PF750 SEVERE INFECTIONS IN ALLOGENEIC STEM CELL TRANSPLANT RECIPIENTS RECEIVING POST‐TRANSPLANT CYCLOPHOSPHAMIDE AS GVHD PROPHYLAXIS: HAPLOIDENTICAL VS MATCHED RELATED OR UNRELATED DONOR TRANSPLANTATION
Authors: Bosch‐Vilaseca A. , García‐Cadenas I. , Esquirol A. , Awol R. , Saavedra S. , Briones J. , Brunet S. , Sierra J. , Martino R. 
Published: June 2019

Background:

Post‐transplantation cyclophosphamide (PTCy) is an effective graft vs host disease (GvHD) prophylaxis strategy in haploidentical stem cell transplant (HaploSCT), with comparable survival outcomes to HLA‐matched SCT. Due to its promising results, some centers are including this strategy in 9/10 or 10/10 HLA‐matched related or unrelated donor SCT (MatchSCT) settings.

Aims:

PTCy has shown to reduce NRM by decreasing GvHD compared to classical immunosuppressive agents, although there are a few studies focusing on the etiology and outcomes of infections after PTCy‐based HaploSCT and MatchSCT.

Methods:

We selected 75 consecutive alloSCT adult patients who received PTCy‐based GvHD prophylaxis in our center from December 2013 to August 2018. Patients were divided in 2 groups: (1)HaploSCT, n = 32; (2)MatchSCT, n = 43. Baseline characteristics are shown in Table1. For each patient, we reported every episode of severe infection, including gram‐positive and gram‐negative bacteremias, pneumonia, viral hemorrhagic cystitis, viral LRTI, CMV and VEB reactivations and/or disease and proven/probable invasive fungal infections (IFI) at different time points after SCT: early (≤30 days post‐SCT) and intermediate/late infections (≥31 days post‐SCT).

Results:

Patients developed a total of 127 severe infectious episodes; 57 of them (45%) were early infections and 70 (55%) were intermediate/late cases, which distributed evenly between the 2 groups. All these infections are shown in Table 2. Bacteremia episodes were the most common cause of severe infection, accounting for 35% of documented infections (51% in group 1 and 49% in group 2). Gram‐positive bacteria CVC infections were the most frequent cause of bacteremia (56%). 72% of all bacterial infections were diagnosed ≤30d post‐SCT. Four episodes of proven/probable IFI were diagnosed ≤100 days after SCT, 3 of them during the early phase post‐SCT. Unsurprisingly, 79% of all viral infections were diagnosed after day +30 (49% HaploSCT and 51% MatchSCT). Most of them were CMV reactivations, with only one case of CMV disease. Among the 50 patients sequentially monitored for EBV viral load (32 in group 1 and 18 in group 2), 3 cases of EBV reactivation were diagnosed in group 1 and received rituximab as preemptive treatment. A total of 16 viral hemorrhagic cystitis episodes were identified (12 in group 1 and 4 in group 2): BK virus‐related (n = 13) and adenovirus (n = 3). Infection‐related mortality (IRM) was the cause of death in 9% of the patients in both groups, with a median follow‐up for survivors of 821 days for group 1 (range 278–1940) and 339 days for the group 2 (range, 64–959). The 1‐year cumulative incidence of IRM was 8.9% (95% CI, 2.7–15) vs 9% (95% CI, 3–14.8) in group 1 and 2, respectively. NRM occurred in 4 (12.5%) and 6 (14%) patients in each group, with a 1‐year cumulative incidence of 12.5% (95% CI, 7–18%) vs 17% (95% CI, 7–27), in group 1 and 2, respectively (p = 0.68). Fifty‐five patients (73.3%) were alive at last follow‐up, with a 1‐year overall survival of 72% (95% CI, 64–80) in group 1 and 80% (95% CI, 72–87) in group 2 (p = 0.5).

Summary/Conclusion:

In our study, IRM was the main cause of 1‐year NRM, although their incidence was low in both groups. With PTCy the 1‐year IRM seems much inferior than with other approaches. In a real life setting this strategy reduces IRM and NRM not only by reducing GvHD, but also by allowing early protective immune reconstitution. The small sample sizes did not allow to reliably compare the types of infections in different engraftment time periods, which will be the objective of future studies.

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