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Stem Cell Transplantation in Hematological Malignancies

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A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Hematology".

Deadline for manuscript submissions: closed (30 November 2021) | Viewed by 14913

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Special Issue Editors

Dr. Pietro Merli

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Guest Editor

Department of Pediatric Hematology/Oncology, Cell and Gene Therapy, IRCCS Bambino Gesù Children's Hospital, Rome, Italy
Interests: haploidentical HSCT; graft manipulation; graft failure; fecal microbiota transplantation; HLH; AML

Dr. Lucia Prezioso

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Guest Editor

Department of Medicine and Surgery, Hematology and BMT Unit, University of Parma, Parma, Italy
Interests: haploidentical HSCT; infectious complications; graft manipulation; immune reconstitution; GVHD

Special Issue Information

Dear Colleagues,

In an “Immunotherapy Era”, allogeneic hematopoietic stem cell transplantation (HSCT), the oldest type of immunotherapy used in hematology clinical practice, is still the sole established curative treatment option for many hematologic malignancies and, less frequently, for other neoplastic disorders.

After more than 60 years of experience in HSCT, in the last several decades the procedure has seen dramatic progress in HLA-matching techniques, choices of conditioning regimens, graft manipulation strategies, graft-versus-host disease prophylaxis and treatment, as well as in supportive care. Moreover, advances in the diagnosis and treatment of many peculiar complications (such as sinusoidal obstruction syndrome/veno-occlusive disease, thrombotic microangiopathy, etc.) have been achieved.

These improvements led to a substantial reduction of transplant-related mortality, widening the application of HSCT in terms of indications (e.g., earlier in the course of the disease) and eligibility (e.g., for unfit patients).

The recent advent of T-cell therapies, in particular of CAR T cells, holds the promise of a revolution in the treatment of certain hematologic malignancies (i.e., those of B-cell origin). In this context, the role of HSCT is also being challenged.

This Special Issue will focus on the role of HSCT in the changing scenario of hematological malignancies treatment.

Dr. Pietro Merli
Dr. Lucia Prezioso
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. Journal of Clinical Medicine 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 2600 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 lymphoblastic leukemia
Acute myeloid leukemia
Graft manipulation
Immune reconstitution
Minimal residual disease
Lymphoma

Published Papers (5 papers)

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Research

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9 pages, 1545 KiB

Open AccessArticle

Early Reconstitution of Antibody Secreting Cells after Allogeneic Stem Cell Transplantation

by Martina Hinterleitner, Clemens Hinterleitner, Elke Malenke, Birgit Federmann, Ursula Holzer, Martin Müller, Wolfgang A. Bethge and Stefan Wirths

J. Clin. Med. 2022, 11(1), 270; https://doi.org/10.3390/jcm11010270 - 05 Jan 2022

Viewed by 1586

Abstract

Immune cell reconstitution after stem cell transplantation is allocated over several stages. Whereas cells mediating innate immunity recover rapidly, adaptive immune cells, including T and B cells, recover slowly over several months. In this study we investigated kinetics and reconstitution of de novo B cell formation in patients receiving CD3 and CD19 depleted haploidentical stem cell transplantation with additional in vivo T cell depletion with monoclonal anti-CD3 antibody. This model enables a detailed in vivo evaluation of hierarchy and attribution of defined lymphocyte populations without skewing by mTOR- or NFAT-inhibitors. As expected CD3⁺ T cells and their subsets had delayed reconstitution (<100 cells/μL at day +90). Well defined CD19⁺ B lymphocytes of naïve and memory phenotype were detected at day +60. Remarkably, we observed a very early reconstitution of antibody-secreting cells (ASC) at day +14. These ASC carried the HLA-haplotype of the donor and secreted the isotypes IgM and IgA more prevalent than IgG. They correlated with a population of CD19⁻ CD27⁻ CD38^low/+ CD138⁻ cells. Of note, reconstitution of this ASC occurred without detectable circulating T cells and before increase of BAFF or other B cell stimulating factors. In summary, we describe a rapid reconstitution of peripheral blood ASC after CD3 and CD19 depleted haploidentical stem cell transplantation, far preceding detection of naïve and memory type B cells. Incidence before T cell reconstitution and spontaneous secretion of immunoglobulins allocate these early ASC to innate immunity, eventually maintaining natural antibody levels. Full article

