PROGNOSTIC RELEVANCE OF SERUM FERRITIN LEVELS IN HODGKIN LYMPHOMA (HL) UNDER TREATMENT WITH ABVD OR EQUIVALENT REGIMENS WITH OR WITHOUT RADIOTHERAPY (RT)
(Abstract release date: 05/19/16)
EHA Library. Vassilakopoulos T. 06/09/16; 132691; E1142
Assoc. Prof. Theodoros Vassilakopoulos
Contributions
Contributions
Abstract
Abstract: E1142
Type: Eposter Presentation
Background
Cytokine-driven inflammatory processes dominate the clinical and laboratory expression of HL, especially in advanced stages. Serum ferritin (SF) levels increase in the context of “acute phase reaction” along with fibrinogen, ESR, cerulloplasmin, haptoglobins etc. Although SF elevations are a well known feature of HL, their prognostic significance has not been adequately evaluated. Recently, Fernandes-Alvarez et al reported that elevated SF levels (>350 μg/L) were an independent prognostic factor in 173 optimally treated patients with classical HL (Leuk Lymphoma 2015).
Aims
To evaluate the prognostic significance of SF levels in a large series of patients with HL treated with ABVD or similar chemotherapy with or without radiotherapy (ABVD±RT).
Methods
We evaluated 309 pts with HL, treated with ABVD or equivalents (±RT), who had available data for SF levels. Median age was 33 yrs (15-87), 54% of patients were male, 34% had B-symptoms, 17% had stage IV disease, 50% had advanced stage (IB,IIB,III,IV), 33% had IPS ≥3, 67% nodular sclerosis histology and 19% mixed cellularity. Failure-free survival (FFS) was defined as time between treatment initiation and toxic death, failure to achieve remission requiring switch to salvage therapy, relapse after remission or last follow-up; deaths in remission of unrelated causes were not counted as events.
Results
Median follow-up of currently alive patients was 41 months. The median SF levels were 149 μg/L (range 6.6-6709.0, interquartile range; IQR 63.9-316.5). As expected, SF levels were lower in females than males (medians 70.6 vs. 240.2, p<0.001). Increased SF levels were highly correlated (p<0.001) with older age, advanced stage, increased IPS and markers of systemic disturbance (B-symptoms, anemia, ESR, CRP, low serum albumin), as well as with beta2-microglobulin, elevated serum LDH (p=0.01) and mixed cellularity (p=0.01 compared to nodular sclerosis). However, there was no correlation with leukocytosis or lymphocytopenia. At a cutoff of 150 μg/L (almost the median), the 5-year FFS was 85% vs. 67% for patients with lower and higher SF levels (p=0.0005). If a gender-based median cutoff was adopted (high levels above the median of each gender), the results were similar (84% vs. 68%, p=0.0006). At the published cutoff of 350 μg/L only 21% of patients had high SF levels and the difference in the outcome was less pronounced (79% vs. 64%; p=0.01). In both early (ΙΑ/ΙΙΑ) and advanced (IB, IIB-IV) stages, SF ≥150 μg/L provided an 8-9% absolute difference in 5-year FFS, which was not however statistically significant (p=0.18 and p=0.16). In multivariate analysis, SF ≥150 μg/L was an independent prognostic factor (p=0.04; HR=1.79) along with advanced stage (p<0.001; HR=2.66), when adjusted for B-symptoms, anemia, LDH and gender. Further adjustment for CRP or ESR did not result to any meaningful alteration of the magnitude of the HR. However, the significance of SF became marginal if stage IV was used instead of “advanced stage”. In models containing SF levels, B-symptoms and IPS, SF displaced IPS.
Conclusion
Elevated SF levels may be an independent prognostic factor in HL treated with ABVD or equivalent regimens ± RT after adjustment for other important variables, including B-symptoms, anemia, ESR and CRP. However, larger patient series are needed in order to extract safe conclusions and determine the optimal cutoff.
Session topic: E-poster
Type: Eposter Presentation
Background
Cytokine-driven inflammatory processes dominate the clinical and laboratory expression of HL, especially in advanced stages. Serum ferritin (SF) levels increase in the context of “acute phase reaction” along with fibrinogen, ESR, cerulloplasmin, haptoglobins etc. Although SF elevations are a well known feature of HL, their prognostic significance has not been adequately evaluated. Recently, Fernandes-Alvarez et al reported that elevated SF levels (>350 μg/L) were an independent prognostic factor in 173 optimally treated patients with classical HL (Leuk Lymphoma 2015).
Aims
To evaluate the prognostic significance of SF levels in a large series of patients with HL treated with ABVD or similar chemotherapy with or without radiotherapy (ABVD±RT).
