Umbilical cord blood transplantation: Pros, cons and beyond

Stanevsky, Anfisa; Gal, Gilad; Nagler, Arnon

doi:10.1016/j.blre.2009.02.001

Cited by 72 publications

(56 citation statements)

References 60 publications

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“…This is consistent with the ability to generate multivirusspecific CTLs from previously cryopreserved units as shown by Hanley et al 23 The increasing use of double CB transplants results in an unpredictable dominance of 1 of the 2 CB units infused. 46 It is not clear what the consequences would be for the survival of virusor leukemia-specific CTLs should these be derived from the nondominant CB unit, and early clinical trials will likely be restricted to patients receiving a single CB unit. Future trials could require generation of virus-and leukemia-specific CTLs from both CB units to optimize antivirus and antitumor activity in the double CB setting.…”

Section: Deriving Human T Lymphocytes From a Single Culture 2701mentioning

confidence: 99%

Derivation of human T lymphocytes from cord blood and peripheral blood with antiviral and antileukemic specificity from a single culture as protection against infection and relapse after stem cell transplantation

Micklethwaite¹,

Savoldo

Hanley³

et al. 2010

Blood

101

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IntroductionInfections, malignant relapse, and graft-versus-host disease (GVHD), continue to cause significant morbidity and mortality after hematopoietic stem cell (HSC) or cord blood (CB) transplantation. Virus infections such as cytomegalovirus (CMV), EpsteinBarr virus (EBV), and adenovirus (AdV) are particularly problematic and remain difficult to treat, especially after umbilical CB transplantation. [1][2][3][4][5] Although ganciclovir/foscarnet may help prevent or treat CMV 6 and CD20-specific antibody may control EBV-associated lymphoproliferation, 7 these drugs are expensive and are often toxic or ineffective due to primary or secondary resistance. 6 Moreover, AdV infections are increasingly common and effective treatments are not currently available. 8 The other major cause of morbidity and mortality is relapse, occurring in more than 30% of transplant recipients with B-cell acute lymphoblastic leukemia (B-ALL), [9][10][11][12] with few appealing therapeutic options and less than 10% long-term survival. 13,14 Although donor lymphocyte infusions can be used after HSC transplantation to treat both viral infections and leukemia relapse, these are associated with potentially life-threatening GVHD, 15 have a low success rate in relapsed B-ALL, 15,16 and are unavailable for CB transplant recipients. An alternative for viral infections is the adoptive transfer of cytotoxic T lymphocytes (CTLs) directed to CMV, 17,18 EBV,19,20 and, more recently, AdV, 21,22 which can rapidly reconstitute antiviral immunity after HSC transplantation without causing GVHD. Infusion of peripheral blood-derived T-lymphocyte lines enriched in cells simultaneously recognizing CMV, EBV, and AdV (multivirus-specific CTLs [MV-CTLs]) reproducibly controls infections due to all 3 viruses after allogeneic HSC transplantation. 21 Importantly, functional CMV-, EBV-, and AdV-specific CTLs can now also be generated from naive T cells isolated from CB units. 23 It is also possible to infuse leukemia-specific CTLs into patients after HSC transplantation 24,25 ; these can be generated by stimulating peripheral blood mononuclear cells with apoptotic leukemic blasts. 25,26 Unfortunately, however, the paucity of antigen-specific CTL precursors and the need to separate graft-versus-tumor from the graft-versus-host effect may require extensive culture to generate sufficient numbers of cells for adoptive T-cell therapy. 25,26 To overcome this difficulty, investigators have used T lymphocytes engineered to express chimeric antigen receptors (CARs) directed to self-antigens expressed by tumor cells. 27,28 For example, T cells expressing a CAR specific for the CD19 molecule 29,30 may be able to prevent or treat leukemia relapse in B-ALL patients as these cells almost invariably express CD19.It would be appealing to combine these approaches to prepare a single product containing CTLs that were virus specific (through The online version of this article contains a data supplement.The publication costs of this article were defrayed in part by page charge paym...

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Section: Deriving Human T Lymphocytes From a Single Culture 2701mentioning

confidence: 99%

Derivation of human T lymphocytes from cord blood and peripheral blood with antiviral and antileukemic specificity from a single culture as protection against infection and relapse after stem cell transplantation

Micklethwaite¹,

Savoldo

Hanley³

et al. 2010

Blood

101

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“…Cord blood (CB) HSCs have numerous phenotypic and functional characteristics that distinguish them from their adult counterparts (1)(2)(3)(4)(5). CB CD34 + cells are thought to be more primitive due to their extensive proliferative capacity, their increased ability to generate hematopoietic colonies in vitro, their capacity to produce erythroid cells, which contain fetal hemoglobins, and the ability of smaller numbers of such cells to reconstitute a myeloablated allogeneic recipient (1).…”

Section: Introductionmentioning

confidence: 99%

“…CB CD34 + cells are thought to be more primitive due to their extensive proliferative capacity, their increased ability to generate hematopoietic colonies in vitro, their capacity to produce erythroid cells, which contain fetal hemoglobins, and the ability of smaller numbers of such cells to reconstitute a myeloablated allogeneic recipient (1). The use of CB cells as HSC grafts for allogeneic stem cell recipients suffering from hematological malignancies and genetic disorders has been limited to children or smaller adult recipients due to the limited number of stem cells present in a single CB collection (1,4,5). These limitations have resulted in an unacceptably high rate of graft failure and delayed engraftment kinetics in adult recipients (1)(2)(3)(4)(5)(6)(7).…”

Section: Introductionmentioning

confidence: 99%

“…The use of CB cells as HSC grafts for allogeneic stem cell recipients suffering from hematological malignancies and genetic disorders has been limited to children or smaller adult recipients due to the limited number of stem cells present in a single CB collection (1,4,5). These limitations have resulted in an unacceptably high rate of graft failure and delayed engraftment kinetics in adult recipients (1)(2)(3)(4)(5)(6)(7). Attempts to overcome these barriers have included several different strategies such as the infusion of two different CB grafts or the ex vivo expansion of CB CD34 + cells using a variety of cytokine combinations that are able to promote HSC cycling and the subsequent division of these CD34 + cells (2,(6)(7)(8)(9).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Epigenetic reprogramming induces the expansion of cord blood stem cells

Chaurasia¹,

Gajzer²,

Schaniel³

et al. 2014

J. Clin. Invest.

143

152

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“…In addition, umbilical cord blood transplantation was shown to be associated with a lower risk of infection transmission in comparison with bone marrow transplantation [67]. On the other hand, the low number of stem cells per cord blood unit represents a limitation that is associated with delayed engraftment of these cells into host targeted tissues [62,68]. However, this obstacle has been tackled with the possibility of combining multiple cord blood units in order to increase the final transplanted cell dose resulting in improved engraftment and survival of the transplanted cells [3,61,64,68].…”

Section: Why Umbilical Cord Blood Stem Cellsmentioning

confidence: 99%