CLINICAL RELEVANCE OF LOW PERCENTAGE OF GLYCOSYLATED FERRITIN IN MANAGEMENT OF ACQUIRED HEMOPHAGOCYTIC LYMPHOHISTIOCYTOSIS: A SINGLE CENTER EXPERIENCE
(Abstract release date: 05/19/16)
EHA Library. Nabergoj M. 06/09/16; 132955; E1406
Dr. Mitja Nabergoj
Contributions
Contributions
Abstract
Abstract: E1406
Type: Eposter Presentation
Background
Hemophagocytic lymphohistiocytosis (HLH) is a rare and life-threatening condition characterized by excessive chaotic and uncontrolled inflammation leading to multiorgan failure and death. HLH can be either primary (familial), when caused by a genetic mutations affecting cytotoxic function, or secondary (acquired), when due to infectious, malignant, rheumatologic or metabolic conditions. Although diagnostic scores have been proposed such as HLH-04 criteria, which were validated only in pediatric patients, and the HScore, HLH diagnosis is still challenging owe to lack of solid criteria allowing differential diagnosis with other multisystem illnesses characterized by fever, hepatic failure, and neurologic symptoms. Recently, a percentage of glycosylated ferritin (GF) <20% has been proposed as highly specific of HLH and useful in the differential diagnosis from other hyperinflammatory syndromes, such severe sepsis and flare of a secondary underlying disease.
Aims
To validate the usefulness of glycosylated ferritin levels in identification of patients with HLH and to evaluate its potential role in predicting treatment outcome.
Methods
Over a 2-year period, nineteen adult (>18 years) patients with a clinical and laboratory pattern consistent with HLH were included in the study. HLH-04 criteria and HScore were applied for HLH diagnosis. The percentage of glycosylated ferritin was measured by an in-house assay (Marinova et al, in press). Specificity and sensitivity for each approach was then calculated.
Results
Ten out of 19 (53%) subjects had clinical and laboratory findings consistent with HLH. In all cases an underlying disorder was identified: infection (n=1), autoimmune disease (n=1), malignancy (n=1), Hodgkin or non Hodgkin lymphoma (n=1 and n=6, respectively). All but one patient (90%) fulfilled the HLH-04 criteria, whereas a high probability HScore (>90%) was present in 7 out of 10 subjects (70%). Nine out of 19 patients (47%) in whom HLH was ruled out, underlying disorders were autoimmune disease (n=1), infection (n=1), AML (n=1), non-Hodgkin lymphoma (n=5). Among these 9 patients, 2 (22%) met at least five HLH-04 criteria and no one had a HScore probability >90%. Ferritin levels failed to differentiate patients with HLH (11565 ± 95161 vs 4669 ± 3541 μg/L, HLH vs non-HLH, p=0,18). When GF was measured in our cohort, a percentage of GF level <20% was observed in 9/10 patients with HLH, whereas all unaffected patients had GF level >20%. We found a negative linear correlation between HScore and GF percentage (p <0,05, r=-0,54) and between HLH-04 criteria and GF percentage (p <0,05, r=-0,47). All three methods were able to significantly discriminate affected patients from unaffected (all p<0,05), but GF level <20% showed higher sensitivity against HScore (90% vs 70%) and better specificity against HLH-04 (100% vs 78%). Moreover, GF shows higher negative predictive value compared to the other diagnostic methods (GF: 90%).Five patients had GF levels measured over the course of the disease. Although the very limited number of patients does not allow to draw any conclusion, two patients who did not show recovery of GF levels >20% within one week after treatment initiation died within one month, while 3 patients who experienced a rise in GF >20% showed a resolution of HLH-related clinical picture and longer survival (median 6 months).
Conclusion
In our study a fraction of glycosylated ferritin <20% showed high concordance between HLH-04 criteria and HScore and it seemed of help in identifying patients affected by HLH when scores are contradictory as well as in excluding false positive cases. Monitoring GF levels over the course of HLH may also allow to predict response to therapy.
Session topic: E-poster
Keyword(s): Ferritin, Fever
Type: Eposter Presentation
Background
Hemophagocytic lymphohistiocytosis (HLH) is a rare and life-threatening condition characterized by excessive chaotic and uncontrolled inflammation leading to multiorgan failure and death. HLH can be either primary (familial), when caused by a genetic mutations affecting cytotoxic function, or secondary (acquired), when due to infectious, malignant, rheumatologic or metabolic conditions. Although diagnostic scores have been proposed such as HLH-04 criteria, which were validated only in pediatric patients, and the HScore, HLH diagnosis is still challenging owe to lack of solid criteria allowing differential diagnosis with other multisystem illnesses characterized by fever, hepatic failure, and neurologic symptoms. Recently, a percentage of glycosylated ferritin (GF) <20% has been proposed as highly specific of HLH and useful in the differential diagnosis from other hyperinflammatory syndromes, such severe sepsis and flare of a secondary underlying disease.
