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Cancers
Special Issues
Novel Therapies for Pediatric Acute Myeloid Leukemia
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Novel Therapies for Pediatric Acute Myeloid Leukemia

A special issue of Cancers (ISSN 2072-6694).

Deadline for manuscript submissions: closed (28 February 2021) | Viewed by 9352

Special Issue Editor

Dr. Sarah K. Tasian

E-Mail Website1 Website2
Guest Editor
Children’s Hospital of Philadelphia, Division of Oncology and Center for Childhood Cancer Research, Philadelphia, United States
Interests: ALL; AML; clinical trials; immunotherapy; kinase inhibitor; precision medicine; signal transduction; xenograft models

Special Issue Information

Dear Colleagues,

Approximately two-thirds of children and adolescents with acute myeloid leukemia (AML) are cured with modern risk-adapted therapy comprised of multi-agent chemotherapy and often hematopoietic stem cell transplantation. Current pediatric regimens are maximally intensive and are associated with both short- and long-term toxicity. Chemotherapy resistance nonetheless remains a major barrier to cure, highlighting a need for new therapies, potentially with alternative mechanisms of action. Recent advances in the molecular genetic characterization of pediatric AML and measurable residual disease (MRD) quantification and the correlation of these data with clinical outcomes have further refined risk stratification and recommended treatment protocols. Finally, increasing the availability of promising novel chemotherapies, small molecule inhibitors, and immunotherapies together with global collaboration has facilitated the development of innovative early-phase clinical trials specifically for children with high-risk or relapsed/refractory AML. This Special Issue provides a comprehensive review of the current biologic and therapeutic landscape of pediatric AML with a focus on precision medicine approaches.

Dr. Sarah K. Tasian
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 (AML)
  • biology
  • chemotherapy
  • clinical trials
  • immunotherapy
  • inhibitor
  • pediatric
  • precision medicine
  • therapy

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Published Papers (2 papers)

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Research

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13 pages, 1022 KiB  
Article
Second Relapse of Pediatric Patients with Acute Myeloid Leukemia: A Report on Current Treatment Strategies and Outcome of the AML-BFM Study Group
by Mareike Rasche, Emma Steidel, Martin Zimmermann, Jean-Pierre Bourquin, Heidrun Boztug, Iveta Janotova, E. Anders Kolb, Thomas Lehrnbecher, Nils von Neuhoff, Naghmeh Niktoreh, Nora Mühlegger, Lucie Sramkova, Jan Stary, Christiane Walter, Ursula Creutzig, Michael Dworzak and Dirk Reinhardt
Cancers 2021, 13(4), 789; https://doi.org/10.3390/cancers13040789 - 14 Feb 2021
Cited by 17 | Viewed by 3107
Abstract
Successful management of relapse is critical to improve outcomes of children with acute myeloid leukemia (AML). We evaluated response, survival and prognostic factors after a second relapse of AML. Among 1222 pediatric patients of the population-based AML-Berlin–Frankfurt–Munster (BFM) study group (2004 until 2017), [...] Read more.
Successful management of relapse is critical to improve outcomes of children with acute myeloid leukemia (AML). We evaluated response, survival and prognostic factors after a second relapse of AML. Among 1222 pediatric patients of the population-based AML-Berlin–Frankfurt–Munster (BFM) study group (2004 until 2017), 73 patients met the quality parameters for inclusion in this study. Central review of source documentation warranted the accuracy of reported data. Treatment approaches included palliation in 17 patients (23%), intensive therapy with curative intent (n = 46, 63%) and other regimens (n = 10). Twenty-five patients (35%) received hematopoietic stem cell transplantation (HSCT), 21 of whom (88%) had a prior HSCT. Survival was poor, with a five-year probability of overall survival (pOS) of 15 ± 4% and 31 ± 9% following HSCT (n = 25). Early second relapse (within one year after first relapse) was associated with dismal outcome (pOS 2 ± 2%, n = 44 vs. 33 ± 9%, n = 29; p < 0.0001). A third complete remission (CR) is required for survival: 31% (n = 14) of patients with intensive treatment achieved a third CR with a pOS of 36 ± 13%, while 28 patients (62%) were non-responders (pOS 7 ± 5%). In conclusion, survival is poor but possible, particularly after a late second relapse and an intensive chemotherapy followed by HSCT. This analysis provides a baseline for future treatment planning. Full article
(This article belongs to the Special Issue Novel Therapies for Pediatric Acute Myeloid Leukemia)
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Review

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20 pages, 1468 KiB  
Review
Redirecting the Immune Microenvironment in Acute Myeloid Leukemia
by Stephanie Sendker, Dirk Reinhardt and Naghmeh Niktoreh
Cancers 2021, 13(6), 1423; https://doi.org/10.3390/cancers13061423 - 20 Mar 2021
Cited by 30 | Viewed by 5633
Abstract
Acute myeloid leukemia is a life-threatening malignant disorder arising in a complex and dysregulated microenvironment that, in part, promotes the leukemogenesis. Treatment of relapsed and refractory AML, despite the current overall success rates in management of pediatric AML, remains a challenge with limited [...] Read more.
Acute myeloid leukemia is a life-threatening malignant disorder arising in a complex and dysregulated microenvironment that, in part, promotes the leukemogenesis. Treatment of relapsed and refractory AML, despite the current overall success rates in management of pediatric AML, remains a challenge with limited options considering the heavy but unsuccessful pretreatments in these patients. For relapsed/refractory (R/R) patients, hematopoietic stem cell transplantation (HSCT) following ablative chemotherapy presents the only opportunity to cure AML. Even though in some cases immune-mediated graft-versus-leukemia (GvL) effect has been proven to efficiently eradicate leukemic blasts, the immune- and chemotherapy-related toxicities and adverse effects considerably restrict the feasibility and therapeutic power. Thus, immunotherapy presents a potent tool against acute leukemia but needs to be engineered to function more specifically and with decreased toxicity. To identify innovative immunotherapeutic approaches, sound knowledge concerning immune-evasive strategies of AML blasts and the clinical impact of an immune-privileged microenvironment is indispensable. Based on our knowledge to date, several promising immunotherapies are under clinical evaluation and further innovative approaches are on their way. In this review, we first focus on immunological dysregulations contributing to leukemogenesis and progression in AML. Second, we highlight the most promising therapeutic targets for redirecting the leukemic immunosuppressive microenvironment into a highly immunogenic environment again capable of anti-leukemic immune surveillance. Full article
(This article belongs to the Special Issue Novel Therapies for Pediatric Acute Myeloid Leukemia)
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