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Cancers
Special Issues
Clinical Research for Hematopoietic Stem Cell Transplant and Cellular Therapy
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Clinical Research for Hematopoietic Stem Cell Transplant and Cellular Therapy

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

Deadline for manuscript submissions: closed (20 February 2024) | Viewed by 6562

Special Issue Editors

Dr. Yvonne A. Efebera

E-Mail Website
Guest Editor
Division of Hematology, Blood and Marrow Transplant, OhioHealth, Columbus, OH 43214, USA
Interests: blood and marrow transplant; cellular therapy; multiple myeloma, amyloidosis
Special Issues, Collections and Topics in MDPI journals
Dr. Nidhi Sharma

E-Mail Website
Guest Editor
Department of Internal Medicine, Division of Hematology, The Ohio State University, Columbus, OH 43210, USA
Interests: blood and marrow transplant; cellular therapy; multiple myeloma; leukemia; lymphoma

Special Issue Information

Dear Colleagues,

The last ten years have seen significant improvements in the field of hematopoietic stem cell transplantation (HSCT) and cellular therapy for newly diagnosed and relapse/refractory patients with hematologic disorders. Improvements in the supportive management and development of novel agents have led to increases in survival outcomes in patients undergoing ASCT for multiple myeloma and lymphoma. Advances in conditioning regimens; the expanding use of alternative donor stem cell sources such as haploidentical stem cells and cord blood; and the use of modern T-cell depletion strategies such as post-transplant cyclophosphamide, have led to better survival outcomes and a reduction in incidences of graft versus host disease (GVHD), while improving the graft versus host disease effect in patients undergoing allo-SCT for a wide range of hematologic disorders. Chimeric antigen receptor T-cell (CAR-T) is approved for relapse and refractory lymphoma, multiple myeloma and some leukemias, especially in patients who are not eligible for HSCT or have progressed after HSCT. CAR-T is also being studied in earlier lines of therapy post HSCT, or as an alternative to HSCT.

In this Special Issue, we welcome papers in hematopoietic stem cell transplantation (HSCT) and cellular therapy in newly diagnosed and relapse/refractory hematologic disorders, and the challenges in deciding on the optimal practice.

Dr. Yvonne A. Efebera
Dr. Nidhi Sharma
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 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

  • stem cell transplant (SCT)
  • autologous SCT
  • Allogeneic SCT
  • acute Graft-versus-host-disease (aGVHD)
  • chronic GVHD
  • Haplo-SCT
  • Infections in SCT
  • maintenance Post SCT
  • GVHD prophylaxis
  • cellular therapy in Hematologic disorders
  • Chimeric-Antigen-Receptor T-cell (CAR-T)

Published Papers (5 papers)

