scholarly journals Decitabine as salvage therapy for primary induction failure of acute myeloid leukemia

2017 ◽  
Vol 56 (8) ◽  
pp. 1120-1121 ◽  
Author(s):  
Pasquale Niscola ◽  
Benedetta Neri ◽  
Gianfranco Catalano ◽  
Luciana Morino ◽  
Marco Giovannini ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Salvage Therapy ◽  
Myeloid Leukemia ◽  
Primary Induction ◽  
Induction Failure ◽  
Acute Myeloid

scholarly journals NUP-98 Rearrangements Led to the Identification of Candidate Biomarkers for Primary Induction Failure in Pediatric Acute Myeloid Leukemia

2021 ◽  
Vol 22 (9) ◽  
pp. 4575
Author(s):  
Vincenza Barresi ◽  
Virginia Di Bella ◽  
Nellina Andriano ◽  
Anna Provvidenza Privitera ◽  
Paola Bonaccorso ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Mutational Analysis ◽  
Integrated Analysis ◽  
Induction Phase ◽  
Pediatric Acute Myeloid Leukemia ◽  
Expression Arrays ◽  
Primary Induction ◽  
Induction Failure ◽  
Acute Myeloid

Conventional chemotherapy for acute myeloid leukemia regimens generally encompass an intensive induction phase, in order to achieve a morphological remission in terms of bone marrow blasts (<5%). The majority of cases are classified as Primary Induction Response (PIR); unfortunately, 15% of children do not achieve remission and are defined Primary Induction Failure (PIF). This study aims to characterize the gene expression profile of PIF in children with Acute Myeloid Leukemia (AML), in order to detect molecular pathways dysfunctions and identify potential biomarkers. Given that NUP98-rearrangements are enriched in PIF-AML patients, we investigated the association of NUP98-driven genes in primary chemoresistance. Therefore, 85 expression arrays, deposited on GEO database, and 358 RNAseq AML samples, from TARGET program, were analyzed for “Differentially Expressed Genes” (DEGs) between NUP98+ and NUP98-, identifying 110 highly confident NUP98/PIF-associated DEGs. We confirmed, by qRT-PCR, the overexpression of nine DEGs, selected on the bases of the diagnostic accuracy, in a local cohort of PIF patients: SPINK2, TMA7, SPCS2, CDCP1, CAPZA1, FGFR1OP2, MAN1A2, NT5C3A and SRP54. In conclusion, the integrated analysis of NUP98 mutational analysis and transcriptome profiles allowed the identification of novel putative biomarkers for the prediction of PIF in AML.

Mitoxantrone and etoposide with or without intermediate dose cytarabine for the treatment of primary induction failure or relapsed acute myeloid leukemia

2012 ◽  
Vol 36 (4) ◽  
pp. 394-396 ◽  
Author(s):  
Steven M. Trifilio ◽  
Alfred W. Rademaker ◽  
Diane Newman ◽  
Katherine Coyle ◽  
Katrin Carlson-Leuer ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Primary Induction ◽  
Induction Failure ◽  
Relapsed Acute Myeloid Leukemia ◽  
Acute Myeloid ◽  
Intermediate Dose

scholarly journals Chidamide increases the sensitivity of refractory or relapsed acute myeloid leukemia cells to anthracyclines via regulation of the HDAC3 -AKT-P21-CDK2 signaling pathway

2020 ◽  
Vol 39 (1) ◽  
Author(s):  
Hao Wang ◽  
Yu-chen Liu ◽  
Cheng-ying Zhu ◽  
Fei Yan ◽  
Meng-zhen Wang ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Signaling Pathway ◽  
Salvage Therapy ◽  
Myeloid Leukemia ◽  
Complete Response ◽  
Dependent Manner ◽  
Induce Cell Cycle Arrest ◽  
Anthracycline Resistance ◽  
Acute Myeloid ◽  
Resistant Cells

