Irreversible neurological defects in the lower extremities after haploidentical stem cell transplantation: Possible association with nelarabine

Abstract

Severe peripheral neuropathy and myelopathy are rare complications after stem cell transplantation (SCT). In our institution, seven patients of precursor T lymphoblastic leukemia/lymphoma without the central nervous involvement who had been treated by nelarabine to control their diseases received SCT from HLA-haploidentical familial donor (HLA-haploidentical SCT) with the conditioning regimen including highdose cytarabine (HDAC). Three of evaluable six patients developed irreversible paresthesia and muscle weakness in both lower extremities after neutrophil engraftment. The results of nerve conduction studies and short latency somatosensory evoked potentials suggested axonal neuropathy of both lower extremities in all three patients and myelopathy in two patients. Negative findings of PET-CT, and analyses of repeated cerebrospinal fluid samples and the bone marrow also indicated that tumor involvement was improbable. In all three patients, the symptoms worsened or persisted despite administration of corticosteroid and intravenous immunoglobulin. The high frequency of the neurological symptoms in our patients previously treated by nelarabine strongly suggested the association of the nelarabine use. Furthermore, the HLA-haploidentical SCT setting and the use of a potentially neurotoxic agent, HDAC might augment the neurotoxicity of nelarabine. It may be desirable that HLA-haploidentical SCT candidates avoid receiving nelarabine. Am.

Pediatric T‐ALL complicated by irreversible nelarabine neurotoxicity

“…Although brain MRI showed no abnormality, spinal MRI after the second round of NEL therapy showed a contiguous high‐intensity region in the dorsal column on T2‐weighted imaging (Fig. a–c), consistent with previous reports . No abnormality was detected in the CSF.…”

“…Frequent neurologic events due to NEL are headache, dizziness, somnolence, peripheral neuropathy, and seizures, but irreversible neurological events have also previously been reported . The symptoms were similar to those of the case presented here, including paresthesia, paraplegia, and bladder and bowel dysfunction, and worsened within a few weeks.…”

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

“…The vast majority also received radiotherapy as part of the planned treatment or in the conditioning regimen. 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.…”

“…To date, eleven cases of irreversible neurological defects in T-ALL patients treated with nelarabine have been described in the last 4 years,9–14 seven of these after stem cell transplantation (SCT) for T-LBL 10,11. Detailed clinical information on these previously reported cases are summarized in Table 1.…”

High-Dose Cyclophosphamide for the Treatment of Refractory T-Cell Acute Lymphoblastic Leukemia in Children

“…9,10 Furthermore, nelarabine is associated with significant risks; most notably severe neurotoxicity. [11][12][13][14] Over a 2-year period, we treated 5 patients with T-ALL (identified as refractory given persistence of disease at levels >0.01% despite multiple rounds of chemotherapy) using cyclophosphamide (CY) at much higher doses than utilized in conventional ALL protocols (2100 mg/m 2 /d on 2 consecutive days). Our decision to explore high-dose CY (HD-CY) as a therapeutic modality in these patients was based on several factors.…”