TRANSPLANT-ASSOCIATED THROMBOTIC MICROANGIOPATHY IS STRONGLY ASSOCIATED WITH SEVERE GRAFT VS HOST DISEASE POST UNRELATED ALLOGENEIC TRANSPLANT FOR HEMATOLOGIC DISEASES
(Abstract release date: 05/19/16)
EHA Library. Sakellari I. 06/09/16; 135060; PB2160
Dr. Ioanna Sakellari
Contributions
Contributions
Abstract
Abstract: PB2160
Type: Publication Only
Background
Allogeneic hematopoietic cell transplantation (HCT) is a curative treatment in hematologic disorders, but morbidity and mortality remain high. Transplant-associated thrombotic microangiopathy (taTMA) is a multifactorial and often fatal syndrome.
Aims
In a retrospective single-centre study we aimed to investigate the incidence of taTMA in patients (pts) undergone HCT from unrelated donors (URD) and identify prognostic factors and treatment outcome.
Methods
We enrolled consecutive pts who underwent URD HCT from 2003 to 2015. TaTMA diagnosis was based on EBMT criteria: increased (>4%) schistocytes in peripheral blood, thrombocytopenia, increased lactate dehydrogenase and decrease in Hb concentration. Anti-thymocyte globulin (ATG, rabbit) was used as standardised part of the conditioning in almost all pts (total dose of 5-7.5mg/kg). Anti-GVHD prophylaxis consisted of cyclosporine or tacrolimus plus methotrexate in myeloablative and mycophenolate mofetil plus cyclosporine in reduced intensity and toxicity conditioning transplants. Upon identification of taTMA, all possible causative factors were fully investigated. The mainstay of treatment strategy was withdrawal of calcineurin inhibitors, plasma infusion and plasma exchange combined with corticosteroid administration and in refractory cases, humanized anti-CD20 monoclonal antibody (Rituximab).
Results
We studied 179 pts (74 male, 105 female), aged 37±14 years, who underwent HCT from matched HLA A/B/C/DRB1 (8/8, n=88) and allele or antigen mismatched (n=91) URD. Grafts derived from peripheral blood (157), bone marrow (18) and umbilical stem cells (4). Conditioning regimens were myeloablative (139), reduced intensity (28) and toxicity (12). Median follow-up was 11.5 (0.1–147.4) months.TaTMA was diagnosed in 29 (16.2%) pts (12 male, 17 female), aged 34±12 years, 78 (9–721) days post-HCT for acute leukemia (21), Hodgkin (3) and non-Hodgkin (1) lymphoma, MDS (2), MPD (1) and aplastic anemia (1). Conditioning regimens were myeloablative in 24 (12 TBI-based) and reduced intensity in 5 pts. Among pts with taTMA, 10 (34%) presented severe (grade III-IV) acute GVHD, 15 (52%) extensive chronic GVHD, 12 (41%) bacterial, 2 (7%) fungal and 21 (71%) viral infectious episodes. In univariate analysis age, gender, diagnosis, disease phase, previous lines of treatment, conditioning (intensity and TBI-based), ABO and HLA incompatibility, infections, acute and chronic GVHD were studied. The presence of taTMA was associated with severe acute and extensive chronic GVHD (p=0.001 and p=0.035 respectively) and TBI-based conditioning (p=0.043). In multivariate analysis, severe acute GVHD was the only independent factor associated with taTMA (β=3.4, p=0.038). Regarding treatment-outcome, 8 pts responded to cyclosporine cessation and plasma infusions. The rest (21) underwent plasma-exchange sessions; in 14 the syndrome resolved, 1 responded to additional Rituximab treatment, while 6/21 pts were refractory and eventually succumbed. Treatment-related mortality was 33.3% (9/29) in taTMA pts and was directly associated with refractory microangiopathic syndrome in 6/29 (20.6%).
Conclusion
Despite the progress achieved concerning classic thrombotic thrombocytopenic purpura and haemolytic uraemic syndrome in terms of diagnosis and novel therapies, taTMA seems to be a far more complex syndrome. Since the pathogenetic factors leading to taTMA are not fully elucidated, treatment of this syndrome often fails. According to our findings, GVHD was the most predisposing factor for the development of taTMA, possibly related to associated endothelial damage.
