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Neurotoxic side effects in children with refractory or relapsed T‐cell malignancies treated with nelarabine based therapy
Author(s) -
Kuhlen Michaela,
Bleckmann Kirsten,
Möricke Anja,
Schrappe Martin,
Vieth Simon,
Escherich Gabriele,
Bronsema Annika,
Vonalt Annika,
Queudeville Ma,
Zwaan C. Michel,
Ebinger Martin,
Debatin KlausMichael,
Klingebiel Thomas,
Koscielniak Ewa,
Rossig Claudia,
Burkhardt Birgit,
Kolb Reinhard,
Eckert Cornelia,
Borkhardt Arndt,
Stackelberg Arend,
ChenSantel Christiane
Publication year - 2017
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/bjh.14877
Subject(s) - medicine , refractory (planetary science) , adverse effect , peripheral neuropathy , neurotoxicity , etoposide , cyclophosphamide , gastroenterology , salvage therapy , chemotherapy , surgery , toxicity , diabetes mellitus , physics , astrobiology , endocrinology
Summary 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.