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The Future of Curative Therapies for Sickle Cell Disease
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The Future of Curative Therapies for Sickle Cell Disease

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

Deadline for manuscript submissions: closed (1 May 2022) | Viewed by 11874

Special Issue Editor

Dr. Courtney Fitzhugh

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Guest Editor
Chief, Laboratory of Early Sickle Mortality Prevention, Cellular and Molecular Therapeutics Branch, NHLBI, NIH, Bethesda, MD, USA
Interests: sickle cell disease; hematopoietic stem cell transplantation; genetic blood disorder

Special Issue Information

Dear Colleagues,

Sickle cell disease (SCD) frequently leads to extensive morbidity, including debilitating pain, chronic organ complications such as stroke, cardiopulmonary complications, and kidney failure, and early mortality. While approximately 100,000 individuals with SCD reside in the United States, millions of people suffer from the disease around the world. The first patient was reported to be cured of SCD in 1984. Since then, approximately 2000 patients have been reported to be cured, primarily in developed countries.

Fortunately, multiple curative options exist for patients with SCD, including myeloablative and non-myeloablative HLA-matched sibling hematopoietic stem cell transplantation (HSCT), non-myeloablative haploidentical HSCT, reduced-intensity matched unrelated donor HSCT, myeloablative gene therapy, and myeloablative gene editing. The results of allogeneic HSCT have substantially improved over the past decade, and results in the majority of patients undergoing gene therapy have been encouraging. Further, the first report of a patient receiving gene editing for SCD was recently published with impressive results.

How will patients with SCD, their family members, and providers choose among these various curative options? This Special Issue aims to provide a single source to describe the most updated results for the different options. Original research articles and reviews are welcome. Research areas may include but are not limited to a debate on which approach looks most promising for children and adults in the future. How can the results of HLA-matched sibling HSCT improve even more for children? What curative options are available for adults who are at early risk for death and for patients who live in developing countries? What are the long-term health effects of curative therapy on the heart, lungs, and kidneys, organs that have been associated with early mortality in adults with SCD? Answers to these questions will help paint a picture of the future of curative therapies for individuals with SCD.

We look forward to receiving your contributions.

Dr. Courtney Fitzhugh
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. 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

  • Sickle cell disease
  • Hematopoietic stem cell transplant
  • HLA-matched sibling
  • Haploidentical
  • Matched unrelated donor
  • Gene therapy
  • Gene editing
  • Late effects

Published Papers (4 papers)

