PBSCs to Replace Bone Marrow for Allogenic Transplantation for Hematological Malignancies
ABSTRACT & COMMENTARY
Synopsis: In a trial to compare peripheral blood and bone marrow as a source of stem cells for allogenic transplantation it was shown that peripheral blood stem cells resulted in quicker hematological recovery and shorter hospital stay. The occurrence of graft vs. host disease and survival were comparable. It appears that peripheral blood-derived stem cells are preferable to bone marrow for allogeneic transplantation.
Source: Powles R, et al. Lancet 2000;355:1231-1237.
The transplantation of autologous peripheral blood stem cell (PBSC) results in earlier hematopoietic-cell repopulation after marrow ablative therapy than autologous bone marrow. This study from the Royal Marsden Hospital (UK) compared bone marrow and PBSC for allogenic transplantation. Adult HLA-identical sibling donors provided bone marrow as well as PBSC. In a double-blind study, 39 patients with malignant hematological disorders were transfused with bone marrow (n = 19) or with PBSC (n = 20) after typical conditioning regimens. For one year after the last transplant, the identity of the product infused remained concealed. The PBSC group was found to have faster neutrophil and platelet recovery than the bone marrow group. Patients in the PBSC group were also discharged from the hospital earlier than the bone marrow patients. At four weeks after transplantation, absolute lymphocyte and CD25 cell counts were increased in the PBSC group. There was no difference in the occurrence of acute or chronic graft vs. host disease (GVHD) and overall survival. Thus, it appears that for patients with hematological malignancies, PBSCs are superior to bone marrow for allogenic transplantation from HLA-identical siblings in terms of earlier engraftment and faster immune recovery.
COMMENT BY WILLIAM B. ERSHLER, MD
Peripheral blood has become the preferred source of stem cells for autologous hematopoietic support after high-dose chemotherapy because of a more rapid hematologic recovery.1,2 Since this has become clear, investigators have also used PBSCs for allogenic transplants as well,3,4 but only one randomized, prospective study had previously been reported.5 There had been several retrospective studies that would suggest the efficacy of this approach, but there remained some controversy about the potential for GVHD and possibly other outcomes such as disease recurrence and survival.
This was a relatively small study, but very well designed. Donors were asked to give both bone marrow and peripheral blood stem cells and the procedures were performed in such a way as the patients and investigators did not know which of the stem cell sources were used until one year after the transplant. Donors had their marrow harvested and then were given recombinant granulocyte colony stimulating factor for five days before PBSC harvest (by standard leukapheresis). Despite (or perhaps because of) the prior marrow donation, PBSC harvest resulted in excellent numbers of nucleated cells including cells positive for CD3, CD4, CD8, CD19, CD25, and CD34, as well as granulocyte-macrophage colony forming units. In fact, PBSC recipients received significantly more of each of these cell types than the bone marrow recipients.
The data showed clearly that neutrophil and platelet recovery were quicker and hospital stay was shorter in the PBSC recipients. GVHD prophylaxis was aggressive for both groups and there was no difference in the development of acute or chronic GVHD between the groups. Similarly, treatment-related deaths were comparable. However, all five of the patients who relapsed with their hematological malignancy were recipients of bone marrow (not PBSCs). This, despite the fact that the initial randomization resulted in more patients with high risk for relapse in the PBSC arm.
Although this was a small study, the research design was well constructed and the findings are to be believed. The take-home message is that for allogenic transplantation for hematological malignancy, PBSCs results in quicker hematological and immune recovery and shorter hospital stays than bone marrow. The development of GVHD occurred comparably, but there is suggestive evidence that disease relapse is less with PBSC transplant. This latter point, and the applicability of PBSCs in other allogeneic transplantation settings (such as between HLA mismatched individuals) remains to be determined.
References
1. Schmitz N, et al. Lancet 1996;347:353-357.
2. Duncan N, et al. Bone Marrow Transplant 1996;18:1175-1178.
3. Bensinger WI, et al. Blood 1995;85:1659-1665.
4. Miflin G, et al. Bone Marrow Transplant 1997;19:9-13.
5. Schmitz N, et al. Bone Marrow Transplant 1998;21: 995-1003.
Which of the following statements about allogeneic stem cell transplantation for hematological malignancy is true?
a. Bone marrow results in quicker hematological recovery than peripheral blood stem cells.
b. Survival for patients transplanted with marrow is greater than those that receive peripheral blood stem cells.
c. Peripheral blood stem cells result in quicker hematological recovery.
d. Survival for patients transplanted with peripheral blood stem cells is greater than those with bone marrow stem cells.
You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
- Award-winning Medical Content
- Latest Advances & Development in Medicine
- Unbiased Content