POST-TRANSPLANT CYCLOPHOSPHAMIDE AS GRAFT-VERSUS-HOST DISEASE PROPHYLAXIS IN PEDIATRIC PATIENTS WITH HEMATOLOGIC MALIGNANCIES TRANSPLANTED FROM HAPLOIDENTICAL AND MATCHED UNRELATED DONORS.
(Abstract release date: 05/19/16)
EHA Library. Abrosimov A. 06/09/16; 133093; E1544
Mr. Andrey Abrosimov
Contributions
Contributions
Abstract
Abstract: E1544
Type: Eposter Presentation
Background
Standard GvHD prophylaxis regimens impair the graft-versus-tumor (GVT) effect, delay immune reconstitution and are associated with high rate of infections. High-dose post-transplantation cyclophosphamide (PTCy) targets alloreactive donor T cells proliferating early after BMT, promotes regulatory T cell and permits rapid immune reconstitution.
Aims
In this pilot trial we evaluate the safety and effects of PTCy in unmanipulated haploidentical and matched unrelated transplantation (MUD) in pediatric patients with hematologic malignancies.
Methods
Twenty eight pediatric patients with high risk hematologic malignancies underwent unmanipulated allogeneic bone marrow (BM) (n=26) or peripheral blood stem cell (PBSC)(n=2) transplantation followed by PTCy between April 2014 and September 2015 with a median follow-up of 9 months (1,5-19). Nineteen patients were transplanted from haploidentical donors and 9 from MUD. The median age was 10,4 years (range 1,9-18); 14 patients with ALL, 4 AML, 8 JMML and 2 with HD; 16 patients were in remission (CR) (14-ALL, 1-AML, 1-HD), 12 had active disease (AD) (8-JMML, 3-AML, 1-HD).In 11 pts this was a second allograft. Twenty-six pts received myeloablative Treosulfan/Melphalan/Fludarabine and 2 pts - reduced-intensity Fludarabine/TAO 2Gy/Thiotepa as conditioning regimen. GvHD prophylaxis consisted of PTCy on day +3, +4 and tacrolimus from day +5 in all pts., 12 (43%) pts. also received ATG (rabbit, thymoglobuline) at 5 mg/kg/course.
Results
Primary engraftment was achieved in 27(96,4%) of 28 pts., the median time to neutrophil and platelet recovery was 20 days (14-45) and 21 days (10-97). Twenty seven (96,4%) patients were in full donor chimerism on day +30. Early mortality was 14,9% (95% CI: 6-36), causes of death included viral infections (n=3); GvHD and viral infection (n=1). Cumulative incidence (CI) of acute GvHD grade ≥ II was 50% (95%CI:34-74), grade III–IV - 34% (95%CI:19-62) and chronic GvHD – 19% (95%CI:8-45). No correlation between the use of ATG and acute/chronic GvHD was noted. CI of relapse was 15,4% (95% CI: 6-38) and was significantly lower in CR vs AD group: 0% vs 36% (95% CI: 17-77), p=0,015. One year event-free survival (EFS) was 69,7% (95%CI: 52-87) and overall survival (OS) - 76% (95%CI: 59-93). One year pOS was significantly lower in the ATG group 58% (95%CI: 30-86) vs non-ATG group 93% (95%CI: 79-100), p=0,039. One year pEFS was 87% for patients in remission and 48% for patients with active disease (p=0,028). There was no significant difference in survival and relapse rate according to donor type.
Conclusion
Our study demonstrates the high rate of engraftment with acceptable transplant-related mortality in pediatric patients with hematological malignancies after unmanipulated HSCT with posttransplant cyclophosphamide. The data need to be confirmed in a larger trial with long-term follow-up.
Session topic: E-poster
Keyword(s): Acute leukemia, Cyclophosphamide, HSCT, Pediatric
Type: Eposter Presentation
Background
Standard GvHD prophylaxis regimens impair the graft-versus-tumor (GVT) effect, delay immune reconstitution and are associated with high rate of infections. High-dose post-transplantation cyclophosphamide (PTCy) targets alloreactive donor T cells proliferating early after BMT, promotes regulatory T cell and permits rapid immune reconstitution.
Aims
In this pilot trial we evaluate the safety and effects of PTCy in unmanipulated haploidentical and matched unrelated transplantation (MUD) in pediatric patients with hematologic malignancies.
