Contributions
Abstract: PB1474
Type: Publication Only
Session title: Bone marrow failure syndromes incl. PNH - Clinical
Background
Idiopathic aplastic anemia (AA) is a rare entity characterized by reduced bone marrow cellularity and consequent pancytopenia due to an immune destruction of the hematopoietic stem cells. Currently there are no defined prognostic scores and therapeutic decision is based on disease severity [according to Camitta’s criteria (CC)] and patient’s fitness.
Aims
Assessment of prognostic factors in AA.
Methods
Unicentric retrospective analysis of patients (pts) diagnosed with AA between 2008 and 2019. Cox proportional hazard regression analysis was used to analyze factors affecting overall survival (OS) and overall response rate (ORR). OS obtained using the Kaplan-Meyer method was compared by the log-rank test. P<0,05 were considered statistically significant.
Results
41 pts diagnosed – 37% male, median age at diagnosis 59 years (18-83 years). No cytogenetic abnormalities were identified and 11 pts had a concomitant paroxysmal nocturnal hemoglobinuria clone [PNH – expression defect >0,1% in ≥2 markers (CD55, CD59, CD16, CD24, CD14) in 2 distinct hematopoietic cell lines]. According to CC, 22 % were classified as moderate AA, 42% severe and 36% very severe.
Six pts under 40 years had a matched sibling donor and underwent allogeneic stem cell transplantation as first line treatment - all of then achieved a complete remission (CR).
Twenty-two pts were treated with immunosuppressive therapy [16 antithymocyte globulin (ATG) + cyclosporine (CsA) and 6 CsA], 3 eltrombopag monotherapy and 8 supportive care only. Two pts did not require therapeutic intervention. ORR in non-transplanted pts was 60%. Although ORR was not statistically different between groups, it appears to be superior with ATG+CsA (75% vs 33% CsA vs 33% eltrombopag; p=NS), with inferior outcomes in pts ≥60 years (33% vs 54%; p=0,047; HR 3,22). Regarding ATG source, ORR was superior with horse vs rabbit origin (89% vs 57%; p=0,017; HR 7,07). In non-transplanted pts, only 3 achieved CR, all treated with ATG+CsA. Macrocytosis (MCV>97fL, excluding vitamin deficit) was associated with superior ORR (40% vs 88%; p=0,042; HR 7,07). Also normal LDH at diagnosis was associated with superior ORR (p=0,019; HR 5,52).
Treatment response is one of the main factors influencing OS - pts with ORR had a superior OS (p<0,001). Median OS of pts with treatment response was 70 months vs 4 months in pts without response vs 1,5 months in pts on supportive care only. There were also differences on OS between pts without treatment response and pts only on supportive care (p=0,023). The presence of PNH clone is also associated with superior OS (p=0,049). Age ≥60 years had a negative impact on OS (p<0,001).
Regarding the CC, only absolute neutrophil count (ANC) <0,5x109/L had a significant impact on OS in both univariate (p=0,009; HR 3,92) and multivariate analysis (p=0,018; HR 4,02), with a negative impact.
Currently, 53,7% of pts are alive. The main cause of death was infection (63%).
No other variable significantly affected prognosis.
Conclusion
Age ≥60 years and ANC <0.5x109/L negatively affected OS. Since ANC was the only statistically significant component of CC to have an impact on OS (pts with low ANC might have a high rate of infection), raises questions regarding the statistical power of the different CC, that maybe should be reviewed.
Treatment response is associated with favorable OS, with macrocytosis and normal LDH appearing associated with a superior ORR. Also the presence of PNH clone is associated with a superior OS.
More robust studies are needed to validate these prognostic factors.
Keyword(s): Aplastic anemia, Prognostic factor
Abstract: PB1474
Type: Publication Only
Session title: Bone marrow failure syndromes incl. PNH - Clinical
Background
Idiopathic aplastic anemia (AA) is a rare entity characterized by reduced bone marrow cellularity and consequent pancytopenia due to an immune destruction of the hematopoietic stem cells. Currently there are no defined prognostic scores and therapeutic decision is based on disease severity [according to Camitta’s criteria (CC)] and patient’s fitness.
Aims
Assessment of prognostic factors in AA.
Methods
Unicentric retrospective analysis of patients (pts) diagnosed with AA between 2008 and 2019. Cox proportional hazard regression analysis was used to analyze factors affecting overall survival (OS) and overall response rate (ORR). OS obtained using the Kaplan-Meyer method was compared by the log-rank test. P<0,05 were considered statistically significant.
Results
41 pts diagnosed – 37% male, median age at diagnosis 59 years (18-83 years). No cytogenetic abnormalities were identified and 11 pts had a concomitant paroxysmal nocturnal hemoglobinuria clone [PNH – expression defect >0,1% in ≥2 markers (CD55, CD59, CD16, CD24, CD14) in 2 distinct hematopoietic cell lines]. According to CC, 22 % were classified as moderate AA, 42% severe and 36% very severe.
Six pts under 40 years had a matched sibling donor and underwent allogeneic stem cell transplantation as first line treatment - all of then achieved a complete remission (CR).
Twenty-two pts were treated with immunosuppressive therapy [16 antithymocyte globulin (ATG) + cyclosporine (CsA) and 6 CsA], 3 eltrombopag monotherapy and 8 supportive care only. Two pts did not require therapeutic intervention. ORR in non-transplanted pts was 60%. Although ORR was not statistically different between groups, it appears to be superior with ATG+CsA (75% vs 33% CsA vs 33% eltrombopag; p=NS), with inferior outcomes in pts ≥60 years (33% vs 54%; p=0,047; HR 3,22). Regarding ATG source, ORR was superior with horse vs rabbit origin (89% vs 57%; p=0,017; HR 7,07). In non-transplanted pts, only 3 achieved CR, all treated with ATG+CsA. Macrocytosis (MCV>97fL, excluding vitamin deficit) was associated with superior ORR (40% vs 88%; p=0,042; HR 7,07). Also normal LDH at diagnosis was associated with superior ORR (p=0,019; HR 5,52).
Treatment response is one of the main factors influencing OS - pts with ORR had a superior OS (p<0,001). Median OS of pts with treatment response was 70 months vs 4 months in pts without response vs 1,5 months in pts on supportive care only. There were also differences on OS between pts without treatment response and pts only on supportive care (p=0,023). The presence of PNH clone is also associated with superior OS (p=0,049). Age ≥60 years had a negative impact on OS (p<0,001).
Regarding the CC, only absolute neutrophil count (ANC) <0,5x109/L had a significant impact on OS in both univariate (p=0,009; HR 3,92) and multivariate analysis (p=0,018; HR 4,02), with a negative impact.
Currently, 53,7% of pts are alive. The main cause of death was infection (63%).
No other variable significantly affected prognosis.
Conclusion
Age ≥60 years and ANC <0.5x109/L negatively affected OS. Since ANC was the only statistically significant component of CC to have an impact on OS (pts with low ANC might have a high rate of infection), raises questions regarding the statistical power of the different CC, that maybe should be reviewed.
Treatment response is associated with favorable OS, with macrocytosis and normal LDH appearing associated with a superior ORR. Also the presence of PNH clone is associated with a superior OS.
More robust studies are needed to validate these prognostic factors.
Keyword(s): Aplastic anemia, Prognostic factor