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Cancers
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New Challenges in Allogeneic Hematopoietic Stem Cell Transplantation for Acute...
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New Challenges in Allogeneic Hematopoietic Stem Cell Transplantation for Acute Myeloid Leukemia

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

Deadline for manuscript submissions: 31 December 2025 | Viewed by 1385

Special Issue Editors

Dr. Federico Mosna

E-Mail Website
Guest Editor
Hematology and Bone Marrow Transplantation Unit (BMTU), Hospital of Bolzano (SABES-ASDAA), Teaching Hospital of Paracelsus Medical University (PMU), 39100 Bolzano, Italy
Interests: clinical hematology; hematopoietic stem cell transplantation; acute leukemias; immunotherapy; mesenchymal stromal cells; stem cell biology; biostatistics
Dr. Irene Cavattoni

E-Mail Website
Guest Editor
Hematology and Bone Marrow Transplantation Unit (BMTU), Hospital of Bolzano (SABES-ASDAA), Teaching Hospital of Paracelsus Medical University (PMU), 39100 Bolzano, Italy
Interests: clinical hematology; hematopoietic stem cell transplantation; acute leukemias; graft versus host disease; immunotherapy

Special Issue Information

Dear Colleagues,

Almost 70 years after the first successful attempt in 1956, allogeneic hematopoietic stem cell transplantation (allo-HSCT) is currently a fundamental treatment option for oncohematological diseases and the precursor of immunotherapy of neoplastic diseases. Its use in patients affected by acute myeloid leukemia (AML) can now be proposed up to old age thanks to major advancements in donor/host matching, pre-transplant conditioning, immunosuppressive therapy, and the prevention and management of infections.

Despite this, treatment-related mortality still ranges between 10 and 30%, mainly due to comorbidity, infectious complications, and the occurrence of graft-versus-host disease (GVHD). Even without these complications, long-term cure of AML is still achieved only in a minority of high-risk patients, as allo-HSCT loses effectiveness when the transplant is performed with active resistant disease, or in the case of genetically adverse, e.g., complex-karyotype or TP53-mutated leukemias.

It is becoming increasingly common, then, to consider allo-HSCT as an additional step, rather than the final act, of the complex journey to cure; post-transplant interventions, ranging from earlier tapering of immunosuppression to various forms of maintenance, are currently being tested to improve outcome. Finally, intense research is being made on the rescue treatment options for relapsing patients, including a second transplantation.

We are pleased to invite authors to contribute with reviews of the literature and other original clinical research on all these topics, especially on the use of allo-HSCT against chemorefractory high-risk AML, on the prevention of relapse after transplantation and the treatment of steroid-refractory GVHD. Biological studies regarding the reconstitution of the immune system following allo-HSCT, the mechanisms of persistence of leukemic stem cells (LSC), and the mechanisms of GVHD resistance to treatment are also welcome.

We look forward to receiving your contributions!

Dr. Federico Mosna
Dr. Irene Cavattoni
Guest Editors

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)
  • allogeneic hematopoietic stem cells transplantation (allo-HSCT)
  • immunotherapy
  • leukemic stem cells
  • graft versus host disease (GVHD)
  • infections in immunodepressed patients
  • immune reconstitution
  • post-transplant management
  • long-term results
  • clinical

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Published Papers (2 papers)

