TCRΑΒ+/CD19+-DEPLETION IN HEMATOPOIETIC STEM CELLS TRANSPLANTATION FROM MATCHED UNRELATED AND HAPLOIDENTICAL DONORS IN PEDIATRIC ACUTE MYELOBLASTIC LEUKEMIA PATIENTS.
(Abstract release date: 05/19/16)
EHA Library. Shasheleva D. 06/09/16; 133070; E1521
Daria Shasheleva
Contributions
Contributions
Abstract
Abstract: E1521
Type: Eposter Presentation
Background
Graft-versus-host disease (GvHD) and GvHD-associated morbidity and mortality are major obstacles to the success of transplantation from unrelated and haploidentical donors. Negative depletion of α/β(+) T cells and CD19+ B lymphocytes is a technology of graft manipulation with a potential to improve GvHD control and immune reconstitution.
Aims
The aim was to study retrospectively the outcomes of TCR-alpha/beta depleted transplants in a group of pediatric acute myeloid leukemia patients with the emphasis on two consequtive GVHD prophylaxis regimens.
Methods
A total of 59 pediatric patients with acute myeloblastic leukemia (17 female, 42 male, median age 9,1 years, range 0,6-22) underwent allogeneic HSCT between May 2012 and June 2015. Twenty two patients received haploidentical graft, 37 - a graft from matched unrelated donor. Disease status at transplant was CR1 in 40 pts., CR≥2 in 10 pts., active disease(AD) in 9 pts. Transplantation in CR1 was performed according to risk stratification scheme in the current institutional AML protocol. For all patients it was first HSCT. TCRαβ+/CD19+ depletion of HSCT with CliniMACS technology was implemented in all cases.All patients received Treosulfan/Melphalan/Fludarabine as conditioning regimen. Two regimens of GvHD prophylaxis were used: regimen 1 (n=31): ATG (horse, ATGAM) 50 mg/kg and post-transplant Tacro/MTX (n=28), or no post-transplant prophylaxis (n=3); regimen 2 (n=28): ATG (rabbit, thymoglobuline) 5 mg/kg, rituximab 200mg/m2 and post-transplant bortezomib (n= 27) or Tacro/MTX (n=1). The median dose of CD34+ cells in transplant was 7,9 x106/kg (range 1-21), TCRα/β - 15x103/kg (range 0,6-210).
Results
Primary engraftment of WBC and platelets was achieved in 58 (98,3%) patients at a median of 14 days, 1 pt. with AD had primary graft failure with no evidence of leukemia and was retransplanted from MUD. No case of graft rejection was registered.Early mortality was low with a +100-day pTRM - 3,4% (95% CI: 0,1-13.2), 3-year pTRM – 10,8% (95%CI: 5-23). The 2 early deaths included viral infections (ADV), four late: bacterial sepsis in 1 pt. and viral infection(ADV and CMV) in 3 pts, all with extensive chronic GvHD.Cumulative incidence (CI) of acute GvHD grade ≥ II was 20,3% (95% CI: 12-34), grade III–IV 8,5 % (95%CI: 4-20) and chronic GvHD – 28% (95% CI: 18-45). No correlation between graft composition and aGvHD was noted. CI of acute GvHD was significantly lower in a group with regimen 2: 7,4% (95% CI: 2-28) vs 31,3% (95% CI: 19-52) in group with regimen 1, p=0,028. Regimen 2 was also effective in prevention of chronic GvHD: CI at 1 year after HSCT was 14% vs 36%, p=0,085Median time of follow-up for survivors is 1,9 years (range 7 months – 3,5 years). CI of relapse at 3 year is 27,6% (95%CI: 18-43). Three year pEFS is 62% (95%CI: 49-75), 3-year pOS - 64% (95%CI: 50-78). There was no significant difference in survival and relapse rate according leukemia subtype, remission status and donor type.
Conclusion
We confirm that the depletion of TCR-alpha/beta and CD19 lymphocytes from the graft ensures high engraftment rate and acceptable transplant-related mortality in pediatric AML patients. All major outcomes were equivalent between transplantation from unrelated and haploidentical donor. GvHD prophylaxis including Thymoglobulin/Rituximab/Bortezomib improves GvHD control in recipients of TCRα/β- depleted grafts in comparison to ATGAM/Tacro/MTX apparently without loss of anti-leukemic activity.
