We present the results of a pilot study using pentamer (PM) and streptamer (ST) multimer complexes for monitoring CMV-specific CD8+ T-cells (CTLs). We analysed 15 patients that underwent allogeneic Stem Cell Transplantation (HSCT). Patient characteristics are summarized in Table 1. All patients and donors were positive for the HLA-A*02:01 allele. PM and ST were directed against the epitope NLVPMVATV (495-503) of the CMV phosphoprotein 65 (pp65). Samples were obtained at 15-day intervals until day +90 and monthly thereafter.

PatientCMV status (D/R)GenderAgeDiagnosisDonorConditioningEngraftment (day)Follow up (months)GVHD (day)
1 +/+ F 43 NHL SIB RIC 24 15 - 
2 -/+ F 33 MDS URD RIC 19 12 - 
3 +/+ M 55 AML SIB MAC 17 14 47 
4 -/+ F 41 AML URD MAC 21 21 - 
5 +/+ F 32 AML SIB MAC 20 13 25 
6 +/+ F 64 MDS SIB RIC 27 14 89 
7 -/+ M 58 CLL URD RIC 23 13 92 
8 +/+ M 57 ALL URD MAC 15 5 - 
9 +/+ F 39 AML URD MAC 20 12 - 
10 -/+ M 42 ALL URD MAC 21 25 - 
11 -/+ M 44 AML URD MAC 12 8 153 
12 +/+ F 65 AML SIB RIC 25 8 - 
13 -/+ M 27 AML SIB MAC 30 3 18 
14 +/+ M 65 AML SIB RIC 19 6 62 
15 +/- F 30 SAA SIB RIC 13 3 - 
PatientCMV status (D/R)GenderAgeDiagnosisDonorConditioningEngraftment (day)Follow up (months)GVHD (day)
1 +/+ F 43 NHL SIB RIC 24 15 - 
2 -/+ F 33 MDS URD RIC 19 12 - 
3 +/+ M 55 AML SIB MAC 17 14 47 
4 -/+ F 41 AML URD MAC 21 21 - 
5 +/+ F 32 AML SIB MAC 20 13 25 
6 +/+ F 64 MDS SIB RIC 27 14 89 
7 -/+ M 58 CLL URD RIC 23 13 92 
8 +/+ M 57 ALL URD MAC 15 5 - 
9 +/+ F 39 AML URD MAC 20 12 - 
10 -/+ M 42 ALL URD MAC 21 25 - 
11 -/+ M 44 AML URD MAC 12 8 153 
12 +/+ F 65 AML SIB RIC 25 8 - 
13 -/+ M 27 AML SIB MAC 30 3 18 
14 +/+ M 65 AML SIB RIC 19 6 62 
15 +/- F 30 SAA SIB RIC 13 3 - 
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Three patterns were observed. In 3 patients (20%) no CMV-specific-CTLs could be detected despite several CMV reactivations, requiring prolonged cumulative antiviral therapy (median 68 days; range 67-136).

In 7 patients (47%) CMV reactivation occurred at a mean of 41 days (10-94) and triggered a rapid increase of CMV-specific-CTLs with a median of 22.7 x 105/L (range 1.3-279.7). The CMV-PCR became immediately negative and antiviral therapy was stopped promptly after a median of 15.5 days (6-23).

Finally, 5 patients (33%) showed an early immune reconstitution with CMV-specific-CTLs detected with a median of 0.7 x 105/L (range 0.2-2.8) in the absence of CMV-PCR reactivation at a median of 21 days (10-34) post-SCT. No CMV-PCR reactivation was observed in this group with a median follow-up of 12 months (5-14).

Discussion

Monitoring CMV-specific-T-cells might be able to distinguish patients at higher risk of recurrent virus reactivation and in need of prolonged antiviral therapy. Patients with increasing CMV-specific-CTLs detectable at the time of CMV-PCR reactivation may only need a short course of antiviral therapy, while those with early CMV-specific-CTLs may be protected from CMV reactivation.

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Conclusion

Using Multimer-based (Pentamer and Streptamer) monitoring of CMV-specific T-cell immune reconstitution after allogeneic HSCT may contribute to the clinical decision regarding when and for how long to commence anti-CMV therapy.

Disclosures:

No relevant conflicts of interest to declare.

Topics:
allogeneic stem cell transplant, cytomegalovirus, t-lymphocytes, complement membrane attack complex, mac protocol, mdc protocol, mitral valve annular calcification, monitored anesthesia care, antiviral agents, polymerase chain reaction
© 2013 by The American Society of Hematology
2013
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