BENEFIT OF RITUXIMAB AS SECOND LINE TREATMENT CHOICE FOR AUTOIMMUNE HEMOLYTIC ANEMIA IN CHILDREN : A PROSPECTIVE FRENCH COHORT.
(Abstract release date: 05/19/16)
EHA Library. Ducassou S. 06/12/16; 135331; S837
Dr. Stéphane Ducassou
Contributions
Contributions
Abstract
Abstract: S837
Type: Oral Presentation
Presentation during EHA21: On Sunday, June 12, 2016 from 09:00 - 09:15
Location: Room H6
Background
Childhood autoimmune hemolytic anemia (AIHA) requires in 30-50% of cases immunosuppressive therapy for steroid resistance or prolonged dependence. Although there are no pediatric guidelines for the second line strategy, in small retrospective studies or rare controlled studies, rituximab appears to be indicated.
Aims
This prospective observational national study reports the practice, efficiency and tolerance of rituximab in non-selected children with isolated AIHA or AIHA in context of Evans syndrome (AIHA/ES).
Methods
For this study, all children under 18 years old, living in France, who had been treated, by rituximab for an AIHA, whatever the context was, between January 1, 2000 and December 31, 2012, registered in the OBS’CEREVANCE cohort, were included. The end point for analysis was December 31, 2013, ensuring more than 1 year’s follow-up for each patient. Response criteria were defined, relapse free survival (RFS) curves were provided, and tolerance was assessed from patient’s medical records.
Results
Sixty one children with AIHA were given rituximab, 375 mg/m²/dose for a median of 4 weekly doses. All patients had previously received steroids, 26 had received one to four supplementary line of treatment. The median age at rituximab initiation was 8.5 [0.3; 17.6] years. The median delay from diagnosis to rituximab was 9.9 [0.2; 153.1] months.With a median follow-up of 4 years (0.3 - 11) from rituximab initiation, 46 patients responded (75%), 40 complete response (CR) and 6 partial response (PR). 20 patients (43%) relapsed in a median delay of 10.8 (1.7-57.6) months after treatment by rituximab The proportion of relapses among responder patients was significantly lower in patient who were treated early after diagnosis (p=0.03). In all children rituximab allowed decrease of steroid therapy.Compared to AIHA/ES, in isolated AIHA, the proportion of CR was significantly higher (74% vs 54%, p=0.02), and RFS was significantly higher (p=0.04).Ten patients were aged less than one year at rituximab initiation. In this subgroup, the median time between diagnosis and rituximab initiation was 1.6 months, shorter than 12 months in the rest of the cohort (p=0.006). Seven patients responded (70%), 6 CR and RFS was 71%.Two children presented allergic reactions. No case of progressive multifocal leuco-encephalopathy was observed. A total of 40 children received IVIg replacement, whose duration was temporary in 31 and prolonged in 9. Five patients died and among them one severe sepsis associated with agranulocytosis could be reliable to rituximab therapy.
Conclusion
In our hands, in this large series of childhood AIHA, rituximab was a valuable second line treatment, allowing steroid withdrawal in 60-70% of cases, with 30% long term responders, even in infants, mainly in isolated AIHA and when it was precociously used. Two serious concerns on safety are abrupt severe neutropenia, and prolonged hypogammaglobulinemia: adequate screening of underlying primitive immune deficiency before treatment is mandatory.
Session topic: Transfusion Medicine
Keyword(s): Autoimmune hemolytic anemia (AIHA), Children, Rituximab
Type: Oral Presentation
Presentation during EHA21: On Sunday, June 12, 2016 from 09:00 - 09:15
Location: Room H6
Background
Childhood autoimmune hemolytic anemia (AIHA) requires in 30-50% of cases immunosuppressive therapy for steroid resistance or prolonged dependence. Although there are no pediatric guidelines for the second line strategy, in small retrospective studies or rare controlled studies, rituximab appears to be indicated.
Aims
This prospective observational national study reports the practice, efficiency and tolerance of rituximab in non-selected children with isolated AIHA or AIHA in context of Evans syndrome (AIHA/ES).
