Loss of marrow reserve from dose-intensified chemotherapy results in impaired hematopoietic reconstitution after autologous transplantation: CD34(+),CD34(+)38(-), and week-6 CAFC assays predict poor engraftment
Sn. Robinson et al., Loss of marrow reserve from dose-intensified chemotherapy results in impaired hematopoietic reconstitution after autologous transplantation: CD34(+),CD34(+)38(-), and week-6 CAFC assays predict poor engraftment, EXP HEMATOL, 28(12), 2000, pp. 1325-1333
Objective. Autologous hematopoietic stem cell transplantation (HSCT) is an
increasingly successful modality for treating a variety of malignant disord
ers in the clinic. Experimental and clinical data suggest that prior exposu
re to cytotoxic agents that damage primitive stem cells results in impaired
hematopoiesis after autologous HSCT. To further investigate the ability to
predict for impaired hematopoiesis, we measured different stent/progenitor
cell populations transplanted and time to engraftment.
Methods. Patients with previously untreated, advanced-stage follicular lymp
homa were treated in sequential prospective protocols with 6-8 cycles of st
andard-dose (SD) cyclophosphamide, doxorubicin, vincristine, and prednisone
(CHOP), or four cycles of a higher-dose (HD) CHOP and granulocyte colony-s
timulating factor, to induce remission prior to high-dose cyclophosphamide,
total body irradiation, and autologous bone marrow transplantation (ABMT).
Cryopreserved marrow samples obtained prior to ABMT were assayed for CD34(
+), CD34(+)38(-), and cobblestone area-forming cell (CAFC) frequencies.
Results. Despite receiving similar numbers of nucleated cells at ABMT, HD-C
HOP patients took significantly longer to attain platelet engraftment than
the SD-CHOP patients. Marrow from the HD-CHOP patients contained significan
tly lower CD34(+), CD34(+)38(-), and week 6-8 CAFC frequencies than marrow
from SD-CHOP-treated patients. Time to platelet engraftment was plotted aga
inst progenitor/stem cell numbers transplanted for each patient and thresho
ld values were developed for all three stem/progenitor cell populations. Th
ese values were 0.5 X 10(6) CD34(+) cells/kg, 0.14 x 10(6) CD34(+)38(-) cel
ls/kg, and 9500 week-6 CAFC/kg transplanted. Approximately 50% of patients
received marrow progenitor/stem cell numbers above the threshold values and
all engrafted without delay. However, transplantation of stem/progenitor c
ell numbers below threshold values did not uniformly predict for delayed pl
atelet engraftment.
Conclusions. These data provide further evidence for the association of low
marrow reserve at ABMT, low numbers of stem/progenitor cells transplanted,
and delayed hematopoietic recovery. However, there remains a group of pati
ents who have rapid platelet engraftment after ABMT despite low numbers of
progenitor/stem cells transplanted. These data suggest the presence of a cr
ucial stem cell population not represented by the stem/progenitor cell popu
lations studied in these experiments. (C) 2000 International Society for Ex
perimental Hematology. Published by Elsevier Science Inc.