Correlation of CD34+ Hematopoietic Stem Cells and CFU in Peripheral Blood Apheresis Products in Patients with Malignant Lymphoproliferative Diseases Before and After Cryopreservation Prior to auto-HSCT

VA Balashova, VI Rugal’, SS Bessmel’tsev, SV Gritsaev, NYu Semenova, SV Voloshin, ZhV Chubukina, AV Shmidt, AD Garifullin, IM Zapreeva, AA Kuzyaeva, II Kostroma, AYu Kuvshinov, AV Chechetkin

Russian Research Institute of Hematology and Transfusiology, 16 2-ya Sovetskaya str., Saint Petersburg, Russian Federation, 191024

For correspondence: Valentina Andreevna Balashova, MD, PhD, 16 2-ya Sovetskaya str., Saint Petersburg, Russian Federation, 191024; Tel.: +7(812)717-19-37; e-mail: vbspb37@mail.ru

For citation: Balashova VA, Rugal’ VI, Bessmel’tsev SS, et al. Correlation of CD34+ Hematopoietic Stem Cells and CFU in Peripheral Blood Apheresis Products in Patients with Malignant Lymphoproliferative Diseases Before and After Cryopreservation Prior to auto-HSCT. Clinical oncohematology. 2018;11(4):368–77.

DOI: 10.21320/2500-2139-2018-11-4-368-377


ABSTRACT

Aim. To establish correlation between CD34+ autologous hematopoietic stem cell (HSC) count and colony-forming units (CFU) in the same peripheral blood apheresis product samples before and after cryopreservation in multiple myeloma and lymphoma patients, and to assess clinical value of these parameters.

Materials & Methods. Cell samples of peripheral blood cytapheresis product and cell cultures were studied before and after cryopreservation in 32 multiple myeloma and 25 lymphoma patients who underwent autologous HSC transplantation. The material was analyzed using culture technique and flow cytometry.

Results. The paper provides information on the relationship between CD34+ HSC count obtained by flow cytometry, and CFU in cell culture obtained by cytapheresis of the same peripheral blood samples. A direct correlation was confirmed between CD34+ count and all the CFUs before and after cryopreservation in lymphoma patients. Correlation between CD34+ count and granulocyte-macrophage CFUs was revealed in multiple myeloma and lymphoma patients before cryopreservation.

Conclusion. The parameter of colony-forming capacity used for the assessment of the functional HSC was shown to be equally reliable criterion for condition evaluation of autotransplant proliferative pool than CD34+ cells. Both methods should be applied for qualitative and quantitative evaluation of an autotransplant for multiple myeloma and lymphoma patients.

Keywords: CD34+ cells, CFU, CFU-GM, correlation, lymphoma, multiple myeloma, apheresis, auto-HSCT.

Received: April 11, 2018

Accepted: July 28, 2018

Read in PDF 


REFERENCES

  1. Lansdorp PM. Self-renewal of stem cells. Biol Blood Marrow Transplant. 1997;3(4):171–8.

  2. Bryder D, Rossi DJ, Weissman IL. Hematopoietic stem cells: the paradigmatic tissue specific stem cell. Am J Pathol. 2006;169(2):338–46. doi: 10.2353/ajpath.2006.060312.

  3. Wodnar-Filipowicz A. Biological properties of haematopoietic stem cells. The EBMT Handbook, 6th edition; 2012. pp. 61–72.

  4. Moreb JS, Salmosinia D, Hsu J, et al. Long-term outcome after autologous stem cell transplantation with adequate peripheral blood stem cell mobilization using plerixafor and G-CSF in poor mobilizer lymphoma and myeloma patients. Adv Hematol. 2011;2011:1–8. doi: 10.1155/2011/517561.

  5. Птушкин В.В., Жуков Н.В., Миненко С.В. и др. Роль высокодозной химиотерапии с трансплантацией стволовых кроветворных клеток у больных с неходжкинскими лимфомами. Онкогематология. 2006;1–2:86–96.

    [Ptushkin VV, Zhukov NV, Minenko SV, et al. Role of high-dose chemotherapy with hematopoietic stem cell transplantation in patients with non-Hodgkin’s lymphomas. Onkogematologiya. 2006;1–2:86–96. (In Russ)]

  6. Avet-Loiseau H, Attal M, Moreau P, et al. Genetic abnormalities and survival in multiple myeloma: the experience of the Intergroup Francophone du Myeloma. Blood. 2007;109(8):3489–95. doi: 10.1182/blood-2006-08-040410.

  7. Avet-Loiseau H, Soulier J, Fermand JP, et al. Impact of high-risk cytogenetics and prior therapy on outcomes in patients with advanced relapsed or refractory multiple myeloma treated with lenalidomide plus dexamethasone. 2010;24(3):623–8. doi: 10.1038/leu.2009.273.

  8. Dabusti M, Lanza F, Campioni D, et al. CXCR4 expression on bone marrow CD34+ cells prior to mobilization can predict mobilization adequacy in patients with hematological malignancy. J Hematother Stem Cell Res. 2003;12(4):425–34. doi: 10.1089/152581603322286051.

