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The combination of clofarabine, etoposide, and cyclophosphamide shows limited efficacy as a bridge to transplant for children with refractory acute leukemia : results of a monitored prospective study

Toporski, Jacek LU ; Król, Ladislav LU orcid ; Dykes, Josefina LU ; Håkansson, Yvonne ; Pronk, Cornelis LU and Turkiewicz, Dominik LU (2021) In Pediatric Hematology and Oncology 38(3). p.216-226
Abstract

Clofarabine has been shown to effectively induce remission in children with refractory leukemia. We conducted a prospective trial (clinicval.trials.gov NCT01025778) to explore the use of clofarabine-based chemotherapy as a bridge-to-transplant approach. Children with refractory acute leukemia were enrolled to receive two induction courses of clofarabine, etoposide, and cyclophosphamide (CloEC). Responding patients were scheduled for T-cell depleted haploidentical hematopoietic stem cell transplantation (HSCT). The primary objective was to improve survival by achieving sufficient disease control to enable stem cell transplantation. Secondary objectives were to evaluate safety and toxicity. Seven children with active disease entered the... (More)

Clofarabine has been shown to effectively induce remission in children with refractory leukemia. We conducted a prospective trial (clinicval.trials.gov NCT01025778) to explore the use of clofarabine-based chemotherapy as a bridge-to-transplant approach. Children with refractory acute leukemia were enrolled to receive two induction courses of clofarabine, etoposide, and cyclophosphamide (CloEC). Responding patients were scheduled for T-cell depleted haploidentical hematopoietic stem cell transplantation (HSCT). The primary objective was to improve survival by achieving sufficient disease control to enable stem cell transplantation. Secondary objectives were to evaluate safety and toxicity. Seven children with active disease entered the study. Two children responded to induction courses and underwent transplantation. Five children did not respond to induction: one died in progression after the first course; two received off-protocol chemotherapy and were transplanted; and two succumbed to progressive leukemia. All transplanted children engrafted and no acute skin graft-versus-host disease > grade I was observed. One child is alive and well 7.5 years after the first CloEC course. One child developed fulminant adenovirus hepatitis and died in continuous complete remission 7 months after start of induction. Two children relapsed and died 6.5 and 7.5 months after enrollment. Infection was the most common toxicity. CloEC can induce responses in some patients with refractory acute leukemia but is highly immunosuppressive, resulting in substantial risk of life-threatening infections. In our study, haploidentical HSCT was feasible with sustained engraftment. No clinically significant organ toxicity was observed. Also, repeating CloEC probably does not increase the chance of achieving remission.

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publishing date
type
Contribution to journal
publication status
published
subject
keywords
Clofarabine, haploidentical stem cell transplantation, pediatric, prospective trial, refractory acute leukemia
in
Pediatric Hematology and Oncology
volume
38
issue
3
pages
216 - 226
publisher
Hemisphere Pub. Corp.
external identifiers
  • pmid:33150834
  • scopus:85095823757
ISSN
0888-0018
DOI
10.1080/08880018.2020.1838012
language
English
LU publication?
no
id
60799539-c2ec-480e-a63d-4c854d5e783c
date added to LUP
2020-11-26 14:30:40
date last changed
2024-04-03 19:18:39
@article{60799539-c2ec-480e-a63d-4c854d5e783c,
  abstract     = {{<p>Clofarabine has been shown to effectively induce remission in children with refractory leukemia. We conducted a prospective trial (clinicval.trials.gov NCT01025778) to explore the use of clofarabine-based chemotherapy as a bridge-to-transplant approach. Children with refractory acute leukemia were enrolled to receive two induction courses of clofarabine, etoposide, and cyclophosphamide (CloEC). Responding patients were scheduled for T-cell depleted haploidentical hematopoietic stem cell transplantation (HSCT). The primary objective was to improve survival by achieving sufficient disease control to enable stem cell transplantation. Secondary objectives were to evaluate safety and toxicity. Seven children with active disease entered the study. Two children responded to induction courses and underwent transplantation. Five children did not respond to induction: one died in progression after the first course; two received off-protocol chemotherapy and were transplanted; and two succumbed to progressive leukemia. All transplanted children engrafted and no acute skin graft-versus-host disease &gt; grade I was observed. One child is alive and well 7.5 years after the first CloEC course. One child developed fulminant adenovirus hepatitis and died in continuous complete remission 7 months after start of induction. Two children relapsed and died 6.5 and 7.5 months after enrollment. Infection was the most common toxicity. CloEC can induce responses in some patients with refractory acute leukemia but is highly immunosuppressive, resulting in substantial risk of life-threatening infections. In our study, haploidentical HSCT was feasible with sustained engraftment. No clinically significant organ toxicity was observed. Also, repeating CloEC probably does not increase the chance of achieving remission.</p>}},
  author       = {{Toporski, Jacek and Król, Ladislav and Dykes, Josefina and Håkansson, Yvonne and Pronk, Cornelis and Turkiewicz, Dominik}},
  issn         = {{0888-0018}},
  keywords     = {{Clofarabine; haploidentical stem cell transplantation; pediatric; prospective trial; refractory acute leukemia}},
  language     = {{eng}},
  number       = {{3}},
  pages        = {{216--226}},
  publisher    = {{Hemisphere Pub. Corp.}},
  series       = {{Pediatric Hematology and Oncology}},
  title        = {{The combination of clofarabine, etoposide, and cyclophosphamide shows limited efficacy as a bridge to transplant for children with refractory acute leukemia : results of a monitored prospective study}},
  url          = {{http://dx.doi.org/10.1080/08880018.2020.1838012}},
  doi          = {{10.1080/08880018.2020.1838012}},
  volume       = {{38}},
  year         = {{2021}},
}