Blood, Vol. 96 No. 3 (August 1), 2000:
pp. 1194-1194
CORRESPONDENCE
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To the Editor: |
Cytomegalovirus infection following transplantation of
autologous CD34-selected progenitor cells
In their report of autologous CD34-selected peripheral blood
stem cell transplantation, Holmberg et al reported a very high incidence (22.6%) of cytomegalovirus (CMV) disease with 4 of the 7 patients who developed disease dying of CMV
infection.1 This high incidence of infection after
autologous transplantation is unusual, leading the authors to
suggest that the process of CD34 selection, which results in 2- to
3-log T-cell depletion, may be responsible for susceptibility to
CMV infection. Based on extensive experience with depletion
technology, however, we think alternative explanations should be considered.
We recently completed a phase III trial that compared autologous
CD34-selected and -unselected peripheral blood progenitor cell
transplantation in 193 patients with chemotherapy-sensitive intermediate-to-advanced-stage multiple myeloma.2,3 Both groups underwent stem cell mobilization with
cyclophosphamide/prednisone/G-CSF and a preparative regimen consisting
of busulfan/cyclophosphamide; patients did not routinely receive
prophylactic immunoglobulin therapy. Although CD34 selection achieved
the same degree of T-cell depletion as described by Holmberg et
al,1 we were unable to detect an increased susceptibility
to infection. The incidence of overall infection was equivalent in
patients receiving CD34-selected and -unselected transplants;
specifically, CMV infection was documented in 2 patients and 1 patient,
respectively. Interstitial pneumonitis occurred in 3 and 2 patients, respectively.
The results of this randomized study suggest to us that, although
the process of CD34 selection does produce significant T-cell depletion, immune reconstitution is apparently sufficient to prevent life-threatening infection in a population of treated patients with multiple myeloma undergoing autologous
transplantation.4 Alternative explanations for the
relatively high incidence of CMV infection in Holmberg et al's
study should focus on pretreatment characteristics. Their study used a
population of more heavily pretreated patients, especially patients who
may have received long-term glucocorticoid immunosuppression
(autoimmune disease patients) or multiple cycles of pretransplant
chemotherapy (oncology patients). A more intensive preparative regimen,
including a greater percentage of patients in the CD34-selection arm
receiving total body irradiation (TBI), may also have contributed to
the high incidence of CMV-related complications and the poor outcome in their study.
Gary John Schiller
Robert Vescio
James Berenson
Transplantation Biology Program
Division of
Hematology/Oncology
University of California Los Angeles
Los
Angeles, CA
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References |
1.
Holmberg LA, Boeckh M, Hooper H, et al.
Increased incidence of cytomegalovirus disease after autologous CD34-selected peripheral blood stem cell transplantation.
Blood.
1999;94:4029-4035[Abstract/Free Full Text].
2. Schiller G, Stewart AK, Vescio R, et al. An update of a phase III study
evaluating CD34 selected versus unselected autologous peripheral blood
progenitor cell transplantation in 190 patients with advanced multiple
myeloma. VII International Multiple Myeloma Workshop. 1999;118.
3.
Stewart AK, Schiller G, Vescio R, et al.
Blood.
1999;94(suppl 1):714a.
4.
Vescio R, Schiller G, Stewart AK, et al.
Multicenter phase III trial to evaluate CD34+ selected versus unselected autologous peripheral blood progenitor cell transplantation in multiple myeloma.
Blood.
1999;93:1858-1868[Abstract/Free Full Text]