دورية أكاديمية
Innovations in conditioning and post-transplant maintenance in AML: genomically informed revelations on the graft-versus-leukemia effect.
| العنوان: | Innovations in conditioning and post-transplant maintenance in AML: genomically informed revelations on the graft-versus-leukemia effect. |
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| المؤلفون: | Murdock HM; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, United States., Ho VT; Bone Marrow Transplant Program, Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, United States., Garcia JS; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, United States. |
| المصدر: | Frontiers in immunology [Front Immunol] 2024 Mar 20; Vol. 15, pp. 1359113. Date of Electronic Publication: 2024 Mar 20 (Print Publication: 2024). |
| نوع المنشور: | Journal Article; Review; Research Support, N.I.H., Extramural |
| اللغة: | English |
| بيانات الدورية: | Publisher: Frontiers Research Foundation] Country of Publication: Switzerland NLM ID: 101560960 Publication Model: eCollection Cited Medium: Internet ISSN: 1664-3224 (Electronic) Linking ISSN: 16643224 NLM ISO Abbreviation: Front Immunol Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: [Lausanne : Frontiers Research Foundation] |
| مواضيع طبية MeSH: | Leukemia, Myeloid, Acute*/genetics , Leukemia, Myeloid, Acute*/therapy , Leukemia, Myeloid, Acute*/complications , Hematopoietic Stem Cell Transplantation*/adverse effects , Hematopoietic Stem Cell Transplantation*/methods , Graft vs Host Disease*/etiology , Graft vs Host Disease*/prevention & control, Humans ; Graft vs Leukemia Effect ; Recurrence |
| مستخلص: | Acute Myeloid Leukemia (AML) is the prototype of cancer genomics as it was the first published cancer genome. Large-scale next generation/massively parallel sequencing efforts have identified recurrent alterations that inform prognosis and have guided the development of targeted therapies. Despite changes in the frontline and relapsed standard of care stemming from the success of small molecules targeting FLT3, IDH1/2, and apoptotic pathways, allogeneic stem cell transplantation (alloHSCT) and the resulting graft- versus -leukemia (GVL) effect remains the only curative path for most patients. Advances in conditioning regimens, graft-vs-host disease prophylaxis, anti-infective agents, and supportive care have made this modality feasible, reducing transplant related mortality even among patients with advanced age or medical comorbidities. As such, relapse has emerged now as the most common cause of transplant failure. Relapse may occur after alloHSCT because residual disease clones persist after transplant, and develop immune escape from GVL, or such clones may proliferate rapidly early after alloHSCT, and outpace donor immune reconstitution, leading to relapse before any GVL effect could set in. To address this issue, genomically informed therapies are increasingly being incorporated into pre-transplant conditioning, or as post-transplant maintenance or pre-emptive therapy in the setting of mixed/falling donor chimerism or persistent detectable measurable residual disease (MRD). There is an urgent need to better understand how these emerging therapies modulate the two sides of the GVHD vs. GVL coin: 1) how molecularly or immunologically targeted therapies affect engraftment, GVHD potential, and function of the donor graft and 2) how these therapies affect the immunogenicity and sensitivity of leukemic clones to the GVL effect. By maximizing the synergistic action of molecularly targeted agents, immunomodulating agents, conventional chemotherapy, and the GVL effect, there is hope for improving outcomes for patients with this often-devastating disease. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2024 Murdock, Ho and Garcia.) |
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| معلومات مُعتمدة: | K08 CA245209 United States CA NCI NIH HHS |
| فهرسة مساهمة: | Keywords: AML; MRD; allogeneic stem cell transplant; genetics; graft-versus-leukemia; maintenance; targeted therapy |
| تواريخ الأحداث: | Date Created: 20240404 Date Completed: 20240405 Latest Revision: 20240415 |
| رمز التحديث: | 20240415 |
| مُعرف محوري في PubMed: | PMC10987864 |
| DOI: | 10.3389/fimmu.2024.1359113 |
| PMID: | 38571944 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1664-3224 |
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| DOI: | 10.3389/fimmu.2024.1359113 |