Ascending myelitis after intensive chemotherapy and radiation therapy in children with cranial parameningeal sarcoma

Abstract

In 1977, a program of early, wide‐field radiation therapy (RT) to the central nervous system and repeated lumbar intrathecal (IT) medications along with systemic chemotherapy was begun by the Intergroup Rhabdomyosarcoma Study (IRS) for patients younger than 21 years of age with cranial parameningeal sarcoma and a high risk of meningeal extension. From 1977 until 1987, 149 eligible patients with high‐risk cranial parameningeal sarcoma were enrolled in IRS trials. None had evidence of lower extremity or sphincter impairment at diagnosis. Five of the 149 (3.4%) had ascending myelitis at 5.5 to 9 months after the initiation of therapy, with loss of sphincter control and inability to walk; this progressed to severe flaccid quadriparesis and necessitated longterm ventilatory support in 4. All five had received vincristine, dactinomycin, cyclophosphamide, and doxorubicin; four also had received cisplatin and three also had received etoposide. All patients received 4770 to 5500 cGy to the primary tumor, and four patients received 3000 cGy of cranial RT. Three patients received cervical RT and two received spinal RT. The patients also received four to seven courses of IT methotrexate, hydrocortisone, and cytosine arabinoside. Three patients died: one after local tumor recurrence with central nervous system extension and two without known recurrence. In one of the latter patients, the results of an autopsy showed necrosis of the cervical spinal cord and caudal medulla. Although the exact cause of this complication is unclear, no additional cases have been reported to the IRS since the protocol was revised in 1987 to reduce the doses of the IT drugs and to limit them to four courses each. Cancer 1992; 69:1498‐1506.

Local Intracerebral Administration of Paclitaxel with the Paclimer® Delivery System: Toxicity Study in a Canine Model

“…Clinical studies using CEDD of paclitaxel showed a similar complication, which was attributed to leakage of paclitaxel into the subarachnoid space (29). Accidental intrathecal administration of other anti-microtubule agents has been shown to produce a wide range of complications and should be avoided (31,32).…”

The sequellae of chemo‐radiation therapy for head and neck cancer in children: Managing impaired growth, development, and other side effects

“…More ominous is the transverse myelopathy seen after intensive intrathecal chemotherapy for parameningeal rhabdomyosarcoma, which has resulted in devastating complications and death [9]. Raney et al report, however, that no additional cases have been seen after reducing the doses and number of cycles of the three intrathecal drugs used (methotrexate, hydrocortisone, and cytarabine) [9].…”

“…Raney et al report, however, that no additional cases have been seen after reducing the doses and number of cycles of the three intrathecal drugs used (methotrexate, hydrocortisone, and cytarabine) [9].…”

Neurotoxicity of Cancer Chemotherapy

“…4 The latency to onset of neurological symptoms is extremely variable, from within a few hours of the first intrathecal chemotherapy injection to several months after completion of a course of several injections. 54 Patients typically develop back or leg pain and a rapidly ascending flaccid paraparesis with a sensory level and bowel/bladder involvement. 53 The syndrome can occur with or without concomitant systemic chemotherapy or spinal irradiation.…”