Abstract
Background
Infections remain a common cause of morbidity and mortality following hematopoietic stem cell transplant (HSCT). Pneumocystis jiroveci pneumonia (PJP) is an opportunistic infection that can occur in HSCT patients, although the association is best demonstrated in allogeneic HSCT, occurring less commonly in autologous HSCT. However, reports on PJP incidence, timing of infection, and outcomes among autologous HSCT cohorts are limited. Furthermore, while current guidelines recommend 3-6 months of prophylaxis against PJP following autologous HSCT, the optimal duration and even necessity of prophylaxis is not well established.
Patients and Methods
We performed a retrospective analysis of all consecutive patients who had autologous HSCT at the University of Michigan Blood and Marrow Transplantation program over a 20-year period from 1/1/2000 through 12/31/2019. The cohort consisted of a total of 2082 patients, 1221 male (58.6%), with median age 56 (range 10 months - 77 years, 91.2% ≥ 18 years). Records were searched for use of PJP prophylaxis over 6-month and 2-year follow-up periods post-HCT to determine rates of prophylaxis and choice of agent. Cases of polymerase-chain reaction (PCR)-confirmed PJP occurring within two years of HSCT were identified. The timing, clinical and laboratory features at diagnosis, use of concurrent immunosuppression, treatment, and outcomes were determined.
Results
Of the 2082 patients undergoing autologous HCT, 704 patients (33.8%) received PJP prophylaxis in the first 6 months following transplant. Prophylaxis rates varied over time, ranging from 14.6% to 80.0% when calculated by year of transplant (Figure 1). Trimethoprim-sulfamethoxazole (TMP-SMX) was the most used prophylaxis agent (70.3%), followed by inhaled pentamidine (31.8%), with intravenous pentamidine (8.1%), dapsone (7.1%), and atovaquone (2.6%) being used less frequently.
There were 9 cases of PJP identified in our cohort, with an incidence of 0.43%. There were 6 males, with median age of 50 (range 34 - 69). Cases occurred a median of 126 days following HSCT (range 65 - 496), with 4 cases occurring after 6 months. None of the patients were on PJP prophylaxis at the time of diagnosis, and only 2 patients had received prophylaxis at any point after transplant. In 8 of 9 cases, patients were receiving concurrent pharmacologic immunosuppression in the form of steroids or maintenance brentuximab (Table 1).
All patients presented with symptoms compatible with PJP, most often with fevers, dyspnea, and cough. Diagnosis was made by PCR from bronchoalveolar lavage specimen in 8 cases, and from sputum sample in 1 case. All patients were lymphopenic at the time of diagnosis, with median absolute lymphocyte count of 400 cells/µL (range 200 - 1100). Patients were most often treated with TMP-SMX. Three patients required transfer to the intensive care unit and 2 were intubated. Ultimately, 2 patients died from PJP infection; the remaining 7 recovered (Table 2).
Conclusion
Our analysis reveals that among a large cohort, incidence of PJP following autologous HSCT is low. This was the case even with relatively modest rates of PJP prophylaxis in the first 6 months following transplant. Most cases of PJP occurred in patients receiving additional immunosuppression and often occurred late following transplant.
Pianko: Karyopharm: Honoraria.
