HUMAN ATRIAL NATRIURETIC PEPTIDE (HANP) THERAPY IN THE EARLY PHASE AFTER ALLOGENEIC STEM CELL TRANSPLANT (ALLO-SCT) PREVENTS DEVELOPMENT OF CHRONIC KIDNEY DISEASE (CKD): RESULTS FROM A PHASE 2 STUDY
(Abstract release date: 05/21/15)
EHA Library. Shimizu H. 06/13/15; 103070; S443
Disclosure(s): Gunma UniversityHematology
Dr. Hiroaki Shimizu
Contributions
Contributions
Abstract
Abstract: S443
Type: Oral Presentation
Presentation during EHA20: From 13.06.2015 12:00 to 13.06.2015 12:15
Location: Room C2
Background
Reducing late complications in allo-SCT recipients is an urgent issue in the field of transplant. One of the most serious complications is renal impairment, which reportedly develops in around 20% of long-term survivors. hANP is commercially available in Japan, and preserves postoperative renal function in patients undergoing cardiovascular surgery. These findings inspired us to investigate the renoprotective effects of hANP administration in allo-SCT recipients.
Aims
The primary objective was to determine the safety, toxicity, and efficacy of hANP administration in the early phase after allo-SCT.
Methods
A prospective phase II study of hANP therapy for preventing renal impairment in allo-SCT recipients was conducted with the permission of the institutional review board. Eligible subjects underwent allo-SCT for the first time between 2009 and 2013 without any restrictions on underlying disease, donor source, or conditioning regimen. After obtaining written informed consent, hANP administration was started the day before transplant at a dose of 0.025 μg/kg/min. This dose was adjusted according to blood pressure and urine volume. Results were compared between the study group and control group who had undergone allo-SCT between 2006 and 2013. We selected a control cohort at the rate of one to three, using an optimal matching method for the following nine factors: age; sex; underlying disease; disease status; conditioning intensity; conditioning with or without total body irradiation (TBI); human leukocyte antigen disparity; donor type; and estimated glomerular filtration rate (eGFR) at baseline.
Results
Eighteen patients (9 men, 9 women; median age, 45 years; range, 18-64 years) were enrolled in this study. Underlying diseases were acute leukemia (n = 6), myelodysplastic syndrome (n = 6), and others (n = 6). Eight, seven, and three patients received transplants from related donors, unrelated donors, and cord blood, respectively, and most patients were conditioned with TBI-containing myeloablative regimens. Median duration of hANP administration was 16 days (range, 3-46 days). Two patients experienced grade 2 hypotension attributable to hANP administration, but both cases resolved immediately upon discontinuation of hANP administration. In addition, hANP administration was discontinued in two patients, due to grade 4 bacterial meningitis and grade 4 sepsis, respectively. For matched-pair analysis, 54 patients were selected, and no significant differences in clinical characteristics were identified between the study and control groups. Although mean eGFR kept declining after transplant in both groups, hANP administration maintained eGFR at a significantly higher level until 30 days after transplant (p < 0.001). Incidences of acute kidney injury within 30 days after transplant did not differ significantly between groups, but that within 90 days was significantly lower in the study group (11.1%) than in the control group (40.7%; p = 0.023). The incidence of CKD by 1 year after transplant was significantly reduced in the study group (0%) compared to the control group (42.9%; p = 0.005). Two-year cumulative incidence of non-relapse mortality and 2-year overall survival rates were similar between groups.
Summary
Our findings demonstrated that hANP administration in the early phase after allo-SCT offers excellent renoprotective effects, resulting in a significant reduction in CKD development, without any serious adverse events in allo-SCT recipients. These findings should be confirmed in a prospective, randomized manner in the near future.
Keyword(s): Allogeneic stem cell transplant, Chronic renal failure
Session topic: Stem cell transplantation: Clinical 2
Type: Oral Presentation
Presentation during EHA20: From 13.06.2015 12:00 to 13.06.2015 12:15
Location: Room C2
Background
Reducing late complications in allo-SCT recipients is an urgent issue in the field of transplant. One of the most serious complications is renal impairment, which reportedly develops in around 20% of long-term survivors. hANP is commercially available in Japan, and preserves postoperative renal function in patients undergoing cardiovascular surgery. These findings inspired us to investigate the renoprotective effects of hANP administration in allo-SCT recipients.
Aims
The primary objective was to determine the safety, toxicity, and efficacy of hANP administration in the early phase after allo-SCT.
