Zusammenfassung
Die Übertragung von Knochenmark und Blutstammzellen hat sich im letzten Jahrzehnt zu einem Standardtherapieverfahren für viele maligne Erkrankungen entwickelt. Autologe Stammzellen werden dem Patienten selbst, allogene Zellen einem HLA-identischen oder HLA-kompatiblen Familien- oder nicht-verwandtem Spender entnommen. Hämatopoetische Stammzellen können aus Blut, Knochenmark oder Nabelschnurblut gewonnen werden. Der Granulozyten-Kolonie-stimulierende Fakor (G-CSF) mobilisiert nach drei- bis fünftägiger Therapie Stammzellen- und Progenitorzellen der Hämatopoese und Lymphopoese in das Blut. Diese Methode ist bei der autologen Transplantation heute Standard und setzt sich auch bei der allogenen Transplantation immer mehr durch. Die Dauer der absoluten Knochenmarkinsuffizienz kann durch Blutstammzellen im Vergleich zur Knochenmarktransplantation deutlich verkürzt werden. Je nach Erkrankung und Krankheitsstadium kann mit hochdosierter und myeloablativer Chemotherapie und der anschließenden Transplantation hämatopoetischer Stammzellen eine langfristige Krankheitsfreiheit oder eine Heilung erreicht werden (siehe Teil II). Die Toxizität der myeloablativen Therapie konnte durch Verbesserungen der Supportivmaßnahmen deutlich gesenkt werden, trotzdem muß mit schweren Komplikationen an Oropharynx, Gastrointestinaltrakt, Leber, Lunge, Haut, Nieren, Harnwegen und Nervensystem gerechnet werden. Nach der allogenen Transplantation können immunkompetente transplantierte Zellen mit dem Empfängerorganismus reagieren. Unterschiede der Minor-Histokompatibilitätsantigene zwischen HLA-identischem Familienspender und Empfänger können T-Lymphozyten aktivieren, die mit den allogenen Stammzellen übertragen wurden. Diese Graftversus-Host-(GvH-)Reaktion kann Haut, Leber, Darm und andere Organe betreffen und zur GvH-Disease (GvHD) führen, die klinisch diskret, aber auch sehr ausgeprägt auftreten kann. Die GvHD tritt bei Differenzen der Major-Histokompatibilitätsantigene zwischen Spender und Empfänger und bei nichtverwandten Spendern häufiger und stärker auf als bei Familienspendern. Die mit dem Schweregrad der GvHD korrelierte Immundefizienz kann zu lebens-bedrohlichen Infektionen führen und den Transplantationserfolg gefährden. Wenn Stammzellen aus Nabelschnurblut gewonnen werden, dann ist auch bei nichtverwandten Spendern wegen der Unreife der Stammzellen und Lymphozyten das Risiko der GvHD gering. Nach allogener Stammzelltransplantation vermindern immunreaktive Zellen das Rezidivrisiko (Graft-versus-Tumor-Effekt: GvT). Klinisch ist dieser Effekt bei hämato- und lymphopoetischen Neoplasien sehr bedeutsam: (Graft-versus-Leukämie-Effekt: GvL).
Summary
The transplantation of hematopoietic and lymphopoetic stem and progenitor cells has become a standard procedure for the treatment of many malignant diseases. Autologous stem cells are derived from the patient himself, allogeneic cells from an HLA-identical or HLA-compatible family or unrelated donor. Hematopoetic stem cells can be obtained from bone marrow, blood and fetal cord blood. After 3 to 5 days treatment, the granulocyte-colony stimulating factor (G-CSF) mobilizes stem- and progenitor cells from the marrow into the blood. This method is now standard in autologous transplantation and is increasingly preferred in allogeneic transplantation. The time to hematopoietic recovery is shorter with blood stem cells than with bone marrow cells. With myeloablative high dose therapy followed by stem cell transplantation, long term disease free survival is possible in many cases and great proportions of patients can be cured (see part II). Improvements of supportive care have reduced toxicity of treatment substantially, however severe complications still occur at oropharynx, gastrointestinal tract, liver, lung, skin, kidney, urinary tract and nervous system. After allogeneic transplantation immunocompetent donor cells can react with the recipients tissue. In HLA-identical donor and recipients differences in the minor histocompatibility antigens account for this graft-versus-host-reaction (GvH), which is mainly mediated by transplanted T-cells. The GvH-reaction can affect skin, liver, gut and other organs and cause clinically relevant GvH-disease (GvHD). The GvHD is more severe in HLA-mis-matched or unrelated transplantations. Immunodeficiency and organ dysfunction due to GvHD may predispose to life threatening infections and impair the outcome of transplantion. Unrelated cord blood stem cells may have a minor risk of inducing acute GvHD, as stem and T-cells are immature. After allogeneic stem cell transplantation, the relapse rate of leukemia or lymphoma is significantly reduced by immunoreactive cells: graft-versus-tumor (GvT) or graftversus-leukemia effect (GvL).
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Link, H., Kolb, HJ., Ebell, W. et al. Die Transplantation hämatopoetischer Stammzellen. Med. Klin. 92, 480–491 (1997). https://doi.org/10.1007/BF03044917
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DOI: https://doi.org/10.1007/BF03044917