Abstract
Background
International guidelines for Pneumocystis jirovecii pneumonia (PJP) prevention recommend prophylaxis for ≥6 months following allogeneic
hematopoietic cell transplantation, and longer in patients with graft-versus-host
disease (GVHD) or on immunosuppressive therapy (IST). These recommendations are based
on cohorts of patients who did not routinely receive anti-thymocyte globulin (ATG)
for GVHD prophylaxis.
Methods
We performed a retrospective chart review of 649 patients, all of whom received ATG
as part of GVHD prophylaxis.
Results
The cumulative incidence of definite PJP was 3.52% at both 3 and 5 years (median follow
up, 1648 days for survivors). PJP occurred in 13 non-GVHD patients between days 207
and 508, due in part to low CD4 T-cell counts (<200 CD4 T cells/µL). PJP occurred
in eight GVHD patients between days 389 and 792, due in part to non-adherence to PJP
prophylaxis guidelines (discontinuation of PJP prophylaxis at <3 months after discontinuation
of IST). Breakthrough PJP infection was not observed in patients receiving prophylaxis
with cotrimoxazole, dapsone or atovaquone, whereas three cases were observed with
inhaled pentamidine.
Discussion
In conclusion, for non-GVHD patients receiving ATG-containing GVHD prophylaxis, 6 months
of PJP prophylaxis is inadequate, particularly if the CD4 T-cell count is <200 cells/µL
or if there is a high incidence of PJP in the community. For patients with GVHD receiving
ATG-containing GVHD prophylaxis, continuing PJP prophylaxis until ≥3 months post-discontinuation
of IST is important. Cotrimoxazole, dapsone and atovaquone are preferred over inhaled
pentamidine.
Keywords
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References
- The incidence, mortality and timing of Pneumocystis jiroveci pneumonia after hematopoietic cell transplantation: a CIBMTR analysis.Bone Marrow Transplant. 2016; 51: 573-580
- Preventing opportunistic infections in bone marrow transplant recipients.Transpl Infect Dis. 1999; 1: 40-49
- Occurrence of Pneumocystis jiroveci pneumonia after allogeneic stem cell transplantation: a 6-year retrospective study.Bone Marrow Transplant. 2005; 36: 879-883
- Late onset Pneumocystis carinii pneumonia following allogeneic bone marrow transplantation.Bone Marrow Transplant. 1996; 17: 1057-1059
- The risk of Pneumocystis carinii pneumonia among men infected with human immunodeficiency virus type 1. Multicenter AIDS Cohort Study Group.N Engl J Med. 1990; 322: 161-165
- Panel on opportunistic infections in HIV-infected adults and adolescents. Guidelines for the prevention and treatment of opportunistic infections in HIV-infected adults and adolescents: Recommendations from the Centers for Disease Control and Prevention, the National Institutes of Health, and the HIV Medicine Association of the Infectious Disease Society of America.MMWR Recomm Rep. 2009; 58: 1-207
- The Impact of Absolute CD4 Count and Percentage Discordance on Pneumocystis Jirovecii Pneumonia Prophylaxis in HIV-Infected Patients.J Int Assoc Provid AIDS Care. 2018; 172325958218759199
- Risk factors for primary Pneumocystis carinii pneumonia in human immunodeficiency virus-infected adolescents and adults in the United States: reassessment of indications for chemoprophylaxis.J Infect Dis. 1998; 178: 1126-1132
- The role of CD4 cell count as discriminatory measure to guide chemoprophylaxis against Pneumocystis jirovecii pneumonia in human immunodeficiency virus-negative immunocompromised patients: A systematic review.Transpl Infect Dis. 2017; 19https://doi.org/10.1111/tid.12651
- Guidelines for preventing infectious complications among hematopoietic cell transplantation recipients: a global perspective.Biol Blood Marrow Transplant. 2009; 15: 1143-1238
- Consensus guidelines for diagnosis, prophylaxis and management of Pneumocystis jirovecii pneumonia in patients with haematological and solid malignancies, 2014.Intern Med J. 2014; 44: 1350-1363
- ECIL guidelines for preventing Pneumocystis jirovecii pneumonia in patients with haematological malignancies and stem cell transplant recipients.J Antimicrob Chemother. 2016; 71: 2397-2404