  9. Ratip S. Mobilization failure in hematopoietic stem cell transplantation. XXXIX Ulusal Hematoloji Kongresi. Antalya, Turkey; 2013. рр. 106–10.

  10. Артюхина З.Е., Семенова Н.Ю., Балашова В.А. и др. Кроветворная ткань и стромальное микроокружение больных множественной миеломой. Вестник гематологии. 2017;13(1):15–8.

    [Artyukhina ZE, Semenova NYu, Balashova VA, et al. Hematopoietic tissue and stromal microenvironment in patients with multiple myeloma. Vestnik gematologii. 2017;13(1):15–8. (In Russ)]

  11. Бессмельцев С.С., Абдулкадыров К.М. Множественная миелома: руководство для врачей. М.: МК, 2016. 504 с.

    [Bessmel’tsev SS, Abdulkadyrov KM. Mnozhestvennaya mieloma: rukovodstvo dlya vrachei. (Multiple myeloma: manual for doctors.) Moscow: MK Publ.; 2016. 504 p. (In Russ)]

  12. Покровская О.С., Менделеева Л.П., Гальцева И.В. и др. Мобилизация гемопоэтических клеток крови у больных миеломной болезнью. Проблемы гематологии и переливания крови. 2003;2:55–65.

    [Pokrovskaya OS, Mendeleeva LP, Gal’tseva IV, et al. Mobilization of hematopoietic cells in myeloma patients. Problemy gematologii i perelivaniya krovi. 2003;2:55–65. (In Russ)]

  13. Покровская О.С. Кроветворная ткань и стромальное микроокружение в процессе интенсивной терапии и мобилизации гемопоэтических стволовых клеток у больных множественной миеломой: Автореф. дис.… канд. мед. наук. М., 2011.

    [Pokrovskaya OS. Krovetvornaya tkan’ i stromal’noe mikrookruzhenie v protsesse intensivnoi terapii i mobilizatsii gemopoeticheskikh stvolovykh kletok u bol’nykh mnozhestvennoi mielomoi. (Hematopoietic tissue and stromal microenvironment in intensive treatment and mobilization of hematopoietic stem cells in multiple myeloma ) [dissertation] Moscow; 2011. (In Russ)]

  14. Haizmann M, O’Meara AC, Moosmann PR, et al. Efficient mobilization of PBSC with vinorelbine/G-CSF in patients with malignant lymphoma. Bone Marrow Transplant. 2009;44(2):75–9. doi: 10.1038/bmt.2008.434.

  15. Haverkos BM, McBride A, O’Donnell L, et al. An effective mobilization strategy for lymphoma patients after failed upfront mobilization with plerixafor. Bone Marrow Transplant. 2014;49(8):1052–5. doi: 10.1038/bmt.2014.90.

  16. Lansdorp PM, Sutherland HJ, Eaves CJ. Selective expression of CD45 isoforms on functional subpopulations of CD34+ hemopoietic cells from human bone marrow. J Exp Med. 1990;172(1):363–6. doi: 10.1084/jem.172.1.363.

  17. Fritsch G, Buchinger P, Printz D, et al. Rapid discrimination of early CD34+ myeloid progenitors using CD45-RA analysis. Blood. 1993;1(9):2301–9.

  18. Fritsch G, Buchinger P, Printz D. Use of flow cytometric CD34 analysis to quantify hematopoietic progenitor cells. Leuk Lymphoma. 1993;10(6):443–51. doi: 10.3109/10428199309148201.

  19. Nissen-Druey C, Tichelli A, Mayer-Monard S. Human hematopoietic colonies in health and disease. Acta Haematol. 2005;113(1):5–10. doi: 10.1159/000081987.

  20. Takano H, Ema H, Sudo K, et al. Asymmetric division and lineage commitment at the level of hematopoietic stem cells: Inference from differentiation in daughter cell and granddaughter cell pairs. J Exp Med. 2004;199(3):295–302. doi: 10.1084/jem.20030929.

  21. Sieburg HB, Cho RH, Dykstra B, et al. The hematopoietic stem compartment consists of a limited number of discrete stem cell subsets. Blood. 2006;107(6):2311–6. doi: 10.1182/blood-2005-07-2970.

  22. Guo Y, Lubbert M, Engelhard M. CD34-hematopoietic stem cells: current concepts and controversies. Stem Cell. 2003;21(1):15–20. doi: 10.1634/stemcells.21-1-15.

  23. Donahue RE, Yang YC, Clark SC. Human P40 T-cell growth factor (interleukin-9) supports erythroid colony formation. Blood. 1990;75(12):2271–5.

  24. Ema H, Suda T, Miura Y, Nakauchi H. Colony formation of clone-sorted human haematopoietic progenitors. Blood. 1990;75(10):1941–6.

  25. Serke S, Sauberlich S, Huhn D. Multiparameter flow-cytometrical quantitation of circulating CD34+ cells: correlation to the quantitation of circulating haemopoietic progenitor cells by in vitro colony-assay. Br J Haematol. 2008;77(4):453–9. doi: 10.1111/j.1365-2141.1991.tb08609.x.

