Pneumocystis Pneumonia in Patients Treated With Rituximab

doi:10.1378/chest.12-0477

Chest

Volume 144, Issue 1, July 2013, Pages 258-265

https://doi.org/10.1378/chest.12-0477 Get rights and content

Background

Pneumocystis pneumonia (PcP) is an opportunistic fungal infection. Although T-cell immunity is classically related to Pneumocystis defense, recent data support roles for B lymphocytes in the development of PcP in animals, and we have observed several cases of PcP in patients receiving rituximab. These observations prompted a systematic review of our experience to define the spectrum of clinical presentations in which PcP has occurred in the setting of rituximab therapy.

Methods

Using a computer-based search, we reviewed the records of patients who received rituximab and developed PcP at Mayo Clinic Rochester over the years 1998 to 2011 to establish the underlying conditions, clinical course, possible risk factors, and potential association between this drug and the development of PcP.

Results

Over this period, 30 patients developed PcP during treatment with rituximab. The underlying diseases included hematologic malignancies in 90% of cases. Glucocorticoids were used in 73% of these patients, under different chemotherapeutic regimens. Three patients (10%) developed PcP in the setting of rituximab without concomitant chemotherapy or significant glucocorticoid exposure. Of these 30 patients, 88% developed acute hypoxemic respiratory failure and 53% required ICU admission. The clinical course was fatal in 30%.

Conclusion

PcP can occur in association with rituximab, with the majority of cases having also received cytotoxic chemotherapy or significant doses of glucocorticoids. The clinical course of cases of PcP in patients treated with rituximab can be quite fulminant, with significant mortality. Primary prophylaxis should be considered in patients at risk, and secondary prophylaxis provided unless immune reconstitution is well assured.

Section snippets

Patient Population

Patients were identified by a computerized search of the epidemiologic database at Mayo Clinic, using the diagnosis “Pneumocystis pneumonia.” A subgroup of adult patients who developed PcP was further identified as also being treated with rituximab over the period of January 1998 through August 2011. This was accomplished by manual review of the medications of all patients with PcP, including rituximab administered at Mayo Clinic. These years were selected because they coincided with the period

Patient Demographic Information

Between January 1998 and August 2011, a total of 30 patients treated with rituximab alone or in combination with another drug developed PcP. In our practice, which has large referral oncology and rheumatology patient bases, HIV-associated PcP represents about 10% of the total PcP cases. Rituximab administration was documented in 14.5% of our total non-HIV cases of PcP during this period. Twenty-two patients (73%) with PcP after receiving rituximab were men. The median age was 70 years (range,

Discussion

Pneumocystis species comprise a genus of fungal pathogens. Pneumocystis jirovecii is the species responsible for infection in humans.¹ Most of our understanding of host defense against Pneumocystis has focused on T lymphocytes. Most notably, during the HIV/AIDS epidemic, PcP became a devastating opportunistic pneumonia in these patients, whose immunologic hallmark was severe suppression of CD4⁺ lymphocytes. The widespread use of antimicrobial prophylaxis and the introduction of highly active

Conclusions

In conclusion, PcP can occur in association with rituximab alone, but most cases have also received either chemotherapy or significant doses of glucocorticoids. The clinical course and mortality of PcP in patients who have received rituximab can be quite fulminant. Primary prophylaxis should be considered in rituximab-treated patients. Importantly, secondary prophylaxis against recurrent PcP should be provided unless immune reconstitution is assured.

Acknowledgments

Author contributions: Dr Limper serves as the guarantor of the manuscript and takes responsibility for the integrity of the work as a whole, from inception to publication.

Dr Martin-Garrido: contributed to the abstraction of the case materials, data analysis, and initial drafts of the manuscript.

Dr Carmona: contributed to the assembly of the initial PcP database, revision of the manuscript, and provision of additional data input.

Dr Specks: contributed to the initial study concept, provision of

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More specifically, in our study, PJ infections were proportionally more frequently reported in older patients than other RTX ADRs. PJ infection is a well-known AE of RTX used in case of malignant pathology [26], but is also described in the treatment of autoimmune disease [27,28]. However, to our knowledge a higher rate of PJ infection in older patients treated for autoimmune disease has not been previously reported.
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Funding/Support: These studies were funded in part by the National Institutes of Health [R01 HL62150] to Dr Limper.

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details.

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Chest

Original ResearchChest InfectionsPneumocystis Pneumonia in Patients Treated With Rituximab

Background

Methods

Results

Conclusion

Section snippets

Patient Population

Patient Demographic Information

Discussion

Conclusions

Acknowledgments

Ann Oncol

Am J Transplant

Diagn Microbiol Infect Dis

Mayo Clin Proc

Mayo Clin Proc

Current insights into the biology and pathogenesis of Pneumocystis pneumonia

Nat Rev Microbiol

B cells are required for generation of protective effector and memory CD4 cells in response to Pneumocystis lung infection

J Immunol

Two cases of Pneumocystis jiroveci pneumonia with non-Hodgkin's lymphoma after CHOP-based chemotherapy containing rituximab

J Clin Exp Hematop

Pneumocystis jiroveci pneumonia in relation to CD4+ lymphocyte count in patients with B-cell non-Hodgkin lymphoma treated with chemotherapy

Leuk Lymphoma

Pneumocystis jiroveci pneumonia following rituximab treatment in Wegener's granulomatosis

Arthritis Care Res (Hoboken)

High incidence of Pneumocystis jirovecii pneumonia in patients receiving biweekly rituximab and cyclophosphamide, adriamycin, vincristine, and prednisone

Leuk Lymphoma

Addition of rituximab to cyclophosphamide, doxorubicin, vincristine, and prednisolone therapy has a high risk of developing interstitial pneumonia in patients with non-Hodgkin lymphoma

Leuk Lymphoma

Late onset Pneumocystis pneumonia in patients receiving rituximab for humoral renal transplant rejection

Nephrology (Carlton)

Three cases of Pneumocystis jirovecii pneumonia (PCP) during first-line treatment with rituximab in combination with CHOP-14 for aggressive B-cell non-Hodgkin's lymphoma

Eur J Haematol

Original Research
Chest Infections
Pneumocystis Pneumonia in Patients Treated With Rituximab