Hyperferritinemia at diagnosis predicts relapse and overall survival in younger AML patients with intermediate-risk cytogenetics

Lebon, Delphine; Vergez, François; Bertoli, Sarah; Harrivel, Véronique; Botton, Stéphane de; Micol, Jean-Baptiste; Marolleau, Jean‐Pierre; Récher, Christian

doi:10.1016/j.leukres.2015.05.001

Cited by 28 publications

(43 citation statements)

References 15 publications

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“…Thus, the AML‐associated elevation in serum ferritin is most likely induced by an underlying inflammatory state rather than alterations in the body's iron stores . We have previously shown that serum ferritin levels correlated with higher CRP levels in de novo AML patients . Although inflammation is a hallmark of cancer, its role has been neglected in AML in which other oncogenic pathways including transcriptional deregulations, sustained proliferative signaling, epigenetic, or metabolic alterations as well as deregulated splicing have been more deeply assessed .…”

Section: Discussionmentioning

confidence: 99%

“…27,28 We have previously shown that serum ferritin levels correlated with higher CRP levels in de novo AML patients. 7 Although inflammation is a hallmark of cancer, its role has been neglected in AML in which other oncogenic pathways including transcriptional deregulations, sustained proliferative signaling, epigenetic, or metabolic alterations as well as deregulated splicing have been more deeply assessed. 29,30 Yet, several aspects of inflammation could be exploited to increase our knowledge in AML pathophysiology and to expand therapeutic opportunities or prognostic markers as exempli- as a pro-inflammatory cytokine and induces NF-kB signaling.…”

Section: Discussionmentioning

confidence: 99%

“…We have recently reported that a high level of serum ferritin at diagnosis was associated with a poor overall survival (OS) in younger patients with de novo acute myeloid leukemia (AML) and intermediate cytogenetic risk . In these patients, the impact of hyperferritinemia was not related to post‐transfusion iron overload.…”

Section: Introductionmentioning

confidence: 99%

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Ferritin heavy/light chain (FTH1/FTL) expression, serum ferritin levels, and their functional as well as prognostic roles in acute myeloid leukemia

Bertoli

Paubelle²,

Bérard

et al. 2018

European J of Haematology

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Objectives We previously reported the prognostic value of serum ferritin in younger patients with intermediate‐risk acute myeloid leukemia (AML). The aims of this study were to confirm this finding in a larger cohort regardless of age and prognostic subgroups, to explore the expression and functional role of ferritin in AML cells as well as the regulation of serum ferritin levels in AML patients. Patients/Materials/Methods Serum ferritin levels at diagnosis were collected in a cohort of 525 patients treated by intensive chemotherapy. In silico, in vitro, and in vivo analyses were conducted to assess the pattern of expression and functional role of FTH1 and FTL in AML. Results We confirmed the independent prognostic value of serum ferritin. In transcriptomic databases, FTH1 and FTL were overexpressed in AML and leukemic stem cells compared to normal hematopoietic stem cells. The gene signature designed from AML patients overexpressing FTH1 revealed a significant enrichment in genes of the immune and inflammatory response including Nf‐KB pathway, oxidative stress, or iron pathways. This gene signature was enriched in cytarabine‐resistant AML cells in a patient‐derived xenograft model. FTH1 protein was also overexpressed in patient's samples and correlated with the in vitro cytotoxic activity of cytarabine. Lastly, we demonstrated that chemotherapy induced an inflammatory response including a significant increase in serum ferritin levels between day 1 and 8 of induction chemotherapy that was blocked by dexamethasone. Conclusion Ferritin is deregulated in most AML patients likely through inflammation, associated with chemoresistance, and could represent a new therapeutic target.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Ferritin heavy/light chain (FTH1/FTL) expression, serum ferritin levels, and their functional as well as prognostic roles in acute myeloid leukemia