Methods
A prospective phase II study of hANP therapy for preventing renal impairment in allo-SCT recipients was conducted with the permission of the institutional review board. Eligible subjects underwent allo-SCT for the first time between 2009 and 2013 without any restrictions on underlying disease, donor source, or conditioning regimen. After obtaining written informed consent, hANP administration was started the day before transplant at a dose of 0.025 μg/kg/min. This dose was adjusted according to blood pressure and urine volume. Results were compared between the study group and control group who had undergone allo-SCT between 2006 and 2013. We selected a control cohort at the rate of one to three, using an optimal matching method for the following nine factors: age; sex; underlying disease; disease status; conditioning intensity; conditioning with or without total body irradiation (TBI); human leukocyte antigen disparity; donor type; and estimated glomerular filtration rate (eGFR) at baseline.
Results
Eighteen patients (9 men, 9 women; median age, 45 years; range, 18-64 years) were enrolled in this study. Underlying diseases were acute leukemia (n = 6), myelodysplastic syndrome (n = 6), and others (n = 6). Eight, seven, and three patients received transplants from related donors, unrelated donors, and cord blood, respectively, and most patients were conditioned with TBI-containing myeloablative regimens. Median duration of hANP administration was 16 days (range, 3-46 days). Two patients experienced grade 2 hypotension attributable to hANP administration, but both cases resolved immediately upon discontinuation of hANP administration. In addition, hANP administration was discontinued in two patients, due to grade 4 bacterial meningitis and grade 4 sepsis, respectively. For matched-pair analysis, 54 patients were selected, and no significant differences in clinical characteristics were identified between the study and control groups. Although mean eGFR kept declining after transplant in both groups, hANP administration maintained eGFR at a significantly higher level until 30 days after transplant (p < 0.001). Incidences of acute kidney injury within 30 days after transplant did not differ significantly between groups, but that within 90 days was significantly lower in the study group (11.1%) than in the control group (40.7%; p = 0.023). The incidence of CKD by 1 year after transplant was significantly reduced in the study group (0%) compared to the control group (42.9%; p = 0.005). Two-year cumulative incidence of non-relapse mortality and 2-year overall survival rates were similar between groups.
Summary
Our findings demonstrated that hANP administration in the early phase after allo-SCT offers excellent renoprotective effects, resulting in a significant reduction in CKD development, without any serious adverse events in allo-SCT recipients. These findings should be confirmed in a prospective, randomized manner in the near future.
Keyword(s): Allogeneic stem cell transplant, Chronic renal failure
Session topic: Stem cell transplantation: Clinical 2
Abstract: S443
Type: Oral Presentation
Presentation during EHA20: From 13.06.2015 12:00 to 13.06.2015 12:15
Location: Room C2
Background
Reducing late complications in allo-SCT recipients is an urgent issue in the field of transplant. One of the most serious complications is renal impairment, which reportedly develops in around 20% of long-term survivors. hANP is commercially available in Japan, and preserves postoperative renal function in patients undergoing cardiovascular surgery. These findings inspired us to investigate the renoprotective effects of hANP administration in allo-SCT recipients.
Aims
The primary objective was to determine the safety, toxicity, and efficacy of hANP administration in the early phase after allo-SCT.
Methods
A prospective phase II study of hANP therapy for preventing renal impairment in allo-SCT recipients was conducted with the permission of the institutional review board. Eligible subjects underwent allo-SCT for the first time between 2009 and 2013 without any restrictions on underlying disease, donor source, or conditioning regimen. After obtaining written informed consent, hANP administration was started the day before transplant at a dose of 0.025 μg/kg/min. This dose was adjusted according to blood pressure and urine volume. Results were compared between the study group and control group who had undergone allo-SCT between 2006 and 2013. We selected a control cohort at the rate of one to three, using an optimal matching method for the following nine factors: age; sex; underlying disease; disease status; conditioning intensity; conditioning with or without total body irradiation (TBI); human leukocyte antigen disparity; donor type; and estimated glomerular filtration rate (eGFR) at baseline.