Methods
Twenty eight pediatric patients with high risk hematologic malignancies underwent unmanipulated allogeneic bone marrow (BM) (n=26) or peripheral blood stem cell (PBSC)(n=2) transplantation followed by PTCy between April 2014 and September 2015 with a median follow-up of 9 months (1,5-19). Nineteen patients were transplanted from haploidentical donors and 9 from MUD. The median age was 10,4 years (range 1,9-18); 14 patients with ALL, 4 AML, 8 JMML and 2 with HD; 16 patients were in remission (CR) (14-ALL, 1-AML, 1-HD), 12 had active disease (AD) (8-JMML, 3-AML, 1-HD).In 11 pts this was a second allograft. Twenty-six pts received myeloablative Treosulfan/Melphalan/Fludarabine and 2 pts - reduced-intensity Fludarabine/TAO 2Gy/Thiotepa as conditioning regimen. GvHD prophylaxis consisted of PTCy on day +3, +4 and tacrolimus from day +5 in all pts., 12 (43%) pts. also received ATG (rabbit, thymoglobuline) at 5 mg/kg/course.
Results
Primary engraftment was achieved in 27(96,4%) of 28 pts., the median time to neutrophil and platelet recovery was 20 days (14-45) and 21 days (10-97). Twenty seven (96,4%) patients were in full donor chimerism on day +30. Early mortality was 14,9% (95% CI: 6-36), causes of death included viral infections (n=3); GvHD and viral infection (n=1). Cumulative incidence (CI) of acute GvHD grade ≥ II was 50% (95%CI:34-74), grade III–IV - 34% (95%CI:19-62) and chronic GvHD – 19% (95%CI:8-45). No correlation between the use of ATG and acute/chronic GvHD was noted. CI of relapse was 15,4% (95% CI: 6-38) and was significantly lower in CR vs AD group: 0% vs 36% (95% CI: 17-77), p=0,015. One year event-free survival (EFS) was 69,7% (95%CI: 52-87) and overall survival (OS) - 76% (95%CI: 59-93). One year pOS was significantly lower in the ATG group 58% (95%CI: 30-86) vs non-ATG group 93% (95%CI: 79-100), p=0,039. One year pEFS was 87% for patients in remission and 48% for patients with active disease (p=0,028). There was no significant difference in survival and relapse rate according to donor type.
Conclusion
Our study demonstrates the high rate of engraftment with acceptable transplant-related mortality in pediatric patients with hematological malignancies after unmanipulated HSCT with posttransplant cyclophosphamide. The data need to be confirmed in a larger trial with long-term follow-up.
Session topic: E-poster
Keyword(s): Acute leukemia, Cyclophosphamide, HSCT, Pediatric
Abstract: E1544
Type: Eposter Presentation
Background
Standard GvHD prophylaxis regimens impair the graft-versus-tumor (GVT) effect, delay immune reconstitution and are associated with high rate of infections. High-dose post-transplantation cyclophosphamide (PTCy) targets alloreactive donor T cells proliferating early after BMT, promotes regulatory T cell and permits rapid immune reconstitution.
Aims
In this pilot trial we evaluate the safety and effects of PTCy in unmanipulated haploidentical and matched unrelated transplantation (MUD) in pediatric patients with hematologic malignancies.
Methods
Twenty eight pediatric patients with high risk hematologic malignancies underwent unmanipulated allogeneic bone marrow (BM) (n=26) or peripheral blood stem cell (PBSC)(n=2) transplantation followed by PTCy between April 2014 and September 2015 with a median follow-up of 9 months (1,5-19). Nineteen patients were transplanted from haploidentical donors and 9 from MUD. The median age was 10,4 years (range 1,9-18); 14 patients with ALL, 4 AML, 8 JMML and 2 with HD; 16 patients were in remission (CR) (14-ALL, 1-AML, 1-HD), 12 had active disease (AD) (8-JMML, 3-AML, 1-HD).In 11 pts this was a second allograft. Twenty-six pts received myeloablative Treosulfan/Melphalan/Fludarabine and 2 pts - reduced-intensity Fludarabine/TAO 2Gy/Thiotepa as conditioning regimen. GvHD prophylaxis consisted of PTCy on day +3, +4 and tacrolimus from day +5 in all pts., 12 (43%) pts. also received ATG (rabbit, thymoglobuline) at 5 mg/kg/course.
