Number of viable CD34+ cells reinfused predicts engraftment in autologous hematopoietic stem cell transplantation

Allan, David S.; Keeney, Michael; Howson‐Jan, Kang; Popma, Jan; Weir, K; Bhatia, Mickie; Sutherland, D. Robert; Chin‐Yee, Ian

doi:10.1038/sj.bmt.1703575

Cited by 198 publications

(190 citation statements)

References 24 publications

(27 reference statements)

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“…[2][3][4] The optimal CD34 + cell dose is widely accepted to be 5 × 10 6 /kg, even though in many centers a threshold of 2 × 10 6 /kg CD34 + cells is used; however, stem cell dose has not been established yet and remains a matter of debate.…”

Section: Cd34 + Stem Cell Dose For Autologous Transplant In the Plerimentioning

confidence: 99%

Mobilized peripheral blood grafts include more than hematopoietic stem cells: the immunological perspective

Saraceni

Shem‐Tov

Olivieri

et al. 2015

Bone Marrow Transplant

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Although stem cell mobilization has been performed for more than 20 years, little is known about the effects of mobilizing agents on apheresis composition and the impact of graft cell subsets on patients' outcome. With the increasing use of plerixafor and the inclusion of poor mobilizers in autologous transplant procedures, new parameters other than CD34 + stem cell dose are emerging; plerixafor seems to mobilize more primitive CD34 + /CD38 − stem cells compared with G-CSF, but their correlation with stable hematopoietic engraftment is still obscure. Immune recovery is as crucial as hematopoietic reconstitution, and higher T and natural killer cells infused within the graft have been correlated with better outcome in autologous transplant; recent studies showed increased mobilization of immune effectors with plerixafor compared with G-CSF, but further data are needed to clarify the clinical impact of these findings. In the allogeneic setting, much evidence suggests that mobilized T-cell alloreactivity is tempered by G-CSF, probably with the mediation of dendritic cells, even though no clear correlation with GVL and GVHD has been found. Plerixafor is not approved in healthy donors yet; early data suggest it might mobilize a GVHD protective balance of immune effectors, but further studies are needed to define its role in allogeneic transplant.

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Section: Cd34 + Stem Cell Dose For Autologous Transplant In the Plerimentioning

confidence: 99%

Mobilized peripheral blood grafts include more than hematopoietic stem cells: the immunological perspective

Saraceni

Shem‐Tov

Olivieri

et al. 2015

Bone Marrow Transplant

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“…Each send-out, from Spring 1996 to Autumn 2004 was chronologically assigned with a unique number (i.e., [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16]. In this way, we analyzed any effect of the EQA program on the results of the participants as a function of time.…”

Section: Data Processing and Parameter Classificationmentioning

confidence: 99%

“…Haematopoietic recovery is dependent on the number as well as the colony-forming capacity of the transplanted HSCs. This emphasizes the need for an adequate prediction of engraftment potency of HSCs in patients after receiving myeloablative therapy followed by HSC transplantation (8)(9)(10)(11). Furthermore, enumeration of CD34þ cells has been shown to be useful in con-siderations of peripheral blood stem cell harvesting (12)(13)(14)(15)(16) and in comparing the efficacy of various PB stem cell mobilization strategies (reviewed by Fruehauf and Kessinger and Sharp) (17,18).…”

mentioning

confidence: 99%

Flow cytometric CD34+ stem cell enumeration: Lessons from nine years' external quality assessment within the Benelux countries

Levering

Preijers

Wieringen

et al. 2007

Cytometry Part B Clinical

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Background: A biannual external quality assurance (EQA) scheme for flow cytometric CD34+ haematopoietic stem cell enumeration has been operational in the Benelux countries since 1996. In an evaluation of the results of 16 send-outs, we studied the effects of the methods used on assay outcome and whether or not this exercise was effective in reducing between-laboratory variation.Methods: Data were analyzed using robust multivariate regression. This approach is relatively insensitive to outliers and is used to assess the effect of methodological aspects of CD34+ cell counting on the bias and variability.Results: Five variables were associated with significant bias of absolute CD34+ cell counts: (i) unique laboratory number (ULN), (ii) gating strategy; (iii) CD34 mAb fluorochrome; (iv) type of flow cytometer, and (v) method of sample preparation. In addition, ULN and platform methodology (i.e., single vs. dual) contributed significantly to the variability of this assay. Overall, the variability in results of CD34+ cell enumeration has declined with time; in particular, after a practical workshop in which participants were trained to use the ''single platform ISHAGE protocol.'' Conclusions: Between-laboratory variation in CD34+ cell enumeration can be reduced by standardization of methodologies between centres. Our approach, i.e., EQA with targeted training and feedback in response to reported results, has been successful in reducing the variability of CD34+ cell enumeration between participants. q 2007 Clinical Cytometry Society

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“…Furthermore, Allan et al 10 have drawn attention not solely to the count of harvested cells, but also the numbers of CD34 þ cells recovered post thaw and subsequently infused, as critical. When cell numbers o2 Â 10 6 , 2--5Â 10 6 or 45 Â 10 6 per kg were compared, decreased HSC counts were found to influence platelet but not neutrophil-recovery speed.…”

Section: Introductionmentioning

confidence: 99%

Is it time to revisit our current hematopoietic progenitor cell quantification methods in the clinic?

Beksaç

Preffer

2011

Bone Marrow Transplant

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In the clinical practice of hematopoietic SCT, the minimum numbers of cells required for a successful engraftment are defined on the basis of their CD45 and CD34 expression profiles. However, the quantity of earlier progenitors or CD34-positive cells at different differentiation stages within stem cell grafts is not generally taken into consideration. During the last decade, various teams have quantified the number of cells expressing various combinations of CD34, CD38, CD133, CD90 co-expression and/or aldehyde dehydrogenase functional capacity using flow cytometry. Some of these studies resulted in the greater appreciation that combinations of these Ags were associated with varied myeloid, erythroid and platelet engraftment rates whereas others showed that the relative absence or presence of these markers could define cells responsible for either short-or long-term engraftment. These findings were also extended to differences between progenitor cell populations found within BM vs peripheral or cord-blood grafts. Cells harvested from donors are also generally frozen and stored; thawed cells have variable levels of viability and functional capacity based on the time tested post thaw, which also can be assessed by flow cytometry. Finally, flow cytometry has the potential for analysis of cells carrying a mesenchymal stem cell phenotype, which may be quiescent within some of the stem cell products. This review will address the need for stem cell subpopulation quantification and summarize existing published data to identify some Ags and functional characteristics that can be applicable to daily clinical practice.

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Number of viable CD34+ cells reinfused predicts engraftment in autologous hematopoietic stem cell transplantation

Cited by 198 publications

References 24 publications

Mobilized peripheral blood grafts include more than hematopoietic stem cells: the immunological perspective

Mobilized peripheral blood grafts include more than hematopoietic stem cells: the immunological perspective

Flow cytometric CD34+ stem cell enumeration: Lessons from nine years' external quality assessment within the Benelux countries

Is it time to revisit our current hematopoietic progenitor cell quantification methods in the clinic?

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