Extremitätenerhalt durch autologe Knochenmarksstammzelltransplantation zur Induktion der Arteriogenese bei kritischer, nicht-revaskularisierbarer Extremitätenischämie

 

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Zusammenfassung

Hintergrund: Die Transplantation von autologen Knochenmarksstammzellen in die ischämische Körperregion kann die Gefäßneubildung, insbesondere das arterielle Kollateralwachstum, induzieren. Wir untersuchten die Wirksamkeit und Sicherheit der Transplantation patienteneigener Knochenmarksstamm- und Vorläuferzellen bei Patienten mit austherapierter, nicht mehr revaskularisierbarer kritischer Extremitätenischämie mit drohender Majoramputation. Patienten und Methoden: Nach mehrfach erfolgloser oder bei primär nicht möglicher Revaskularisation und nach maximaler konservativer Therapie wurde bei 51 Patienten mit kritischer Extremitätenischämie eine autologe Knochenmarkszelltransplantation (aKMT) in das ischämische Bein durchgeführt. Bei den ersten 12 Patienten wurden die Knochenmarkszellen mit der Ficoll-Dichtegradientenmethode isoliert (hier im Mittel transplantiert 1,1 ± 1,1 × 10⁹ KM-Zellen), Patienten 13–51 erhielten über eine „point-of-care“, bettseitig durchgeführte Dichtezentrifugation gewonnene Knochenmarkszellkonzentrate (3,0 ± 1,7 × 10⁹ Zellen). Der Extremitätenerhalt gelang bei 59 % innerhalb von 6 Monaten und bei 53 % inner­halb der Nachbeobachtung (Mittelwert: 411 ± 261 Tage, Streubreite: von 175 bis 1186 Tagen). Die Durchblutungsparameter Knöchel-Arm-Index (KAI) und transkutaner Sauerstoffdruck (tcpO₂) zeigten einen Anstieg bei den Patienten mit konsekutivem Extremitä­ten­erhalt (Ausgangswert KAI 0,33 ± 0,18, nach 6 Monaten 0,46 ± 0,15; tcpO₂ 12 ± 12, nach 6 Monaten 25 ± 15 mmHg). Bei den schlussendlich major­amputierten Patienten zeigte sich keine signifikante Veränderung. Die Ansprechrate und der ­klinische Verlauf waren bei beiden Zellisolationsmethoden gleich. Klinisch besonders wichtig ist die Verbesserung des Rutherfordstadiums bei den Patienten mit Extremitätenerhalt von initial 4,9 auf 3,3 nach 6 Monaten (p = 0,0001). Die Dosis der Schmerzmedikation konnte um etwa 60 % reduziert werden, und die standardisierte Gehstrecke verbesserte sich von null auf 40 m. Es traten keine Therapie-assoziierten Todesfälle auf, drei schwere unerwünschte Ereignisse periinterventionell heilten folgenlos ab. Spätkomplikationen traten nicht auf. Schlussfolgerungen: Für einen Teil der austherapierten Patienten mit kritischer Extremitätenischämie stellt die aKMT eine sichere und effektive Methode zum Extremitätenerhalt dar.

Abstract

Background: Bone marrow cell transplantation has been shown to induce angiogenesis and thus improve ischaemic artery disease. This study eval­uates the effects of intramuscular bone marrow cell transplantation in patients with limb-threatening critical limb ischaemia with a very high risk for major amputation. Methods and Results: After failed or impossible operative and / or interventional revascularisation and after unsuccessful maximum conservative therapy, 51 patients with impending major amputation due to severe critical limb ischaemia had autologous bone marrow cells (BMC) transplant­ed into the ischaemic leg. Patients 1–12 received Ficoll-isolated bone marrow mononuclear cells (total cell number 1.1 ± 1.1 × 10⁹), patients 13–51 received point of care isolated bone marrow total nucleated cells (3.0 ± 1.7 × 10⁹). Limb salvage was 59 % at 6 months and 53 % at last follow-up (mean: 411 ± 261 days, range: 175–1186 days). Per­fusion measured with the ankle-brachial ­index (ABI) and transcutaneous oxygen tension (tcpO₂) at baseline and after 6 months increased in ­patients with consecutive limb salvage (ABI 0.33 ± 0.18 to 0.46 ± 0.15, tcpO₂ 12 ± 12 to 25 ± 15 mmHg) and did not change in patients eventually undergoing major amputation. No differences in clinical outcome between the isolation methods were seen. Clinically most important, patients with limb salvage improved from a mean Rutherford category of 4.9 at baseline to 3.3 at 6 months (p = 0.0001). Analgesics consumption was reduced by 62 %. ­Total walking distance improved in non-amputees from zero to 40 metres. Three severe peri­procedural adverse events resolved without se­quel­ae, and no unexpected long-term adverse events occurred. Conclusions: In no-option patients with end-stage critical limb ischaemia due to peripheral ­artery disease, bone marrow cell transplantation is a safe procedure which can improve leg perfusion sufficiently to reduce major amputations and permit durable limb salvage.

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Dr. B. Amann

Franziskuskrankenhaus · Innere Abteilung

Berlin

Germany

Phone: 0 30 / 2 63 80

Fax: 0 30 / 26 38 36 09

Email: amann@franziskus-berlin.de