(This article belongs to the Special Issue Stem Cell Transplantation in Hematological Malignancies)

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11 pages, 248 KiB

Open AccessArticle

Allogeneic Stem Cell Transplantation for Adult T-Cell Leukemia/Lymphoma—Romanian Experience

by Alina D. Tanase, Andrei Colita, Oana G. Craciun, Lavinia Lipan, Zsofia Varady, Laura Stefan, Adela Ranete, Sergiu Pasca, Horia Bumbea, Mihaela Andreescu, Viola Popov, Alexandru Bardas, Daniel Coriu, Anca Roxana Lupu, Ciprian Tomuleasa, Anca Colita and Olivier Hermine

J. Clin. Med. 2020, 9(8), 2417; https://doi.org/10.3390/jcm9082417 - 28 Jul 2020

Cited by 12 | Viewed by 2148

Abstract

Adult T-cell leukemia/lymphoma (ATLL) is a rare and aggressive mature T-cell malignancy caused by the human T lymphoma virus I (HTLV-I) affecting 3–5% of HTLV-1 carriers and is usually diagnosed in endemic regions. Romania is a region with high prevalence of HTLV-1 infection and ATLL and with low median age at diagnosis for aggressive types. We performed a retrospective analysis of post-transplant outcome in the first Romanian patients with ATLL receiving hematopoietic stem cell allotransplant. The study population included eight patients (three males, five females), with median age of 39.5 (range 26–57), with acute (one case) and lymphoma type (seven cases) that received peripheral stem cells (PBSC) from matched related (MRD) and unrelated donors (MUD) after reduced intensity conditioning. Graft versus host disease (GVHD) developed in six patients. Relapse occurred in four cases (50%) at a median time of 5-months post-transplant. Six patients died: four cases with disease-related deaths and two patients with GVHD-related deaths. The median survival post-transplant was 19.5 months (range 2.3–44.2 months). The post-transplant survival at 1-year was 62.5%, at 2-years 50%, and at 3-years 37.5%. In our opinion allogeneic transplant improves outcome in aggressive type ATLL. Full article

(This article belongs to the Special Issue Stem Cell Transplantation in Hematological Malignancies)

16 pages, 2623 KiB

Open AccessArticle

Optimizing Preparative Regimen for Umbilical Cord Blood Transplantation in Adult Acute Leukemia Patients: Acute Lymphoblastic Leukemia Requires Myeloablative Conditioning but Not Acute Myeloid Leukemia

by Ja Min Byun, Junshik Hong, Doyeun Oh, Ho-Young Yhim, Young Rok Do, Joon Seong Park, Chul Won Jung, Deok-Hwan Yang, Jong-Ho Won, Hong Ghi Lee, Joon Ho Moon, Yeung-Chul Mun, Deog-Yeon Jo, Jae Joon Han, Je-Hwan Lee, Jae Hoon Lee, Junglim Lee and Sung-Soo Yoon