Session topic: E-poster
Keyword(s): Graft-versus-host disease (GVHD), Thrombotic thrombocytopenic purpura (TTP), Transplant-related mortality, Unrelated donor stem cell transplant
Type: Publication Only
Background
Allogeneic hematopoietic cell transplantation (HCT) is a curative treatment in hematologic disorders, but morbidity and mortality remain high. Transplant-associated thrombotic microangiopathy (taTMA) is a multifactorial and often fatal syndrome.
Aims
In a retrospective single-centre study we aimed to investigate the incidence of taTMA in patients (pts) undergone HCT from unrelated donors (URD) and identify prognostic factors and treatment outcome.
Methods
We enrolled consecutive pts who underwent URD HCT from 2003 to 2015. TaTMA diagnosis was based on EBMT criteria: increased (>4%) schistocytes in peripheral blood, thrombocytopenia, increased lactate dehydrogenase and decrease in Hb concentration. Anti-thymocyte globulin (ATG, rabbit) was used as standardised part of the conditioning in almost all pts (total dose of 5-7.5mg/kg). Anti-GVHD prophylaxis consisted of cyclosporine or tacrolimus plus methotrexate in myeloablative and mycophenolate mofetil plus cyclosporine in reduced intensity and toxicity conditioning transplants. Upon identification of taTMA, all possible causative factors were fully investigated. The mainstay of treatment strategy was withdrawal of calcineurin inhibitors, plasma infusion and plasma exchange combined with corticosteroid administration and in refractory cases, humanized anti-CD20 monoclonal antibody (Rituximab).
Results
We studied 179 pts (74 male, 105 female), aged 37±14 years, who underwent HCT from matched HLA A/B/C/DRB1 (8/8, n=88) and allele or antigen mismatched (n=91) URD. Grafts derived from peripheral blood (157), bone marrow (18) and umbilical stem cells (4). Conditioning regimens were myeloablative (139), reduced intensity (28) and toxicity (12). Median follow-up was 11.5 (0.1–147.4) months.TaTMA was diagnosed in 29 (16.2%) pts (12 male, 17 female), aged 34±12 years, 78 (9–721) days post-HCT for acute leukemia (21), Hodgkin (3) and non-Hodgkin (1) lymphoma, MDS (2), MPD (1) and aplastic anemia (1). Conditioning regimens were myeloablative in 24 (12 TBI-based) and reduced intensity in 5 pts. Among pts with taTMA, 10 (34%) presented severe (grade III-IV) acute GVHD, 15 (52%) extensive chronic GVHD, 12 (41%) bacterial, 2 (7%) fungal and 21 (71%) viral infectious episodes. In univariate analysis age, gender, diagnosis, disease phase, previous lines of treatment, conditioning (intensity and TBI-based), ABO and HLA incompatibility, infections, acute and chronic GVHD were studied. The presence of taTMA was associated with severe acute and extensive chronic GVHD (p=0.001 and p=0.035 respectively) and TBI-based conditioning (p=0.043). In multivariate analysis, severe acute GVHD was the only independent factor associated with taTMA (β=3.4, p=0.038). Regarding treatment-outcome, 8 pts responded to cyclosporine cessation and plasma infusions. The rest (21) underwent plasma-exchange sessions; in 14 the syndrome resolved, 1 responded to additional Rituximab treatment, while 6/21 pts were refractory and eventually succumbed. Treatment-related mortality was 33.3% (9/29) in taTMA pts and was directly associated with refractory microangiopathic syndrome in 6/29 (20.6%).
Conclusion
Despite the progress achieved concerning classic thrombotic thrombocytopenic purpura and haemolytic uraemic syndrome in terms of diagnosis and novel therapies, taTMA seems to be a far more complex syndrome. Since the pathogenetic factors leading to taTMA are not fully elucidated, treatment of this syndrome often fails. According to our findings, GVHD was the most predisposing factor for the development of taTMA, possibly related to associated endothelial damage.