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Research

15 pages, 1389 KB  
Article
Safety of Post-Transplant Cyclophosphamide-Based Prophylaxis in AML Patients with Pre-Existing Cardiac Morbidity Undergoing Allogeneic Hematopoietic Cell Transplantation
by Arnau Torrent-Rodríguez, Enric Cascos, Víctor Navarro Garcés, Estefanía Pérez-López, Mónica Baile-González, Carlos Martín Rodríguez, María Jesús Pascual Cascón, Marta Luque, Albert Esquirol, Carmen Martín Calvo, Felipe Peña-Muñoz, Inmaculada Heras Fernando, Itziar Oiartzabal Ormtegi, Adolfo Jesús Sáez Marín, Sara Fernández-Luis, Juan José Domínguez-García, Sara Villar Fernández, José Luis López Lorenzo, Miguel Fernández de Sanmamed Girón, Leslie González Pinedo, Lucía García-Maño, Ana Pilar González-Rodriguez, Tamara Torrado, Silvia Filaferro, Pascual Basalobre, Guillermo Ortí, Montserrat Rovira, Manuel Jurado Chacón and María Queralt Salasadd Show full author list remove Hide full author list
Cancers 2025, 17(19), 3128; https://doi.org/10.3390/cancers17193128 - 26 Sep 2025
Abstract
Background: Post-transplant cyclophosphamide (PTCy) is a standard graft-versus-host disease (GVHD) prophylaxis in allogeneic hematopoietic cell transplantation (allo-HCT). While effective, concerns remain about cyclophosphamide-related cardiotoxicity, especially in patients with pre-existing cardiac morbidity, a population often underrepresented in clinical trials. Objectives: To assess the incidence [...] Read more.
Background: Post-transplant cyclophosphamide (PTCy) is a standard graft-versus-host disease (GVHD) prophylaxis in allogeneic hematopoietic cell transplantation (allo-HCT). While effective, concerns remain about cyclophosphamide-related cardiotoxicity, especially in patients with pre-existing cardiac morbidity, a population often underrepresented in clinical trials. Objectives: To assess the incidence and outcomes of early (ECE, ≤100 days) and late (LCE, >100 days) cardiac events in acute myeloid leukemia (AML) patients with and without baseline cardiac morbidity undergoing allo-HCT with PTCy. Study Design: Retrospective multicenter study by the Grupo Español de Trasplante Hematopoyético y Terapia Celular (GETH-TC) including 461 AML patients (62 with cardiac morbidity) transplanted between 2012 and 2022. Cardiac morbidity was defined by documented cardiac disease or left ventricular ejection fraction < 45%. Cumulative incidence, overall survival (OS), and non-relapse mortality (NRM) were analyzed using competing risks models and adjusted with propensity score matching (PSM) and inverse probability weighting (IPW). Results: Cardiac events occurred in 13.2% of patients: 11% vs. 7% ECE (p = 0.93) and 8% vs. 5.3% LCE (p = 0.85) in those with vs. without cardiac morbidity. Most ECEs were arrhythmias or heart failure. Adjusted analyses confirmed no significant differences in CE incidence, OS, or NRM between groups. Two-year OS was 69% vs. 70% (p = 0.50); NRM was 18% vs. 17% (p = 0.20). ECE was associated with higher mortality in both groups. Conclusions: PTCy is feasible in AML patients with pre-existing cardiac morbidity when combined with comprehensive cardiovascular evaluation and cardio-oncology follow-up, supporting its safe use in broader patient populations with appropriate cardiologic support. Full article
(This article belongs to the Special Issue New Challenges in Allogeneic Hematopoietic Stem Cell Transplantation for Acute Myeloid Leukemia)
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19 pages, 4034 KB  
Article
Whole-Blood Longitudinal Molecular Profiling Maps the Road of Graft Versus Host Disease (GVHD)
by Merav Bar, Mohammed El Anbari, Darawan Rinchai, Mohammed Toufiq, Dhanya Kizhakayil, Harshitha S. Manjunath, Rebecca Mathew, Irene Cavattoni, Sabine Forer, Marco Recla, Hani Bibawi, Ahmad Alater, Reem Yahia, Clarisa Brown, Nancy L. Miles, Phuong Vo, Davide Bedognetti, Sara Tomei, Ayman Saleh, Chiara Cugno, Damien Chaussabel and Sara Deolaadd Show full author list remove Hide full author list
Cancers 2025, 17(5), 802; https://doi.org/10.3390/cancers17050802 - 26 Feb 2025
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Abstract
Background: Graft versus host disease (GVHD) and the graft versus tumor (GVT) effect after allogeneic hematopoietic cell transplantation (allo-HCT) result from complex interactions between the donor immune system and the recipient environment. High-temporal longitudinal monitoring might be necessary to identify triggering events of [...] Read more.
Background: Graft versus host disease (GVHD) and the graft versus tumor (GVT) effect after allogeneic hematopoietic cell transplantation (allo-HCT) result from complex interactions between the donor immune system and the recipient environment. High-temporal longitudinal monitoring might be necessary to identify triggering events of GVHD and GVT and to intercept these events before their occurrence. But it would require an overall considerable amount of blood by venipuncture, which is unfeasible in such a fragile population. Methods: In this study, we implemented a targeted multiplex microfluidics q-PCR-based transcriptional fingerprint assay (TFA) on 50 µL of blood collected by a simple fingerstick to evaluate post-allo-HCT systemic immune perturbations associated with the development of GVHD. Fluctuations of a panel of 264 genes were measured in 31 allo-HCT patients by frequent (weekly or biweekly) analysis of 50 µL serial blood samples. Cross-sectional and longitudinal analyses correlated with detailed clinical annotations were performed. Results: Signatures of neutrophil activation and interferon (IFN) characterized the onset of acute GVHD, while an ongoing cytotoxic response was modulated in chronic mild GVHD and protein-synthesis and B-cell-related signatures characterized late acute/overlap GVHD. An unexpected erythroid signature distinguished patients with acute and mild chronic GVHD. Conclusions: Our micro-invasive approach unveiled the molecular heterogeneity of GVHD and identified hierarchically important biological processes conducive to different forms of GVHD. These findings increase our understanding of GVHD and reveal potentially targetable alterations. This approach might be implemented clinically to intercept GVHD before its occurrence and to modulate therapeutic interventions accordingly. Full article
(This article belongs to the Special Issue New Challenges in Allogeneic Hematopoietic Stem Cell Transplantation for Acute Myeloid Leukemia)
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