Page 2017 - Hematology_ Basic Principles and Practice ( PDFDrive )

1788 Part XI Transfusion Medicine

TABLE Bone Marrow Versus Cytokine Stimulated Peripheral Blood Stem Cells as Graft Source of Choice for Hematopoietic Stem
118.3 Cell Transplantation
Preferred Graft Source
Disease Category Recipient Age Group Type of Donor (Unstimulated BM vs. Cytokine Stimulated PB HSPC)
Nonmalignant (e.g., severe aplastic anemia) All ages Sibling BM HSPCs
Malignant Pediatric Sibling BM HSPCs
Malignant Adult Sibling PB or BM HSPCs (PB HSPCs preferred in
high-risk leukemia)
Malignant Adult Matched unrelated donor PB or BM HSPCs (PB HSPCs preferred if high
graft failure risk; BM HSPCs if high cGVHD
risk, prior immunosuppression)
BM, Bone marrow; cGVHD, chronic graft-versus-host disease; HSPC, hematopoietic stem and progenitor cell; PB, peripheral blood.

during most cell collection procedures and therapeutic cell deple- limited by the lack of a standardized assay; however, time and level
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tions, no volume replacement beyond the anticoagulant and saline of increase of donor peripheral blood WBC and CD34 cell counts
priming solution is required. Problems of decreased availability and after administration of mobilizing agents have proved to be useful
high cost of albumin have led some centers to develop protocols for indicators. Despite ongoing problems with interlaboratory standard-
alternatives to plasma-derived volume expanders, such as hydroxy- ization, flow cytometric analysis of cells labeled with a fluorochrome-
ethyl starch (HES), for full- or partial-volume replacement with conjugated CD34 antibody are used for “real-time” decision making
plasma exchange. One center has used a combination of 3% HES about the timing and adequacy of PB HSPC collections. Several
and 5% albumin mixture successfully, but patients did experience prestimulation donor variables are important. Increasing age, white
mild adverse events more frequently than did historical control ethnicity, and female gender are associated with significantly lower
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subjects. Although such solutions are generally well tolerated, post–G-CSF CD34 cell counts, which would favor younger males
extensive replacement with HES in patients undergoing longer as donors when high cell doses are required. 26
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courses of plasmapheresis, especially those with impaired renal func- Several clinical scale devices for CD34 cell enrichment of leuka-
tion, can result in diffuse tissue accumulation of the larger starch pheresis collections by immunoabsorption or immunomagnetic
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molecules (acquired lysosomal storage). techniques are available. This “positive selection” of CD34 hemato-
poietic cells also results in reduced numbers of cells that do not
express the CD34 antigen, such as T lymphocytes. T-cell–reduced
HEMATOPOEITIC STEM CELL COLLECTION products may confer a lower risk of GVHD, and the ability to
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produce apheresis products enriched for CD34 cells facilitates graft
Blood cell separators developed for hemapheresis are used to collect manipulations for experimental cell therapies such as ex vivo expan-
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peripheral blood cells for cellular therapy. The most common applica- sion of CD34 cells. However, some studies suggest a higher incidence
tion of apheresis technology for cell therapy indications is the collec- of engraftment failure and possibly delayed immune reconstitution
tion of HPCs from peripheral blood after administration of in certain patient populations when transplants are performed with
recombinant hematopoietic growth factor or chemotherapy, or both, highly purified CD34-selected, T-cell–depleted products.
to “mobilize” large numbers of HPCs into the circulation. The col- Over the last decade, PB HSPCs have surpassed bone marrow
lected mononuclear cell fraction contains a subset of progenitor cells HSPCs as the predominant graft source in the clinical setting for
that, on infusion, can home to and reconstitute the bone marrow in various hematopoietic stem cell transplants. PB HSPCs are the graft
patients who receive ablative radiation or chemotherapy, or both. of choice in 99% of conditions where autologous transplants are
Similarly, donor leukocytes obtained from leukapheresis procedures indicated. For allogeneic transplants, especially which use stem cells
may be used for donor lymphocyte infusion or subject to further from matched unrelated donors or in pediatric transplants, bone
processing for immunotherapy. marrow stem cells still remain the popular graft source. PB HSPC
transplants result in higher rates of clinically significant chronic
Peripheral Blood Hematopoietic Stem and GVHD in these situations. Table 118.3 provides a summary of
comparisons of bone marrow versus PB HSPCs in different types of
Progenitor Cells allogeneic stem cell transplants.
From a donor perspective, the discomfort and inconvenience of
Pluripotent HPCs, and quite possibly primordial hematopoietic stem multiple-day cytokine administration may be a significant deterrent.
cells capable of reconstituting the bone marrow and the immune Most donors experience some degree of malaise and bone pain, and
system, have long been known to circulate in the peripheral blood. some donors require hospitalization for more serious adverse reac-
Numerous studies have confirmed the potential for rapid and durable tions to G-CSF administration. However, a large prospective trial of
engraftment of peripheral blood hematopoietic stem and progenitor the National Marrow Donor Program found intensity and duration
cells (PB HSPCs) mobilized into the circulation by hematopoietic of pain in the pericollection period (during G-CSF administration
growth factors harvested by large-volume leukapheresis procedures before apheresis among PB HSPC donors and following bone marrow
and subsequently administered to patients with marrow aplasia after biopsy procedure in bone marrow HSPC donors) was similar for
high-dose chemotherapy. The concentration of hematopoietic stem persons undergoing HSPC collection by either apheresis or bone
and progenitor cells in the peripheral blood can be increased by the marrow biopsy. Further, 3% of bone marrow donors reported ongoing
administration of cytokines such as granulocyte colony-stimulating low-grade site pain after 6 months of completing the procedure
factor (G-CSF) and granulocyte-macrophage colony-stimulating whereas recovery was complete for PB HSPC donors by this time.
factor (GM-CSF) and by the administration of chemotherapy. Risk factors for worse toxicities, including older age, female gender,
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CD34 hematopoietic cell numbers in the peripheral blood generally and obesity were similar among bone marrow and PB HSPC donors.
rise 20- to 40-fold (from 1–3 cells/µL to 40–70 cells/µL) after While concerns remain regarding the hypothetic long-term effects of
administration of G-CSF alone, and they increase 100- to 1000-fold exposure of healthy donors to growth factors, another recent prospec-
when chemotherapy rebound is enhanced by administration of tive study with more than 20,000 donor-years of follow-up, showed
G-CSF. Efforts to define optimal collection conditions have been no evidence of increased risk for cancer, autoimmune illness, and