title: Aerosolized pentamidine as pneumocystis prophylaxis after bone marrow transplantation is inferior to other regimens and is associated with decreased survival and an increased risk of other infections.
abstract: Pneumocystis carinii pneumonia (PCP) is a life-threatening but preventable infection that may occur after bone marrow transplantation (BMT). Although various prophylactic regimens have been used in this setting to prevent active infection, their efficacy, toxicity profile, and impact on outcomes are poorly described in this patient group. We undertook a retrospective cohort study in which we reviewed the records of 451 adult patients who underwent BMT for hematologic malignancies, aplastic anemia, or myelodysplasia over a 7-year period at the Brigham and Women's Hospital. Post-BMT PCP prophylaxis consisted of aerosolized pentamidine (AP) 150 mg every 2 weeks or 300 mg per month, trimethoprim/sulfamethoxazole (TMP/SMX) 160/800 mg orally b.i.d. 3 times per week, or dapsone 100 mg orally each day. Prophylaxis was continued for 1 year post-BMT in all patients when clinically feasible. One hundred twenty-one patients were unevaluable because of death or relapse <60 days after BMT (n = 89), loss to follow-up upon hospital discharge (n = 20), or other reasons (n = 12). Three eligible patients did not receive any prophylaxis and were not further evaluated. Of the 327 patients analyzed, 133 underwent autologous BMT, 4 syngeneic BMT, 159 related allogeneic BMT, and 31 unrelated allogeneic BMT. Graft-versus-host disease prophylaxis in the 190 patients receiving allogeneic BMT consisted of T-cell depletion with anti-CD5 and complement in 58 patients and cyclosporine/methotrexate or FK506 with or without steroids in 132 patients. Eight of 327 (2.4%) documented PCP cases were identified, 0 of 105 in patients receiving only TMP/SMX. Four cases occurred in patients receiving only AP (4/44, 9.1%; odds ratio [OR] relative to TMP/SMX 23.4, 95% confidence interval [CI] 1.2, 445.2); 1 in patients receiving only dapsone (1/31, 3.2%; OR not significant); 2 in patients receiving more than 1 prophylactic regimen (2/147 1.4%; OR not significant); and 1 >1 year post-BMT in a patient who was off PCP prophylaxis. Although the patients receiving only AP had a significantly lower probability of treatment-related toxicity than those receiving TMP/SMX (OR 0.19 [95% CI 0.04, 0.851), the probability of their acquiring other serious non-PCP infections was increased (OR 2.2 [95% CI 1.0, 4.6]), and the probability of their dying by 1 year post-BMT was significantly higher (OR 5.2 [95% CI 2.4, 26.6]), even when adjusted for variables such as type of BMT (autologous versus allogeneic; high versus low risk) and sex. Although AP is associated with fewer toxicities, the data show that it is inferior to TMP/SMX in preventing PCP in the post-BMT setting and is associated with an increased risk of other infections and a higher mortality at 1 year after BMT.
authors.affiliation: Department of Adult Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA. michael_vasconcelles@dfci.harvard.edu
authors.forename: M J
authors.initials: MJ
authors.lastname: Vasconcelles
authors.forename: M V
authors.initials: MV
authors.lastname: Bernardo
authors.forename: C
authors.initials: C
authors.lastname: King
authors.forename: E A
authors.initials: EA
authors.lastname: Weller
authors.forename: J H
authors.initials: JH
authors.lastname: Antin
mesh_terms: D000280:Administration, Inhalation; D000293:Adolescent; D000328:Adult; D000335:Aerosol Propellants; D000368:Aged; D000935:Antifungal Agents / Q000627:therapeutic use* / Q000633:toxicity; D016026:Bone Marrow Transplantation / Q000009:adverse effects* / Q000379:methods; D015331:Cohort Studies; D003131:Combined Modality Therapy; D003622:Dapsone / Q000008:administration & dosage / Q000633:toxicity; D004341:Drug Evaluation; D005260:Female; D006086:Graft vs Host Disease / Q000188:drug therapy / Q000209:etiology; D019337:Hematologic Neoplasms / Q000150:complications / Q000188:drug therapy; D006801:Humans; D007239:Infections / Q000188:drug therapy / Q000209:etiology; D008297:Male; D008875:Middle Aged; D010419:Pentamidine / Q000008:administration & dosage* / Q000627:therapeutic use*; D016720:Pneumocystis Infections / Q000188:drug therapy / Q000209:etiology / Q000517:prevention & control*; D012189:Retrospective Studies; D013420:Sulfamethoxazole / Q000008:administration & dosage / Q000633:toxicity; D015996:Survival Rate; D014295:Trimethoprim / Q000008:administration & dosage / Q000633:toxicity
chemical_list: D000335:Aerosol Propellants; D000935:Antifungal Agents; D010419:Pentamidine; D003622:Dapsone; D014295:Trimethoprim; D013420:Sulfamethoxazole