Contributions
Abstract: PB2173
Type: Publication Only
Background
Reduced intensity allogeneic stem cell transplantation (RIST) is now commonly applied for elderly patients with acute leukemia (AL) or myelodysplastic syndromes (MDS). However, the factors affecting graft-versus-host disease-free, relapse-free survival (GRFS) and overall survival (OS) remain obscure.
Aims
To identify such factors and to clarify the clinical significance of RIST with various graft sources, we retrospectively analyzed patients with AL or MDS who received RIST in our hospital.
Methods
The study included patients with acute myeloid leukemia (n=73), acute lymphoid leukemia (n=31) or MDS (n=25), who received fludarabine (Flu)/melphalan (Mel)-based RIST between 2004 and 2015 as the first transplantation.
Results
There were a total of 129 patients, including 3 in low risk (L), 74 in intermediate risk (I), 36 in high risk (H) and 16 in very high risk (V), classified by the refined disease risk index (rDRI). The median age was 58 years (range: 18-68 years), with 73 males and 56 females. Conditioning regimens contained Flu (125mg/m2) combined with Mel (80mg/m2, n=21 or 140mg/m2, n=108). Total body irradiation (4Gy) was used in 96 patients who received transplantation from unrelated donors or HLA mismatched related donors. Bone marrow (BM) or peripheral blood stem cell (PB) from related donors was used in 40 patients, BM or PB from unrelated donors in 33 and cord blood (CB) from unrelated donors in 56. Primary graft failure occurred in 7 patients and death before engraftment was observed in two. After a median follow-up of 46 months (range: 15-144 months) for the survivors, the 1-year GRFS, disease free survival (DFS) and OS were 57%, 61% and 70%, respectively. On univariate analysis for all patients, pre-transplant factors associated with the 1-year GRFS included stem cell sources (BM/PB vs CB: 44% vs 68%, p=0.005), donors (related vs unrelated: 38% vs 62%, p=0.012), disease (AL vs MDS: 60% vs 28%, p<0.001) and rDRI (L/I vs H/V: 65% vs 38%, p=0.003). On multivariate analysis, BM/PB (HR 2.0, 95% CI 1.0-4.0, p=0.039), MDS (HR 2.6, 95% CI 1.5-4.6, p=0.001) and H/V rDRI (HR 2.1, 95% CI 1.2-3.5, p=0.006) were associated with a worse GRFS. The 5-year OS, cumulative incidence of relapse (CIR) and non-relapse mortality (NRM) were 55%, 36% and 18%, respectively. On univariate analysis, significant prognostic factors were hematopoietic cell transplantation-specific comorbidity index (HCT-CI) (score 0 vs >= 1: 78% vs 48%, p=0.007), disease (AL vs MDS: 59% vs 40%, p=0.004) and rDRI (L/I vs H/V: 64% vs 43%, p=0.003) for the 5-year OS, donors (related vs unrelated: 53% vs 27%, p=0.005) and rDRI (L/I vs HV: 27% vs 48%, p=0.005) for CIR, and age (< 60 vs >= 60: 10% vs 28%, p=0.021), donors (related vs unrelated: 8% vs 23%, p=0.034) and disease (AL vs MDS: 13% vs 36%, p=0.003) for NRM. On multivariate analysis, HCT-CI score >= 1 (HR 3.1, 95% CI 1.3-7.4, p=0.009) and MDS (HR 2.4, 95% CI 1.3-4.5, p=0.005) were adversely associated with OS, so were H/V rDRI (HR 2.5, 95%CI 1.4-4.7, p=0.003) and MDS (HR 3.7, 95%CI 1.6-8.8, p=0.002) for CIR and NRM, respectively.
Conclusion
Our data suggest that Flu/Mel-based RIST was a promising strategy for patients with hematologic malignancy, irrespective of (?) donor or stem cell sources. However, GRFS and OS of MDS were significantly worse than those of AL, and MDS is strongly associated with high NRM even with RIST. This indicates that we should pay more attention to NRM in MDS.