Methods
For this study, all children under 18 years old, living in France, who had been treated, by rituximab for an AIHA, whatever the context was, between January 1, 2000 and December 31, 2012, registered in the OBS’CEREVANCE cohort, were included. The end point for analysis was December 31, 2013, ensuring more than 1 year’s follow-up for each patient. Response criteria were defined, relapse free survival (RFS) curves were provided, and tolerance was assessed from patient’s medical records.
Results
Sixty one children with AIHA were given rituximab, 375 mg/m²/dose for a median of 4 weekly doses. All patients had previously received steroids, 26 had received one to four supplementary line of treatment. The median age at rituximab initiation was 8.5 [0.3; 17.6] years. The median delay from diagnosis to rituximab was 9.9 [0.2; 153.1] months.With a median follow-up of 4 years (0.3 - 11) from rituximab initiation, 46 patients responded (75%), 40 complete response (CR) and 6 partial response (PR). 20 patients (43%) relapsed in a median delay of 10.8 (1.7-57.6) months after treatment by rituximab The proportion of relapses among responder patients was significantly lower in patient who were treated early after diagnosis (p=0.03). In all children rituximab allowed decrease of steroid therapy.Compared to AIHA/ES, in isolated AIHA, the proportion of CR was significantly higher (74% vs 54%, p=0.02), and RFS was significantly higher (p=0.04).Ten patients were aged less than one year at rituximab initiation. In this subgroup, the median time between diagnosis and rituximab initiation was 1.6 months, shorter than 12 months in the rest of the cohort (p=0.006). Seven patients responded (70%), 6 CR and RFS was 71%.Two children presented allergic reactions. No case of progressive multifocal leuco-encephalopathy was observed. A total of 40 children received IVIg replacement, whose duration was temporary in 31 and prolonged in 9. Five patients died and among them one severe sepsis associated with agranulocytosis could be reliable to rituximab therapy.
Conclusion
In our hands, in this large series of childhood AIHA, rituximab was a valuable second line treatment, allowing steroid withdrawal in 60-70% of cases, with 30% long term responders, even in infants, mainly in isolated AIHA and when it was precociously used. Two serious concerns on safety are abrupt severe neutropenia, and prolonged hypogammaglobulinemia: adequate screening of underlying primitive immune deficiency before treatment is mandatory.
Session topic: Transfusion Medicine
Keyword(s): Autoimmune hemolytic anemia (AIHA), Children, Rituximab
Abstract: S837
Type: Oral Presentation
Presentation during EHA21: On Sunday, June 12, 2016 from 09:00 - 09:15
Location: Room H6
Background
Childhood autoimmune hemolytic anemia (AIHA) requires in 30-50% of cases immunosuppressive therapy for steroid resistance or prolonged dependence. Although there are no pediatric guidelines for the second line strategy, in small retrospective studies or rare controlled studies, rituximab appears to be indicated.
Aims
This prospective observational national study reports the practice, efficiency and tolerance of rituximab in non-selected children with isolated AIHA or AIHA in context of Evans syndrome (AIHA/ES).
Methods
For this study, all children under 18 years old, living in France, who had been treated, by rituximab for an AIHA, whatever the context was, between January 1, 2000 and December 31, 2012, registered in the OBS’CEREVANCE cohort, were included. The end point for analysis was December 31, 2013, ensuring more than 1 year’s follow-up for each patient. Response criteria were defined, relapse free survival (RFS) curves were provided, and tolerance was assessed from patient’s medical records.
Results
Sixty one children with AIHA were given rituximab, 375 mg/m²/dose for a median of 4 weekly doses. All patients had previously received steroids, 26 had received one to four supplementary line of treatment. The median age at rituximab initiation was 8.5 [0.3; 17.6] years. The median delay from diagnosis to rituximab was 9.9 [0.2; 153.1] months.With a median follow-up of 4 years (0.3 - 11) from rituximab initiation, 46 patients responded (75%), 40 complete response (CR) and 6 partial response (PR). 20 patients (43%) relapsed in a median delay of 10.8 (1.7-57.6) months after treatment by rituximab The proportion of relapses among responder patients was significantly lower in patient who were treated early after diagnosis (p=0.03). In all children rituximab allowed decrease of steroid therapy.Compared to AIHA/ES, in isolated AIHA, the proportion of CR was significantly higher (74% vs 54%, p=0.02), and RFS was significantly higher (p=0.04).Ten patients were aged less than one year at rituximab initiation. In this subgroup, the median time between diagnosis and rituximab initiation was 1.6 months, shorter than 12 months in the rest of the cohort (p=0.006). Seven patients responded (70%), 6 CR and RFS was 71%.Two children presented allergic reactions. No case of progressive multifocal leuco-encephalopathy was observed. A total of 40 children received IVIg replacement, whose duration was temporary in 31 and prolonged in 9. Five patients died and among them one severe sepsis associated with agranulocytosis could be reliable to rituximab therapy.
