Allogeneic hematopoietic stem cells from sources other than bone marrow: biological and technical aspects

Identification and characterization of hematopoietic stem cells in peripheral blood (PB) and cord blood (CB) have suggested feasible alternatives to conventional allogeneic bone marrow (BM) transplantation. The growing interest in this use of allogeneic stem cells has prompted the Working Group on CD34-positive Hematopoietic Cells to review this subject by analyzing its biological and technical aspects.

The method used for preparing this review was informal consensus development. Members of the Working Group met three times, and the participants at these meetings examined a list of problems previously prepared by the chairman. They discussed the individual points in order to reach an agreement on the various concepts, and eventually approved the final manuscript. Some of the authors of the present review have been working in the field of hematopoietic stem cell biology and processing, and have contributed original papers published in peer-reviewed journals. In addition, the material examined in the present review includes articles and abstracts published in journals covered by the Science Citation Index and Medline.

Several studies have now shown that hematopoietic stem cells collected from peripheral blood after the administration of G-CSF, or from cord blood upon delivery, are capable of supporting rapid and complete reconstitution of BM function in allogeneic recipients. Perhaps more importantly, reinfusion of large numbers of HLA-matched T-cells from PB collections or T-cells with various degrees of HLA disparity from CB did not result in a higher incidence or greater severity of acute graft-versus-host disease than expected with BM. Based on the data reviewed, operative guidelines for mobilization, collection and graft processing are provided.

It should be remembered that despite the growing interest, these procedures must be still considered as advanced clinical research and should be included in formal clinical trials aimed at demonstrating their definitive role in stem cell transplantation. In this regard, a large European randomized study is currently comparing PB and BM allografts. However, the possibility of collecting large quantities of hematopoietic progenitor-stem cells, perhaps with reduced allo-reactivity, offers an exciting perspective for widening the number of potential stem cell donors and greater leeway for graft manipulation than is possible with BM.