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Incidence of subsequent malignancies after total body irradiation-based allogeneic HSCT in children with ALL - long-term follow-up from the prospective ALL-SCT 2003 trial

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Item Type:Article
Title:Incidence of subsequent malignancies after total body irradiation-based allogeneic HSCT in children with ALL - long-term follow-up from the prospective ALL-SCT 2003 trial
Creators Name:Eichinger, A. and Poetschger, U. and Glogova, E. and Bader, P. and Basu, O. and Beier, R. and Burkhardt, B. and Classen, C.F. and Claviez, A. and Corbacioglu, S. and Deubzer, H.E. and Greil, J. and Gruhn, B. and Güngör, T. and Kafa, K. and Kühl, J.S. and Lang, P. and Lange, B.S. and Meisel, R. and Müller, I. and Sauer, M.G. and Schlegel, P.G. and Schulz, A. and Stachel, D. and Strahm, B. and Wawer, A. and Peters, C. and Albert, M.H.
Abstract:Total body irradiation (TBI)-based conditioning is associated with superior leukemia-free survival in children with ALL undergoing HSCT. However, the risk for subsequent malignant neoplasms (SMN) remains a significant concern. We analyzed 705 pediatric patients enrolled in the prospective ALL-SCT-BFM-2003 trial and its subsequent registry. Patients >2 years received conditioning with TBI 12 Gy/etoposide (n = 558) and children ≤2 years of age or with contraindications for TBI received busulfan/cyclophosphamide/etoposide (n = 110). The 5- and 10-year cumulative incidence of SMN was 0.02 ± 0.01 and 0.13 ± 0.03, respectively. In total, 39 SMN (34 solid tumors, 5 MDS/AML) were diagnosed in 33 patients at a median of 5.8 years (1.7-13.4), exclusively in the TBI group. Of 33 affected patients, 21 (64%) are alive at a median follow-up of 5.1 years (0-9.9) after diagnosis of their first SMN. In univariate analysis, neither age at HSCT, donor type, acute GVHD, chronic GVHD, nor CMV constituted a significant risk factor for SMN. The only significant risk factor was TBI versus non-TBI based conditioning. This analysis confirms and quantifies the increased risk of SMN in children with ALL after conditioning with TBI. Future strategies to avoid TBI will need careful tailoring within prospective, controlled studies to prevent unfavorable outcomes.
Keywords:Acute Lymphocytic Leukaemia, Medical Research
Source:Leukemia
ISSN:0887-6924
Publisher:Nature Publishing Group
Date:12 September 2022
Official Publication:https://doi.org/10.1038/s41375-022-01693-z
PubMed:View item in PubMed

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