COMPREHENSIVE LONG-TERM FOLLOW-UP OF PAROXYSMAL NOCTURNAL HEMOGLOBINURIA: A REPORT FROM A SINGLE CENTRE
(Abstract release date: 05/19/16)
EHA Library. Sempere A. 06/09/16; 134664; PB1764
Dr. Amparo Sempere
Contributions
Contributions
Abstract
Abstract: PB1764
Type: Publication Only
Background
Paroxysmal nocturnal hemoglobinuria (PNH) is a rare life-threatening acquired clonal hematopoietic stem cell disorder characterized by chronic complement activation associated with intravascular hemolysis, thrombosis, and bone marrow failure. Before the availability of anti-complement therapy with eculizumab, treatment remained largely supportive, since the only curative procedure available is allogeneic hematopoietic stem cell transplantation (HSCT), which is associated with substantial morbidity and mortality.
Aims
This study was planned to report on the management and clinical course in a series of PNH patients in a tertiary reference centre reflecting trends in diagnosis and management through the last four decades.
Methods
This descriptive, observational, single centre study evaluated patients diagnosed with PNH between January 1979 and January 2016. An electronic case report form was completed for each patient using clinical data collected from digital or paper medical records. Patients were divided into three groups according to the Parker classification: classic, associated with another bone marrow failure syndrome (BMFS) or subclinical.
Results
A total of 37 patients (mean age 37.2 years ± 20.6, 20 male (54%)] were included. A large number of diagnoses were made after 2008 (16 patients, 43%), related to improvements in flow cytometry (FC) analysis. The median follow-up time was 6.9 years [IQR: 3.4-15.2]. Nine patients (24%) were diagnosed with classic PNH, 26 (70%) with BMFS; and 2 (5%) with subclinical PNH.Median values for laboratory parameters at diagnosis were: serum lactate dehydrogenase (LDH) 489 UI/L [IQR: 404-1123]; hemoglobin 9.8 g/dL [IQR: 9.1-10.9]; haptoglobin 10 mg/dL [IQR: 7.8-57]; and serum creatinine 0.8 mg/dL [IQR: 0.6-1.1]. At diagnosis 68% of patients presented with pancytopenia.All 20 patients with FC data had GPI-deficient granulocytes (median 5.5% [IQR: 1-31]), as well as GPI-deficient monocytes (median 3% [IQR: 0.5-39.5]). Seven patients had type III erythrocytes (median 2.7% [IQR: 0.4-12]). As expected, FC analysis showed that the GPI-deficient cell clone size was higher in classic PNH than BMFS.A total of 15 patients (41%) required transfusion support. The most frequent therapy was immunosuppression (70%). Twelve (32%) patients, 3 of whom had classic PNH, underwent allogeneic hematopoietic stem cell transplantation (HSCT) at a mean age of 30 years (range 23–37 years). The stem cell source was peripheral blood in eight patients (67%), bone marrow in three (25%) and umbilical cord blood in one. Only two patients received eculizumab (5%).Two patients with classic PNH had a history of severe thrombotic complications (Budd-Chiari syndrome, pulmonary thromboembolism). At last follow-up, eight (22%) patients had died (3 with classic PNH, 5 with BMFS). The leading causes of death were hemorrhage and HSCT-related complications.
Conclusion
PNH is a rare disease with a highly variable clinical outcome. Improvements in FC techniques have contributed substantially to detect new cases in recent years. Long-term follow-up studies like ours facilitate a better understanding of the natural history of PNH and contribute to improve the management of our PNH patients.
Session topic: E-poster
Keyword(s): HSCT, Long-term follow-up, PNH, Treatment
Type: Publication Only
Background
Paroxysmal nocturnal hemoglobinuria (PNH) is a rare life-threatening acquired clonal hematopoietic stem cell disorder characterized by chronic complement activation associated with intravascular hemolysis, thrombosis, and bone marrow failure. Before the availability of anti-complement therapy with eculizumab, treatment remained largely supportive, since the only curative procedure available is allogeneic hematopoietic stem cell transplantation (HSCT), which is associated with substantial morbidity and mortality.
Aims
This study was planned to report on the management and clinical course in a series of PNH patients in a tertiary reference centre reflecting trends in diagnosis and management through the last four decades.
Methods
This descriptive, observational, single centre study evaluated patients diagnosed with PNH between January 1979 and January 2016. An electronic case report form was completed for each patient using clinical data collected from digital or paper medical records. Patients were divided into three groups according to the Parker classification: classic, associated with another bone marrow failure syndrome (BMFS) or subclinical.
