Neuroophthalmological side effects following intrathecal administration of liposomal cytarabine for central nervous system prophylaxis in three adolescents with acute myeloid leukaemia

Abstract

Three adolescents with central nervous system (CNS) negative acute myeloid leukaemia (AML) refused cranial irradiation for CNS prophylaxis. Instead, these patients received four doses of 50 mg of intrathecal (IT) liposomal cytarabine on day 1, 15, 43 and 71 of maintenance therapy. Corticosteroids were given to prevent chemical arachnoiditis. All patients developed bilateral papilloedema after the third or fourth dose of liposomal cytarabine, local side effects were observed in two patients. Under prolonged dexamethasone therapy, side effects resolved completely. As reversible neuroophthalmological side effects caused by intrathecal liposomal cytarabine can also be observed under low-dose maintenance therapy in patients with CNS negative AML, it should be used with caution in children and adolescents.

Phase 2 study of intrathecal, long‐acting liposomal cytarabine in the prophylaxis of lymphomatous meningitis in human immunodeficiency virus‐related non‐Hodgkin lymphoma

“…31 There is only limited experience in the prophylactic setting in patients with aggressive lymphoma in the general population, whereas some data have been published in patients with acute lymphocytic or myeloid leukemia. 39,46,47 Meningeal involvement in patients with HIV-NHL is common, and it confers a dismal prognosis; therapy …”

Intrathecal Liposomal Cytarabine in Relapsed or Refractory Infant and Pediatric Leukemias: The Children's Hospital of Philadelphia Experience and Review of the Literature

“…Reports of ITlipAC as prophylaxis or consolidation therapy show similarly pervasive toxicities with the 50-mg dose in children and adolescents, 14,18 whereas a report using the 35-mg dose in 1 patient did not identify toxicity. 17 Benesch et al, 9 did not report use of prophylactic DEX or earlier history of CNS lesion, and all 3 children described developed some neurotoxicity attributable to ITlipAC.…”

“…Adults and children receiving ITlipAC for solid tumors or for CNS prophylaxis or consolidation of remission of leukemia were excluded. 13,14,17,18 Results of a Phase I pediatric ITlipAC trial 7 are summarized in the results section; however, as this study includes children with both brain tumors and leukemic meningitis and does not give specific details about the clinical course of individual patients, results from this paper are not included in the composite table or analysis. …”

Liposomal cytarabine is effective and tolerable in the treatment of central nervous system relapse of acute lymphoblastic leukemia and very aggressive lymphoma

“…22,23 It is often impossible to distinguish whether this syndrome is due to subclinical leukemic infiltration of the optical nerve or due to toxicity. It may respond to steroids with complete recovery but also to further chemotherapy.…”

“…In addition, several cases of cauda equina or conus medullaris syndrome were reported. [23][24][25] This syndrome may also respond to steroids and be completely reversible. In one study, in which the affected patients had a history of spinal cord surgery or subarachnoid hemorrhage, the authors speculated that a disturbance of cerebrospinal fluid flow may be one possible explanation for increased lumbar toxicity.…”