Contributions
Abstract: EP1229
Type: E-Poster Presentation
Session title: Stem cell transplantation - Clinical
Background
Cord blood transplantation (CBT) and HLA-mismatched transplantation has become established alternative stem cell sources for patients with hematological malignancies. HLA-mismatched transplantation with post-transplant cyclophosphamide has spread rapidly and demonstrated favorable outcomes. Likewise, several studies indicated the potential of HLA-haploidentical transplantation with low-dose antithymocyte globulin, especially for high-risk diseases. On the other hand, significant progress in the management of CBT has led to comparable outcomes of HLA-matched and mismatched unrelated transplantation, showing better outcomes for patients with minimal residual disease.
Aims
To compare the outcomes of CBT and HLA-mismatched transplantation using low-dose ATG, we performed a retrospective study using data from the Japanese registry.
Methods
A total of 7899 patients aged 0-70 years with hematological malignancies who received their first allogeneic hematopoietic cell transplantation between 2009-2018 were eligible. A total of 7034 and 865 patients who underwent single CBT and HLA 1-3 antigen-mismatched related stem cell transplantation using ATG (mismatched-ATG) were included. The primary endpoint was overall survival (OS) and secondary endpoints were relapse-free survival (RFS), GVHD-relapse-free survival (GRFS), non-relapse mortality (NRM), relapse, neutrophil engraftment, platelet engraftment, grade Ⅱ-Ⅳ acute GVHD, grade III-IV acute GVHD, chronic GVHD and extensive chronic GVHD.
Results
The median age in the CBT and mismatched-ATG groups were 53 and 47 years, respectively (p<0.001). High risk diseases and reduced-intensity condition were more frequent in the mismatched-ATG group (43.4% vs 66.1% and 36.6% vs 66.2%). In the mismatched-ATG group, the most common combination of GVHD prophylaxis was ATG plus cyclosporine A (CsA) or tacrolimus (TAC), and steroid (66.6%), whereas it was CsA or TAC plus methotrexate (MTX) in the CBT group (66.5%). In the mismatched-ATG group, 1 antigen mismatched transplant was included (16.5%) and median total dose of ATG was 2.5 (0.42-10.0) mg/kg. Median follow-up time in survivors was 3.3 and 3.4 years in the CBT and mismatched-ATG groups, respectively. OS after CBT was significantly higher than that of mismatched-ATG (3-year OS: 47.2%, 32.4%, P<0.001 and adjusted hazard ratio (aHR) 0.76, P<0.001). RFS and GRFS of CBT were also higher than mismatched-ATG (aHR 0.79, p<0.001 and aHR 0.70, p<0.001). Neutrophil and platelet engraftment were significantly lower (85% vs 94.8% and 60.2% vs 65.2%), whereas the incidence of grade Ⅲ to Ⅳacute GVHD and extensive chronic GVHD was significantly lower in the CBT group (aHR 0.44, p<0.001 and aHR 0.62, p<0.001). In the subgroup analysis, superiority of CBT to mismatched-ATG was observed in each disease group (AML: aHR 0.87, 95% confidence interval (CI) 0.75-1.00, ALL: aHR 0.70, 95% CI 0.55-0.89, MDS: aHR 0.79, 95%CI 0.52-1.19, and lymphoma: aHR 0.64, 95%CI 0.52-0.79). Favorable OS of CBT was confirmed regardless the disease risk (standard risk: aHR 0.63, 95%CI 0.53-0.75, high risk: aHR 0.83, 95%CI 0.73-0.93) and HLA mismatch (0-1: aHR 0.85, 95%CI 0.67-1.08, 2-3: aHR 0.74, 95%CI 0.67-0.83).
Conclusion
We observed favorable outcomes of CBT compared to mismatched-ATG, consistently the same according to the patient generations, disease, and disease risk. CBT may be the better choice alternative to HLA mismatched related transplant using low-dose ATG.
