Contributions
Abstract: S797
Type: Oral Presentation
Presentation during EHA22: On Sunday, June 25, 2017 from 08:45 - 09:00
Location: Room N105
Background
Allogeneic hematopoietic stem cell transplantation (alloHCT) is widely used for the treatment of adults with acute lymphoblastic leukemia (ALL). Although the choice of pre transplantation conditioning has never been a subject of a randomized trial, results of many retrospective studies suggested advantage of total body irradiation (TBI)-based over chemotherapy-based regimens. TBI is most frequently administered in combination with either cyclophosphamide (Cy/TBI) or etoposide (Vep/TBI).
Aims
The goal of this study was to retrospectively compare the outcome of alloHCT using Cy/TBI or Vep/TBI as conditioning.
Methods
Adult patients with Ph-negative ALL (n=1498) treated with alloHCT from either HLA-identical sibling (n=696) or unrelated donor (n=802), in CR1 (n=1186) or CR2 (n=312), between year 2000 – 2015, were included in the analysis. Peripheral blood was used as a source of stem cells in 62% of the patients, while bone marrow in 38% of the patients, respectively. Conditioning was myeloablative in all cases (the median TBI dose was 12Gy); 1346 patients were treated with Cy/TBI while 152 patients with Vep/TBI. Patients in the Vep/TBI group were younger (median 28 y. vs. 30 y., p=0.04), treated in more recent period (median year of HCT: 2009 vs. 2007, p=0.009) and treated more frequently in CR1 (87% vs. 78%, p=0.001).
Results
In a univariate analysis, as compared to Cy/TBI, the use of Vep/TBI was associated with significantly reduced incidence of relapse (17% vs. 30% at 5 years, p=0.007), increased rate of leukemia-free survival (LFS, 60% vs. 50%, p=0.04) as well as improved “GVHD and relapse-free survival” (GRFS, 43% vs. 33%, p=0.04). No significant effect could be observed in terms of the incidence of non-relapse mortality, acute or chronic GVHD. In a multivariate model the use of Vep/TBI was associated with reduced risk of relapse (HR=0.62, p=0.04) while the effect on other study end-points was no longer significant. Among other factors, recipient age (HR=1.17 per every 10 years, p=<0.0001), year of alloHCT (HR=0.97 per every year, p=0.001) and disease stage (HR=2.14 for CR2, p<0.0001) had significant influence on the risk of treatment failure, either relapse or non-relapse mortality. The risk of relapse was additionally increased for sibling vs. unrelated donor transplants (HR=1.47, p=0.01) and donor/recipient gender combination other than female/male (HR=1.37, p=0.04).
Conclusion
Conditioning regimen based on etoposide combined with TBI appears more effective than the cyclophosphamide TBI combination for adult patients with Ph-negative ALL treated with alloHCT. Further, prospective studies are needed to confirm our observation and potentially discriminate subgroup of patients who are most likely to benefit from the use of etoposide.
Session topic: 22. Stem cell transplantation - Clinical
Keyword(s): Total body irradiation, Allogeneic hematopoietic stem cell transplant, Acute lymphoblastic leukemia
Abstract: S797
Type: Oral Presentation
Presentation during EHA22: On Sunday, June 25, 2017 from 08:45 - 09:00
Location: Room N105
Background
Allogeneic hematopoietic stem cell transplantation (alloHCT) is widely used for the treatment of adults with acute lymphoblastic leukemia (ALL). Although the choice of pre transplantation conditioning has never been a subject of a randomized trial, results of many retrospective studies suggested advantage of total body irradiation (TBI)-based over chemotherapy-based regimens. TBI is most frequently administered in combination with either cyclophosphamide (Cy/TBI) or etoposide (Vep/TBI).
Aims
The goal of this study was to retrospectively compare the outcome of alloHCT using Cy/TBI or Vep/TBI as conditioning.
Methods
Adult patients with Ph-negative ALL (n=1498) treated with alloHCT from either HLA-identical sibling (n=696) or unrelated donor (n=802), in CR1 (n=1186) or CR2 (n=312), between year 2000 – 2015, were included in the analysis. Peripheral blood was used as a source of stem cells in 62% of the patients, while bone marrow in 38% of the patients, respectively. Conditioning was myeloablative in all cases (the median TBI dose was 12Gy); 1346 patients were treated with Cy/TBI while 152 patients with Vep/TBI. Patients in the Vep/TBI group were younger (median 28 y. vs. 30 y., p=0.04), treated in more recent period (median year of HCT: 2009 vs. 2007, p=0.009) and treated more frequently in CR1 (87% vs. 78%, p=0.001).
Results
In a univariate analysis, as compared to Cy/TBI, the use of Vep/TBI was associated with significantly reduced incidence of relapse (17% vs. 30% at 5 years, p=0.007), increased rate of leukemia-free survival (LFS, 60% vs. 50%, p=0.04) as well as improved “GVHD and relapse-free survival” (GRFS, 43% vs. 33%, p=0.04). No significant effect could be observed in terms of the incidence of non-relapse mortality, acute or chronic GVHD. In a multivariate model the use of Vep/TBI was associated with reduced risk of relapse (HR=0.62, p=0.04) while the effect on other study end-points was no longer significant. Among other factors, recipient age (HR=1.17 per every 10 years, p=<0.0001), year of alloHCT (HR=0.97 per every year, p=0.001) and disease stage (HR=2.14 for CR2, p<0.0001) had significant influence on the risk of treatment failure, either relapse or non-relapse mortality. The risk of relapse was additionally increased for sibling vs. unrelated donor transplants (HR=1.47, p=0.01) and donor/recipient gender combination other than female/male (HR=1.37, p=0.04).
Conclusion
Conditioning regimen based on etoposide combined with TBI appears more effective than the cyclophosphamide TBI combination for adult patients with Ph-negative ALL treated with alloHCT. Further, prospective studies are needed to confirm our observation and potentially discriminate subgroup of patients who are most likely to benefit from the use of etoposide.
Session topic: 22. Stem cell transplantation - Clinical
Keyword(s): Total body irradiation, Allogeneic hematopoietic stem cell transplant, Acute lymphoblastic leukemia