PROPHYLAXIS OF GRAFT VERSUS HOST DISEASE IN PATIENTS WITH APLASTIC ANEMIA AFTER ALLOGENEIC BONE MARROW TRANSPLANTATION WITH BONE MARROW DONOR DERIVED MULTIPOTENT MESENCHYMAL STROMAL CELLS
(Abstract release date: 05/19/16)
EHA Library. Koroleva O. 06/09/16; 135083; PB2183
Dr. Olga Koroleva
Contributions
Contributions
Abstract
Abstract: PB2183
Type: Publication Only
Background
Aplastic anemia (AA) is a rare disease characterized by bone marrow failure and pancytopenia. Allogeneic bone marrow transplantation (allo-BMT) is a standard treatment for young patients with a HLA-identical sibling donor. Incidence of acute and chronic graft versus host disease (GVHD) is 13% and 14%, respectively. If paroxysmal nocturnal hemoglobinuria clone (PNH) is detected in AA patients the incidence of acute and chronic GVHD increases up to 47% and 70%, respectively. It is known that multipotent mesenchymal stromal cells (MMSC) injection for GVHD prophylaxis after HLA- identical sibling donor transplants significantly decreases incidence of GVHD (ClinicalTrials.gov ID – NCT 01941394).
Aims
Estimate the effectiveness of MMSC injection for GVHD prophylaxis in patients with AA after allo-BMT.
Methods
Nine patients (6 males and 3 females) with AA received allo-BMT from HLA-identical sibling donor in our center between December 2011 and December 2015. Median patients age at the time of transplantation was 24 years (range 17-33). PNH clone was detected in 8 patients (the median granulocytes PNH clone size was 2,5% /range 0,19-97,1%/). PHN clone with intravascular hemolysis (LDH more then 1,5 ULN) was revealed in 2 patients. There were no thrombotic events in all patients. Eight patients received allo-BMT as first line therapy, for one patient allo-BMT was performed for relapse after immunosuppression therapy. The non-myeloablative conditioning regimen was used (ATG (100 mg/kg) for 4 days, fludarabine (100 mg/m2) for 4 days, and cyclophosphamide (100 mg/kg) for 4 days). For graft versus host disease (GVHD) prophylaxis cyclosporine and methotrexate were used. MMSC were infused intravenously at the moment of WBC count recovery to 1*109/l. On average, 1.09 (1.0-1.2) x 106 MMSC per kilogram of the patient’s body weight were injected.
Results
One patient had graft failure at day + 30 after allo-BMT. Other patients had stable engraftment. Leucocytes recovery occurred at median 21 days (range 17-25). Patients had no complications after MMSC injection. Only in 1 out of 8 patients (12,5%) acute GVHD was diagnosed, despite the presence of PNH clone in 7 out of 8 patients. Acute GVHD with liver involvement (grade III) was developed at 27 days in the patient with chronic hepatitis B virus infection. PNH clone elimination in 6 patients occurred during 1-18 mounts after allo-BMT. All 8 patients had undulating mixed donor chimerism (85-100%) at different time after allo-BMT. One patient with mixed donor chimerism has graft rejection at day + 286. No chronic GVHD in any patients developed. All patients are alive with a median follow-up 16 months (range 1-49).
Conclusion
We can suggest that in patients with AA bone marrow donor MMSC administration at the moment of leukocytes count recovery after allo-BMT is an effective method for acute GVHD prevention.
Session topic: E-poster
Keyword(s): Allogeneic bone marrow transplant, Aplastic anemia, Graft-versus-host disease (GVHD), Mesenchymal cells
Type: Publication Only
Background
Aplastic anemia (AA) is a rare disease characterized by bone marrow failure and pancytopenia. Allogeneic bone marrow transplantation (allo-BMT) is a standard treatment for young patients with a HLA-identical sibling donor. Incidence of acute and chronic graft versus host disease (GVHD) is 13% and 14%, respectively. If paroxysmal nocturnal hemoglobinuria clone (PNH) is detected in AA patients the incidence of acute and chronic GVHD increases up to 47% and 70%, respectively. It is known that multipotent mesenchymal stromal cells (MMSC) injection for GVHD prophylaxis after HLA- identical sibling donor transplants significantly decreases incidence of GVHD (ClinicalTrials.gov ID – NCT 01941394).
