Immune Reconstitution And Infections

To date, few reports have analyzed immune reconstitution after nonmyeloablative HCT. Mohty et al. showed that early CD8+ T lymphocyte and NK-cell recoveries after HCT with a reduced-intensity conditioning regimen take place, whereas naive CD4+CD45RA+ T lymphocytes remained below normal values during the first months after the transplant.52 Similar results were reported by Baron et al.44 We recently compared immune reconstitution after conventional and non-myeloablative transplantation.53 During the first 6 months, absolute lymphocyte subset counts were similar, but counts of cytomegalovirus (CM V)-specific T-helper lymphocytes were higher at days 30 and 90 in the nonmyeloablative patient group. Conventional transplant recipients had higher naïve CD4 and CD8 counts 1 year after the HCT, probably reflecting lower counts of recent thymic emigrants in nonmyeloabla-tive recipients; this finding might be related to the older age of nonmyeloablative recipients.

Mohty et al. analyzed infectious complications occurring during the first 6 months after HLA-identical sibling transplantation with an ATG-based reduced-intensity conditioning regimen.54 The 6 month cumulative incidences of bacteremia, positive CMV antigenemia, and fungal infection were 25, 42, and 8%, respectively.

Junghanss et al. compared the incidence of post-transplant CMV infections in 56 nonmyeloablative recipients with that in 112 matched controls who were treated by conventional HCT during the same time period.55 CMV disease occurred in neither low- and intermediate-risk CMV nonmyeloablative or control patients. The 100-day incidence of CMV disease for high-risk CMV patients (defined as recipients serologi-cally positive for CMV) was 9% in the nonmyeloabla-tive group versus 19% (P = 0.08) in the control group. However, the 1-year probability of CMV disease for high-risk CMV patients was similar in the two groups (P = 0.87). The onset of CMV disease was significantly delayed in the nonmyeloablative group compared to the control group (medians of 130 days vs 52 days, P = 0.02). These results agreed with the evolution of CMV-specific immunity after nonmyeloablative or conventional HCT, and emphasized that nonmyeloablative HCT recipients should receive CMV surveillance beyond day 100 and preemptive ganciclovir treatment similar to that routinely given to recipients of mye-loablative regimens.

The same authors analyzed the incidence of bacterial infections during the first 100 days and of fungal infections during the first year posttransplantation.56

The 30- and 100-day incidences of bacteremia were 9 and 27% in the nonmyeloablative group versus 27% (P = 0.01) and 41% (P = 0.07) in the control group, respectively. Invasive aspergillosis occurred at a similar rate (15% in the nonmyeloablative group vs 9% in the control group, P = NS). Fukuda et al. analyzed risks and outcomes of invasive fungal infections in 163 nonmyeloablative HCT recipients. The 1-year cumulative incidence of proven or probable invasive fungal infections, invasive mold infections, invasive aspergillosis, and invasive candidiasis were 19, 15, 14, and 5%, respectively. Invasive mold infections occurred late (median 107 days) after nonmyeloabla-tive HCT. Risks factors were GvHD and CMV disease. Nonrelapse mortality in nonmyeloablative recipients' was 22%, of which 39% were mold infection related.

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