Annals of Hematology

, Volume 82, Supplement 2, pp S105–S117 | Cite as

Antimicrobial therapy of unexplained fever in neutropenic patients

Guidelines of the Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Oncology (DGHO), Study Group Interventional Therapy of Unexplained Fever, Arbeitsgemeinschaft Supportivmassnahmen in der Onkologie (ASO) of the Deutsche Krebsgesellschaft (DKG—German Cancer Society)
  • H. Link
  • A. Böhme
  • O. A. Cornely
  • K. Höffken
  • O. Kellner
  • W. V. Kern
  • R. Mahlberg
  • G. Maschmeyer
  • M. R. Nowrousian
  • H. Ostermann
  • M. Ruhnke
  • O. Sezer
  • X. Schiel
  • M. Wilhelm
  • H. W. Auner
Article

Abstract

Cytostatic chemotherapy of hematological malignancies is often complicated by neutropenia, which increases the risk of infections, especially if the neutrophil count is below 500/μl. Frequently, fever is the first, and in most patients the only, sign of an infection. Unexplained fever is defined as follows: temperature of ≥38.3°C or ≥38.0°C for at least 1 h, or measured twice within 12 h, if the neutrophil count is <500/μl or <1000/μl with predicted decline to 500/μl. Different risk categories can be identified according to the duration of neutropenia: low risk ≤5 days, intermediate risk 6–9 days, high risk ≥10 days. An empirical mono- or duotherapy with antipseudomonal and antistreptococcal agents should be initiated immediately. In the low risk patient group, oral therapy with cipro-, levo-, or ofloxacin combined with amoxicillin/clavulanic acid is permissible. For standard and high risk patients, monotherapy can be carried out with either ceftazidime, cefepime, piperacillin with tazobactam or a carbapenem. In duotherapy, a single dose of an aminoglycoside is combined with acylaminopenicillin or a cephalosporin of the third or fourth generation. The addition of glycopeptides in empirical therapy should only be considered in the presence of severe mucositis, or if a catheter-associated infection is suspected. If fever persists after 72–96 h of first-line therapy with antibiotics, the regimen should be modified (with the exception of e.g. coagulase-negative staphylococci infections, because these infections take longer to respond). Intermediate risk patients should additionally receive an aminoglycoside after monotherapy (penicillin or a cephalosporin). If a carbapenem was administered for monotherapy, this can be followed by a quinolone and/or a glycopeptide. In the high risk group, the same modifications should be made as in the intermediate risk group but with additional systemic antifungal treatment. In the presence of unexplained fever, fluconazole can be administered at first, but if this fails, amphotericin B (conventional or liposomal), itraconazole, voriconazole or caspofungin should be started. After defervescence to <38°C, treatment should be continued for 7 days if the neutrophil count is <1000/μl, and for 2 days if the neutrophil count is >1000/μl.

Keywords

Unexplained fever Neutropenia Neutropenic fever Antibiotic therapy Antifungal therapy 

