Stem cell component therapy: supplementation of unmanipulated marrow with CD34 enriched peripheral blood stem cells

Abstract

Summary:Eleven patients with hematologic malignancies and two with aplastic anemia were treated using unmanipulated marrow and immunoselected CD34 ؉ blood cells. Donors began G-CSF (10 g/kg) injections 1 day after undergoing bone marrow harvest. Blood stem cells were collected on day 5 of G-CSF. Peripheral blood lymphocytes were depleted via CD34-positive selection. If, after marrow and blood harvest, less than 2.0 ؋ 10 6 CD34 cells/kg were mobilized, leukapheresis was repeated on day 6. Median time to an absolute neutrophil count greater than 500 l was day 10; transfusion-independent platelet count greater than 20 000/ l was day 13; average hospital discharge was day 14; and average inpatient hospital charges were 101 870 US dollars. Acute GVHD grade II occurred in five of 13 patients. No patient developed grade III or IV acute GVHD. At a median follow-up of 10 months, no patient has developed extensive chronic GVHD. Allografts of unmanipulated bone marrow supplemented with G-CSF-mobilized and CD34 immunoselected blood cells may prevent an increased risk of GVHD while preserving the rapid engraftment kinetics of peripheral blood. Supplementation of marrow with CD34 enriched blood cells appears to result in rapid engraftment, early hospital discharge, lower inpatient charges, decreased regimen-related toxicity, and no apparent increase in GVHD.

Supplemental peripheral blood stem cells to decrease marrow rejection in adult patients with severe aplastic anemia

“…In terms of engraftment, our results appear superior to other studies, taking the multiple transfusions and long disease duration into consideration. Engraftment of neutrophils and platelets occurred on days 12 and 17, respectively, which are comparable with the results of high-dose stem cell transplants, previously reported [13,14].…”

“…Feasibility studies into the use of the combination of unmanipulated marrow and T-cell depleted PBSC as the stem cell source for allogeneic BMT have shown rapid engraftment without increasing the risk of GVHD [13,14]. No similar data are yet available for SAA.…”

HLA-matched sibling transplantation with BM and CD34+-purified PBSCs in adult patients with high-risk severe aplastic anemia to overcome graft rejection without an increase in GVHD

“…4 A new trial assessing the addition of fludarabine (FLU) to a reduced dose of CY with ATG has shown good engraftment in heavily sensitized patients, whereas a high incidence of acute and chronic GVHD was also noted in that study. 13 On the basis of feasibility studies conducted by other groups, 15,16 we have applied a method that uses the combination of unmanipulated BM and T-cell-depleted PBSCs as a source of stem cells for high-risk patients with SAA to ensure engraftment. Our pilot studies showed a reduction in graft rejection and a faster engraftment speed, without any apparent increase in GVHD.…”

Clinical Utility in Maximizing CD34 + Cell Count in Stem Cell Grafts

“…2) [4]. This approach would contribute to the rapid engraftment kinetics of peripheral blood stem cells, allowing for an increase in stem cell dose without an increased risk of chronic GVHD.…”

“…In allogeneic transplantations, CD34 + dose correlates with early and late hematopoiesis and hospital charges. It is possible but unproven that CD34 + dose may impact on survival, and possibly GVHD [4,5].…”