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Cancers
Special Issues
The Clinical Trials and Management of Acute Myeloid Leukemia
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The Clinical Trials and Management of Acute Myeloid Leukemia

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Clinical Research of Cancer".

Deadline for manuscript submissions: 19 September 2025 | Viewed by 2916

Special Issue Editor

Dr. Margaret T. Kasner

E-Mail Website
Guest Editor
1. Department of Medical Oncology, Philadelphia, Thomas Jefferson University, Philadelphia, PA 19107, USA
2. Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA 19107, USA
Interests: acute myeloid leukemia; clinical trials; translational research; targeted therapies
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues, 

Acute myeloid leukemia (AML) has always posed a therapeutic challenge due to its molecular and cytogenetic complexity. For the first time in decades, advances in treatment through the approval of novel agents and combinations, have been made. Long-term disease-free survival had plateaued at less than 30% at 5 years; however, in the last few years, a small, but steady increase has been seen thanks to the advancements in novel therapies. The exploration of novel mechanisms and immune system enhancement as therapeutic targets for the treatment of AML continues.

This Special Issue will highlight the clinical trials and advances in supportive care for acute myeloid leukemia. 

You may choose our Joint Special Issue in Current Oncology.

Dr. Margaret T. Kasner
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • acute myeloid leukemia
  • clinical trials
  • translational research
  • targeted therapies
  • novel agents

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Published Papers (3 papers)

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Research

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14 pages, 2426 KiB  
Article
Dose-Reduced FLA-IDA in Combination with Venetoclax Is an Effective and Safe Salvage Therapy in Relapsed and Refractory Acute Myeloid Leukemia (R/R AML)
by Martin Schönrock, Piet Sonnemann, Nina Michalowski, Michael Heuser, Felicitas Thol, Francis Ayuketang Ayuk, Christine Wolschke, Evgeny Klyuchnikov, Carsten Bokemeyer, Walter Fiedler and Sophia Cichutek
Cancers 2024, 16(22), 3872; https://doi.org/10.3390/cancers16223872 - 19 Nov 2024
Viewed by 654
Abstract
Background: Despite the development of targeted therapies in first-line AML, complete remissions (CR) cannot be achieved in 30–40%, and relapse rates remain high. In R/R AML the intensive treatment regimen of fludarabine, cytarabine, idarubicin combined with venetoclax (FLA-VIDA) showed improved remission rates compared [...] Read more.
Background: Despite the development of targeted therapies in first-line AML, complete remissions (CR) cannot be achieved in 30–40%, and relapse rates remain high. In R/R AML the intensive treatment regimen of fludarabine, cytarabine, idarubicin combined with venetoclax (FLA-VIDA) showed improved remission rates compared to FLA-IDA. In this retrospective single-center analysis, we investigated the efficacy and safety of dose-reduced FLA-IDA with and without venetoclax to minimize the risk of infectious complications and excessive myelosuppression; Methods: Between 2011 and 2023, 89 R/R AML patients were treated with dose-reduced FLA-IDA (fludarabine 30 mg/m2 day 1–4, cytarabine 2000 mg/m2 day 1–4, idarubicin 10 mg/m2 day 1 + 4). From 2019 onwards, venetoclax was added (day 1 100 mg, day 2 200 mg, day 3–14 400 mg); Results: Significantly improved response rates were observed with 60.0% vs. 38.8% CR/CRi (p = 0.0297) and 74.5% vs. 47.3% (p = 0.032) CR/CRi/MLFS for FLA-VIDA vs. FLA-IDA. Further, with FLA-VIDA significantly improved event-free survival (EFS) was observed (p = 0.026). Overall survival (OS) was similar in FLA-VIDA and FLA-IDA treated patients. The most common treatment-related toxicities were hematological adverse events, but they were comparable between groups. The time to neutrophil and platelet recovery were similar in responding patients treated with FLA-VIDA vs. FLA-IDA; Conclusions: Dose-reduced FLA-VIDA significantly improved response rates without increases in toxicity, showing promise for an improved R/R AML treatment. Full article
(This article belongs to the Special Issue The Clinical Trials and Management of Acute Myeloid Leukemia)
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12 pages, 1748 KiB  
Article
A Phase I Trial of Sirolimus with “7&3” Induction Chemotherapy in Patients with Newly Diagnosed Acute Myeloid Leukemia
by Neil Palmisiano, Grace Jeschke, Lindsay Wilde, Onder Alpdogan, Matthew Carabasi, Joanne Filicko-O’Hara, Dolores Grosso, Thomas Klumpp, Ubaldo Martinez, John Wagner, Martin P. Carroll, Alexander Perl and Margaret Kasner
Cancers 2023, 15(21), 5129; https://doi.org/10.3390/cancers15215129 - 25 Oct 2023
Viewed by 1249
Abstract
Chemotherapy remains a primary treatment for younger AML patients, though many relapse. Data from our group have shown that highly phosphorylated S6 in blasts may predict response to sirolimus given with chemotherapy. We report the results of a phase I study of this [...] Read more.
Chemotherapy remains a primary treatment for younger AML patients, though many relapse. Data from our group have shown that highly phosphorylated S6 in blasts may predict response to sirolimus given with chemotherapy. We report the results of a phase I study of this combination in newly diagnosed AML and the pharmacodynamic analysis of pS6 before and after treatment. Subjects received sirolimus (12 mg on day 1, 4 mg daily, days 2–10), then idarubicin and cytarabine (days 4–10). Response was assessed at hematologic recovery or by day 42 using a modified IWG criteria. Fifty-five patients received sirolimus. Toxicity was similar to published 7 + 3 data, and 53% had high-, 27% intermediate-, and 20% favorable-risk disease. Forty-four percent of the high-risk patients entered into CR/CRp. Seventy-nine percent of the intermediate-risk subjects had a CR/CRp. All favorable-risk patients had a CR by day 42; 9/11 remained alive and in remission with a median follow-up of 660 days. Additionally, 41/55 patients had adequate samples for pharmacodynamic analysis. All patients demonstrated activation of S6 prior to therapy, in contrast to 67% seen in previous studies of relapsed AML. mTORC1 inhibition was observed in 66% of patients without enrichment among patients who achieved remission. We conclude that sirolimus and 7 + 3 is a well-tolerated and safe regimen. mTORC1 appears to be activated in almost all patients at diagnosis of AML. Inhibition of mTORC1 did not differ based on response, suggesting that AML cells may have redundant signaling pathways that regulate chemosensitivity in the presence of mTORC1 inhibition. Full article
(This article belongs to the Special Issue The Clinical Trials and Management of Acute Myeloid Leukemia)
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Review

