Blood, Vol. 95 No. 12 (June 15), 2000:
pp. 4016-4018
CORRESPONDENCE
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To the Editor: |
High incidence of symptomatic cytomegalovirus infection
in multiple myeloma patients undergoing autologous peripheral blood
stem cell transplantation
Holmberg et al1 report on 268 cases of
malignant diseases treated with autologous peripheral blood
stem cell transplantation (APBSCT); an increased incidence of
cytomegalovirus (CMV) disease was observed in patients who had
autologous CD34+ selected cell infusion: 7 out of 31 cases
(22.6%) developed CMV disease and 4 of them died. In univariate and
multivariate analysis, only CD34 selection was significant for the
development of CMV disease. Holmberg et al1 hypothesize
that the delayed immune reconstitution observed after the infusion of
CD34-selected cells increases susceptibility to CMV infection and disease.
In patients receiving allogeneic bone marrow transplantation
the incidence of CMV infection, defined as either evidence of any level of quantitative PP65 antigenemia or a positive blood or
mouth culture, ranges from 42% to 69%. The incidence of CMV disease
was up to 23% in patients with concomitant GvHD2;
posttransplant immunosuppression, concomitant GvHD, and
immunosuppressive therapy to treat such complications may be partially
responsible. Wingard et al3 reported a 45% incidence of
CMV infection in a cohort of 143 autologous BMTs, which was similar to
the infection rate observed in patients undergoing allogeneic
transplant. Nevertheless, the incidence of CMV disease in autologous
transplantation was only 2%. In a retrospective study of the EBMT
group, the incidence of CMV pneumonia in autologous transplant was
0.8%.3
The high incidence of CMV disease noticed by Holmberg et
al1 had never been observed in previous series of
patients undergoing autologous transplant; Holmberg et al indicate the
CD34+ cell selection as the only predictive factor of CMV
infection and disease; nevertheless, the incidence of CMV disease in
multiple myeloma (MM) patients was 5 of 32 (15%): 4 of 5 had received
selected cell transplant.
At our institution, 106 CMV seropositive patients affected with
hematological malignancies received APBSCT after massive chemotherapy. They were affected with MM (33 cases), non-Hodgkin lymphomas (NHL) (42 cases), Hodgkin disease (HD) (18 cases), acute nonlymphoid leukemia
(ANLL) (8 cases), and chronic granulocytic leukemia (CGL) (5 cases).
The median age was 42 years (range, 18 to 61). Sixty patients were
males, and 46, females. All patients received unselected peripheral
blood stem cells mobilised with G-CSF and cyclophosphamide (CY) given
at the dose of 4000 mg/m2. Conditioning
regimen was as follows: patients with MM received melphalan and
thiotepa (14 cases) or a modified BEM regimen including carmustine 600 mg/m2, etoposide 30 mg/kg, and melphalan 200 mg/m2 (19 cases); patients with HD or NHL had carmustine,
etoposide, and CY in association (BCV). Patients with ANLL or CGL had
busulphan (BU) and CY at standard dose. The weekly screening of PP65
antigenemia was not routinely performed because the low incidence of
CMV disease usual in patients undergoing autologous bone marrow
transplantation. CMV antigenemia was effected only in patients with
fever unresponsive to a wide spectrum of antibiotic therapy, joint
pain, weakness or diarrhea, cough, or unexplained dyspnea or
leucopenia. Patients with positive CMV antigenemia received prompt
treatment with ganciclovir at the dose of 5 mg/kg every 12 hours over 3 weeks; in these selected patients, the weekly screening of antigenemia
was thereafter performed.
One episode of CMV symptomatic infection was noticed in 8 patients (7.5%). The median time to CMV reactivation ranged from day +15 to day +374. The main characteristics of patients who developed CMV infection are reported in the Table.
Six out of 8 patients (75%) were affected with MM; the crude incidence
of CMV infection in MM patients was 18%, and only 2 of 73 patients (2.7%) affected with NHL, HD, or ANLL had CMV complication
(P = .011). In our experience, the diagnosis of
MM seems to be predictive of CMV infection; we can hypothesize that the
immunosuppressive status related to the underlying disease may have a role.
In previous studies, the incidence of CMV infection was never related
to the diagnosis of MM probably because the low number of autologous
bone marrow transplants performed before the use of peripheral blood
stem cells become more general. Although many patients affected with MM
receive APBSCT, there are not prospective studies exploring the
incidence of CMV infection and disease in this subset of
patients. We believe that, given the increased incidence of symptomatic
CMV infection observed in our study, close monitoring and anti-CMV
therapy are needed in patients with MM receiving autologous peripheral
blood progenitor cell transplantation and particularly in those
receiving CD34+ selected cell transplant.
Emilio Paolo Alessandrino
Marzia Varettoni
Anna Amelia Colombo
Daniela Caldera
Paolo Bernasconi
Luca Malcovati
Centro trapianti di midollo osseo
Divisione di Ematologia
IRCCS Policlinico S. Matteo
Pavia, Italy
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References |
1.
Holmberg LA, Boeckh M, Hooper H, et al.
Increased incidence of cytomegalovirus disease after autologous CD34
selected perypheral blood stem cell transplantation.
Blood.
1999;94:4029-4035[Abstract/Free Full Text].
2.
Wingard JR, Chen DY, Burns WH, et al.
Cytomegalovirus infection after autologous bone marrow transplantation with comparison to infection after allogeneic bone marrow transplantation.
Blood.
1988;71:1432-1437[Abstract/Free Full Text].
3.
Ljungman P, Biron P, Bosi A, et al.
Cytomegalovirus interstitial pneumonia in autologous bone marrow transplant recipients.
Bone Marrow Transplantation.
1994;13:209-212[Medline]
[Order article via Infotrieve].
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Response: |
Incidence of cytomegalovirus infection and disease after
autologous CD34-selected peripheral blood stem cell transplants
We found the observations of Emilio P. Alessandrino et al to
be very interesting. Our groups, however, defined cytomegalovirus (CMV)
infection and disease differently. As is outlined in our paper,1 we defined CMV infection as either evidence of any quantitative pp65 antigenemia or a positive blood or marrow culture. We
defined CMV disease as a positive shell viral or
conventional culture of bronchoalveolar lavage fluid, lung biopsy, or
gastric/duodenal biopsy in association with symptoms. Unlike
Alessandrino et al's group, our group of patients was transplanted for
a number of different hematologic and nonhematologic malignancies and
autoimmune diseases.
As is outlined in our paper, we found that 6 of 19 (31.6%) and 34 of
172 (19.8%) developed a CMV infection, and 7 of 31 (22.6%) and 10 of
237 (4.2%) developed CMV disease in the CD34-selected and -unselected
groups, respectively. Two of 3 CD34-selected patients and 3 of 5 unselected patients had no evidence of CMV antigenemia prior to
developing CMV disease.
By univariate logistic regression analysis, steroid use and CD34
selection were associated with a highly significant chance for
developing CMV infection, ie, OR of 3.0 (P = .003) and
OR of 2.69 (P = .04), respectively. Only CD34
selection was highlysignificant for the development of CMV disease: OR
of 6.62 (P = <.001).
We agree with Alessandrino et al that close monitoring for CMV should
be done in autologous transplant patients at high risk for developing
CMV disease and infection.
Leona A. Holmberg
William I. Bensinger
Fred Hutchinson Cancer Research Center
University of
Washington School of Medicine
Seattle, WA
| |
Reference |
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.
