cell Transplantation in TKI Era?

Objective: To investigate the efficacy and indications of autologous hematopoietic stem cell transplantation (AUTO-SCT) for the treatment of Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph + ALL) in TKI era. Methods: To retrospectively evaluate the outcome of 86 patients with Ph+ALL who have received AUTO-SCT and matched sibling donor-SCT (MSD-SCT) between May 2005 and December 2016, and further analyze the effect of various risk factors on prognosis. Result: Among the patients, 31 of patients received AUTO-SCT and 55 of patients received MSD-SCT. The 3-year overall survival (OS) of AUTO group and MSD group was 58.8±10.7% and 66.4±6.7%( P=.934), respectively, and 3-year leukemia-free survival (LFS) was 63.6±9.5%、60.5±7.1%( P=.641), respectively. Whereas the relapse rates (RR) for two groups were 36.7 ± 9.7% and 20.1± 5.9% (P= .147), respectively, and transplant-related deaths mortality (TRM) was 0 and 19.4 ± 5.6% (P= .013), respectively. For the patients who achieved complete molecular remission and sustained remission before transplantation, and with no extramedullary infiltration by induction therapy within three months (sMR3), OS of AUTO group and MSD group was 90.9±8.7%,79.6±9.2%( P=.329), respectively and the LFS was 91.7±8.0%,69.3±10.7%( P=.114),respectively. Whereas RR were 8.3±8.3%,21.2±10.0%( P=.304),respectively, and TRM was 0,9.5±6.6%( P=.242), respectively. For the patients who did not reach sMR3, the OS for AUTO group and MSD group was 33.3±13.8% and 58.1±9.0%( P=.475), respectively, and LFS was 37.3±13.3%,55.5±9.1% (P=.407). While RR were 62.7±14.3% and 18.8±7.1%( P=.007), respectively, and TRM was 0 and 25.7±8.1%( P=.037), respectively. The prognostic factor that affected OS, LFS was whether patients can reach the sMR3, while transplant type was the prognostic factor that affected TRM. The Logistic regression analysis showed that WBC<30×10⁹/L at the onset (OR=3.365,95% confidence interval (CI) 1.280-8.846, P=.014) and the application of second generation of TKI (OR=3.582,95% confidence interval (CI) 1.151-11.145, P=.028) were independent prognostic factors for reaching sMR3. Conclusion: More patients with Ph+ALL can reach sMR3 with second generation TKI, while AUTO-SCT is a safe and effective alternative therapy of allogeneic transplantation for these patients.