Blood, Vol. 92 No. 5 (September 1), 1998:
pp. 1820-1831
Comparative Analysis of Autografting in Chronic Myelogenous
Leukemia: Effects of Priming Regimen and Marrow or Blood Origin of
Stem Cells
Catherine M. Verfaillie,
Ravi Bhatia,
Michael Steinbuch,
Todd DeFor,
Betsy Hirsch,
Jeffrey S. Miller,
Daniel Weisdorf, and
Philip
B. McGlave
From the Department of Medicine, Stem Cell Biology Program, Bone
Marrow Transplantation Program, and Department of Laboratory Medicine
at the University of Minnesota, Minneapolis, MN; and The City of Hope
Medical Center, Duarte, CA.
The aims of this study were (1) to evaluate the effect of
intermediate (cyclophosphamide alone) or intensive (mitoxantrone, cytosine arabinoside, cyclophosphamide) priming on the cytogenetic response in mobilized bone marrow (BM) or peripheral blood (PB) progenitors in patients with chronic myelogenous leukemia (CML), (2) to
determine the incidence of cytogenetic remissions after mobilized
progenitor transplantation in CML, and (3) to determine the effect of
in vivo priming on the ability to select Philadelphia chromosome-negative (Ph-negative)
CD34+HLA-DR
cells from mobilized BM or PB
in quantities sufficient for transplantation. Between February 1994 and
March 1997, 44 patients were enrolled in three sequential protocols.
Although the duration of neutropenia after only cyclophosphamide
mobilization was shorter, clinical morbidity for the intermediate and
intensive priming protocols was similar. Cytogenetic responses in
mobilized PB progenitors were similar after mobilization with either
intermediate or intensive chemotherapy. The degree of Ph negativity in
the mobilized product correlated with disease stage at the time of
mobilization (early chronic phase [ECP] > late CP > accelerated
phase). Cytogenetic responses after transplantation with mobilized
progenitors obtained after the different regimens were similar. The
cytogenetic status of the graft predicted the cytogenetic status of
marrow obtained 3 weeks after transplantation whereas cytogenetic
responses 3, 6, and 12 months after transplantation correlated with the
number of BCR/ABL-negative CD34+HLA-DR
cells, but not the number of Ph-negative metaphases in the graft. In
patients with ECP CML, mobilized PB collections yielded significantly more CD34+HLA-DR cells than from steady
state or mobilized BM. CD34+HLA-DR cells
were Ph negative and polyclonal (X-chromosome inactivation) in the
majority of ECP CML patients, before and after mobilization and
irrespective of the mobilization regimen. Because infusion of large
numbers of Ph-negative CD34+HLA-DR cells
predicted superior outcome after transplantation, approaches in which
CD34+HLA-DR cells are selected from
mobilized PB may result in longer lasting and clinically significant
cytogenetic responses after transplantation.
© 1998 by The American Society of Hematology.
