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Autologous Stem Cell Transplantation or New Cellular Therapies for Neoplasias

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

Deadline for manuscript submissions: closed (29 February 2024) | Viewed by 18992

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Special Issue Editor

Prof. Dr. Gabriela Maria Baerlocher

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Guest Editor

Laboratory for Hematopoiesis and Molecular Genetics, Department of BioMedical Research (DBMR), University of Bern, 3008 Bern, Switzerland
Interests: new cellular therapies; molecular cancer biology; hematopoiesis; cancer molecular genetics; cellular proliferation and senescence

Special Issue Information

Dear Colleagues,

This Special Issue in Cancers focuses on new insights and advances in all steps of autologous stem and progenitor cell transplantation or new cellular therapies as well as on their outcome. Autologous hematopoietic stem and progenitor cell transplantation is a cornerstone in the therapy of patients with certain types of cancer and new cellular therapy approaches have recently evolved as clinical treatment options. The procedure of autologous hematopoietic stem cell transplantation allows applying higher-dose chemotherapy for the treatment of the malignant disease while avoiding excessively prolonged or irreversible myelosuppression whereas new cellular therapies aim to enhance the immune system to target tumor cells more specifically. The processes of autologous stem cell transplantation or new cellular therapies include many different steps: the selection of patients for the treatment; the use of cytokines in combination or without chemotherapy for the mobilization of stem and progenitor or immune cells to the peripheral blood; the harvesting, processing, storage and infusion of autologous stem and progenitor or immune cells; and the monitoring of adverse reactions, events and cellular recovery with and after transplantation or infusion, as well as the outcomes of patients after several years.

Prof. Dr. Gabriela Maria Baerlocher
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 short 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

autologous stem cell transplantation
neoplasia
progenitor cell transplantation
cancer therapy
chemotherapy
myelosuppression
cancer treatment
bone marrow

Published Papers (7 papers)

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Research

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14 pages, 2508 KiB

Open AccessArticle

Preclinical Validation of an Advanced Therapy Medicinal Product Based on Cytotoxic T Lymphocytes Specific for Mutated Nucleophosmin (NPM1^mut) for the Treatment of NPM1^mut-Acute Myeloid Leukemia

by Marica De Cicco, Ivana Lagreca, Sabrina Basso, Patrizia Barozzi, Stella Muscianisi, Alba Bianco, Giovanni Riva, Sara Di Vincenzo, Chiara Pulvirenti, Davide Sapuppo, Mariangela Siciliano, Vittorio Rosti, Anna Candoni, Marco Zecca, Fabio Forghieri, Mario Luppi and Patrizia Comoli

Cancers 2023, 15(10), 2731; https://doi.org/10.3390/cancers15102731 - 12 May 2023

Viewed by 1704

Abstract

Acute myeloid leukemia (AML) with nucleophosmin (NPM1) genetic mutations is the most common subtype in adult patients. Refractory or relapsed disease in unfit patients or after allogeneic hematopoietic stem cell transplantation (allo-HSCT) has a poor prognosis. NPM1-mutated protein, stably expressed on tumor cells but not on normal tissues, may serve as an ideal target for NPM1-mutated AML immunotherapy. The study aim was to investigate the feasibility of producing mutated-NPM1-specific cytotoxic T cells (CTLs) suitable for somatic cell therapy to prevent or treat hematologic relapse in patients with NPM1-mutated AML. T cells were expanded or primed from patient or donor peripheral blood mononuclear cells by NPM1-mutated protein-derived peptides, and tested for leukemia antigen-targeted cytotoxic activity, cytokine production and hematopoietic precursor inhibitory effect. We found that mutated-NPM1-specific CTLs, displaying specific cytokine production and high-level cytotoxicity against patients’ leukemia blasts, and limited inhibitory activity in clonogenic assays, could be obtained from both patients and donors. The polyfunctional mutated-NPM1-specific CTLs included both CD8+ and CD4+ T cells endowed with strong lytic capacity. Our results suggest that mutated-NPM1-targeted CTLs may be a useful therapeutic option to control low-tumor burden relapse following conventional chemotherapy in older NPM1-mutated AML patients or eradicate persistent MRD after HSCT. Full article

(This article belongs to the Special Issue Autologous Stem Cell Transplantation or New Cellular Therapies for Neoplasias)

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15 pages, 2265 KiB

Open AccessArticle

Higher Age (≥60 Years) Increases the Risk for Adverse Events during Autologous Hematopoietic Stem Cell Transplantation

by Monika Haubitz, Vittoria S. von Petersdorff, Ingrid Helsen, Claudio Brunold, Elisabeth Oppliger Leibundgut and Gabriela M. Baerlocher

