VI Autologous Bone Marrow Transplantation.pdf - Blog Science ...

AUTOGRAFTING WITH G-CSF-MOBILIZED BLOOD STEM CELLS IN
PATIENTS WITH CHEMOSENSITIVE MALIGNANCIES
R. Haas, R. Ehrhardt, S. Hohaus, W. Hunstein
Department of Internal Medicine V, University of Heidelberg,
Hospitalstr. 3,6900 Heidelberg, Germany
SUMMARY
Thirty-four patients (pt) with chemosensitive malignancies were treated
with G-CSF either during steady-state hematopoiesis or starting 24 hours after
cytotoxic chemotherapy. Blood stem cell collection was performed and monitored
by assessment of CD34+ cells in the peripheral blood (PB) (R = 0.84, p <
0.001 for CD34+ cells/ul of PB and the number of CD34+ cells/kg harvested per
leukapheresis). The yield of hematopoietic progenitor cells (CFU-GM and BFU-
E) varied substantially between individuals and was, mainly dependent on the
amount of previous chemotherapy. The 15 patients with > 5 x lOVkg CD34+
cells in their autografts had significantly less cycles of previous chemotherapy (3
versus 11, p < 0.001). However, patients receiving G-CSF post-chemotherapy
had a higher collection efficiency compared with the administration during
steady-state hematopoiesis. Analyzing the antigenic profile of the CD34+ cells,
the proportion of CD34+/HLA-DR- or CD34+/CD38- cells representing
noncommitted hematopoietic stem cells was consistently < 5%. In contrast, the
vast majority of CD34+ cells was found to coexpress the lineage associated
markers CD33 or CD71. A distinct population of CD34+ cells expressing CD19
above the control level was not detectable suggesting that early lymphoid progenitor
cells are not induced by G-CSF to enter the circulation. Following highdose
conditioning therapy 22 patients were autografted with the G-CSF-exposed
blood stem cells. Except for two patients (one toxic death, one early relapse),
complete engraftment was achieved after a median time of 15 days for 0.5 x 10 9
/
1 neutrophils and 13 days for 20 x 10 9
/1 platelets. The number of CD34 positive
cells transplanted proved to be highly predictive for platelet recovery (R = - 0.74,
p < 0.001). Patients transplanted with more than 5 x 10 6
/kg CD34+ cells reached
an unsubstituted platelet count > 20 x 10 9
/1 with a median time of only 10 days.
Our data demonstrate that complete and sustained engraftment can be achieved
following myeloablative pretransplant conditioning therapy with G-CSF-exposed
blood stem cells without additional bone marrow support or growth factor
administration.
INTRODUCTION
Peripheral blood stem cells (PBSC) are being increasingly used for
autografting in patients with malignant diseases to circumvent the myelotoxic
effects of high-dose therapy. During the past few years, different cytokine-based
mobilization regimens have been explored to improve blood stem cell collection.
Recently, G-CSF has emerged as a potent mobilizing agent. 23
232 SIXTH INTERNATIONAL SYMPOSIUM ON AUTOLOGOUS BONE MARROW TRANSPLANTATION