Are Colony Stimulating Factors (G-CSF) Still Needed in Treatment of Severe Aplastic Anemia in Children?

Allogenic bone marrow transplantation is the first choice in children with severe acquired aplastic anemia (SAA), but if there is no matched sibling donor, the immunosuppressive therapy (IST) which consists of ATG combined with cyclosporine A, steroids and/or colony stimulating factors (G-CSF), is the best way of treatment.

In last two decades there was a trend to add G-CSF to combination of ATG and CSA. Nowadays there is much uncertainty about this practice. There are discussion whether it really reduces early infectious mortality. There are suggestions too, that long term using of G-CSF can play role in developing clonal disorders.

The aim of this study was to assess the influence of period of using colony stimulating factors for the event free survival (EFS), and progression free survival (PFS), infectious side effects, clonality and relapses in patients with SAA.

The group of 55 children with SAA and vSAA (23 girls and 32 boys,) were retrospectively analyzed. The median age of children was 10 years (range 6mth-17,5 years). IST (Thymoglobuline, steroids, CSA, and/or GSF-CS) was given according to the protocol of The European Blood and Marrow Transplant (EBMT) Severe Aplastic Anemia Working Party.G-CSF was administered at the dose of 5μg/kg/mc, in 52 patients. The median period of administration was 32 days (range 0–187 days)

The response to the treatment was assessed on 84, 112,180 and 360 day. Relative risk test and Kaplan–Meier estimator, the univariate analysis and multivariate Cox regression models, test were used to estimate the influence of the period of G-CSF therapy for EFS, PFS, relapse free survival, clonality, toxicity and other side effects in children with aplastic anemia

The 2- year probability of event free survival (EFS) was 71,52%. The 5 and 10 –year EFS was 57,7%. Progression free survival (PFS) was 66,53%, at 2 years and 59,13% at 5- and 10 years. The relapse rate was 1,81%. The 2-year probability of not having relapse was 87,68%. Relapse free survival was 75,16% at 5 and 10 years. There was 15 deaths (27,27%), 5 early and 10 late deaths. Infections were the main causes of death. There was one transformation to paroxysmal nocturnal haemoglobinuria (PNH) and no transformation to MDS or AML. There was no significant correlation between EFS, PFS and the duration of G-CSF treatment (p > 0,05 log rank). There was tendency for longer PFS and EFS in patient who had G-CSF administered for shorter period. Relative risk (RR) for patients who didn't receive G-CSF was connected with 28% lower infection rate. RR for children receiving

G-CSF for 1–10 days was 0,55.No infectious episodes were observed in children who were treated with G-CSF for 11 – 21 days. RR for patients treated from 21 to 28 day was 1,71. Patients who were given G-CSF for more than 28 days had RR=1,15. During the G-CSF therapy we observed muscular pains, and capillary leak syndrome, but these side effects didn't influence survival (p>0,05 log-rank)

The duration of G-CSF therapy has no impact on the survival (EFS, PFS), but it is a significant factor concerning infection rate. Colony stimulating factor shouldn't be routinely used. Period of administration should be as short as possible.

No relevant conflicts of interest to declare.