References1

  1. 1.
    Recommendations for preventing the spread of vancomycin resistance: recommendations of the Hospital Infection Control Practises Advisory Committee (HICPAC) (1995) MMWR Rec Rep 44 (RR-12):1–13Google Scholar
  2. 2.
    Behre G, Link H, Maschmeyer G, Meyer P, Paaz U, Wilhelm M, Hiddemann W (1998) Meropenem monotherapy versus combination therapy with ceftazidime and amikacin for empirical treatment of febrile neutropenic patients. Ann Hematol 76:73–78CrossRefPubMedGoogle Scholar
  3. 3.
    Bochud P-Y, Calandra T, Francioli P (1994) Bacteremia due to viridans streptococci: a review. Am J Med 97:256–264PubMedGoogle Scholar
  4. 4.
    Boogaerts M, Winston DJ, Bow EJ, Garber G, Reboli AC, Schwarer AP, Novitzky N, Boehme A, Chwetzoff E, De Beule K (2001) Intravenous and oral itraconazole versus intravenous amphotericin B deoxycholate as empirical antifungal therapy for persistent fever in neutropenic patients with cancer who are receiving broad-spectrum antibacterial therapy. A randomized, controlled trial. Ann Intern Med 135:412–422PubMedGoogle Scholar
  5. 5.
    Cometta A, Baumgartner JD, Lew D, Zimmerli W, Pittet D, Chopart P, Schaad U, Herter C, Eggimann P, Huber O, et al. (1994) Prospective randomized comparison of imipenem monotherapy with imipenem plus netilmicin for treatment of severe infections in nonneutropenic patients. Antimicrob Agents Chemother 38:1309–1313PubMedGoogle Scholar
  6. 6.
    Cometta A, Calandra T, Gaya H, Zinner SH, DeBock R, Del Favero A, Bucaneve G, Crokaert F, Kern WV, Klastersky J, Langenaeken J, Micozzi A, Padmos A, Paesmans M, Viscoli C, Glauser MP (1996) Monotherapy with meropenem versus combination therapy with ceftazidime plus amikacin as empiric therapy for fever in granulocytopenic patients with cancer. Antimicrob Agents Chemother 40:1108–1115PubMedGoogle Scholar
  7. 7.
    Cometta A, Zinner S, De Bock R, Calandra T, Gaya H, Klastersky J, Langenaeken J, Paesmans M, Viscoli C, Glauser MP (1995) Piperacillin-tazobactam plus amikacin versus ceftazidime plus amikacin as empiric therapy for fever in granulocytopenic patients with cancer. The International Antimicrobial Therapy Cooperative Group of the European Organization for Research and Treatment of Cancer. Antimicrob Agents Chemother 39:445–452Google Scholar
  8. 8.
    Cornely O, Hiddemann W, Link H, Maschmeyer G, Glaß B, Buchheidt D, Wilhelm M, Büchner T, Lipp T, Haas R, Heinemann V, Helmerking M, Adam D (1998) Interventional antimicrobial therapy in febrile neutropenic patients. Paul-Ehrlich-Society for Chemotherapy (PEG) Study II. Plunkett W (ed) Acute Leukemias VII; Experimental approaches and novel therapies. Springer, Berlin Heidelberg New York, pp 1045–1049Google Scholar
  9. 9.
    Cornely OA, Reichert D, Buchheidt D, Maschmeyer G, Wilhelm M, Schiel X, Glaß B, Fätkenheuer G, Link H, Helmerking M, Adam D, Hiddemann W, for the Paul Ehrlich Gesellschaft (2001) Three armed multicenter randomized study on the empiric treatment of neutropenic fever in a high risk patient population (PEG study III). 41th Interscience Conference on antimicrobial agents and chemotherapy, 16-19 December 2002, Chicago, p L-775Google Scholar
  10. 10.
    Cornely OA, Schirmacher P (2001) Clinical picture: Bacterial translocation in neutropenic sepsis. Lancet 358:1842CrossRefPubMedGoogle Scholar
  11. 11.
    Davis DD, Raebel MA (1998) Ambulatory management of chemotherapy-induced fever and neutropenia in adult cancer patients. Ann Pharmacother 32:1317–1323Google Scholar
  12. 12.
    de Pauw BE, Deresinski SC, Feld R, Lane Allman EF, Donnelly JP (1994) Ceftazidime compared with piperacillin and tobramycin for the empiric treatment of fever in neutropenic patients with cancer. A multicenter randomized trial. The Intercontinental Antimicrobial Study Group. Ann Intern Med 120:834–844PubMedGoogle Scholar
  13. 13.
    Deaney NB, Tate H (1996) A meta-analysis of clinical studies of imipenem-cilastatin for empirically treating febrile neutropenic patients. J Antimicrob Chemother 37:975–986Google Scholar
  14. 14.