Session topic: 22. Stem cell transplantation - Clinical
Keyword(s): RIST
Abstract: PB2173
Type: Publication Only
Background
Reduced intensity allogeneic stem cell transplantation (RIST) is now commonly applied for elderly patients with acute leukemia (AL) or myelodysplastic syndromes (MDS). However, the factors affecting graft-versus-host disease-free, relapse-free survival (GRFS) and overall survival (OS) remain obscure.
Aims
To identify such factors and to clarify the clinical significance of RIST with various graft sources, we retrospectively analyzed patients with AL or MDS who received RIST in our hospital.
Methods
The study included patients with acute myeloid leukemia (n=73), acute lymphoid leukemia (n=31) or MDS (n=25), who received fludarabine (Flu)/melphalan (Mel)-based RIST between 2004 and 2015 as the first transplantation.
Results
There were a total of 129 patients, including 3 in low risk (L), 74 in intermediate risk (I), 36 in high risk (H) and 16 in very high risk (V), classified by the refined disease risk index (rDRI). The median age was 58 years (range: 18-68 years), with 73 males and 56 females. Conditioning regimens contained Flu (125mg/m2) combined with Mel (80mg/m2, n=21 or 140mg/m2, n=108). Total body irradiation (4Gy) was used in 96 patients who received transplantation from unrelated donors or HLA mismatched related donors. Bone marrow (BM) or peripheral blood stem cell (PB) from related donors was used in 40 patients, BM or PB from unrelated donors in 33 and cord blood (CB) from unrelated donors in 56. Primary graft failure occurred in 7 patients and death before engraftment was observed in two. After a median follow-up of 46 months (range: 15-144 months) for the survivors, the 1-year GRFS, disease free survival (DFS) and OS were 57%, 61% and 70%, respectively. On univariate analysis for all patients, pre-transplant factors associated with the 1-year GRFS included stem cell sources (BM/PB vs CB: 44% vs 68%, p=0.005), donors (related vs unrelated: 38% vs 62%, p=0.012), disease (AL vs MDS: 60% vs 28%, p<0.001) and rDRI (L/I vs H/V: 65% vs 38%, p=0.003). On multivariate analysis, BM/PB (HR 2.0, 95% CI 1.0-4.0, p=0.039), MDS (HR 2.6, 95% CI 1.5-4.6, p=0.001) and H/V rDRI (HR 2.1, 95% CI 1.2-3.5, p=0.006) were associated with a worse GRFS. The 5-year OS, cumulative incidence of relapse (CIR) and non-relapse mortality (NRM) were 55%, 36% and 18%, respectively. On univariate analysis, significant prognostic factors were hematopoietic cell transplantation-specific comorbidity index (HCT-CI) (score 0 vs >= 1: 78% vs 48%, p=0.007), disease (AL vs MDS: 59% vs 40%, p=0.004) and rDRI (L/I vs H/V: 64% vs 43%, p=0.003) for the 5-year OS, donors (related vs unrelated: 53% vs 27%, p=0.005) and rDRI (L/I vs HV: 27% vs 48%, p=0.005) for CIR, and age (< 60 vs >= 60: 10% vs 28%, p=0.021), donors (related vs unrelated: 8% vs 23%, p=0.034) and disease (AL vs MDS: 13% vs 36%, p=0.003) for NRM. On multivariate analysis, HCT-CI score >= 1 (HR 3.1, 95% CI 1.3-7.4, p=0.009) and MDS (HR 2.4, 95% CI 1.3-4.5, p=0.005) were adversely associated with OS, so were H/V rDRI (HR 2.5, 95%CI 1.4-4.7, p=0.003) and MDS (HR 3.7, 95%CI 1.6-8.8, p=0.002) for CIR and NRM, respectively.
Conclusion
Our data suggest that Flu/Mel-based RIST was a promising strategy for patients with hematologic malignancy, irrespective of (?) donor or stem cell sources. However, GRFS and OS of MDS were significantly worse than those of AL, and MDS is strongly associated with high NRM even with RIST. This indicates that we should pay more attention to NRM in MDS.
Session topic: 22. Stem cell transplantation - Clinical
Keyword(s): RIST