Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
Current Hematologic Malignancy Reports
Published in: Current Hematologic Malignancy Reports 1/2016

01-02-2016 | Stem Cell Transplantation (R Maziarz, Section Editor)

Ex Vivo Expansion or Manipulation of Stem Cells to Improve Outcome of Umbilical Cord Blood Transplantation

Author: Mitchell E. Horwitz

Published in: Current Hematologic Malignancy Reports | Issue 1/2016

Login to get access

Abstract

The outcome of umbilical cord blood transplantation for adult patients with hematologic malignancies now rivals that of matched unrelated donor transplantation. However, delayed hematopoietic and immunologic recovery remains a source of significant morbidity and mortality. Multiple strategies are now being studied to overcome these limitations. One strategy involves ex vivo expansion of the umbilical cord blood unit prior to transplantation. A second strategy involves exposure of the umbilical cord blood graft to compounds aimed at improving homing and engraftment following transplantation. Such a strategy may also address the problem of slow hematopoietic recovery as well as the increased risk of graft failure. Many of these strategies are now being tested in late phase multi-center clinical trials. If proven cost-effective and efficacious, they may alter the landscape of donor options for allogeneic stem cell transplantation.
Literature
1.
Sebrango A et al. Haematopoietic transplants combining a single unrelated cord blood unit and mobilized haematopoietic stem cells from an adult HLA-mismatched third party donor. Comparable results to transplants from HLA-identical related donors in adults with acute leukaemia and myelodysplastic syndromes. Best Pract Res Clin Haematol. 2010;23(2):259–74.CrossRefPubMed
2.
Liu H et al. Reduced-intensity conditioning with combined haploidentical and cord blood transplantation results in rapid engraftment, low GVHD, and durable remissions. Blood. 2011;118(24):6438–45.CrossRefPubMedPubMedCentral
3.
Peffault de Latour R et al. Similar overall survival using sibling, unrelated donor, and cord blood grafts after reduced-intensity conditioning for older patients with acute myelogenous leukemia. Biol Blood Marrow Transplant. 2013;19(9):1355–60.CrossRefPubMed
4.
Smith AR et al. Hematopoietic cell transplantation for children with acute lymphoblastic leukemia in second complete remission: similar outcomes in recipients of unrelated marrow and umbilical cord blood versus marrow from HLA matched sibling donors. Biol Blood Marrow Transplant. 2009;15(9):1086–93.CrossRefPubMed
5.
Jaroscak J et al. Augmentation of umbilical cord blood (UCB) transplantation with ex vivo-expanded UCB cells: results of a phase 1 trial using the AastromReplicell system. Blood. 2003;101(12):5061–7.CrossRefPubMed
6.
Scaradavou A et al. Double unit grafts successfully extend the application of umbilical cord blood transplantation in adults with acute leukemia. Blood. 2013;121(5):752–8.CrossRefPubMedPubMedCentral
7.
Barker JN et al. Transplantation of 2 partially HLA-matched umbilical cord blood units to enhance engraftment in adults with hematologic malignancy. Blood. 2005;105(3):1343–7.CrossRefPubMed
8.
Milner LA et al. A human homologue of the Drosophila developmental gene, Notch, is expressed in CD34+ hematopoietic precursors. Blood. 1994;83(8):2057–62.PubMed
9.
Delaney C et al. Dose-dependent effects of the Notch ligand Delta1 on ex vivo differentiation and in vivo marrow repopulating ability of cord blood cells. Blood. 2005;106(8):2693–9.CrossRefPubMedPubMedCentral
10.
11.
Gutman JA et al. Single-unit dominance after double-unit umbilical cord blood transplantation coincides with a specific CD8+ T-cell response against the nonengrafted unit. Blood. 2010;115(4):757–65.CrossRefPubMedPubMedCentral
12.
Moretta A et al. In vitro evaluation of graft-versus-graft alloreactivity as a tool to identify the predominant cord blood unit before double cord blood transplantation. Biol Blood Marrow Transplant J Am Soc Blood Marrow Transplant. 2012;18(7):1108–18.CrossRef
13.
Delaney C. Infusion of Non-HLA matched, off-the-shelf ex vivo expanded cord blood progenitor cells in patients undergoing myeloablative cord blood transplantation is safe and decreases the time to neutrophil recovery. Biol Blood Marrow Transplant. 2012;18(2):S203.CrossRef
14.
Peled T et al. Linear polyamine copper chelator tetraethylenepentamine augments long-term ex vivo expansion of cord blood-derived CD34+ cells and increases their engraftment potential in NOD/SCID mice. Exp Hematol. 2004;32(6):547–55.CrossRefPubMed
15.
Peled T et al. Pre-clinical development of cord blood-derived progenitor cell graft expanded ex vivo with cytokines and the polyamine copper chelator tetraethylenepentamine. Cytotherapy. 2004;6(4):344–55.CrossRefPubMed
16.
de Lima M et al. Transplantation of ex vivo expanded cord blood cells using the copper chelator tetraethylenepentamine: a phase I/II clinical trial. Bone Marrow Transplant. 2008.
17.
Stiff PM et al. StemEx® (copper chelation based) ex vivo expanded Umbilical Cord Blood Stem Cell Transplantation (UCBT) accelerates engraftment and improves 100 day survival in myeloablated patients compared to a registry cohort undergoing double unit UCBT: results of a multicenter study of 101 patients with hematologic malignancies. Blood. 2013;122(295):3060.
18.
Peled T et al. Nicotinamide, a SIRT1 inhibitor, inhibits differentiation and facilitates expansion of hematopoietic progenitor cells with enhanced bone marrow homing and engraftment. Exp Hematol. 2012;40(4):342–55.e1.CrossRefPubMed
19.
20.
Briddell RA et al. Recombinant rat stem cell factor synergizes with recombinant human granulocyte colony-stimulating factor in vivo in mice to mobilize peripheral blood progenitor cells that have enhanced repopulating potential. Blood. 1993;82(6):1720–3.PubMed
21.
McNiece I et al. Ex vivo expansion of cord blood mononuclear cells on mesenchymal stem cells. Cytotherapy. 2004;6(4):311–7.CrossRefPubMed
22.
23.
24.
Wagner JE et al. StemRegenin-1 (SR1) Expansion Culture Abrogates the Engraftment Barrier Associated with Umbilical Cord Bood Transplantation. Abstract to be presented at the 56th American Society of Hematology Meeting and Exposition. 2014.
25.
26.
27.
Ratajczak J et al. Mobilization studies in mice deficient in either C3 or C3a receptor (C3aR) reveal a novel role for complement in retention of hematopoietic stem/progenitor cells in bone marrow. Blood. 2004;103(6):2071–8.CrossRefPubMed
28.
Reca R et al. Functional receptor for C3a anaphylatoxin is expressed by normal hematopoietic stem/progenitor cells, and C3a enhances their homing-related responses to SDF-1. Blood. 2003;101(10):3784–93.CrossRefPubMed
29.
Brunstein CG et al. Complement fragment 3a priming of umbilical cord blood progenitors: safety profile. Biol Blood Marrow Transplant. 2013;19(10):1474–9.CrossRefPubMedPubMedCentral
30.
Hidalgo A et al. Functional selectin ligands mediating human CD34(+) cell interactions with bone marrow endothelium are enhanced postnatally. J Clin Invest. 2002;110(4):559–69.CrossRefPubMedPubMedCentral
31.
Robinson SN et al. Fucosylation with fucosyltransferase VI or fucosyltransferase VII improves cord blood engraftment. Cytotherapy. 2014;16(1):84–9.CrossRefPubMed
32.
Xia L et al. Surface fucosylation of human cord blood cells augments binding to P-selectin and E-selectin and enhances engraftment in bone marrow. Blood. 2004;104(10):3091–6.CrossRefPubMed
33.
Popat U et al. Enforced fucosylation of cord blood hematopoietic cells accelerates neutrophil and platelet engraftment after transplantation. Blood. 2015;125(19):2885–92.CrossRefPubMed
34.
Metadata
Title
Ex Vivo Expansion or Manipulation of Stem Cells to Improve Outcome of Umbilical Cord Blood Transplantation
Author
Mitchell E. Horwitz
Publication date
01-02-2016
Publisher
Springer US
Published in
Current Hematologic Malignancy Reports / Issue 1/2016
Print ISSN: 1558-8211
Electronic ISSN: 1558-822X
DOI
https://doi.org/10.1007/s11899-015-0297-7