Aims
To validate the usefulness of glycosylated ferritin levels in identification of patients with HLH and to evaluate its potential role in predicting treatment outcome.
Methods
Over a 2-year period, nineteen adult (>18 years) patients with a clinical and laboratory pattern consistent with HLH were included in the study. HLH-04 criteria and HScore were applied for HLH diagnosis. The percentage of glycosylated ferritin was measured by an in-house assay (Marinova et al, in press). Specificity and sensitivity for each approach was then calculated.
Results
Ten out of 19 (53%) subjects had clinical and laboratory findings consistent with HLH. In all cases an underlying disorder was identified: infection (n=1), autoimmune disease (n=1), malignancy (n=1), Hodgkin or non Hodgkin lymphoma (n=1 and n=6, respectively). All but one patient (90%) fulfilled the HLH-04 criteria, whereas a high probability HScore (>90%) was present in 7 out of 10 subjects (70%). Nine out of 19 patients (47%) in whom HLH was ruled out, underlying disorders were autoimmune disease (n=1), infection (n=1), AML (n=1), non-Hodgkin lymphoma (n=5). Among these 9 patients, 2 (22%) met at least five HLH-04 criteria and no one had a HScore probability >90%. Ferritin levels failed to differentiate patients with HLH (11565 ± 95161 vs 4669 ± 3541 μg/L, HLH vs non-HLH, p=0,18). When GF was measured in our cohort, a percentage of GF level <20% was observed in 9/10 patients with HLH, whereas all unaffected patients had GF level >20%. We found a negative linear correlation between HScore and GF percentage (p <0,05, r=-0,54) and between HLH-04 criteria and GF percentage (p <0,05, r=-0,47). All three methods were able to significantly discriminate affected patients from unaffected (all p<0,05), but GF level <20% showed higher sensitivity against HScore (90% vs 70%) and better specificity against HLH-04 (100% vs 78%). Moreover, GF shows higher negative predictive value compared to the other diagnostic methods (GF: 90%).Five patients had GF levels measured over the course of the disease. Although the very limited number of patients does not allow to draw any conclusion, two patients who did not show recovery of GF levels >20% within one week after treatment initiation died within one month, while 3 patients who experienced a rise in GF >20% showed a resolution of HLH-related clinical picture and longer survival (median 6 months).
Conclusion
In our study a fraction of glycosylated ferritin <20% showed high concordance between HLH-04 criteria and HScore and it seemed of help in identifying patients affected by HLH when scores are contradictory as well as in excluding false positive cases. Monitoring GF levels over the course of HLH may also allow to predict response to therapy.
Session topic: E-poster
Keyword(s): Ferritin, Fever
Abstract: E1406
Type: Eposter Presentation
Background
Hemophagocytic lymphohistiocytosis (HLH) is a rare and life-threatening condition characterized by excessive chaotic and uncontrolled inflammation leading to multiorgan failure and death. HLH can be either primary (familial), when caused by a genetic mutations affecting cytotoxic function, or secondary (acquired), when due to infectious, malignant, rheumatologic or metabolic conditions. Although diagnostic scores have been proposed such as HLH-04 criteria, which were validated only in pediatric patients, and the HScore, HLH diagnosis is still challenging owe to lack of solid criteria allowing differential diagnosis with other multisystem illnesses characterized by fever, hepatic failure, and neurologic symptoms. Recently, a percentage of glycosylated ferritin (GF) <20% has been proposed as highly specific of HLH and useful in the differential diagnosis from other hyperinflammatory syndromes, such severe sepsis and flare of a secondary underlying disease.
Aims
To validate the usefulness of glycosylated ferritin levels in identification of patients with HLH and to evaluate its potential role in predicting treatment outcome.
Methods
Over a 2-year period, nineteen adult (>18 years) patients with a clinical and laboratory pattern consistent with HLH were included in the study. HLH-04 criteria and HScore were applied for HLH diagnosis. The percentage of glycosylated ferritin was measured by an in-house assay (Marinova et al, in press). Specificity and sensitivity for each approach was then calculated.
