Nelarabine neurotoxicity with concurrent intrathecal chemotherapy: Case report and review of literature

Abstract

Severe nelarabine neurotoxicity in a patient who received concurrent intrathecal (IT) chemotherapy is reported. A 37-year-old Caucasian woman with a history of T-cell lymphoblastic lymphoma was admitted for relapsed disease. She was originally treated with induction chemotherapy followed by an autologous transplant. She developed relapsed disease 10 months later with leukemic involvement. She was re-induced with nelarabine 1500 mg/m(2) on days 1, 3, and 5 with 1 dose of IT cytarabine 100 mg on day 2 as central nervous system (CNS) prophylaxis. At the time of treatment, she was on continuous renal replacement therapy due to sequelae of tumor lysis syndrome (TLS). She tolerated therapy well, entered a complete remission, and recovered her renal function. She received a second cycle of nelarabine without additional IT prophylaxis one month later. A week after this second cycle, she noted numbness in her lower extremities. Predominantly sensory, though also motor and autonomic, peripheral neuropathy started in her feet, ascended proximally to the mid-thoracic region, and eventually included her distal upper extremities. A magnetic resonance imaging (MRI) of her spine demonstrated changes from C2 to C6 consistent with subacute combined degeneration. Nelarabine was felt to be the cause of her symptoms. Her neuropathy stabilized and showed slight improvement and ultimately received an unrelated, reduced-intensity allogeneic transplant while in complete remission, but relapsed disease 10 weeks later. She is currently being treated with best supportive care. To our knowledge, this is the first published case report of severe neurotoxicity caused by nelarabine in a patient who received concurrent IT chemotherapy.

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

“…Dat Ngo et al. 12 described a case in which neurotoxicity from nelarabine was developed following its use with concomitant intrathecal therapy. Currently, this combination is not described in the summary of product characteristics.…”

“…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, 7–9,15,16 five received intravenous immunoglobulins 8–10 (leading to clinical worsening following its administration in one of the cases 9 ), four underwent intensive rehabilitation, 7,9,12,16 two received vitamin supplements including vitamin B12, 9,15 and two were treated with therapeutic plasma exchange. 9,15 Our patient received corticosteroid therapy, intensive rehabilitation, therapeutic plasma exchange, and vitamin supplements with vitamins B12 and B6 for the treatment of neurotoxicity.…”

“…This led to a slight improvement of paraplegia which may have been more severe as a result of the meningitis that occurred during the Allo-HSCT. With regard to the degree of response in the other cases, a single case of reversible neuropathy, 16 one case of progression to irreversible paraplegia, 7 and three cases of improvement of neurological impairment 8,9,12 have been described. In the remaining nine cases, the neurological status was not specified.…”

ClinicaI Reversible Myelopathy in T-Cell Lymphoblastic Lymphoma Treated with Nelarabine and Radiotherapy: Report of a Case and Review of Literature of an Increasing Complication

“…In the report from Kawakami et al, an excess of nelarabine neurotoxicity (up to 50%) was detected after HLA-haploidentical SCT 11. In the recent paper from Ngo et al, concurrent administration of single dose intrathecal cytosine arabinoside was felt to exert an additive neurotoxic effect due to the close timing of administration to nelarabine 14. MRI findings, when reported, are superimposable resulting in T2-weighted and FLAIR hyperintensity predominantly at thoracic or cervical level.…”

Severe, reversible nelarabine‐induced neuropathy and myelopathy

“…Papayannidis et al (2010) and Gollard and Selco (2013) reported cases of irreversible paraplegia. Ngo et al (2014) reported severe nelarabine peripheral neurotoxicity in a patient who received concurrent intrathecal chemotherapy. A complete and long-term description was still missing and, in most cases, limited follow-up due to hematological disease progression, suggested it is irreversible.…”