Session topic: E-poster
Keyword(s): Acute myeloid leukemia, Haploidentical stem cell transplantation, Pediatric, Processing
Type: Eposter Presentation
Background
Graft-versus-host disease (GvHD) and GvHD-associated morbidity and mortality are major obstacles to the success of transplantation from unrelated and haploidentical donors. Negative depletion of α/β(+) T cells and CD19+ B lymphocytes is a technology of graft manipulation with a potential to improve GvHD control and immune reconstitution.
Aims
The aim was to study retrospectively the outcomes of TCR-alpha/beta depleted transplants in a group of pediatric acute myeloid leukemia patients with the emphasis on two consequtive GVHD prophylaxis regimens.
Methods
A total of 59 pediatric patients with acute myeloblastic leukemia (17 female, 42 male, median age 9,1 years, range 0,6-22) underwent allogeneic HSCT between May 2012 and June 2015. Twenty two patients received haploidentical graft, 37 - a graft from matched unrelated donor. Disease status at transplant was CR1 in 40 pts., CR≥2 in 10 pts., active disease(AD) in 9 pts. Transplantation in CR1 was performed according to risk stratification scheme in the current institutional AML protocol. For all patients it was first HSCT. TCRαβ+/CD19+ depletion of HSCT with CliniMACS technology was implemented in all cases.All patients received Treosulfan/Melphalan/Fludarabine as conditioning regimen. Two regimens of GvHD prophylaxis were used: regimen 1 (n=31): ATG (horse, ATGAM) 50 mg/kg and post-transplant Tacro/MTX (n=28), or no post-transplant prophylaxis (n=3); regimen 2 (n=28): ATG (rabbit, thymoglobuline) 5 mg/kg, rituximab 200mg/m2 and post-transplant bortezomib (n= 27) or Tacro/MTX (n=1). The median dose of CD34+ cells in transplant was 7,9 x106/kg (range 1-21), TCRα/β - 15x103/kg (range 0,6-210).
Results
Primary engraftment of WBC and platelets was achieved in 58 (98,3%) patients at a median of 14 days, 1 pt. with AD had primary graft failure with no evidence of leukemia and was retransplanted from MUD. No case of graft rejection was registered.Early mortality was low with a +100-day pTRM - 3,4% (95% CI: 0,1-13.2), 3-year pTRM – 10,8% (95%CI: 5-23). The 2 early deaths included viral infections (ADV), four late: bacterial sepsis in 1 pt. and viral infection(ADV and CMV) in 3 pts, all with extensive chronic GvHD.Cumulative incidence (CI) of acute GvHD grade ≥ II was 20,3% (95% CI: 12-34), grade III–IV 8,5 % (95%CI: 4-20) and chronic GvHD – 28% (95% CI: 18-45). No correlation between graft composition and aGvHD was noted. CI of acute GvHD was significantly lower in a group with regimen 2: 7,4% (95% CI: 2-28) vs 31,3% (95% CI: 19-52) in group with regimen 1, p=0,028. Regimen 2 was also effective in prevention of chronic GvHD: CI at 1 year after HSCT was 14% vs 36%, p=0,085Median time of follow-up for survivors is 1,9 years (range 7 months – 3,5 years). CI of relapse at 3 year is 27,6% (95%CI: 18-43). Three year pEFS is 62% (95%CI: 49-75), 3-year pOS - 64% (95%CI: 50-78). There was no significant difference in survival and relapse rate according leukemia subtype, remission status and donor type.
Conclusion
We confirm that the depletion of TCR-alpha/beta and CD19 lymphocytes from the graft ensures high engraftment rate and acceptable transplant-related mortality in pediatric AML patients. All major outcomes were equivalent between transplantation from unrelated and haploidentical donor. GvHD prophylaxis including Thymoglobulin/Rituximab/Bortezomib improves GvHD control in recipients of TCRα/β- depleted grafts in comparison to ATGAM/Tacro/MTX apparently without loss of anti-leukemic activity.