Aims
Estimate the effectiveness of MMSC injection for GVHD prophylaxis in patients with AA after allo-BMT.
Methods
Nine patients (6 males and 3 females) with AA received allo-BMT from HLA-identical sibling donor in our center between December 2011 and December 2015. Median patients age at the time of transplantation was 24 years (range 17-33). PNH clone was detected in 8 patients (the median granulocytes PNH clone size was 2,5% /range 0,19-97,1%/). PHN clone with intravascular hemolysis (LDH more then 1,5 ULN) was revealed in 2 patients. There were no thrombotic events in all patients. Eight patients received allo-BMT as first line therapy, for one patient allo-BMT was performed for relapse after immunosuppression therapy. The non-myeloablative conditioning regimen was used (ATG (100 mg/kg) for 4 days, fludarabine (100 mg/m2) for 4 days, and cyclophosphamide (100 mg/kg) for 4 days). For graft versus host disease (GVHD) prophylaxis cyclosporine and methotrexate were used. MMSC were infused intravenously at the moment of WBC count recovery to 1*109/l. On average, 1.09 (1.0-1.2) x 106 MMSC per kilogram of the patient’s body weight were injected.
Results
One patient had graft failure at day + 30 after allo-BMT. Other patients had stable engraftment. Leucocytes recovery occurred at median 21 days (range 17-25). Patients had no complications after MMSC injection. Only in 1 out of 8 patients (12,5%) acute GVHD was diagnosed, despite the presence of PNH clone in 7 out of 8 patients. Acute GVHD with liver involvement (grade III) was developed at 27 days in the patient with chronic hepatitis B virus infection. PNH clone elimination in 6 patients occurred during 1-18 mounts after allo-BMT. All 8 patients had undulating mixed donor chimerism (85-100%) at different time after allo-BMT. One patient with mixed donor chimerism has graft rejection at day + 286. No chronic GVHD in any patients developed. All patients are alive with a median follow-up 16 months (range 1-49).
Conclusion
We can suggest that in patients with AA bone marrow donor MMSC administration at the moment of leukocytes count recovery after allo-BMT is an effective method for acute GVHD prevention.
Session topic: E-poster
Keyword(s): Allogeneic bone marrow transplant, Aplastic anemia, Graft-versus-host disease (GVHD), Mesenchymal cells
Abstract: PB2183
Type: Publication Only
Background
Aplastic anemia (AA) is a rare disease characterized by bone marrow failure and pancytopenia. Allogeneic bone marrow transplantation (allo-BMT) is a standard treatment for young patients with a HLA-identical sibling donor. Incidence of acute and chronic graft versus host disease (GVHD) is 13% and 14%, respectively. If paroxysmal nocturnal hemoglobinuria clone (PNH) is detected in AA patients the incidence of acute and chronic GVHD increases up to 47% and 70%, respectively. It is known that multipotent mesenchymal stromal cells (MMSC) injection for GVHD prophylaxis after HLA- identical sibling donor transplants significantly decreases incidence of GVHD (ClinicalTrials.gov ID – NCT 01941394).
Aims
Estimate the effectiveness of MMSC injection for GVHD prophylaxis in patients with AA after allo-BMT.
Methods
Nine patients (6 males and 3 females) with AA received allo-BMT from HLA-identical sibling donor in our center between December 2011 and December 2015. Median patients age at the time of transplantation was 24 years (range 17-33). PNH clone was detected in 8 patients (the median granulocytes PNH clone size was 2,5% /range 0,19-97,1%/). PHN clone with intravascular hemolysis (LDH more then 1,5 ULN) was revealed in 2 patients. There were no thrombotic events in all patients. Eight patients received allo-BMT as first line therapy, for one patient allo-BMT was performed for relapse after immunosuppression therapy. The non-myeloablative conditioning regimen was used (ATG (100 mg/kg) for 4 days, fludarabine (100 mg/m2) for 4 days, and cyclophosphamide (100 mg/kg) for 4 days). For graft versus host disease (GVHD) prophylaxis cyclosporine and methotrexate were used. MMSC were infused intravenously at the moment of WBC count recovery to 1*109/l. On average, 1.09 (1.0-1.2) x 106 MMSC per kilogram of the patient’s body weight were injected.
