Donor and recipient CMV serostatus and outcome of pediatric allogeneic HSCT for acute leukemia in the era of CMV-preemptive therapy

Abstract

In the era of cytomegalovirus (CMV)-preemptive therapy, it is unclear whether CMV serostatus of donor or recipient affects outcome of allogeneic hematopoietic stem cell transplantation (HSCT) among children with leukemia. To investigate, consecutive patients aged 0-18 who underwent primary HSCT for acute leukemia in 1997-2007 (HLA-matched sibling or unrelated donor, myeloablative conditioning, unmanipulated bone marrow or peripheral blood, preemptive therapy, no CMV prophylaxis) were followed retrospectively through January 2008. Treatment failure (relapse or death) was analyzed using survival-based proportional hazards regression. Competing risks (relapse and nonrelapse mortality, NRM) were analyzed using generalized linear models of cumulative incidence-based proportional hazards. Excluding 4 (2.8%) patients lacking serostatus of donor or recipient, there were 140 subjects, of whom 50 relapsed and 24 died in remission. Pretransplant CMV seroprevalence was 55.7% in recipients, 57.1% in donors. Thirty-five (25.0%) grafts were from seronegative donor to seronegative recipient (D-/R-). On univariate analysis, D-/R- grafts were associated with shorter relapse-free survival (RFS) than other grafts (median 1.06 versus 3.15 years, P < .05). Adjusted for donor type, diagnosis, disease stage, recipient and donor age, female-to-male graft, graft source, and year, D-/R- graft was associated with relapse (hazards ratio 3.15, 95% confidence interval 1.46-6.76) and treatment failure (2.45, 1.46-4.12) but not significantly with NRM (2.00, 0.44-9.09). In the current era, children who undergo allogeneic HSCT for acute leukemia have reduced risk of relapse and superior RFS when recipient and/or donor is CMV-seropositive before transplantation. However, no net improvement in RFS would be gained from substituting seropositive unrelated for seronegative sibling donors.

Figure 1. Relapse-free Survival, By Donor/Recipient CMV Serostatus (n=140)

Number of subjects at baseline, year 1, year 2, and year 3 were, for D−/R− graft, 35, 16, 8, and 6, and for other grafts, 105, 59, 44, and 33, respectively.

Figure 2. Cumulative Incidence of Relapse and Non-Relapse Mortality (NRM), By onor/Recipient CMV Serostatus (n=140)

Cumulative incidence is indicated using solid lines for relapse, dashed lines for NRM. Gray olor corresponds to D−/R− Graft, black to Other Grafts.