Elderly haematological patients with chemotherapy-induced febrile neutropenia have similar rates of infection and outcome to younger adults: a prospective study of risk-adapted therapy
Julio García-Suárez
Service of Haematology, Príncipe de Asturias University Hospital, Department of Medicine, University of Alcalá, Alcalá de Henares, Madrid, Spain
Search for more papers by this authorIsabel Krsnik
Service of Haematology, Príncipe de Asturias University Hospital, Department of Medicine, University of Alcalá, Alcalá de Henares, Madrid, Spain
Search for more papers by this authorEduardo Reyes
Service of Haematology, Príncipe de Asturias University Hospital, Department of Medicine, University of Alcalá, Alcalá de Henares, Madrid, Spain
Search for more papers by this authorDunia De Miguel
Service of Haematology, Príncipe de Asturias University Hospital, Department of Medicine, University of Alcalá, Alcalá de Henares, Madrid, Spain
Search for more papers by this authorNuria Hernanz
Service of Haematology, Príncipe de Asturias University Hospital, Department of Medicine, University of Alcalá, Alcalá de Henares, Madrid, Spain
Search for more papers by this authorMohamed Barr-Alí
Service of Haematology, Príncipe de Asturias University Hospital, Department of Medicine, University of Alcalá, Alcalá de Henares, Madrid, Spain
Search for more papers by this authorCarmen Burgaleta
Service of Haematology, Príncipe de Asturias University Hospital, Department of Medicine, University of Alcalá, Alcalá de Henares, Madrid, Spain
Search for more papers by this authorJulio García-Suárez
Service of Haematology, Príncipe de Asturias University Hospital, Department of Medicine, University of Alcalá, Alcalá de Henares, Madrid, Spain
Search for more papers by this authorIsabel Krsnik
Service of Haematology, Príncipe de Asturias University Hospital, Department of Medicine, University of Alcalá, Alcalá de Henares, Madrid, Spain
Search for more papers by this authorEduardo Reyes
Service of Haematology, Príncipe de Asturias University Hospital, Department of Medicine, University of Alcalá, Alcalá de Henares, Madrid, Spain
Search for more papers by this authorDunia De Miguel
Service of Haematology, Príncipe de Asturias University Hospital, Department of Medicine, University of Alcalá, Alcalá de Henares, Madrid, Spain
Search for more papers by this authorNuria Hernanz
Service of Haematology, Príncipe de Asturias University Hospital, Department of Medicine, University of Alcalá, Alcalá de Henares, Madrid, Spain
Search for more papers by this authorMohamed Barr-Alí
Service of Haematology, Príncipe de Asturias University Hospital, Department of Medicine, University of Alcalá, Alcalá de Henares, Madrid, Spain
Search for more papers by this authorCarmen Burgaleta
Service of Haematology, Príncipe de Asturias University Hospital, Department of Medicine, University of Alcalá, Alcalá de Henares, Madrid, Spain
Search for more papers by this authorAbstract
Summary. We prospectively evaluated 131 consecutive episodes of fever and chemotherapy-induced neutropenia in 85 adults with haematological malignancies to determine whether older patients (aged < 60 years) have different causes of fever and outcome than younger adults (aged < 60 years). Patients were stratified into high-risk and low-risk groups according to previously published criteria. High-risk patients received ceftazidime plus amikacin and low-risk patients received ceftazidime alone. All patients were hospitalized until fever and neutropenia resolved. Ninety one high-risk episodes were documented: 56 occurring in older patients (mean age 69 years) and 35 in younger adults (mean age 45 years). Non-Hodkgin's lymphoma and acute myeloid leukaemia were the most frequent underlying neoplasias in both age groups. Intensity of chemotherapy was similar in both age groups. Mean neutrophil count at entry, median duration of neutropenia, rate of documented infection, incidence of bacteraemia, response to therapy, overall mortality and infectious mortality were similar in the two high-risk age subgroups. The elderly subgroup had a trend to have more Gram-negative infections and the younger patients more Gram-positive infections. In addition, 40 low-risk episodes were registered: 29 in elderly patients (mean age 68 years) and 11 in younger patients (mean age 44 years). Elderly low-risk patients had more concurrent diseases that younger ones (P = 0·124). Mean neutrophil count at entry, median duration of severe neutropenia and rate of response were similar in the two age subgroups. All low-risk patients survived. In conclusion, elderly haematological cancer patients with febrile neutropenia show similar rates of infection and outcome to younger ones.
References
- Armitage, J.O. & Potter, J.F. (1984) Aggressive chemotherapy for diffuse histiocytic lymphoma in the elderly. Journal of the American Geriatrics Society, 32, 269–273.
- Balducci, L. & Corcoran, M.B. (2000) Antineoplastic chemotherapy of the older cancer patient. Hematology/Oncology Clinics of North America, 14, 193–212.
- Balducci, L., Hardy, C.L. & Lyman, G.H. (2001) Hematopoietic growth factors in the older cancer patient. Current Opinion in Hematology, 8, 170–187.
