bone marrow transplantation

Hematopoietic stem cell transplantation in AML patients with t(8;21)(q22;q22) translocation

BONE MARROW TRANSPLANTATION , , ,

N.N. Mamayev, A.V. Gorbunova, T.L. Gindina, I.M. Barkhatov, S.N. Bondarenko, M.Yu. Averyanova, О.V. Pirogova, O.V. Goloshchapov, Ye.V. Kondakova, and B.V. Afanasyev

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

ABSTRACT

The outcomes of bone marrow transplantation for treatment of relapses in 7 AML patients with t(8;21)(q22;q22) translocation are presented and analyzed. Two of them were transplanted in the 1st remission, and 5 patients received HSCT during resistance to the therapy. Three patients underwent unrelated allo-HSCT with various sources of HSC. Three others were treated with related allo-, auto-, or haplo-HSCT, respectively. In the last patient, auto-HSCT followed by related haplo-HSCT was performed. The course of disease was monitored using the serial levels of both AML1-ETO and WT1 gene expression. The high AML1-ETO levels and t(8;21) translocation were detected in all studied patients, whereas no FLT3 gene mutations were found in any patients, and a classic V617F JAK2 mutation was present in 1 patient. The levels of AML1-ETO and WT1 gene expression decreased in parallel with the relapse reduction in 2 patients, but remained elevated in 3 other patients despite the normalization of bone marrow morphologic picture, including 2 cases of development of extramedullary AML relapses. Relapses were accompanied by the high levels of the above gene expression. The study led to the conclusion that bone marrow transplantation is indicated for some AML patients with t(8;21) translocation. The treatment efficacy can be monitored using serial measurements of WT1 gene expression levels.

Keywords: AML with t(8;21) translocation, bone marrow transplantation, AML1-ETO and WT1 gene expression monitoring, molecular monitoring during treatment of leukemia.

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Refernces

  1. Zander A.R., Bacher U., Finke J. Allogeneic stem cell transplantation in acute myeloid leukemia establishment of indications on the basis of individual risk stratification. Arztebl. Int. 2008; 105(39): 663–9.
  2. Numata A., Fujimaki K., Aoshima T. et al. Retrospective analysis of treatment outcomes in 70 patients with t(8;21) acute myeloid leukemia. Rinsho Ketsueki 2012; 53(7): 698–704.
  3. Kawamura M., Kaku H., Ito T. et al. FLT3-internal tandem duplication in a pediatric patient with t(8;21) acute myeloid leukemia. Cancer Genet. Cytogenet. 2010; 203(2): 292–6.
  4. Chen Y.M., Liu T.F., Ruan M. et al. Prognosis and chromosomal abnormalities in 79 children with t(8;21) acute myeloid leukemia. Zhongguo Yi Xue Ke Xue Yuan Xue Bao 2009; 31(5): 542–6.
  5. Mamaev N., Mamaeva S. Two cases of acute myeloblastic leukemia (M2 type) with karyotypes 45X,-X,t(6;8)(q27;q22),inv(9) and 46,XY,t(8;21) (q22;q22),del(9)(q22). Cancer Genet. Cytogenet. 1985; 18(2): 105–11.
  6. Мамаев Н.Н., Горбунова А.В., Гиндина Т.Л. и др. Лейкозы и миело- диспластические синдромы с высокой экспрессией гена EVI1: теоретиче- ские и клинические аспекты. Клин. онкогематол. 2012; 5(4): 361–4. [Mamayev N.N., Gorbunova A.V., Gindina T.L. i dr. Leykozy i miyelodisplasticheskiye sindromy s vysokoy ekspressiyey gena EVI1: teoreticheskiye i klinicheskiye aspekty (Leukemias and myelodisplastic syndromes with high EVI1 gene expression: theoretical and clinical aspects. In: Clin. oncohematol.). Klin. onkogematol. 2012; 5(4): 361–4.]
  7. Forman S.J., Rowe J.M. The myth of the second remission of acute leukemia in the adult. Blood 2013; 121(7): 1077–82.
  8. Kuwatsuka Y., Miyamura K., Suzuki R. et al. Hematopoietic stem cell transplantation for core binding factor acute myeloid leukemia: t(8;21) and inv(16) represent different clinical outcomes. Blood 2009; 113: 2096–103.
  9. 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. 2012; 47(4): 499–507.
  10. Candoni A., Toffoletti E., Gallina R. et al. Monitoring of minimal residual disease by quantitative WT1 gene expression following reduced intensity conditioning allogeneic stem cell transplantation in acute myeloid leukemia. Clin. Transplant. 2011; 25: 308–16.
  11. Lange T., Hubmann M., Burkhardt R. et al. Monitoring of WT1 expression in PB and CD34+ donor chimerism of BM predicts early relapse in AML and MDS patients after hematopoietic cell transplantation with reduced-intensity conditioning. Leukemia 2011; 25: 498–505.
  12. Kwon M., Martinez-Laperche C., Infante M. et al. Evaluation of minimal residual disease by real-time quantitative PCR of Wilms’ Tumor 1 expression in patients with acute myelogenous leukemia after allogeneic stem cell transplantation: Correlation with flow cytometry and chimerism. Biol. Blood Marrow Transplant. 2012; 18: 1235–42.