ArticleJournal of internal medicine2022
Targeting SAMHD1 with hydroxyurea in first-line cytarabine-based therapy of newly diagnosed acute myeloid leukaemia: Results from the HEAT-AML trial.
Article in Journal of internal medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT06199557 (A Phase 1/2 Multicenter Open-label Study to Investigate Treatment of Hydroxyurea in Combination With Valproic Acid), which is not on this map. Cited by 13 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
A Phase 1/2 Multicenter Open-label Study to Investigate Treatment of Hydroxyurea in Combination With Valproic Acid (VPA), or 6- Mercaptopurine in Combination With VPA in Patients With AML or HR-MDS Unfit for Standard Therapy
Who cites it
13 citing papers in PubMed, 17 citations in OpenAlex.
- Targeting IMPDH to inhibit SAMHD1 inCell cycle (Georgetown, Tex.) · 2026Article
- The Role of SAMHD1 in Viral Resistance and Transduction Efficiency Challenges in Pediatric Hematological Malignancies: Mechanistic Insights and Clinical Perspectives.European journal of haematology · 2026Review
- IMPDH inhibition enhances cytarabine efficacy in SAMHD1-expressing leukaemia cells via guanine nucleotide depletion.Molecular oncology · 2026Article
- Enhancing the Nucleoside Analog Response with Translational Therapeutic Approaches to Overcome Resistance.Cells · 2026Review
- Addition of hydroxyurea (hydroxycarbamide) enhances the efficacy of fludarabine/cytarabine-based salvage regimens against acute myeloid leukaemia.British journal of haematology · 2025Article
- Precision oncology to overcome resistance in R/R AML in children and adults requires combinations of cytotoxic, targeted, and immunological treatments.Journal of internal medicine · 2025Review
- SAMHD1 shapes deoxynucleotide triphosphate homeostasis by interconnecting the depletion and biosynthesis of different dNTPs.Nature communications · 2025Article
- AHR signaling pathway mediates mitochondrial oxidative phosphorylation which leads to cytarabine resistance.Acta biochimica et biophysica Sinica · 2024Article
- Identification and evaluation of small-molecule inhibitors against the dNTPase SAMHD1 via a comprehensive screening funnel.iScience · 2024Article
- Hypomethylating agents plus modified priming regimens compared with venetoclax-based regimens based on molecular characteristics for newly diagnosed patients with acute myeloid leukemia: a multi-center cohort study.Annals of hematology · 2023Article
- Activation of STING by SAMHD1 Deficiency Promotes PANoptosis and Enhances Efficacy of PD-L1 Blockade in Diffuse Large B-cell Lymphoma.International journal of biological sciences · 2023Article
- Targeting SAMHD1 with hydroxyurea in first-line cytarabine-based therapy of newly diagnosed acute myeloid leukaemia: Results from the HEAT-AML trial.Journal of internal medicine · 2022Article
- Functionalist Oncology to Model the Contextuality of Dynamics and Treatment in Acute Myeloid Leukaemia.IET systems biologyArticle
Corrections and comments
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Authors and funding
25 authors at 10 institutions in 3 countries.
Funding
Abstract
backgroundTreatment of newly diagnosed acute myeloid leukaemia (AML) is based on combination chemotherapy with cytarabine (ara-C) and anthracyclines. Five-year overall survival is below 30%, which has partly been attributed to cytarabine resistance. Preclinical data suggest that the addition of hydroxyurea potentiates cytarabine efficacy by increasing ara-C triphosphate (ara-CTP) levels through targeted inhibition of SAMHD1.
objectivesIn this phase 1 trial, we evaluated the feasibility, safety and efficacy of the addition of hydroxyurea to standard chemotherapy with cytarabine/daunorubicin in newly diagnosed AML patients.
methodsNine patients were enrolled and received at least two courses of ara-C (1 g/m
resultsThe most common grade 3-4 toxicity was febrile neutropenia (100%). No unexpected toxicities were observed. Pharmacokinetic analyses showed a significant increase in median ara-CTP levels (1.5-fold; p = 0.04) in patients receiving doses of 1 g hydroxyurea. Ex vivo, diagnostic leukaemic bone marrow blasts from study patients were significantly sensitised to ara-C by a median factor of 2.1 (p = 0.0047). All nine patients (100%) achieved complete remission, and all eight (100%) with validated MRD measurements (flow cytometry or real-time quantitative polymerase chain reaction [RT-qPCR]) had an MRD level <0.1% after two cycles of chemotherapy. Treatment was well-tolerated, and median time to neutrophil recovery >1.0 × 10
conclusionTargeted inhibition of SAMHD1 by the addition of hydroxyurea to conventional AML therapy is safe and appears efficacious within the limitations of the small phase 1 patient cohort. These results need to be corroborated in a larger study.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.