Stable donor hematopoiesis reconstitution after post-transplantation relapse of acute myeloid leukemia in patient with inv(3)(q21q26), –7 and EVI1 oncogene overexpression treated by donor lymphocyte infusions and hypomethylating agents

N.N. Mamaev, A.V. Gorbunova, T.L. Gindina, O.A. Slesarchuk, V.N. Ovechkina, S.N. Bondarenko, O.V. Goloshchapov, V.M. Kravtsova, and B.V. Afanasev

I.P. Pavlov Saint Petersburg State Medical University, R.M. Gorbacheva Institute of Pediatric Oncology, Hematology and Transplantology, Saint Petersburg, Russian Federation


ABSTRACT

We present the case of successful treatment of post-transplantation relapse of prognostically unfavorable AML with inv(3)(q21q26), –7 and EVI1 oncogene overexpression, when stable donor hematopoiesis reconstitution was achieved due to one high-dose cytarabine course, DLI, and hypomethylating agents (decitabine, 5-azacitidine). Possible molecular mechanisms of this effect are discussed with respect to the new approaches to management of such patients.

Keywords: acute myeloid leukemia, inv(3)(q21q26), EVI1 high expression, hematopoietic stem cell transplantation, relapse, treatment, donor lymphocyte infusions, hypomethylating agents.

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REFERENCES

  1. Мамаев Н.Н., Горбунова А.В., Гиндина Т.Л. и др. Лейкозы и миелодис- пластические синдромы с высокой экспрессией гена EVI1: теоретические и клинические аспекты. Клин. онкогематол. 2012; 5(4): 361–4.[Mamayev N.N., Gorbunova A.V., Gindina T.L. et al. Leukemias and myelodisplastic syndromes with high EVI1 gene expression: theoretical and clinical aspects. Klin. onkogematol. 2012; 5(4): 361–4. (In Russ.)].
  2. Barrett A.J., Battiwalla M. Relapse after allogeneic stem cell transplantation. Expert. Rev. Hematol. 2010; 3(4): 429–41.
  3. Arellano M.L., Langston A., Winton E. et al. Treatment of relapsed acute leukemia after allogeneic transplantation: a single center experience. Biol. Blood Marrow Transplant. 2007; 13(1): 116–23.
  4. Porter D.L., Alyea E.P., Antin J.H. et al. NCI First International Workshop on the biology, prevention, and treatment of relapse after allogeneic hematopoietic stem cell transplantation: Report from the Committee on Treatment of Relapse after Allogeneic Hematopoietic Stem Cell Transplantation. Biol. Blood Marrow Transplant. 2010; 16: 1467–503.
  5. Pavletic S.Z., Kumar S., Mohty M. et al. NCI First International Workshop on the biology, prevention, and treatment of relapse after allogeneic hematopoietic stem cell transplantation: Report from the Committee on the Epidemiology and Natural History of Relapse following Allogeneic Cell Transplantation. Biol. Blood Marrow Transplant. 2010; 16: 871–90.
  6. Wang Y., Liu D.-H., Fan Z.-P. et al. Prevention of relapse using DLI can increase survival following HLA-identical transplantation in patients with advanced-stage acute leukemia: a multi-center study. Clin. Transplant. 2012. doi: 10.111/j.1399-0012.2012.01626.x.
  7. Lubbert M., Bertz H., Wasch R. et al. Efficacy of a 3-day, low-dose treatment with 5-azacytidine followed by donor lymphocyte infusions in older patients with acute myeloid leukemia or chronic myelomonocytic leukemia relapsed after allografting. Bone Marrow Transplant. 2009; 45(4): 627–32.
  8. Craddock C., Quek L., Goardon N. et al. Azacitidine fails to eradicate leukemic stem/progenitor cell populations in patients with acute myeloid leukemia and myelodysplasia. Leukemia 2012; doi: 10.1038/leu.2012.312.
  9. Candoni A., Tiribelli M., Toffoletti E. et al. Quantitative assessment of WT1 gene expression after allogeneic stem cell transplantation is a useful tool for monitoring minimal residual disease in acute myeloid leukemia. Eur. J. Haematol. 2009; 82(1): 61–8.
  10. Zhao X.-S., Jin S., Zhu H.-H. et al. Wilms’ tumor gene 1 expression: an independent acute leukemia prognostic indicator following allogeneic hematopoietic SCT. Bone Marrow Transplant. 2011. doi:10.1038/bmt.2011.121.