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Br J Haematol. 2017 Oct;179(2):272-283. doi: 10.1111/bjh.14877. Epub 2017 Aug 2.

Neurotoxic side effects in children with refractory or relapsed T-cell malignancies treated with nelarabine based therapy.

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Department of Paediatric Oncology, Haematology and Clinical Immunology, University Children's Hospital, Medical Faculty, Heinrich Heine University, Duesseldorf, Germany.
Department of Paediatrics, University Hospital Schleswig-Holstein, Kiel, Germany.
Clinic of Paediatric Haematology and Oncology, Medical Centre, Hamburg-Eppendorf, Germany.
Department of General Paediatrics, Oncology/Haematology, University Children's Hospital, Tuebingen, Germany.
Department of Paediatric Oncology/Haematology, Erasmus MC-Sophia Children's Hospital, Rotterdam, the Netherlands.
Department of Paediatrics and Adolescent Medicine, University Medical Centre, Ulm, Germany.
Department of Paediatrics, University Hospital, Frankfurt, Germany.
Department of Paediatric Oncology, Haematology and Immunology, Klinikum Stuttgart, Olgahospital, Germany.
Paediatric Haematology and Oncology, University Children's Hospital Muenster, Muenster, Germany.
Department of General Paediatrics, Haematology/Oncology, Klinikum Oldenburg, Germany.
Department of Paediatric Oncology, Haematology, BMT, Charité University Medicine, Berlin, Germany.


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.


Ara-G; T-ALL; T-LBL; nelarabine; neurotoxicity

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