Results
Eighteen patients (9 men, 9 women; median age, 45 years; range, 18-64 years) were enrolled in this study. Underlying diseases were acute leukemia (n = 6), myelodysplastic syndrome (n = 6), and others (n = 6). Eight, seven, and three patients received transplants from related donors, unrelated donors, and cord blood, respectively, and most patients were conditioned with TBI-containing myeloablative regimens. Median duration of hANP administration was 16 days (range, 3-46 days). Two patients experienced grade 2 hypotension attributable to hANP administration, but both cases resolved immediately upon discontinuation of hANP administration. In addition, hANP administration was discontinued in two patients, due to grade 4 bacterial meningitis and grade 4 sepsis, respectively. For matched-pair analysis, 54 patients were selected, and no significant differences in clinical characteristics were identified between the study and control groups. Although mean eGFR kept declining after transplant in both groups, hANP administration maintained eGFR at a significantly higher level until 30 days after transplant (p < 0.001). Incidences of acute kidney injury within 30 days after transplant did not differ significantly between groups, but that within 90 days was significantly lower in the study group (11.1%) than in the control group (40.7%; p = 0.023). The incidence of CKD by 1 year after transplant was significantly reduced in the study group (0%) compared to the control group (42.9%; p = 0.005). Two-year cumulative incidence of non-relapse mortality and 2-year overall survival rates were similar between groups.
Summary
Our findings demonstrated that hANP administration in the early phase after allo-SCT offers excellent renoprotective effects, resulting in a significant reduction in CKD development, without any serious adverse events in allo-SCT recipients. These findings should be confirmed in a prospective, randomized manner in the near future.
Keyword(s): Allogeneic stem cell transplant, Chronic renal failure
Session topic: Stem cell transplantation: Clinical 2
Type: Oral Presentation
Presentation during EHA20: From 13.06.2015 12:00 to 13.06.2015 12:15
Location: Room C2
Background
Reducing late complications in allo-SCT recipients is an urgent issue in the field of transplant. One of the most serious complications is renal impairment, which reportedly develops in around 20% of long-term survivors. hANP is commercially available in Japan, and preserves postoperative renal function in patients undergoing cardiovascular surgery. These findings inspired us to investigate the renoprotective effects of hANP administration in allo-SCT recipients.
Aims
The primary objective was to determine the safety, toxicity, and efficacy of hANP administration in the early phase after allo-SCT.
Methods
A prospective phase II study of hANP therapy for preventing renal impairment in allo-SCT recipients was conducted with the permission of the institutional review board. Eligible subjects underwent allo-SCT for the first time between 2009 and 2013 without any restrictions on underlying disease, donor source, or conditioning regimen. After obtaining written informed consent, hANP administration was started the day before transplant at a dose of 0.025 μg/kg/min. This dose was adjusted according to blood pressure and urine volume. Results were compared between the study group and control group who had undergone allo-SCT between 2006 and 2013. We selected a control cohort at the rate of one to three, using an optimal matching method for the following nine factors: age; sex; underlying disease; disease status; conditioning intensity; conditioning with or without total body irradiation (TBI); human leukocyte antigen disparity; donor type; and estimated glomerular filtration rate (eGFR) at baseline.
Results
Eighteen patients (9 men, 9 women; median age, 45 years; range, 18-64 years) were enrolled in this study. Underlying diseases were acute leukemia (n = 6), myelodysplastic syndrome (n = 6), and others (n = 6). Eight, seven, and three patients received transplants from related donors, unrelated donors, and cord blood, respectively, and most patients were conditioned with TBI-containing myeloablative regimens. Median duration of hANP administration was 16 days (range, 3-46 days). Two patients experienced grade 2 hypotension attributable to hANP administration, but both cases resolved immediately upon discontinuation of hANP administration. In addition, hANP administration was discontinued in two patients, due to grade 4 bacterial meningitis and grade 4 sepsis, respectively. For matched-pair analysis, 54 patients were selected, and no significant differences in clinical characteristics were identified between the study and control groups. Although mean eGFR kept declining after transplant in both groups, hANP administration maintained eGFR at a significantly higher level until 30 days after transplant (p < 0.001). Incidences of acute kidney injury within 30 days after transplant did not differ significantly between groups, but that within 90 days was significantly lower in the study group (11.1%) than in the control group (40.7%; p = 0.023). The incidence of CKD by 1 year after transplant was significantly reduced in the study group (0%) compared to the control group (42.9%; p = 0.005). Two-year cumulative incidence of non-relapse mortality and 2-year overall survival rates were similar between groups.
Summary
Our findings demonstrated that hANP administration in the early phase after allo-SCT offers excellent renoprotective effects, resulting in a significant reduction in CKD development, without any serious adverse events in allo-SCT recipients. These findings should be confirmed in a prospective, randomized manner in the near future.
Keyword(s): Allogeneic stem cell transplant, Chronic renal failure
Session topic: Stem cell transplantation: Clinical 2
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