- Prevention of infection due to Pneumocystis spp. in human immunodeficiency virus-negative immunocompromised patients.Clin Microbiol Rev. 2004; 17: 770-782
- Pneumocystis carinii pneumonia without acquired immunodeficiency syndrome. More patients, same risk.Arch Intern Med. 1995; 155: 1125-1128
- The value of Pneumocystis carinii antibody and antigen detection for diagnosis of Pneumocystis carinii pneumonia after marrow transplantation.Am Rev Respir Dis. 1979; 120: 1283-1287
- Nonbacterial pneumonia after allogeneic marrow transplantation: a review of ten years' experience.Rev Infect Dis. 1982; 4: 1119-1132
- Pneumocystis carinii pneumonitis following bone marrow transplantation.Bone Marrow Transplant. 1992; 10: 267-272
- Infections in hematopoietic cell transplant recipients: Results from the organ transplant infection project, a multicenter, prospective, cohort study.Open Forum Infect Dis. 2017; 4 (ofx050)
- Incidence, risk factors, and mortality from pneumonia developing late after hematopoietic stem cell transplantation.Bone Marrow Transplant. 2003; 32: 515-522
- Thymoglobulin prevents chronic graft-versus-host disease, chronic lung dysfunction, and late transplant-related mortality: long-term follow-up of a randomized trial in patients undergoing unrelated donor transplantation.Biol Blood Marrow Transplant. 2006; 12: 560-565
- Optimal dose of rabbit thymoglobulin in conditioning regimens for unmanipulated, haploidentical, hematopoietic stem cell transplantation: Long-term outcomes of a prospective randomized trial.Cancer. 2017; 123: 2881-2892
- Pretreatment with anti-thymocyte globulin versus no anti-thymocyte globulin in patients with haematological malignancies undergoing haemopoietic cell transplantation from unrelated donors: a randomised, controlled, open-label, phase 3, multicentre trial.Lancet Oncol. 2016; 17: 164-173
- et al. Immune reconstitution after anti-thymocyte globulin-conditioned hematopoietic cell transplantation.Cytotherapy. 2012; 14: 1258-1275
- Influence of anti-thymocyte globulin as part of the conditioning regimen on immune reconstitution following matched related bone marrow transplantation.J Hematother Stem Cell Res. 2003; 12: 237-242
- Rabbit antithymocyte globulin (thymoglobulin) impairs the thymic output of both conventional and regulatory CD4+ T cells after allogeneic hematopoietic stem cell transplantation in adult patients.Haematologica. 2013; 98: 23-30
- Development and validation of a test dose strategy for once-daily i.v. busulfan: importance of fixed infusion rate dosing.Biol Blood Marrow Transplant. 2012; 18: 295-301
- Influence of busulfan exposure on allogeneic transplant outcome using a fludarabine/busulfan/thymoglobulin/total body irradiation preparative regimen for adult acute myelogenous leukemia.Bone Marrow Transplantation. 2010; 45 (Abstract P403): 83
- The addition of 400 cGY total body irradiation to a regimen incorporating once-daily intravenous busulfan, fludarabine, and antithymocyte globulin reduces relapse without affecting nonrelapse mortality in acute myelogenous leukemia.Biol Blood Marrow Transplant. 2010; 16: 509-514
- 1994 Consensus Conference on Acute GVHD Grading.Bone Marrow Transplant. 1995; 15: 825-828
- National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease: I. The 2014 Diagnosis and Staging Working Group report.Biol Blood Marrow Transplant. 2015; 21 (389-401.e1)
- Development and validation of a Pneumocystis jirovecii real-time polymerase chain reaction assay for diagnosis of Pneumocystis pneumonia.Can J Infect Dis Med Microbiol. 2015; 26: 263-267
- Evaluation of quantitative FTD-Pneumocystis jirovecii kit for Pneumocystis infection diagnosis.Diagn Microbiol Infect Dis. 2017; 89: 212-217
- Current understanding of Pneumocystis immunology.Future Microbiol. 2010; 5: 43-65
- Primary prophylaxis of bacterial infections and Pneumocystis jirovecii pneumonia in patients with hematological malignancies and solid tumors: guidelines of the Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Oncology (DGHO).Ann Hematol. 2013; 92: 433-442
