Infections after T-replete haploidentical transplantation and high-dose cyclophosphamide as graft-versus-host disease prophylaxis

Abstract

Background: Recently, a platform of T-cell replete haploidentical hematopoietic stem cell transplantation (haplo-HSCT) using post-transplant cyclophosphamide (Cy) has shown high reproducibility and acceptable safety profile.

Method: This prospective cohort analysis allowed us to collect data on infections among 70 consecutive recipients of haplo-HSCT affected by various hematologic malignancies.

Results: After a median follow-up of 23 months, cumulative incidence of viral infections was 70% (95% confidence interval [CI] 59-81) at 100 days and 77% (95% CI 67-87) at 1 year; 35 of 65 patients at risk had CMV reactivation (54%) and the rate of polyomavirus-virus-associated cystitis was 19% (13/70). Cumulative incidence of bacterial and fungal infections at 1 year were 63% (95% CI 51-75) and 12% (95% CI 4-19), respectively. Of note, only 1 invasive fungal infection occurred beyond 1 year after transplant (day +739).

Conclusion: In conclusion, despite a high rate of viral infections in the early period, present data suggest a satisfactory infectious profile after T-cell replete haplo-HSCT using post-transplant Cy. These results may help clinicians to improve both prophylactic and therapeutic antimicrobial strategies in this emerging haploidentical setting.

Keywords: T-cell replete; antimicrobial prophylaxis; cyclophosphamide; haploidentical stem cell transplantation; hematologic malignancies; infections.

Figure 1

Cumulative incidence of infections after haploidentical hematopoietic stem cell transplantation (haplo‐HSCT). Cumulative incidence of first bacterial, fungal, and viral infections is shown here according to cumulative incidence method and competing risks (see text).

Figure 2

Bacterial, fungal, and viral infections at different post‐transplant intervals. Incidence of infections is here expressed as number of events per 1000 patient (pt)‐days at 4 post‐transplant intervals: from day 0 to +30, from +31 to +100, from +101 to +180, from +181 to +365. Haplo‐HSCT, haploidentical hematopoietic stem cell transplantation.

Figure 3

Lymphocyte subset counts by flow cytometry analysis. Subsets are graphically presented as boxplots; (A) CD3⁺/CD4⁺ cells; (B) CD3⁺/CD8⁺ cells; (C) CD19⁺ cells; (D) CD16⁺/CD56⁺ cells. Blood samples were collected on the planned day ±3 days according to logistical and/or clinical reasons: day +7 (n = 11), +28 (n = 12), +60 (n = 10), +100 (n = 4). Time points at days +14 and +21 are not reported in the Figure, because of close similarity to the very low values measured at day +7.