For Publishers
DiscoveryMetadataPeer reviewHostingPublishing
For Researchers
JoinPublishReviewCollect
Register
Blog
About
Search
Advanced search
My ScienceOpen
Search
For Publishers
For Researchers
Blog
About
8
views
25
references
 Top references
cited by
4
    
0 reviews
 Review
0
comments
 Comment
0
recommends
+1 Recommend
0 collections
    0
    shares
      816
      similar
       All similar
      • Record: found
      • Abstract: found
      • Article: not found

      Haploidentical bone marrow transplant with posttransplant cyclophosphamide for sickle cell disease: An update

      review-article

      Read this article at

      ScienceOpenPublisherPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Hematopoietic cell transplant (HCT) can cure both children and adults with sickle cell disease. Outcomes have historically been poor for the vast majority of patients who lack a matched sibling donor. However, the development of haploidentical HCT (haplo-HCT) with high doses of posttransplant cyclophosphamide (PTCy) has allowed for curative long-term potential with favorable transplant-related outcomes, though this has not obviated the potential for graft rejection from human leukocyte antigen mismatch and repeated red blood cell transfusions. Accordingly, multiple strategies have been developed to improve outcomes, the majority of which are based on the Johns Hopkins platform from 2012. Presently, we aim to discuss results from pertinent studies and compare outcomes with the two most recent approaches involving either thiotepa plus 200-cGy total body irradiation or 400-cGy total body irradiation. Direct comparisons are required to determine the optimized curative potential. Transplant-eligible patients must be referred to tertiary medical centers for consideration of haplo-HCT.

          Related collections

          Most cited references25

          • Record: found
          • Abstract: found
          • Article: not found

          HLA match likelihoods for hematopoietic stem-cell grafts in the U.S. registry.

          Loren Gragert, Mary Eapen, Eric Williams … (2014)
          Hematopoietic stem-cell transplantation (HSCT) is a potentially lifesaving therapy for several blood cancers and other diseases. For patients without a suitable related HLA-matched donor, unrelated-donor registries of adult volunteers and banked umbilical cord-blood units, such as the Be the Match Registry operated by the National Marrow Donor Program (NMDP), provide potential sources of donors. Our goal in the present study was to measure the likelihood of finding a suitable donor in the U.S. registry. Using human HLA data from the NMDP donor and cord-blood-unit registry, we built population-based genetic models for 21 U.S. racial and ethnic groups to predict the likelihood of identifying a suitable donor (either an adult donor or a cord-blood unit) for patients in each group. The models incorporated the degree of HLA matching, adult-donor availability (i.e., ability to donate), and cord-blood-unit cell dose. Our models indicated that most candidates for HSCT will have a suitable (HLA-matched or minimally mismatched) adult donor. However, many patients will not have an optimal adult donor--that is, a donor who is matched at high resolution at HLA-A, HLA-B, HLA-C, and HLA-DRB1. The likelihood of finding an optimal donor varies among racial and ethnic groups, with the highest probability among whites of European descent, at 75%, and the lowest probability among blacks of South or Central American descent, at 16%. Likelihoods for other groups are intermediate. Few patients will have an optimal cord-blood unit--that is, one matched at the antigen level at HLA-A and HLA-B and matched at high resolution at HLA-DRB1. However, cord-blood units mismatched at one or two HLA loci are available for almost all patients younger than 20 years of age and for more than 80% of patients 20 years of age or older, regardless of racial and ethnic background. Most patients likely to benefit from HSCT will have a donor. Public investment in donor recruitment and cord-blood banks has expanded access to HSCT. (Funded by the Office of Naval Research, Department of the Navy, and the Health Resources and Services Administration, Department of Health and Human Services.).
          Article 0 comments Cited 283 times – based on 0 reviews     Review now
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Aldehyde dehydrogenase expression drives human regulatory T cell resistance to posttransplantation cyclophosphamide.