Methods
We evaluated 309 pts with HL, treated with ABVD or equivalents (±RT), who had available data for SF levels. Median age was 33 yrs (15-87), 54% of patients were male, 34% had B-symptoms, 17% had stage IV disease, 50% had advanced stage (IB,IIB,III,IV), 33% had IPS ≥3, 67% nodular sclerosis histology and 19% mixed cellularity. Failure-free survival (FFS) was defined as time between treatment initiation and toxic death, failure to achieve remission requiring switch to salvage therapy, relapse after remission or last follow-up; deaths in remission of unrelated causes were not counted as events.
Results
Median follow-up of currently alive patients was 41 months. The median SF levels were 149 μg/L (range 6.6-6709.0, interquartile range; IQR 63.9-316.5). As expected, SF levels were lower in females than males (medians 70.6 vs. 240.2, p<0.001). Increased SF levels were highly correlated (p<0.001) with older age, advanced stage, increased IPS and markers of systemic disturbance (B-symptoms, anemia, ESR, CRP, low serum albumin), as well as with beta2-microglobulin, elevated serum LDH (p=0.01) and mixed cellularity (p=0.01 compared to nodular sclerosis). However, there was no correlation with leukocytosis or lymphocytopenia. At a cutoff of 150 μg/L (almost the median), the 5-year FFS was 85% vs. 67% for patients with lower and higher SF levels (p=0.0005). If a gender-based median cutoff was adopted (high levels above the median of each gender), the results were similar (84% vs. 68%, p=0.0006). At the published cutoff of 350 μg/L only 21% of patients had high SF levels and the difference in the outcome was less pronounced (79% vs. 64%; p=0.01). In both early (ΙΑ/ΙΙΑ) and advanced (IB, IIB-IV) stages, SF ≥150 μg/L provided an 8-9% absolute difference in 5-year FFS, which was not however statistically significant (p=0.18 and p=0.16). In multivariate analysis, SF ≥150 μg/L was an independent prognostic factor (p=0.04; HR=1.79) along with advanced stage (p<0.001; HR=2.66), when adjusted for B-symptoms, anemia, LDH and gender. Further adjustment for CRP or ESR did not result to any meaningful alteration of the magnitude of the HR. However, the significance of SF became marginal if stage IV was used instead of “advanced stage”. In models containing SF levels, B-symptoms and IPS, SF displaced IPS.
Conclusion
Elevated SF levels may be an independent prognostic factor in HL treated with ABVD or equivalent regimens ± RT after adjustment for other important variables, including B-symptoms, anemia, ESR and CRP. However, larger patient series are needed in order to extract safe conclusions and determine the optimal cutoff.
Session topic: E-poster
Abstract: E1142
Type: Eposter Presentation
Background
Cytokine-driven inflammatory processes dominate the clinical and laboratory expression of HL, especially in advanced stages. Serum ferritin (SF) levels increase in the context of “acute phase reaction” along with fibrinogen, ESR, cerulloplasmin, haptoglobins etc. Although SF elevations are a well known feature of HL, their prognostic significance has not been adequately evaluated. Recently, Fernandes-Alvarez et al reported that elevated SF levels (>350 μg/L) were an independent prognostic factor in 173 optimally treated patients with classical HL (Leuk Lymphoma 2015).
Aims
To evaluate the prognostic significance of SF levels in a large series of patients with HL treated with ABVD or similar chemotherapy with or without radiotherapy (ABVD±RT).
Methods
We evaluated 309 pts with HL, treated with ABVD or equivalents (±RT), who had available data for SF levels. Median age was 33 yrs (15-87), 54% of patients were male, 34% had B-symptoms, 17% had stage IV disease, 50% had advanced stage (IB,IIB,III,IV), 33% had IPS ≥3, 67% nodular sclerosis histology and 19% mixed cellularity. Failure-free survival (FFS) was defined as time between treatment initiation and toxic death, failure to achieve remission requiring switch to salvage therapy, relapse after remission or last follow-up; deaths in remission of unrelated causes were not counted as events.
