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  • Commentary and Mini Review
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Commentary and Mini-Review

High stem cell dose in haemopoietic transplantation: is it always beneficial?

Leukemia volume 17, pages 1467–1469 (2003)Cite this article

In Leukemia 2003, Monty et al1 report new data suggesting that higher doses of CD34+ peripheral blood stem cells (PBSCs) are associated with increased mortality after allogeneic HLA-identical sibling transplantation. This is in sharp contrast to the general belief that the higher the quantity of progenitor cells infused to the patients, the better the results after the transplant. However, there are very recent data suggesting that this belief might be too simplistic. The specific clinical effect of the amount of progenitor cells might vary depending on several factors, among others: (a) the type of transplant, autologous or allogeneic, (b) the source of progenitor cells, either from umbilical cord, from bone marrow, or from peripheral blood, (c) the presence and the quantity of accessory cells, not only T cells, but also dendritic cells (myeloid and plasmacytoid) and mesenchymal cells, (d) the degree of HLA compatibility, and (e) the underlying disease and the phase of the disease.

In the Spanish registry of acute myeloblastic leukaemia (AML), we have recently analysed the outcome of 239 patients, diagnosed with AML in first complete remission and submitted to an autologous bone marrow transplant (BMT), depending on the number of mononuclear cells in the graft. Those patients receiving a higher quantity than the median had a trend for a lower transplant-related mortality. However, this group of patients also showed a trend for a higher incidence of relapse. In the end, the number of mononuclear cells did not influence disease-free survival. Indeed, bone marrow as the source of progenitor cells for autologous transplants has been reduced significantly. Currently, 95% of autologous transplants are performed using leucoaphaeresis of peripheral blood, because of the easy collection of a high amount of PBSCs. It is clear now that infusion of a high quantity of progenitor cells is associated with a rapid haemopoietic recovery and with a very low probability of graft failure and poor engraftment.2 It also seems evident that there is a threshold CD34+ cell dose below which engraftment is delayed, and that the positive linear correlation of the number of CD34 cells and kinetics of engraftment reaches a limit, above which an increase in the number of progenitor cells does not provide any additional benefit.3 Does this positive influence of CD34+ cells on haemopoietic recovery result in a better outcome of the patients? Not in the case of AML. In the Spanish registry of AML, we have analysed the effect of infusing a high quantity of peripheral blood CD34+ cells in AML patients in first complete remission. Transplant-related mortality was not influenced by the quantity of CD34+ cells administered, but relapse was significantly higher in the group of patients receiving a high amount of progenitor cells. Two recent studies published in Leukemia4,5 and commented on by de Witte,6 have shown very similar results. The EORTC and GIMEMA Leukemia groups have addressed this question in a randomized study (AML-10) comparing autologous BMT and autologous peripheral blood stem cell transplantation (PBSCT).4 In this study, blood stem cells were mobilized in patients recovering from consolidation chemotherapy. These patients were subsequently randomized to undergo an auto-BMT or an auto-PBSCT. The authors encountered a variable yield of mobilized CD34+ cells and hypothesized that a decreased ability to mobilize stem cells may reflect a chemotherapy-induced reduction in the number of normal and leukaemic stem cells. The 342 patients were categorized into four groups according to the stem cell yield: a group with no harvest, a group with a low yield (<1 × l06 CD34 cells/kg), with an intermediate yield (1–6.9 106 CD34− cells/kg), and with a high yield (≥7 × 106 CD34+ cells/kg). The 3-year disease-free survival rates of these groups were respectively, 47, 65, 50 and 27% (P=0.0002) and the relapse incidences were 48, 30, 43 and 72% (P<0.0001). Multivariate Cox's proportional-hazards model showed that the CD34+ yield was the second most important independent prognostic variable (P=0.005) after cytogenetics. Similarly, in the second study by the Free University Medical Center group in Amsterdam,5 stem cells were mobilized with G-CSF during the recovery phase of the first consolidation course. They also observed the association of a high percentage of CD34 cells in aphaeresis products of 71 AML patients with a high relapse risk (P=0.006) and a decreased disease-free survival (P=0.003). As stated by de Witte,6 this result probably is reflecting a greater sensitivity to chemotherapy among poor-mobilizer patients, that high numbers of mobilized stem cells obtained during the recovery phase of the first consolidation course indicate inadequate in vivo purging in the majority of patients with AML and that additional chemotherapy or alternative therapy is mandatory to prevent relapse in this high-risk group of patients. Needless to say, these results may vary depending on the disease. At the University of Salamanca, Spain, 100 non-Hodgkin's lymphoma cases were submitted to receive auto-PBSCT. The quantity of CD34+ cells infused to the patients had no impact on transplant-related mortality, relapse rate, or disease-free survival.7

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References

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  1. Department of Hematology, Institute of Hematology and Oncology, Hospital Clinic, University of Barcelona, Villarroel 170, Barcelona, Spain

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Urbano-Ispizua, A. High stem cell dose in haemopoietic transplantation: is it always beneficial?. Leukemia 17, 1467–1469 (2003). https://doi.org/10.1038/sj.leu.2402977

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