Session topic: E-poster
Keyword(s): Graft-versus-host disease (GVHD), Thrombotic thrombocytopenic purpura (TTP), Transplant-related mortality, Unrelated donor stem cell transplant
Abstract: PB2160
Type: Publication Only
Background
Allogeneic hematopoietic cell transplantation (HCT) is a curative treatment in hematologic disorders, but morbidity and mortality remain high. Transplant-associated thrombotic microangiopathy (taTMA) is a multifactorial and often fatal syndrome.
Aims
In a retrospective single-centre study we aimed to investigate the incidence of taTMA in patients (pts) undergone HCT from unrelated donors (URD) and identify prognostic factors and treatment outcome.
Methods
We enrolled consecutive pts who underwent URD HCT from 2003 to 2015. TaTMA diagnosis was based on EBMT criteria: increased (>4%) schistocytes in peripheral blood, thrombocytopenia, increased lactate dehydrogenase and decrease in Hb concentration. Anti-thymocyte globulin (ATG, rabbit) was used as standardised part of the conditioning in almost all pts (total dose of 5-7.5mg/kg). Anti-GVHD prophylaxis consisted of cyclosporine or tacrolimus plus methotrexate in myeloablative and mycophenolate mofetil plus cyclosporine in reduced intensity and toxicity conditioning transplants. Upon identification of taTMA, all possible causative factors were fully investigated. The mainstay of treatment strategy was withdrawal of calcineurin inhibitors, plasma infusion and plasma exchange combined with corticosteroid administration and in refractory cases, humanized anti-CD20 monoclonal antibody (Rituximab).
Results
We studied 179 pts (74 male, 105 female), aged 37±14 years, who underwent HCT from matched HLA A/B/C/DRB1 (8/8, n=88) and allele or antigen mismatched (n=91) URD. Grafts derived from peripheral blood (157), bone marrow (18) and umbilical stem cells (4). Conditioning regimens were myeloablative (139), reduced intensity (28) and toxicity (12). Median follow-up was 11.5 (0.1–147.4) months.TaTMA was diagnosed in 29 (16.2%) pts (12 male, 17 female), aged 34±12 years, 78 (9–721) days post-HCT for acute leukemia (21), Hodgkin (3) and non-Hodgkin (1) lymphoma, MDS (2), MPD (1) and aplastic anemia (1). Conditioning regimens were myeloablative in 24 (12 TBI-based) and reduced intensity in 5 pts. Among pts with taTMA, 10 (34%) presented severe (grade III-IV) acute GVHD, 15 (52%) extensive chronic GVHD, 12 (41%) bacterial, 2 (7%) fungal and 21 (71%) viral infectious episodes. In univariate analysis age, gender, diagnosis, disease phase, previous lines of treatment, conditioning (intensity and TBI-based), ABO and HLA incompatibility, infections, acute and chronic GVHD were studied. The presence of taTMA was associated with severe acute and extensive chronic GVHD (p=0.001 and p=0.035 respectively) and TBI-based conditioning (p=0.043). In multivariate analysis, severe acute GVHD was the only independent factor associated with taTMA (β=3.4, p=0.038). Regarding treatment-outcome, 8 pts responded to cyclosporine cessation and plasma infusions. The rest (21) underwent plasma-exchange sessions; in 14 the syndrome resolved, 1 responded to additional Rituximab treatment, while 6/21 pts were refractory and eventually succumbed. Treatment-related mortality was 33.3% (9/29) in taTMA pts and was directly associated with refractory microangiopathic syndrome in 6/29 (20.6%).
Conclusion
Despite the progress achieved concerning classic thrombotic thrombocytopenic purpura and haemolytic uraemic syndrome in terms of diagnosis and novel therapies, taTMA seems to be a far more complex syndrome. Since the pathogenetic factors leading to taTMA are not fully elucidated, treatment of this syndrome often fails. According to our findings, GVHD was the most predisposing factor for the development of taTMA, possibly related to associated endothelial damage.