Abstract Background Induction therapy for acute myeloid leukemia (AML) is an anthracycline-based chemotherapy regimen. However, many patients experience a relapse or exhibit refractory disease (R/R). There is an urgent need for more effective regimens to reverse anthracycline resistance in these patients. Methods In this paper, Twenty-seven R/R AML patients with anthracycline resistance consecutively received chidamide in combination with anthracycline-based regimen as salvage therapy at the Chinese PLA General Hospital. Results Of the 27 patients who had received one course of salvage therapy, 13 achieved a complete response and 1 achieved a partial response. We found that the HDAC3-AKT-P21-CDK2 signaling pathway was significantly upregulated in anthracycline-resistant AML cells compared to non-resistant cells. AML patients with higher levels of HDAC3 had lower event-free survival (EFS) and overall survival (OS) rates. Moreover, anthracycline-resistant AML cells are susceptible to chidamide, a histone deacetylase inhibitor which can inhibit cell proliferation, increase cell apoptosis and induce cell-cycle arrest in a time- and dose-dependent manner. Chidamide increases the sensitivity of anthracycline-resistant cells to anthracycline drugs, and these effects are associated with the inhibition of the HDAC3-AKT-P21-CDK2 signaling pathway. Conclusion Chidamide can increase anthracycline drug sensitivity by inhibiting HDAC3-AKT-P21-CDK2 signaling pathway, thus demonstrating the potential for application.

Analysis of Efficacy and Prognostic Factors of CLAG Treatment in Chinese Patients with Refractory or Relapsed Acute Myeloid Leukemia

2018 ◽  
Vol 141 (1) ◽  
pp. 43-53 ◽  
Author(s):  
Li Wang ◽  
Jun Xu ◽  
Xiaolong Tian ◽  
Tingting Lv ◽  
Guolin Yuan
Keyword(s):  
Acute Myeloid Leukemia ◽  
High Risk ◽  
Risk Stratification ◽  
Salvage Therapy ◽  
Myeloid Leukemia ◽  
Median Overall Survival ◽  
Remission Rate ◽  
Chinese Patients ◽  
Acute Myeloid

Background/Aims: The aim of this work was to investigate the efficacy and predictive factors of CLAG treatment in refractory or relapsed (R/R) acute myeloid leukemia (AML) patients. Methods: Sixty-seven R/R AML patients were enrolled in this prospective cohort study and treated by a CLAG regimen: 5 mg/m2/day cladribine (days 1–5), 2 g/m2/day cytarabine (days 1–5), and 300 μg/day filgrastim (days 0–5). The median follow-up duration was 10 months. Results: A total of 57 out of 67 patients were evaluable for remission after CLAG therapy, of whom 57.9% achieved a complete remission (CR) and the overall remission rate was 77.2%. The median overall survival (OS) was 10.0 months, with a 1-year OS of 40.3 ± 6.0% and 3-year OS of 16.7 ± 5.7%. CR at first induction after the initial diagnosis was associated with a favorable CR. Age above 60 years, high risk stratification, second or higher salvage therapy, and bone marrow (BM) blasts ≥42.1% were correlated with an unfavorable CR. Secondary disease, age ≥60 years, high risk stratification, and second or higher salvage therapy were associated with worse OS. Patients developed thrombocytopenia (41, 61%), febrile neutropenia (37, 55%), leukopenia (33, 49%), neutropenia (18, 27%), and anemia (9, 13%). Conclusion: CLAG was effective and well tolerated for R/R AML. BM blasts ≥42.1%, age ≥60 years, high risk stratification, and second or higher salvage therapy were independent factors for a poor prognosis.

scholarly journals Fate of Patients with Newly Diagnosed Acute Myeloid Leukemia Who Fail Primary Induction Therapy

2015 ◽  
Vol 21 (3) ◽  
pp. 559-564 ◽  
Author(s):  
Megan Othus ◽  
Frederick R. Appelbaum ◽  
Stephen H. Petersdorf ◽  
Kenneth J. Kopecky ◽  
Marilyn Slovak ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Induction Therapy ◽  
Myeloid Leukemia ◽  
Newly Diagnosed ◽  
Primary Induction ◽  
Acute Myeloid
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