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Autografting

Ewing Sarcoma tumor cells express CD34: implications for autologous stem cell transplantation

Bone Marrow Transplantation volume 39, pages 589–594 (2007)Cite this article

Abstract

The significance of tumor cell contamination in marrow and peripheral blood stem cell (PBSC) collections of patients with solid tumors remains controversial. Various methods have been developed to purge tumor cells from autologous stem cell products, including CD34+ selection. PBSC harvests from patients with Ewing family of tumors (EFT) were analyzed for contaminating tumor cells prior and after CD34+ selection using reverse transcription-polymerase chain reaction (RT-PCR) and flow cytometry (FC) analyzes. The expression of CD34 was studied by RT-PCR and FC in 14 primary tumors and 13 PBSC harvests, respectively. Tumor cells were identified in the harvests by both methods. In two patients, contaminating tumor cells were evident by RT-PCR only after positive selection. FC analysis confirmed a higher level of tumor cells in the CD34+ fraction. In an attempt to explore this finding, expression of CD34 was detected in 93% of primary tumors and 67% of contaminated harvests. As CD34 is expressed on EFT cells, these cells may be enriched following CD34+ selection of harvests, although the total number of tumor cells is reduced. Other methods of purging, rather than CD34+ selection, should be explored in patients with EFT undergoing autologous stem cell transplantation.

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References

  1. Shimoni A, Korbling M . Tumor cell contamination in re-infused stem cell autografts: does it have clinical significance? Critical Rev Oncol/Hematol 2002; 41: 241–250.

    Article  Google Scholar 

  2. Vogel W, Scheding S, Kanz L, Brugger W . Clinical applications of CD34+ peripheral blood progenitor cells (PBPC). Stem Cells 2000; 18: 87–92.

    Article  CAS  Google Scholar 

  3. Voso MT, Hohaus S, Moos M, Pforsich M, Cremer FW, Schlenk RF et al. Autografting with CD34+ peripheral blood stem cells: retained engraftment capability and reduced tumour cell content. Br J Haematol 1999; 104: 382–391.

    Article  CAS  Google Scholar 

  4. Shpall EJ, LeMaistre CF, Holland K, Ball E, Jones RB, Saral R et al. A prospective randomized trial of buffy coat versus CD34-selected autologous bone marrow support in high-risk breast cancer patients receiving high-dose chemotherapy. Blood 1997; 1: 4313–4320.

    Google Scholar 

  5. Tchirkov A, Kanold J, Giollant M, Halle-Haus P, Berger M, Rapatel C et al. Molecular monitoring of tumor cell contamination in leukapheresis products from stage IV neuroblastoma patients before and after positive CD34 selection. Med Pediatr Oncol 1998; 30: 228–232.

    Article  CAS  Google Scholar 

  6. Lode HN, Handgretinger R, Schuermann U, Seitz T, Klingebiel T, Niethammer D et al. Detection of neuroblastoma cells in CD34+ selected peripheral stem cells using a combination of tyrosine hydroxylase nested RT-PCR and anti-ganglioside G-D2 immunocytochemistry. Eur J Cancer 1997; 33: 2024–2030.

    Article  CAS  Google Scholar 

  7. Vescio R, Schiller G, Stewart AK, Ballester O, Noga S, Rugo H et al. Multicenter phase III trial to evaluate CD34(+) selected versus unselected autologous peripheral blood progenitor cell transplantation in multiple myeloma. Blood 1999; 93: 1858–1868.

    CAS  PubMed  Google Scholar 

  8. Gupta D, Bybee A, Cooke F, Giles C, Davis JG, McDonald C et al. CD34+ selected peripheral blood progenitor cell transplantation in patients with multiple myeloma: tumour cell contamination and outcome. Br J Haematol 1999; 104: 166–177.

    Article  CAS  Google Scholar 

  9. Ginsberg JP, Woo SY, Johnson ME, Hick MJ, Horowitz ME . Ewing sarcoma family of tumours: Ewing's sarcoma of bone and soft tissue and the peripheral primitive neuroectodermal tumours. In: Pizzo PA, Poplack DG (eds). Principle and Practice of Pediatric Oncology. Lippincott, Williams and Wilkins: Philadelphia, 2002, pp 973–1016.

