Neurotoxic Side Effects In Children With Refractory Or Relapsed T-Cell Malignancies Treated With Nelarabine Based Therapy

The prognosis in children with refractory or relapsed (r/r) T-cell acute lymphoblastic leukaemia (T-ALL) or lymphoblastic lymphoma (T-LBL) is poor. Nelarabine (Ara-G) has successfully been used as salvage therapy in these children, but has been associated with significant, even fatal, neurotoxicities. We retrospectively analysed 52 patients with r/r T-ALL/T-LBL aged <= 19 years who were treated with Ara-G alone (n = 25) or in combination with cyclophosphamide and etoposide (n = 27). The majority of patients (45/52) received 1-2 cycles of Ara-G. Seventeen patients (32.7%) had refractory disease, 28 (53.8%) were in first relapse and 7 (13.5%) were in second relapse. A response to Ara-G was achieved in 20 patients and 15 (28.8%) were in remission at last follow-up. Twelve patients (23.1%) had neurotoxic adverse effects (neuro-AE) of any grade, of whom 7 (13.5%) developed neurotoxicity >= grade III. The most frequent neuro-AEs were peripheral motor neuropathy (19.2%), peripheral sensory neuropathy (11.5%) and seizures (9.6%). Three patients died of central neuro-AE after 1-2 cycles of combination therapy. Patients with neurotoxicity were significantly older (median 15.17 years) than those without (10.34 years, P = 0.017). No differences were observed between mono-and combination therapy concerning outcome and neuro-AE. The incidence of neuro-AE was not associated with concurrent intrathecal therapy or prior central nervous system irradiation.