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Outcome of Children With Hypodiploid Acute Lymphoblastic Leukemia : A Retrospective Multinational Study

Pui, Ching-Hon ; Rebora, Paola ; Schrappe, Martin ; Attarbaschi, Andishe ; Baruchel, Andre ; Basso, Giuseppe ; Cavé, Hélène ; Elitzur, Sarah ; Koh, Katsuyoshi and Liu, Hsi-Che , et al. (2019) In Journal of Clinical Oncology 37(10). p.770-779
Abstract

PURPOSE: We determined the prognostic factors and utility of allogeneic hematopoietic cell transplantation among children with newly diagnosed hypodiploid acute lymphoblastic leukemia (ALL) treated in contemporary clinical trials.

PATIENTS AND METHODS: This retrospective study collected data on 306 patients with hypodiploid ALL who were enrolled in the protocols of 16 cooperative study groups or institutions between 1997 and 2013. The clinical and biologic characteristics, early therapeutic responses as determined by minimal residual disease (MRD) assessment, treatment with or without MRD-stratified protocols, and allogeneic transplantation were analyzed for their impact on outcome.

RESULTS: With a median follow-up of 6.6... (More)

PURPOSE: We determined the prognostic factors and utility of allogeneic hematopoietic cell transplantation among children with newly diagnosed hypodiploid acute lymphoblastic leukemia (ALL) treated in contemporary clinical trials.

PATIENTS AND METHODS: This retrospective study collected data on 306 patients with hypodiploid ALL who were enrolled in the protocols of 16 cooperative study groups or institutions between 1997 and 2013. The clinical and biologic characteristics, early therapeutic responses as determined by minimal residual disease (MRD) assessment, treatment with or without MRD-stratified protocols, and allogeneic transplantation were analyzed for their impact on outcome.

RESULTS: With a median follow-up of 6.6 years, the 5-year event-free survival rate was 55.1% (95% CI, 49.3% to 61.5%), and the 5-year overall survival rate was 61.2% (95% CI, 55.5% to 67.4%) for the 272 evaluable patients. Negative MRD at the end of remission induction, high hypodiploidy with 44 chromosomes, and treatment in MRD-stratified protocols were associated with a favorable prognosis, with a 5-year event-free survival rate of 75% (95% CI, 66.0% to 85.0%), 74% (95% CI, 61.0% to 89.0%), and 62% (95% CI, 55.0% to 69.0%), respectively. After exclusion of patients with high hypodiploidy with 44 chromosomes and adjustment for waiting time to transplantation and for covariables in a Poisson model, disease-free survival did not differ significantly ( P = .16) between the 42 patients who underwent transplantation and the 186 patients who received chemotherapy only, with an estimated 5-year survival rate of 59% (95% CI, 46.5% to 75.0%) versus 51.5% (95% CI, 44.7% to 59.4%), respectively. Transplantation produced no significant impact on outcome compared with chemotherapy alone, especially among the subgroup of patients who achieved a negative MRD status upon completion of remission induction.

CONCLUSION: MRD-stratified treatments improved the outcome for children with hypodiploid ALL. Allogeneic transplantation did not significantly improve outcome overall and, in particular, for patients who achieved MRD-negative status after induction.

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Contribution to journal
publication status
published
subject
in
Journal of Clinical Oncology
volume
37
issue
10
pages
10 pages
publisher
American Society of Clinical Oncology
external identifiers
  • pmid:30657737
  • scopus:85062218632
ISSN
0732-183X
DOI
10.1200/JCO.18.00822
language
English
LU publication?
yes
id
f199dbd5-3e8c-452c-bdde-4c914faf67e7
date added to LUP
2019-05-27 13:13:41
date last changed
2024-02-15 08:38:20
@article{f199dbd5-3e8c-452c-bdde-4c914faf67e7,
  abstract     = {{<p>PURPOSE: We determined the prognostic factors and utility of allogeneic hematopoietic cell transplantation among children with newly diagnosed hypodiploid acute lymphoblastic leukemia (ALL) treated in contemporary clinical trials.</p><p>PATIENTS AND METHODS: This retrospective study collected data on 306 patients with hypodiploid ALL who were enrolled in the protocols of 16 cooperative study groups or institutions between 1997 and 2013. The clinical and biologic characteristics, early therapeutic responses as determined by minimal residual disease (MRD) assessment, treatment with or without MRD-stratified protocols, and allogeneic transplantation were analyzed for their impact on outcome.</p><p>RESULTS: With a median follow-up of 6.6 years, the 5-year event-free survival rate was 55.1% (95% CI, 49.3% to 61.5%), and the 5-year overall survival rate was 61.2% (95% CI, 55.5% to 67.4%) for the 272 evaluable patients. Negative MRD at the end of remission induction, high hypodiploidy with 44 chromosomes, and treatment in MRD-stratified protocols were associated with a favorable prognosis, with a 5-year event-free survival rate of 75% (95% CI, 66.0% to 85.0%), 74% (95% CI, 61.0% to 89.0%), and 62% (95% CI, 55.0% to 69.0%), respectively. After exclusion of patients with high hypodiploidy with 44 chromosomes and adjustment for waiting time to transplantation and for covariables in a Poisson model, disease-free survival did not differ significantly ( P = .16) between the 42 patients who underwent transplantation and the 186 patients who received chemotherapy only, with an estimated 5-year survival rate of 59% (95% CI, 46.5% to 75.0%) versus 51.5% (95% CI, 44.7% to 59.4%), respectively. Transplantation produced no significant impact on outcome compared with chemotherapy alone, especially among the subgroup of patients who achieved a negative MRD status upon completion of remission induction.</p><p>CONCLUSION: MRD-stratified treatments improved the outcome for children with hypodiploid ALL. Allogeneic transplantation did not significantly improve outcome overall and, in particular, for patients who achieved MRD-negative status after induction.</p>}},
  author       = {{Pui, Ching-Hon and Rebora, Paola and Schrappe, Martin and Attarbaschi, Andishe and Baruchel, Andre and Basso, Giuseppe and Cavé, Hélène and Elitzur, Sarah and Koh, Katsuyoshi and Liu, Hsi-Che and Paulsson, Kajsa and Pieters, Rob and Silverman, Lewis B and Stary, Jan and Vora, Ajay and Yeoh, Allen and Harrison, Christine J and Valsecchi, Maria Grazia}},
  issn         = {{0732-183X}},
  language     = {{eng}},
  month        = {{04}},
  number       = {{10}},
  pages        = {{770--779}},
  publisher    = {{American Society of Clinical Oncology}},
  series       = {{Journal of Clinical Oncology}},
  title        = {{Outcome of Children With Hypodiploid Acute Lymphoblastic Leukemia : A Retrospective Multinational Study}},
  url          = {{http://dx.doi.org/10.1200/JCO.18.00822}},
  doi          = {{10.1200/JCO.18.00822}},
  volume       = {{37}},
  year         = {{2019}},
}