pregnancy

Management of Chronic Myeloid Leukemia Patients During Pregnancy (Analysis of Literature and Practical Recommendations)

MYELOID TUMORS , , , , ,

EYu Chelysheva1, AG Turkina1, ES Polushkina2, MA Vinogradova2, RG Shmakov2

1 National Medical Hematology Research Center, 4a Novyi Zykovskii pr-d, Moscow, Russian Federation, 125167

2 VI Kulakov National Medical Research Center of Obstetrics, Gynecology and Perinatology, 4 Akademika Oparina str., Moscow, Russian Federation, 117997

For correspondence: Ekaterina Yur’evna Chelysheva, MD, PhD, 4a Novyi Zykovskii pr-d, Moscow, Russian Federation, 125167; Tel.: +7(495)612-48-60; e-mail: denve@bk.ru

For citation: Chelysheva EYu, Turkina AG, Polushkina ES, et al. Management of Chronic Myeloid Leukemia Patients During Pregnancy (Analysis of Literature and Clinical Experience). Clinical oncohematology. 2019;12(2):202–10.

DOI: 10.21320/2500-2139-2019-12-2-202-210

ABSTRACT

Background. The tyrosine kinase inhibitors (TKI) era is marked by a long-term favorable prognosis of chronic myeloid leukemia (CML). In this context CML patients of reproductive age are faced with major issues of family planning with due regard to the risk of TKI treatment interruption during pregnancy. Additionally, TKI impact is another potential risk to the fetus.

Aim. To develop differentiated approach to CML treatment during pregnancy.

Materials & Methods. Analysis includes literature data and clinical experience based on 166 pregnancies of 120 CML patients from CML Pregnancy Registry.

Results. Pregnancy planning is recommended after achieving stable and deep molecular response (with BCR-ABL > 0.01 %, IS) within the period of at least 2 years. At conception TKI therapy does not have to be interrupted. However, early pregnancy detection and TKI treatment interruption after pregnancy confirmation are of vital importance due to teratogenic risks. Furthermore, no TKI may be administered during organogenetic period, i.e. up to the 15th week of gestation. In the absence or loss of complete hematologic response and growth of BCR-ABL > 1 % after the 15th week of gestation imatinib or nilotinib administration is justified in the interest of pregnant patients taking into account limited transfer of these drugs through placenta. In the absence of complete hematologic response before the 15th week of gestation interferon-α can be administered. With BCR-ABL < 1 % patients can be either followed-up without therapy or they can receive interferon-α throughout pregnancy. Dasatinib, bosutinib, and other TKI are contraindicated at any stage of pregnancy. There are no special recommendations for childbirth, delivery is to be adapted to obstetric conditions. Breast feeding is not recommended because of the lack of practical evidence for its safety.

Conclusion. A regular molecular monitoring of BCR-ABL and hematologic status is indispensable, health condition of fetus should be continuously monitored as well. CML patient management should be conducted by cooperating hematologists and gynecologists.

Keywords: chronic myeloid leukemia, pregnancy, tyrosine kinase inhibitors, imatinib, nilotinib, dasatinib, bosutinib.

Received: January 9, 2019

Accepted: March 20, 2019

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Thrombophilia and Pregnancy

HEMOSTASIS , ,

MV Galaiko, OV Rybina, MS Litvinenko, YuV Klimov, BYu Al’tshuler, AV Gubkin

NA Semashko Central Clinical Hospital No. 2, 2 Budaiskaya str., Moscow, Russian Federation, 129128

For correspondence: Andrei Vladimirovich Gubkin, PhD, 2 Budaiskaya str., Moscow, Russian Federation, 129128; e-mail: gubkinav@gmail.com

For citation: Galaiko MV, Rybina OV, Litvinenko MS, et al. Thrombophilia and Pregnancy. Clinical oncohematology. 2017;10(3):409–22 (In Russ).