-
Bash, R.O.,
Katz, J.A.,
Cash, J.V. &
Buchanan, G.R. (1994) Safety and cost effectiveness of early hospital discharge of lower risk children with cancer admitted for fever and neutropenia.
Cancer, 74, 189–196.
10.1002/1097-0142(19940701)74:1<189::AID-CNCR2820740130>3.0.CO;2-7 CAS PubMed Web of Science® Google Scholar
- Bastion, Y., Blay, J.-Y., Divine, M., Brice, P., Bordessoule, D., Sebban, C., Blanc, M., Tilly, H., Lederlin, P., Deconinck, E., Salles, B., Dumontet, C., Briere, J. & Coiffier, B. (1997) Elderly patients with aggressive non-Hodgkin's lymphoma: disease presentation, response to treatment and survival. A Groupe d'Etude des Lymphomes de l'Adulte on 453 patients older than 69 years. Journal of Clinical Oncology, 15, 2945–2953.
-
Begg, C.B. &
Carbone, P. (1983) Clinical trials and drug toxicity in the elderly. The experience of the Eastern Cooperative Oncology Group.
Cancer, 52, 1986–1992.
10.1002/1097-0142(19831201)52:11<1986::AID-CNCR2820521103>3.0.CO;2-7 CAS PubMed Web of Science® Google Scholar
- Bodey, G.P. (2001) Pseudomonas aeruginosa infections in cancer patients. Current Opinion in Infectious Diseases, 14, 403–407.
- Crossley, K.B. & Peterson, P.K. (2000) Infections in the elderly. In: Principles and Practice of Infectious Diseases 5th edn. (ed. by G.L. Mandell, J.E. Bennett & R. Dolin) pp. 3164–3169. Churchill Livingstone, New York.
- EORTC International Antimicrobial Therapy Cooperative Group and the National Cancer Institute of Canada-Clinical Trials Group (1991) Vancomycin added to empirical combination antibiotic therapy for fever in granulocytopenic cancer patients. Journal of Infectious Diseases, 163, 951–958.
- Ferrara, F., Morabito, F., Latagliata, R., Martino, B., Annunziata, M., Oliva, E., Schiavone, E.M., Pollio, F., Palmieri, S., Gianfaldoni, G. & Leoni, F. (2001) Aggressive salvage treatment is not appropriate for the majority of elderly patients with acute myeloid leukemia relapsing after first complete remission. Haematologica, 86, 814–820.
- Freifeld, A., Marchigiani, D. & Walsh, T. (1999) A double-blind comparison of empirical oral and intravenous antibiotic therapy for low-risk febrile patients with neutropenia during cancer chemotherapy. New England Journal of Medicine, 341, 305–311.
- Gaynor, E.R. & Fisher, R.I. (1995) Chemotherapy of intermediate-grade non-Hodgkin's lymphoma: ‘more’ or ‘less’ better? Oncology (Huntington), 9, 1273–1279.
-
Gelman, R.S. &
Taylor, S.G. (1984) Cyclophosphamide, Methotrexate and 5Fluoracil chemotherapy in women more than 65 year old with advanced breast cancer. The elimination of age trends in toxicity by using doses based on creatinine clearance.
Journal of Clinical Oncology, 2, 1406–1414.
10.1200/JCO.1984.2.12.1404 Google Scholar
- Govannozzi-Bannon, S., Rademaker, A., Lai, G. & Benson, A.B. (1994) Treatment tolerance of elderly cancer patients entered onto phase II clinical trials. An Illinois Cancer Center Study. Journal of Clinical Oncology, 12, 2447–2452.
- Hughes, W.T., Armstrong, D., Bodey, G.P., Brown, A.E., Edwards, J.E., Feld, R., Pizzo, P., Rolston, K.V., Shenep, J.L. & Young, L.S. (1997) 1997 guidelines for the use of antimicrobial agents in neutropenic patients with unexplained fever. Clinical Infectious Diseases, 25, 551–573.
- Karthaus, M., Wolf, H.H., Kampfe, D., Egerer, G., Ritter, J., Peters, G., Sudhoff, T., Franke, A., Heil, G., Kullmann, K.H. & Jurgens, H. (1998) Ceftriaxone monotherapy in the treatment of low-risk febrile neutropenia. Chemotherapy, 44, 343–354.
- Kern, W.V., Cometta, A., De Bock, R., Langenaeken, J., Paesmans, M. & Gaya, H. (1999) Oral versus intravenous empirical antimicrobial therapy for fever in patients with granulocytopenia who are receiving cancer chemotherapy. New England Journal of Medicine, 341, 312–318.
- Kibbler, C.C. & Prentice, H.G. (1999) Pathogen ‘shift’ in febrile neutropenia. Current Opinion in Infectious Diseases, 12, 351–354.
- Klastersky, J., Paesmans, M., Rubenstein, E.B., Boyer, M., Elting, L., Feld, R., Gallagher, J., Herrstedt, J., Rapoport, B., Rolston, K. & Talcott, J. (2000) The Multinational Association for supportive Care in Cancer risk index: a multinational scoring system for identifying low-risk febrile neutropenic cancer patients. Journal of Clinical Oncology, 18, 3038–3051.