    Dompeling EC, Donnelly JP, Deresinski SC, Feld R, Lane-Allman EF, de Pauw BE (1996) Early identification of neutropenic patients at risk of grampositive bacteraemia and the impact of empirical administration of vancomycin. Eur J Cancer 32A:1332–1339CrossRefGoogle Scholar
  15. 15.
    Edwards JE Jr, Bodey GP, Bowden RA, Buchner T, de Pauw BE, Filler SG, Ghannoum MA, Glauser M, Herbrecht R, Kauffman CA, Kohno S, Martino P, Meunier F, Mori T, Pfaller MA, Rex JH, Rogers TR, Rubin RH, Solomkin J, Viscoli C, Walsh TJ, White M (1997) International Conference for the Development of a Consensus on the Management and Prevention of Severe Candidal Infections. Clin Infect Dis 25:43–59Google Scholar
  16. 16.
    Ehninger G, Schuler U, Brammer S, Aulitzky W, Binder C, Boehme E, Egerer G, Ganser A, Peschel C, Schwerdfeger R, Silling G, Zander A, Wandt H (2002) Intravenous Followed by Oral Itraconazole Versus Intravenous Amphotericin B as Empirical Antifungal Therapy for Febrile Neutropenic Haematological Cancer Patients. Blood :Abst 3631.http://www.abstracts-on-line.com/abstracts/hemphiladelphia02/search/results.asp?Num=0%2E1328043Google Scholar
  17. 17.
    EORTC (1993) Efficacy and toxicity of single daily doses of amikacin and ceftriaxone versus multiple daily doses of amikacin and ceftazidime for infection in patients with cancer and granulocytopenia. The International Antimicrobial Therapy Cooperative Group of the European Organization for Research and Treatment of Cancer. Ann Intern Med 119:584–593PubMedGoogle Scholar
  18. 18.
    EORTC, International Antimicrobial Therapy Cooperative Group (1987) Ceftazidime combined with a short or long course of amikacin for empirical therapy of gram-negative bacteremia in cancer patients with granulocytopenia. N Engl J Med 317:1692–1698Google Scholar
  19. 19.
    EORTC, International Antimicrobial Therapy Cooperative Group (1989) Empiric antifungal therapy in febrile granulocytopenic patients. Am J Med 86:668–672PubMedGoogle Scholar
  20. 20.
    Erjavec Z, de Vries Hospers HG, van Kamp H, Van der Waaij D, Halie MR, Daenen SM (1994) Comparison of imipenem versus cefuroxime plus tobramycin as empirical therapy for febrile granulocytopenic patients and efficacy of vancomycin and aztreonam in case of failure. Scand J Infect Dis 26:585–595Google Scholar
  21. 21.
    European Organization for Research and Treatment of Cancer (EORTC) International Antimicrobial Therapy Cooperative Group (1991) Vancomycin added to empirical combination antibiotic therapy for fever in granulocytopenic cancer patients. European Organization for Research and Treatment of Cancer (EORTC) International Antimicrobial Therapy Cooperative Group and the National Cancer Institute of Canada-Clinical Trials Group [published erratum appears in J Infect Dis 1991 Oct;164(4):832] [see comments]. J Infect Dis 163:951-958Google Scholar
  22. 22.
    Freifeld A, Marchigiani D, Walsh T, Chanock S, Lewis L, Hiemenz J, Hiemenz S, Hicks JE, Gill V, Steinberg SM, Pizzo PA (1999) A double-blind comparison of empirical oral and intravenous antibiotic therapy for low-risk febrile patients with neutropenia during cancer chemotherapy [see comments]. N Engl J Med 341:305–311PubMedGoogle Scholar
  23. 23.
    Freifeld AG, Walsh T, Marshall D, Gress J, Steinberg SM, Hathorn J, Rubin M, Jarosinski P, Gill V, Young RC, Pizzo PA (1995) Monotherapy for fever and neutropenia in cancer patients: A randomized comparison of ceftazidime versus imipenem. J Clin Oncol 13:165–176PubMedGoogle Scholar
  24. 24.
    Furno P, Bucaneve G, Del Favero A (2002) Monotherapy or aminoglycoside-containing combinations for empirical antibiotic treatment of febrile neutropenic patients: a meta-analysis. Lancet Infect Dis 2:231–242CrossRefGoogle Scholar
  25. 25.
    Gilbert DN, Dworkin RJ, Raber SR, Leggett JE (1997) Outpatient parenteral antimicrobial-drug therapy. N Engl J Med 337:829–838CrossRefGoogle Scholar
  26. 26.
    Herbrecht R, Denning DW, Patterson TF, Bennett JE, Greene RE, Oestmann JW, Kern WV, Marr KA, Ribaud P, Lortholary O, Sylvester R, Rubin RH, Wingard JR, Stark P, Durand C, Caillot D, Thiel E, Chandrasekar PH, Hodges MR, Schlamm HT, Troke PF, de Pauw B (2002) Voriconazole versus amphotericin B for primary therapy of invasive aspergillosis. N Engl J Med 347:408–415Google Scholar