            C. G. Kanakry, S. Ganguly, M Zahurak … (2013)
            High-dose, posttransplantation cyclophosphamide (PTCy) is an effective strategy for preventing graft-versus-host disease (GVHD) after allogeneic blood or marrow transplantation (alloBMT). However, the mechanisms by which PTCy modulates alloimmune responses are not well understood. We studied early T cell reconstitution in patients undergoing alloBMT with PTCy and the effects of mafosfamide, a cyclophosphamide (Cy) analog, on CD4(+) T cells in allogeneic mixed lymphocyte reactions (MLRs) in vitro. Patients exhibited reductions in naïve, potentially alloreactive conventional CD4(+) T cells with relative preservation of memory CD4(+)Foxp3(+) T cells. In particular, CD4(+)CD45RA(-)Foxp3(+hi) effector regulatory T cells (Tregs) recovered rapidly after alloBMT and, unexpectedly, were present at higher levels in patients with GVHD. CD4(+)Foxp3(+) T cells from patients and from allogeneic MLRs expressed relatively high levels of aldehyde dehydrogenase (ALDH), the major in vivo mechanism of Cy resistance. Treatment of MLR cultures with the ALDH inhibitor diethylaminobenzaldehyde reduced the activation and proliferation of CD4(+) T cells and sensitized Tregs to mafosfamide. Finally, removing Tregs from peripheral blood lymphocyte grafts obviated PTCy's GVHD-protective effect in a xenogeneic transplant model. Together, these findings suggest that Treg resistance to Cy through expression of ALDH may contribute to the clinical activity of PTCy in preventing GVHD.
            Article 0 comments Cited 115 times – based on 0 reviews     Review now
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              HLA-haploidentical bone marrow transplantation with posttransplant cyclophosphamide expands the donor pool for patients with sickle cell disease.

              Julian Fuchs, T. J. Jones, Robert Brodsky … (2012)
              Allogeneic marrow transplantation can cure sickle cell disease; however, HLA-matched donors are difficult to find, and the toxicities of myeloablative conditioning are prohibitive for most adults with this disease. We developed a nonmyeloablative bone marrow transplantation platform using related, including HLA-haploidentical, donors for patients with sickle cell disease. The regimen consisted of antithymocyte globulin, fludarabine, cyclophosphamide, and total body irradiation, and graft-versus-host disease prophylaxis with posttransplantation high-dose cyclophosphamide, mycophenolate mofetil, and tacrolimus or sirolimus. After screening 19 patients, we transplanted 17, 14 from HLA-haploidentical and 3 from HLA-matched related donors. Eleven patients engrafted durably. With a median follow-up of 711 days (minimal follow up 224 days), 10 patients are asymptomatic, and 6 patients are off immunosupression. Only 1 patient developed skin-only acute graft-versus-host disease that resolved without any therapy; no mortality was seen. Nonmyeloablative conditioning with posttransplantation high-dose cyclophosphamide expands the donor pool, making marrow transplantation feasible for most patients with sickle cell disease, and is associated with a low risk of complications, even with haploidentical related donors. Graft failure, 43% in haploidentical pairs, remains a major obstacle but may be acceptable in a fraction of patients if the majority can be cured without serious toxicities.
              Article 0 comments Cited 106 times – based on 0 reviews     Review now
                Bookmark
                All references

                Author and article information

                Contributors
                Adetola A. Kassim
                Journal
                Journal ID (nlm-ta): Hematol Oncol Stem Cell Ther
                Journal ID (iso-abbrev): Hematol Oncol Stem Cell Ther
                Title: Hematology/Oncology and Stem Cell Therapy
                Publisher: King Faisal Specialist Hospital & Research Centre. Published by Elsevier Ltd.
                ISSN (Print): 1658-3876
                ISSN (Electronic): 1658-3876
                Publication date PMC-release: 12 March 2020
                Publication date (Electronic): 12 March 2020
                Electronic Location Identifier:
                Affiliations
                [a ]Department of Medicine, Division of Hematology/Oncology, Vanderbilt-Meharry Center for Excellence in Sickle Cell Disease, Vanderbilt University Medical Center, Nashville, TN, USA
                [b ]College of Medicine, Division of Pediatric Hematology & Oncology, Lagos University Teaching Hospital, Idi-Araba, Lagos, Nigeria
                [c ]Department of Paediatrics, St. Mary’s Hospital, Imperial College, London, United Kingdom
                Author notes
                [* ]Corresponding author.at: Department of Medicine, Division of Hematology/Oncology, Vanderbilt-Meharry Center for Excellence in Sickle Cell Disease, Vanderbilt University Medical Center, Nashville, TN, USA. adetola.kassim@ 123456vumc.org
                Article
                Publisher ID: S1658-3876(20)30025-X
                DOI: 10.1016/j.hemonc.2020.01.002
                PMC ID: 7118612
                PubMed ID: 32202252
                SO-VID: 53f699ed-2b5a-4121-9ba3-858cd625cf90
                Copyright © © 2020 King Faisal Specialist Hospital & Research Centre. Published by Elsevier Ltd.
                License:

                Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

                History
                Date received : 13 January 2020
                Date accepted : 28 January 2020
                Categories
                Subject: Article

                Keywords: cyclophosphamide,haploidentical transplant,sickle cell disease,thiotepa,total body irradiation
                Data availability:
                Keywords: cyclophosphamide, haploidentical transplant, sickle cell disease, thiotepa, total body irradiation

                Comments

                Comment on this article

                scite_

                Similar content816

                See all similar

                Cited by4

                See all cited by

                Most referenced authors684

                See all reference authors