Other articles of this Issue 1/2016

Current Hematologic Malignancy Reports 1/2016 Go to the issue

Chronic Lymphocytic Leukemias (N Jain, Section Editor)

Richter Syndrome in Chronic Lymphocytic Leukemia

Chronic Lymphocytic Leukemias (N Jain, Section Editor)

Chronic Lymphocytic Leukemia: Exploiting Vulnerabilities with Targeted Agents

Chronic Lymphocytic Leukemias (N Jain, Section Editor)

Evolving Strategies for the Treatment of Chronic Lymphocytic Leukemia in the Upfront Setting

Stem Cell Transplantation (R Maziarz, Section Editor)

The Difficulties of Informed Consent in Stem Cell Transplant

Stem Cell Transplantation (R Maziarz, Section Editor)

Myelofibrosis—When Do We Select Transplantation or Non-transplantation Therapeutic Options?

Chronic Lymphocytic Leukemias (N Jain, Section Editor)

Immunotherapy in Chronic Lymphocytic Leukaemia (CLL)
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Reserve your place

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

Read more

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Pediatric Cardiology Video

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

Cardiopulmonary Comorbidity Video

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Valvular Heart Disease Video

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

Watch now

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

16-04-2024 Type 2 Diabetes News

Incentivised to exercise

11-04-2024 Lifestyle Modifications News

New intervention for STEMI-related cardiogenic shock

10-04-2024 Myocardial Infarction News

» View more highlights on the ACC 2024 congress hub page

Image Credits