Session topic: E-poster
Keyword(s): Graft-versus-host disease (GVHD), Thrombotic thrombocytopenic purpura (TTP), Transplant-related mortality, Unrelated donor stem cell transplant
Type: Publication Only
Background
Allogeneic hematopoietic cell transplantation (HCT) is a curative treatment in hematologic disorders, but morbidity and mortality remain high. Transplant-associated thrombotic microangiopathy (taTMA) is a multifactorial and often fatal syndrome.
Aims
In a retrospective single-centre study we aimed to investigate the incidence of taTMA in patients (pts) undergone HCT from unrelated donors (URD) and identify prognostic factors and treatment outcome.
Methods
We enrolled consecutive pts who underwent URD HCT from 2003 to 2015. TaTMA diagnosis was based on EBMT criteria: increased (>4%) schistocytes in peripheral blood, thrombocytopenia, increased lactate dehydrogenase and decrease in Hb concentration. Anti-thymocyte globulin (ATG, rabbit) was used as standardised part of the conditioning in almost all pts (total dose of 5-7.5mg/kg). Anti-GVHD prophylaxis consisted of cyclosporine or tacrolimus plus methotrexate in myeloablative and mycophenolate mofetil plus cyclosporine in reduced intensity and toxicity conditioning transplants. Upon identification of taTMA, all possible causative factors were fully investigated. The mainstay of treatment strategy was withdrawal of calcineurin inhibitors, plasma infusion and plasma exchange combined with corticosteroid administration and in refractory cases, humanized anti-CD20 monoclonal antibody (Rituximab).
Results
We studied 179 pts (74 male, 105 female), aged 37±14 years, who underwent HCT from matched HLA A/B/C/DRB1 (8/8, n=88) and allele or antigen mismatched (n=91) URD. Grafts derived from peripheral blood (157), bone marrow (18) and umbilical stem cells (4). Conditioning regimens were myeloablative (139), reduced intensity (28) and toxicity (12). Median follow-up was 11.5 (0.1–147.4) months.TaTMA was diagnosed in 29 (16.2%) pts (12 male, 17 female), aged 34±12 years, 78 (9–721) days post-HCT for acute leukemia (21), Hodgkin (3) and non-Hodgkin (1) lymphoma, MDS (2), MPD (1) and aplastic anemia (1). Conditioning regimens were myeloablative in 24 (12 TBI-based) and reduced intensity in 5 pts. Among pts with taTMA, 10 (34%) presented severe (grade III-IV) acute GVHD, 15 (52%) extensive chronic GVHD, 12 (41%) bacterial, 2 (7%) fungal and 21 (71%) viral infectious episodes. In univariate analysis age, gender, diagnosis, disease phase, previous lines of treatment, conditioning (intensity and TBI-based), ABO and HLA incompatibility, infections, acute and chronic GVHD were studied. The presence of taTMA was associated with severe acute and extensive chronic GVHD (p=0.001 and p=0.035 respectively) and TBI-based conditioning (p=0.043). In multivariate analysis, severe acute GVHD was the only independent factor associated with taTMA (β=3.4, p=0.038). Regarding treatment-outcome, 8 pts responded to cyclosporine cessation and plasma infusions. The rest (21) underwent plasma-exchange sessions; in 14 the syndrome resolved, 1 responded to additional Rituximab treatment, while 6/21 pts were refractory and eventually succumbed. Treatment-related mortality was 33.3% (9/29) in taTMA pts and was directly associated with refractory microangiopathic syndrome in 6/29 (20.6%).
Conclusion
Despite the progress achieved concerning classic thrombotic thrombocytopenic purpura and haemolytic uraemic syndrome in terms of diagnosis and novel therapies, taTMA seems to be a far more complex syndrome. Since the pathogenetic factors leading to taTMA are not fully elucidated, treatment of this syndrome often fails. According to our findings, GVHD was the most predisposing factor for the development of taTMA, possibly related to associated endothelial damage.
Session topic: E-poster
Keyword(s): Graft-versus-host disease (GVHD), Thrombotic thrombocytopenic purpura (TTP), Transplant-related mortality, Unrelated donor stem cell transplant
{{ help_message }}
{{filter}}