Response: T cells are required for the CMV-induced antileukemia effect after transplant

With great interest we read the letter by Thomson and coworkers who reported the results of their retrospective study evaluating the antileukemic effect of a CMV-replication after T cell–depleted transplantation using Campath in 100 patients with AML¹ . Further, they evaluated the effect of a CMV-specific cellular therapy on the relapse incidence in 19 patients with AML after T cell–depleted transplantation. They found a 5-year cumulative incidence of relapse (CIR) of 22% in CMV PCR-positive patients versus 28% in PCR-negative patients, which was not statistically significant (P = .4658), whereas no difference in the 5-year CIR was found in 19 patients receiving a CMV-specific cellular therapy compared with 81 patients receiving no CMV-specific cellular therapy. Because of the small number of patients and the heterogeneity of donors and disease stages of patients in their study, they also found no statistical significant differences in the CIR with regard to disease stage in their patients (1.CR versus > 1.CR), or donor type (unrelated versus sibling donor), which might have influenced the incidence of relapse in AML after transplant, too. Furthermore, the time interval between the application of cellular therapy at a median of 32 days after transplant and time for inclusion of patients surviving 50 days in the study was too short to observe possible antileukemic effects from a CMV reactivation after transplant. In our study we addressed this issue by including only patients surviving 100 days after transplant.² 

However, we could confirm in a further retrospective study that patients with AML (n = 60) after myeloablative T cell–depleted transplantation using Campath (50 mg or 100 mg total dosage) did not benefit from a CMV-reactivation. The 5-year CIR for patients with CMV replication after transplant was 52.5% versus 50% in patients without detection of CMV replication (n.s.). These data as well as the study by Thomson and coworkers indicate clearly that T cells are required for the CMV-induced antileukemic effect after transplant. This is further supported indirectly by a multicentre study published recently by Craddock and coworkers who evaluated factors predicting outcome after unrelated donor stem cell transplantation without T-cell depletion in primary refractory AML.³  By performing a multivariate analysis they found that besides fewer than 3 courses of induction chemotherapy and a lower percentage of bone marrow blasts at transplant, patient CMV seropositivity was associated with an improved 5-year survival.³ 

Thomson and coworkers have questioned the role of CMV-specific T cells with regard to relapse.¹  The limited data provided by the authors are not sufficient enough to rule out an involvement of CMV-specific T cells in the antileukemic effect on AML of CMV-reactivation after transplant, since the number of applied CMV-specific T cells is comparably small with usually 1 × 10⁵ T cells per kg/body weight of recipients in relation to the higher number of T cells of a non-T cell–depleted graft.^4,5  However, how the complex mechanisms of CMV replication after transplant influence the relapse incidence remain unclear.

We appreciate this single-center analysis by Thomson et al and are eagerly awaiting results from other centers.