Complete paraplegia after Nelarabine treatment in a T‐cell acute lymphoblastic leukemia adult patient
Authors: Cristina Papayannidis, Ilaria Iacobucci, Maria Chiara Abbenante, Antonio Curti, Stefania Paolini, Sarah Parisi, Michele Baccarani, Giovanni Martinelli
Journal: American Journal of Hematology (2010)

A 30–year-old man was diagnosed with ALL T-lineage immunophenotype, (CD7+, CD13+, CD45+, MPO-), normal karyotype, with no CNS involvement (negative lumbar puncture) and treated with a cycle of induction chemotherapy, including Vincristine, L-Asparaginase, and Adriamycin, with complete morphological remission. Two consolidation cycles were then administered, followed by maintenance chemotherapy with oral 6-Mecaptopurine (6-MP) and Methotrexate (MTX). As a matched bone marrow donor was not detected, the patient could not receive a stem cells transplantation. Hence, as expected, three years after diagnosis, because of the development of hyperleukocytosis (WBC 22,500/mm3) a first relapse was documented, with the presence of translocation (5;14) in 30 out of 30 metaphases. The patient underwent four cycles of savage chemotherapy, obtaining a second complete morphologic and cytogenetic remission after which he was treated with steroids, MTX, and 6-MP, as maintenance. Six months later, a second relapse occurred, and he received a cycle of chemotherapy with Nelarabine at the adult standard dosage (1,500 mg/sqm/daily on days 1, 3, and 5), which was well-tolerated. The iatrogenic bone marrow aplasia was complicated by two febrile episodes, fully resolved with antibacterial therapy, and by liver toxicity (Grade III according to WHO classification) characterized by increased cytonecrosis indexes. As a complete remission was documented, 28 days later the patient received a second cycle of Nelarabine, at the same dosage. On the third day of therapy, the patient reported the onset of severe paresthesias in his legs, bilaterally, rapidly extended to the anterior abdominal wall and to the gluteus skin. Moreover, he revealed a significant defect in maintaining equilibrium and a reduced ability in walking. A neurologic detailed examination showed a strong-force defect, especially involving legs, and a severe difficulty in standing. Lasègue sign was negative, whereas Babinski sign was detected, bilaterally. Neither force nor sensitivity defects were found at his upper arms. Alterations of urinary and bowel functions were also reported. Based on the clinical suspicion of a massive spinal cord pressure, a lumbo-sacral MRI was immediately performed, which showed, at the level of the fifth dorsal vertebra, an alteration of the intra-marrow signal, with longitudinal extension of 2 cm, and anteroposterior and lateral diameter of 0.6 and 0.8 cm, respectively (Image 1). This radiological image was consistent with transverse acute myelitis; a lumbar puncture was performed, which was negative for both CNS leukemic and infective involvement, and for ischemic damage. Therefore, the patient received steroid intravenous therapy, with only a mild and transitory improvement of the paresthesias, and no change on equilibrium and autonomic defects. A MRI with an angiographic detailed study, repeated seven days later, showed no changes. These symptoms did not further improve despite intensive rehabilitation physiotherapy. The patient maintained complete morphologic remission for 8 months, without therapy. Having ruled out ischemic and hemorrhagic etiology, and a leukemic infiltration, the worsening of sensory and motor defects and the rapid loss of autonomic functions were most likely related to cumulative drug toxicity, mainly ascribable to the administration of Nelarabine. Nelarabine is a new purine analogue, approved by FDA for the treatment of patients with T-ALL and T-cell lymphoblastic lymphoma (T-LBL) whose disease has not responded to or has relapsed following at least two chemotherapy regimens. Neurologic toxicity is dose limiting for both pediatric and adult patients [1]. Major neurologic adverse events in adult population, usually include Grade I–II somnolence, dizziness, hypoesthesia, headache, paresthesia, and depressed level of consciousness. So far, rare cases of Grade III peripheral neurological disorders or ataxia have been described. Despite the high efficacy of Nelarabine [2], neurological toxicity should always be considered and carefully monitored during treatment. To the best of our knowledge, we have reported here the first case of a T-ALL patient with a lasting hematological response induced by Nelarabine, which was associated with severe and irreversible neurological toxicity, consistent with a complete paraplegia. Sagittal T2 image of the thoracic spine demonstrates abnormal hypointense marrow signal in the vertebral bodies consistent with leukemic infiltration. In addition, there is abnormal hyperintense T2 signal in the mid-thoracic spinal cord at T5 consistent with transverse myelitis (arrow).