New strategies in hematopoietic stem cell transplantation: G-CSF-mobilized unprocessed whole blood

Abstract

Transplantation of mobilized peripheral blood stem cells (PBSC) for rescue of bone marrow function after high-dose chemo-/radiotherapy is widely used in hematologic malignancies and solid tumors. Mobilization of stem cells to the peripheral blood can be achieved by cytokine treatment of the patients. The main advantage of autologous PBSC transplantation over bone marrow transplantation is the faster recovery of neutrophil and platelet counts. The threshold number of PBSC required for adequate rescue of bone marrow is thought to be about 2 x 10(6) CD34+ cells/kg, if the stem cells are collected by leukapheresis and subsequently cryopreserved. We show that this critical number could be further reduced to as few as 0.2 x 10(6) cells/kg. In 30 patients with multiple myeloma and 25 patients with bad risk lymphoma 1 liter of granulocyte colony-stimulating factor (G-CSF)-mobilized unprocessed whole blood (stored at 4 degrees C for 1-3 days) was used for transplantation. Compared to a historical control group, a significant reduction in the duration of neutropenia, thrombocytopenia and the length of hospital stay was documented. Furthermore, the effect of stem cell support was reflected by a lower need for platelet and red cell transfusions and a reduced antibiotic use. Considering the data as a whole, a cost saving of about 50% was achieved. To date, this easy to perform method of transplantation is only feasible following high-dose therapies that are completed within 72 h, since longer storage of unprocessed blood is accompanied by a substantial loss of progenitor cell function. Ongoing investigations include attempts to prolong storage times for whole blood.

Circulating hematopoietic stem cells serve as novel targets for in utero gene therapy

“…transplantation into NOD/SCID mice, compared with either full-gestational CB or adult BM stem cells. These circulating fetal stem cells (SCID repopulating cell, SRC) were found to be highly enriched within the CD34+CD38-Lin-subfraction and were predicted to provide adequate numbers of stem cells for the reconstitution of fetal recipients (12), as determined by calculating the number of FB-SRC required for a fetal recipient weighing less than 0.5 kg (15-17) at 12-18 weeks of gestation extrapolated from successful reconstitution correlates in adult patients receiving autologous stem cell transplants (18)(19)(20).…”

Optimising parameters for peripheral blood leukapheresis after r-metHuG-CSF (filgrastim) and r-metHuSCF (ancestim) in patients with multiple myeloma: a temporal analysis of CD34+ absolute counts and subsets

“…50,51 Whole blood donation as a source of PBSC has the potential to entirely eliminate the requirement for leukapheresis and avoid the loss of stem cells associated with cryopreservation. 52,53 In addition to measuring the absolute yield of CD34 + cells, we monitored the kinetics of subsets of CD34 + cells mobilized using this regimen. We observed a temporal increase in all subsets from day 9 to day 11, with the exception of CD90.…”