SUCCESSFUL HEMATOPOIETIC STEM CELL TRANSPLANTATION IN TEN PATIENTS WITH SEVERE CONGENITAL NEUTROPENIA USING AN INTENSIVE IMMUNOMYELOSUPPRESSIVE CONDITIONING REGIMEN: THE RESULTS OF A SINGLE INSTITUTE
(Abstract release date: 05/19/16)
EHA Library. Mizoguchi Y. 06/12/16; 135326; S832
Dr. Yoko Mizoguchi
Contributions
Contributions
Abstract
Abstract: S832
Type: Oral Presentation
Presentation during EHA21: On Sunday, June 12, 2016 from 09:00 - 09:15
Location: Room H5
Background
Severe congenital neutropenia (SCN) is a rare heterogeneous genetic disorder categorized as a bone marrow failure syndrome. The main clinical feature of patients with SCN is recurrent bacterial infections from early infancy due to severe chronic neutropenia. Majority of SCN patients have benefitted by the treatment with granulocyte colony-stimulating factor (G-CSF). However, patients on long-term G-CSF therapy have a relative risk of developing myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML). The only curable treatment for SCN patients is hematopoietic stem cell transplantation (HSCT). Recently, HSCT with reduced intensity conditioning (RIC) regimens have been applied to the treatment for SCN patients prior to malignant transformation. However, the optimal conditions of HSCT for SCN patients have not been established.
Aims
In this study, we conducted bone marrow cell transplantations (BMT) in ten patients with SCN using an immunomyelosuppressive conditioning regimen to minimize early and late transplant-related morbidity in Hiroshima University Hospital.
Methods
A total of eleven HSCT procedures were performed in ten patients with SCN from 2009 to 2015. Four of ten patients had experienced the engraftment failure of initial HSCT and three of them were referred to our hospital for re-transplantation. Nine of ten patients (90%) had a heterozygous mutation in the ELANE gene. Bone marrow cells (BM) were obtained from five HLA-matched related (MRD), three HLA-matched unrelated (MUD), and three HLA-mismatched unrelated (7/8) donors (MMUD), respectively. Conditioning regimen consisted of fludarabine (125 mg/m2), cyclophosphamide (140 mg/m2), melpharan (90 mg/m2), and total body irradiation (3.6 Gy). Antithymocyte globulin (ATG, 10–12 mg/kg) was also administered, but two patients from MRD did not receive ATG, and one patient from MUD received low-dose ATG (i.e., 2.5 mg/kg instead of 10–12 mg/kg). Short-term methotrexate and tacrolimus were administered for the prophylaxis of graft-versus-host disease (GVHD).
Results
Engraftment of neutrophils was observed within post-transplant 24 days in all but 1 case who developed graft failure. This case, who had undergone initial HSCT with MUD-derived bone marrow using our conditioning regimen with low-dose ATG (2.5 mg/kg), was rescued by second HSCT with BM from another MUD receiving the same conditioning regimen with a 12 mg/kg of ATG. Two patients received HSCT from HLA-matched related donor developed stable mixed chimerism without neutropenia in peripheral blood. Although one patient who received donor lymphocyte infusion due to mixed chimerism developed acute GVHD grade Ⅱ and limited chronic GVHD, the others did not develop severe GVHD (acute GVHD gradeⅡ-III 9%, chronic GVHD 9% respectively). All patients are alive for 6 months to 8 years after HSCT with no signs of severe infections or transplantation-related morbidity.
Conclusion
Our results demonstrate that BMT together with a sufficient immunosuppressive conditioning regimen may be a feasible and effective treatment for SCN patients, irrespective of initial engraftment failure. The excellent results in our cohort suggest that indications for proceeding to HSCT could be extended to patients without malignant transformation. The further analyses of accumulated cases are necessary to assess the efficacy, safety, and less late adverse effects related to HSCT including fertility.
Session topic: Non-malignant hematopoietic disorders
Keyword(s): HSCT, Severe congenital neutropenia
Type: Oral Presentation
Presentation during EHA21: On Sunday, June 12, 2016 from 09:00 - 09:15
Location: Room H5
Background
Severe congenital neutropenia (SCN) is a rare heterogeneous genetic disorder categorized as a bone marrow failure syndrome. The main clinical feature of patients with SCN is recurrent bacterial infections from early infancy due to severe chronic neutropenia. Majority of SCN patients have benefitted by the treatment with granulocyte colony-stimulating factor (G-CSF). However, patients on long-term G-CSF therapy have a relative risk of developing myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML). The only curable treatment for SCN patients is hematopoietic stem cell transplantation (HSCT). Recently, HSCT with reduced intensity conditioning (RIC) regimens have been applied to the treatment for SCN patients prior to malignant transformation. However, the optimal conditions of HSCT for SCN patients have not been established.