  27. 27.
    Hidalgo M, Hornedo J, Lumbreras C, Trigo JM, Colomer R, Perea S, Gomez C, Ruiz A, Garcia-Carbonero R, Cortes-Funes H (1999) Outpatient therapy with oral ofloxacin for patients with low risk neutropenia and fever: a prospective, randomized clinical trial. Cancer 85:213–219CrossRefPubMedGoogle Scholar
  28. 28.
    Hughes WT, Armstrong D, Bodey GP, Bow EJ, Brown AE, Calandra T, Feld R, Pizzo PA, Rolston KV, Shenep JL, Young LS (2002) 2002 guidelines for the use of antimicrobial agents in neutropenic patients with cancer. Clin Infect Dis 34:730–751CrossRefPubMedGoogle Scholar
  29. 29.
    Kaplan AH, Weber DJ, Davis L, Israel F, Wells RJ (1991) Short courses of antibiotics in selected febrile neutropenic patients. Am J Med Sci 302:353–354Google Scholar
  30. 30.
    Kern WV, 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. International Antimicrobial Therapy Cooperative Group of the European Organization for Research and Treatment of Cancer [see comments]. N Engl J Med 341:312–318PubMedGoogle Scholar
  31. 31.
    Klastersky J, Paesmans M, Rubenstein EB, 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. J Clin Oncol 18:3038–3051PubMedGoogle Scholar
  32. 32.
    Link H, Hess CF, Albers P, Schmoll H-J, Reimers HJ, von Minckwitz G, Nowrousian MR, Welte K (2001) Rationale Therapie mit den hämatopoetischen Wachstumsfaktoren G-CSF und GM-CSF. Onkologe 7:1329–1341CrossRefGoogle Scholar
  33. 33.
    Link H, Hiddemann W, Maschmeyer G, Buchheidt D, Glass B, Cornely OA, Wilhelm M, Helmerking M, Adam D, and the PEG-Study group (1997) Antimicrobial therapy in neutropenic patients with unexplained fever, PEG-Study II. Onkologie 20 (Suppl 1):132Google Scholar
  34. 34.
    Link H, Maschmeyer G, Meyer P, Hiddemann W, Stille W, Helmerking M, Adam D, for the study group of the Paul Ehrlich Society for Chemotherapy (1994) Interventional antimicrobial therapy in febrile neutropenic patients. Ann Hematol 69:231–243PubMedGoogle Scholar
  35. 35.
    Malik IA, Moid I, Aziz Z, Khan S, Suleman M (1998) A randomized comparison of fluconazole with amphotericin B as empiric anti-fungal agents in cancer patients with prolonged fever and neutropenia. Am J Med 105:478–483PubMedGoogle Scholar
  36. 36.
    Marr KA (2002) Empirical antifungal therapy--new options, new tradeoffs. N Engl J Med 346:278–280CrossRefPubMedGoogle Scholar
  37. 37.
    Mora-Duarte J, Betts R, Rotstein C, Colombo AL, Thompson-Moya L, Smietana J, Lupinacci R, Sable C, Kartsonis N, Perfect J, the Caspofungin Invasive Candidiasis Study Group (2002) Comparison of Caspofungin and Amphotericin B for Invasive Candidiasis. N Engl J Med 347:2020–2029CrossRefPubMedGoogle Scholar
  38. 38.
    Mullen CA, Buchanan GR (1990) Early hospital discharge of children with cancer treated for fever and neutropenia: identification and management of the low-risk patient. J Clin Oncol 8:1998–2004PubMedGoogle Scholar
  39. 39.
    Ozer H, Armitage JO, Bennett CL, Crawford J, Demetri GD, Pizzo PA, Schiffer CA, Smith TJ, Somlo G, Wade JC, Wade JL, III, Winn RJ, Wozniak AJ, Somerfield MR (2000) 2000 update of recommendations for the use of hematopoietic colony- stimulating factors: evidence-based, clinical practice guidelines. http://www.jco.org/cgi/content/full/18/20/3558. J Clin Oncol 18:3558–3585 Google Scholar
  40. 40.
    Pizzo PA (1999) Review Articles: Fever in Immunocompromised Patients. N Engl J Med 341:893–900CrossRefGoogle Scholar
  41. 41.
    Pizzo PA, Ladisch S, Robichaud K (1980) Treatment of gram-positive septicemia in cancer patients. Cancer 45:206–207PubMedGoogle Scholar
  42. 42.
    Pizzo PA, Robichaud KJ, Gill FA, Witebsky FG (1982) Empiric antibiotic and antifungal therapy for cancer patients with prolonged fever and granulocytopenia. Am J Med 72:101–111Google Scholar
  43. 43.
    Pizzo PA, Robichaud KJ, Gill FA, Witebsky FG, Levine AS, Deisseroth AB, Glaubiger DL, Maclowry JD, Magrath IT, Poplack DG, Simon RM (1979) Duration of empiric antibiotic therapy in granulocytopenic patients with cancer. Am J Med 67:194–200Google Scholar
  44. 44.