Results
Median follow-up of currently alive patients was 41 months. The median SF levels were 149 μg/L (range 6.6-6709.0, interquartile range; IQR 63.9-316.5). As expected, SF levels were lower in females than males (medians 70.6 vs. 240.2, p<0.001). Increased SF levels were highly correlated (p<0.001) with older age, advanced stage, increased IPS and markers of systemic disturbance (B-symptoms, anemia, ESR, CRP, low serum albumin), as well as with beta2-microglobulin, elevated serum LDH (p=0.01) and mixed cellularity (p=0.01 compared to nodular sclerosis). However, there was no correlation with leukocytosis or lymphocytopenia. At a cutoff of 150 μg/L (almost the median), the 5-year FFS was 85% vs. 67% for patients with lower and higher SF levels (p=0.0005). If a gender-based median cutoff was adopted (high levels above the median of each gender), the results were similar (84% vs. 68%, p=0.0006). At the published cutoff of 350 μg/L only 21% of patients had high SF levels and the difference in the outcome was less pronounced (79% vs. 64%; p=0.01). In both early (ΙΑ/ΙΙΑ) and advanced (IB, IIB-IV) stages, SF ≥150 μg/L provided an 8-9% absolute difference in 5-year FFS, which was not however statistically significant (p=0.18 and p=0.16). In multivariate analysis, SF ≥150 μg/L was an independent prognostic factor (p=0.04; HR=1.79) along with advanced stage (p<0.001; HR=2.66), when adjusted for B-symptoms, anemia, LDH and gender. Further adjustment for CRP or ESR did not result to any meaningful alteration of the magnitude of the HR. However, the significance of SF became marginal if stage IV was used instead of “advanced stage”. In models containing SF levels, B-symptoms and IPS, SF displaced IPS.
Conclusion
Elevated SF levels may be an independent prognostic factor in HL treated with ABVD or equivalent regimens ± RT after adjustment for other important variables, including B-symptoms, anemia, ESR and CRP. However, larger patient series are needed in order to extract safe conclusions and determine the optimal cutoff.
Session topic: E-poster
Type: Eposter Presentation
Background
Cytokine-driven inflammatory processes dominate the clinical and laboratory expression of HL, especially in advanced stages. Serum ferritin (SF) levels increase in the context of “acute phase reaction” along with fibrinogen, ESR, cerulloplasmin, haptoglobins etc. Although SF elevations are a well known feature of HL, their prognostic significance has not been adequately evaluated. Recently, Fernandes-Alvarez et al reported that elevated SF levels (>350 μg/L) were an independent prognostic factor in 173 optimally treated patients with classical HL (Leuk Lymphoma 2015).
Aims
To evaluate the prognostic significance of SF levels in a large series of patients with HL treated with ABVD or similar chemotherapy with or without radiotherapy (ABVD±RT).
Methods
We evaluated 309 pts with HL, treated with ABVD or equivalents (±RT), who had available data for SF levels. Median age was 33 yrs (15-87), 54% of patients were male, 34% had B-symptoms, 17% had stage IV disease, 50% had advanced stage (IB,IIB,III,IV), 33% had IPS ≥3, 67% nodular sclerosis histology and 19% mixed cellularity. Failure-free survival (FFS) was defined as time between treatment initiation and toxic death, failure to achieve remission requiring switch to salvage therapy, relapse after remission or last follow-up; deaths in remission of unrelated causes were not counted as events.
Results
Median follow-up of currently alive patients was 41 months. The median SF levels were 149 μg/L (range 6.6-6709.0, interquartile range; IQR 63.9-316.5). As expected, SF levels were lower in females than males (medians 70.6 vs. 240.2, p<0.001). Increased SF levels were highly correlated (p<0.001) with older age, advanced stage, increased IPS and markers of systemic disturbance (B-symptoms, anemia, ESR, CRP, low serum albumin), as well as with beta2-microglobulin, elevated serum LDH (p=0.01) and mixed cellularity (p=0.01 compared to nodular sclerosis). However, there was no correlation with leukocytosis or lymphocytopenia. At a cutoff of 150 μg/L (almost the median), the 5-year FFS was 85% vs. 67% for patients with lower and higher SF levels (p=0.0005). If a gender-based median cutoff was adopted (high levels above the median of each gender), the results were similar (84% vs. 68%, p=0.0006). At the published cutoff of 350 μg/L only 21% of patients had high SF levels and the difference in the outcome was less pronounced (79% vs. 64%; p=0.01). In both early (ΙΑ/ΙΙΑ) and advanced (IB, IIB-IV) stages, SF ≥150 μg/L provided an 8-9% absolute difference in 5-year FFS, which was not however statistically significant (p=0.18 and p=0.16). In multivariate analysis, SF ≥150 μg/L was an independent prognostic factor (p=0.04; HR=1.79) along with advanced stage (p<0.001; HR=2.66), when adjusted for B-symptoms, anemia, LDH and gender. Further adjustment for CRP or ESR did not result to any meaningful alteration of the magnitude of the HR. However, the significance of SF became marginal if stage IV was used instead of “advanced stage”. In models containing SF levels, B-symptoms and IPS, SF displaced IPS.
Conclusion
Elevated SF levels may be an independent prognostic factor in HL treated with ABVD or equivalent regimens ± RT after adjustment for other important variables, including B-symptoms, anemia, ESR and CRP. However, larger patient series are needed in order to extract safe conclusions and determine the optimal cutoff.
Session topic: E-poster
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