TREOSULFAN-BASED CONDITIONING AND UNMANIPULATED PERIPHERAL BLOOD HAPLOIDENTICAL TRANSPLANTATION (HAPLOSCT) FOR PRIMARY REFRACTORY AND RELAPSED AML: RESULTS IN 63 PATIENTS.
(Abstract release date: 05/19/16)
EHA Library. Lorentino F. 06/09/16; 135053; PB2153
Dr. Francesca Lorentino
Contributions
Contributions
Abstract
Abstract: PB2153
Type: Publication Only
Background
Allogeneic stem cell transplantation is the only potentially curative therapy for primary refractory (PR-AML) and relapsed acute myeloid leukemia (R-AML) patients (pts). HaploSCT could be an option for eligible pts whose clinical status warrants expedient treatment and who could benefit from a more potent alloreactivity.
Aims
retrospective analysis of 63 consecutive pts with PR-AML and R-AML who received a first unmanipulated haploSCT at our center
Methods
we retrospectively analyzed 63 pts undergoing a first unmanipulated haploSCT from January 2006 to December 2015. PR-AML was defined as the failure to achieve hematological remission following induction treatment.
Results
median age was 56 years (y) (20-77); 40% of pts were classified as PR-AML after a median of 2 induction courses (1-5), while 60% of pts had R-AML (51% 1st and 9% 2nd relapses). Median blast cell count in bone marrow was 33% (55-93%); median HCT-comorbidity index by Sorror et al. (HCT-CI) was 2 (0-8). Overall, 51% of pts received a reduced intensity conditioning (RIC) regimen based on Treosulfan (14 g/m2/d from -6 to -4), Fludarabine (30 mg/m2/d from -6 to -2) and anti-thymocyte globulin (ATG); 49% underwent a myeloablative conditioning (MAC) based on the same Treosulfan-Fludarabine schedule with the addiction of TBI 4Gy and ATG (23%) or Melphalan 70 mg/m2/d from -2 to -1 (26%). Source of stem cells were T-cell repleted G-CSF-mobilized peripheral blood stem cells from haploidentical familiar donors. All pts received post-grafting immunosuppression with mycophenolate mofetil and sirolimus; moreover, pts undergoing the Treo-Flu-Mel conditioning received post transplant Cyclophosphamide (PTCy) as backbone for GvHD prophylaxis.The complete remission (CR) rate was 78% after a median of 30 days (d) (21-41). Neutrophil engraftment occurred in 92% of pts with a median of 16 d (9-51). The 100-d cumulative incidence (CI) of grade≥2 acute GvHD (aGvHD) was 30±10% and of grade≥3 aGvHD 19±8%; the 2y CI of chronic GvHD was 14±8%.With a median follow-up for survivors of 24 months (4-95), the 2y probabilities of leukemia-free survival (LFS) and overall survival (OS) were 13±7% and 14±7%, respectively. For pts who achieved CR, the 2-y LFS and OS were 17±8% and 18±8%, respectively; CI of relapse at 1y and 2 y were 45±13% and 53±14%, respectively, with a median time to relapse of 160 d (47-727); CI of non-relapse mortality (NRM) at 1y and 2 y was 30±12%, with a median time of 63 d (42-375).In univariate analysis, the only factors influencing 2y-LFS were the intensity of conditioning regimen (29±14% for MAC and 5±4% for RIC recipients, p 0.05) and HCT-CI (35±13% if ≤2 and 4±3% if >2, p 0.01).In a Cox-multivariate model including pts age, blasts percentage, cytogenetic risk, HCT-CI, intensity of conditioning regimen, GvHD prophylaxis backbone (ATG Vs PTCy), disease status (PR- Vs R-AML) and interval from diagnosis to haploSCT, the only predictive factor for better LFS was an HCT-CI ≤2 with an hazard ratio of 0.46 (95% confidence interval: 0.2-0.8, p 0.01).
Conclusion
A consistent proportion of PR-AML and R-AML pts can achieve CR after an unmanipulated haploSCT. Median time to relapse of 160 days opens the window to early post transplant treatment aimed at a remission prolongation and enhancement of immune control.
Session topic: E-poster
Keyword(s): Acute myeloid leukemia, Haploidentical stem cell transplantation, Refractory
Type: Publication Only
Background
Allogeneic stem cell transplantation is the only potentially curative therapy for primary refractory (PR-AML) and relapsed acute myeloid leukemia (R-AML) patients (pts). HaploSCT could be an option for eligible pts whose clinical status warrants expedient treatment and who could benefit from a more potent alloreactivity.
Aims
retrospective analysis of 63 consecutive pts with PR-AML and R-AML who received a first unmanipulated haploSCT at our center
Methods
we retrospectively analyzed 63 pts undergoing a first unmanipulated haploSCT from January 2006 to December 2015. PR-AML was defined as the failure to achieve hematological remission following induction treatment.
