Vasconcelles M J, Bernardo M V, King C, Weller E A, Antin J H
Department of Adult Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA.
Biol Blood Marrow Transplant. 2000;6(1):35-43. doi: 10.1016/s1083-8791(00)70050-4.
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.
卡氏肺孢子虫肺炎（PCP）是一种可危及生命但可预防的感染，可能发生在骨髓移植（BMT）后。尽管在此情况下已采用各种预防方案来预防活动性感染，但在该患者群体中，它们的疗效、毒性特征及对预后的影响鲜有描述。我们进行了一项回顾性队列研究，回顾了在7年期间于布莱根妇女医院接受BMT治疗血液系统恶性肿瘤、再生障碍性贫血或骨髓增生异常综合征的451例成年患者的记录。BMT后的PCP预防措施包括每2周雾化吸入喷他脒（AP）150mg或每月300mg、口服甲氧苄啶/磺胺甲噁唑（TMP/SMX）160/800mg，每日2次，每周3次，或每日口服氨苯砜100mg。在临床可行的情况下，所有患者在BMT后均持续预防1年。121例患者因BMT后<60天死亡或复发（n = 89）、出院后失访（n = 20）或其他原因（n = 12）而无法评估。3例符合条件的患者未接受任何预防措施，未作进一步评估。在分析的327例患者中，133例接受了自体BMT，4例接受了同基因BMT，159例接受了亲缘异体BMT，31例接受了非亲缘异体BMT。190例接受异体BMT的患者中，移植物抗宿主病预防措施包括58例患者采用抗CD5和补体进行T细胞清除，132例患者采用环孢素/甲氨蝶呤或FK506加或不加类固醇。在327例记录的PCP病例中，有8例（2.4%）被确诊，接受单纯TMP/SMX治疗的105例患者中无病例发生。4例发生在仅接受AP治疗的患者中（4/44，9.1%；相对于TMP/SMX的优势比[OR]为23.4，95%置信区间[CI]为1.2，445.2）；1例发生在仅接受氨苯砜治疗的患者中（1/31，3.2%；OR无统计学意义）；2例发生在接受不止一种预防方案的患者中（2/147，1.4%；OR无统计学意义）；1例发生在停止PCP预防治疗超过1年的BMT后患者中。尽管仅接受AP治疗的患者与治疗相关毒性的发生率显著低于接受TMP/SMX治疗的患者（OR 0.19[95%CI 0.04，0.85]），但其发生其他严重非PCP感染的可能性增加（OR 2.2[95%CI 1.0，4.6]），且BMT后1年死亡的可能性显著更高（OR 5.2[95%CI 2.4，26.6]），即使对BMT类型（自体与异体；高风险与低风险）和性别等变量进行校正后也是如此。尽管AP的毒性较小，但数据表明，在BMT后预防PCP方面，它不如TMP/SMX，且与其他感染风险增加及BMT后1年死亡率较高相关。
