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Klin Padiatr 2000; 212(4): 145-152
DOI: 10.1055/s-2000-9668
HÄMATOLOGIE UND HÄMOSTASEOLOGIE

Georg Thieme Verlag Stuttgart ·New York

Schwere angeborene Neutropenie: Neue Aspekte der Diagnostik und Therapie

Severe congenital neuropenia: Diagnosis and therapy:C.  Zeidler, B.  Schwinzer, K.  Welte
  • Internationales Register für schwere chronische Neutropenien (SCNIR), Datencoordinationszentrum für Europa
  • Kinderklinik, Medizinische Hochschule Hannover, Hannover
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Publication History

Publication Date:
31 December 2000 (online)

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Zusammenfassung:

Die schwere kongenitale Neutropenie (CN; Kostmann-Syndrom) ist eine hämatologische Erkrankung, die durch einen Ausreifungsarrest der Myelopoese auf der Myelozyten/Promyelozyten Stufe charakterisiert ist. Dieser Ausreifungsarrest resultiert in einer schweren Neutropenie mit absoluten Neutrophilenzahlen (ANZ) < 200/μl, verbunden mit schweren bakteriellen Infektionen bereits im frühen Kindesalter. Klinische Daten von mehr als 300 Patienten mit CN, die seit 1994 durch das Internationale Register für schwere chronische Neutropenien (SCNIR) gesammelt wurden, zeigen, dass mehr als 90 Prozent der Patienten auf eine Behandlung mit rekombinantem humanen Granulozyten-Kolonien stimulierenden Faktor (rHuG-CSF) mit einem Anstieg der ANZ auf mehr als 1000/μl ansprechen. Bei diesen Patienten wird eine tägliche subkutane Injektion von rHuG-CSF mit einer individuellen Dosis im Bereich zwischen 0,3 bis 120 μg/kg/Tag benötigt, um die ANZ über 1000/μl zu halten. Als Nebeneffekte wurden bei einem Teil dieser Patientengruppe Splenomegalie, Thrombozytopenie, Osteoporose und maligne Transformation in MDS/Leukämie dokumentiert. Ob und wie die rHuG-CSF-Therapie diese unerwarteten Entwicklungen beeinflusst, bleibt ungeklärt, da keine historischen Vergleichskontrollen zur Verfügung stehen. Für Patienten, die nicht auf eine Therapie mit rHuG-CSF ansprechen und die weiterhin an schweren, zum Teil lebensgefährlichen bakteriellen Infektionen leiden, ist eine Transplantation mit hämatopoetischen Stammzellen derzeit die einzige verfügbare Behandlung.

Severe congenital neutropenia (CN; Kostmann syndrome) is a hematologic disorder characterized by a maturation arrest of myelopoiesis at the promyelocyte/myelocyte stage of development. This arrest results in severe neutropenia with absolute neutrophil counts (ANC) less than 0.2 × 109/l associated with severe systemic bacterial infections from early infancy. Data on over 300 patients with CN collected by the Severe Chronic Neutropenia International Registry (SCNIR) since 1994 indicate that > 90 % of these patients respond to recombinant human granulocyte-colony stimulating factor (rHuG-CSF) treatment with an ANC >1.0 × 109/l. In these patients rHuG-CSF is required daily as subcutaneous injection with individual doses ranging between 0.27 and 120 mcg/kg/day to maintain ANC above 1.0 × 109/l. Adverse events documented in this group of patients include splenomegaly, thrombocytopenia, osteoporosis and malignant transformation into MDS/leukemia. If and how rHuG-CSF treatment impacts on these adverse events remains unclear since there are no historical controls for comparison. For those patients who are refractory to rHuG-CSF treatment and continue to have severe and often life-threatening bacterial infections, hematopoietic stem cell transplantation (HSCT) is still the only currently available treatment.

Schlüsselwörter:

Neutropenie - G-CSF - Diagnose - Therapie

Key words:

Neutropenia - G-CSF- diagnosis - therapy

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Cornelia Zeidler

Kinderklinik Medizinische Hochschule Hannover

30623 Hannover

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