The incidence, mortality and timing of Pneumocystis jiroveci pneumonia after hematopoietic cell transplantation: a CIBMTR analysis

Abstract

Pneumocystis jiroveci pneumonia (PJP) is associated with high morbidity and mortality after hematopoietic stem cell transplantation (HSCT). Little is known about PJP infections after HSCT because of the rarity of disease given routine prophylaxis. We report the results of a Center for International Blood and Marrow Transplant Research study evaluating the incidence, timing, prophylaxis agents, risk factors and mortality of PJP after autologous (auto) and allogeneic (allo) HSCT. Between 1995 and 2005, 0.63% allo recipients and 0.28% auto recipients of first HSCT developed PJP. Cases occurred as early as 30 days to beyond a year after allo HSCT. A nested case cohort analysis with supplemental data (n=68 allo cases, n=111 allo controls) revealed that risk factors for PJP infection included lymphopenia and mismatch after HSCT. After allo or auto HSCT, overall survival was significantly poorer among cases vs controls (P=0.0004). After controlling for significant variables, the proportional hazards model revealed that PJP cases were 6.87 times more likely to die vs matched controls (P<0.0001). We conclude PJP infection is rare after HSCT but is associated with high mortality. Factors associated with GVHD and with poor immune reconstitution are among the risk factors for PJP and suggest that protracted prophylaxis for PJP in high-risk HSCT recipients may improve outcomes.

Figure 1

This chart summarizes the cases included in the supplemental data collection for allogeneic and autologous HSCT recipients.

Figure 2. Timing of PJP after allogeneic HSCT

This chart shows the relationship between time after allogeneic HSCT and development of PJP disease.

Figure 3. Relative Risk (RR) of PJP control/case after allogeneic (allo) HSCT

The relative risk of controls to PJP cases for risk factors after allo HSCT shows that non-Caucasian ethnicity, peripheral blood stem cell source, T cell depletion (TCD) in vivo and donor mismatch were high in PJP cases vs. controls were significantly associated with PJP infection compared to controls after allo HSCT.

Figure 4. Acute and Chronic Graft vs. Host Disease (GVHD) in PJP Cases versus Controls

Prevalence of acute and chronic GVHD after allo HSCT in PJP cases was higher than in controls.

Figure 5. PJP Prophylaxis agent association with breakthrough risk after allo-HSCT (a) and auto- HSCT (b)

Using secondary forms, the use of PJP prophylaxis agents was interrogated in PJP cases and controls after allo HSCT (a) and auto HSCT (b). Notably, missing data was included as a variable (TMP/SMX of time? = trimethoprim/sulfamethoxazole of uncertain timing in relation to PJP disease or control time point, IV PENT= intravenous pentamidine, INH = inhaled), none= the center confirmed the absence of PJP prophylaxis).

Figure 5. PJP Prophylaxis agent association with breakthrough risk after allo-HSCT (a) and auto- HSCT (b)

Using secondary forms, the use of PJP prophylaxis agents was interrogated in PJP cases and controls after allo HSCT (a) and auto HSCT (b). Notably, missing data was included as a variable (TMP/SMX of time? = trimethoprim/sulfamethoxazole of uncertain timing in relation to PJP disease or control time point, IV PENT= intravenous pentamidine, INH = inhaled), none= the center confirmed the absence of PJP prophylaxis).

Figure 6

Kaplan Meier survival for PJP cases and controls after allo (a) and auto (b) HSCT

Figure 6

Kaplan Meier survival for PJP cases and controls after allo (a) and auto (b) HSCT