title: Efficacy and Toxicity of Intrathecal Liposomal Cytarabine in First-line Therapy of Childhood Acute Lymphoblastic Leukemia.
abstract: We investigated efficacy and toxicity of replacing conventional triple (cytarabine, methotrexate, and hydrocortisone) intrathecal therapy (TIT) with liposomal cytarabine during maintenance therapy among 40 acute lymphoblastic leukemia patients. Twenty-eight of 29 patients in the TIT arm received TIT and 9/11 in the liposomal cytarabine arm received liposomal cytarabine. Arachnoiditis occurred in all initial 5 patients given liposomal cytarabine and intrathecal prednisolone succinate. Subsequently liposomal cytarabine was given with systemic dexamethasone. Neurotoxicity occurred at 6/27 liposomal cytarabine administrations with concomitant dexamethasone (22%). More liposomal cytarabine-treated patients experienced neurotoxicity in relation to intrathecal therapy during at least 1 cycle compared with TIT-treated patients (6/9 [67%] vs. 3/28 [11%], P=0.002). Apart from intermittent lower extremity sensory pain in 1 liposomal cytarabine-treated patient, no permanent adverse neurological sequelae were observed. In intention-to-treat analysis, projected 5-year event-free survival (pEFS-5y) was borderline higher for patients in the liposomal cytarabine arm compared with the TIT arm (1.0 vs. 0.69, P=0.046). However, pEFS-5y and projected 5-year relapse-free survival did not differ signficantly between patients treated with liposomal cytarabine or TIT (1.0 vs. 0.73, P=0.10; 1.0 vs. 0.76, P=0.12). Larger prospective trials are needed to explore whether liposomal cytarabine should be used as first-line prevention of relapse.
authors: *Department of Paediatrics and Adolescent Medicine, The University Hospital Rigshospitalet ‡Section of Biostatistics, Department of Public Health ‡‡The Institute of Clinical medicine, The Faculty of Medicine, University of Copenhagen, Copenhagen, Denmark †Department of Pediatrics, Astrid Lindgrens Hospital, Stockholm ¶Department of Pediatrics, Institution of Clinical Sciences, Sahlgrenska University Hospital, Gothenburg ††Department of Pediatrics, Skåne University Hospital, Lund, Sweden §Department of Pediatrics, Landspitali University Hospital, Reykjavík, Iceland ∥Division of Hematology-Oncology and Stem Cell Transplantation, Children and Adolescents, Helsinki **Department of Clinical Chemistry, Institute of Diagnostics, University of Oulu, Oulu, Finland #Department of Pediatrics, St Olavs Hospital, Trondheim University Hospital, Trondheim, Norway, NY.
authors: Mette
authors: M
authors: Levinsen
authors: Arja
authors: A
authors: Harila-Saari
authors: Kathrine
authors: K
authors: Grell
authors: Olafur Gisli
authors: OG
authors: Jonsson
authors: Mervi
authors: M
authors: Taskinen
authors: Jonas
authors: J
authors: Abrahamsson
authors: Kim
authors: K
authors: Vettenranta
authors: Ann
authors: A
authors: Åsberg
authors: Juha
authors: J
authors: Risteli
authors: Jesper
authors: J
authors: Heldrup
authors: Kjeld
authors: K
authors: Schmiegelow
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D003561:Cytarabine / Q000008:administration & dosage* / Q000633:toxicity; D003907:Dexamethasone / Q000008:administration & dosage; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007223:Infant; D007278:Injections, Spinal / Q000009:adverse effects; D008081:Liposomes / Q000627:therapeutic use; D060046:Maintenance Chemotherapy / Q000379:methods; D008297:Male; D020258:Neurotoxicity Syndromes / Q000209:etiology; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000150:complications / Q000188:drug therapy*; D012537:Scandinavian and Nordic Countries
chemical_list: D008081:Liposomes; D003561:Cytarabine; D003907:Dexamethasone