Results
median age was 56 years (y) (20-77); 40% of pts were classified as PR-AML after a median of 2 induction courses (1-5), while 60% of pts had R-AML (51% 1st and 9% 2nd relapses). Median blast cell count in bone marrow was 33% (55-93%); median HCT-comorbidity index by Sorror et al. (HCT-CI) was 2 (0-8). Overall, 51% of pts received a reduced intensity conditioning (RIC) regimen based on Treosulfan (14 g/m2/d from -6 to -4), Fludarabine (30 mg/m2/d from -6 to -2) and anti-thymocyte globulin (ATG); 49% underwent a myeloablative conditioning (MAC) based on the same Treosulfan-Fludarabine schedule with the addiction of TBI 4Gy and ATG (23%) or Melphalan 70 mg/m2/d from -2 to -1 (26%). Source of stem cells were T-cell repleted G-CSF-mobilized peripheral blood stem cells from haploidentical familiar donors. All pts received post-grafting immunosuppression with mycophenolate mofetil and sirolimus; moreover, pts undergoing the Treo-Flu-Mel conditioning received post transplant Cyclophosphamide (PTCy) as backbone for GvHD prophylaxis.The complete remission (CR) rate was 78% after a median of 30 days (d) (21-41). Neutrophil engraftment occurred in 92% of pts with a median of 16 d (9-51). The 100-d cumulative incidence (CI) of grade≥2 acute GvHD (aGvHD) was 30±10% and of grade≥3 aGvHD 19±8%; the 2y CI of chronic GvHD was 14±8%.With a median follow-up for survivors of 24 months (4-95), the 2y probabilities of leukemia-free survival (LFS) and overall survival (OS) were 13±7% and 14±7%, respectively. For pts who achieved CR, the 2-y LFS and OS were 17±8% and 18±8%, respectively; CI of relapse at 1y and 2 y were 45±13% and 53±14%, respectively, with a median time to relapse of 160 d (47-727); CI of non-relapse mortality (NRM) at 1y and 2 y was 30±12%, with a median time of 63 d (42-375).In univariate analysis, the only factors influencing 2y-LFS were the intensity of conditioning regimen (29±14% for MAC and 5±4% for RIC recipients, p 0.05) and HCT-CI (35±13% if ≤2 and 4±3% if >2, p 0.01).In a Cox-multivariate model including pts age, blasts percentage, cytogenetic risk, HCT-CI, intensity of conditioning regimen, GvHD prophylaxis backbone (ATG Vs PTCy), disease status (PR- Vs R-AML) and interval from diagnosis to haploSCT, the only predictive factor for better LFS was an HCT-CI ≤2 with an hazard ratio of 0.46 (95% confidence interval: 0.2-0.8, p 0.01).
Conclusion
A consistent proportion of PR-AML and R-AML pts can achieve CR after an unmanipulated haploSCT. Median time to relapse of 160 days opens the window to early post transplant treatment aimed at a remission prolongation and enhancement of immune control.
Session topic: E-poster
Keyword(s): Acute myeloid leukemia, Haploidentical stem cell transplantation, Refractory
Abstract: PB2153
Type: Publication Only
Background
Allogeneic stem cell transplantation is the only potentially curative therapy for primary refractory (PR-AML) and relapsed acute myeloid leukemia (R-AML) patients (pts). HaploSCT could be an option for eligible pts whose clinical status warrants expedient treatment and who could benefit from a more potent alloreactivity.
Aims
retrospective analysis of 63 consecutive pts with PR-AML and R-AML who received a first unmanipulated haploSCT at our center
Methods
we retrospectively analyzed 63 pts undergoing a first unmanipulated haploSCT from January 2006 to December 2015. PR-AML was defined as the failure to achieve hematological remission following induction treatment.
Results
median age was 56 years (y) (20-77); 40% of pts were classified as PR-AML after a median of 2 induction courses (1-5), while 60% of pts had R-AML (51% 1st and 9% 2nd relapses). Median blast cell count in bone marrow was 33% (55-93%); median HCT-comorbidity index by Sorror et al. (HCT-CI) was 2 (0-8). Overall, 51% of pts received a reduced intensity conditioning (RIC) regimen based on Treosulfan (14 g/m2/d from -6 to -4), Fludarabine (30 mg/m2/d from -6 to -2) and anti-thymocyte globulin (ATG); 49% underwent a myeloablative conditioning (MAC) based on the same Treosulfan-Fludarabine schedule with the addiction of TBI 4Gy and ATG (23%) or Melphalan 70 mg/m2/d from -2 to -1 (26%). Source of stem cells were T-cell repleted G-CSF-mobilized peripheral blood stem cells from haploidentical familiar donors. All pts received post-grafting immunosuppression with mycophenolate mofetil and sirolimus; moreover, pts undergoing the Treo-Flu-Mel conditioning received post transplant Cyclophosphamide (PTCy) as backbone for GvHD prophylaxis.The complete remission (CR) rate was 78% after a median of 30 days (d) (21-41). Neutrophil engraftment occurred in 92% of pts with a median of 16 d (9-51). The 100-d cumulative incidence (CI) of grade≥2 acute GvHD (aGvHD) was 30±10% and of grade≥3 aGvHD 19±8%; the 2y CI of chronic GvHD was 14±8%.With a median follow-up for survivors of 24 months (4-95), the 2y probabilities of leukemia-free survival (LFS) and overall survival (OS) were 13±7% and 14±7%, respectively. For pts who achieved CR, the 2-y LFS and OS were 17±8% and 18±8%, respectively; CI of relapse at 1y and 2 y were 45±13% and 53±14%, respectively, with a median time to relapse of 160 d (47-727); CI of non-relapse mortality (NRM) at 1y and 2 y was 30±12%, with a median time of 63 d (42-375).In univariate analysis, the only factors influencing 2y-LFS were the intensity of conditioning regimen (29±14% for MAC and 5±4% for RIC recipients, p 0.05) and HCT-CI (35±13% if ≤2 and 4±3% if >2, p 0.01).In a Cox-multivariate model including pts age, blasts percentage, cytogenetic risk, HCT-CI, intensity of conditioning regimen, GvHD prophylaxis backbone (ATG Vs PTCy), disease status (PR- Vs R-AML) and interval from diagnosis to haploSCT, the only predictive factor for better LFS was an HCT-CI ≤2 with an hazard ratio of 0.46 (95% confidence interval: 0.2-0.8, p 0.01).
