Cibmtr Retrospective Analysis Reveals Incidence, Mortality, and Timing of Pneumocystis Jiroveci Pneumonia (PCP) after Hematopoietic Stem Cell Transplantation (HSCT)

Pneumocystis jiroveci pneumonia (formerly PCP) is associated with high morbidity and mortality after HSCT.  Little is known about PCP infections after HSCT due to presumed rarity of disease after the advent of prophylaxis. We report results of a CIBMTR study evaluating the incidence, timing, prophylaxis agents, risk factors, and mortality of PCP in autologous (auto) and allogeneic (allo) HSCT recipients.  For recipients of first HSCT captured between 1995 and 2005, PCP infection was documented in 0.63% (n=177) of allo (n=27,934) and 0.28% (n=52) of auto (n=18525) HSCT.  After allo-HSCT, cases were distributed early and late after HSCT (Table 1).  A nested case control study was performed controlling for auto vs. allo, primary disease, and alive at PCP diagnosis, to evaluate risk factors for PCP, the influence of PCP prophylaxis agents on the risk of PCP, and the effect of PCP on overall survival using supplemental data (n=68 allo cases, n=111 allo controls).  In univariate analysis, PCP infection was higher among recipients who were not Caucasian (p=0.001), received PB (vs. BM) (p=0.027), campath/ATG (p = 0.02), less well-matched grafts (p = <0.001), and had lymphopenia (p<0.001) or steroids (p <0.001) in the 30 days prior to PCP. Other risk factors are described by onset time of PCP after HSCT (Table 1).  Prophylaxis agents varied but the use of Bactrim was lower in cases occurring late.   There were more cases with grade 3-4 acute GVHD and chronic GVHD vs. controls. After allo HSCT, overall survival (OS) was significantly poorer among cases vs. controls [1 year: 41% vs. 73% (p<0.0001); 5 year: 25% vs. 56% (p<0.0001)].  Similarly, following auto HSCT, OS was lower in cases vs. controls (1year: 42% vs. 86% (p=0.0004); 5 year: 13% vs. 52% (p=0.0003)).  After controlling for significant variables (age, disease status, GVHD prophylaxis, year of HSCT, aGVHD), proportional hazards model revealed that PCP cases were 6.87x more likely to die vs. matched controls (p<0.0001, CI 4.84-9.75).  Thus, these data reveal that: PCP infection is rare after HSCT; PCP occurs both early and late after HSCT; mismatch, GVHD prophylaxis, and GVHD and steroids are risk factors for PCP; and PCP infection is associated with higher mortality rate after allo and auto HSCT.  Furthermore, our data suggest opportunities to improve supportive care, starting PCP prophylaxis early post-HSCT and continuing for those with these newly identified risk factors: GVHD, steroid exposure, or poor immune reconstitution.

Table 1: Timing of PCP infection after HSCT and differences among cases vs. controls

Factor	<60 days	60-270 days	>270 days
Proportion of PCP cases	26%	51%	24%
Bactrim prophylaxis*	36% vs. 35%	14% vs. 43%	11% vs. 21%
Grade 3-4 aGVHD*	29% vs. 17%	31% vs. 24%	42% vs. 21%
cGVHD*			79% vs. 44%

*Cases vs. controls; performed on nested case control analysis from data collected on secondary forms of allo HSCT (n= 117).