| Added by | lklinares |
|---|---|
| Group name | EquipeLL |
| Item Type | Journal Article |
| Title | Dexamethasone in hyperleukocytic acute myeloid leukemia |
| Creator | Bertoli et al. |
| Author | Sarah Bertoli |
| Author | Muriel Picard |
| Author | Emilie Bérard |
| Author | Emmanuel Griessinger |
| Author | Clément Larrue |
| Author | Pierre Luc Mouchel |
| Author | François Vergez |
| Author | Suzanne Tavitian |
| Author | Edwige Yon |
| Author | Jean Ruiz |
| Author | Eric Delabesse |
| Author | Isabelle Luquet |
| Author | Laetitia Karine Linares |
| Author | Estelle Saland |
| Author | Martin Carroll |
| Author | Gwenn Danet-Desnoyers |
| Author | Audrey Sarry |
| Author | Françoise Huguet |
| Author | Jean Emmanuel Sarry |
| Author | Christian Récher |
| Abstract | Patients with acute myeloid leukemia and a high white blood cell count are at increased risk of early death and relapse. Because mediators of inflammation contribute to leukostasis and chemoresistance, dexamethasone added to chemotherapy could improve outcomes. This retrospective study evaluated the impact of adding or not adding dexamethasone to chemotherapy in a cohort of 160 patients with at least 50×109 white blood cells. In silico studies, primary samples, leukemic cell lines, and xenograft mouse models were used to explore the antileukemic activity of dexamethasone. There was no difference with respect to induction death rate, response, and infections between the 60 patients in the dexamethasone group and the 100 patients in the no dexamethasone group. Multivariate analysis showed that dexamethasone was significantly associated with improved relapse incidence (adjusted sub-HR: 0.30; 95% CI: 0.14-0.62; P=0.001), disease-free survival (adjusted HR: 0.50; 95% CI: 0.29-0.84; P=0.010), event-free survival (adjusted HR: 0.35; 95% CI: 0.21-0.58; P<0.001), and overall survival (adjusted HR: 0.41; 95% CI: 0.22-0.79; P=0.007). In a co-culture system, dexamethasone reduced the frequency of leukemic long-term culture initiating cells by 38% and enhanced the cytotoxicity of doxorubicin and cytarabine. In a patient-derived xenograft model treated with cytarabine, chemoresistant cells were enriched in genes of the inflammatory response modulated by dexamethasone. Dexamethasone also demonstrated antileukemic activity in NPM1-mutated samples. Dexamethasone may improve the outcome of acute myeloid leukemia patients receiving intensive chemotherapy. This effect could be due to the modulation of inflammatory chemoresistance pathways and to a specific activity in acute myeloid leukemia with NPM1 mutation. |
| Publication | Haematologica |
| Volume | 103 |
| Issue | 6 |
| Pages | 988-998 |
| Date | 06 2018 |
| Journal Abbr | Haematologica |
| Language | eng |
| DOI | 10.3324/haematol.2017.184267 |
| ISSN | 1592-8721 |
| Library Catalog | PubMed |
| Extra | PMID: 29519869 PMCID: PMC6058767 |
| Tags | Adolescent, Adult, Aged, Antineoplastic Agents, Hormonal, Dexamethasone, Drug Resistance, Neoplasm, Female, Gene Expression Regulation, Leukemic, Humans, Kaplan-Meier Estimate, Leukemia, Myeloid, Acute, Leukocytosis, Male, Middle Aged, Mutation, Nuclear Proteins, original, Prognosis, Recurrence, Remission Induction, Treatment Outcome, Young Adult |
| Date Added | 2024/12/03 - 09:12:56 |
| Date Modified | 2024/12/03 - 09:12:56 |
| Notes and Attachments | PubMed entry (Attachment) Texte intégral (Attachment) |
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