Pulmonary Infections Complicating Hematological Disorders

ABSTRACT

Pulmonary infections are second in importance only to septicemia as a cause of infectious morbidity and mortality in patients with hematological disorders. The differential diagnosis of the pneumonitis syndrome includes not only infection but also a multitude of noninfectious causes. In addition, the diagnosis may be difficult, owing to the subtlety of the clinical signs as a consequence of the impaired inflammatory response. Radiographic findings are often nonspecific, and invasive procedures and microbiological exams are required to establish the cause of pulmonary disease and to choose a specific therapy. However, invasive diagnostic procedures are often precluded by the poor general conditions and (particularly in acute leukemia patients) by concurrent thrombocytopenia. The approach to all infectious complications, including those of the lower respiratory tract, in immunocompromised patients with hematological diseases, is based on aggressive prevention strategies and the empirical administration of broad-spectrum antimicrobials eventually followed by a clinically or microbiologically guided treatment modification. With regard to the antimicrobial treatment, given the variety of infectious and noninfectious causes of pulmonary infiltrates in patients with hematological diseases, the diversity of the underlying immunocompromised state, and the spectrum of clinical findings, no single general therapeutic algorithm can be applied.

KEYWORDS

Pneumonia - neutropenia - leukemia - “hematopoietic stem cell transplant”

