Abstract
We prospectively tested the hypothesis that prevention of herpes simplex virus infection with acyclovir might also reduce the incidence of bacterial infections in adult patients with acute leukaemia. During the first induction therapy a double-blind, randomized and placebo-controlled study was undertaken. Fifty-two patients were treated with 200 mg acyclovir orally four times daily throughout the induction period, whereas 55 patients received placebo. The groups were comparable with regard to age, cytotoxic chemotherapy and duration of neutropenia. Bacteraemias were significantly fewer in the acyclovir group (20 versus 41 episodes; P=0.007). The number of isolated microorganisms causing bacterial or fungal infections was also lower during acyclovir prophylaxis (52 isolates, versus 93 isolates; P=0.02). There was no significant differenc between the groups with regard to the number of clinically documented infections or fevers of unknown origin. Herpes simplex virus isolations occurred only in the placebo group (P=0.001). Thus, oral acyclovir prophylaxis was associated with reductions of all microbiologically documented infections suggesting that prevention of herpes simplex virus reactivation in acute leukaemia patients may reduce the occurrence of other infections.
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References
Abramson JS, Mills EL (1988) Depression of neutrophil function induced by viruses and its role in secondary microbial infections. Rev Infect Dis 10:326–341
Anderson H, Scarffe JH, Sutton RNP, Hickmott E, Brigden D, Burke C (1984) Oral acyclovir prophylaxis against herpes simplex virus in non-Hodgkin lymphoma and acute lymphoblastic leukemia patients receiving remission induction therapy. A randomised double blind, placebo controlled trial. Br J Cancer 50:45–49
Buss DH, Scharyj M (1979) Herpesvirus infection in esophagus and other visceral organs in adults. Incidence and clinical significance. Am J Med 66:457–462
EORTC (1978) Three antibiotic regimens in the treatment of infection in febrile granulocytic patients with cancer. J Infect Dis 137:14–29
Gale RP, Cline MJ (1977) High remission induction rate in acute leukaemia. Lancet I:497–499
Gerson SL, Friedman HM, Cines DB (1985) Viral infection of vascular endothelial cells alters production of colony-stimulating activity. J Clin Invest 76:1382–1390
Gluckman E, Devergie A, Melo R, Nebout T, Lotsberg J, Zhao XM, Gomez-Morales M, Mazeron MC (1983) Prophylaxis of herpes infections after bone-marrow transplantation by oral acyclovir. Lancet II:706–708
Hann IM, Prentice HG, Blacklock HA, Ross MGR, Brigden D, Rosling AE, Burke C, Crawford DH, Brumfitt W, Hoffbrand AV (1983) Acyclovir prophylaxis against herpes virus infections in severely immunocompromised patients: randomised double blind trial. Br Med J 287:384–388
Heimdahl A, Mattsson T, Dahllöf G, Lönnqvist B, Ringdén O (1989) The oral cavity as a portal of entry for local and systemic early infections in patients treated with bone marrow transplantation. Oral Surg Oral Med Oral Pathol 68:711–716
Lam MT, Pazin GJ, Armstrong JA, Monto HO (1981) Herpes simplex infection in acute myelogenous leukemia and other hematologic malignancies: a prospective study. Cancer 48:2168–2171
Leynette E, Balows A, Hauser W Jr, Shadowy HJ (eds) (1980) Manual of clinical microbiology, 3rd edn. American Society of Microbiology, Washington, DC
Lundgren G, Wilczek H, Lönnqvist B, Lindholm A, Wahren B, Ringdén O (1985) Acyclovir prophylaxis in bone marrow transplant recipients. Scand J Infect Dis Suppl 47:137–144
Newman KA, Schimpff SC, Young VM, Wiernik PH (1981) Lessons learned from surveillance cultures in patients with acute nonlymphocytic leukemia. Usefulness for epidemiologic, preventive and therapeutic research. Am J Med 70:423–431
