High Risk Langerhans Cell Histiocytosis in Children: The role of salvage in improving the outcome. A single center experience.

Abstract Background: In pediatric multi-system high risk organs (RO+) Langerhans cell histiocytosis (LCH), failing 1st line treatment has the highest mortality. Hereby we aim to present the outcome of salvage whether due to disease progression (DP) at end of induction or afterwards reactivation (REA). Sixty-seven RO+ LCH patients, treated between mid-2007 and end 2019 were retrospectively analyzed. They were subjected to the LCH III protocol era, having 1st line intermediate dose methotrexate induction (ID MTX) but without salvage by 2-Cda based regimen (2-CdABR) and that of LCH IV protocol without ID MTX but with 2-CdABR salvage. Results: Twenty-two patients showed DP. Of them 9 received 2-CdABR where 5 patients survived in better status. All the remaining 13 not receiving 2-CdABR died. Otherwise, 20 patients showed REA (RO+ mode n=12). Out of those 8 patients receiving 2-CdABR for REA RO+ mode, only one survived in better status. The overall survival (OS) of those undergoing DP was 27% CI 14-54 versus REA 67% CI 49-93 p 0.004. OS of DP with 2-CdABR was 56% CI=31-97.7 versus without 8 % CI 2-51, p<0.001. While OS of REA with 2-CdABR was 38% CI=13-100 versus without 74 % CI 53-100 p value 0.7. Conclusion: 2-CdABR rescued DP RO+LCH in relation to regimen without. Its impact on REA remains controversial in relation to other salvage regimen.