    Rolston KV, Berkey P, Bodey GP, Anaissie EJ, Khardori NM, Joshi JH, Keating MJ, Holmes FA, Cabanillas FF, Elting L (1992) A comparison of imipenem to ceftazidime with or without amikacin as empiric therapy in febrile neutropenic patients. Arch Intern Med 152:283–291CrossRefGoogle Scholar
  45. 45.
    Schrank JH Jr, Kelly JW, McAllister CK (1995) Randomized comparison of cefepime and ceftazidime for treatment of hospitalized patients with gram-negative bacteremia. Clin Infect Dis 20:56–58Google Scholar
  46. 46.
    Talcott JA, Siegel RD, Finberg R, Goldman L (1992) Risk assessment in cancer patients with fever and neutropenia: a prospective, two-center validation of a prediction rule. J Clin Oncol 10:316–322PubMedGoogle Scholar
  47. 47.
    Talcott JA, Whalen A, Clark J, Rieker PP, Finberg R (1994) Home antibiotic therapy for low-risk cancer patients with fever and neutropenia: a pilot study of 30 patients based on a validated prediction rule. J Clin Oncol 12:107–114PubMedGoogle Scholar
  48. 48.
    Tomiak AT, Yau JC, Huan SD, Cripps MC, Goel R, Perrault DJ, Bourcier JD, Prosser IA, Soltys KM, Evans WK, et al. (1994) Duration of intravenous antibiotics for patients with neutropenic fever. Ann Oncol 5:441–445Google Scholar
  49. 49.
    Uzun O, Anaissie EJ (1999) Outpatient therapy for febrile neutropenia: who, when, and how? J Antimicrob Chemother 43:317–320Google Scholar
  50. 50.
    Viscoli C, Castagnola E, Van Lint MT, Moroni C, Garaventa A, Rossi MR, Fanci R, Menichetti F, Caselli D, Giacchino M, Congiu M (1996) Fluconazole versus amphotericin B as empirical antifungal therapy of unexplained fever in granulocytopenic cancer patients: A pragmatic, multicentre, prospective and randomised clinical trial. Eur J Cancer 32A:814–820PubMedGoogle Scholar
  51. 51.
    Walsh T, Sable C, de Pauw B, Donowitz G, Maertens J, Baden L, Bourque M, Lupinacci R, Nguyen B, Teppler H (2003) A Randomized, Double-blind, Multicenter Trial of Caspofungin (CAS) v Liposomal Amphotericin B (LAMB) for Empirical Antifungal Therapy (EAFRx) of Persistently Febrile Neutropenic (PFN) Patients (Pt). Abstract book: 43th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC), Chicago, p M-1761Google Scholar
  52. 52.
    Walsh TJ (2002) Echinocandins -- An Advance in the Primary Treatment of Invasive Candidiasis. N Engl J Med 347:2070–2072CrossRefGoogle Scholar
  53. 53.
    Walsh TJ, Finberg RW, Arndt C, Hiemenz J, Schwartz C, Bodensteiner D, Pappas P, Seibel N, Greenberg RN, Dummer S, Schuster M, Holcenberg JS (1999) Liposomal amphotericin B for empirical therapy in patients with persistent fever and neutropenia. National Institute of Allergy and Infectious Diseases Mycoses Study Group. N Engl J Med 340:764–771PubMedGoogle Scholar
  54. 54.
    Walsh TJ, Pappas P, Winston DJ, Lazarus HM, Petersen F, Raffalli J, Yanovich S, Stiff P, Greenberg R, Donowitz G, Schuster M, Reboli A, Wingard J, Arndt C, Reinhardt J, Hadley S, Finberg R, Laverdiere M, Perfect J, Garber G, Fioritoni G, Anaissie E, Lee J (2002) Voriconazole compared with liposomal amphotericin B for empirical antifungal therapy in patients with neutropenia and persistent fever. N Engl J Med 346:225–234PubMedGoogle Scholar
  55. 55.
    White MH, Bowden RA, Sandler ES, Graham ML, Noskin GA, Wingard JR, Goldman M, van Burik JA, McCabe A, Lin JS, Gurwith M, Miller CB (1998) Randomized, double-blind clinical trial of amphotericin B colloidal dispersion vs. amphotericin B in the empirical treatment of fever and neutropenia. Clin Infect Dis 27:296–302Google Scholar
  56. 56.
    Wingard JR, White MH, Anaissie E, Raffalli J, Goodman J, Arrieta A (2000) A randomized, double-blind comparative trial evaluating the safety of liposomal amphotericin B versus amphotericin B lipid complex in the empirical treatment of febrile neutropenia. L Amph/ABLC Collaborative Study Group. Clin Infect Dis 31:1155–1163CrossRefGoogle Scholar
  57. 57.
    Winston DJ, Hathorn JW, Schuster MG, Schiller GJ, Territo MC (2000) A multicenter, randomized trial of fluconazole versus amphotericin B for empiric antifungal therapy of febrile neutropenic patients with cancer. Am J Med 108:282–289PubMedGoogle Scholar

