Leukemic transformation of donor cells: is it possible?


Aim. To genotype tumor cells in the recurrence of leukemia after allogenic transplantation of bone marrow (TBM).
Material and methods. Standard cytogenetics and fluorescent hybridization in situ (FISH) with a probe to the centrometic sites of X/Y chromosomes were used in examination of 2 patients with acute promyelocyte and acute non-differentiated leukemia after allogenic TBM from donors of the opposite gender. Bone marrow was studied 1, 2, 3, 6, 9, 12, 15, 17, 18 months after the transplantation. Results. One of the patient in leukemia recurrence there were 72% cells with one X chromosome with unknown origin 28% donor cells were with genotype XX. The primary archival cytological sample of the recipients bone marrow 68% cells did not contain Ychromosome. Thus, the clone with Yloss is the recipient's clone and leukemia after transplantation developed from the recipient's cells The other
patient had only 8% dividing cells with her karyotype XX with translocation t(10; 11) while 92% metaphases were donor's ones; the interphase cells ratio was 75% of host cells and 25% donor cells. This confirms leukemia origin from the recipient's cells.
Conclusion. High sensitive quantitative method FISH indicates a true correlation between the host and donor cells and is a method of choice for genotyping leukemic cells in recurrence after transplantation of bone marrow. While standard caryotyping depends on mytotic activity of donor and host cell populations, use of only one cytogenetic test for determination of leukemia origin after ТВМ may provoke diagnostic errors.


  1. Cooley L. D., Sears D. A., Udden M. M. et al. Donor cell leukemia: report of a case occurring years after allogeneic bone marrow transplantation and review of the literature. Am. J. Hematol. 2000; 63: 46-53.
  2. Heinze В., Arnold R., Rutzen-Loesevltz L., Fliedner Т. М. The role of stable chromosome aberrations as biological indicators of radiation effect: studies in patients after total body irradiation and bone marrow transplantation. Stem Cells 1995; 13 (1): 191-198.
  3. Au W. Y., Chan E. C., Siu L. L. Leukaemic relapse of donor origin after allogeneic bone marrow transplantation from a donor who later developed bronchogenic carcinoma, Br. J. Haematol. 2002; 119 (3): 777-780.
  4. McCann S. R., Lawler M., Bacigalupo A. Recurrence of Philadelphia chromosome-positive leukemia in donor cells after bone marrow transplantation for chronic granulocytic leukemia. Leukemia and Lymphoma 1993; 10 (6): 419-425.
  5. Lawler M., Locasciulli A., Longoni D. et al. Leukaemic transformation of donor cells in a patient receiving a second allogeneic bone marrow transplant for severe aplastic anaemia. Bone Marrow Transplant. 2002; 29 (5): 453-456.
  6. McCann S. R., Lawler M., Gardiner N. et al. Donor leukemia following allogeneic bone marrow transplantation. Leukemia 1994; 8 (1): 133-135.
  7. Van Dekken H., Hagenbeek A., Bauman J. G. Detection of host cells following sex-mismatched bone marrow transplantation by fluorescent in situ hybridization with a Y-chromosome specific probe. Leukemia 1989; 3 (10): 724-728.
  8. Зотиков Е. А., Бабаева А. Г., Порешина Л. П. Клеточный химеризм и химеризм клетки при трансплантации костного мозга. М.; 2003.
  9. Виноградова О. А. Мониторинг химеризма и минимальной остаточной болезни у больных хроническим миелолейкозом после трансплантации стволовых гемопоэтических клеток: Дис. ... канд. мед. наук. М.; 2001.
  10. Mitelman F., ed. fSCN (1995) Recommendations of the International Standing Committee on Human Cytogenetic Nomenclature. Basel: S. Karger; 1995.
  11. Виноградова О. А., Савченко В. Г., Неверова А. Л. и др. Изучение динамики смешанного химеризма методом флюоресцентной гибридизации in situ у больных хроническим миелолейкозом после аллогенной трансплантации костного мозга. Тер. арх. 2001; 7: 26-34.
  12. Palka G., Stuppia L., Bartolomeo P. et al. FISH detection of mixed chimerism in 33 patients submitted to bone marrow transplantation. Bone Marrow Transplant. 1996; 17: 231-236.
  13. Mitelman F. Cancer cytogenetics. New York; 1995.
  14. Groupe Francais de Cytogenetique Hematologique. Cancer Genet. Cytogenet. 1990; 44: 169-179.
  15. Кобзев Ю. Н. Диагностическое значение флюоресцентной гибридизации in situ и многоцветного спектрального кариотипирования в клинической цитогенетике лейкозов: Дис. ... канд. мед. наук. М.; 1999.
  16. Fialkow P. J., Thomas E. D., Bryant J. I., Neiman P. E. Leukemic transformation of engrafted human marrow cells in vivo. Lancet 1972; 1: 1310-1313.
  17. Anastasi J., Thangavelu M., Vardiman J. W. et al. Interphase cytogenetic analysis detects minimal residual disease in a case of acute lymphoblastic leukemia and resolves the question of origin of relapse after allogeneic bone marrow transplantation. Blood 1991; 77(5): 1087-1091.
  18. Spinelli O., Giussani U., Borleri G. et al. Need for an accurate molecular diagnosis to assess the donor origin of leukemia relapse after allogeneic stem cell transplantation. Haematologica 2000; 85 (11): 1153-1157.
  19. Hambach L., Eder M., Dammann E. et al. Donor cell-derived acute myeloid leukemia developing 14 months after matched unrelated bone marrow transplantation for chronic myeloid leukaemia. Bone Marrow Transplant. 2001; 28 (7): 705-707.
  20. Gopcsa L., Barta A., Banyai A. et al. Acute myeloid leukaemia of donor cell origin developing 5 years after allogeneic bone marrow transplantation for chronic myeloid leukaemia. Bone Marrow Transplant. 2002; 29 (5): 449-452.
  21. Au W. Y., Lam С. С., Lie A. K. et al. T-cell large granular lymphocyte leukemia of donor origin after allogeneic bone marrow transplantation. Am.J. Clin. Pathol. 2003; 120 (4): 626-630.

Copyright (c) 2004 Vinogradova O.A., Savchenko V.G., Domracheva E.V., Parovichnikova E.N., Dyachenko L.V., Alimova G.A., Mendeleeva L.P., Lyubimova L.S., Sokolov A.N., Zhelnova E.I., Pokrovskaya O.S.

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