Conclusion
A consistent proportion of PR-AML and R-AML pts can achieve CR after an unmanipulated haploSCT. Median time to relapse of 160 days opens the window to early post transplant treatment aimed at a remission prolongation and enhancement of immune control.
Session topic: E-poster
Keyword(s): Acute myeloid leukemia, Haploidentical stem cell transplantation, Refractory
Type: Publication Only
Background
Allogeneic stem cell transplantation is the only potentially curative therapy for primary refractory (PR-AML) and relapsed acute myeloid leukemia (R-AML) patients (pts). HaploSCT could be an option for eligible pts whose clinical status warrants expedient treatment and who could benefit from a more potent alloreactivity.
Aims
retrospective analysis of 63 consecutive pts with PR-AML and R-AML who received a first unmanipulated haploSCT at our center
Methods
we retrospectively analyzed 63 pts undergoing a first unmanipulated haploSCT from January 2006 to December 2015. PR-AML was defined as the failure to achieve hematological remission following induction treatment.
Results
median age was 56 years (y) (20-77); 40% of pts were classified as PR-AML after a median of 2 induction courses (1-5), while 60% of pts had R-AML (51% 1st and 9% 2nd relapses). Median blast cell count in bone marrow was 33% (55-93%); median HCT-comorbidity index by Sorror et al. (HCT-CI) was 2 (0-8). Overall, 51% of pts received a reduced intensity conditioning (RIC) regimen based on Treosulfan (14 g/m2/d from -6 to -4), Fludarabine (30 mg/m2/d from -6 to -2) and anti-thymocyte globulin (ATG); 49% underwent a myeloablative conditioning (MAC) based on the same Treosulfan-Fludarabine schedule with the addiction of TBI 4Gy and ATG (23%) or Melphalan 70 mg/m2/d from -2 to -1 (26%). Source of stem cells were T-cell repleted G-CSF-mobilized peripheral blood stem cells from haploidentical familiar donors. All pts received post-grafting immunosuppression with mycophenolate mofetil and sirolimus; moreover, pts undergoing the Treo-Flu-Mel conditioning received post transplant Cyclophosphamide (PTCy) as backbone for GvHD prophylaxis.The complete remission (CR) rate was 78% after a median of 30 days (d) (21-41). Neutrophil engraftment occurred in 92% of pts with a median of 16 d (9-51). The 100-d cumulative incidence (CI) of grade≥2 acute GvHD (aGvHD) was 30±10% and of grade≥3 aGvHD 19±8%; the 2y CI of chronic GvHD was 14±8%.With a median follow-up for survivors of 24 months (4-95), the 2y probabilities of leukemia-free survival (LFS) and overall survival (OS) were 13±7% and 14±7%, respectively. For pts who achieved CR, the 2-y LFS and OS were 17±8% and 18±8%, respectively; CI of relapse at 1y and 2 y were 45±13% and 53±14%, respectively, with a median time to relapse of 160 d (47-727); CI of non-relapse mortality (NRM) at 1y and 2 y was 30±12%, with a median time of 63 d (42-375).In univariate analysis, the only factors influencing 2y-LFS were the intensity of conditioning regimen (29±14% for MAC and 5±4% for RIC recipients, p 0.05) and HCT-CI (35±13% if ≤2 and 4±3% if >2, p 0.01).In a Cox-multivariate model including pts age, blasts percentage, cytogenetic risk, HCT-CI, intensity of conditioning regimen, GvHD prophylaxis backbone (ATG Vs PTCy), disease status (PR- Vs R-AML) and interval from diagnosis to haploSCT, the only predictive factor for better LFS was an HCT-CI ≤2 with an hazard ratio of 0.46 (95% confidence interval: 0.2-0.8, p 0.01).
Conclusion
A consistent proportion of PR-AML and R-AML pts can achieve CR after an unmanipulated haploSCT. Median time to relapse of 160 days opens the window to early post transplant treatment aimed at a remission prolongation and enhancement of immune control.
Session topic: E-poster
Keyword(s): Acute myeloid leukemia, Haploidentical stem cell transplantation, Refractory
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