Copyright information

© Springer-Verlag 2003

Authors and Affiliations

  • H. Link
    • 1
  • A. Böhme
    • 3
  • O. A. Cornely
    • 4
  • K. Höffken
    • 2
  • O. Kellner
    • 5
  • W. V. Kern
    • 6
  • R. Mahlberg
    • 7
  • G. Maschmeyer
    • 8
  • M. R. Nowrousian
    • 9
  • H. Ostermann
    • 10
  • M. Ruhnke
    • 11
  • O. Sezer
    • 11
  • X. Schiel
    • 10
  • M. Wilhelm
    • 12
  • H. W. Auner
    • 13
  1. 1.Dept. of Internal Medicine I (Head: H. Link)Medizinische Klinik I, Westpfalz-KlinikumKaiserslauternGermany
  2. 2.Dept. of Internal Medicine II (Head: K. Höffken)Friedrich Schiller UniversityJenaGermany
  3. 3.Dept. of Internal Medicine III (Head: D. Hoelzer)University HospitalFrankfurt/MainGermany
  4. 4.Dept. of Internal Medicine I (Head: V. Diehl)University of CologneKölnGermany
  5. 5.Dept. of Internal Medicine IV (Head: H. Schmoll), Oncology-HematologyMartin Luther UniversityHalleGermany
  6. 6.Dept. Internal Medicine II, InfectiologyUniversity Medical CenterFreiburgGermany
  7. 7.Dept. of Internal Medicine IMutterhaus der Borromäerinnen (Head: M. Clemens)TrierGermany
  8. 8.Dept. of Internal Medicine, Hematology and Oncology (Head: B. Dörken)University Medical Center Charité, Campus Virchow-Klinikum, Humboldt UniversityBerlinGermany
  9. 9.Dept. of Internal Medicine, (Head: S. Seeber)University Medical CenterEssenGermany
  10. 10.Dept. of Internal Medicine III (Head: W. Hiddemann)University Medical Center Grosshadern, Ludwig Maximilian UniversityMünchenGermany
  11. 11.Dept. of Internal Medicine IIUniversity Medical Center Charité (Head: K. Possinger)BerlinGermany
  12. 12.Dept. of Internal Medicine V (Head: M. Wilhelm)Klinikum Nürnberg NordNürnbergGermany
  13. 13.Division of Hematology (Head: W. Linkesch)Karl-Franzens University HospitalGrazAustria

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