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Improved post-transplant outcomes since 2000 for Ph-positive acute lymphoblastic leukemia in first remission: A study
Ali Bazarbachi1, Myriam Labopin2, Iman Abou Dalle1
1Bone Marrow Transplantation Program, Department of Internal Medicine American University of Beirut Medical Center Beirut Lebanon.
Allogeneic hematopoietic cell transplantation (allo-HCT) remains a curative treatment for patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) in their first complete remission (CR1). Recent results using the combination of blinatumomab and second- or third-generation tyrosine kinase inhibitors have challenged the necessity of allo-HCT in CR1. Here we assessed real-world changes over time in transplant characteristics and outcomes in adult patients with Ph+ ALL in CR1, using a large dataset from the European Society for Blood and Marrow Transplantation registry. A total of 3292 patients (45% female; median age 45 years) who underwent allo-HCT from 2001 to 2020 were included. Over four periods (2001-2005, 2006-2010, 2011-2015, and 2016-2020), the 3-year cumulative incidence of relapse decreased from 41% to 19%, and non-relapse mortality decreased from 25% to 17% (p < 0.001 for both). Correspondingly, 3-year leukemia-free survival (LFS) improved from 34% to 64%, and overall survival (OS) from 47% to 75% (p < 0.001 for both). Graft versus host disease-free and relapse-free survival also improved from 26% to 49% (p < 0.001). Factors negatively affecting LFS included older age, male gender, male donor and measurable residual disease (MRD) positivity pre-transplant, while total body conditioning (TBI) positively affected LFS. OS was positively influenced by younger age, female gender, matched sibling donor, TBI, and T cell depletion. Importantly, improvement in post-transplant outcomes over time was observed regardless of pre-transplant MRD status. In conclusion, we observed an impressive improvement over time in post-transplant outcomes of Ph+ ALL. These large-scale data can serve as a benchmark for future studies.
Allogeneic hematopoietic cell transplantation (allo-HCT) remains a curative treatment for patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) in their first complete remission (CR1). Recent results using the combination of blinatumomab and second- or third-generation tyrosine kinase inhibitors have challenged the necessity of allo-HCT in CR1. Here we assessed real-world changes over time in transplant characteristics and outcomes in adult patients with Ph+ ALL in CR1, using a large dataset from the European Society for Blood and Marrow Transplantation registry. A total of 3292 patients (45% female; median age 45 years) who underwent allo-HCT from 2001 to 2020 were included. Over four periods (2001-2005, 2006-2010, 2011-2015, and 2016-2020), the 3-year cumulative incidence of relapse decreased from 41% to 19%, and non-relapse mortality decreased from 25% to 17% (p < 0.001 for both). Correspondingly, 3-year leukemia-free survival (LFS) improved from 34% to 64%, and overall survival (OS) from 47% to 75% (p < 0.001 for both). Graft versus host disease-free and relapse-free survival also improved from 26% to 49% (p < 0.001). Factors negatively affecting LFS included older age, male gender, male donor and measurable residual disease (MRD) positivity pre-transplant, while total body conditioning (TBI) positively affected LFS. OS was positively influenced by younger age, female gender, matched sibling donor, TBI, and T cell depletion. Importantly, improvement in post-transplant outcomes over time was observed regardless of pre-transplant MRD status. In conclusion, we observed an impressive improvement over time in post-transplant outcomes of Ph+ ALL. These large-scale data can serve as a benchmark for future studies.