Aims
In this study, we conducted bone marrow cell transplantations (BMT) in ten patients with SCN using an immunomyelosuppressive conditioning regimen to minimize early and late transplant-related morbidity in Hiroshima University Hospital.
Methods
A total of eleven HSCT procedures were performed in ten patients with SCN from 2009 to 2015. Four of ten patients had experienced the engraftment failure of initial HSCT and three of them were referred to our hospital for re-transplantation. Nine of ten patients (90%) had a heterozygous mutation in the ELANE gene. Bone marrow cells (BM) were obtained from five HLA-matched related (MRD), three HLA-matched unrelated (MUD), and three HLA-mismatched unrelated (7/8) donors (MMUD), respectively. Conditioning regimen consisted of fludarabine (125 mg/m2), cyclophosphamide (140 mg/m2), melpharan (90 mg/m2), and total body irradiation (3.6 Gy). Antithymocyte globulin (ATG, 10–12 mg/kg) was also administered, but two patients from MRD did not receive ATG, and one patient from MUD received low-dose ATG (i.e., 2.5 mg/kg instead of 10–12 mg/kg). Short-term methotrexate and tacrolimus were administered for the prophylaxis of graft-versus-host disease (GVHD).
Results
Engraftment of neutrophils was observed within post-transplant 24 days in all but 1 case who developed graft failure. This case, who had undergone initial HSCT with MUD-derived bone marrow using our conditioning regimen with low-dose ATG (2.5 mg/kg), was rescued by second HSCT with BM from another MUD receiving the same conditioning regimen with a 12 mg/kg of ATG. Two patients received HSCT from HLA-matched related donor developed stable mixed chimerism without neutropenia in peripheral blood. Although one patient who received donor lymphocyte infusion due to mixed chimerism developed acute GVHD grade Ⅱ and limited chronic GVHD, the others did not develop severe GVHD (acute GVHD gradeⅡ-III 9%, chronic GVHD 9% respectively). All patients are alive for 6 months to 8 years after HSCT with no signs of severe infections or transplantation-related morbidity.
Conclusion
Our results demonstrate that BMT together with a sufficient immunosuppressive conditioning regimen may be a feasible and effective treatment for SCN patients, irrespective of initial engraftment failure. The excellent results in our cohort suggest that indications for proceeding to HSCT could be extended to patients without malignant transformation. The further analyses of accumulated cases are necessary to assess the efficacy, safety, and less late adverse effects related to HSCT including fertility.
Session topic: Non-malignant hematopoietic disorders
Keyword(s): HSCT, Severe congenital neutropenia
Abstract: S832
Type: Oral Presentation
Presentation during EHA21: On Sunday, June 12, 2016 from 09:00 - 09:15
Location: Room H5
Background
Severe congenital neutropenia (SCN) is a rare heterogeneous genetic disorder categorized as a bone marrow failure syndrome. The main clinical feature of patients with SCN is recurrent bacterial infections from early infancy due to severe chronic neutropenia. Majority of SCN patients have benefitted by the treatment with granulocyte colony-stimulating factor (G-CSF). However, patients on long-term G-CSF therapy have a relative risk of developing myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML). The only curable treatment for SCN patients is hematopoietic stem cell transplantation (HSCT). Recently, HSCT with reduced intensity conditioning (RIC) regimens have been applied to the treatment for SCN patients prior to malignant transformation. However, the optimal conditions of HSCT for SCN patients have not been established.
Aims
In this study, we conducted bone marrow cell transplantations (BMT) in ten patients with SCN using an immunomyelosuppressive conditioning regimen to minimize early and late transplant-related morbidity in Hiroshima University Hospital.
Methods
A total of eleven HSCT procedures were performed in ten patients with SCN from 2009 to 2015. Four of ten patients had experienced the engraftment failure of initial HSCT and three of them were referred to our hospital for re-transplantation. Nine of ten patients (90%) had a heterozygous mutation in the ELANE gene. Bone marrow cells (BM) were obtained from five HLA-matched related (MRD), three HLA-matched unrelated (MUD), and three HLA-mismatched unrelated (7/8) donors (MMUD), respectively. Conditioning regimen consisted of fludarabine (125 mg/m2), cyclophosphamide (140 mg/m2), melpharan (90 mg/m2), and total body irradiation (3.6 Gy). Antithymocyte globulin (ATG, 10–12 mg/kg) was also administered, but two patients from MRD did not receive ATG, and one patient from MUD received low-dose ATG (i.e., 2.5 mg/kg instead of 10–12 mg/kg). Short-term methotrexate and tacrolimus were administered for the prophylaxis of graft-versus-host disease (GVHD).