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Research

13 pages, 1810 KiB  
Article
Donor Lymphocyte Infusion in the Treatment of Post-Transplant Relapse of Acute Myeloid Leukemias and Myelodysplastic Syndromes Significantly Improves Overall Survival: A French–Italian Experience of 134 Patients
by Eugenia Accorsi Buttini, Cristina Doran, Michele Malagola, Vera Radici, Marco Galli, Vicky Rubini, Alessandro Leoni, Mirko Farina, Nicola Polverelli, Federica Re, Simona Bernardi, Mohamad Mohty, Domenico Russo and Eolia Brissot
Cancers 2024, 16(7), 1278; https://doi.org/10.3390/cancers16071278 - 26 Mar 2024
Viewed by 597
Abstract
Background: Disease relapse after allogeneic stem cell transplantation (allo-SCT) is the main challenge for curing acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). We investigated the overall survival (OS) after allo-SCT relapse according to different therapeutic approaches. Methods: We analyzed 134 patients who [...] Read more.
Background: Disease relapse after allogeneic stem cell transplantation (allo-SCT) is the main challenge for curing acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). We investigated the overall survival (OS) after allo-SCT relapse according to different therapeutic approaches. Methods: We analyzed 134 patients who relapsed after allo-SCT performed between 2015 and 2021 at Saint-Antoine University Hospital, Paris and Spedali Civili di Brescia, Brescia. Of these, 103 (77%) were treated, comprising 69/103 (67%) who received therapy in overt relapse and 34/103 (33%) who were treated in a pre-emptive manner when molecular/cytogenetics recurrence or mixed chimerism occurred. The treatment was donor lymphocyte infusion (DLI)-based for 40/103 (39%) patients. Results: The 1-, 2-, and 5-year OS of patients treated with DLI (n = 40) was 67%, 34%, and 34%, respectively, for those treated preventively (n = 20) and 43%, 20%, and 20%, respectively, for those treated in overt relapse (n = 20) (p < 0.01). The 1-, 2-, and 5-year OS of patients treated without DLI (n = 63) was 54%, 40%, and 26%, respectively, for those treated preventively (n = 14) and 17%, 5%, and 0%, respectively, for those treated in overt relapse (n = 49) (p < 0.01). Conclusions: Relapse treatment with a pre-emptive strategy was associated with improved outcomes, particularly when DLI was employed. Full article
(This article belongs to the Special Issue Clinical Research for Hematopoietic Stem Cell Transplant and Cellular Therapy)
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11 pages, 241 KiB  
Article
Incidence of Catheter-Associated Bloodstream Infections in Stem Cell Recipients—Should We Be “PICCy”?
by Sławomir Milczarek, Piotr Kulig, Oliwia Piotrowska, Alina Zuchmańska, Ewa Wilk-Milczarek and Bogusław Machaliński
Cancers 2024, 16(6), 1239; https://doi.org/10.3390/cancers16061239 - 21 Mar 2024
Viewed by 1777
Abstract
The management of patients undergoing HSCT requires a multipurpose central venous catheter. Peripheral catheters (PCs), such as peripherally inserted central catheters (PICCs) and MidLine catheters (MLCs), appear to be adequate vascular catheters to be used for stem cell infusion, although their utilization in [...] Read more.
The management of patients undergoing HSCT requires a multipurpose central venous catheter. Peripheral catheters (PCs), such as peripherally inserted central catheters (PICCs) and MidLine catheters (MLCs), appear to be adequate vascular catheters to be used for stem cell infusion, although their utilization in this indication is not yet common. We analyzed the infectious complications such as blood stream infection (BSI), febrile neutropenia (FN) and central line-associated bloodstream infection (CLBSI) in patients undergoing stem cell infusion through PC and conventionally inserted central catchers (CICCs), and evaluated their impacts on transplantation outcomes. Our results reveal no statistically significant differences between different types of catheter in terms of FN, BSI and CLABSI. Moreover, transplantation outcomes were comparable between the groups. Interestingly, according to our data, there were no differences in terms of abovementioned infectious complications between individuals who received antibiotic prophylaxis and those who did not. Our study has shown that infection complications are independent of the intravenous device and antibiotic prophylaxis. Considering that PCs are not associated with life-threatening complications, they should be considered more frequently in the stem cell transplantation setting. Full article
