Survival after T cell–depleted haploidentical stem cell transplantation is improved using the mother as donor

Stangel, Martin; Ruggeri, Loredana; Mancusi, Antonella; Bernardo, Maria Ester; Angelis, Claudia De; Bucher, Christoph; Locatelli, Franco; Aversa, Franco; Velardi, Andrea

doi:10.1182/blood-2008-01-135285

Cited by 219 publications

(185 citation statements)

References 28 publications

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“…Stern et al [6] analyzed the results of 118 T-cell depleted stem cell haplo-identical transplants. Multivariate analysis confirmed donor sex in parental transplantation to be an independent prognostic factor for survival.…”

Section: Fetal-maternal Microchimerismmentioning

confidence: 99%

Concise Review: Expanding Roles for Hematopoietic Cellular Therapy and the Blood Transfusion Services

Hodby

Pamphilon

2011

Stem Cells

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Hematopoietic stem cells (HSCs) have remained at the forefront of stem cell research for the past 50 years, since the therapeutic potential of bone marrow transplantation was realized. Uniquely, among stem and progenitor cells, research progress has been made in parallel between the laboratory benchtop and hospital bedside during this period. Integral to this work has been the role of the transfusion medicine services in the collection, storage, and processing of HSCs. The next decade promises to bring further developments: with new fields of cellular therapies, stem cell vaccination, and stem cell drug testing opening up. This article summarizes exciting areas of research concerning the behavior and potential clinical applications of HSCs. For the purposes of clarity, we describe in turn the trafficking and transfer of HSCs; ex vivo expansion of HSC units from different sources; and finally, applications of specifically selected subsets of hematopoietic cells and their progeny.

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Section: Fetal-maternal Microchimerismmentioning

confidence: 99%

Concise Review: Expanding Roles for Hematopoietic Cellular Therapy and the Blood Transfusion Services

Hodby

Pamphilon

2011

Stem Cells

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“…35,36 In a large Center for International BMT Registry (CIBMTR) analysis, the incidence of acute GVHD was significantly lower following transplants from a noninherited maternal Ag-mismatched sibling donor than from a noninherited paternal Ag-mismatched sibling donor. 35 TRM was also found to be higher following transplants from a maternal or a paternal donor compared with transplants from a noninherited maternal Ag-mismatched sibling.…”

Section: Optimizing Donor Selectionmentioning

confidence: 99%

“…In this analysis as well as a retrospective analysis by Ruggeri and colleagues, transplant outcomes were more favorable when a maternal rather than a paternal donor was used. 36 The principal of these apparent advantages, as well as the potential advantage of using UCB units that are matched for the noninherited maternal Ag, is that in utero leukocyte trafficking may lead to the development of long-lasting feto-maternal microchimerism and specific transplantation tolerance. Identification of donor-specific antibodies (DSAs) by a sensitive solid phase/single-Ag assay has been shown to correlate with a high risk of graft rejection; therefore, donors ideally should be chosen in whom donorspecific antibodies are not present.…”

Section: Optimizing Donor Selectionmentioning

confidence: 99%

The great debate: haploidentical or cord blood transplant

Ballen

Spitzer

2010

Bone Marrow Transplant

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One of the truly revolutionary advances in hematopoietic cell transplantation (HCT) is the increasingly successful use of alternative donors, thereby allowing the delivery of a potentially curative transplant to B75% of patients who do not have an HLA-matched sibling donor. A substantial proportion of the need has been met by HLA-matched volunteer unrelated donors, but an unmet need still exists, particularly among minority populations and for people who need a more immediate source of hematopoietic cells. Two such sources, umbilical cord blood (UCB) and haploidentical related donors, have filled most of this need, and outcomes following transplants from these donor sources are very promising. UCB has the advantages of ready availability and is less capable of causing GVHD but hematological recovery and immune reconstitution are slow. Haploidentical HCT is characterized by the nearly uniform and immediate availability of a donor and the availability of the donor for post transplant cellular immunotherapy, but is complicated by a high risk of GVHD and poor immune reconstitution when GVHD is prevented by vigorous ex vivo or in vivo T-cell depletion. This review will discuss the pertinent issues that affect the choice of one donor source over another and offer recommendations regarding the optimal utilization of these donor sources. Bone Marrow Transplantation (2011) 46, 323-329; doi:10.1038/bmt.2010; published online 1 November 2010 Keywords: haploidentical transplant; cord blood transplant; alternative donors; GVHD IntroductionOnly 30% of patients have a matched sibling donor, and therefore the majority of patients who need an allogeneic transplant will need to find alternative hematopoietic cell sources. The National Marrow Donor Program and its cooperative international registries boast an estimated 12 million volunteer donors. It is estimated that B60% of Caucasian patients will be able to find a suitably matched unrelated donor and proceed to transplant. The outlook is worse for African-American patients and other minorities -African Americans represent 12% of the US population, but only 5% of unrelated transplants. Therefore, an estimated 5000 patients yearly are candidates for either a mismatched related donor (haploidentical), umbilical cord blood (UCB) or mismatched unrelated donor transplant. This review will focus on adults, and the advantages and disadvantages of the haploidentical and UCB approaches.Haploidentical and UCB hematopoietic cell transplants (HCTs) have never been compared in a randomized fashion. In general, haploidentical HCTs are cheaper and easier to schedule, but may be associated with a higher risk of graft failure and GVHD. UCB, especially use of double UCB rather than single UCB units, are expensive and have a high risk of infection; however, the risk of severe GVHD is low. There may be some subgroups of patients (based on disease, match, and so on) who might be better served by one graft source over another. In this paper, we will review the clinical outcome data for each approach...

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“…For 60-70% of patients of Northwest European descent, this will be a 10 out of 10 allele-matched unrelated donor. For other patients, a single allele-mismatched unrelated donor, a matched or one HLA class I Ag-mismatched but inherited maternal Ag-matched cord blood unit, 7 a T-cell-depleted KIR ligand incompatible maternal graft 3 or a T-cell-replete haploidentical inherited maternal Ag-mismatched sibling donor may all provide excellent alternatives. 8 A T-cellreplete maternal donor will become a third option, providing that it will be possible to reliably determine whether the mother has sufficient numbers of T-regulator cells to provide a graft that will not cause severe GVHD.…”

Section: New Developments In Donor Selectionmentioning

confidence: 99%

“…If neither an HLA-identical sibling nor an NK alloimmune mother is available, 3 an extended family search can provide a suitable donor in about 15% of such searches, if (one of) the haplotype(s) is frequent. 4,5 If an unrelated donor is the only option, putative immunity of the mother against the inherited paternal Ags of her child and the immune response (that is, tolerance and/or immunity) of the child against noninherited maternal Ags should be taken into account.…”

Section: New Developments In Donor Selectionmentioning

confidence: 99%