Session topic: E-poster
Keyword(s): Acute myeloid leukemia, Haploidentical stem cell transplantation, Pediatric, Processing
Abstract: E1521
Type: Eposter Presentation
Background
Graft-versus-host disease (GvHD) and GvHD-associated morbidity and mortality are major obstacles to the success of transplantation from unrelated and haploidentical donors. Negative depletion of α/β(+) T cells and CD19+ B lymphocytes is a technology of graft manipulation with a potential to improve GvHD control and immune reconstitution.
Aims
The aim was to study retrospectively the outcomes of TCR-alpha/beta depleted transplants in a group of pediatric acute myeloid leukemia patients with the emphasis on two consequtive GVHD prophylaxis regimens.
Methods
A total of 59 pediatric patients with acute myeloblastic leukemia (17 female, 42 male, median age 9,1 years, range 0,6-22) underwent allogeneic HSCT between May 2012 and June 2015. Twenty two patients received haploidentical graft, 37 - a graft from matched unrelated donor. Disease status at transplant was CR1 in 40 pts., CR≥2 in 10 pts., active disease(AD) in 9 pts. Transplantation in CR1 was performed according to risk stratification scheme in the current institutional AML protocol. For all patients it was first HSCT. TCRαβ+/CD19+ depletion of HSCT with CliniMACS technology was implemented in all cases.All patients received Treosulfan/Melphalan/Fludarabine as conditioning regimen. Two regimens of GvHD prophylaxis were used: regimen 1 (n=31): ATG (horse, ATGAM) 50 mg/kg and post-transplant Tacro/MTX (n=28), or no post-transplant prophylaxis (n=3); regimen 2 (n=28): ATG (rabbit, thymoglobuline) 5 mg/kg, rituximab 200mg/m2 and post-transplant bortezomib (n= 27) or Tacro/MTX (n=1). The median dose of CD34+ cells in transplant was 7,9 x106/kg (range 1-21), TCRα/β - 15x103/kg (range 0,6-210).
Results
Primary engraftment of WBC and platelets was achieved in 58 (98,3%) patients at a median of 14 days, 1 pt. with AD had primary graft failure with no evidence of leukemia and was retransplanted from MUD. No case of graft rejection was registered.Early mortality was low with a +100-day pTRM - 3,4% (95% CI: 0,1-13.2), 3-year pTRM – 10,8% (95%CI: 5-23). The 2 early deaths included viral infections (ADV), four late: bacterial sepsis in 1 pt. and viral infection(ADV and CMV) in 3 pts, all with extensive chronic GvHD.Cumulative incidence (CI) of acute GvHD grade ≥ II was 20,3% (95% CI: 12-34), grade III–IV 8,5 % (95%CI: 4-20) and chronic GvHD – 28% (95% CI: 18-45). No correlation between graft composition and aGvHD was noted. CI of acute GvHD was significantly lower in a group with regimen 2: 7,4% (95% CI: 2-28) vs 31,3% (95% CI: 19-52) in group with regimen 1, p=0,028. Regimen 2 was also effective in prevention of chronic GvHD: CI at 1 year after HSCT was 14% vs 36%, p=0,085Median time of follow-up for survivors is 1,9 years (range 7 months – 3,5 years). CI of relapse at 3 year is 27,6% (95%CI: 18-43). Three year pEFS is 62% (95%CI: 49-75), 3-year pOS - 64% (95%CI: 50-78). There was no significant difference in survival and relapse rate according leukemia subtype, remission status and donor type.
Conclusion
We confirm that the depletion of TCR-alpha/beta and CD19 lymphocytes from the graft ensures high engraftment rate and acceptable transplant-related mortality in pediatric AML patients. All major outcomes were equivalent between transplantation from unrelated and haploidentical donor. GvHD prophylaxis including Thymoglobulin/Rituximab/Bortezomib improves GvHD control in recipients of TCRα/β- depleted grafts in comparison to ATGAM/Tacro/MTX apparently without loss of anti-leukemic activity.
