Advertisement

Infections in Patients with Hematologic Malignancies

  • Genovefa Papanicolaou
  • Jayesh Mehta
Chapter
Part of the Current Clinical Oncology book series (CCO)

Abstract

Hematologic malignancies are a heterogeneous group of diseases with differing clinical manifestations, disease course, response to therapy, and long-term outcome. More intensive therapies are also being extended to older age groups and to patients with significant comorbidities, which were traditionally excluded from such treatment. These intensive treatment approaches are associated with multiple complications; infections from a wide variety of pathogenic and opportunistic organisms being amongst the commonest and the most serious. Infections affect quality of life, delay potentially saving chemotherapy and pose a substantial burden for the health care system and remain an important cause of death. In this chapter we outline the common immune defects and associated infections frequently seen in patients with ­hematologic malignancies.

Keywords

Leukemia Lymphoma Multiple myeloma Infections Serious Immune dysfunction New chemotherapy Old age 

References

  1. 1.
    Burnett AK. Acute myeloid leukemia: treatment of adults under 60 years. Rev Clin Exp Hematol. 2002;6(1):26–45; discussion 86–7.Google Scholar
  2. 2.
    Koistinen P et al. Long-term outcome of intensive chemotherapy for adults with de novo acute myeloid leukaemia (AML): the nationwide AML-92 study by the Finnish Leukaemia Group. Eur J Haematol. 2007;78(6):477–86.PubMedCrossRefGoogle Scholar
  3. 3.
    Chamilos G et al. Invasive fungal infections in patients with hematologic malignancies in a tertiary care cancer center: an autopsy study over a 15-year period (1989–2003). Haematologica. 2006;91(7):986–9.PubMedGoogle Scholar
  4. 4.
    Elonen E et al. Comparison between four and eight cycles of intensive chemotherapy in adult acute myeloid leukemia: a randomized trial of the Finnish Leukemia Group. Leukemia. 1998;12(7):1041–8.PubMedCrossRefGoogle Scholar
  5. 5.
    Castaigne S et al. Randomized comparison of double induction and timed-sequential induction to a “3 + 7” induction in adults with AML: long-term analysis of the Acute Leukemia French Association (ALFA) 9000 study. Blood. 2004;104(8):2467–74.PubMedCrossRefGoogle Scholar
  6. 6.
    Hersh EM et al. Causes of death in acute leukemia: a ten-year study of 414 patients from 1954–1963. JAMA. 1965;193:105–9.PubMedCrossRefGoogle Scholar
  7. 7.
    Caggiano V et al. Incidence, cost, and mortality of neutropenia hospitalization associated with chemotherapy. Cancer. 2005;103(9):1916–24.PubMedCrossRefGoogle Scholar
  8. 8.
    Dale DC. The benefits of haematopoietic growth factors in the management of gynaecological oncology. Eur J Gynaecol Oncol. 2004;25(2):133–44.PubMedGoogle Scholar
  9. 9.
    Darmon M et al. Impact of neutropenia duration on short-term mortality in neutropenic critically ill cancer patients. Intensive Care Med. 2002;28(12):1775–80.PubMedCrossRefGoogle Scholar
  10. 10.
    Kuderer NM et al. Mortality, morbidity, and cost associated with febrile neutropenia in adult cancer patients. Cancer. 2006;106(10):2258–66.PubMedCrossRefGoogle Scholar
  11. 11.
    Talcott JA et al. Risk assessment in cancer patients with fever and neutropenia: a prospective, two-center validation of a prediction rule. J Clin Oncol. 1992;10(2):316–22.PubMedGoogle Scholar
  12. 12.
    Rossini F. Prognosis of infections in elderly patients with haematological diseases. Support Care Cancer. 1996;4(1):46–50.PubMedCrossRefGoogle Scholar
  13. 13.
    Elting LS et al. Outcomes of bacteremia in patients with cancer and neutropenia: observations from two decades of epidemiological and clinical trials. Clin Infect Dis. 1997;25(2):247–59.PubMedCrossRefGoogle Scholar
  14. 14.
    Malik I, Hussain M, Yousuf H. Clinical characteristics and therapeutic outcome of patients with febrile neutropenia who present in shock: need for better strategies. J Infect. 2001;42(2):120–5.PubMedCrossRefGoogle Scholar