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Review

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11 pages, 559 KiB  
Review
Across the Myeloablative Spectrum: Hematopoietic Cell Transplant Conditioning Regimens for Pediatric Patients with Sickle Cell Disease
by Emily Limerick and Allistair Abraham
J. Clin. Med. 2022, 11(13), 3856; https://doi.org/10.3390/jcm11133856 - 3 Jul 2022
Cited by 3 | Viewed by 1958
Abstract
One out of every five hundred African American children in the United States has sickle cell disease (SCD). While multiple disease-modifying therapies are available, hematopoietic cell transplantation (HCT) remains the only curative option for children with SCD. HLA-matched sibling HCT has demonstrated excellent [...] Read more.
One out of every five hundred African American children in the United States has sickle cell disease (SCD). While multiple disease-modifying therapies are available, hematopoietic cell transplantation (HCT) remains the only curative option for children with SCD. HLA-matched sibling HCT has demonstrated excellent efficacy, but its availability remains limited; alternative donor strategies are increasingly explored. While Busulfan-Cyclophosphamide has become the most widespread conditioning regimen employed in HCT for pediatric SCD, many other regimens have been examined. This review explores different conditioning regimens across the intensity spectrum: from myeloablative to non-myeloablative. We describe survival and organ function outcomes in pediatric SCD patients who have received HCT and discuss the strengths and weaknesses of the various conditioning intensities. Finally, we posit novel directions in allogeneic HCT for SCD. Full article
(This article belongs to the Special Issue The Future of Curative Therapies for Sickle Cell Disease)
21 pages, 390 KiB  
Review
Long-Term Health Effects of Curative Therapies on Heart, Lungs, and Kidneys for Individuals with Sickle Cell Disease Compared to Those with Hematologic Malignancies
by Courtney D. Fitzhugh, Emmanuel J. Volanakis, Ombeni Idassi, Josh A. Duberman, Michael R. DeBaun and Debra L. Friedman
J. Clin. Med. 2022, 11(11), 3118; https://doi.org/10.3390/jcm11113118 - 31 May 2022
Cited by 4 | Viewed by 2187
Abstract
The goal of curing children and adults with sickle cell disease (SCD) is to maximize benefits and minimize intermediate and long-term adverse outcomes so that individuals can live an average life span with a high quality of life. While greater than 2000 individuals [...] Read more.
The goal of curing children and adults with sickle cell disease (SCD) is to maximize benefits and minimize intermediate and long-term adverse outcomes so that individuals can live an average life span with a high quality of life. While greater than 2000 individuals with SCD have been treated with curative therapy, systematic studies have not been performed to evaluate the long-term health effects of hematopoietic stem cell transplant (HSCT) in this population. Individuals with SCD suffer progressive heart, lung, and kidney disease prior to curative therapy. In adults, these sequalae are associated with earlier death. In comparison, individuals who undergo HSCT for cancer are heavily pretreated with chemotherapy, resulting in potential acute and chronic heart, lung, and kidney disease. The long-term health effects on the heart, lung, and kidney for children and adults undergoing HSCT for cancer have been extensively investigated. These studies provide the best available data to extrapolate the possible late health effects after curative therapy for SCD. Future research is needed to evaluate whether HSCT abates, stabilizes, or exacerbates heart, lung, kidney, and other diseases in children and adults with SCD receiving myeloablative and non-myeloablative conditioning regimens for curative therapy. Full article
(This article belongs to the Special Issue The Future of Curative Therapies for Sickle Cell Disease)
21 pages, 370 KiB  
Review
Fertility after Curative Therapy for Sickle Cell Disease: A Comprehensive Review to Guide Care
by Robert Sheppard Nickel, Jacqueline Y. Maher, Michael H. Hsieh, Meghan F. Davis, Matthew M. Hsieh and Lydia H. Pecker
J. Clin. Med. 2022, 11(9), 2318; https://doi.org/10.3390/jcm11092318 - 21 Apr 2022
Cited by 20 | Viewed by 3853
Abstract
Curative therapy for sickle cell disease (SCD) currently requires gonadotoxic conditioning that can impair future fertility. Fertility outcomes after curative therapy are likely affected by pre-transplant ovarian reserve or semen analysis parameters that may already be abnormal from SCD-related damage or hydroxyurea treatment. [...] Read more.
Curative therapy for sickle cell disease (SCD) currently requires gonadotoxic conditioning that can impair future fertility. Fertility outcomes after curative therapy are likely affected by pre-transplant ovarian reserve or semen analysis parameters that may already be abnormal from SCD-related damage or hydroxyurea treatment. Outcomes are also likely affected by the conditioning regimen. Conditioning with myeloablative busulfan and cyclophosphamide causes serious gonadotoxicity particularly among post-pubertal females. Reduced-intensity and non-myeloablative conditioning may be acutely less gonadotoxic, but more short and long-term fertility outcome data after these approaches is needed. Fertility preservation including oocyte/embryo, ovarian tissue, sperm, and experimental testicular tissue cryopreservation should be offered to patients with SCD pursing curative therapy. Regardless of HSCT outcome, longitudinal post-HSCT fertility care is required. Full article
(This article belongs to the Special Issue The Future of Curative Therapies for Sickle Cell Disease)

Other

Jump to: Review

21 pages, 601 KiB  
Perspective
Debating the Future of Sickle Cell Disease Curative Therapy: Haploidentical Hematopoietic Stem Cell Transplantation vs. Gene Therapy
by Adetola A. Kassim and Alexis Leonard
J. Clin. Med. 2022, 11(16), 4775; https://doi.org/10.3390/jcm11164775 - 16 Aug 2022
Cited by 5 | Viewed by 3232
Abstract
Hematopoietic stem cell transplantation (HSCT) is a well-established curative therapy for patients with sickle cell disease (SCD) when using a human leukocyte antigen (HLA)-matched sibling donor. Most patients with SCD do not have a matched sibling donor, thereby significantly limiting the accessibility of [...] Read more.
Hematopoietic stem cell transplantation (HSCT) is a well-established curative therapy for patients with sickle cell disease (SCD) when using a human leukocyte antigen (HLA)-matched sibling donor. Most patients with SCD do not have a matched sibling donor, thereby significantly limiting the accessibility of this curative option to most patients. HLA-haploidentical HSCT with post-transplant cyclophosphamide expands the donor pool, with current approaches now demonstrating high overall survival, reduced toxicity, and an effective reduction in acute and chronic graft-vs.-host disease (GvHD). Alternatively, autologous genetic therapies appear promising and have the potential to overcome significant barriers associated with allogeneic HSCT, such as donor availability and GvHD. Here the authors each take a viewpoint and discuss what will be the future of curative options for patients with SCD outside of a matched sibling transplantation, specifically haploidentical HSCT vs. gene therapy. Full article
(This article belongs to the Special Issue The Future of Curative Therapies for Sickle Cell Disease)
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