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Editorials
malignant clonal hematopoietic diseases, which are rele- vant events affecting event-free survival after 6 months, would contribute considerably to predicting long-term outcomes.
The age-dependent association between response and absolute lymphocyte counts in the study by Zaimoku et al. is an interesting but not fully understood finding. The
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question of why lower absolute lymphocyte counts in children below 10 years predict complete response, while the reverse is true in older children and adults remains unanswered. A confirmatory study would be needed to validate the conflicting results. These paradoxical results remind us of another study in which pediatric patients with very SAA treated with IST showed unexpectedly
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Figure 1. Survival outcomes of patients with severe aplastic anemia treated with immunosuppressive therapy or hematopoietic stem cell transplantation and a treatment algorithm. (A) Comparison of overall survival (OS) and event-free survival (EFS) of patients with severe aplastic anemia (SAA) 30 years of age and younger treated for SAA with immunosuppressive therapy (IST) with or without granulocyte colony-stimulating factor (from unpublished data of the dataset of a randomized study5). Events were defined as refractoriness to first IST, relapse of SAA, development of clinical paroxysmal nocturnal hemoglobinuria or transformation into a myelodysplastic syndrome or acute leukemia. OS at 15 years is 89% and EFS 27% There is a great divergence between OS and EFS, meaning that children and young adults treated with IST, despite an excellent overall survival, still have a substantial number of complications later in life. These patients could, therefore, be consid- ered as candidates for an alternative donor hematopoietic cell transplantation (HCT) if no matched sibling donor is available. (B, C) Survival outcomes in terms of OS (B) and EFS (C) following upfront-unrelated HCT in children with SAA. The divergence of OS and EFS is much less in patients treated with HCT than in those treated with IST (Figure from Dufour C et al.8). (D) The algorithm for first-line treatment adapted from the recommendations of the European Blood and Marrow Transplant Severe Aplastic Anemia Working Party (SAA-WP).10 Treatment with eltrombopag has been added in red, since it is not yet officially in the guideline. According to the recommendations of the SAA-WP, patients <20 years) could be considered for first-line HCT with a matched unrelated donor (MUD) if the donor is available within 2 to 3 months. The pretreatment predictive values discussed in the study by Zaimoku et al.4 could be helpful for decision-making. Indeed, patients with factors predict- ing an unfavorable response to IST could be the patients considered for first-line transplantation from a MUD. HSCT: hematopoietic stem cell transplantation; SE: standard error; MSD: matched sibling donor; ATG: antithymocyte globulin; CSA: cyclosporine A; MTX: methotrexate; hATG: horse antithymocyte globulin; EPAG: eltrom- bopag; BMT: bone marrow transplantation.
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