    Google Scholar 

  10. Delattre O, Zucman J, Melot T, Garau XS, Zucker JM, Lenoir GM et al. The Ewing family of tumors – a subgroup of small round cell tumors defined by specific chimeric transcripts. N Eng J Med 1994; 331: 294–299.

    Article  CAS  Google Scholar 

  11. Sorensen PH, Lessnick SL, Lopez-Terrada D, Liu XF, Triche TJ, Denny CT . A second Ewing's sarcoma translocation, t(21;22), fuses the EWS gene to another ETS-family transcription factor, ERG. Nat Genet 1994; 6: 146–151.

    Article  CAS  Google Scholar 

  12. Jeon I-S, Davis JN, Braun BS, Sublett JE, Roussel MF, Denny CT et al. A variant Ewing's sarcoma translocation (7;22) fuses the EWS gene to the ETS gene ETV1. Oncogene 1995; 10: 1229–1234.

    CAS  PubMed  Google Scholar 

  13. Kaneko Y, Yoshida K, Handa M, Toyoda Y, Nishihira H, Tanaka Y et al. Fusion of an ETS-family gene, E1AF, to EWS by t(17;22)(q12;q12) chromosome translocation in an undifferentiated sarcoma of infancy. Genes Chromosomes Cancer 1996; 15: 115–121.

    Article  CAS  Google Scholar 

  14. Peter M, Couturier J, Pacquement H, Michon J, Thomas G, Magdelenat H et al. A new member of the ETS family fused to EWS in Ewing tumors. Oncogene 1997; 14: 1159–1164.

    Article  CAS  Google Scholar 

  15. Toretsky JA, Neckers L, Wexler LH . Detection of (11;22)(q24;q12) translocation-bearing cells in peripheral blood progenitor cells of patients with Ewing's Sarcoma Family of Tumors. J Natl Cancer Inst 1995; 87: 385–386.

    Article  CAS  Google Scholar 

  16. Leung W, Chen AR, Klann RC, Moss TJ, Davis JM, Noga SJ et al. Frequent detection of tumor cells in hematopoietic grafts in neuroblastoma and Ewing's sarcoma. Bone Marrow Transplant 1998; 22: 971–979.

    Article  CAS  Google Scholar 

  17. Thomson B, Hawkins D, Felgenhauer J, Radich JP . RT-PCR evaluation of peripheral blood, bone marrow and peripheral blood stem cells in children and adolescents undergoing VACIME chemotherapy for Ewing's sarcoma and alveolar rhabdomyosarcoma. Bone Marrow Transplant 1999; 24: 527–533.

    Article  CAS  Google Scholar 

  18. Fischmeister G, Zoubek A, Jugovic D, Witt V, Ladenstein R, Fritsch G et al. Low incidence of molecular evidence for tumour in PBPC harvests from patients with high risk Ewing tumours. Bone Marrow Transplant 1999; 24: 405–409.

    Article  CAS  Google Scholar 

  19. Yaniv I, Cohen IJ, Stein J, Zilberstein J, Liberzon E, Atlas O et al. Tumor cells are present in stem cell harvests of Ewing's sarcoma patients and their persistence following transplantation predicts relapse. Pediatr Blood Cancer 2004; 42: 404–409.

    Article  CAS  Google Scholar 

  20. Schumm M, Lang P, Taylor G, Kuci S, Klingebiel T, Buhring HJ et al. Isolation of highly purified autologous and allogeneic peripheral CD34+ cells using the CliniMACS device. J Hematother 1999; 8: 209–218.

    Article  CAS  Google Scholar 

  21. Ginsberg JP, de Alava E, Ladanyi M, Wexler LH, Kovar H, Paulussen M et al. EWS–FLI1 and EWS–ERG gene fusions are associated with similar clinical phenotypes in Ewing's sarcoma. J Clin Oncol 1999; 17: 1809–1814.

    Article  CAS  Google Scholar 

  22. Zoubek A, Pfleiderer C, Salzer-Kuntschik M, Amann G, Windhager R, Fink FM et al. Variability of EWS chimaeric transcripts in Ewing tumours: a comparison of clinical and molecular data. Br J Cancer 1994; 70: 908–913.