DOI: 10.21320/2500-2139-2017-10-3-409-422

ABSTRACT

Background. Women with a predisposition to thrombosis (thrombophilia) during pregnancy develop pathological hypercoagulation, which can lead to early and late pregnancy losses. The most significant polymorphisms of thrombophilia genes include antithrombin III deficiency, protein C deficiency, Leiden mutation, hereditary hyperhomocysteinemia, and mutations of other clotting factors. In addition, several forms of thrombophilia are caused by hyperaggregation. Currently, heparin and its derivatives are considered the safest and most effective agents for the prevention and therapy of thrombosis. However, it is impossible to evaluate the efficacy of heparins using only standard methods (activated partial thromboplastin time, thrombin time, prothrombin time) and markers of intravascular coagulation activation (soluble fibrin-monomer complexes, D-dimer) due to their insufficient sensitivity. One of the new tests of qualitative and quantitative evaluation of the plasma coagulation system is thrombodynamics test, which allows to detect even minimal coagulation disturbances.

Aim. The aim was to evaluate the use of the thrombodynamics test in women with first trimester pregnancy pathology. The authors aimed to show the high sensitivity of this test for the monitoring of treatment with low molecular weight heparins (LMWH).

Methods. The study included 23 pregnant women with pregnancy pathology and/or history of thrombosis and threatening miscarriage in the first trimester. The women were aged 22–38 years (median age 30 years). The complex evaluation of the hemostatic system was performed using the thrombodynamics test.

Results. LMWH therapy with the thrombodynamics monitoring was administered to 20 of 23 women. The statistically significant changes were observed only for thrombodynamics indices (p < 0.05). The total of 14 women delivered healthy children at 38–40 weeks (all patients received LMWH in the first trimester).

Conclusion. The thrombodynamics test was the most reliable method of monitoring LMWH therapy, since it allows recording even minimal coagulation disturbances.

Keywords: thrombophilia, pregnancy, thrombodynamics.

Received: February 27, 2017

Accepted: May 8, 2017

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Diagnosis and Treatment of Thrombotic Thrombocytopenic Purpura Developed During Gestation: Literature Review and Case Report

RARE HEMATOLOGICAL TUMORS AND SYNDROMES , , , , , , ,

V.V. Voitsekhovskii1, L.B. Filatov2, A.V. Pivnik3, P.V. Avdonin4, T.V. Esenina5, A.G. Sudakov5

1 Amur State Medical Academy, 95 Gor’kogo str., Blagoveshchensk, Amur Oblast, Russian Federation, 675000

2 Yekaterinburg Consultative and Diagnostic Centre, 5 Suvorovskii per., Yekaterinburg, Sverdlov Oblast, Russian Federation, 620039

3 D.D. Pletnev Moscow Clinical Scientific and Practical Center under the Department of Healthcare, 86 sh. Entuziastov, Moscow, Russian Federation, 111123

4 N.K. Kol’tsov Institute of Developmental Biology, 26 Vavilova str., Moscow, Russian Federation, 119334

5 Amur Regional Clinical Hospital, 26 Voronkova str., Blagoveshchensk, Amur Oblast, Russian Federation, 675028

For correspondence: V.V. Voitsekhovskii, DSci, Associate Professor, 95 Gor’kogo str., Blagoveshchensk, Amur Oblast, Russian Federation, 675000; Tel: +7(4162)42-94-97; e-mail: voitsehovsckij@yandex.ru

For citation: Voitsekhovskii V.V., Filatov L.B., Pivnik A.V., Avdonin P.V., Esenina T.V., Sudakov A.G. Diagnosis and Treatment of Thrombotic Thrombocytopenic Purpura Developed During Gestation: Literature Review and Case Report. Klin. Onkogematol. 2014; 7(4): 587–598 (In Russ.).

ABSTRACT

This paper presents a literature review on state of art in issues of etiology, pathogenesis, clinical features and diagnosis of thrombotic thrombocytopenic purpura (ТТP or Moschcowitz’s disease). Data on a rare pathology of congenital ТТP (Upshaw—Schulman syndrome) and its manifestation during pregnancy are summarized. Various aspects of differential diagnosis for microangiopathic hemolytic anemia (МАHA), complicated issues in differential diagnosis for thrombotic microangiopathies (ТТP, hemolytic uremic syndrome, HELLP syndrome) during pregnancy are discussed. Specificity of clinical manifestations and differential diagnosis for acquired and congenital TTP in pregnant patients are considered. Issues of TTP treatment during pregnancy are exposed in detail.

Keywords: thrombotic thrombocytopenic purpura, congenital thrombotic thrombocytopenic purpura, Upshaw-Schulman syndrome, thrombotic microangiopathy, microangiopathic hemolytic anemia, ADAMTS-13, HELLP syndrome, pregnancy.

Accepted: October 3, 2014

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