Session topic: E-poster
Keyword(s): Acute myeloid leukemia, Haploidentical stem cell transplantation, Pediatric, Processing
Type: Eposter Presentation
Background
Graft-versus-host disease (GvHD) and GvHD-associated morbidity and mortality are major obstacles to the success of transplantation from unrelated and haploidentical donors. Negative depletion of α/β(+) T cells and CD19+ B lymphocytes is a technology of graft manipulation with a potential to improve GvHD control and immune reconstitution.
Aims
The aim was to study retrospectively the outcomes of TCR-alpha/beta depleted transplants in a group of pediatric acute myeloid leukemia patients with the emphasis on two consequtive GVHD prophylaxis regimens.
Methods
A total of 59 pediatric patients with acute myeloblastic leukemia (17 female, 42 male, median age 9,1 years, range 0,6-22) underwent allogeneic HSCT between May 2012 and June 2015. Twenty two patients received haploidentical graft, 37 - a graft from matched unrelated donor. Disease status at transplant was CR1 in 40 pts., CR≥2 in 10 pts., active disease(AD) in 9 pts. Transplantation in CR1 was performed according to risk stratification scheme in the current institutional AML protocol. For all patients it was first HSCT. TCRαβ+/CD19+ depletion of HSCT with CliniMACS technology was implemented in all cases.All patients received Treosulfan/Melphalan/Fludarabine as conditioning regimen. Two regimens of GvHD prophylaxis were used: regimen 1 (n=31): ATG (horse, ATGAM) 50 mg/kg and post-transplant Tacro/MTX (n=28), or no post-transplant prophylaxis (n=3); regimen 2 (n=28): ATG (rabbit, thymoglobuline) 5 mg/kg, rituximab 200mg/m2 and post-transplant bortezomib (n= 27) or Tacro/MTX (n=1). The median dose of CD34+ cells in transplant was 7,9 x106/kg (range 1-21), TCRα/β - 15x103/kg (range 0,6-210).
Results
Primary engraftment of WBC and platelets was achieved in 58 (98,3%) patients at a median of 14 days, 1 pt. with AD had primary graft failure with no evidence of leukemia and was retransplanted from MUD. No case of graft rejection was registered.Early mortality was low with a +100-day pTRM - 3,4% (95% CI: 0,1-13.2), 3-year pTRM – 10,8% (95%CI: 5-23). The 2 early deaths included viral infections (ADV), four late: bacterial sepsis in 1 pt. and viral infection(ADV and CMV) in 3 pts, all with extensive chronic GvHD.Cumulative incidence (CI) of acute GvHD grade ≥ II was 20,3% (95% CI: 12-34), grade III–IV 8,5 % (95%CI: 4-20) and chronic GvHD – 28% (95% CI: 18-45). No correlation between graft composition and aGvHD was noted. CI of acute GvHD was significantly lower in a group with regimen 2: 7,4% (95% CI: 2-28) vs 31,3% (95% CI: 19-52) in group with regimen 1, p=0,028. Regimen 2 was also effective in prevention of chronic GvHD: CI at 1 year after HSCT was 14% vs 36%, p=0,085Median time of follow-up for survivors is 1,9 years (range 7 months – 3,5 years). CI of relapse at 3 year is 27,6% (95%CI: 18-43). Three year pEFS is 62% (95%CI: 49-75), 3-year pOS - 64% (95%CI: 50-78). There was no significant difference in survival and relapse rate according leukemia subtype, remission status and donor type.
Conclusion
We confirm that the depletion of TCR-alpha/beta and CD19 lymphocytes from the graft ensures high engraftment rate and acceptable transplant-related mortality in pediatric AML patients. All major outcomes were equivalent between transplantation from unrelated and haploidentical donor. GvHD prophylaxis including Thymoglobulin/Rituximab/Bortezomib improves GvHD control in recipients of TCRα/β- depleted grafts in comparison to ATGAM/Tacro/MTX apparently without loss of anti-leukemic activity.
Session topic: E-poster
Keyword(s): Acute myeloid leukemia, Haploidentical stem cell transplantation, Pediatric, Processing
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