High incidence of Pneumocystis jirovecii pneumonia in allogeneic hematopoietic cell transplant recipients in the modern era.

BACKGROUND: International guidelines for Pneumocystis jirovecii pneumonia (PJP) prevention recommend prophylaxis for ≥6 months following allogeneic hematopoietic cell transplantation, and longer in patients with graft-versus-host disease (GVHD) or on immunosuppressive therapy (IST). These recommendations are based on cohorts of patients who did not routinely receive anti-thymocyte globulin (ATG) for GVHD prophylaxis. METHODS: We performed a retrospective chart review of 649 patients, all of whom received ATG as part of GVHD prophylaxis. RESULTS: The cumulative incidence of definite PJP was 3.52% at both 3 and 5 years (median follow up, 1648 days for survivors). PJP occurred in 13 non-GVHD patients between days 207 and 508, due in part to low CD4 T-cell counts (<200 CD4 T cells/µL). PJP occurred in eight GVHD patients between days 389 and 792, due in part to non-adherence to PJP prophylaxis guidelines (discontinuation of PJP prophylaxis at <3 months after discontinuation of IST). Breakthrough PJP infection was not observed in patients receiving prophylaxis with cotrimoxazole, dapsone or atovaquone, whereas three cases were observed with inhaled pentamidine. DISCUSSION: In conclusion, for non-GVHD patients receiving ATG-containing GVHD prophylaxis, 6 months of PJP prophylaxis is inadequate, particularly if the CD4 T-cell count is <200 cells/µL or if there is a high incidence of PJP in the community. For patients with GVHD receiving ATG-containing GVHD prophylaxis, continuing PJP prophylaxis until ≥3 months post-discontinuation of IST is important. Cotrimoxazole, dapsone and atovaquone are preferred over inhaled pentamidine.

Risk Factors for the Incidence of and the Mortality due to Post-Transplant Lymphoproliferative Disorder after Hematopoietic Cell Transplantation.

Post-transplant lymphoproliferative disorder (PTLD) is a potentially serious complication that occurs following hematopoietic cell transplantation (HCT), in which B cells transformed by Epstein-Barr virus (EBV) proliferate uncontrollably. It is unknown whether risk factors for the incidence of PTLD are identical to those for mortality due to PTLD, a clinically more important outcome. We sought to determine the risk factors influencing the incidence of PTLD and those influencing mortality due to PTLD in a cohort of 1184 allogenic HCT recipients. All patients were predisposed to PTLD, because their graft-versus-host disease (GVHD) prophylaxis included antithymocyte globulin. The overall PTLD incidence was 9.0%, and mortality due to PTLD was 1.1%. In multivariate analysis, risk factors for PTLD incidence include donor+/recipient- (D+/R-) EBV serostatus (subhazard ratio [SHR], 3.3; P = .002), use of a donor other than an HLA-matched sibling donor (non-MSD) (SHR, 1.7; P = .029), receipt of total body irradiation (TBI; SHR, 3.3; P = .008), and the absence of GVHD (SHR, 3.3; P < .001). The sole risk factor for mortality due to PTLD among all patients was D+/R- serostatus (SHR, 5.8; P = .022). Risk factors for mortality due to PTLD among patients who developed PTLD were use of a bone marrow (BM) graft (compared with peripheral blood stem cells [PBSCs]; SHR, 22.8; P < .001) and extralymphatic involvement (SHR, 14.6; P < .001). Interestingly, whereas the absence of GVHD was a risk factor for PTLD incidence, there was a trend toward the presence of GVHD as a risk factor for PTLD mortality (SHR, 4.2; P = .093). Likewise, whereas use of a BM graft was a risk factor for PTLD mortality, there was a trend toward use of a PBSC graft as a risk factor for PTLD incidence (SHR, 0.44; P = .179). Some risk factors for the incidence of PTLD are identical to the risk factors for mortality due to PTLD (ie, D+/R- serostatus), whereas other risk factors are disparate. Specifically, TBI was identified as a risk factor for PTLD incidence but not for PTLD mortality; the absence of GVHD was a risk factor for PTLD incidence, whereas the presence of GVHD was possibly a risk factor for PTLD mortality; and receipt of a PBSC graft was possibly a risk factor for PTLD incidence, whereas receipt of a BM graft was a risk factor for PTLD mortality.