CD34-Subpopulations and Clonogenic Progenitors in Mobilized Peripheral Blood Cells from Patients with Acute Myeloid Leukemia

Zusammenfassung

Hintergrund: Der Einsatz von autologen peripheren Blutvorläufer/Stammzellen als Bestandteil der dosisintensivierten Therapieprotokolle für Patienten mit akuter myeloischer Leukämie (AML) ist klinischer Forschungsgegenstand. Methoden: Wir untersuchten den Anteil von CD 34⁺38^– und CD 34⁺DR^– Subpopulationen, klonogenen Vorläuferzellen und koloniebildenden Zellen in der Langzeitkultur (LTC-DC) von peripheren Blutproben von Patienten mit AML nach Chemotherapie und G-CSF, das zur Mobilisierung gegeben wurde. Die Ergebnisse wurden mit denen einer Kontrollpopulation von Patienten mit nicht-hämatologischen malignen Erkrankungen verglichen. Ergebnisse: Wir beobachteten eine geringere Anzahl an CD 34⁺ Zellen (31.2 ± 14.8 vs. 114 ± 36/?l) und eine Reduktion auf weniger als 15 % klonogene Vorläuferzellen (CFU) und LTC-DC unter den mononukleären Zellen des peripheren Bluts von Patienten mit AML nach Konsolidierungstherapie. Im Gegensatz dazu war die Qualität der CD34⁺ Zellen im Vergleich zur Kontrollpopulation mit einem moderat reduzierten Anteil an CFU/CD34⁺ Zellen (5.0 ± 5 % vs. 10.0 ± 2.8 %), einer fast identischen Häufigkeit von LTC-DC/CD34⁺ Zellen (0.5+0.1% vs. 0.6+0.2%), und einem höheren Anteil von CD34⁺38^– Zellen/CD34⁺ Zellen (8.4+1.8 % vs. 3,8+1.1 %) nicht signifikant vermindert. Zusammenfassung: Diese Daten bestätigen, dass es möglich ist mittels Chemotherapie und G-CSF, CD34⁺ Zellen in das periphere Blut von AML Patienten zu mobilisieren. Allerdings sollte die geringe absolute Anzahl an CFU und LTC-DC nach Behandlung mit hochdosiertem Ara-C bei der Planung zukünftiger Behandlungsprotokolle Berücksichtigung finden.

Abstract

Background: The use of autologous peripheral blood progenitor/stem cells as part of dose-intensified treatment protocols for patients with acute myeloid leukemia (AML) is under current clinical investigation. Methods: We analyzed the frequency of CD 34⁺ 38^– and CD 34⁺DR^– subpopulations, clonogenic cells and long-term culture-derived clonogenic cells (LTC-DC) in peripheral blood (PB) samples from patients with AML after chemotherapy and G-CSF given for mobilization in comparison to a control population of patients with non-hematological malignancies. Results: We observed a lower number of CD 34⁺ cells (31.2 ± 14.8 vs. 114 ± 36 /µl) and a reduction to less than 15 % for clonogenic progenitors (CFU) and LTC-DC in peripheral blood mononuclear cells from AML patients after consolidation therapy. In contrast, the quality of these CD 34⁺ cells was not significantly impaired after consolidation therapy determined by a moderately reduced frequency of CFU/CD34⁺ cells (5.0 ± 1.5 % vs. 10.0 ± 2.8 %), a nearly identical frequency of LTC-DC/CD34⁺ cells (0.5 ± 0.1 % vs. 0.6 ± 0.2 %), and a higher percentage of CD 34⁺38^– cells/CD34⁺ cells (8.4 ± 1.8 % vs. 3.8 ± 1.1 %) in comparison to the control population. Conclusion: Our data confirm that it is possible to mobilize CD 34⁺ cells into the peripheral blood of AML patients using chemotherapy and G-CSF. Nevertheless, the low absolute number of CFU and LTC-DC after high-dose ara-C treatment for AML has to be taken into consideration for the design of treatment protocols using autologous progenitor/stem cell transplantation.

myeloische Leukämie - Akute myeloische Leukämie - Stammzellen - Konsolidationstherapie - G-CSF

Acute myeloid leukemia - stem cells - consolidation therapy - G-CSF

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