Impact of Ptcy-Based Prophylaxis on Early Infectious Complications in Adults Undergoing Peripheral Blood Allo-HCT

INTRODUCTION PTCY-based prophylaxis was progressively implemented at our HCT Program for adults undergoing peripheral blood (PB) allo-HCT independently of the selected donor type. However, despite the efficacy provided in GVHD prevention, the incidences of infections among these patients remain high.

Although PTCY-based prophylaxis is spreading rapidly in the allo-HCT Community very few studies so far have compared the incidence of infectious complications in patients receiving PTCY with that in patients receiving other prophylaxis. This study aims to investigate whether PTCY affects the probability of infectious complications diagnosed during the first 180 days after allo-HCT, and to explore the impact of these infections in post-transplant survival.

METHODS Between the years 2012 and 2021, 426 consecutive adults with hematological malignancies underwent PB allo-HCT at or Institution, and all were included in the study. All patients received levofloxacin 500 mg daily from day +1 until neutrophil engraftment. No patient received letermovir.

The study cohort was divided into two groups according to the GVHD prophylaxis: PTCY-based vs. others. The cumulative incidence functions (CIF) of infectious complications were estimated considering death as competing event, and after censoring the post-transplant follow-up at day +180. Moreover, in patients presenting more than one infection / viral reactivation during the study period, only the first episode was accounted as an event. Lastly, in the evaluation of post-transplant outcomes, patient´s follow-up was censored at 1 year.

RESULTS 244 (57.2%) out of 426 patients received PTCY-based prophylaxis. Baseline characteristics were balanced, except for the proportion of allo-HCT performed from alternative donors (MMUD and haploidentical donors) that was higher in the PTCY-group than in the other (30.5% vs. 3.7% P<0.001).

A total of 421 patient's primary engrafted. The median of days to neutrophil and platelet engraftment was higher in the PTCY-group (17 vs. 14 days, P<0.001 and 18 vs. 11, P<0.001). Patients receiving PTCY had less grade II-IV (Day +100 CIF: 23.8% vs 39.8%, P<0.001) and III-IV acute GVHD (Day +100 CIF: 5.7% vs. 13.8%, P=0.002), and moderate/severe chronic GVHD (6.4% vs. 31.6%, P<0.001) than patients receiving other prophylaxis. The estimated 1-year OS, RFS, NRM and CIR was 73.6%, 63.4%, 17.1% and 19.5% for patients receiving PTCY and 64.6% (P=0.048), 55.2% (P=0.090), 15.5% (P=0.473) and 29.3% (P=0.017) for those who did not.

As reported in Figure 1, the proportions of bloodstream infections (BSI) were higher in patients receiving PTCY (Day +30 CIF: 39.3% vs. 14.9%, P<0.001). Rates of CMV reactivation (Day +180 CIF: 52.1% vs. 51.9%, P=0.358) and disease (Day +180 CIF: 9.1% vs. 10.5%, P=0.643) were comparable between the two groups. The proportions of VHH6 reactivation or infection (Day +180 CIF 10.7% vs.1.1%. P<0.001), and of grade 2-4 BK hemorrhagic cystitis (HC) (Day +180 CIF: 25.4% VS. 9.4%, P<0.001) were higher in the PTCY group. The median of days to peri-engraftment BSI, CMV reactivation, CMV disease and BK hemorrhagic cystitis diagnosis was shorter in the PTCY-group.

As reported in Table 1, a relatively low day 30 infection-related mortality rate was associated with peri-engraftment BSI and viral complications, except for the CMV disease. Moreover, the diagnosis of CMV reactivation and disease and BK HC were found to be predictors for higher NRM and lower OS.

CONCLUSIONS PTCY-based prophylaxis provides an effective GVHD prevention. However, its use increases the probability for BSI, diagnosed during the peri-engraftment phase, and BK HC and VHH6 infection during the early post-transplant period. Moreover, viral complications were diagnosed earlier in patients receiving PTCY.

Rates of CMV reactivation and disease were high in the two groups, and importantly, the diagnosis of these complications had a negative impact on post-transplant outcomes. Prophylaxis with letermovir has been implemented at our program, and future analysis will explore the results derived from its implementation.

Lastly, despite the low mortality rate directly attributed to BK HC, the presence of this complication increased the probability of mortality at 1 year. Based on these results, further refinements will be done focussed on preventing HC after PTCY administration.

Cid:Pharm-Olam: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; MacoPharma: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Grifols: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Fresenius Kabi: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Sanofi: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Kawasumi Laboratories: Research Funding; Cerus: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; TerumoBCT: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Rosinol Dachs:GlaxoSmithKline: Honoraria; Sanofi: Honoraria; Takeda: Honoraria; Amgen: Honoraria; BMS-Celgene: Honoraria; Janssen: Honoraria.