Contributions
Abstract: PB1827
Type: Publication Only
Background
Acquired Aplastic Anemia(AAA) is a rare bone marrow failure syndrome characterized by peripheral blood pancytopenia and marrow aplasia, probably caused by an immune-mediated destruction of hematopoietic stem and progenitor cells. Treatment includes hematopoietic stem-cell transplantation (HSCT), particularly by a matched sibling donor or immunosuppressive therapy(IST) with anti-thymocyte globulin(ATG) and cyclosporine A(CSA). Eltrombopag(ELT), a small, oral, non-peptide thrombopoietin receptor agonist has been shown to improve trilineage hematopoiesis and was recently approved as front-line treatment for AA in adults.
Aims
We report the therapeutic approach of children with AAA, treated in our Department in the last 5years.
Methods
Sixteen children (10males/6females) of mean age 8.7 (range:2-16years) were diagnosed with severe AAA since 2012. Causative agents or concurrent events included treatment with NSAIDs(1/16), infuenza virus infection(1/16), autoimmune hepatitis(1/16), transaminasemia of unknown etiology(2/16). Diagnosis was established by bone marrow aspirate and biopsy. Other bone marrow failure syndromes, either inherited (Fanconi anemia, Shwachman-Diamond syndrome) or acquired (Paroxysmal Nocturnal Hemoglobinuria) and hypoplastic myelodysplastic syndromes were excluded.
Results
Should a fully-matched sibling donor be available, patient underwent HSCT (3 patients). One patient received autologous cord blood, after standard HSCT preparatory regimen. The remaining 12 patients were treated with standard IST. ELT was added to IST as an off-label treatment, after approval from regulatory authorities in 11 patients. It was initiated on day 0, ≤4weeks or >4weeks post IST in 3,6 and 2patients respectively. ELT was given at a starting dose between 25-150mg/d depending on age/weight of the patient and it was further adjusted for platelet count >100,000 and <150,000/mm3 (max dose 150mg/d).
All 4 patients having received HSCT as first line treatment achieved complete remission. Of the patients treated with IST, 1 patient is still under ELT treatment showing progressive improvement of peripheral blood values 4 months post IST, 8 patients are in remission after receiving ELT treatment for a mean time of 10.7 months. Treatment with ELT was well tolerated and there was no evidence of clonal evolution or marrow fibrosis. The remaining 3patients (including the one that did not receive ELT) failed IST, and subsequently underwent MUD-HSCT (3, 4 and 18 months post IST, respectively), with fatal outcome in 2 and severe morbidity in 1 (renal failure).
Conclusion
Survival in severe AAA has remarkably improved due to early therapeutic interventions (allo-HSCT or immunosuppressive therapy) and improved supportive care. This small series of children with AAA underlines the option of new effective, well-tolerated modalities including autologous cord blood transplantation and adding ELT in IST, and the possible significant mortality/morbidity of MUD when used as a 2nd line therapy. ELT seems to enhance tri-linear recovery in children, in a manner similar to the one observed in adults with AA. Long-term-follow-up remains important to identify possible late complications (clonal evolution, leukemia or autoimmunity).
Session topic: 12. Bone marrow failure syndromes incl. PNH - Clinical
Keyword(s): Aplastic anemia, HSCT, Immunosuppressive therapy, Thrombopoietin (TPO)
Abstract: PB1827
Type: Publication Only
Background
Acquired Aplastic Anemia(AAA) is a rare bone marrow failure syndrome characterized by peripheral blood pancytopenia and marrow aplasia, probably caused by an immune-mediated destruction of hematopoietic stem and progenitor cells. Treatment includes hematopoietic stem-cell transplantation (HSCT), particularly by a matched sibling donor or immunosuppressive therapy(IST) with anti-thymocyte globulin(ATG) and cyclosporine A(CSA). Eltrombopag(ELT), a small, oral, non-peptide thrombopoietin receptor agonist has been shown to improve trilineage hematopoiesis and was recently approved as front-line treatment for AA in adults.
Aims
We report the therapeutic approach of children with AAA, treated in our Department in the last 5years.
Methods
Sixteen children (10males/6females) of mean age 8.7 (range:2-16years) were diagnosed with severe AAA since 2012. Causative agents or concurrent events included treatment with NSAIDs(1/16), infuenza virus infection(1/16), autoimmune hepatitis(1/16), transaminasemia of unknown etiology(2/16). Diagnosis was established by bone marrow aspirate and biopsy. Other bone marrow failure syndromes, either inherited (Fanconi anemia, Shwachman-Diamond syndrome) or acquired (Paroxysmal Nocturnal Hemoglobinuria) and hypoplastic myelodysplastic syndromes were excluded.
Results
Should a fully-matched sibling donor be available, patient underwent HSCT (3 patients). One patient received autologous cord blood, after standard HSCT preparatory regimen. The remaining 12 patients were treated with standard IST. ELT was added to IST as an off-label treatment, after approval from regulatory authorities in 11 patients. It was initiated on day 0, ≤4weeks or >4weeks post IST in 3,6 and 2patients respectively. ELT was given at a starting dose between 25-150mg/d depending on age/weight of the patient and it was further adjusted for platelet count >100,000 and <150,000/mm3 (max dose 150mg/d).
All 4 patients having received HSCT as first line treatment achieved complete remission. Of the patients treated with IST, 1 patient is still under ELT treatment showing progressive improvement of peripheral blood values 4 months post IST, 8 patients are in remission after receiving ELT treatment for a mean time of 10.7 months. Treatment with ELT was well tolerated and there was no evidence of clonal evolution or marrow fibrosis. The remaining 3patients (including the one that did not receive ELT) failed IST, and subsequently underwent MUD-HSCT (3, 4 and 18 months post IST, respectively), with fatal outcome in 2 and severe morbidity in 1 (renal failure).
Conclusion
Survival in severe AAA has remarkably improved due to early therapeutic interventions (allo-HSCT or immunosuppressive therapy) and improved supportive care. This small series of children with AAA underlines the option of new effective, well-tolerated modalities including autologous cord blood transplantation and adding ELT in IST, and the possible significant mortality/morbidity of MUD when used as a 2nd line therapy. ELT seems to enhance tri-linear recovery in children, in a manner similar to the one observed in adults with AA. Long-term-follow-up remains important to identify possible late complications (clonal evolution, leukemia or autoimmunity).
Session topic: 12. Bone marrow failure syndromes incl. PNH - Clinical
Keyword(s): Aplastic anemia, HSCT, Immunosuppressive therapy, Thrombopoietin (TPO)