Hematopoietic stem cells (HSCs), still represent a certain mystery in biology, have a unique property of dividing into equal cells and repopulating the hematopoietic tissue. This potential enables their use in transplantation treatments. The quality of the HSC grafts for transplantation is evaluated by flow cytometric determination of the CD34(+) cells, which enables optimal timing of the first apheresis and the acquisition of maximal yield of the peripheral blood stem cells (PBSCs). To identify a more efficient method for evaluating CD34(+) cells, we compared the following alternative methods with the reference method: hematopoietic progenitor cells (HPC) enumeration (using the Sysmex XE-2100 analyser), detection of CD133(+) cells, and quantification of aldehyde dehydrogenase activity in the PBSCs. 266 aphereses (84 patients) were evaluated. In the preapheretic blood, the new methods produced data that were in agreement with the reference method. The ROC curves have shown that for the first-day apheresis target, the optimal predictive cut-off value was 0.032 cells/mL for the HPC method (sensitivity 73.4%, specificity 69.3%). HPC method exhibited a definite practical superiority as compared to other methods tested. HPC enumeration could serve as a supplementary method for the optimal timing of the first apheresis; it is simple, rapid, and cheap.

4th Department of Internal Medicine Hematology Charles University Medical Faculty and Teaching Hospital Sokolska Street 581 500 05 Hradec Kralove Czech Republic

Institute of Immunology and Allergology Charles University Medical Faculty and Teaching Hospital Sokolska Street 581 500 05 Hradec Kralove Czech Republic

Zobrazit více v PubMed

Letestu R, Marzac C, Audat F, et al. Use of hematopoietic progenitor cell count on the Sysmex XE-2100 for peripheral blood stem cell harvest monitoring. Leukemia and Lymphoma. 2007;48(1):89–96. PubMed

Linn YC, Heng KK, Rohimah S, Goh YT. Peripheral blood progenitor cell mobilization in three groups of subjects: a comparison of leukapheresis yield and timing. Journal of Clinical Apheresis. 2000;15:217–223. PubMed

Gratama JW, Sutherland DR, Keeney M, Papa S. Flow cytometric enumeration and immunophenotyping of hematopoietic stem and progenitor cells. Journal of Biological Regulators and Homeostatic Agents. 2001;15(1):14–22. PubMed

Watts MJ, Sullivan AM, Jamieson E, et al. Progenitor-cell mobilization after low-dose cyclophosphamide and granulocyte colony-stimulating factor: an analysis of progenitor-cell quantity and quality and factors predicting for these parameters in 101 pretreated patients with malignant lymphoma. Journal of Clinical Oncology. 1997;15(2):535–546. PubMed

Zhang C, Chen X, Zhang X, et al. Mobilization of peripheral blood stem cells for autologous transplantation patients with hematological malignancies: influence of disease, mobilization method, age and sex. Transfusion and Apheresis Science. 2008;39(1):21–28. PubMed

Cooling L, Hoffmann S, Herrst M, Muck C, Armelagos H, Davenport R. A prospective randomized trial of two popular mononuclear cell collection sets for autologous peripheral blood stem cell collection in multiple myeloma. Transfusion. 2010;50(1):100–119. PubMed

Yang S-M, Chen H, Chen Y-H, Zhu H-H, Zhao T, Liu K-Y. Dynamics of monocyte count: a good predictor for timing of peripheral blood stem cell collection. Journal of Clinical Apheresis. 2012;27(4):193–199. PubMed

Yu J, Leisenring W, Fritschle W, et al. Enumeration of HPC in mobilized peripheral blood with the Sysmex SE9500 predicts final CD34+ cell yield in the apheresis collection. Bone Marrow Transplantation. 2000;25(11):1157–1164. PubMed

Fallon P, Gentry T, Balber AE, et al. Mobilized peripheral blood SSCloALDHbr cells have the phenotypic and functional properties of primitive haematopoietic cells and their number correlates with engraftment following autologous transplantation. British Journal of Haematology. 2003;122(1):99–108. PubMed

Storms RW, Trujillo AP, Springer JB, et al. Isolation of primitive human hematopoietic progenitors on the basis of aldehyde dehydrogenase activity. Proceedings of the National Academy of Sciences of the United States of America. 1999;96(16):9118–9123. PubMed PMC

Lioznov MV, Freiberger P, Kröger N, Zander AR, Fehse B. Aldehyde dehydrogenase activity as a marker for the quality of hematopoietic stem cell transplants. Bone Marrow Transplantation. 2005;35(9):909–914. PubMed

Yin AH, Miraglia S, Zanjani ED, et al. AC133, a novel marker for human hematopoietic stem and progenitor cells. Blood. 1997;90(12):5002–5012. PubMed

Belada D, Trneny M. Diagnostic and Therapeutic Guidelines. Hradec Králové, Czech Republic: HK CREDIT; 2007.