REFERENCES

• 1 Tenholder M F, Hooper R G. Pulmonary infiltrates in leukemia.  Chest. 1980;  78 468-473
• 2 Rubin R H, Greene R. Clinical approach to compromised host with fever and pulmonary infiltrates. In: Rubin RH and Young LS Clinical Approach to Infection in the Compromised Host. 4th ed. New York; Kluwer Academic/Plenum 2002: 111-162
• 3 Horak D A. Pulmonary complications after hematopoietic cell transplantation. In: Blume KG, Forman SJ, Appelbaum FR Thomas' Hematopoietic Cell Transplantation. 3rd ed. 2004: 873-882
• 4 Denning D W. Invasive aspergillosis.  Clin Infect Dis. 1998;  26 781-805
• 5 Poletti V, Trisolini R, Tura S. Pulmonary disease in patients with hematologic malignancies.  Sarcoidosis Vasc Diff Lung Dis. 2002;  19 29-45
• 6 Morrison V A. The infectious complications of chronic lymphocytic leukemia.  Semin Oncol. 1998;  25 98-106
• 7 Kontoyiannis D P, Ruoff K, Hooper D C. Nocardia bacteremia: report of 4 cases and review of the literature.  Medicine. 1998;  77 255-267
• 8 Marr K A, Carter R A, Crippa F, Wald A, Corey L. Epidemiology and outcome of mould infections in hematopoietic stem cell transplant recipients.  Clin Infect Dis. 2002;  34 909-917
• 9 Marr K A, Carter R A, Boeckh M, Martin P, Corey L. Invasive aspergillosis in allogeneic stem cell transplant recipients: changes in epidemiology and risk factors.  Blood. 2002;  100 4358-4366
• 10 Lin S J, Schranz J, Teutsch S M. Aspergillosis case-fatality rate: systematic review of the literature.  Clin Infect Dis. 2001;  32 358-366
• 11 Pinto P S. The CT halo sign.  Radiology. 2004;  230 109-110
• 12 Franquet T, Muller N L, Gimenez A, Guembe P, de La Torre J, Bague S. Spectrum of pulmonary aspergillosis: histologic, clinical, and radiologic findings.  Radiographics. 2001;  21 825-837
• 13 Sonnet S, Buitrago-Tellez C H, Tamm M, Christen S, Steinbrich W. Direct detection of angioinvasive pulmonary aspergillosis in immunosuppressed patients:preliminary results with high-resolution 16-MDCT angiography.  AJR Am J Roentgenol. 2005;  185 746-751
• 14 Martino P, Girmenia C, Venditti M. Spontaneous pneumothorax complicating pulmonary mycetoma in patients with acute leukemia.  Rev Infect Dis. 1990;  12 611-617
• 15 Gorelik O, Cohen N, Shpirer I et al.. Fatal haemoptysis induced by invasive pulmonary aspergillosis in patients with acute leukaemia during bone marrow and clinical remission: report of two cases and review of the literature.  J Infect. 2000;  41 277-282
• 16 Gefter W B, Weingrad T R, Epstein D M, Ochs R H, Miller W T. Semiinvasive pulmonary aspergillosis.  Radiology. 1981;  140 313-321
• 17 Rodriguez M, Fishman J A. Prevention of infection due to Pneumocystis spp. in human immunodeficiency virus-negative immunocompromised patients.  Clin Microbiol Rev. 2004;  17 770-782
• 18 Thomas C F, Limper A H. Pneumocystis pneumonia.  N Engl J Med. 2004;  350 2487-2498
• 19 Meijer E, Boland G J, Verdonck L F. Prevention of cytomegalovirus disease in recipients of allogeneic stem cell transplants.  Clin Microbiol Rev. 2003;  16 647-657
• 20 Konoplev S, Champlin R E, Giralt S et al.. Cytomegalovirus pneumonia in adult autologous blood and marrow transplant recipients.  Bone Marrow Transplant. 2001;  27 877-881
• 21 Gentile G. Post-transplant HHV-6 Diseases.  Herpes. 2000;  7 24-27
• 22 Couch R B, Englunf J A, Whimbey E. Respiratory viral infections in immunocompetent and immunocompromised persons.  Am J Med. 1997;  102(3A) 2-9
• 23 Whimbey E, Englund J A, Couch R B. Community respiratory virus infections in immunocompromised patients with cancer.  Am J Med. 1997;  102(3A) 10-18
• 24 Bowden R A. Respiratory virus infections after marrow transplant: the Fred Hutchinson Cancer Research Center experience.  Am J Med. 1997;  102(3A) 27-30
• 25 Ebbert J O, Limper A H. Respiratory syncytial virus pneumonitis in immunocompromised adults:clinical features and outcome.  Respiration. 2005;  72 263-269
• 26 Ljungman P. Respiratory virus infections in bone marrow transplant recipients: the European perspective.  Am J Med. 1997;  102(3A) 44-47
• 27 Marcolini J A, Malik S, Suki D, Whimbey E, Bodey G P. Respiratory disease due to parainfluenza virus in adult leucemia patients.  Eur J Clin Microbiol Infect Dis. 2003;  22 79-84
• 28 Gentile G, Micozzi A, Girmenia C et al.. Pneumonia in allogenic and autologous bone marrow recipients: a retrospective study.  Chest. 1993;  104 371-375
• 29 Fukuda T, Boeckh M, Carter R A et al.. Risks and outcomes of invasive fungal infections in recipients of allogeneic hematopoietic stem cell transplants after nonmyeloablative conditioning.  Blood. 2003;  102 827-833
• 30 Hughes W T, Armstrong D, Bodey G P et al.. 2002 guidelines for the use of antimicrobial agents in neutropenic patients with cancer.  Clin Infect Dis. 2002;  34 730-751
• 31 Bow E J, Laverdiere M, Lussier N, Rotstein C, Cheang M S, Ioannou S. Antifungal prophylaxis for severely neutropenic chemotherapy recipients: a meta analysis of randomized-controlled clinical trials.  Cancer. 2002;  94 3230-3246
• 32 Cornely O A, Ullmann A J, Karthaus M. Evidence-based assessment of primary antifungal prophylaxis in patients with hematologic malignancies.  Blood. 2003;  101 3365-3372
• 33 Girmenia C, Martino P. New antifungal drugs and new clinical trials: interpreting results may be difficult.  Curr Opin Oncol. 2003;  15 283-288
• 34 Herbrecht R, Denning D W, Patterson T F et al.. Voriconazole versus amphotericin B for primary therapy of invasive aspergillosis.  N Engl J Med. 2002;  347 408-415
• 35 Denning D W, Ribaud P, Milpied N. Efficacy and safety of voriconazole in the treatment of acute invasive aspergillosis.  Clin Infect Dis. 2002;  34 563-571
• 36 Aliff T B, Maslak P G, Jurcic J G. Refractory aspergillus pneumonia in patients with acute leukemia.  Cancer. 2003;  97 1025-1032
• 37 Maertens J, Raad I, Petrikkos G et al.. Efficacy and safety of caspofungin for treatment of invasive aspergillosis in patients refractory to or intolerant of conventional antifungal therapy.  Clin Infect Dis. 2004;  39 1563-1571
• 38 Johnson L B, Kauffman C A. Voriconazole: a new triazole antifungal agent.  Clin Infect Dis. 2003;  36 630-637
• 39 Deresinski S C, Stevens D A. Caspofungin.  Clin Infect Dis. 2003;  36 1445-1457
• 40 Centers for Disease Control and Prevention; Infectious Disease Society of America; American Society of Blood and Marrow Transplantation. . Guidelines for preventing opportunistic infections among hematopoietic stemcell transplant recipients.  MMWR Recomm Rep. 2000;  49(RR-10) 1-125 , CE1-7
• 41 Tablan O C, Anderson L J, Besser R, Bridges C, Hajjeh R. CDC: Healthcare Infection Control Practices Advisory Committee Guidelines for preventing health-care-associated pneumonia, 2003: recommendations of CDC and the Healthcare Infection Control Practices Advisory Committee.  MMWR Recomm Rep. 2004;  53(RR-3) 1-36