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New Therapies for Acute Myeloid Leukemia

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: 20 February 2025 | Viewed by 1823

Special Issue Editor


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Guest Editor
Servicio de Hematología, Hospital Clínico San Carlos, IdISSC, School of Medicine, Universidad Complutense de Madrid, 28040 Madrid, Spain
Interests: hematology; acute myeloid leukemia

Special Issue Information

Dear Colleagues,

Acute myeloid leukemia (AML) is a high-mortality disease whose frequency and lethality increase with age. The standard treatment for eligible patients is based on the use of intensive chemotherapy with protocols that have not changed in decades. Usually, older and unfit patients cannot even receive these treatments. Demethylating agents and BCL2 inhibitors have been lately used in AML cases, but the results are still disappointing. Thus, new treatments are urgently needed for AML as it is the most common acute leukemia in adults, with the fifth worst survival rate among all cancers.

The discovery of gene mutations and rearrangements has allowed a new classification of AML with prognostic implications. Treatments targeting these molecular alterations have been recently developed. The increasing knowledge on the metabolic particularities of the leukemic cells and their epigenetic modifications have further opened new avenues for treating AML. Finally, immunotherapy with refined indications and new designs appears to be an important therapeutic tool. In this IJMS Special Issue, new therapies for AML will be explored in the hope of improving the prognosis of this condition.

Dr. Eduardo Anguita
Guest Editor

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Keywords

  • acute myeloid leukemia
  • BCL2 inhibitors
  • leukemic cells
  • new therapies for AML
  • prognostic implications

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Published Papers (1 paper)

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Research

18 pages, 1811 KiB  
Article
Determinants of Interpatient Variability in Treosulfan Pharmacokinetics in AML Patients Undergoing Autologous Stem Cell Transplantation
by Selin G. Ayçiçek, Dilara Akhoundova, Ulrike Bacher, Michael Hayoz, Yolanda Aebi, Carlo R. Largiadèr and Thomas Pabst
Int. J. Mol. Sci. 2024, 25(15), 8215; https://doi.org/10.3390/ijms25158215 - 27 Jul 2024
Cited by 2 | Viewed by 1014
Abstract
Limited data on treosulfan pharmacokinetics in adults, particularly regarding autologous stem cell transplantation (ASCT) in acute myeloid leukemia (AML), is available to date. Furthermore, correlations between treosulfan exposure, toxicity, and clinical outcome remain understudied. In this single-center retrospective study, we analyzed data from [...] Read more.
Limited data on treosulfan pharmacokinetics in adults, particularly regarding autologous stem cell transplantation (ASCT) in acute myeloid leukemia (AML), is available to date. Furthermore, correlations between treosulfan exposure, toxicity, and clinical outcome remain understudied. In this single-center retrospective study, we analyzed data from 55 AML patients who underwent HDCT with treosulfan (14 g/m2) and melphalan (140 mg/m2 or 200 mg/m2) (TreoMel) between August 2019 and November 2023 at the University Hospital of Bern. We assessed treosulfan pharmacokinetics and correlations with several physiological parameters with potential impact on its interpatient variability. We further analyzed how treosulfan exposure correlates with toxicity and clinical outcomes. Women above 55 years showed higher area under the curve (AUC) levels (median: 946 mg*h/L, range: 776–1370 mg*h/L), as compared to women under 55 (median: 758 mg*h/L, range: 459–1214 mg*h/L, p = 0.0487). Additionally, women above 55 showed higher peak levels (median: 387 mg/L, range: 308–468 mg/L), as compared to men of the same age range (median: 326 mg/L, range: 264–395 mg/L, p = 0.0159). Treosulfan levels varied significantly with body temperature, liver enzymes, hemoglobin/hematocrit., and treosulfan exposure correlated with diarrhea severity in women over 55 (p = 0.0076). Our study revealed age- and gender-related variability in treosulfan pharmacokinetics, with higher plasma levels observed in female patients above 55. Moreover, our data suggest that treosulfan plasma levels may vary with several physiological parameters and that higher treosulfan exposure may impact toxicity. Our study underlines the need for further research on treosulfan pharmacokinetics, especially in older patients undergoing HDCT in the ASCT setting. Full article
(This article belongs to the Special Issue New Therapies for Acute Myeloid Leukemia)
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