Severe, reversible nelarabine‐induced neuropathy and myelopathy

Alberti, Paola; Parma, Matteo; Pioltelli, Pietro; Pogliani, Enrico Maria; Terruzzi, Elisabetta; Stasia, Alessandra; Doni, Elisa; Cecchetti, Caterina; Cavaletti, Guido

doi:10.1111/jns.12173

Cited by 7 publications

(11 citation statements)

References 8 publications

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“…The ease with which it crosses the blood-brain barrier 6 supports the hypothesis suggested by authors such as Papayannidis et al 7 that, under certain unknown circumstances, a selective destruction of the dorsal spinal cord could occur. Other authors such as Alberti et al 8 or Lalayanni et al 9 postulate a potential autoimmune aetiology like Guillain-Barr e syndrome, given the similarity of the signs and symptoms. Table 1 shows the 14 cases that have been published describing the neurotoxicity produced by nelarabine.…”

Section: Discussionmentioning

confidence: 99%

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Nelarabine-associated myelopathy in a patient with acute lymphoblastic leukaemia: Case report

Amer-Salas

González-Morcillo

Rodríguez-Camacho

et al. 2020

J Oncol Pharm Pract

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Introduction Nelarabine is a purine analogue approved for the treatment of patients with T-cell lymphoblastic lymphoma and T-cell acute lymphoblastic leukaemia (T-ALL) that have relapsed or are refractory to two previous chemotherapy regimens. Adverse reactions to nelarabine include neurological toxicity, the pathophysiological mechanisms of which are unknown, although the administration of intrathecal therapy at therapeutic doses given concomitantly with high-dose systemic chemotherapy that crosses the blood–brain barrier may potentiate neurotoxicity. Case report We report a case of a 29-year-old woman with a diagnosis of relapsed T-ALL who developed severe myelopathy and polyneuropathy of toxic origin that led to paraplegia, upper-limb paresis, and dysautonomia after the first cycle of nelarabine. Management and outcome Rehabilitation and pharmacological treatments were initiated early, but no evidence of a significant clinical change was obtained. Discussion Neurotoxicity is a dose-dependent side effect of nelarabine. It is therefore important to consider previously administered neurotoxic drugs before using nelarabine and to monitor patients closely so as to be able to act promptly in case of toxicity. In accordance with the data obtained and based on the Naranjo algorithm, the adverse reaction could be considered possible.

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Section: Discussionmentioning

confidence: 99%

“…No treatment was given or specified in five of the cases reviewed. 11,14 Among the nine patients who did receive therapy, five received corticosteroids, [7][8][9]15,16 Asparaginase IV Figure 1. Chemotherapy regimens administered.…”

Section: Discussionmentioning

confidence: 99%

Nelarabine-associated myelopathy in a patient with acute lymphoblastic leukaemia: Case report

Amer-Salas

González-Morcillo

Rodríguez-Camacho

et al. 2020

J Oncol Pharm Pract

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“…Nelarabine, a purine nucleoside analogue used in lymphoblastic T‐cell lymphoma, can cause severe neurotoxicity, mostly presenting with acute polyradiculoneuritis. This side effect is more likely occurring upon intrathecal administration …”

Section: Chemotherapy‐induced Neurotoxicitymentioning

confidence: 99%

“…This side effect is more likely occurring upon intrathecal administration. 126,127 Finally, peripheral nervous system involvement in course of chronic graft-versus-host disease (cGvHD), a major side effect of allo- with mixed large and small fibers neuropathies, the latter associated with pain.…”

Section: Vinka Alkaloids (Vincristine Vinblastine Vinorelbine and mentioning

confidence: 99%

Peripheral nervous system involvement in lymphomas

Briani

Visentin

Campagnolo

et al. 2019

J Peripheral Nervous Sys

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The peripheral nervous system may be involved at any stage in the course of lymphoproliferative diseases. The different underlying mechanisms include neurotoxicity secondary to chemotherapy, direct nerve infiltration (neurolymphomatosis), infections, immune‐mediated, paraneoplastic or metabolic processes and nutritional deficiencies. Accordingly, the clinical features are heterogeneous and depend on the localization of the damage (ganglia, roots, plexi, and peripheral nerves) and on the involved structures (myelin, axon, and cell body). Some clinical findings, such a focal or diffuse involvement, symmetric or asymmetric pattern, presence of pain may point to the correct diagnosis. Besides a thorough medical history and neurological examination, neurophysiological studies, cerebrospinal fluid analysis, nerve biopsy (in selected patients with suspected lymphomatous infiltration) and neuroimaging techniques (magnetic resonance neurography and nerve ultrasound) may be crucial for a proper diagnostic workup.

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“…This is certainly not the case for relapsed and/or refractory (r/r) B-cell acute lymphoblastic leukemia (B-ALL) patients, whose life expectancy has increased considerably in the last years after the introduction of anti-CD22 antibodies, bi-specific T-cell engagers (BITEs) and, lately, chimeric antigen receptors (CARs). Although nelarabine, a cytotoxic DNA damaging agent, has improved the survival of T-ALL relapsing patients [ 45 , 46 , 47 ], its dose-limiting toxicity [ 48 , 49 , 50 ], together with the absence of alternatives, underscore the need for new targeted therapies. However, the shared expression of surface markers between normal and leukemic T cells has limited the development of new targeted immunotherapies against T-cell malignancies and particularly, against T-ALL.…”

Section: Introductionmentioning

confidence: 99%

Facts and Challenges in Immunotherapy for T-Cell Acute Lymphoblastic Leukemia

Bayón-Calderón

Toribio

González-García

2020

IJMS

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T-cell acute lymphoblastic leukemia (T-ALL), a T-cell malignant disease that mainly affects children, is still a medical challenge, especially for refractory patients for whom therapeutic options are scarce. Recent advances in immunotherapy for B-cell malignancies based on increasingly efficacious monoclonal antibodies (mAbs) and chimeric antigen receptors (CARs) have been encouraging for non-responding or relapsing patients suffering from other aggressive cancers like T-ALL. However, secondary life-threatening T-cell immunodeficiency due to shared expression of targeted antigens by healthy and malignant T cells is a main drawback of mAb—or CAR-based immunotherapies for T-ALL and other T-cell malignancies. This review provides a comprehensive update on the different immunotherapeutic strategies that are being currently applied to T-ALL. We highlight recent progress on the identification of new potential targets showing promising preclinical results and discuss current challenges and opportunities for developing novel safe and efficacious immunotherapies for T-ALL.

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Severe, reversible nelarabine‐induced neuropathy and myelopathy

Cited by 7 publications

References 8 publications

Nelarabine-associated myelopathy in a patient with acute lymphoblastic leukaemia: Case report

Nelarabine-associated myelopathy in a patient with acute lymphoblastic leukaemia: Case report

Peripheral nervous system involvement in lymphomas

Facts and Challenges in Immunotherapy for T-Cell Acute Lymphoblastic Leukemia

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