hypomethylating agents

EVI1-Positive Leukemias and Myelodysplastic Syndromes: Theoretical and Clinical Aspects (Literature Review)

AUTOIMMUNE THROMBOCYTOPENIA , , , ,

NN Mamaev, AI Shakirova, EV Morozova, TL Gindina

RM Gorbacheva Scientific Research Institute of Pediatric Oncology, Hematology and Transplantation; IP Pavlov First Saint Petersburg State Medical University, 6/8 L’va Tolstogo str., Saint Petersburg, Russian Federation, 197022

For correspondence: Prof. Nikolai Nikolaevich Mamaev, MD, PhD, 6/8 L’va Tolstogo str., Saint Petersburg, Russian Federation, 197022; e-mail: nikmamaev524@gmail.com

For citation: Mamaev NN, Shakirova AI, Morozova EV, Gindina TL. EVI1-Positive Leukemias and Myelodysplastic Syndromes: Theoretical and Clinical Aspects (Literature Review). Clinical oncohematology. 2021;14(1):103–17. (In Russ).

DOI: 10.21320/2500-2139-2021-14-1-103-117

ABSTRACT

The present review provides the analysis of theoretical background and therapy of prognostically poorest EVI1-positive myeloid leukemias and myelodysplastic syndromes which is performed at the RM Gorbacheva Scientific Research Institute of Pediatric Oncology, Hematology and Transplantation. The focus is on the evidence of the dominating role of EVI1 gene in impaired epigenetic regulation of hematopoiesis and, thus, on the feasibility of allogeneic hematopoietic stem cell transplantation with hypomethylating agents and/or trans-retinoic acid used for these diseases treatment.

Keywords: EVI1, acute myeloid leukemia, chronic myeloid leukemia, myelodysplastic syndrome, allo-HSCT, hypomethylating agents, trans-retinoic acid.

Received: September 12, 2020

Accepted: December 6, 2020

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Статистика Plumx английский

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The Role of Hypomethylating Agents Prior to Allogeneic Hematopoietic Stem Cells Transplantation in Acute Myeloid Leukemia and Myelodysplastic Syndrome

BONE MARROW TRANSPLANTATION , , , ,

VN Ovechkina1, SN Bondarenko1, EV Morozova1, IS Moiseev1, AA Osipova1, TL Gindina1, AI Shakirova1, TA Bykova1, AD Kulagin1, IA Samorodova2, EV Karyakina3, EA Ukrainchenko4, LS Zubarovskaya1, BV Afanas’ev1

1 RM Gorbacheva Scientific Research Institute of Pediatric Hematology and Transplantation; Pavlov First Saint Petersburg State Medical University, 6/8 L’va Tolstogo str., Saint Petersburg, Russian Federation, 197022

2 Municipal Clinical Hospital No. 31, 3 Dinamo pr-t, Saint Petersburg, Russian Federation, 197110

3 Municipal Hospital No. 15, 4 Avangardnaya str., Saint Petersburg, Russian Federation, 198205

4 Aleksandrov Hospital, 4 Solidarnosti pr-t, Saint Petersburg, Russian Federation, 193312

For correspondence: Varvara Nikolaevna Ovechkina, 6/8 L’va Tolstogo str., Saint Petersburg, Russian Federation, 197022; Tel.: +7(812)338-62-72; e-mail ovetchkina@gmail.com

For citation: Ovechkina VN, Bondarenko SN, Morozova EV, et al. The Role of Hypomethylating Agents Prior to Allogeneic Hematopoietic Stem Cells Transplantation in Acute Myeloid Leukemia and Myelodysplastic Syndrome. Clinical oncohematology. 2017;10(3):351–7 (In Russ).

DOI: 10.21320/2500-2139-2017-10-3-351-357

ABSTRACT

Background & Aims. The aim of the study was to evaluate the efficacy and safety of azacytidine and decitabine prior to allogeneic hematopoietic stem cell transplantation (allo-HSCT) in acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), chronic myelomonocytic leukemia and juvenile myelomonocytic leukemia.

