Page 11 - Haematologica May 2020

Editorials
or survival in SAA, they also provide reassurance that G- References
CSF does not worsen the already significant risk of clonal disease in the post-IST setting. Although their findings definitely do not support the routine use of G-CSF added to IST, they indicate that for high-risk patients with delayed cell count recovery or severe infections, G-CSF may be reasonably added to front-line IST without signif- icant concern for long-term consequences.
However, the most clinically significant findings from this trial have nothing to do with the original questions regarding the risks and benefits of G-CSF in SAA! Regardless of randomization, fully half of all surviving SAA patients experienced significant long-term complica- tions including not only clonal events and relapse, but an array of treatment-related morbidities such as osteonecrosis and kidney disease. Indeed, apart from relapse, non-hematologic complications were more com- mon than clinically relevant clonal progression: 13-16% had chronic kidney disease, with unsurprisingly a higher risk in those requiring prolonged cyclosporine therapy. Furthermore, younger age was not protective against long-term, treatment-related complications. These and prior data indicate that such complications will continue to compound throughout life, underscoring the impor- tance of well-informed initial treatment decisions and fur- ther supporting the recommendation for front-line allo- geneic SCT in children and younger adults, perhaps employing rapidly available haploidentical family donors given the progressively improving outcomes in the era of post-transplant treatment with cyclophosphamide.15
Finally, it is important to mention that in the current era, IST has begun to be augmented not with G-CSF, but instead with the thrombopoietin agonist eltrombopag. Unlike G-CSF, thrombopoietin can act directly on primi- tive HSPC, which express its receptor, MPL. Initial trials in patients with refractory SAA demonstrated the short- term safety and efficacy of this oral drug as a single agent.16,17 In a large but single-arm trial at our institution, the addition of eltombopag to IST resulted in improved overall response and complete response in comparison to those in a large historical cohort treated with IST alone.18 Despite these improved outcome measures, relapse appeared to be just as frequent, and assessment of the impact on clonal progression requires longer follow-up and results from the European ongoing randomized con- trolled trial of the addition of eltrombopag to IST are awaited. The report from Tichelli and colleagues pub- lished in this issue of Haematologica educates us regarding the necessity of very long-term and careful analyses of large numbers of patients to inform decisions regarding the best treatment approach for patients with SAA.
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