Smythe J, Pawson R, Stacey K, Benjamin S, Watt S. The Use of the Sysmex XE 2100 Haematology Analyser to Quickly Predict the Mobilisation of Peripheral Blood stem Cells for Transplant. Oxford, UK: National Blood Service, NHS Blood and Transplant; 2007. http://www.bbts.org.uk/

Takekawa K, Yamane T, Suzuki K, Hino M, Tatsumi N. Identification of hematopoietic stem cells by the SE-9000 automated hematology analyzer in peripheral blood stem cell harvest samples. Acta Haematologica. 1997;98(1):54–55. PubMed

Yamane Y, Takekawa K, Tatsumi N. Possibility of identification of hematopoietic stem cells using a conventional blood cell counter. European Journal of Haematology. 1995;55(3):207–208. PubMed

Storms RW, Safford K, Rice H, Colvin OM, Smith CA. Aldehyde dehydrogenase is expressed by primitive CD34+ hematopoietic progenitors [abstract] Biology of Blood and Marrow Transplantation. 2003;9(supplement):p. 18. Abstract 32.

Storms RW, Green PD, Safford KM, et al. Distinct hematopoietic progenitor compartments are delineated by the expression of aldehyde dehydrogenase and CD34. Blood. 2005;106(1):95–102. PubMed PMC

Kikuchi-Taura A, Soma T, Matsuyama T, Stern DM, Taguchi A. A new protocol for quantifying CD34+ Cells in peripheral blood of patients with cardiovascular disease. Texas Heart Institute Journal. 2006;33(4):427–429. PubMed PMC

Keeney M, Chin-Yee I, Weir K, Popma J, Nayar R, Sutherland DR. Single platform flow cytometric absolute CD34+ cell counts based on the ISHAGE guidelines. International Society of Hematotherapy and Graft Engineering. Cytometry. 1998;34:61–70. PubMed

Fawcett T. An introduction to ROC analysis. Pattern Recognition Letters. 2006;27(8):861–874.

Gutensohn K, Magens M, Krüger W, Kröger N, Kühnl P. Comparison of flow cytometry vs. a haematology cell analyser-based method to guide the optimal time-point for peripheral blood stem cell apheresis. Vox Sanguinis. 2006;90(1):53–58. PubMed

Oelschlaegel U, Bornhaeuser M, Thiede C, Ehninger G, Hoelig K. HPC enumeration with the Sysmex XE-2100 can guide flow cytometric CD34+ measurements and timing of leukaphereses. Cytotherapy. 2003;5(5):414–419. PubMed

Lee J-L, Kim S-B, Lee G-W, et al. Clinical usefulness of the hematopoietic progenitor cell counts in predicting the optimal timing of peripheral blood stem cell harvest. Journal of Korean Medical Science. 2003;18(1):27–35. PubMed PMC

Pollard Y, Watts MJ, Grant D, Chavda N, Linch DC, Machin SJ. Use of the haemopoietic progenitor cell count of the Sysmex SE-9500 to refine apheresis timing of peripheral blood stem cells. British Journal of Haematology. 1999;106(2):538–544. PubMed

Yu J, Leisenring W, Bensinger WI, Holmberg LA, Rowley SD. The predictive value of white cell or CD34+ cell count in the peripheral blood for timing apheresis and maximizing yield. Transfusion. 1999;39(5):442–450. PubMed

Min KK, Kim S, Jang G, et al. A randomized comparison of peripheral blood hematopoietic progenitor cell level of 5/mm3 versus 50/mm3 as a surrogate marker to initiate efficient autologous blood stem cell collection. Journal of Clinical Apheresis. 2007;22(5):277–282. PubMed

Vogel W, Kopp H, Kanz L, Einsele H. Correlations between hematopoietic progenitor cell counts as measured by Sysmex and CD34+ cell harvest yields following mobilization with different regimens. Journal of Cancer Research and Clinical Oncology. 2002;128(7):380–384. PubMed

Keating S, Suciu S, de Witte T, et al. The stem cell mobilizing capacity of patients with acute myeloid leukemia in complete remission correlates with relapse risk: results of the EORTC-GIMEMA AML-10 trial. Leukemia. 2003;17(1):60–67. PubMed

Apperley J, Carreras E, Gluckman E, Masszi T. The EBMT Handbook: Haemopoietic Stem Cell Transplantation. 6th edition. Genoa, Italy: European School of Haematology; 2012. (Edited by Forum Service Editore).

Akashi K, Traver D, Miyamoto T, Weissman IL. A clonogenic common myeloid progenitor that gives rise to all myeloid lineages. Nature. 2000;404(6774):193–197. PubMed

Cai J, Weiss ML, Rao MS. In search of ‘stemness’. Experimental Hematology. 2004;32(7):585–598. PubMed PMC