AML with t(8;21) translocation

Results of Allogeneic Hematopoietic Stem Cell Transplantation in Patients with Acute Myeloid Leukemia with t(8;21)(q22;q22)/RUNX1-RUNX1T1 and Additional Cytogenetic Abnormalities

BONE MARROW TRANSPLANTATION , ,

TL Gindina, NN Mamaev, SN Bondarenko, ES Nikolaeva, OA Slesarchuk, AS Borovkova, OV Paina, SV Razumova, AL Alyanskii, LS Zubarovskaya, BV Afanas’ev

R.M. Gorbacheva Scientific Research Institute of Pediatric Hematology and Transplantation; Academician I.P. Pavlov First St. Petersburg State Medical University, 6/8 L’va Tolstogo str., Saint Petersburg, Russian Federation, 197022

For correspondence: Tat’yana Leonidovna Gindina, PhD, 6/8 L’va Tolstogo str., Saint Petersburg, Russian Federation, 197022; Tel.: +7(812)233-12-43; e-mail: cytogenetics.bmt.lab@gmail.com

For citation: Gindina TL, Mamaev NN, Bondarenko SN, et al. Results of Allogeneic Hematopoietic Stem Cell Transplantation in Patients with Acute Myeloid Leukemia with t(8;21)(q22;q22)/RUNX1-RUNX1T1 and Additional Cytogenetic Abnormalities. Clinical oncohematology. 2016;9(2):148–54 (In Russ).

DOI: 10.21320/2500-2139-2016-9-2-148-154

ABSTRACT

Aim. To evaluate the impact of additional chromosomal aberrations on outcomes of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with acute myeloid leukemia (AML) with t(8;21)(q22;q22)/RUNX1-RUNX1T1 translocation.

Methods. Twenty-five AML patients with t(8;21)(q22;q22)/RUNX1-RUNX1T1 translocation (10 women and 15 men, aged from 2 to 58 years; median 20.2) were examined. Analysis of overall (OS) and event-free survival (EFS) predictors after allo-HSCT in patients with different clinical, transplant and cytogenetic characteristics was performed.

Results. The additional cytogenetic abnormalities were found in 13 (52 %) patients before the transplantation, at that, complex karyotype with three or more chromosomal abnormalities were registered in 9 (69 %) patients. The univariate analysis showed that OS and EFS after allo-HSCT differed in patients with different characteristics such as age (p = 0.03; p = 0.0006), clinical status at transplantation (p = 0.0002; p = 0,006), donor type (p = 0.0003; p = 0.002), the interval from diagnosis of leukemia to allo-HSCT (p = 0,008, for OS only), additional cytogenetic abnormalities (p = 0.03; p = 0.009) and complex karyotype (p = 0.004; p = 0.0003), respectively. In multivariate analysis, independent predictors of OS were donor type (p = 0.01), the interval from diagnosis of leukemia to allo-HSCT (p = 0.01), and additional cytogenetic abnormalities in karyotype (p = 0.04), as well as donor type (p = 0.04) and patient’s age (p = 0.004) for EFS.

Conclusion. AML with t(8;21)(q22;q22)/RUNX1-RUNX1T1 translocation is a heterogeneous disease. The prognosis in patients with the additional cytogenetic abnormalities, especially in those with the complex karyotype, is worse both after the standard chemotherapy (i.e. before allo-HSCT), and after allo-HSCT.

Keywords: AML with t(8;21) translocation, allo-HSCT, cytogenetic abnormalities.

Received: February 6, 2016

Accepted: February 15, 2016

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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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