Rapid induction of single donor chimerism after double umbilical cord blood transplantation preceded by reduced intensity conditioning: results of the HOVON 106 phase II study

Somers, Judith A.E.; Braakman, Eric; Holt, Bronno van der; Petersen, Eefke; Marijt, Erik W.A.; Huisman, Cynthia; Sintnicolaas, K.; Oudshoorn, Machteld; Groenendijk-Sijnke, Marlies; Brand, Anneke; Cornelissen, Jan J.

doi:10.3324/haematol.2014.106690

Cited by 23 publications

(24 citation statements)

References 43 publications

(66 reference statements)

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“…We focused on alloreactive CD4+ T-cells based on the earlier observation that CD4+ T-cells expand early after dUCBT and that CD4+ T-cell chimerism predicts for ultimate unit predominance (6,8). Our observations firmly supported the hypothesis that these alloreactive CD4+ T-cells play a pivotal role in graft predominance after dUCBT.…”

Section: Summary Of Earlier Reported Resultssupporting

confidence: 66%

“…Importantly, hematopoietic recovery after dUCBT generally originates from only a single cord blood unit, designated as the predominant (PD)-CBU (1)(2)(3). Single donor chimerism is readily documented within 3 months post-transplant in the majority of patients (1)(2)(3)(4)(5), but actually may occur as early as 7-14 days after transplantation (6)(7)(8)(9). Graft predominance was earlier suggested to be T-cell mediated, as higher doses of graft CD3+ T-cells and also early recovery of alloreactive, IFN-gamma secreting CD8+ T-cells appeared associated with graft predominance (5,10,11).…”

Section: Introductionmentioning

confidence: 99%

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Graft predominance after double umbilical cord blood transplantation: a review

Cornelissen¹,

Kalin²,

Lamers³

2017

Stem Cell Investig.

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Several parameters are involved in graft predominance after double umbilical cord blood transplantation (dUCBT), of which T-cell alloreactivity between the grafts is now considered to be the major denominator. We recently showed that alloreactive CD4+ T-cells originating from the predominant CBU recognize HLA-class II allele mismatches and can readily be detected in the majority of patients. In addition, it was shown that HLA-class II allele-specific CD4+ T-cells were able to recognize primary leukemic cells when the mismatched HLA-class II allele was shared between the rejected CBU and the patient. These results further underscored the role of alloreactive T-cells, notably class II specific CD4+ T-cells, in graftversus-graft reactions and in graft-versus-leukemia after dUCBT.

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Section: Summary Of Earlier Reported Resultssupporting

confidence: 66%

Section: Introductionmentioning

confidence: 99%

Graft predominance after double umbilical cord blood transplantation: a review

Cornelissen¹,

Kalin²,

Lamers³

2017

Stem Cell Investig.

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“…In 2009, Eurocord published criteria for cell dose, advising to infuse two units if cell dose can otherwise not be met. Some studies of DUCB show engraftment as early as 12 days [16] with also reports as late as 36 days [17]. Within cohorts, there is considerable variability among subjects, and it is impossible to exactly predict engraftment in an individual patient.…”

Section: Ducb Transplantationmentioning

confidence: 97%

Topping it up: methods to improve cord blood transplantation outcomes by increasing the number of CD34+ cells

Lindemans

Besien

2015

Cytotherapy

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“…18,19 Studies have suggested that the outcome of cord blood grafting is better when the CBU contains higher numbers of cells, or when double CBU grafts, and/or better HLA-C matched grafts are used. [20][21][22][23][24] While allele level matching was recently found to be associated with better transplant outcomes, high resolution typing for HLA-A-B-C and DRB1 would probably show 8/8 matching in only 10% of recipient/cord blood pairs. 25 Requiring a higher level of matching for cord blood will result in fewer matching units, in particular for non-NWE patients.…”

Section: Discussionmentioning

confidence: 99%

The increase of the global donor inventory is of limited benefit to patients of non-Northwestern European descent

et al. 2016

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© Ferrata Storti Foundation IntroductionAllogeneic hematopoietic progenitor cell transplantation plays an important role in treatment of hematooncological diseases. For patients lacking a matched related donor, an unrelated donor (UD) or cord blood unit (CBU) may provide a valuable alternative. Alternative donors are identified through registries of volunteer unrelated donors or public cord blood banks. In the past decade, the identification and availability of UD and UCB have improved. Bone Marrow Donors Worldwide (BMDW), the file of registered unrelated donors, almost tripled (from 7.4 million donors in 2001 to over 21 million in December 2012), while the inventory of unrelated CBU grew from 87,000 in 2001 to over 500,000.1 To date (2016) the number of registered donors has increased to over 27 million, and currently over 650.000 CBU are registered. Increased knowledge of the HLA system, more well-typed donors, and the availability of several search-related software tools 2-5 have facilitated and speeded up the efficiency of the search process. [6][7][8] Simultaneously searching for a back-up donor can minimize the delay if a donor is unexpectedly not fit or unavailable to donate.9 Given these recent improvements, we set out to address the questions of whether a higher percentage of patients in need of an UD/CBU may actually reach transplantation nowadays, whether the time needed to identify an UD/CBU has decreased, and whether possible factors can be identified for potential improvement. We addressed the questions in a large cohort of 3,365 consecutive UD searches performed between 2001-2012 in the Netherlands, including searches for Dutch patients of Northwestern European (NWE) and non-Northwestern European (non-NWE) descent. Methods The patients and donor searchesEuropdonor Foundation, the Dutch Stem cell donor registry, coordinates the UD searches in the Netherlands, serving a population of 16.8 million inhabitants. There were eight adult and two pediatric stem cell transplantation units in 2012 in the Netherlands, and the number of new searches increased to approximately 500 annually. All UD and CBU searches performed from 2001 until 2012 for the patients of all Dutch transplantation centers were included (n=3,365, Figure 1) for the initial 'donor found' analysis, and divided into two periods: cohort I, 2001-2006 (n=1,093) and cohort II, 2007II, -2012. Patients for whom a search was cancelled in less time than the median search time for the given year, and for whom no donor was yet identified were excluded for the 'donor found' analysis (cohort I, n=75; cohort II, n=131), leaving 3,124 evaluable search cases. Each cohort was split according to NWE and non-NWE descent. Patients were assigned to NWE or non-NWE background based upon self-identified descent.10 Descendants from the Netherlands, Germany, Belgium, Luxembourg, Great Britain, Ireland, and Scandinavia were considered NWE. The non-NWE group consisted of patients with self-reported genetic ancestry in Northern Africa (n=51), Sub-Saharan A...

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Rapid induction of single donor chimerism after double umbilical cord blood transplantation preceded by reduced intensity conditioning: results of the HOVON 106 phase II study

Cited by 23 publications

References 43 publications

Graft predominance after double umbilical cord blood transplantation: a review

Graft predominance after double umbilical cord blood transplantation: a review

Topping it up: methods to improve cord blood transplantation outcomes by increasing the number of CD34+ cells

The increase of the global donor inventory is of limited benefit to patients of non-Northwestern European descent

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