Donor CMV Status Influence On the Outcome of Allogeneic Stem Cell Transplantation (HSCT); A Study by the Infectious Diseases Working Party (IDWP) of the EBMT

Abstract ⁴⁶⁵

A previous study from the IDWP of the EBMT showed that CMV seropositive patients undergoing unrelated donor HSCT had increased NRM and decreased survival if they were grafted from a CMV seronegative donor. This finding has been controversial and we therefore decided to revisit the question with a larger number of patients and including new factors such as conditioning intensity.

Patients were selected from the EBMT database who had received an allogeneic HSCT from 1992 – 2008 and for whom both the donor and recipient CMV status were known. Patients receiving cord blood grafts were excluded. 54660 patients were identified and included in the study; 32320 seropositive and 22340 seronegative patients. The different donor categories (sibling, mis-matched family, unrelated) were analyzed separately. Cox multivariate models were fitted to estimate the effect of donor serological status (positive versus negative) on outcome both in CMV seropositive and CMV seronegative patients adjusted for year of HSCT, donor and patient gender, recipient age, stem cell source, diagnosis, use of alemtuzumab or ATG, country, and conditioning intensity (RIC vs. MAC).

Seronegative patients receiving grafts from seropositive unrelated donors had an decreased overall survival (OS; HR 1.13; p<.01); relapse free survival (RFS; HR 1.10; <p<.01) and increased non-relapse mortality (NRM; HR 1.13; p<;.01) while no significant effect was seen on relapse incidence (RI; HR 1.06). There were no significant effects in patients receiving HLA-identical or mis-matched family donors. Seropositive patients receiving grafts from seropositive unrelated donors had improved OS (HR 0.91; p<.01), RFS (HR 0.94; p<.05), and decreased NRM (HR 0.87; p<.01) if they had received MAC. No effect of donor serostatus was seen in patients receiving unrelated donor grafts after RIC. No effect of donor status was seen on RI. There were no significant effects in patients receiving HLA-identical or mis-matched family donors. Based on the recent study of Elmaagacli et al showing a decreased relapse risk in patients transplanted for AML of early CMV replication, a separate analysis regarding RI was performed only in AML patients in first CR. However, no effect of donor serostatus on RI was found in either seropositive or seronegative patients.

In this analysis we confirm the negative effect on OS, RFS, and NRM if a CMV seropositive unrelated donor is selected for a CMV seronegative patient. It therefore remains important to select a seronegative donor when the patient is seronegative. For a CMV seropositive patient our data support the choice of a CMV seropositive donor if the patient is planned to receive a myeloablative conditioning regimen.