Abstract
BACKGROUND: The outcome of adult patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) improved markedly with the introduction of tyrosine kinase inhibitors (TKIs), which allow achieving high rate of molecular remissions. However, allogeneic hematopoietic stem cell transplantation (allo-SCT) performed in first complete remission still remains a standard of care. In a recent study we demonstrated significant improvement of results of autologous hematopoietic stem cell transplantation (auto-SCT) in the era of TKIs [Giebel S, et al.; Eur J Cancer 2014;50:411-7]. The goal of the current analysis was to compare results of auto-SCT and allo-SCT for adult patients with Ph+ ALL in first molecular remission.
PATIENTS AND METHODS: 569 adult patients with Ph+ ALL, treated between 2007-2014 with either auto-SCT (n=67), allo-SCT from matched sibling donor (MSD, n=255) or unrelated donor (URD, n=247) were included in the analysis. The median age for respective groups was 46 (20-65) years, 41 (18-65) years and 40 (18-65) years (p=0.002). Conditioning regimen was myeloablative in all cases and based on either total body irradiation (TBI) (64% in auto-SCT, 78% in MSD-SCT, 74% in URD-SCT) or chemotherapy. Based on available data, all auto-SCT recipients and 95% of allo-SCT recipients were treated with TKIs.
RESULTS: In a univariate analysis the incidence of relapse at two years was 47% after auto-SCT, 28% after MSD-SCT and 19% after URD-SCT (p=0.0002). Respective rates of non-relapse mortality (NRM) were 2%, 18% and 22% (p=0.001). The probabilities of leukemia-free survival (LFS) were 52%, 55%, and 60% (p=0.69) while overall survival (OS) rates were 70%, 70% and 69% (p=0.58), respectively. The incidence of chronic graft-versus-host disease (GVHD) for recipients of allo-SCT was 43%.
In a multivariate model adjusted for other potential risk factors, the risk of relapse was significantly reduced for URD-SCT as compared to auto-SCT (Hazard Ratio = 0.47, p=0.002). The risk of NRM was increased for both MSD-SCT (HR=14.1, p=0.009) and URD-SCT (HR=16.1; p=0.006). Compared to auto-SCT, a chance of LFS was similar for MSD-SCT (HR=1.1, p=0.53) and URD-SCT (HR=1.03, p=0.9). When referred to auto-SCT, there was a tendency to increased risk of the overall mortality after URD-SCT (HR=1.6, p=0.08) and MSD-SCT (HR=1.5, p=0.12). Among other factors, the use of TBI was associated with reduced risk of relapse (HR=0.65, p=0.02), while increased chance of LFS (HR=0.74, p=0.04) and OS (HR=0.67, p=0.01).
CONCLUSIONS: In the era of TKIs results of myeloablative auto-SCT, MSD-SCT and URD-SCT for patients with Ph+ ALL in first molecular remission are comparable. In view of these findings auto-SCT appears an attractive treatment option allowing avoidance of chronic GVHD. Further prospective studies are needed to better discriminate patients who benefit from allo-SCT or for whom the use of auto-SCT may be sufficient. Regardless the type of donor, TBI-based regimens should be considered preferable type of conditioning for adult patients with Ph+ ALL.
No relevant conflicts of interest to declare.
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