Results
Engraftment of neutrophils was observed within post-transplant 24 days in all but 1 case who developed graft failure. This case, who had undergone initial HSCT with MUD-derived bone marrow using our conditioning regimen with low-dose ATG (2.5 mg/kg), was rescued by second HSCT with BM from another MUD receiving the same conditioning regimen with a 12 mg/kg of ATG. Two patients received HSCT from HLA-matched related donor developed stable mixed chimerism without neutropenia in peripheral blood. Although one patient who received donor lymphocyte infusion due to mixed chimerism developed acute GVHD grade Ⅱ and limited chronic GVHD, the others did not develop severe GVHD (acute GVHD gradeⅡ-III 9%, chronic GVHD 9% respectively). All patients are alive for 6 months to 8 years after HSCT with no signs of severe infections or transplantation-related morbidity.
Conclusion
Our results demonstrate that BMT together with a sufficient immunosuppressive conditioning regimen may be a feasible and effective treatment for SCN patients, irrespective of initial engraftment failure. The excellent results in our cohort suggest that indications for proceeding to HSCT could be extended to patients without malignant transformation. The further analyses of accumulated cases are necessary to assess the efficacy, safety, and less late adverse effects related to HSCT including fertility.
Session topic: Non-malignant hematopoietic disorders
Keyword(s): HSCT, Severe congenital neutropenia
Type: Oral Presentation
Presentation during EHA21: On Sunday, June 12, 2016 from 09:00 - 09:15
Location: Room H5
Background
Severe congenital neutropenia (SCN) is a rare heterogeneous genetic disorder categorized as a bone marrow failure syndrome. The main clinical feature of patients with SCN is recurrent bacterial infections from early infancy due to severe chronic neutropenia. Majority of SCN patients have benefitted by the treatment with granulocyte colony-stimulating factor (G-CSF). However, patients on long-term G-CSF therapy have a relative risk of developing myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML). The only curable treatment for SCN patients is hematopoietic stem cell transplantation (HSCT). Recently, HSCT with reduced intensity conditioning (RIC) regimens have been applied to the treatment for SCN patients prior to malignant transformation. However, the optimal conditions of HSCT for SCN patients have not been established.
Aims
In this study, we conducted bone marrow cell transplantations (BMT) in ten patients with SCN using an immunomyelosuppressive conditioning regimen to minimize early and late transplant-related morbidity in Hiroshima University Hospital.
Methods
A total of eleven HSCT procedures were performed in ten patients with SCN from 2009 to 2015. Four of ten patients had experienced the engraftment failure of initial HSCT and three of them were referred to our hospital for re-transplantation. Nine of ten patients (90%) had a heterozygous mutation in the ELANE gene. Bone marrow cells (BM) were obtained from five HLA-matched related (MRD), three HLA-matched unrelated (MUD), and three HLA-mismatched unrelated (7/8) donors (MMUD), respectively. Conditioning regimen consisted of fludarabine (125 mg/m2), cyclophosphamide (140 mg/m2), melpharan (90 mg/m2), and total body irradiation (3.6 Gy). Antithymocyte globulin (ATG, 10–12 mg/kg) was also administered, but two patients from MRD did not receive ATG, and one patient from MUD received low-dose ATG (i.e., 2.5 mg/kg instead of 10–12 mg/kg). Short-term methotrexate and tacrolimus were administered for the prophylaxis of graft-versus-host disease (GVHD).
Results
Engraftment of neutrophils was observed within post-transplant 24 days in all but 1 case who developed graft failure. This case, who had undergone initial HSCT with MUD-derived bone marrow using our conditioning regimen with low-dose ATG (2.5 mg/kg), was rescued by second HSCT with BM from another MUD receiving the same conditioning regimen with a 12 mg/kg of ATG. Two patients received HSCT from HLA-matched related donor developed stable mixed chimerism without neutropenia in peripheral blood. Although one patient who received donor lymphocyte infusion due to mixed chimerism developed acute GVHD grade Ⅱ and limited chronic GVHD, the others did not develop severe GVHD (acute GVHD gradeⅡ-III 9%, chronic GVHD 9% respectively). All patients are alive for 6 months to 8 years after HSCT with no signs of severe infections or transplantation-related morbidity.
Conclusion
Our results demonstrate that BMT together with a sufficient immunosuppressive conditioning regimen may be a feasible and effective treatment for SCN patients, irrespective of initial engraftment failure. The excellent results in our cohort suggest that indications for proceeding to HSCT could be extended to patients without malignant transformation. The further analyses of accumulated cases are necessary to assess the efficacy, safety, and less late adverse effects related to HSCT including fertility.
Session topic: Non-malignant hematopoietic disorders
Keyword(s): HSCT, Severe congenital neutropenia
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