Results
A total of 37 patients (mean age 37.2 years ± 20.6, 20 male (54%)] were included. A large number of diagnoses were made after 2008 (16 patients, 43%), related to improvements in flow cytometry (FC) analysis. The median follow-up time was 6.9 years [IQR: 3.4-15.2]. Nine patients (24%) were diagnosed with classic PNH, 26 (70%) with BMFS; and 2 (5%) with subclinical PNH.Median values for laboratory parameters at diagnosis were: serum lactate dehydrogenase (LDH) 489 UI/L [IQR: 404-1123]; hemoglobin 9.8 g/dL [IQR: 9.1-10.9]; haptoglobin 10 mg/dL [IQR: 7.8-57]; and serum creatinine 0.8 mg/dL [IQR: 0.6-1.1]. At diagnosis 68% of patients presented with pancytopenia.All 20 patients with FC data had GPI-deficient granulocytes (median 5.5% [IQR: 1-31]), as well as GPI-deficient monocytes (median 3% [IQR: 0.5-39.5]). Seven patients had type III erythrocytes (median 2.7% [IQR: 0.4-12]). As expected, FC analysis showed that the GPI-deficient cell clone size was higher in classic PNH than BMFS.A total of 15 patients (41%) required transfusion support. The most frequent therapy was immunosuppression (70%). Twelve (32%) patients, 3 of whom had classic PNH, underwent allogeneic hematopoietic stem cell transplantation (HSCT) at a mean age of 30 years (range 23–37 years). The stem cell source was peripheral blood in eight patients (67%), bone marrow in three (25%) and umbilical cord blood in one. Only two patients received eculizumab (5%).Two patients with classic PNH had a history of severe thrombotic complications (Budd-Chiari syndrome, pulmonary thromboembolism). At last follow-up, eight (22%) patients had died (3 with classic PNH, 5 with BMFS). The leading causes of death were hemorrhage and HSCT-related complications.
Conclusion
PNH is a rare disease with a highly variable clinical outcome. Improvements in FC techniques have contributed substantially to detect new cases in recent years. Long-term follow-up studies like ours facilitate a better understanding of the natural history of PNH and contribute to improve the management of our PNH patients.
Session topic: E-poster
Keyword(s): HSCT, Long-term follow-up, PNH, Treatment
Abstract: PB1764
Type: Publication Only
Background
Paroxysmal nocturnal hemoglobinuria (PNH) is a rare life-threatening acquired clonal hematopoietic stem cell disorder characterized by chronic complement activation associated with intravascular hemolysis, thrombosis, and bone marrow failure. Before the availability of anti-complement therapy with eculizumab, treatment remained largely supportive, since the only curative procedure available is allogeneic hematopoietic stem cell transplantation (HSCT), which is associated with substantial morbidity and mortality.
Aims
This study was planned to report on the management and clinical course in a series of PNH patients in a tertiary reference centre reflecting trends in diagnosis and management through the last four decades.
Methods
This descriptive, observational, single centre study evaluated patients diagnosed with PNH between January 1979 and January 2016. An electronic case report form was completed for each patient using clinical data collected from digital or paper medical records. Patients were divided into three groups according to the Parker classification: classic, associated with another bone marrow failure syndrome (BMFS) or subclinical.
Results
A total of 37 patients (mean age 37.2 years ± 20.6, 20 male (54%)] were included. A large number of diagnoses were made after 2008 (16 patients, 43%), related to improvements in flow cytometry (FC) analysis. The median follow-up time was 6.9 years [IQR: 3.4-15.2]. Nine patients (24%) were diagnosed with classic PNH, 26 (70%) with BMFS; and 2 (5%) with subclinical PNH.Median values for laboratory parameters at diagnosis were: serum lactate dehydrogenase (LDH) 489 UI/L [IQR: 404-1123]; hemoglobin 9.8 g/dL [IQR: 9.1-10.9]; haptoglobin 10 mg/dL [IQR: 7.8-57]; and serum creatinine 0.8 mg/dL [IQR: 0.6-1.1]. At diagnosis 68% of patients presented with pancytopenia.All 20 patients with FC data had GPI-deficient granulocytes (median 5.5% [IQR: 1-31]), as well as GPI-deficient monocytes (median 3% [IQR: 0.5-39.5]). Seven patients had type III erythrocytes (median 2.7% [IQR: 0.4-12]). As expected, FC analysis showed that the GPI-deficient cell clone size was higher in classic PNH than BMFS.A total of 15 patients (41%) required transfusion support. The most frequent therapy was immunosuppression (70%). Twelve (32%) patients, 3 of whom had classic PNH, underwent allogeneic hematopoietic stem cell transplantation (HSCT) at a mean age of 30 years (range 23–37 years). The stem cell source was peripheral blood in eight patients (67%), bone marrow in three (25%) and umbilical cord blood in one. Only two patients received eculizumab (5%).Two patients with classic PNH had a history of severe thrombotic complications (Budd-Chiari syndrome, pulmonary thromboembolism). At last follow-up, eight (22%) patients had died (3 with classic PNH, 5 with BMFS). The leading causes of death were hemorrhage and HSCT-related complications.