  15. 15.
    Styrt B. Infection associated with asplenia: risks, mechanisms, and prevention. Am J Med. 1990;88(5N):33N–42.PubMedGoogle Scholar
  16. 16.
    Norris RP, Vergis EN, Yu VL. Overwhelming postsplenectomy infection: a critical review of etiologic pathogens and management. Infect Med. 1996;13:779–83.Google Scholar
  17. 17.
    Torres HA et al. Characteristics and outcome of respiratory syncytial virus infection in patients with leukemia. Haematologica. 2007;92(9):1216–23.PubMedCrossRefGoogle Scholar
  18. 18.
    Zuccotti G, Sepkowitz KA. Management of infection in oncology patients: infection control. In: Wingard JR, Bowden RA, editors. Infections in oncology patients. Philadelphia, PA: Martin Dunitz; 2003.Google Scholar
  19. 19.
    Hachem RY et al. Aspergillus terreus: an emerging amphotericin B-resistant opportunistic mold in patients with hematologic malignancies. Cancer. 2004;101(7):1594–600.PubMedCrossRefGoogle Scholar
  20. 20.
    Uzun O et al. Risk factors and predictors of outcome in patients with cancer and breakthrough candidemia. Clin Infect Dis. 2001;32(12):1713–7.PubMedCrossRefGoogle Scholar
  21. 21.
    Anaissie EJ et al. Predictors of adverse outcome in cancer patients with candidemia. Am J Med. 1998;104(3):238–45.PubMedCrossRefGoogle Scholar
  22. 22.
    Bodey GP et al. Quantitative relationships between circulating leukocytes and infection in patients with acute leukemia. Ann Intern Med. 1966;64(2):328–40.PubMedCrossRefGoogle Scholar
  23. 23.
    Pizzo PA. Fever in immunocompromised patients. N Engl J Med. 1999;341(12):893–900.PubMedCrossRefGoogle Scholar
  24. 24.
    Rolston KV et al. The spectrum of Gram-positive bloodstream infections in patients with hematologic malignancies, and the in vitro activity of various quinolones against Gram-positive bacteria isolated from cancer patients. Int J Infect Dis. 2006;10(3):223–30.PubMedCrossRefGoogle Scholar
  25. 25.
    Safdar A et al. Changing trends in etiology of bacteremia in patients with cancer. Eur J Clin Microbiol Infect Dis. 2006;25(8):522–6.PubMedCrossRefGoogle Scholar
  26. 26.
    Donowitz GR, et al. Infections in the neutropenic patient – new views of an old problem. Hematology Am Soc Hematol Educ Program. 2001;113–39.Google Scholar
  27. 27.
    Lautenbach E et al. Changes in the prevalence of vancomycin-resistant enterococci in response to antimicrobial formulary interventions: impact of progressive restrictions on use of vancomycin and third-generation cephalosporins. Clin Infect Dis. 2003;36(4):440–6.PubMedCrossRefGoogle Scholar
  28. 28.
    Safdar N, Maki DG. The commonality of risk factors for nosocomial colonization and infection with antimicrobial-resistant Staphylococcus aureus, enterococcus, gram-negative bacilli, Clostridium difficile, and Candida. Ann Intern Med. 2002;136(11):834–44.PubMedCrossRefGoogle Scholar
  29. 29.
    Gonzalez-Barca E et al. Prognostic factors influencing mortality in cancer patients with neutropenia and bacteremia. Eur J Clin Microbiol Infect Dis. 1999;18(8):539–44.PubMedCrossRefGoogle Scholar
  30. 30.
    Pagano L et al. Bacteremia in patients with hematological malignancies. Analysis of risk factors, etiological agents and prognostic indicators. Haematologica. 1997;82(4):415–9.PubMedGoogle Scholar
  31. 31.
    Norgaard M et al. Risk of bacteraemia and mortality in patients with haematological malignancies. Clin Microbiol Infect. 2006;12(3):217–23.PubMedCrossRefGoogle Scholar
  32. 32.
    Bochud PY et al. Bacteremia due to viridans streptococcus in neutropenic patients with cancer: clinical spectrum and risk factors. Clin Infect Dis. 1994;18(1):25–31.PubMedCrossRefGoogle Scholar
  33. 33.
    Elting LS, Bodey GP, Keefe BH. Septicemia and shock syndrome due to viridans streptococci: a case-control study of predisposing factors. Clin Infect Dis. 1992;14(6):1201–17.PubMedCrossRefGoogle Scholar
  34. 34.