Keyword(s): Antithrombin, Cord blood transplant, Mismatched
Abstract: EP1229
Type: E-Poster Presentation
Session title: Stem cell transplantation - Clinical
Background
Cord blood transplantation (CBT) and HLA-mismatched transplantation has become established alternative stem cell sources for patients with hematological malignancies. HLA-mismatched transplantation with post-transplant cyclophosphamide has spread rapidly and demonstrated favorable outcomes. Likewise, several studies indicated the potential of HLA-haploidentical transplantation with low-dose antithymocyte globulin, especially for high-risk diseases. On the other hand, significant progress in the management of CBT has led to comparable outcomes of HLA-matched and mismatched unrelated transplantation, showing better outcomes for patients with minimal residual disease.
Aims
To compare the outcomes of CBT and HLA-mismatched transplantation using low-dose ATG, we performed a retrospective study using data from the Japanese registry.
Methods
A total of 7899 patients aged 0-70 years with hematological malignancies who received their first allogeneic hematopoietic cell transplantation between 2009-2018 were eligible. A total of 7034 and 865 patients who underwent single CBT and HLA 1-3 antigen-mismatched related stem cell transplantation using ATG (mismatched-ATG) were included. The primary endpoint was overall survival (OS) and secondary endpoints were relapse-free survival (RFS), GVHD-relapse-free survival (GRFS), non-relapse mortality (NRM), relapse, neutrophil engraftment, platelet engraftment, grade Ⅱ-Ⅳ acute GVHD, grade III-IV acute GVHD, chronic GVHD and extensive chronic GVHD.
Results
The median age in the CBT and mismatched-ATG groups were 53 and 47 years, respectively (p<0.001). High risk diseases and reduced-intensity condition were more frequent in the mismatched-ATG group (43.4% vs 66.1% and 36.6% vs 66.2%). In the mismatched-ATG group, the most common combination of GVHD prophylaxis was ATG plus cyclosporine A (CsA) or tacrolimus (TAC), and steroid (66.6%), whereas it was CsA or TAC plus methotrexate (MTX) in the CBT group (66.5%). In the mismatched-ATG group, 1 antigen mismatched transplant was included (16.5%) and median total dose of ATG was 2.5 (0.42-10.0) mg/kg. Median follow-up time in survivors was 3.3 and 3.4 years in the CBT and mismatched-ATG groups, respectively. OS after CBT was significantly higher than that of mismatched-ATG (3-year OS: 47.2%, 32.4%, P<0.001 and adjusted hazard ratio (aHR) 0.76, P<0.001). RFS and GRFS of CBT were also higher than mismatched-ATG (aHR 0.79, p<0.001 and aHR 0.70, p<0.001). Neutrophil and platelet engraftment were significantly lower (85% vs 94.8% and 60.2% vs 65.2%), whereas the incidence of grade Ⅲ to Ⅳacute GVHD and extensive chronic GVHD was significantly lower in the CBT group (aHR 0.44, p<0.001 and aHR 0.62, p<0.001). In the subgroup analysis, superiority of CBT to mismatched-ATG was observed in each disease group (AML: aHR 0.87, 95% confidence interval (CI) 0.75-1.00, ALL: aHR 0.70, 95% CI 0.55-0.89, MDS: aHR 0.79, 95%CI 0.52-1.19, and lymphoma: aHR 0.64, 95%CI 0.52-0.79). Favorable OS of CBT was confirmed regardless the disease risk (standard risk: aHR 0.63, 95%CI 0.53-0.75, high risk: aHR 0.83, 95%CI 0.73-0.93) and HLA mismatch (0-1: aHR 0.85, 95%CI 0.67-1.08, 2-3: aHR 0.74, 95%CI 0.67-0.83).
Conclusion
We observed favorable outcomes of CBT compared to mismatched-ATG, consistently the same according to the patient generations, disease, and disease risk. CBT may be the better choice alternative to HLA mismatched related transplant using low-dose ATG.
Keyword(s): Antithrombin, Cord blood transplant, Mismatched