Conclusion
PNH is a rare disease with a highly variable clinical outcome. Improvements in FC techniques have contributed substantially to detect new cases in recent years. Long-term follow-up studies like ours facilitate a better understanding of the natural history of PNH and contribute to improve the management of our PNH patients.
Session topic: E-poster
Keyword(s): HSCT, Long-term follow-up, PNH, Treatment
Type: Publication Only
Background
Paroxysmal nocturnal hemoglobinuria (PNH) is a rare life-threatening acquired clonal hematopoietic stem cell disorder characterized by chronic complement activation associated with intravascular hemolysis, thrombosis, and bone marrow failure. Before the availability of anti-complement therapy with eculizumab, treatment remained largely supportive, since the only curative procedure available is allogeneic hematopoietic stem cell transplantation (HSCT), which is associated with substantial morbidity and mortality.
Aims
This study was planned to report on the management and clinical course in a series of PNH patients in a tertiary reference centre reflecting trends in diagnosis and management through the last four decades.
Methods
This descriptive, observational, single centre study evaluated patients diagnosed with PNH between January 1979 and January 2016. An electronic case report form was completed for each patient using clinical data collected from digital or paper medical records. Patients were divided into three groups according to the Parker classification: classic, associated with another bone marrow failure syndrome (BMFS) or subclinical.
Results
A total of 37 patients (mean age 37.2 years ± 20.6, 20 male (54%)] were included. A large number of diagnoses were made after 2008 (16 patients, 43%), related to improvements in flow cytometry (FC) analysis. The median follow-up time was 6.9 years [IQR: 3.4-15.2]. Nine patients (24%) were diagnosed with classic PNH, 26 (70%) with BMFS; and 2 (5%) with subclinical PNH.Median values for laboratory parameters at diagnosis were: serum lactate dehydrogenase (LDH) 489 UI/L [IQR: 404-1123]; hemoglobin 9.8 g/dL [IQR: 9.1-10.9]; haptoglobin 10 mg/dL [IQR: 7.8-57]; and serum creatinine 0.8 mg/dL [IQR: 0.6-1.1]. At diagnosis 68% of patients presented with pancytopenia.All 20 patients with FC data had GPI-deficient granulocytes (median 5.5% [IQR: 1-31]), as well as GPI-deficient monocytes (median 3% [IQR: 0.5-39.5]). Seven patients had type III erythrocytes (median 2.7% [IQR: 0.4-12]). As expected, FC analysis showed that the GPI-deficient cell clone size was higher in classic PNH than BMFS.A total of 15 patients (41%) required transfusion support. The most frequent therapy was immunosuppression (70%). Twelve (32%) patients, 3 of whom had classic PNH, underwent allogeneic hematopoietic stem cell transplantation (HSCT) at a mean age of 30 years (range 23–37 years). The stem cell source was peripheral blood in eight patients (67%), bone marrow in three (25%) and umbilical cord blood in one. Only two patients received eculizumab (5%).Two patients with classic PNH had a history of severe thrombotic complications (Budd-Chiari syndrome, pulmonary thromboembolism). At last follow-up, eight (22%) patients had died (3 with classic PNH, 5 with BMFS). The leading causes of death were hemorrhage and HSCT-related complications.
Conclusion
PNH is a rare disease with a highly variable clinical outcome. Improvements in FC techniques have contributed substantially to detect new cases in recent years. Long-term follow-up studies like ours facilitate a better understanding of the natural history of PNH and contribute to improve the management of our PNH patients.
Session topic: E-poster
Keyword(s): HSCT, Long-term follow-up, PNH, Treatment
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