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Efficacy and Toxicity of Intrathecal Liposomal Cytarabine in First-line Therapy of Childhood Acute Lymphoblastic Leukemia

Levinsen, Mette ; Harila-Saari, Arja ; Grell, Kathrine ; Jonsson, Olafur Gisli ; Taskinen, Mervi ; Abrahamsson, Jonas ; Vettenranta, Kim ; Åsberg, Ann ; Risteli, Juha and Heldrup, Jesper LU , et al. (2016) In Journal of Pediatric Hematology/Oncology 38(8). p.602-609
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... (More)

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.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Lymphoblastic Leukemia, Childhood, Intrathecal Liposomal Cytarabine
in
Journal of Pediatric Hematology/Oncology
volume
38
issue
8
pages
602 - 609
publisher
Lippincott Williams & Wilkins
external identifiers
  • scopus:84984620250
  • pmid:27571129
  • wos:000388015600020
ISSN
1077-4114
DOI
10.1097/MPH.0000000000000642
language
English
LU publication?
yes
id
adb654a4-b2ac-4da0-890f-88772851ac31
date added to LUP
2016-09-21 11:32:21
date last changed
2025-10-19 21:04:36
@article{adb654a4-b2ac-4da0-890f-88772851ac31,
  abstract     = {{<p>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.</p>}},
  author       = {{Levinsen, Mette and Harila-Saari, Arja and Grell, Kathrine and Jonsson, Olafur Gisli and Taskinen, Mervi and Abrahamsson, Jonas and Vettenranta, Kim and Åsberg, Ann and Risteli, Juha and Heldrup, Jesper and Schmiegelow, Kjeld}},
  issn         = {{1077-4114}},
  keywords     = {{Lymphoblastic Leukemia; Childhood; Intrathecal Liposomal Cytarabine}},
  language     = {{eng}},
  month        = {{08}},
  number       = {{8}},
  pages        = {{602--609}},
  publisher    = {{Lippincott Williams & Wilkins}},
  series       = {{Journal of Pediatric Hematology/Oncology}},
  title        = {{Efficacy and Toxicity of Intrathecal Liposomal Cytarabine in First-line Therapy of Childhood Acute Lymphoblastic Leukemia}},
  url          = {{http://dx.doi.org/10.1097/MPH.0000000000000642}},
  doi          = {{10.1097/MPH.0000000000000642}},
  volume       = {{38}},
  year         = {{2016}},
}