The primary prophylaxis of pneumocystis pneumonia by low-dose trimethoprim-sulfamethoxazole during R-CHOP therapy

Background

Pneumocystis pneumonia (PCP) is frequently observed in immunocompromised patients. Currently, oral administration of trimethoprim-sulfamethoxazole (TMP-SMX) at a dose of 1 tablet daily (7 tablets/week) or 2 tablets twice a day, twice a week (8 tablets/week) is considered as standard for prophylaxis. However, they sometimes induce unpleasant toxicities such as rash, leukopenia and renal dysfunction. To avoid them, dose reduction of TMP-SMX could be considerable. Rituximab plus CHOP therapy (R-CHOP) is a standard treatment for B-cell lymphoma. Since rituximab is immunosuppressive, prophylaxis of PCP is widely introduced. In our institute, low-dose TMP-SMX has been employed in such situations. To assess the efficacy and tolerability of the regimen, retrospective analysis was performed.

Methods

We reviewed patients with newly diagnosed B-cell lymphoma who completed 6 to 8 cycles of R-CHOP in our institute. In all patients, low-dose TMP-SMX consisting of 1 tablet twice a day, twice a week (4 tablets/week) was started simultaneously with R-CHOP. To improve medication adherence, administration day was fixed on Tuesday and Friday.

Results

From January 2009 to September 2014, 292 patients with a median age of 67 (21-89) were treated. They included diffuse large B-cell lymphoma (n = 213), follicular lymphoma (n = 65), mantle cell lymphoma (n = 6) and others (n = 8). The median length of prophylaxis from the last day of R-CHOP was 5.7 (0.6-16.6) months. The median lymphocyte count decreased from 1.1 (0.07-19.2) to 0.4 (0.03-1.4) x 10⁹/L during treatment. Of 292 patients, 291 showed no evidence of PCP. Although 1 patient developed PCP, the diagnosis was given on day 12 of the first cycle indicating that the patient already had PCP before the initiation of prophylaxis. In the other 291 patients, TMP-SMX was well tolerated and no related adverse event was observed.

Conclusions

Four tablets of TMP-SMX a week may be sufficient to prevent PCP during R-CHOP. In addition, minimum toxicities are expected by this method. As demonstrated in our study, the elderly patients who need R-CHOP are increasing. In this context, our data provide a valuable insight into the total strategy of lymphoma treatment.

Clinical trial identification

Legal entity responsible for the study

Chiba Cancer Center

Funding

Chiba Cancer Center

Disclosure

All authors have declared no conflicts of interest.