    Tunkel AR, Sepkowitz KA. Infections caused by viridans streptococci in patients with neutropenia. Clin Infect Dis. 2002;34(11):1524–9.PubMedCrossRefGoogle Scholar
  35. 35.
    Pizzo PA et al. Empiric antibiotic and antifungal therapy for cancer patients with prolonged fever and granulocytopenia. Am J Med. 1982;72(1):101–11.PubMedCrossRefGoogle Scholar
  36. 36.
    Hughes WT et al. 1997 Guidelines for the use of antimicrobial agents in neutropenic patients with unexplained fever. Infectious Diseases Society of America. Clin Infect Dis. 1997;25(3):551–73.PubMedCrossRefGoogle Scholar
  37. 37.
    Edmond MB et al. Nosocomial bloodstream infections in United States hospitals: a three-year analysis. Clin Infect Dis. 1999;29(2):239–44.PubMedCrossRefGoogle Scholar
  38. 38.
    Pfaller MA et al. International surveillance of bloodstream infections due to Candida species: frequency of occurrence and in vitro susceptibilities to fluconazole, ravuconazole, and voriconazole of isolates collected from 1997 through 1999 in the SENTRY antimicrobial surveillance program. J Clin Microbiol. 2001;39(9):3254–9.PubMedCrossRefGoogle Scholar
  39. 39.
    Anttila VJ et al. Hepatosplenic candidiasis in patients with acute leukemia: incidence and prognostic implications. Clin Infect Dis. 1997;24(3):375–80.PubMedCrossRefGoogle Scholar
  40. 40.
    Kontoyiannis DP, Bodey GP. Invasive aspergillosis in 2002: an update. Eur J Clin Microbiol Infect Dis. 2002;21(3):161–72.PubMedCrossRefGoogle Scholar
  41. 41.
    Pagano L et al. The epidemiology of fungal infections in patients with hematologic malignancies: the SEIFEM-2004 study. Haematologica. 2006;91(8):1068–75.PubMedGoogle Scholar
  42. 42.
    Walsh TJ, Hiemenz JW, Anaissie E. Recent progress and current problems in treatment of invasive fungal infections in neutropenic patients. Infect Dis Clin North Am. 1996;10(2):365–400.PubMedCrossRefGoogle Scholar
  43. 43.
    Roden MM et al. Epidemiology and outcome of zygomycosis: a review of 929 reported cases. Clin Infect Dis. 2005;41(5):634–53.PubMedCrossRefGoogle Scholar
  44. 44.
    Kontoyiannis DP et al. Zygomycosis in a tertiary-care cancer center in the era of Aspergillus-active antifungal therapy: a case-control observational study of 27 recent cases. J Infect Dis. 2005;191(8):1350–60.PubMedCrossRefGoogle Scholar
  45. 45.
    Chandrasekar PH. Fungi other than Candida and Aspergillus. In: Bowden RA, editor. Infections in oncology patients. Philadelphia, PA: Martin Dunitz; 2003.Google Scholar
  46. 46.
    Bogomolski-Yahalom V, Matzner Y. Disorders of neutrophil function. Blood Rev. 1995;9(3):183–90.PubMedCrossRefGoogle Scholar
  47. 47.
    Serbina NV et al. Monocyte-mediated defense against microbial pathogens. Annu Rev Immunol. 2008;26:421–52.PubMedCrossRefGoogle Scholar
  48. 48.
    Wade JC. Viral infections in patients with hematological malignancies. Hematology Am Soc Hematol Educ Program. 2006;368–74.Google Scholar
  49. 49.
    Huang H et al. Lamivudine for the prevention of hepatitis B virus reactivation after high-dose chemotherapy and autologous hematopoietic stem cell transplantation for patients with advanced or relapsed non-Hodgkin’s lymphoma single institution experience. Expert Opin Pharmacother. 2009;10(15):2399–406.PubMedCrossRefGoogle Scholar
  50. 50.
    Uchiyama M, Tamai Y, Ikeda T. Low-dose acyclovir against reactivation of varicella zoster virus after unrelated cord blood transplantation. Int J Infect Dis. 2009;14(5):e451–2.PubMedCrossRefGoogle Scholar
  51. 51.
    Waecker Jr NJ et al. Nosocomial transmission of Mycobacterium bovis bacille Calmette-Guerin to children receiving cancer therapy and to their health care providers. Clin Infect Dis. 2000;30(2):356–62.PubMedCrossRefGoogle Scholar
  52. 52.
    Pei SN et al. Reactivation of hepatitis B virus following rituximab-based regimens: a serious complication in both HBsAg-positive and HBsAg-negative patients. Ann Hematol. 2009;89(3):255–62.PubMedCrossRefGoogle Scholar
  53. 53.