- Lancet, J.E., Willman, C.L. & Bennett, J.M. (2000) Acute myelogenous leukemia and aging: clinical interactions. Hematology/Oncology Clinics of North America, 16, 251–268.
- Löwenberg, B. (2001) Managing therapy in older adult patients with acute myeloid leukaemia. Seminars in Hematology, 38, 10–16.
- Mackowiak, P.A. & Durack, D.T. (2000) Fever of unknown origin. In: Principles and Practice of Infectious Diseases. 5th edn. pp. 622–633. Churchill Livingstone, New York.
- Morittu, L., Earl, H.M., Souhami, R.L., Ash, C.M., Tobias, J.S., Geddes, D.M., Harper, P.G. & Spiro, S.G. (1989) Patients at risk of chemotherapy-associated toxicity in small cell lung cancer. British Journal of Cancer, 59, 801–814.
- Mullen, C.A. (2001) Which children with fever and neutropenia can be safely treated as outpatients? British Journal of Haematology, 112, 832–837.
- Pizzo, P.A., Hathorn, J.R., Hiemenz, J., Browne, M., Commers, J., Cotton, D., Gress, J., Longo, D., Marshall, D., McKnight, J., Rubin, M., Skelton, J., Thaler, M. & Wesley, R. (1986) A randomised trial comparing ceftazidime alone with combination antibiotic treatment in cancer patients with fever and neutropenia. New England Journal of Medicine, 315, 552–558.
- Rackoff, W.R., Gonin, R., Robinson, C., Kreissman, S.G. & Breitfeld, P.B. (1996) Predicting the risk of bacteraemia in children with fever and neutropenia. Journal of Clinical Oncology, 14, 919–924.
- Rolston, K.V.I. (1999) New trends in patient management: risk-based therapy for febrile patients with neutropenia. Clinical Infectious Diseases, 29, 515–521.
- Rowe, J.M. (2000) Treatment of acute myelogenous leukemia in older adults. Leukemia, 14, 480–487.
- Schimpff, S.C. (1985) Overview of empiric antibiotic therapy for the febrile neutropenic patient. Reviews of Infectious Diseases, 7, s734–s740.
- Sonneveld, P., De Ridder, M., Van Der Lelie, H., Nieuwenhuis, K., Schouten, H., Mulder, A., Van Reijswoud, I., Hop, W. & Lowenberg, B. (1995) Comparison of doxorubicin and mitoxantrone in the treatment of elderly patients with advanced diffuse non-Hodgkin's lymphoma using CHOP vs CNOP chemotherapy. Journal of Clinical Oncology, 13, 2530–2539.
- Stone, R.M., Berg, D.T., George, S.L., Dodge, R.K., Paciucci, P.A., Schulman, P., Lee, E.J., Moore, J.O., Powell, B.L. & Schiffer, C.A. (1995) Granulocyte-stimulating factor after initial chemotherapy for elderly patients with primary acute myelogenous leukaemia. New England Journal of Medicine, 332, 1671–1677.
- Talcott, J.A., Finberg, R., Mayer, R.J. & Goldman, L. (1988) The medical course of cancer patients with fever and neutropenia. Clinical identification of a low-risk subgroup at presentation. Archives of Internal Medicine, 148, 2561–2568.
- Talcott, J.A., Siegel, R.D., Finberg, R. & Goldman, L. (1992) Risk assessment in cancer patients with fever and neutropenia: a prospective, two-center validation of a prediction rule. Journal of Clinical Oncology, 10, 316–322.
- Tirelli, U., Errante, D., Van Glabbeke, M., Teodorovic, I., Kluin-Nelemans, J.C., Thomas, J., Bron, D., Rosti, G., Somers, R., Zagonel, V. & Noordijk, E.M. (1998) CHOP is the standard regimen in patients ≥ 70 years of age with intermediate and high grade Non-Hodgkin's lymphoma: results of a randomized study of the European organization for the Research and Treatment of Cancer Lymphoma Cooperative Study. Journal of Clinical Oncology, 16, 27–34.
-
Yancik, R. (1997) Cancer burden in the aged: an epidemiologic and demographic overview.
Cancer, 80, 1273–1283.
10.1002/(SICI)1097-0142(19971001)80:7<1273::AID-CNCR13>3.0.CO;2-4 CAS PubMed Web of Science® Google Scholar
- Zinzani, P.G., Storti, S., Zaccaria, A., Moretti, L., Magagnoli, M., Pavone, E., Gentilini, P., Guardigni, L., Gobbi, M., Fattori, P.P., Falini, B., Lauta, V.M., Bendandi, M., Gherlinzoni, F., De Renzo, A., Zaja, F., Mazza, P., Volpe, E., Bocchia, M., Aitini, E., Tabanelli, M., Leone, G. & Tura, S. (1999) Elderly aggressive histology non-Hodgkin's lymphoma: first line VNCOP-B regimen: experience on 350 patients. Blood, 94, 33–38.