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      Pneumocystis jiroveci prophylaxis in patients undergoing Bendamustine treatment: the need for a standardized protocol

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          Key Clinical Message

          The decision for PJP prophylaxis depends on a physician's evaluation of multiple variables. The high rate of PJP infection described in this article combined with the known impaired T-cell function post Bendamustine treatment justifies considering all patients for PJP prophylaxis when they receive Bendamustine treatment.

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          Bendamustine in combination with rituximab for previously untreated patients with chronic lymphocytic leukemia: a multicenter phase II trial of the German Chronic Lymphocytic Leukemia Study Group.

          Karl-Anton Kreuzer, Clemens Wendtner, Michael Kneba … (2012)
          We investigated the safety and efficacy of bendamustine and rituximab (BR) in previously untreated patients with chronic lymphocytic leukemia (CLL). In all, 117 patients, age 34 to 78 years, 46.2% of patients at Binet stage C, and 25.6% of patients age 70 years or older received BR chemoimmunotherapy for first-line treatment of CLL. Bendamustine was administered at a dose of 90 mg/m(2) on days 1 and 2 combined with 375 mg/m(2) rituximab on day 0 of the first course and 500 mg/m(2) on day 1 during subsequent courses for up to six courses. Overall response rate was 88.0% (95% CI, 80.7% to 100.0%) with a complete response rate of 23.1% and a partial response rate of 64.9%. Ninety percent of patients with del(11q), 94.7% with trisomy 12, 37.5% with del(17p), and 89.4% with unmutated IGHV status responded to treatment. After a median observation time of 27.0 months, median event-free survival was 33.9 months, and 90.5% of patients were alive. Grade 3 or 4 severe infections occurred in 7.7% of patients. Grade 3 or 4 adverse events for neutropenia, thrombocytopenia, and anemia were documented in 19.7%, 22.2%, and 19.7% of patients, respectively. Chemoimmunotherapy with BR is effective and safe in patients with previously untreated CLL.
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            Prophylaxis of Pneumocystis pneumonia in immunocompromised non-HIV-infected patients: systematic review and meta-analysis of randomized controlled trials.

            Leonard Leibovici, Nicola H. Green, Liat Vidal … (2007)
            To assess the efficacy of prophylaxis for Pneumocystis pneumonia (PCP), caused by Pneumocystis jirovecii (formerly Pneumocystis carinii), for immunocompromised non-HIV-infected patients by conducting a systematic review and meta-analysis. We searched for randomized controlled trials that compared prophylaxis using antibiotics effective against P jirovecii, given orally or intravenously, vs placebo, no intervention, or antibiotics with no activity against P jirovecii. In addition, we included trials that compared different PCP prophylactic regimens or administration schedules. The search included the Cochrane Central Register of Controlled Trials, PubMed, Latin American and Caribbean Health Sciences Literature, and conference proceedings. No language, year, or publication restrictions were applied. Two reviewers (H.G. and M.P.) independently searched, selected trials, extracted data, and performed methodological quality assessment. Relative risks (RRs) with 95% confidence intervals (CIs) are reported. Meta-analysis was performed using the random-effects model. Twelve randomized trials were identified, including 1245 patients (50% children) who had undergone autologous bone marrow or solid organ transplant or who had hematologic cancer. When trimethoprim-sulfamethoxazole was administered, a 91% reduction was observed in the occurrence of PCP (RR, 0.09; 95% CI, 0.02-0.32); the number needed to treat was 15 (95% CI, 13-20) patients, with no heterogeneity. Pneumocystis pneumonia-related mortality was significantly reduced (RR, 0.17; 95% CI, 0.03-0.94), whereas all-cause mortality did not differ significantly (RR, 0.79; 95% CI, 0.18-3.46). Adverse events that required discontinuation occurred in 3.1% of adults and none of the children, and all were reversible. No differences between once-daily and thrice-weekly administration schedules were found. Balanced against severe adverse events, PCP prophylaxis is warranted when the risk for PCP is higher than 3.5% for adults. Adverse events are less frequent in children, for whom prophylaxis might be warranted at lower PCP incidence rates.
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              Clinical picture of Pneumocystis jiroveci pneumonia in cancer patients.

              Guillaume Bollée, Claudine Sarfati, Guillaume Thiery … (2007)
              Pneumocystis pneumonia (PCP) is common in patients with HIV infection but may also occur in patients with other causes of immunodeficiency, including hematologic and solid malignancies. To better describe the clinical picture of PCP as to maintain a high level of suspicion in adequate cases, we studied 56 cancer patients with PCP and compared them to 56 cancer patients with bacterial pneumonia. Among 56 PCP patients, 44 patients (78.6%) had hematologic malignancies (18 recipients of bone marrow transplantation) and 12 patients had solid tumors. The time since diagnosis was 24 months (range, 4 to 49 months). All patients with solid tumors and 20 patients (45.4%) with hematologic malignancies were receiving steroids. Only six patients were receiving PCP prophylaxis. The main symptoms were fever (85.7%), dyspnea (78.6%), and cough (57.1%). Time from symptom onset was 7 days (range, 3 to 14 days). PCP presented as severe pneumonia (Pao(2), 58 mm Hg [range, 50 to 70 mm Hg]) with bilateral interstitial infiltrates (80.4%) and bilateral ground-glass attenuation (89.3%) by CT. Of the 24 ICU patients (42.9%), 16 patients (19.6%) required mechanical ventilation. Eleven patients (19.6%) died. Compared to 56 patients with bacterial pneumonia, PCP patients were more likely to have non-Hodgkin lymphoma and be receiving long-term steroids; they had longer times since diagnosis, longer symptom duration, higher frequencies of fever and of diffuse lung disease (diffuse crackles, bilateral infiltrates, and hypoxemia), higher frequency of ground-glass opacities, and lower frequency of pleural involvement. PCP presents as subacute, febrile, hypoxemic, and diffuse pulmonary involvement in patients with solid tumors or hematologic malignancies receiving long-term steroids.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Clin Case Rep
                Journal ID (iso-abbrev): Clin Case Rep
                Journal ID (publisher-id): ccr3
                Title: Clinical Case Reports
                Publisher: BlackWell Publishing Ltd (Oxford, UK )
                ISSN (Print): 2050-0904
                ISSN (Electronic): 2050-0904
                Publication date (Print): April 2015
                Publication date (Electronic): 09 February 2015
                Volume: 3
                Issue: 4
                Pages: 255-259
                Affiliations
                [1 ]Department of Haematology, University Hospital Limerick Limerick, Ireland
                [2 ]Graduate Entry Medical School, University of Limerick Limerick, Ireland
                Author notes
                Correspondence Tarig Mohammed Abkur, Department of Haematology, University Hospital Limerick, St. Nessan road, Dooradoyle, CO. Limerick, Ireland. Tel: +353-61-301111; Fax: +353-61-425902; E-mail: tarig1982@ 123456hotmail.com

                Funding Information No sources of funding were declared for this study.

                Article
                DOI: 10.1002/ccr3.195
                PMC ID: 4405313
                SO-VID: feebf7d1-0357-400c-bd1d-10157978a05e
                Copyright © © 2015 The Authors. Clinical Case Reports published by John Wiley & Sons Ltd.
                License:

                This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

                History
                Date received : 18 August 2014
                Date revision received : 24 November 2014
                Date accepted : 04 December 2014
                Categories
                Subject: Case Reports

                Keywords: bendamustine,pneumocystis,trimethoprim/sulfamethoxazole
                Data availability:
                Keywords: bendamustine, pneumocystis, trimethoprim/sulfamethoxazole

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