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The Reply

  • Pierre Fillatre
    Affiliations
    Maladies Infectieuses et Réanimation Médicale, Hôpital Pontchaillou, Rennes, France

    CIC-Inserm-0203, Faculté de Médecine, Université Rennes 1, Rennes, France
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  • Matthieu Revest
    Affiliations
    Maladies Infectieuses et Réanimation Médicale, Hôpital Pontchaillou, Rennes, France

    CIC-Inserm-0203, Faculté de Médecine, Université Rennes 1, Rennes, France

    INSERM U835, Faculté de Médecine, Université Rennes 1, Rennes, France
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  • Pierre Tattevin
    Affiliations
    Maladies Infectieuses et Réanimation Médicale, Hôpital Pontchaillou, Rennes, France

    CIC-Inserm-0203, Faculté de Médecine, Université Rennes 1, Rennes, France

    INSERM U835, Faculté de Médecine, Université Rennes 1, Rennes, France
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      We appreciate the comments of Roux et al on our article published in The American Journal of Medicine
      • Fillatre P.
      • Decaux O.
      • Jouneau S.
      • et al.
      Incidence of Pneumocystis jiroveci pneumonia among groups at risk in HIV-negative patients.
      and agree with most of the points they raised. Indeed, no one would argue that all patients with acute leukemia are not at equal risk of Pneumocystis jiroveci pneumonia.
      Firstly, as already stated in our article, the level of immunosuppression results from both the impairment in immunity related to the underlying disease itself and from the immunosuppressive effect of drugs used to control these diseases, particularly corticosteroids.
      Secondly, we aimed to characterize non HIV-infected immunocompromised patients who developed Pneumocystis jiroveci pneumonia over the last 2 decades in our area to better target the immunodeficiency states where increased use of trimethoprim-sulfamethoxazole prophylaxis may be beneficial. Among the 154 non-HIV-infected patients diagnosed with Pneumocystis jiroveci pneumonia during the years 1990-2010, 8 were previously followed for acute leukemia, which translates into an estimated incidence of ∼56 cases per 100,000 patient-year in this group. Of note, 6 were acute myeloid leukemia, which most likely reflects the limited use of trimethoprim-sulfamethoxazole in patients with acute myeloid leukemia, as compared with acute lymphoblastic leukemia, for whom Pneumocystis jiroveci pneumonia prophylaxis is systematic in most places.
      Recent guidelines from the German Society of Hematology and Oncology issued 2 levels of recommendations for Pneumocystis jiroveci pneumonia prophylaxis in patients with acute leukemia: 1) strong evidence (A-I) in patients with acute lymphoblastic leukemia; 2) risk status not entirely conclusive (C-III) in patients with acute myeloid leukemia.
      • Neumann S.
      • Krause S.W.
      • Maschmeyer G.
      • Schiel X.
      • von Lilienfeld-Toal M.
      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).
      Our study suggests that it may be beneficial to lower the threshold for trimethoprim-sulfamethoxazole prophylaxis in patients with acute myeloid leukemia, given the high incidence of Pneumocystis jiroveci pneumonia observed in this group with current practices.
      • Fillatre P.
      • Decaux O.
      • Jouneau S.
      • et al.
      Incidence of Pneumocystis jiroveci pneumonia among groups at risk in HIV-negative patients.
      Although the study design did not allow the identification of specific risk factors to estimate the risk of Pneumocystis jiroveci pneumonia in this group, corticosteroid cumulative/daily doses, or CD4 T cell count would appear as potential surrogate markers.
      According to the President's Council of Advisors on Science and Technology, personalized medicine refers to “the tailoring of medical treatment to the individual characteristics of each patient, which depends on the ability to classify individuals into subpopulations that differ in their susceptibility to a particular disease or their response to a specific treatment. Preventive or therapeutic interventions can then be concentrated on those who will benefit, sparing expense and side effects for those who will not”.
      • Goldberger J.J.
      • Buxton A.E.
      Personalized medicine vs guideline-based medicine.
      Our study adds a brick to the wall of personalized medicine for patients with hematological malignancies by providing original data to better identify patients who may benefit from increased use of Pneumocystis jiroveci pneumonia prophylaxis. We did not state, at any time, that all patients with acute leukemia are at equal risk.

      References

        • Fillatre P.
        • Decaux O.
        • Jouneau S.
        • et al.
        Incidence of Pneumocystis jiroveci pneumonia among groups at risk in HIV-negative patients.
        Am J Med. 2014 Jul 21; ([Epub ahead of print])https://doi.org/10.1016/j.amjmed.2014.07.10
        • Neumann S.
        • Krause S.W.
        • Maschmeyer G.
        • Schiel X.
        • von Lilienfeld-Toal M.
        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
        • Goldberger J.J.
        • Buxton A.E.
        Personalized medicine vs guideline-based medicine.
        JAMA. 2013; 309: 2559-2560

      Linked Article

      • All Patients with Leukemia Are Not Equally at Risk of Contracting Pneumocystis jirovecii Pneumonia
        The American Journal of MedicineVol. 128Issue 1
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          We read with interest the article of Fillatre et al1 about Pneumocystis jirovecii pneumonia in patients not infected with human immunodeficiency virus (HIV).1 Among those at risk, they define a group called “leukemia.” The same amalgam was made in a previous study in hematological patients.2 It is suggested that among these patients with acute respiratory failure, the diagnostic and therapeutic approaches are based on the attitude, called “DIRECT.”3 It is to analyze the clinical picture from: Delay since malignancy onset or hematopoietic stem cells transplantation (HSCT), since symptom onset and since implementation of antibiotics/prophylaxis; pattern of Immune deficiency; Radiographic appearance; Experience and knowledge of the literature; Clinical picture (including ongoing chemoprophylaxis and effective antibiotic therapy); and findings by high-resolution computed Tomography.
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