Bertoli

Paubelle²,

Bérard

et al. 2018

European J of Haematology

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“…Hyperferritinemia is a poor risk factor in patients with hematologic malignancies, probably because of the adverse impact of body iron accumulation in transfusion-dependent patients 24252627. However, hyperferritinemia might also affect prognosis through mechanisms other than iron accumulation, because several studies have demonstrated that even patients with hyperferritinemia at diagnosis without prior transfusion have poor prognosis 2829. We could not perform a multivariate analysis because of the small study sample, so further study is necessary to elucidate the exact prognostic impact of baseline variables, such as serum ferritin, LDH, and BM blast percentage, and to identify patients that will likely benefit from decitabine treatment.…”

Section: Discussionmentioning

confidence: 99%

Decitabine as a First-Line Treatment for Older Adults Newly Diagnosed with Acute Myeloid Leukemia

et al. 2017

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PurposeDecitabine, a DNA hypomethylating agent, was recently approved for use in Korea for older adults with acute myeloid leukemia (AML) who are not candidates for standard chemotherapy. This study aimed to evaluate the role of decitabine as a first-line treatment for older adults with AML.Materials and MethodsTwenty-four patients with AML who received at least one course of decitabine (20 mg/m2/d intravenously for 5 days every 4 weeks) as a first-line therapy at Severance Hospital were evaluated retrospectively.ResultsThe median age of the patients was 73.5 years. The longest follow-up duration was 502 days. A total of 113 cycles of treatment were given to 24 patients, and the median number of cycles was four (range, 1–14). Thirteen patients dropped out because of death, no or loss of response, patient refusal, or transfer to another hospital. Twenty-one (87.5%) and 12 (50%) patients completed the second and fourth cycles, respectively, and responses to treatment were evaluated in 17. A complete response (CR) or CR with incomplete blood-count recovery was achieved in six (35.3%) patients, and the estimated median overall survival was 502 days. Ten patients developed grade >2 hematologic or non-hematologic toxicities. In univariate analysis, bone marrow blasts, lactate dehydrogenase, serum ferritin level, and bone marrow iron were significantly associated with response to decitabine.ConclusionFive-day decitabine treatment showed acceptable efficacy in older patients with AML who are unfit for conventional chemotherapy, with a CR rate 35.3% and about a median overall survival of 18 months.

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“…We recently reported that elevated fibrinogen levels were associated with adverse survival in newly diagnosed AML patients . Moreover, increased serum ferritin levels were predictive of adverse overall and relapse‐free survival in young intermediate‐risk AML patients and, also, in a cohort of AML patients when adjusting for CRP levels . Elevated pretreatment CRP and ferritin levels were positively associated with the incidence of systemic inflammation during anti‐leukemic induction chemotherapy .…”

Section: Introductionmentioning

confidence: 97%

Simple acute phase protein score to predict long‐term survival in patients with acute myeloid leukemia

Heini

Hugo

Berger

et al. 2019

Hematological Oncology

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High levels of acute phase reactants can be associated with adverse outcome in patients with various solid tumor types. For patients with acute myeloid leukemia (AML), this correlation is unknown. We retrospectively investigated the prognostic value of pretreatment acute phase protein levels in 282 consecutive newly diagnosed AML patients undergoing at least one cycle of intensive induction chemotherapy. We applied a new score integrating pre-treatment C-reactive protein (CRP), fibrinogen, and albumin levels termed the CFA ratio, and we stratified patients into two groups: Patients with a CFA ratio below 3.06 had decisively better progression-free (26.2 vs 7.7 months; P < .001), disease-free (56.4 vs 8.7 months; P < .001), and overall survival (61.2 vs 13.8 months; P < .001).

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Hyperferritinemia at diagnosis predicts relapse and overall survival in younger AML patients with intermediate-risk cytogenetics

Cited by 28 publications

References 15 publications

Ferritin heavy/light chain (FTH1/FTL) expression, serum ferritin levels, and their functional as well as prognostic roles in acute myeloid leukemia

Ferritin heavy/light chain (FTH1/FTL) expression, serum ferritin levels, and their functional as well as prognostic roles in acute myeloid leukemia

Decitabine as a First-Line Treatment for Older Adults Newly Diagnosed with Acute Myeloid Leukemia

Simple acute phase protein score to predict long‐term survival in patients with acute myeloid leukemia

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