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CORRESPONDENCE We would like to comment on the recent report by
Chakrabarti et al1 on the risk of cytomegalovirus
(CMV) infection following nonmyeloablative allogeneic
transplantation. The conditioning regimen utilized by the authors
consisted of fludarabine, melphalan, and a total dose of 100 mg of
alemtuzumab (Campath-1H) given over 5 days. They found an 84.3%
probability of CMV infection in patients at high (seropositive
recipient) or intermediate (seronegative recipient, seropositive donor)
risk. The authors suggested that the use of alemtuzumab in the
conditioning regimen was responsible for the high rate of CMV infection
observed and that attenuation of the alemtuzumab dose might
reduce this risk. We would like to report on our experience of CMV
infection following reduced intensity transplantations using a lower
dose of Campath (50 mg) that suggests that this might not be
the case. Between January 1997 and June 2002, 2 reduced intensity
conditioning regimens containing Campath were used
concurrently. BEAM-Campath (Carmustine [BCNU] 300 mg/m2 day A total of 69 patients underwent transplantation, of which 36 were at risk of CMV infection (CMV seropositive recipient or donor).
Patients received unmanipulated bone marrow or granulocyte colony-stimulating factor (G-CSF)-mobilized peripheral blood stem cells from a sibling (n = 25) or matched unrelated donor
(n = 11). Detailed patient characteristics are shown in Table
1. In brief, the median age was 50.1 years (range, 23.6-59.9 years), 18 patients received fludarabine as part of the conditioning regimen (Flu
BEAM-Campath or FMC), and 18 received BEAM-Campath.
CMV screening was undertaken weekly by polymerase chain reaction
(PCR) from day +14 to day +120. CMV infection was defined as
PCR positivity on one assay confirmed on repeat testing.
Overall, 28 (77.8%) of 36 patients developed CMV infection. We
analyzed a number of risk factors for the development of CMV infection
in this cohort including type of transplantation, use of fludarabine in
the conditioning, and the type of Campath used. As
reported by Chakrabarti et al, there was no significant difference in
the risk of CMV infection between recipients of sibling and unrelated
transplantations. However, there was a significantly higher rate of CMV
infection in those patients receiving fludarabine (17 of 18) and those
not receiving fludarabine (11 of 18; Fisher exact test,
P = .041; Figure
1). There was no significant difference in the incidence of CMV infection
between patients receiving alemtuzumab (15 of 16) and those receiving
Campath-1G antibodies (13 of 20).
The median time to CMV infection was 7.3 weeks (range, 2.3-15.1 weeks).
Patients receiving fludarabine-containing regimens had significantly
earlier infection at a median of 4.3 weeks (range, 2.3- 15.1 weeks)
compared to a median of 7.8 weeks (range, 5.3-12.3 weeks) after
transplantation in the BEAM-Campath group (Figure 1; log-rank
Our overall incidence of CMV infection is similar to that reported by Chakrabarti et al.1 We had been concerned that a change to alemtuzumab would be associated with an increased risk of CMV infection as the humanized antibody has a longer half-life in vivo than Campath-1G antibodies2,3 and potentially may cause more prolonged immune suppression. However, we did not find an increased incidence of CMV infection in the alemtuzumab group. Chakrabarti et al suggested that a reduction in the dose of alemtuzumab might reduce the risk of CMV infection. Our data, which uses half the dose of alemtuzumab, suggest that this may not be the case. Rather, we found that the inclusion of fludarabine in the conditioning regimen was associated with both a higher incidence of CMV infection and infection at an earlier time after transplantation. Fludarabine is highly immunosuppressive and even as a single agent can result in CMV reactivation.4,5 We suggest that the combination of fludarabine and Campath is permissive to a higher risk of CMV infection and earlier CMV infection following reduced intensity allogeneic transplantations compared with patients who receive non-fludarabine-containing regimens such as BEAM-Campath. This may reflect the additional suppression by fludarabine of host CMV-specific T cells prior to the transplantation that might otherwise survive reduced intensity conditioning and thus offer some protection against CMV infection in the posttransplantation period.
Rowena D. Bainton, Jennifer L. Byrne, Barbara J. Davy, and Nigel H. Russell
References
1.
Chakrabarti S, MacKinnon S, Chopra R, et al.
High incidence of CMV infection after nonmyeloablative stem cell transplantation: potential role of Campath-1H in delaying immune reconstitution.
Blood.
2002;99:4357-4363 2. Cull G, Haynes A, Byrne J, et al. Preliminary experience of allogeneic stem cell transplantation for lymphoproliferative disorders using BEAM-Campath conditioning: an effective regimen with low procedure-related toxicity. Br J Haematol. 2000;108:754-760[CrossRef][Medline] [Order article via Infotrieve]. 3. Rebello P, Cwynarsky K, Varughese M, et al. Pharmacokinetics of Campath-1H in bone marrow transplant patients. Cytotherapy. 2001;3:261-267[CrossRef][Medline] [Order article via Infotrieve]. 4. Schilling P, Vadhan-Raj S. Concurrent CMV and Pneumocysitis pneumonia after fludarabine for CLL. N Eng J Med. 1990;323:833-834[Medline] [Order article via Infotrieve]. 5. Dean M, Gor D, Macmahon M, et al. Quantification of CMV viraemia in a case of transfusion-related graft versus host disease associated with a purine analogue. Br J Haematol. 1997;99:162-164[Medline] [Order article via Infotrieve].   CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
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6, cytosine arabinoside 200 mg/m2
days 
2, P < .001).
