Clinical Efficacy of Chelation Therapy in Patients with Low-Risk Myelodysplastic Syndrome

SV Gritsaev, II Kostroma, AA Zhernyakova

Russian Research Institute of Hematology and Transfusiology, 16 2-ya Sovetskaya str., Saint Petersburg, Russian Federation, 191024

For correspondence: Sergei Vasil’evich Gritsaev, MD, PhD, 16 2-ya Sovetskaya str., Saint Petersburg, Russian Federation, 191024; Tel.: +7(812)717-54-68; e-mail: gritsaevsv@mail.ru

For citation: Gritsaev SV, Kostroma II, Zhernyakova AA. Clinical Efficacy of Chelation Therapy in Patients with Low-Risk Myelodysplastic Syndrome. Clinical oncohematology. 2019;12(2):120–4.

DOI: 10.21320/2500-2139-2019-12-2-120-124


ABSTRACT

The present literature review provides evidence that in patients with low-risk myelodysplastic syndrome and transfusion dependence blood parameters and survival rates can be improved by administration of iron chelators. Dose adequacy and therapy duration underlie clinical efficacy of chelators. Toxicity can be reduced by administrating a new formula of deferasirox that does not need to be dissolved in liquid before consuming.

Keywords: myelodysplastic syndrome, low risk, transfusion dependence, iron chelators, survival.

Received: August 20, 2018

Accepted: February 2, 2019

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REFERENCES

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

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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Acute Myeloblastic Leukemia and Myelodysplastic Syndrome: Azacitidine for Prophylactic and Preventive Purposes after Allogeneic Hematopoietic Stem Cell Transplantation

VN Ovechkina1, SN Bondarenko1, EV Morozova1, IS Moiseev1, OA Slesarchuk1, AG Smirnova1, OS Uspenskaya2, YaV Gudozhnikova1, AA Osipova1, VS Sergeev1, NN Mamaev1, LS Zubarovskaya1, BV Afanas’ev1

1 RM Gorbacheva Scientific Research Institute of Pediatric Hematology and Transplantation; Academician IP Pavlov First St. Petersburg State Medical University, 12 Rentgena str., Saint Petersburg, Russian Federation, 197022

2 Leningrad District Clinical Hospital, 45–49 Lunacharskogo pr-t, Saint Petersburg, Russian Federation, 194291

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. 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 (In Russ).

DOI: 10.21320/2500-2139-2017-10-1-45-51


ABSTRACT

Aim. To evaluate the effectiveness of preventive and prophylactic post-transplantation therapy using azacitidine (5-AZA) in patients at high risk of post-transplantation relapse.

Methods. 136 patients were included in the study performed by the pairwise comparison: 68 of them received 5-AZA after allo-HSCT and 68 patients were included in the historical control group. 5-AZA was prescribed for prophylactic or preventive purposes. The results were assessed according to the OS, RR, EFS, DUM, and relapse-free and GVHR-free survival.

Results. 1-year OS was 76 % in the 5-AZA group (95% CI 60–84 %) and 44 % in the reference group (95% CI 33–55 %) (= 0.001); 2-year OS was 63 % (95% CI 39–67 %) and 37 % (95% CI 26–48 %) (= 0.007), respectively. The relapse rate (RR) in the 5-AZA group was 34 % (95% CI 22–46 %) during 1 year and 51 % (95% CI 38–64 %) in the reference group (= 0.02). 1- and 2-year disease unrelated mortality (DUM) was similar: 5 % in the 5-AZA group (95% CI 0.1–14.0 %) and 25 % (95% CI 13–37 %) in the reference group (= 0.005). 1-year EFS was 76 % in the 5-AZA group (95% CI 61–85 %) and 44 % in the reference group (95% CI 33–55 %) (= 0.001); 2-year EFS was 63 % (95% CI 39–67 %) and 37 % (95% CI 26–48 %) (= 0.01), respectively. 1-year relapse-free and GVHR-free survival was 55 % in the 5-AZA group (95% CI 41–69 %) and 28 % in the reference group (95% CI 17–39 %) (= 0.001); 2-year relapse-free and GVHR-free survival was 47 % (95% CI 32–62 %) and 27 % (95% CI 17–37 %) (= 0.002), respectively.

Conclusion. The use of 5-AZA for prophylactic and preventive purposes after allo-HSCT does not increase the risk of GVHR and DUM, does not suppress the GVL effect and can be used in combination with the donor lymphocyte infusion (DLI). The therapy with 5-AZA is safe during the early period after allo-HSCT. The drug does not suppress the GVL effect and can be used in high risk patients to prevent early post-transplantation relapse. The use of 5-AZA in combination with DLI does not increase the incidence of severe GVHR.

Keywords: acute myeloblastic leukemia, myelodysplastic syndrome, allogeneic hematopoietic stem cell transplantation, hypomethylating therapy, azacitidine.

Received: July 18, 2016

Accepted: December 17, 2016

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Principles of Pathomorphological Differential Diagnosis of Myelodysplastic Syndromes

AM Kovrigina1, SA Glinkina1, VV Baikov2

1 Hematology Research Center, 4а Novyi Zykovskii pr-d, Moscow, Russian Federation, 125167

2 R.M. Gorbacheva Scientific Research Institute of Pediatric Hematology and Transplantation; Academician I.P. Pavlov First St. Petersburg State Medical University, 12 Rentgena str., Saint Petersburg, Russian Federation, 197022

For correspondence: Alla Mikhailovna Kovrigina, PhD, 4а Novyi Zykovskii pr-d, Moscow, Russian Federation, 125167; Tel.: +7(495)612-61-12; e-mail: kovrigina.alla@gmail.com

For citation: Kovrigina AM, Glinkina SA, Baikov VV. Principles of Pathomorphological Differential Diagnosis of Myelodysplastic Syndromes. Clinical oncohematology. 2015;8(1):62–8 (In Russ).


ABSTRACT

The article dwells on the diagnosis of myelodysplastic syndromes (MDS) in bone marrow trephine biopsies. The paper describes problems of a complex approach to differential diagnostics of MDS and non-clonal/reactive changes in hematopoiesis. It is emphasized that clinical and laboratory data, as well as data on patient’s medical history should be submitted to a pathologist. The authors substantiate the algorithm for the morphological investigation of a bone marrow trephine bioptate, including evaluation of cellularity, stromal patterns, and morphological signs of dysplasia. The diagnostic value of histochemistry and immunohistochemistry is discussed.


Keywords: myelodysplastic syndrome, bone marrow trephine biopsy, pathomorphology, differential diagnostics.

Received: October 22, 2014

Accepted: November 10, 2014

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