Results
One patient had graft failure at day + 30 after allo-BMT. Other patients had stable engraftment. Leucocytes recovery occurred at median 21 days (range 17-25). Patients had no complications after MMSC injection. Only in 1 out of 8 patients (12,5%) acute GVHD was diagnosed, despite the presence of PNH clone in 7 out of 8 patients. Acute GVHD with liver involvement (grade III) was developed at 27 days in the patient with chronic hepatitis B virus infection. PNH clone elimination in 6 patients occurred during 1-18 mounts after allo-BMT. All 8 patients had undulating mixed donor chimerism (85-100%) at different time after allo-BMT. One patient with mixed donor chimerism has graft rejection at day + 286. No chronic GVHD in any patients developed. All patients are alive with a median follow-up 16 months (range 1-49).
Conclusion
We can suggest that in patients with AA bone marrow donor MMSC administration at the moment of leukocytes count recovery after allo-BMT is an effective method for acute GVHD prevention.
Session topic: E-poster
Keyword(s): Allogeneic bone marrow transplant, Aplastic anemia, Graft-versus-host disease (GVHD), Mesenchymal cells
Type: Publication Only
Background
Aplastic anemia (AA) is a rare disease characterized by bone marrow failure and pancytopenia. Allogeneic bone marrow transplantation (allo-BMT) is a standard treatment for young patients with a HLA-identical sibling donor. Incidence of acute and chronic graft versus host disease (GVHD) is 13% and 14%, respectively. If paroxysmal nocturnal hemoglobinuria clone (PNH) is detected in AA patients the incidence of acute and chronic GVHD increases up to 47% and 70%, respectively. It is known that multipotent mesenchymal stromal cells (MMSC) injection for GVHD prophylaxis after HLA- identical sibling donor transplants significantly decreases incidence of GVHD (ClinicalTrials.gov ID – NCT 01941394).
Aims
Estimate the effectiveness of MMSC injection for GVHD prophylaxis in patients with AA after allo-BMT.
Methods
Nine patients (6 males and 3 females) with AA received allo-BMT from HLA-identical sibling donor in our center between December 2011 and December 2015. Median patients age at the time of transplantation was 24 years (range 17-33). PNH clone was detected in 8 patients (the median granulocytes PNH clone size was 2,5% /range 0,19-97,1%/). PHN clone with intravascular hemolysis (LDH more then 1,5 ULN) was revealed in 2 patients. There were no thrombotic events in all patients. Eight patients received allo-BMT as first line therapy, for one patient allo-BMT was performed for relapse after immunosuppression therapy. The non-myeloablative conditioning regimen was used (ATG (100 mg/kg) for 4 days, fludarabine (100 mg/m2) for 4 days, and cyclophosphamide (100 mg/kg) for 4 days). For graft versus host disease (GVHD) prophylaxis cyclosporine and methotrexate were used. MMSC were infused intravenously at the moment of WBC count recovery to 1*109/l. On average, 1.09 (1.0-1.2) x 106 MMSC per kilogram of the patient’s body weight were injected.
Results
One patient had graft failure at day + 30 after allo-BMT. Other patients had stable engraftment. Leucocytes recovery occurred at median 21 days (range 17-25). Patients had no complications after MMSC injection. Only in 1 out of 8 patients (12,5%) acute GVHD was diagnosed, despite the presence of PNH clone in 7 out of 8 patients. Acute GVHD with liver involvement (grade III) was developed at 27 days in the patient with chronic hepatitis B virus infection. PNH clone elimination in 6 patients occurred during 1-18 mounts after allo-BMT. All 8 patients had undulating mixed donor chimerism (85-100%) at different time after allo-BMT. One patient with mixed donor chimerism has graft rejection at day + 286. No chronic GVHD in any patients developed. All patients are alive with a median follow-up 16 months (range 1-49).
Conclusion
We can suggest that in patients with AA bone marrow donor MMSC administration at the moment of leukocytes count recovery after allo-BMT is an effective method for acute GVHD prevention.
Session topic: E-poster
Keyword(s): Allogeneic bone marrow transplant, Aplastic anemia, Graft-versus-host disease (GVHD), Mesenchymal cells
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