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16 pages, 790 KiB  
Review
Synergistic Strategies for KMT2A-Rearranged Leukemias: Beyond Menin Inhibitor
by Sandra Cantilena, Mohamed AlAmeri, Noelia Che, Owen Williams and Jasper de Boer
Cancers 2024, 16(23), 4017; https://doi.org/10.3390/cancers16234017 - 29 Nov 2024
Viewed by 522
Abstract
KMT2A-rearranged leukemias are a highly aggressive subset of acute leukemia, characterized by poor prognosis and frequent relapses despite intensive treatment. Menin inhibitors, which target the critical KMT2A–menin interaction driving leukemogenesis, have shown promise in early clinical trials. However, resistance to these inhibitors, often [...] Read more.
KMT2A-rearranged leukemias are a highly aggressive subset of acute leukemia, characterized by poor prognosis and frequent relapses despite intensive treatment. Menin inhibitors, which target the critical KMT2A–menin interaction driving leukemogenesis, have shown promise in early clinical trials. However, resistance to these inhibitors, often driven by menin mutations or alternative oncogenic pathways, remains a significant challenge. This review explores combination therapies aimed at overcoming resistance and improving patient outcomes. Potential strategies include inhibiting DOT1L, a histone methyltransferase essential for KMT2A-driven transcription, and BRD4, a regulator of transcriptional super-enhancers. Additionally, targeting MYC, a key oncogene frequently upregulated in KMT2A-rearranged leukemia, offers another approach. Direct inhibition of KMT2A-fusion proteins and c-MYB, a transcription factor critical for leukemic stem cell maintenance, is also explored. By integrating these diverse strategies, we propose a comprehensive therapeutic paradigm that targets multiple points of the leukemic transcriptional and epigenetic network. These combination approaches aim to disrupt key oncogenic pathways, reduce resistance, and enhance treatment efficacy, ultimately providing more durable remissions and improved survival for patients with KMT2A-rearranged leukemias. Full article
(This article belongs to the Special Issue The Clinical Trials and Management of Acute Myeloid Leukemia)
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