Results
Ten out of 19 (53%) subjects had clinical and laboratory findings consistent with HLH. In all cases an underlying disorder was identified: infection (n=1), autoimmune disease (n=1), malignancy (n=1), Hodgkin or non Hodgkin lymphoma (n=1 and n=6, respectively). All but one patient (90%) fulfilled the HLH-04 criteria, whereas a high probability HScore (>90%) was present in 7 out of 10 subjects (70%). Nine out of 19 patients (47%) in whom HLH was ruled out, underlying disorders were autoimmune disease (n=1), infection (n=1), AML (n=1), non-Hodgkin lymphoma (n=5). Among these 9 patients, 2 (22%) met at least five HLH-04 criteria and no one had a HScore probability >90%. Ferritin levels failed to differentiate patients with HLH (11565 ± 95161 vs 4669 ± 3541 μg/L, HLH vs non-HLH, p=0,18). When GF was measured in our cohort, a percentage of GF level <20% was observed in 9/10 patients with HLH, whereas all unaffected patients had GF level >20%. We found a negative linear correlation between HScore and GF percentage (p <0,05, r=-0,54) and between HLH-04 criteria and GF percentage (p <0,05, r=-0,47). All three methods were able to significantly discriminate affected patients from unaffected (all p<0,05), but GF level <20% showed higher sensitivity against HScore (90% vs 70%) and better specificity against HLH-04 (100% vs 78%). Moreover, GF shows higher negative predictive value compared to the other diagnostic methods (GF: 90%).Five patients had GF levels measured over the course of the disease. Although the very limited number of patients does not allow to draw any conclusion, two patients who did not show recovery of GF levels >20% within one week after treatment initiation died within one month, while 3 patients who experienced a rise in GF >20% showed a resolution of HLH-related clinical picture and longer survival (median 6 months).
Conclusion
In our study a fraction of glycosylated ferritin <20% showed high concordance between HLH-04 criteria and HScore and it seemed of help in identifying patients affected by HLH when scores are contradictory as well as in excluding false positive cases. Monitoring GF levels over the course of HLH may also allow to predict response to therapy.
Session topic: E-poster
Keyword(s): Ferritin, Fever
Type: Eposter Presentation
Background
Hemophagocytic lymphohistiocytosis (HLH) is a rare and life-threatening condition characterized by excessive chaotic and uncontrolled inflammation leading to multiorgan failure and death. HLH can be either primary (familial), when caused by a genetic mutations affecting cytotoxic function, or secondary (acquired), when due to infectious, malignant, rheumatologic or metabolic conditions. Although diagnostic scores have been proposed such as HLH-04 criteria, which were validated only in pediatric patients, and the HScore, HLH diagnosis is still challenging owe to lack of solid criteria allowing differential diagnosis with other multisystem illnesses characterized by fever, hepatic failure, and neurologic symptoms. Recently, a percentage of glycosylated ferritin (GF) <20% has been proposed as highly specific of HLH and useful in the differential diagnosis from other hyperinflammatory syndromes, such severe sepsis and flare of a secondary underlying disease.
Aims
To validate the usefulness of glycosylated ferritin levels in identification of patients with HLH and to evaluate its potential role in predicting treatment outcome.
Methods
Over a 2-year period, nineteen adult (>18 years) patients with a clinical and laboratory pattern consistent with HLH were included in the study. HLH-04 criteria and HScore were applied for HLH diagnosis. The percentage of glycosylated ferritin was measured by an in-house assay (Marinova et al, in press). Specificity and sensitivity for each approach was then calculated.
Results
Ten out of 19 (53%) subjects had clinical and laboratory findings consistent with HLH. In all cases an underlying disorder was identified: infection (n=1), autoimmune disease (n=1), malignancy (n=1), Hodgkin or non Hodgkin lymphoma (n=1 and n=6, respectively). All but one patient (90%) fulfilled the HLH-04 criteria, whereas a high probability HScore (>90%) was present in 7 out of 10 subjects (70%). Nine out of 19 patients (47%) in whom HLH was ruled out, underlying disorders were autoimmune disease (n=1), infection (n=1), AML (n=1), non-Hodgkin lymphoma (n=5). Among these 9 patients, 2 (22%) met at least five HLH-04 criteria and no one had a HScore probability >90%. Ferritin levels failed to differentiate patients with HLH (11565 ± 95161 vs 4669 ± 3541 μg/L, HLH vs non-HLH, p=0,18). When GF was measured in our cohort, a percentage of GF level <20% was observed in 9/10 patients with HLH, whereas all unaffected patients had GF level >20%. We found a negative linear correlation between HScore and GF percentage (p <0,05, r=-0,54) and between HLH-04 criteria and GF percentage (p <0,05, r=-0,47). All three methods were able to significantly discriminate affected patients from unaffected (all p<0,05), but GF level <20% showed higher sensitivity against HScore (90% vs 70%) and better specificity against HLH-04 (100% vs 78%). Moreover, GF shows higher negative predictive value compared to the other diagnostic methods (GF: 90%).Five patients had GF levels measured over the course of the disease. Although the very limited number of patients does not allow to draw any conclusion, two patients who did not show recovery of GF levels >20% within one week after treatment initiation died within one month, while 3 patients who experienced a rise in GF >20% showed a resolution of HLH-related clinical picture and longer survival (median 6 months).
Conclusion
In our study a fraction of glycosylated ferritin <20% showed high concordance between HLH-04 criteria and HScore and it seemed of help in identifying patients affected by HLH when scores are contradictory as well as in excluding false positive cases. Monitoring GF levels over the course of HLH may also allow to predict response to therapy.
Session topic: E-poster
Keyword(s): Ferritin, Fever
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