PF179 DIFFERENT IMPACT OF BCR BREAKPOINT ON THE OUTCOME OF ALLOGENEIC HEMATOPOIETIC CELL TRANSPLANTATION FROM DIFFERENT GRAFT SOURCE FOR PH+ALL IN THE ERA OF TKI

Abstract

Background:Prognostic significance of different BCR breakpoints in Philadelphia chromosome‐positive acute lymphoblastic leukemia (Ph+ALL) has not been established. BCR‐ABL1–positive cells outside the B‐lineage compartment was reported in 40% of adult patients with Ph+ALL and the frequency was different between patients with minor BCR (mi‐bcr) and those with Major BCR (Ma‐bcr). This could suggest the possibility of biological differences in Ph+ALL according to BCR breakpoint. In the era of tyrosine kinase inhibitors (TKIs), allogeneic hematopoietic cell transplantation (allo‐HCT) is still considered to be a choice to cure Ph+ALL. Different effect of unrelated graft source was reported on the outcome of allo‐HCT with positive minimal residual disease (MRD) in a recent study.Aims:We aimed to clarify the impact of BCR breakpoint as well as MRD status and graft source on the outcome of allo‐HCT for Ph+ALL in the era of TKI.Methods:We analyzed data from a registry database for 803 adult Ph+ALL patients who underwent unrelated allo‐HCT in the first complete remission. BCR breakpoint was mi‐bcr in 627 patients (78%), and Ma‐bcr in 154 (19%).Results:Overall survival (OS) rates at 4 years were 64% in mi‐bcr and 61% in Ma‐bcr among patients who underwent unrelated bone marrow or peripheral blood transplantation (UBMT) (P = 0.43), and 65% in mi‐bcr and 67% in Ma‐bcr among patients who underwent unrelated cord blood transplantation (UCBT) (P = 0.53). Similarly, the cumulative incidence of relapse or non‐relapse mortality (NRM) was not significantly different between patients with mi‐bcr and those with Ma‐bcr in either UBMT or UCBT (Relapse: UBMT, 20% in mi‐bcr and 18% in Ma‐bcr at 4 years, P = 0.73; UCBT, 20% in mi‐bcr and 15% in Ma‐bcr at 4 years, P = 0.35; NRM: UBMT, 25% in mi‐bcr and 30% in Ma‐bcr at 4 years, P = 0.31; UCBT, 23% in mi‐bcr and 26% in Ma‐bcr at 4 years, P = 0.98). BCR breakpoint was not a significant prognostic factor in multivariate analyses, regardless of graft source. However, in subanalyses, Ma‐bcr was a significant risk factor for survival and NRM in multivariate analyses among patients with MRD(+) at UBMT [Ma‐bcr (vs. mi‐bcr): OS: Hazard ratio (HR) 2.29, 95%CI 1.38 to 3.80, P = 0.001; NRM: HR 3.29, 95%CI 1.72 to 6.27, P < 0.001]. NRM was higher in patients with Ma‐bcr than in those with mi‐bcr among patients with MRD(+) at UBMT (44 % in Ma‐bcr vs. 14% in mi‐bcr at 4 years, P < 0.001), which led to lower survival rate in patients with Ma‐bcr.Summary/Conclusion:BCR breakpoint was a significant prognostic factor in Ph+ALL patients with MRD(+) at UBMT. This is the first study reporting the possibility of significant impact of BCR breakpoint on MRD‐based transplant outcome in Ph+ALL in the era of TKI.