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Die Rationale für Knochenmarkuntersuchungen bei Patienten mit entzündlich-rheumatischen Erkrankungen

Rationale for bone marrow examination in patients with inflammatory rheumatic diseases

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Summary

OBJECTIVE: Inflammatory rheumatic diseases and the applied immunosuppressive treatments can lead to bone marrow depressions and promote hematologic malignancies. Our objective was to explore indications for and results of bone marrow examinations in a large cohort. METHODS: Between 1990 and 2004 146 bone marrow examinations in 3638 patients were performed due to abnormal laboratory results. Medical history, results of bone marrow examination (morphology, histology) and cytogenetic data were investigated retrospectively. RESULTS: Patients' (67.8% female) mean age at bone marrow examination was 53.5 years (SD 15.5), median disease duration 2.9 years. Indications for bone marrow examination were changes in peripheral blood counts in 81.7%. In 52 patients (35.6%) clinically relevant, partially neoplastic bone marrow changes (5 non-Hodgkin lymphoma, 9 myelodysplastic syndromes (MDS)/acute myeloid leukemia (AML) and 3 myeloproliferative neoplasias) were evident. Medication history showed intake of hydroxy-/chloroquine (13.5%), methotrexate (17.3%), cyclosporin (7.7%), sulfasalazine (7.7%), mycophenolatmofetil, gold, leflunomide (each 1.9%), azathioprine (aza, 25.0%) or cyclophosphamide (cyc, 7.7%) prior to bone marrow examination. 7 out of 9 patients, who developed MDS/AML had been treated with either azathioprine alone or additionally with cyclophosphamide (n = 3). CONCLUSION: One third of our patients showed relevant bone marrow changes that might be associated to therapy. The risk seems to be increased especially in patients with inflammatory rheumatic diseases who had received azathioprine alone or in combination with cyclophosphamide. Health care providers should bear in mind the risk of hematologic malignancies and monitor patients closely in this respect. Bone marrow examination should be performed in case of changes in peripheral blood counts; especially clinically relevant anemia, granulocytes < 2,500/µl, thrombocytes < 100,000/µl and relevant changes over time should lead to bone marrow examinations.

Zusammenfassung

FRAGESTELLUNG UND ZIEL: Entzündlich-rheumatische Erkrankungen und deren immunsuppressive Therapie können zu hämatologischen Erkrankungen führen. Ziel der vorliegenden Studie war es, die Indikationen von Knochenmarkpunktion und Knochenmarkbefunde bei einer großen Patientengruppe zu analysieren. MATERIAL UND METHODEN: Zwischen 1990 and 2004 wurden bei 146 von 3638 Patienten mit entzündlichrheumatischen Systemerkrankungen wegen Laborveränderungen Knochenmarkpunktionen durchgeführt. Die Auswertung der Zytomorphologie, Histologie, Zytogenetik, und der Vorgeschichte inklusive Labor erfolgte retrospektiv. ERGEBNISSE: Das mittlere Alter der Pat. (67,8% weiblich) bei Knochenmarkpunktion betrug 53,5 ± 15,5 Jahre, die mediane Krankheitsdauer 2,9 Jahre. 81,7% der Patienten zeigten Blutbildveränderungen. 52 Pat. (35,6%) hatten klinisch relevante, teils neoplastische Knochenmarkveränderungen (5 Non-Hodgkin-Lymphome, 9 myelodysplastische Syndrome (MDS)/eine akute myeloische Leukämie (AML) und 3 myeloproliferative Neoplasien). 13,5% dieser 52 Pat. hatten Hydroxy-/Chloroquin eingenommen, 17,3% Methotrexat, 7,7% Ciclosporin A, 7,7% Sulfasalazin, je 1,9% Mycophenolatmofetil, Gold und Leflunomid, 25% Azathioprin und 7,7% Cyclophosphamid. 7 von 9 Patienten, die ein MDS/AML entwickelten, waren nur mit Azathioprin oder zusätzlich mit Cyclophosphamid (n = 3) therapiert. ZUSAMMENFASSUNG: Ein Drittel der punktierten Patienten zeigte relevante Knochenmarkveränderungen, die möglicherweise therapieassoziiert sind. Insbesondere scheint bei Patienten mit entzündlich-rheumatischen Erkrankungen, die Azathioprin mit oder ohne Cyclophosphamid erhalten haben, das Risiko für therapieassoziierte Knochenmarkerkrankungen erhöht zu sein. Die an der Behandlung Beteiligten sollten deshalb stets das Risiko neoplastischer hämatologischer Erkrankungen bedenken und die Patienten engmaschig hinsichtlich ihres Auftretens kontrollieren. Knochenmarkpunktionen sind insbesondere bei Blutbildveränderungen indiziert, wenn eine klinisch relevante Anämie, Leukozyten < 2.500/µl, Thrombozyten < 100.000/µl und vor allem Veränderungen der Parameter im Verlauf zu beobachten sind.

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Authors and Affiliations

  1. Klinik für Endokrinologie, Diabetologie und Rheumatologie, Heinrich-Heine-Universität Düsseldorf, Düsseldorf, Germany

    Jutta G. Richter, Pascal Goßen & Matthias Schneider

  2. Klinik für Hämatologie, Onkologie und Klinische Immunologie, Heinrich-Heine-Universität Düsseldorf, Düsseldorf, Germany

    Ulrich Germing & Sabine Blum

  3. Institut für Humangenetik und Anthropologie, Heinrich-Heine-Universität Düsseldorf, Düsseldorf, Germany

    Barbara Hildebrandt

  4. Institut für Pathologie, Heinrich-Heine-Universität Düsseldorf, Düsseldorf, Germany

    Stefan Braunstein

  5. Deutsches Rheuma-Forschungszentrum, Berlin, Germany

    Dörte Huscher

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  1. Jutta G. Richter
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  2. Pascal Goßen
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Correspondence to Jutta G. Richter.

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Richter, J., Goßen, P., Germing, U. et al. Die Rationale für Knochenmarkuntersuchungen bei Patienten mit entzündlich-rheumatischen Erkrankungen. Wien Klin Wochenschr 121, 690–699 (2009). https://doi.org/10.1007/s00508-009-1264-x

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