Donor Serostatus Has an Impact on Cytomegalovirus-Specific Immunity, Cytomegaloviral Disease Incidence, and Survival in Seropositive Hematopoietic Cell Transplant Recipients

Abstract

More cytomegalovirus (CMV)-specific T cells are transferred with grafts from CMV seropositive than seronegative donors. We hypothesized that seropositive recipients of grafts from seropositive donors (D+R+) have higher counts of CMV-specific T cells than seropositive recipients of grafts from seronegative donors (D-R+), and that this is clinically relevant in the setting of in vivo T cell depletion using rabbit-antihuman thymocyte globulin (ATG). We reviewed charts of 298 ATG-conditioned, seropositive recipients for CMV reactivation (pp65 antigenemia or CMV DNAemia above institutional threshold for preemptive therapy), recurrent CMV reactivation, CMV disease, and death. In 77 of these patients, we enumerated CMV-specific T cells. Median follow-up was 564 days. CMV-specific CD4+ and, to a lesser degree, CD8+ T cell counts were higher in D+R+ than D-R+ patients. D+R+ patients had lower cumulative incidence of CMV reactivation (21% versus 48%, P < .001), recurrent reactivation (4% versus 15%, P = .003), CMV disease (3% versus 13%, P = .005) and mortality (42% versus 56%, P = .006). We conclude that in the setting of in vivo T cell depletion using ATG, seropositive donors should be used for seropositive recipients. For scenarios where only seronegative donors are available, strategies to improve CMV-specific immunity (e.g., donor vaccination) should be explored.

The patient’s CMV serological status affects clinical outcome after T-cell replete haplo-HSCT and post-transplant cyclophosphamide

“…The present results are consistent with reports from other transplant settings, in particular when ATG is administered as GvHD prophylaxis and when the donor is CMV seronegative; [11][12][13] similarly, the profound state of immune suppression here prevents or impairs the prompt recovery of anti-CMV immunity, this latter recently associated with a better protection from overall infections in the context of haplo-HSCT with PT-Cy. 14 Abbreviations: BM = bone marrow; HCT-CI = hematopoietic cell transplantation-specific comorbidity index; MAC = myeloablative conditioning; MDS = myelodisplastic syndrome; MPS = myeloproliferative syndrome; NMA = nonmyeloablative; RIC = reduced-intensity conditioning.…”

CMV promotes recipient T-cell immunity following reduced-intensity T-cell–depleted HSCT, significantly modulating chimerism status

“…4 Furthermore, 60% of the cohort underwent myeloablative conditioning. Interestingly, our assertion that strategies that result in full donor chimerism might offer little antiviral protection in the context of R1/D2 transplants is supported by the clinical outcome data of these studies, 4,5 as well as by a smaller study that demonstrated persistence of recipient-derived CMV-specific T cells in T-deplete but not T-replete HSCT. 12 The latter study used an in vitro T-cell depletion strategy with Campath-1M plus complement, which results in depletion of mainly donor T cells while leaving recipient T cells intact.…”

“…This may explain the apparent discrepancy between our results and those in a large group of patients undergoing HSCT incorporating antithymocyte globulin. 5 Although reconstitution of CMV-specific T-cell immunity was slower in those with CMV seronegative donors, with a coincident increase in CMVrelated complications, almost 50% of the cohort developed clinically significant GvHD, and chimerism was fully donor in all evaluable R1/D2 patients by 3 months post-HSCT.…”

“…1,2 In high-risk cases in which the recipient is seropositive, this is likely to be the most prolonged when the donor is seronegative (D2), as immunity is then reliant on the development of a primary immune response. [3][4][5] After myeloablative conditioning, the establishment of protective immunity may be delayed still further by the incorporation of T-cell depletion strategies aimed at reducing the risk for graft-vs-host disease (GvHD).…”

Late-Onset Cytomegalovirus (CMV) in Lung Transplant Recipients: Can CMV Serostatus Guide the Duration of Prophylaxis?

“…None of the D-/R+ LTx patients included in this analysis developed CMV disease and only 5.9% developed CMV infection. The marked difference in the observed rates of CMV infection or disease between D-/R+ and D+/R+ patient may be related to R+ LTx patients having only partial immunity to the CMV strain carried by the D+ organ (17). Whereas recipients of D-organs have preexisting T cell-specific immunity to protect against reactivation of their native CMV strain, many recipients of D+ organs may require several months to develop T cell-specific immunity that confers protection against CMV superinfection by the donor strain.…”