(This article belongs to the Special Issue Clinical Research for Hematopoietic Stem Cell Transplant and Cellular Therapy)
14 pages, 2684 KiB  
Article
Allogeneic Stem Cell Transplantation in Multiple Myeloma: Risk Factors and Outcomes in the Era of New Therapeutic Options—A Single-Center Experience
by Irene Strassl, Alexander Nikoloudis, Sigrid Machherndl-Spandl, Veronika Buxhofer-Ausch, Michaela Binder, Dagmar Wipplinger, Olga Stiefel, Emine Kaynak, Robert Milanov, Christoph Aichinger, Stefanie Nocker, Thomas Bauer, Stefanie Kreissl, Michael Girschikofsky, Andreas Petzer, Ansgar Weltermann and Johannes Clausen
Cancers 2023, 15(24), 5738; https://doi.org/10.3390/cancers15245738 - 7 Dec 2023
Viewed by 1066
Abstract
Background: Despite major treatment advances, multiple myeloma remains incurable. The outcome of patients who are refractory to immunomodulatory agents, proteasome inhibitors, and anti-CD38 monoclonal antibodies is poor, and improved treatment strategies for this difficult-to-treat patient population are an unmet medical need. Methods: This [...] Read more.
Background: Despite major treatment advances, multiple myeloma remains incurable. The outcome of patients who are refractory to immunomodulatory agents, proteasome inhibitors, and anti-CD38 monoclonal antibodies is poor, and improved treatment strategies for this difficult-to-treat patient population are an unmet medical need. Methods: This retrospective, unicentric analysis included 38 patients with relapsed/refractory multiple myeloma or plasma cell leukemia who underwent allogeneic stem cell transplantation (allo-HSCT) between 2013 and 2022. Survival outcomes, relapse incidence, and non-relapse mortality were calculated according to remission status, date of allo-HSCT, cytogenetic risk status, timing, and number of previous autologous HSCTs. Results: The median PFS was 13.6 months (95% CI, 7.7–30.4) and the median OS was 51.4 months (95% CI, 23.5–NA) in the overall cohort. The cumulative incidence of relapse at 3 years was 57%, and non-relapse mortality was 16%. The median PFS and OS were significantly longer in patients with very good partial remission (VGPR) or better compared to patients with less than VGPR at the time of allo-HSCT (mPFS 29.7 months (95% CI, 13.7–NA) vs. 6.5 months (95% CI, 2.6–17.0); p = 0.009 and mOS not reached vs. 18.6 months (95% CI, 7.0–NA); p = 0.006). Conclusion: For selected patients, allo-HSCT may result in favorable overall survival, in part by providing an appropriate hemato-immunological basis for subsequent therapies. Full article
(This article belongs to the Special Issue Clinical Research for Hematopoietic Stem Cell Transplant and Cellular Therapy)
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15 pages, 2535 KiB  
Article
Trends in Outcome of Hematopoietic Stem Cell Transplantation: 5000 Transplantations and 30 Years of Single-Center Experience
by Ludmila Stepanovna Zubarovskaya, Ivan Sergeevich Moiseev, Maria Dmidrievna Vladovskaya, Natalia Borisovna Mikhailova, Elena Vladislavovna Morozova, Tatyana Alexandrovna Bykova, Yulia Yurievna Vlasova, Olesya Vladimirovna Paina, Ilya Viktorovich Kazantsev, Olga Alexandrovna Slesarchuk, Anna Gennadyevna Smirnova, Anna Alekseevna Osipova, Liliya Vladimirovna Stelmakh, Alexey Yurievich Polushin, Oleg Valerievich Goloshchapov, Maxim Pavlovich Bogomolny, Maria Arkadievna Estrina, Marina Olegovna Popova, Maxim Anatolievich Kucher, Alisa Georgievna Volkova, Alexander Leonidovich Alyansky, Dmitrii Eduardovich Pevtcov, Natalia Evgenievna Ivanova, Elena Vitalievna Babenko, Nikolai Nikolaevich Mamaev, Tatiana Leonidovna Gindina, Alina Alexandrovna Vitrishchak, Alexei Borisovich Chukhlovin, Elena Vladimirovna Semenova, Sergei Nicolaevich Bondarenko, Alexander Dmitrievich Kulagin and Boris Vladimirovich Afanasyevadd Show full author list remove Hide full author list
Cancers 2023, 15(19), 4758; https://doi.org/10.3390/cancers15194758 - 28 Sep 2023
Viewed by 946
Abstract
In this single-center analysis, we evaluated the trends in 5185 hematopoietic cell transplantations performed between 1990 and 2022. The study group comprised 3237 allogeneic (alloHCT) and 1948 autologous (autoHCT) hematopoietic cell transplantations. In the multivariate analysis, there was an improvement in event-free-survival (EFS) [...] Read more.