    Gabriel DA et al. The effect of oral mucositis on morbidity and mortality in bone marrow transplant. Semin Oncol. 2003;30(6 Suppl 18):76–83.PubMedCrossRefGoogle Scholar
  54. 54.
    Sonis ST. The biologic role for nuclear factor-kappaB in disease and its potential involvement in mucosal injury associated with anti-neoplastic therapy. Crit Rev Oral Biol Med. 2002;13(5):380–9.PubMedCrossRefGoogle Scholar
  55. 55.
    Sonis ST et al. Perspectives on cancer therapy-induced mucosal injury: pathogenesis, measurement, epidemiology, and consequences for patients. Cancer. 2004;100(9 Suppl):1995–2025.PubMedCrossRefGoogle Scholar
  56. 56.
    Schimpff SC et al. Origin of infection in acute nonlymphocytic leukemia. Significance of hospital acquisition of potential pathogens. Ann Intern Med. 1972;77(5):707–14.PubMedCrossRefGoogle Scholar
  57. 57.
    Weinstock DM et al. Colonization, bloodstream infection, and mortality caused by vancomycin-resistant enterococcus early after allogeneic hematopoietic stem cell transplant. Biol Blood Marrow Transplant. 2007;13(5):615–21.PubMedCrossRefGoogle Scholar
  58. 58.
    David DS et al. Visceral varicella-zoster after bone marrow transplantation: report of a case series and review of the literature. Am J Gastroenterol. 1998;93(5):810–3.PubMedCrossRefGoogle Scholar
  59. 59.
    Ravandi F, Anaissie E, O’Brien S. Infections in chronic leukemias and other hematological malignancies. In: Wingard JR, Bowden RA, editors. Infections in oncology patients. Philadelphia, PA: Martin Dunitz; 2003.Google Scholar
  60. 60.
    Molica S, Levato D, Levato L. Infections in chronic lymphocytic leukemia. Analysis of incidence as a function of length of follow-up. Haematologica. 1993;78(6):374–7.PubMedGoogle Scholar
  61. 61.
    Tam CS et al. A new model for predicting infectious complications during fludarabine-based combination chemotherapy among patients with indolent lymphoid malignancies. Cancer. 2004;101(9):2042–9.PubMedCrossRefGoogle Scholar
  62. 62.
    Anaissie EJ et al. Infection in patients with chronic lymphocytic leukemia treated with fludarabine. Ann Intern Med. 1998;129(7):559–66.PubMedCrossRefGoogle Scholar
  63. 63.
    Lungman P. Viral infections: current diagnosis and treatment. Hematol J. 2004;5:S63–8.CrossRefGoogle Scholar
  64. 64.
    Sandherr M et al. Antiviral prophylaxis in patients with haematological malignancies and solid tumours: Guidelines of the Infectious Diseases Working Party (AGIHO) of the German Society for Hematology and Oncology (DGHO). Ann Oncol. 2006;17(7):1051–9.PubMedCrossRefGoogle Scholar
  65. 65.
    O’Brien SM et al. Results of the fludarabine and cyclophosphamide combination regimen in chronic lymphocytic leukemia. J Clin Oncol. 2001;19(5):1414–20.PubMedGoogle Scholar
  66. 66.
    Cavalli-Bjorkman N et al. Fatal adenovirus infection during alemtuzumab (anti-CD52 monoclonal antibody) treatment of a patient with fludarabine-refractory B-cell chronic lymphocytic leukemia. Med Oncol. 2002;19(4):277–80.PubMedCrossRefGoogle Scholar
  67. 67.
    Kennedy B, Hillmen P. Immunological effects and safe administration of alemtuzumab (MabCampath) in advanced B-cLL. Med Oncol. 2002;19(Suppl):S49–55.PubMedGoogle Scholar
  68. 68.
    Rai KR et al. Alemtuzumab in previously treated chronic lymphocytic leukemia patients who also had received fludarabine. J Clin Oncol. 2002;20(18):3891–7.PubMedCrossRefGoogle Scholar
  69. 69.
    Laurenti L et al. Cytomegalovirus reactivation during alemtuzumab therapy for chronic lymphocytic leukemia: incidence and treatment with oral ganciclovir. Haematologica. 2004;89(10):1248–52.PubMedGoogle Scholar
  70. 70.
    Rawstron AC et al. Early prediction of outcome and response to alemtuzumab therapy in chronic lymphocytic leukemia. Blood. 2004;103(6):2027–31.PubMedCrossRefGoogle Scholar
  71. 71.
    Rieger K et al. Efficacy and tolerability of alemtuzumab (CAMPATH-1H) in the salvage treatment of B-cell chronic ­lymphocytic leukemia – change of regimen needed? Leuk Lymphoma. 2004;45(2):345–9.PubMedCrossRefGoogle Scholar