Cancers 2023, 15(5), 1584; https://doi.org/10.3390/cancers15051584 - 03 Mar 2023

Viewed by 1059

Abstract

Autologous hematopoietic stem cell transplantation (autoHSCT) is a standard of care for patients with hemato-oncologic diseases. This procedure is highly regulated, and a quality assurance system needs to be in place. Deviations from defined processes and outcomes are reported as adverse events (AEs: any untoward medical occurrence temporally associated with an intervention that may or may not have a causal relationship), including adverse reactions (ARs: a response to a medicinal product which is noxious and unintended). Only a few reports on AEs cover the procedure of autoHSCT from collection until infusion. Our aim was to investigate the occurrence and severity of AEs in a large data set of patients who were treated by autoHSCT. In this retrospective, observational, single-center study on 449 adult patients during the years 2016–2019, AEs occurred in 19.6% of the patients. However, only 6.0% of patients had ARs, which is a low rate compared to the percentages (13.5–56.9%) found in other studies; 25.8% of the AEs were serious and 57.5% were potentially serious. Larger leukapheresis volumes, lower numbers of collected CD34+ cells and larger transplant volumes significantly correlated with the occurrence and number of AEs. Importantly, we found more AEs in patients >60 years (see graphical abstract). By preventing potentially serious AEs of quality and procedural issues, AEs could be reduced by 36.7%. Our results provide a broad view on AEs and point out steps and parameters for the potential optimization of the autoHSCT procedure, especially in elderly patients. Full article

(This article belongs to the Special Issue Autologous Stem Cell Transplantation or New Cellular Therapies for Neoplasias)

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Graphical abstract

13 pages, 1014 KiB

Open AccessArticle

Impact of Mobilization Strategies on Peripheral Blood Stem Cell Collection Efficiency and Product Quality: A Retrospective Single-Center Study

by Patricija Rajsp, Manuela Branka, Nelly Besson, Andreas Tanzmann and Nina Worel

Cancers 2022, 14(24), 6259; https://doi.org/10.3390/cancers14246259 - 19 Dec 2022

Cited by 2 | Viewed by 2298

Abstract

Autologous stem cell transplantation is routinely used in the management of several hematological diseases, solid tumors, and immune disorders. Peripheral blood stem cell (PBSC) collection performed by apheresis is the preferred source of stem cells. In this study, the potential impact of mobilization regimens on the performance of the Spectra Optia^® continuous mononuclear cell collection system was evaluated. We performed a retrospective data analysis for patients undergoing autologous PBSC collection at the Medical University Vienna, Vienna General Hospital between September 2016 and June 2018. Collections were divided into two main groups according to the mobilization regimen received: without (210 collections) or with (99 collections) plerixafor. Assessed variables included product characteristics and collection efficiency (CE). Overall, product characteristics were similar between the groups. Median CD34+ CE2 was 50.1% versus 53.0%, and CE1 was 66.9% versus 69.9% following mobilization without and with plerixafor, respectively; the difference was not statistically significant. Simple linear regression showed a very weak positive correlation between the mobilization method and CE1 or CE2 (mobilization with plerixafor increased CE2 by 4.106%). In conclusion, the Spectra Optia^® apheresis system led to high CE and a good quality of PBSC products when mobilization regimens with or without plerixafor were used. Full article

(This article belongs to the Special Issue Autologous Stem Cell Transplantation or New Cellular Therapies for Neoplasias)

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15 pages, 2331 KiB

Open AccessArticle

SIRT1-SIRT7 Expression in Patients with Lymphoproliferative Disorders Undergoing Hematopoietic Stem Cell Mobilization

by Mateusz Nowicki, Agnieszka Wierzbowska, Emilia Stec-Martyna, Dominika Kulczycka-Wojdala, Grzegorz Nowicki and Anna Szmigielska-Kapłon

Cancers 2022, 14(5), 1213; https://doi.org/10.3390/cancers14051213 - 25 Feb 2022

Cited by 7 | Viewed by 1782

Abstract

Sirtuins are involved in the fate of hematopoietic stem cells (HSCs), including their metabolism, stress response, differentiation, migration, and apoptosis. The aim of this study was to explore SIRT1-7 expression during HSC mobilization. The study included 50 patients with lymphoproliferative disorders (39 multiple myeloma, 11 lymphoma). Samples were taken before mobilization (day 0) and on the day of first apheresis (day A). The sirtuin expression was evaluated by the Droplet Digital PCR (ddPCR) method. A significant increase of the SIRT1, SIRT2, SIRT3, SIRT5, SIRT6, and SIRT7 levels measured at day A as compared to baseline was observed. The study revealed a positive correlation between SIRT5, SIRT6, and SIRT7 expression and the CD34+ peak value in peripheral blood and the number of CD34+ cells collected on day A. Patients from the SIRT7 “high expressors” group collected more CD34+ cells on day A than “low expressors”. Upregulated expressions of SIRT3 and SIRT7 on the day of first apheresis were observed in patients in complete remission status (CR) as compared to the non-CR group. Our results suggest that the investigated sirtuins may influence the HSC migration and hematopoietic landscape during mobilization. SIRT5, SIRT6, and SIRT7 may be associated with the efficacy of HSC mobilization. Full article

(This article belongs to the Special Issue Autologous Stem Cell Transplantation or New Cellular Therapies for Neoplasias)

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Review

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14 pages, 748 KiB

Open AccessReview

Vaccination Therapy for Acute Myeloid Leukemia: Where Do We Stand?