J. Clin. Med. 2020, 9(7), 2310; https://doi.org/10.3390/jcm9072310 - 21 Jul 2020

Cited by 1 | Viewed by 2204

Abstract

Cord blood transplantation (CBT) is a valuable alternative to bone marrow transplantation in adults without readily available donors. We conducted this study to investigate the feasibility of CBT for adult patients with acute leukemia with regards to impact of different conditioning and graft-versus-host disease (GVHD) prophylaxis regimens on clinical outcomes. From 16 centers in Korea, 41 acute myeloid leukemia (AML) and 29 ALL (acute lymphoblastic leukemia) patients undergoing CBT were enrolled. For AML patients, the neutrophil engraftment was observed in 87.5% of reduced intensity conditioning (RIC) and 72.0% of myeloablative conditioning (MAC) (p = 0.242). The median RFS was 5 months and OS 7 months. Conditioning regimen did not affect relapse free survival (RFS) or overall survival (OS). GVHD prophylaxis using calcineurin inhibitors (CNI) plus methotrexate was associated with better RFS compared to CNI plus ATG (p = 0.032). For ALL patients, neutrophil engraftment was observed in 55.6% of RIC and 90.0% of MAC (p = 0.034). The median RFS was 5 months and OS 19 months. MAC regimens, especially total body irradiation (TBI)-based regimen, were associated with both longer RFS and OS compared to other conditioning regimens. In conclusion, individualized conditioning regimens will add value in terms of enhancing safety and efficacy of CBT. Full article

(This article belongs to the Special Issue Stem Cell Transplantation in Hematological Malignancies)

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Review

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11 pages, 271 KiB

Open AccessReview

Sexual and Emotional Health after Allogeneic Hematopoietic Cell Transplantation: A Comprehensive Review and Guidelines from the Francophone Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC)

by Tamim Alsuliman, Ludovic Jondreville, Caroline Baylet, Marie-Pierre Dann, Natacha De Bentzmann, Marie-Laure Fontoura, Carole Genty, Anne Huynh, Diane Ibled, Ibrahim Yakoub-Agha, Lara Mercier, Catherine Poirot, Sophie Porcheron, Catherine Tourette-Turgis, Jean-Paul Vernant, Dominique Vexiau-Robert and Stéphanie Nguyen

J. Clin. Med. 2022, 11(5), 1196; https://doi.org/10.3390/jcm11051196 - 23 Feb 2022

Cited by 1 | Viewed by 2105

Abstract

A person’s sexual and emotional life is greatly impacted after allogeneic hematopoietic stem cell transplantation (allo-HSCT). This topic is not addressed very much by patients and caregivers. Physical, endocrine and genital chronic graft versus host disease (cGVHD)-related disorders are multiple and intertwined with psychological disorders. The Francophone Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC) has issued recommendations for a better gynecological monitoring of female recipients after allo-HCT. A patient booklet was also offered to patients in the form of questions and answers to facilitate discussions between patients and caregivers and to improve the management of sexual and emotional life after transplant. Full article

(This article belongs to the Special Issue Stem Cell Transplantation in Hematological Malignancies)

19 pages, 639 KiB

Open AccessReview

Cytokine Release Syndrome in the Immunotherapy of Hematological Malignancies: The Biology behind and Possible Clinical Consequences

by Tor Henrik Anderson Tvedt, Anh Khoi Vo, Øystein Bruserud and Håkon Reikvam

J. Clin. Med. 2021, 10(21), 5190; https://doi.org/10.3390/jcm10215190 - 06 Nov 2021

Cited by 20 | Viewed by 6105

Abstract

Cytokine release syndrome (CRS) is an acute systemic inflammatory syndrome characterized by fever and multiple organ dysfunction associated with (i) chimeric antigen receptor (CAR)-T cell therapy, (ii) therapeutic antibodies, and (iii) haploidentical allogeneic stem cell transplantation (haplo-allo-HSCT). Severe CRS can be life-threatening in some cases and requires prompt management of those toxicities and is still a great challenge for physicians. The pathophysiology of CRS is still not fully understood, which also applies to the identifications of predictive biomarkers that can forecast these features in advance. However, a broad range of cytokines are involved in the dynamics of CRS. Treatment approaches include both broad spectrum of immunosuppressant, such as corticosteroids, as well as more specific inhibition of cytokine release. In the present manuscript we will try to review an update regarding pathophysiology, etiology, diagnostics, and therapeutic options for this serious complication. Full article

(This article belongs to the Special Issue Stem Cell Transplantation in Hematological Malignancies)

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