  26. Bensinger WI, Longin K, Appelbaum F, et al. Peripheral blood stem cells (PBSCs) collected after recombinant granulocyte colony stimulating factor (rhG-CSF): An analysis of factors correlating with the tempo of engraftment after transplantation. Br J Haematol. 1994;87(4):825–31. doi: 10.1111/j.1365-2141.1994.tb06744.x.

  27. Bensinger WI, Appelbaum F, Rowley S, et al. Factors that influence collection and engraftment of autologous peripheral blood stem cells. J Clin Oncol. 1995;13(10):2547–55. doi: 10.1200/jco.1995.13.10.2547.

  28. Weaver CH, Haselton B, Birch R, et al. An analysis of engrafment kinetics as a function of the CD34 content of peripheral blood progenitor cell collections in 692 patients after administration of myeloablative chemotherapy. Blood. 1995;86(10):3961–9.

  29. Weaver CH, Potz J, Redmond J, et al. Engraftment and outcomes of patients receiving myeloablative therapy followed by autologous peripheral blood cells with a low CD34+ cell content. Bone Marrow Transplant. 1997;19(11):1103–10. doi: 10.1038/sj.bmt.1700808.

  30. 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. J Clin Oncol. 1997;15(2):535–46. doi: 10.1200/jco.1997.15.2.535.

  31. Serke S, Watts M, Knudsen LM, et al. In-vitro clonogenity of mobilized peripheral blood CD34 expressing cells: inverse correlation to both relative and absolute number of CD34-expressing cells. Br J Haematol. 1996;95(2):234–40. doi: 10.1046/j.1365-2141.1996.d01-1918.x.

  32. Fritsch G, Emminger W, Buchinger P, et al. CD34-positive cell proportions in peripheral blood correlate with colony-forming capacity. Exp Hematol. 1991;19(11):1079–83.

  33. Fritsch G, Emminger W, Buchinger P, et al. CD34 analysis in peripheral blood correlates with colony-forming capacity. Progr Clin Biol Res. 1992;377:531–6.

  34. Scott MA, Ager S, Apperley JF, et al. Peripheral blood progenitor cell harvesting in multiple myeloma and malignant lymphoma. Leuk Lymphoma. 1995;19(5–6):479–84. doi: 10.3109/10428199509112208.

  35. Buzzi M, Granchi D, Bacci G, et al. CD34+ cells and clonogenicity of peripheral blood stem cells during chemotherapy treatment in association with granulocyte colony stimulating factor in osteosarcoma. J Chemother. 1999;11(4):293–300. doi: 10.1179/joc.1999.11.4.293.

  36. Андреева Л.Ю., Тупицын Н.Н., Овумян Г.Ш. и др. Гемопоэтические предшественники в крови онкологических больных: взаимосвязь колониеобразования и экспрессии CD Вестник РОНЦ им. Н.Н. Блохина РАМН. 2000;11(1):5–10.

    [Andreeva LYu, Tupitsyn NN, Ovumyan GSh, et al. Hematopoietic progenitors in blood of cancer patients: relationship between colony formation and CD34 expression. Vestnik RONTs im NN Blokhina RAMN. 2000;11(1):5–10. (In Russ)]

  37. Healy LE, Nirsimloo N, Scott M, et al. In vitro proliferation by cells mobilized into the peripheral blood for collection and autologous transplantation. Exp Hematol. 1994;22(13):1278–82.

  38. Magagnoli M, Spina M, Balzarotti M, et al. IGEV regimen and a fixed dose of lenograstim: an effective mobilization regimen in pretreated Hodgkin’s lymphoma patients. Bone Marrow Transplant. 2007;40(11):1019–25. doi: 10.1038/sj.bmt.1705862.

  39. Koutna I, Peterkova M, Simara P, et al. Proliferation and differentiation potential CD133+ and CD34+ populations from the bone marrow and mobilized peripheral blood. Ann Hematol. 2011;90(2):127–37. doi: 10.1007/s00277-010-1058-2.

  40. Балашова В.А., Ругаль В.И., Грицаев С.В. и др. Колониеобразующая способность гемопоэтических стволовых клеток мобилизованной периферической крови больных множественной миеломой до и после криоконсервирования. Трансфузиология. 2016;17(4):63–70.

    [Balashova VA, Rugal’ VI, Gritsaev SV, et al. Colony-forming capacity of hematopoietic stem cells of mobilized peripheral blood in multiple myeloma patients before and after cryopreservation. Transfuziologiya. 2016;17(4):63–70. (In Russ)]

  41. Балашова В.А., Ругаль В.И., Бессмельцев С.С. и др. Колониеобразующая способность гемопоэтических стволовых клеток мобилизованной периферической крови больных злокачественными лимфомами до и после криоконсервирования. Medline. 2018;19(3):45–54.

    [Balashova VA., Rugal VI., Bessmeltsev SS. et al. Colonyforming capacity of hematopoietic stem cells of mobilized peripheral blood in patients with malignant lymphomas before and after cryopreservation. Medline. 2018;19(3):45–54. (In Russ)]