Conclusion
In our hands, in this large series of childhood AIHA, rituximab was a valuable second line treatment, allowing steroid withdrawal in 60-70% of cases, with 30% long term responders, even in infants, mainly in isolated AIHA and when it was precociously used. Two serious concerns on safety are abrupt severe neutropenia, and prolonged hypogammaglobulinemia: adequate screening of underlying primitive immune deficiency before treatment is mandatory.
Session topic: Transfusion Medicine
Keyword(s): Autoimmune hemolytic anemia (AIHA), Children, Rituximab
Type: Oral Presentation
Presentation during EHA21: On Sunday, June 12, 2016 from 09:00 - 09:15
Location: Room H6
Background
Childhood autoimmune hemolytic anemia (AIHA) requires in 30-50% of cases immunosuppressive therapy for steroid resistance or prolonged dependence. Although there are no pediatric guidelines for the second line strategy, in small retrospective studies or rare controlled studies, rituximab appears to be indicated.
Aims
This prospective observational national study reports the practice, efficiency and tolerance of rituximab in non-selected children with isolated AIHA or AIHA in context of Evans syndrome (AIHA/ES).
Methods
For this study, all children under 18 years old, living in France, who had been treated, by rituximab for an AIHA, whatever the context was, between January 1, 2000 and December 31, 2012, registered in the OBS’CEREVANCE cohort, were included. The end point for analysis was December 31, 2013, ensuring more than 1 year’s follow-up for each patient. Response criteria were defined, relapse free survival (RFS) curves were provided, and tolerance was assessed from patient’s medical records.
Results
Sixty one children with AIHA were given rituximab, 375 mg/m²/dose for a median of 4 weekly doses. All patients had previously received steroids, 26 had received one to four supplementary line of treatment. The median age at rituximab initiation was 8.5 [0.3; 17.6] years. The median delay from diagnosis to rituximab was 9.9 [0.2; 153.1] months.With a median follow-up of 4 years (0.3 - 11) from rituximab initiation, 46 patients responded (75%), 40 complete response (CR) and 6 partial response (PR). 20 patients (43%) relapsed in a median delay of 10.8 (1.7-57.6) months after treatment by rituximab The proportion of relapses among responder patients was significantly lower in patient who were treated early after diagnosis (p=0.03). In all children rituximab allowed decrease of steroid therapy.Compared to AIHA/ES, in isolated AIHA, the proportion of CR was significantly higher (74% vs 54%, p=0.02), and RFS was significantly higher (p=0.04).Ten patients were aged less than one year at rituximab initiation. In this subgroup, the median time between diagnosis and rituximab initiation was 1.6 months, shorter than 12 months in the rest of the cohort (p=0.006). Seven patients responded (70%), 6 CR and RFS was 71%.Two children presented allergic reactions. No case of progressive multifocal leuco-encephalopathy was observed. A total of 40 children received IVIg replacement, whose duration was temporary in 31 and prolonged in 9. Five patients died and among them one severe sepsis associated with agranulocytosis could be reliable to rituximab therapy.
Conclusion
In our hands, in this large series of childhood AIHA, rituximab was a valuable second line treatment, allowing steroid withdrawal in 60-70% of cases, with 30% long term responders, even in infants, mainly in isolated AIHA and when it was precociously used. Two serious concerns on safety are abrupt severe neutropenia, and prolonged hypogammaglobulinemia: adequate screening of underlying primitive immune deficiency before treatment is mandatory.
Session topic: Transfusion Medicine
Keyword(s): Autoimmune hemolytic anemia (AIHA), Children, Rituximab
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