In this single-center analysis, we evaluated the trends in 5185 hematopoietic cell transplantations performed between 1990 and 2022. The study group comprised 3237 allogeneic (alloHCT) and 1948 autologous (autoHCT) hematopoietic cell transplantations. In the multivariate analysis, there was an improvement in event-free-survival (EFS) after autoHCT (HR 0.6, 95% CI 0.4–0.7, p < 0.0001) due to reduced cumulative incidence of relapse in the last five years (56% in 2010–2014 vs. 38% in 2015–2022). An improvement in EFS after alloHCT over time was observed (HR 0.33, 95% CI 0.23–0.48, p < 0.0001), which was due to reduced non-relapse mortality. No difference in cumulative relapse incidence was observed over the last decade for allografted patients. Survival after autoHCT improved in Hodgkin’s disease (HR 0.1, 95% CI 0.1–0.3), multiple myeloma (HR 0.4, 95% CI 0.2–0.7) and solid tumors (HR 0.2, 95% CI 0.2–0.4), while after alloHCT, improvement was observed in acute myeloid leukemia (HR 0.3, 95% CI 0.1–0.5), acute lymphoblastic leukemia (HR 0.2, 95% CI 0.1–0.5), Hodgkin’s disease (HR 0.1, 95% CI 0.0–0.4), non-Hodgkin’s lymphomas and chronic lymphocytic leukemia (HR 0.2, 95% CI 0.0–0.6), inborn diseases (HR 0.2, 95% CI 0.2–0.4) and acquired aplastic anemia with matched related donors and matched unrelated donors (HR 0.3, 95% CI 0.2–0.8). Full article
(This article belongs to the Special Issue Clinical Research for Hematopoietic Stem Cell Transplant and Cellular Therapy)
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19 pages, 6180 KiB  
Article
Hematopoietic Stem Cell (HSC)-Independent Progenitors Are Susceptible to Mll-Af9-Induced Leukemic Transformation
by Cristiana Barone, Roberto Orsenigo, Anna Cazzola, Elisabetta D’Errico, Arianna Patelli, Giulia Quattrini, Barbara Vergani, Silvia Bombelli, Sofia De Marco, Cristina D’Orlando, Cristina Bianchi, Biagio Eugenio Leone, Raffaella Meneveri, Andrea Biondi, Giovanni Cazzaniga, Terence Howard Rabbitts, Silvia Brunelli and Emanuele Azzoni
Cancers 2023, 15(14), 3624; https://doi.org/10.3390/cancers15143624 - 14 Jul 2023
Viewed by 1484
Abstract
Infant acute myeloid leukemia (AML) is a heterogeneous disease, genetically distinct from its adult counterpart. Chromosomal translocations involving the KMT2A gene (MLL) are especially common in affected infants of less than 1 year of age, and are associated with a dismal [...] Read more.
Infant acute myeloid leukemia (AML) is a heterogeneous disease, genetically distinct from its adult counterpart. Chromosomal translocations involving the KMT2A gene (MLL) are especially common in affected infants of less than 1 year of age, and are associated with a dismal prognosis. While these rearrangements are likely to arise in utero, the cell of origin has not been conclusively identified. This knowledge could lead to a better understanding of the biology of the disease and support the identification of new therapeutic vulnerabilities. Over the last few years, important progress in understanding the dynamics of fetal hematopoiesis has been made. Several reports have highlighted how hematopoietic stem cells (HSC) provide little contribution to fetal hematopoiesis, which is instead largely sustained by HSC-independent progenitors. Here, we used conditional Cre-Lox transgenic mouse models to engineer the Mll-Af9 translocation in defined subsets of embryonic hematopoietic progenitors. We show that embryonic hematopoiesis is generally permissive for Mll-Af9-induced leukemic transformation. Surprisingly, the selective introduction of Mll-Af9 in HSC-independent progenitors generated a transplantable myeloid leukemia, whereas it did not when introduced in embryonic HSC-derived cells. Ex vivo engineering of the Mll-Af9 rearrangement in HSC-independent progenitors using a CRISPR/Cas9-based approach resulted in the activation of an aberrant myeloid-biased self-renewal program. Overall, our results demonstrate that HSC-independent hematopoietic progenitors represent a permissive environment for Mll-Af9-induced leukemic transformation, and can likely act as cells of origin of infant AML. Full article
(This article belongs to the Special Issue Clinical Research for Hematopoietic Stem Cell Transplant and Cellular Therapy)
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