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

Abstract

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.

Larger number of invariant natural killer T cells in PBSC allografts correlates with improved GVHD-free and progression-free survival

“…4 Little is known on the effects of the graft immune cell subpopulation on the graft alloreactivity and on GVT and GVHD. Recently, Reshef et al analyzed CD4…”

Multi-color immune-phenotyping of CD34 subsets reveals unexpected differences between various stem cell sources

“…We have thus reenacted and translated into clinical routine application what the above authors described in their extensive functional analyses, and we show that the composition of the CD34 subsets differs substantially between the three CD34 sources examined. We assume that routine application of the presented protocol will allow high from medium or poor quality transplant materials to be distinguished and may thus predict engraftment characteristics as addressed by several authors, [6][7][8]15,24 but this will have to be proven in future studies. The present results show clearly that PBSC contain significantly higher proportions of MPP, LMPP and EMP than BMd.…”

“…However, one important issue concerning repopulation and engraftment after hematopoietic stem cell transplantation is to define distinct subsets of CD34 + cells. [6][7][8] Markers like CD45RA and CD38 were suggested in research experiments. [9][10][11][12] Expression studies of CD34 with CD10, CD38, CD45RA or CD90 led to the discovery of functional HSPC-subpopulations and to the presentation of the classic model of the human hematopoietic lineage tree.…”

Mobilization policy in multiple myeloma: minimum target or law of redundancy? Two different approaches by the two sides of the Atlantic Ocean

“…Furthermore, recent data suggest that PLX may increase mobilization of the more primitive CD34+/CD38-HPCs, and this stem cell subset is thought to be responsible for rapid engraftment after ASCT. 11 LEN has great activity in MM; however, in several MM patients previously treated with LEN G-CSF alone failed to mobilize HPCs. In a large retrospective study, mobilization failed in 25% of MM patients who had previously received LEN, compared with a failure rate of 4% in patients not previously treated with LEN; moreover, the failure rate was 78% in patients who received more than three courses of LEN, compared with 16% in patients who received three courses or less.…”