Results
Primary engraftment was achieved in 27(96,4%) of 28 pts., the median time to neutrophil and platelet recovery was 20 days (14-45) and 21 days (10-97). Twenty seven (96,4%) patients were in full donor chimerism on day +30. Early mortality was 14,9% (95% CI: 6-36), causes of death included viral infections (n=3); GvHD and viral infection (n=1). Cumulative incidence (CI) of acute GvHD grade ≥ II was 50% (95%CI:34-74), grade III–IV - 34% (95%CI:19-62) and chronic GvHD – 19% (95%CI:8-45). No correlation between the use of ATG and acute/chronic GvHD was noted. CI of relapse was 15,4% (95% CI: 6-38) and was significantly lower in CR vs AD group: 0% vs 36% (95% CI: 17-77), p=0,015. One year event-free survival (EFS) was 69,7% (95%CI: 52-87) and overall survival (OS) - 76% (95%CI: 59-93). One year pOS was significantly lower in the ATG group 58% (95%CI: 30-86) vs non-ATG group 93% (95%CI: 79-100), p=0,039. One year pEFS was 87% for patients in remission and 48% for patients with active disease (p=0,028). There was no significant difference in survival and relapse rate according to donor type.
Conclusion
Our study demonstrates the high rate of engraftment with acceptable transplant-related mortality in pediatric patients with hematological malignancies after unmanipulated HSCT with posttransplant cyclophosphamide. The data need to be confirmed in a larger trial with long-term follow-up.
Session topic: E-poster
Keyword(s): Acute leukemia, Cyclophosphamide, HSCT, Pediatric
Type: Eposter Presentation
Background
Standard GvHD prophylaxis regimens impair the graft-versus-tumor (GVT) effect, delay immune reconstitution and are associated with high rate of infections. High-dose post-transplantation cyclophosphamide (PTCy) targets alloreactive donor T cells proliferating early after BMT, promotes regulatory T cell and permits rapid immune reconstitution.
Aims
In this pilot trial we evaluate the safety and effects of PTCy in unmanipulated haploidentical and matched unrelated transplantation (MUD) in pediatric patients with hematologic malignancies.
Methods
Twenty eight pediatric patients with high risk hematologic malignancies underwent unmanipulated allogeneic bone marrow (BM) (n=26) or peripheral blood stem cell (PBSC)(n=2) transplantation followed by PTCy between April 2014 and September 2015 with a median follow-up of 9 months (1,5-19). Nineteen patients were transplanted from haploidentical donors and 9 from MUD. The median age was 10,4 years (range 1,9-18); 14 patients with ALL, 4 AML, 8 JMML and 2 with HD; 16 patients were in remission (CR) (14-ALL, 1-AML, 1-HD), 12 had active disease (AD) (8-JMML, 3-AML, 1-HD).In 11 pts this was a second allograft. Twenty-six pts received myeloablative Treosulfan/Melphalan/Fludarabine and 2 pts - reduced-intensity Fludarabine/TAO 2Gy/Thiotepa as conditioning regimen. GvHD prophylaxis consisted of PTCy on day +3, +4 and tacrolimus from day +5 in all pts., 12 (43%) pts. also received ATG (rabbit, thymoglobuline) at 5 mg/kg/course.
Results
Primary engraftment was achieved in 27(96,4%) of 28 pts., the median time to neutrophil and platelet recovery was 20 days (14-45) and 21 days (10-97). Twenty seven (96,4%) patients were in full donor chimerism on day +30. Early mortality was 14,9% (95% CI: 6-36), causes of death included viral infections (n=3); GvHD and viral infection (n=1). Cumulative incidence (CI) of acute GvHD grade ≥ II was 50% (95%CI:34-74), grade III–IV - 34% (95%CI:19-62) and chronic GvHD – 19% (95%CI:8-45). No correlation between the use of ATG and acute/chronic GvHD was noted. CI of relapse was 15,4% (95% CI: 6-38) and was significantly lower in CR vs AD group: 0% vs 36% (95% CI: 17-77), p=0,015. One year event-free survival (EFS) was 69,7% (95%CI: 52-87) and overall survival (OS) - 76% (95%CI: 59-93). One year pOS was significantly lower in the ATG group 58% (95%CI: 30-86) vs non-ATG group 93% (95%CI: 79-100), p=0,039. One year pEFS was 87% for patients in remission and 48% for patients with active disease (p=0,028). There was no significant difference in survival and relapse rate according to donor type.
Conclusion
Our study demonstrates the high rate of engraftment with acceptable transplant-related mortality in pediatric patients with hematological malignancies after unmanipulated HSCT with posttransplant cyclophosphamide. The data need to be confirmed in a larger trial with long-term follow-up.
Session topic: E-poster
Keyword(s): Acute leukemia, Cyclophosphamide, HSCT, Pediatric
{{ help_message }}
{{filter}}