Materials & Methods. The research included 62 patients who received hypomethylating agents (HMA) prior to allo-HSCT. The median age was 28 years (range from 1 to 68 years), the study population consisted of 27 (43.5 %) women and 35 (56.5 %) men.

Results. The overall response (complete + partial remission) was observed in 42 % (n = 26) of cases. At the time of allo-HSCT no disease progression was observed in 41 (66 %) patients. The multivariant analysis showed the overall survival (OS) statistically significantly increased with the graft retention (hazard ratio [HR] 0.002; 95% confidence interval [95% CI] 0.001–0.74; p = 0.03), and also with the administration of HMA after allo-HSCT (HR 0.24; 95% CI 0.08–0.67; p = 0.007). The response (stabilisation, partial or complete remission) due to HMA administration prior to allo-HSCT (HR 6.4; 95% CI 0.75–54.0; p = 0.08) was associated with improved OS. The event-free survival (EFS) was significantly higher with the response to azacytidine and decitabine at the time of allo-HSCT (HR 38.9; 95% CI 1.3–1198.0; p = 0.03) and with the graft retention (HR 0.02; 95% CI 0.005–0.1; p = 0.001). In patients with MDS compared with AML (HR 2.3; 95% CI 0.9–22.0; p = 0.08), there was a tendency to EFS improvement. Progression-free survival rates were higher in patients with a number of blast cells in the bone marrow less than 31 % at the time of diagnosis (HR 1.1; 95% CI 1.1–9.9; p = 0.01).

Conclusion. The use of azacytidine and decitabine prior to allo-HSCT allows to safely control the tumor mass in patients with MDS and to maintain the achieved remission with AML. In patients with a response to HMA, the best OS and EFS values are seen after allo-HSCT.

Keywords: acute myeloid leukemia, myelodysplastic syndrome, allogeneic hematopoietic stem cell transplantation, hypomethylating agents, azacitidine, decitabine.

Received: December 19, 2016

Accepted: March 9, 2017

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    [Ovechkina VN, Bondarenko SN, Morozova EV, et al. Acute Myeloblastic Leukemia and Myelodysplastic Syndrome: Azacitidine for Prophylactic and Preventive Purposes after Allogeneic Hematopoietic Stem Cell Transplantation. Clinical oncohematology. 2017;10(1):45–51. doi: 10.21320/2500-2139-2017-10-1-45-51. (In Russ)]
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Hypomethylating Agents in Oncohematology

REVIEWS , , , ,

AD Shirin, OYu Baranova

NN Blokhin Russian Cancer Research Center, 24 Kashirskoye sh., Moscow, Russian Federation, 115478

For correspondence: Anton Dmitrievich Shirin, PhD, 24 Kashirskoye sh., Moscow, Russian Federation, 115478; Tel.: +7(499)324-28-24; e-mail: shirin-anton@mail.ru

For citation: Shirin AD, Baranova OYu. Hypomethylating Agents in Oncohematology. Clinical oncohematology. 2016;9(4):369–82 (In Russ).

DOI: 10.21320/2500-2139-2016-9-4-369-382

ABSTRACT

The review describes epigenetic processes, including methylation of nuclear and mitochondrial DNA, as well as RNA. It dwells on mechanisms of demethylation and corresponding medicinal products. It presents detailed information on results of numerous large randomized studies intended to evaluate hypomethylating agents (azanucleosides). Special attention is paid to outcomes of azanucleoside therapy in patients with acute myeloid leukemias. The article describes several prognostic systems and treatment algorithms for myelodysplastic syndromes. Two azanucleosides have been approved in Russia to date: azacitidine (for SQ administration) and decitabine (for IV administration). International authors analyze the experience in oral and subcutaneous administration of decitabine. However, the problem of off-label use of hypomethylating agents is still open. The review gives a brief description of ongoing clinical trials with azanucleosides.

Keywords: epigenetics, acute myeloid leukemias, myelodysplastic syndromes, azacitidine, decitabine, hypomethylating agents, azanucleosides.

Received: May 10, 2016

Accepted: May 20, 2016

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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

BONE MARROW TRANSPLANTATION , , , , , ,

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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