  72. 72.
    Wendtner CM et al. Consolidation with alemtuzumab in patients with chronic lymphocytic leukemia (CLL) in first remission – ­experience on safety and efficacy within a randomized multicenter phase III trial of the German CLL Study Group (GCLLSG). Leukemia. 2004;18(6):1093–101.PubMedCrossRefGoogle Scholar
  73. 73.
    Lin TS et al. Filgrastim and alemtuzumab (Campath-1H) for refractory chronic lymphocytic leukemia. Leukemia. 2005;19(7):1207–10.PubMedCrossRefGoogle Scholar
  74. 74.
    Lundin J et al. Phase II trial of subcutaneous anti-CD52 monoclonal antibody alemtuzumab (Campath-1H) as first-line treatment for patients with B-cell chronic lymphocytic leukemia (B-CLL). Blood. 2002;100(3):768–73.PubMedCrossRefGoogle Scholar
  75. 75.
    Keating MJ et al. Therapeutic role of alemtuzumab (Campath-1H) in patients who have failed fludarabine: results of a large international study. Blood. 2002;99(10):3554–61.PubMedCrossRefGoogle Scholar
  76. 76.
    Keating MJ et al. Long-term follow-up of patients with chronic lymphocytic leukemia (CLL) receiving fludarabine regimens as ­initial therapy. Blood. 1998;92(4):1165–71.PubMedGoogle Scholar
  77. 77.
    Keating MJ et al. Early results of a chemoimmunotherapy regimen of fludarabine, cyclophosphamide, and rituximab as initial therapy for chronic lymphocytic leukemia. J Clin Oncol. 2005;23(18):4079–88.PubMedCrossRefGoogle Scholar
  78. 78.
    Tam C et al. Early and late infectious consequences of adding rituximab to fludarabine and cyclophosphamide in patients with indolent lymphoid malignancies. Haematologica. 2005;90(5):700–2.PubMedGoogle Scholar
  79. 79.
    Blade, J, Rosinol L. Complications of multiple myeloma. Hematol Oncol Clin North Am. 2007;21(6):1231–46, xi.Google Scholar
  80. 80.
    Hargreaves RM et al. Immunological factors and risk of infection in plateau phase myeloma. J Clin Pathol. 1995;48(3):260–6.PubMedCrossRefGoogle Scholar
  81. 81.
    Savage DG, Lindenbaum J, Garrett TJ. Biphasic pattern of bacterial infection in multiple myeloma. Ann Intern Med. 1982;96(1):47–50.PubMedCrossRefGoogle Scholar
  82. 82.
    San Miguel JF et al. Bortezomib plus melphalan and prednisone for initial treatment of multiple myeloma. N Engl J Med. 2008;359(9):906–17.PubMedCrossRefGoogle Scholar
  83. 83.
    Lortholary O et al. Invasive aspergillosis as an opportunistic infection in nonallografted patients with multiple myeloma: a European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the Intergroupe Francais du Myelome. Clin Infect Dis. 2000;30(1):41–6.PubMedCrossRefGoogle Scholar
  84. 84.
    Fisher RI et al. Persistent immunologic abnormalities in long-term survivors of advanced Hodgkin’s disease. Ann Intern Med. 1980;92(5):595–9.PubMedCrossRefGoogle Scholar
  85. 85.
    Dalton JA et al. Cutaneous T-cell lymphoma. Int J Dermatol. 1997;36(11):801–9.PubMedCrossRefGoogle Scholar
  86. 86.
    Posner LE et al. Septicemic complications of the cutaneous T-cell lymphomas. Am J Med. 1981;71(2):210–6.PubMedCrossRefGoogle Scholar
  87. 87.
    Axelrod PI, Lorber B, Vonderheid EC. Infections complicating mycosis fungoides and Sezary syndrome. JAMA. 1992;267(10):1354–8.PubMedCrossRefGoogle Scholar
  88. 88.
    Thursky KA et al. Spectrum of infection, risk and recommendations for prophylaxis and screening among patients with lymphoproliferative disorders treated with alemtuzumab. Br J Haematol. 2006;132(1):3–12.PubMedCrossRefGoogle Scholar
  89. 89.
    National Comprehensive Cancer Network. Clinical practice ­guidelines in oncology: prevention and treatment of cancer related infections (v.2.2009). Jenkintown, PA: NCCN; 2009.Google Scholar
  90. 90.
    Marshall BG et al. Increased inflammatory cytokines and new collagen formation in cutaneous tuberculous and sarcoidosis. Thorax. 1996;51(12):1253–61.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  1. 1.Infectious Diseases ServiceMemorial Sloan-Kettering Cancer CenterNew YorkUSA

Personalised recommendations