Format

Send to

Choose Destination
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.

Author information

1
Department of Paediatric Oncology, Haematology and Clinical Immunology, University Children's Hospital, Medical Faculty, Heinrich Heine University, Duesseldorf, Germany.
2
Department of Paediatrics, University Hospital Schleswig-Holstein, Kiel, Germany.
3
Clinic of Paediatric Haematology and Oncology, Medical Centre, Hamburg-Eppendorf, Germany.
4
Department of General Paediatrics, Oncology/Haematology, University Children's Hospital, Tuebingen, Germany.
5
Department of Paediatric Oncology/Haematology, Erasmus MC-Sophia Children's Hospital, Rotterdam, the Netherlands.
6
Department of Paediatrics and Adolescent Medicine, University Medical Centre, Ulm, Germany.
7
Department of Paediatrics, University Hospital, Frankfurt, Germany.
8
Department of Paediatric Oncology, Haematology and Immunology, Klinikum Stuttgart, Olgahospital, Germany.
9
Paediatric Haematology and Oncology, University Children's Hospital Muenster, Muenster, Germany.
10
Department of General Paediatrics, Haematology/Oncology, Klinikum Oldenburg, Germany.
11
Department of Paediatric Oncology, Haematology, BMT, Charité University Medicine, Berlin, Germany.

Abstract

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.

KEYWORDS:

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

PMID:
28771662
DOI:
10.1111/bjh.14877
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Wiley
Loading ...
Support Center