    Article  CAS  Google Scholar 

  23. Hafer R, Voigt A, Gruhn B, Zintl F . Neuroblastoma cells can express the hematopoietic progenitor cell antigen CD34 as detected at surface protein and mRNA level. J Neuroimmunol 1999; 96: 201–206.

    Article  CAS  Google Scholar 

  24. Chang A, Benda PM, Wood BL, Kussick SJ . Lineage specific identification of nonhematopoietic neoplasms by flow cytometry. Am J Clin Pathol 2003; 119: 643–655.

    Article  Google Scholar 

  25. Donovan J, Temel J, Zuckerman A, Gribben J, Fang J, Pierson G et al. CD34 selection as a stem cell purging strategy for neuroblastoma: preclinical and clinical studies. Med Pediatr Oncol 2000; 35: 677–682.

    Article  CAS  Google Scholar 

  26. Voigt A, Hafer R, Gruhn B, Zintl F . Expression of CD34 and other haematopoietic antigens on neuroblastoma cells: consequences for autologous bone marrow and peripheral blood stem cell transplantation. J Neuroimmunol 1997; 78: 117–126.

    Article  CAS  Google Scholar 

  27. Weiss SW, Nickoloff BJ . CD34 is expressed by a distinctive cell population in peripheral nerve, nerve sheath tumors, and related lesions. Am J Surg Pathol 1993; 17: 1039–1045.

    Article  CAS  Google Scholar 

  28. Yamane H, Kiura K, Tabata M, Bessho A, Tsuchida T, Motoda K et al. Small cell lung cancer can express CD34 antigen. Anticancer Res 1997; 17: 3627–3632.

    CAS  PubMed  Google Scholar 

  29. Ohali A, Avigad S, Zaizov R, Ophir R, Horn-Saban S, Cohen IJ et al. Prediction of high risk Ewing Sarcoma by gene expression profiling. Oncogene 2004; 23: 8997–9006.

    Article  CAS  Google Scholar 

  30. Merino ME, Navid F, Christensen BL, Toretsky JA, Helman LJ, Cheung NK et al. Immunomagnetic purging of Ewing's sarcoma from blood and bone marrow: quantification by real-time polymerase chain reaction. J Clin Oncol 2001; 19: 3649–3659.

    Article  CAS  Google Scholar 

  31. Paulus U, Schmitz N, Viehmann K, von Neuhoff N, Dreger P . Combined positive/negative selection for highly effective purging of PBPC grafts: towards clinical application in patients with B-CLL. Bone Marrow Transplant 1997; 20: 415–420.

    Article  CAS  Google Scholar 

  32. Mohr M, Dalmis F, Hilgenfeld E, Oelmann E, Zuhlsdorf M, Kratz-Albers K et al. Simultaneous immunomagnetic CD34+ cell selection and B-cell depletion in peripheral blood progenitor cell samples of patients suffering from B-cell Non-Hodgkin's lymphoma. Clin Cancer Res 2001; 7: 51–57.

    CAS  PubMed  Google Scholar 

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Author notes

  1. M Feinmesser: Deceased.

Authors and Affiliations

  1. Pediatric Hematology Oncology, Schneider Children's Medical Center of Israel, Petah Tikva, Israel

    I Yaniv, J Stein, D Luria, I J Cohen, S Manor, A Grunshpan, Y Sverdlov, Y Kodman, R Zaizov & S Avigad

  2. Molecular Oncology, Felsenstein Medical Research Center, Rabin Medical Campus, Petah Tikva, Israel

    I Yaniv, E Liberzon, R Zaizov & S Avigad

  3. Pathology Department, Sourasky Medical Center, Tel Aviv, Israel

    J Issakov

  4. Pathology Department, Rabin Medical Center, Petah Tikva, Israel

    M Feinmesser

  5. Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel

    I Yaniv, J Stein, D Luria, J Issakov, M Feinmesser & S Avigad

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  1. I Yaniv
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Correspondence to S Avigad.

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Yaniv, I., Stein, J., Luria, D. et al. Ewing Sarcoma tumor cells express CD34: implications for autologous stem cell transplantation. Bone Marrow Transplant 39, 589–594 (2007). https://doi.org/10.1038/sj.bmt.1705640

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  • DOI: https://doi.org/10.1038/sj.bmt.1705640

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