A Cytomegalovirus Reactivation Is Associated with An Improved Progression-Free Survival Rate In Patients with Lymphoma After Allogeneic Transplant

Cytomegalovirus reactivation (HCMV) occurs frequently after hematopoetic stem cell transplantation and is often associated with an increased treatment-related mortality. Recently we have demonstrated that a HCMV-reactivation is associated with a reduced relapse risk and improved overall survival rate for patients with acute myeloid leukemia, but not for patients with chronic myeloid leukemia after allogeneic transplant. Now, we aimed to evaluate the effects of a HCMV-reactivation in patients transplanted for lymphoma.

We performed a retrospective study in a cohort of 67 patients (44 male/23 female) with lymphoma, who were transplanted with an unmanipulated graft from an unrelated donor (URD) after conditioning with a reduced-intensity regimen (n=9) or myeloablative regimen (n=58) in our centre. 48 patients were transplanted from HLA-matched donors, whereas 19 patients received a transplant from an URD with a HLA-mismatch. ATG was given to 19 of 67 patients. The median age of patients was 42 years (range 18–67). 25 patients were diagnosed with diffuse large B-cell lymphoma, 14 pts with follicular lymphoma, 13 pts with T-cell lymphoma, 10 pts with mantle cell lymphoma, 2 ptswith transformed B-cell lymphoma, 3 pts with Hodgkin's lymphoma. The median IPI score was 2 (n=50) prior to transplant, the median score for FLIPI was 2 (n= 14).

A HCMV-reactivation occurred in 27 of 67 transplanted patients (40%) and was documented by CMV-related matrix protein pp65 antigenemia test and routinely accompanied by a CMV preemptive therapy with valganciclovir or ganciclovir.

In in-vitro experiments we exposed the human T cell lymphoma cell line Karpas 299 to HCMV and measured the apoptosis rate by FACS and HCMV copy numbers by real-time RT-PCR 14 days after exposure.

We found an improved 4-year progression-free-survival rate (PFS) in patients with a HMC reactivation. The cumulative incidence of 4-year PFS was 55.9% in patients with HCMV-reactivation versus 38.7% in patients without a HCMV reactivation after transplant (p=0.049). The 4-year overall survival was 64.9% versus 46% without a HCMV reactivation (p=0.16). The incidence of acute GVHD grade 2–4 and chronic GVHD was not different in both groups (42 and 43% for acute GVHD and 46% and 45% for chronic GVHD). In in-vitro experiments we could not detect the induction of apoptosis by HCMV in the T cell lymphoma cell line Karpas 299 nor an increase of HCMV DNA after HCMV exposure demonstrating that the lymphoma cellline was not infected by HCMV.

The pathway how HCMV induces an anti-lymphoma effect is not clear yet and seems to be different from that in AML, in which HCMV infects AML cells directly as shown earlier. Nevertheless, a HCMV reactivation seems to improve the outcome for patients with lymphoma after transplant, which is of clinical interest.

No relevant conflicts of interest to declare.