Palmblad J, Lönnqvist B, Carlsson B, Grimfors G, Järnmark M, Lerner R, Ljungman P, Nyström-Rosander C, Petrini B, Öberg G (1992) Oral ketoconazole prophylaxis for Candida infections during induction therapy for acute leukaemia in adults: more bacteriaemias. J Intern Med 231:363–370
Paul C, Tidefelt U, Gahrton G, Björkhlm M, Järnmark M, Killander A, Kimby E, Liliemark J, Lindeberg A, Lindquist R, Lockner D, Lönnqvist B, Mellstedt H, Merk K, Palmblad J, Peterson C, Simonsson B, Stalfelt A-M, Sundström C, Wadman B, Wedelin C, Udén AM, Öberg G, Öst Å (1991) A randomized comparison of doxorubicin and doxorubicin-DNA in the treatment of acute non lymphoblastic leukemia. Leukemia Lymphoma 3:355–364
Pizzo PA, Robichaud KJ, Edwards BK, Schumaker C, Kramer BS, Johnson A (1983) Oral antibiotic prophylaxis in patients with cancer: a double-blind randomized placebo-controlled trial. J Pediatr 102:125–133
Ringdén O, Heimdahl A, Lönnqvist B, Malmborg A-S, Wilczek H (1984) Decreased incidence of Viridans streptococcal septicemia in allogenic bone marrow transplant recipients after the introduction of acyclovir. Lancet I:744
Rouse BT, Horohov DW (1986) Immunosuppression in viral infections. Rev Infect Dis 8:850–873
Sánches-Fayos J, Outeirino E, Villalobos C, Paniagua C, Calabuig T, Lite M, Figuera A, Pérez-Rus G, Prieto E, Serrano J, Escudero A (1985) Acute lymphoblastic leukaemia in adults: results of a “total-therapy” programme in 47 patients over 15 years old. Br J Haematol 59:686–696
Saral R, Burns WH, Laskin OL, Santos GW, Lietman PS (1981) Acyclovir prophylaxis of herpes-simplex-virus infections. A randomized, double-blind, controlled trial in bonemarrow-transplant recipients. N Engl J Med 305:63–67
Saral R, Ambinder RF, Burns WH, Angelopoulos CM, Griffin DE, Burke PJ, Lietman PS (1983) Acyclovir prophylaxis against herpex simplex virus infection in patients with leukemia. A randomized, double-blind, placebo-controlled study. Ann Intern Med 99:773–776
Schimpff SC (1981) Surveillance cultures. J Infect Dis 144:81–84
Sundqvist V-A, Linde A, Wahren B (1984) Virus-specific immunoglobulin G subclasses in herpes simplex and varicallazoster virus infections. J Clin Microbiol 20:94–98
Wade JC, Newton B, Flournoy N, Meyers JD (1984) Oral acyclovir for prevention of herpes simplex virus reactivation after marrow transplantation. Ann Intern Med 100:823–828
Wong K, Hirsch MS (1984) Herpes virus infections in patients with neoplastic disease. Am J Med 75:464–478
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The following investigators participated in this study: Magnus Björkholm, Karl Merk, Anders Åhre, Department of Medicine, Danderyd Hospital, Danderyd; Lars Engstedt, Ann-Maria Udén, Department of Medicine, Stockholm Söder Hospital, Stockholm; Gösta Gahrton, Ragnhild Lindquist, Dieter Lockner, Christer Paul, Department of Medicine, Huddinge Hospital, Huddinge; Andreas Killander, Bengt Simonsson, Department of Medicine, University Hospital, Uppsala; Bengt Wadman, Ann-Marie Stalfelt, Department of Medicine, Medical Centre Hospital, Örebro; Christer Sundström, Department of Pathology, University Hospital, Uppsala; Åke Öst, Department of Pathology, Karolinska Hospital, Stockholm; Bo Johansson, Christina Simonsson-Lindemalm, Håkan Mellstedt, Christina Wedelin, Radiumhemmet, Karolinska Hospital, Stockholm
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Lönnqvist, B., Palmblad, J., Ljungman, P. et al. Oral acyclovir as prophylaxis for bacterial infections during induction therapy for acute leukaemia in adults. Support Care Cancer 1, 139–144 (1993). https://doi.org/10.1007/BF00366060
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DOI: https://doi.org/10.1007/BF00366060