by Kordelia Barbullushi, Nicolò Rampi, Fabio Serpenti, Mariarita Sciumè, Sonia Fabris, Pasquale De Roberto and Nicola Stefano Fracchiolla

Cancers 2022, 14(12), 2994; https://doi.org/10.3390/cancers14122994 - 17 Jun 2022

Cited by 11 | Viewed by 2667

Abstract

Immunotherapy is changing the therapeutic landscape of many hematologic diseases, with immune checkpoint inhibitors, bispecific antibodies, and CAR-T therapies being its greatest expression. Unfortunately, immunotherapy in acute myeloid leukemia (AML) has given less brilliant results up to now, and the only approved drug is the antiCD33 antibody-drug conjugate gemtuzumab ozogamicin. A promising field of research in AML therapy relies on anti-leukemic vaccination to induce remission or prevent disease relapse. In this review, we analyze recent evidence on AML vaccines and their biological mechanisms. The principal proteins that have been exploited for vaccination strategies and have reached clinical experimental phases are Wilm’s tumor 1, proteinase 3, and RHAMM. the majority of data deals with WT1-base vaccines, given also the high expression and mutation rates of WT1 in AML cells. Stimulators of immune responses such as TLR7 agonist and interleukin-2 have also proven anti-leukemic activity both in vivo and in vitro. Lastly, cellular vaccines mainly based on autologous or allogeneic off-the-shelf dendritic cell-based vaccines showed positive results in terms of T-cell response and safety, also in elderly patients. Compared to other immunotherapeutic strategies, anti-AML vaccines have the advantage of being a less toxic and a more manageable approach, applicable also to elderly patients with poorer performance status, and may be used in combination with currently available therapies. As for the best scenario in which to use vaccination, whether in a therapeutic, prophylactic, or preemptive setting, further studies are needed, but available evidence points to poorer results in the presence of active or high-burden disease. Given the poor prognosis of relapsed/refractory or high-risk AML, further research is urgently needed to better understand the biological pathways that sustain its pathogenesis. In this setting, research on novel frontiers of immunotherapy-based agents, among which vaccines represent important actors, is warranted to develop new and efficacious strategies to obtain long-term disease control by immune patrolling. Full article

(This article belongs to the Special Issue Autologous Stem Cell Transplantation or New Cellular Therapies for Neoplasias)

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12 pages, 274 KiB

Open AccessReview

Autologous Stem Cell Transplantation in Hodgkin Lymphoma—Latest Advances in the Era of Novel Therapies

by Yazeed Samara and Matthew Mei

Cancers 2022, 14(7), 1738; https://doi.org/10.3390/cancers14071738 - 29 Mar 2022

Cited by 4 | Viewed by 2442

Abstract

Standard treatment for relapsed and/or refractory (r/r) Hodgkin lymphoma (HL) consists of salvage therapy, historically consisting of multiagent cytotoxic chemotherapy, followed by autologous stem cell transplantation (autoHCT) in responding patients. With this approach, most patients can proceed to autoHCT, of whom approximately half are cured. However, the introduction of the novel agents brentuximab vedotin (BV) and the checkpoint inhibitors (CPI) nivolumab and pembrolizumab has changed the decision making and peri-transplant decision making, as early incorporation of one or more of these agents can reduce or even eliminate the need for cytotoxic chemotherapy prior to autoHCT. Furthermore, post-autoHCT maintenance therapy with BV has also been shown to decrease relapse in high-risk rel/ref HL patients. In this review, we survey the current data regarding autoHCT in HL with a focus on pre-autoHCT salvage as well as maintenance strategies, and we also talk about the emerging data challenging the long-held dogma of chemosensitivity being a requirement for successful autoHCT. Full article

(This article belongs to the Special Issue Autologous Stem Cell Transplantation or New Cellular Therapies for Neoplasias)

11 pages, 2175 KiB

Open AccessReview

Cytopenia after CAR-T Cell Therapy—A Brief Review of a Complex Problem

by Naman Sharma, Patrick M. Reagan and Jane L. Liesveld

Cancers 2022, 14(6), 1501; https://doi.org/10.3390/cancers14061501 - 15 Mar 2022

Cited by 45 | Viewed by 5570

Abstract

Chimeric Antigen Receptor T-cell (CAR-T) immunotherapy has emerged as an efficacious and life extending treatment modality with high response rates and durable remissions in patients with relapsed and refractory non-Hodgkin lymphoma (NHL), follicular lymphoma, and B-cell acute lymphoblastic leukemia (B-ALL) as well as in other diseases. Prolonged or recurrent cytopenias after CAR-T therapy have increasingly been reported at varying rates, and the pathogenesis of this complication is not yet well-understood but is likely contributed to by multiple factors. Current studies reported are primarily retrospective, heterogeneous in terms of CAR-Ts used and diseases treated, non-uniform in definitions of cytopenias and durations for end points, and vary in terms of recommended management. Prospective studies and correlative laboratory studies investigating the pathophysiology of prolonged cytopenias will enhance our understanding of this phenomenon. This review summarizes knowledge of these cytopenias to date. Full article

(This article belongs to the Special Issue Autologous Stem Cell Transplantation or New Cellular Therapies for Neoplasias)

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