- Pneumocystis jiroveci pneumonia in relation to CD4+ lymphocyte count in patients with B-cell non-Hodgkin lymphoma treated with chemotherapy.Leuk Lymphoma. 2010; 51: 1816-1821
- Pneumocystis jirovecii pneumonia in patients with and without human immunodeficiency virus infection.J Microbiol Immunol Infect. 2008; 41: 478-482
- A controlled trial of aerosolized pentamidine or trimethoprim-sulfamethoxazole as primary prophylaxis against Pneumocystis carinii pneumonia in patients with human immunodeficiency virus infection. The Dutch AIDS Treatment Group.N Engl J Med. 1992; 327: 1836-1841
- Intermittent trimethoprim-sulfamethoxazole compared with dapsone-pyrimethamine for the simultaneous primary prophylaxis of Pneumocystis pneumonia and toxoplasmosis in patients infected with HIV.Ann Intern Med. 1995; 122: 755-761
- A randomized trial of three antipneumocystis agents in patients with advanced human immunodeficiency virus infection. NIAID AIDS Clinical Trials Group.N Engl J Med. 1995; 332: 693-699
- Comparative trial of dapsone versus trimethoprim/sulfamethoxazole for primary prophylaxis of Pneumocystis carinii pneumonia.J Acquir Immune Defic Syndr. 1992; 5: 341-347
- A randomized trial of daily and thrice-weekly trimethoprim-sulfamethoxazole for the prevention of Pneumocystis carinii pneumonia in human immunodeficiency virus-infected persons. Terry Beirn Community Programs for Clinical Research on AIDS (CPCRA).Clin Infect Dis. 1999; 29: 775-783
- A comparison of the effectiveness of three regimens in the prevention of Pneumocystis carinii pneumonia in human immunodeficiency virus-infected patients.Arch Intern Med. 1992; 152: 523-528
- Use of low-dose trimethoprim-sulfamethoxazole thrice weekly for primary and secondary prophylaxis of Pneumocystis carinii pneumonia in human immunodeficiency virus-infected patients.Antimicrob Agents Chemother. 1991; 35: 1705-1709
- Studies on dapsone induced haemolytic anaemia. I. Methaemoglobin production and G-6-PD activity in correlation with dapsone dosage.Br J Dermatol. 1979; 100: 427-432
- Dapsone-induced methemoglobinemia: a dose-related occurrence?.Cancer. 2011; 117 (Epub 2011 Jan 18): 3485-3492https://doi.org/10.1002/cncr.25904
- A controlled study of inhaled pentamidine for primary prevention of Pneumocystis carinii pneumonia.N Engl J Med. 1991; 324: 1079-1083
- Breakthrough Pneumocystis jiroveci pneumonia under pentamidine prophylaxis: imaging findings revisited.Hong Kong Med J. 2009; 15: 490-491
- Effect of long-term primary aerosolized pentamidine prophylaxis on breakthrough Pneumocystis carinii pneumonia.Eur Respir J. 1996; 9: 1006-1012
- Aerosolized pentamidine prophylaxis for Pneumocystis carinii pneumonia after allogeneic marrow transplantation.Transpl Infect Dis. 2002; 4: 66-74
Bosch M, Dhadda M, Hoegh-Petersen M, Liu Y, Hagel LM, Podgorny P, et al. Immune reconstitution after anti-thymocyte globulin-conditioned hematopoietic cell transplantation. Unpublished raw data.
- Prophylactic effect of trimethoprim-sulfamethoxazole for pneumocystis pneumonia in patients with rheumatic diseases exposed to prolonged high-dose glucocorticoids.Ann Rheum Dis. 2018; 77: 644-649
- Early chemoprophylaxis with trimethoprim-sulphamethoxazole for HIV-1-infected adults in Abidjan, Côte d'Ivoire: a randomised trial. Cotrimo-CI Study Group.Lancet. 1999; 353: 1463-1468
- Co-trimoxazole as prophylaxis against opportunistic infections in HIV-infected Zambian children (CHAP): a double-blind randomised placebo-controlled trial.Lancet. 2004; 364: 1865-1871
- Primary prevention with cotrimoxazole for HIV-1-infected adults: results of the pilot study in Dakar, Senegal.J Acquir Immune Defic Syndr. 2001; 26: 130-136
- Value of bronchoalveolar lavage in the diagnosis of pulmonary infection in acquired immune deficiency syndrome.Thorax. 1986; 41: 345-349
- Diagnostic yield of bronchoalveolar lavage following renal transplantation.Transpl Infect Dis. 2001; 3: 2-7
Article Info
Publication History
Published online: December 27, 2019
Accepted:
November 12,
2019
Received:
July 19,
2019
Identification
Copyright
Crown Copyright © 2019. Published by Elsevier Inc. on behalf of International Society for Cell and Gene Therapy. All rights reserved.
