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DOI: 10.1160/TH16-02-0099
Haematological malignancies in pregnancy: An overview with an emphasis on thrombotic risks
Publikationsverlauf
Received:
07. Februar 2016
Accepted after major revision:
29. Juni 2016
Publikationsdatum:
02. Dezember 2017 (online)
![](https://www.thieme-connect.de/media/10.1055-s-00035024/201604/lookinside/thumbnails/10-1160-th16-02-0099-1.jpg)
Summary
With increase of maternal age, the incidence of haematological malignancies during pregnancy is rising and posing diagnostic and treatment challenges. Lymphoma is the fourth most common malignancy diagnosed in pregnancy; Hodgkin lymphoma is more frequent in pregnant women than non-Hodgkin lymphoma (NHL). The proportion of highly aggressive lymphomas in pregnant women is significantly higher than in non-pregnant women of reproductive age. Reproductive organ involvement is observed in almost half of pregnant women with NHL. The association of acute leukaemia and pregnancy is infrequent and it is assumed that pregnancy does not accelerate the disease course. Both cancer and pregnancy induce a procoagulant state which can lead to maternal venous thromboembolism (VTE) and placental occlusion. Pregnancy in woman with myeloproliferative neoplasms (MPN) promotes thrombotic environment, associating with an augmented risk of placental thrombosis, intrauterine growth retardation or loss and maternal thrombotic events.Haematological malignancies during pregnancy often require urgent diagnosis and management and are associated with potential adverse fetal outcomes. Most chemotherapeutic agents are teratogenic and should be avoided during the first trimester. Their use during the second and third trimesters may cause intrauterine growth restriction, premature birth and intrauterine fetal death. All chemotherapeutic drugs should be administered only after a detailed discussion with the patient and with close fetal monitoring. Chemotherapy and biological agents might also augment thrombotic risk. Guidelines for VTE prophylaxis in pregnant women with hematologic malignancies, apart from MPN, are currently unavailable, and therefore, clinical judgment should be made in each case.
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References
- 1 Hurley TJ, McKinnell JV, Irani MS.. Haematologic malignancies in pregnancy. Obstet Gynecol Clin North Am 2005; 32: 595-614.
- 2 Abadi U, Koren G, Lishner M.. Leukaemia and lymphoma in pregnancy. Haematol Oncol Clin North Am 2011; 25: 277-291. vii
- 3 Heit JA.. Epidemiology of venous thromboembolism. Nat Rev Cardiol 2015; 12: 464-474.
- 4 Bleau N, Patenaude V, Abenhaim HA.. Risk of venous thrombo-embolic events in pregnant patients with cancer. J Matern Fetal Neonatal Med 2016; 29: 380-384.
- 5 Lishner M, Avivi I, Apperley JF. et al. Haematologic Malignancies in Pregnancy: Management Guidelines From an International Consensus Meeting. J Clin Oncol. 2015 Epub ahead of print
- 6 Piccin A, Murphy WG, Smith OP.. Circulating microparticles: pathophysiology and clinical implications. Blood Rev 2007; 21: 157-171.
- 7 Aharon A, Brenner B.. Microparticles, thrombosis and cancer. Best Pract Res Clin Haematol 2009; 22: 61-69.
- 8 Tzoran I, Rebibo-Sabbah A, Brenner B. et al. Disease dynamics in patients with acute myeloid leukaemia: New biomarkers. Exp Haematol 2015; 43: 936-943.
- 9 Nadir Y, Brenner B.. Heparanase coagulation and cancer progression. Best Pract Res Clin Haematol 2009; 22: 85-92.
- 10 Nadir Y, Kenig Y, Drugan A. et al. Involvement of heparanase in vaginal and cesarean section deliveries. Thromb Res 2010; 126: e444-450.
- 11 Muller AM, Ihorst G, Mertelsmann R. et al. Epidemiology of non-Hodgkin's lymphoma (NHL): trends, geographic distribution, and etiology. Ann Haematol 2005; 84: 1-12.
- 12 Pereg D, Koren G, Lishner M.. The treatment of Hodgkin's and non-Hodgkin's lymphoma in pregnancy. Haematologica 2007; 92: 1230-1237.
- 13 Stewart Jr. HL, Monto RW.. Hodgkin's disease and pregnancy. Am J Obstet Gynecol 1952; 63: 570-578.
- 14 Woo SY, Fuller LM, Cundiff JH. et al. Radiotherapy during pregnancy for clinical stages IA-IIA Hodgkin's disease. Int J Radiat Oncol Biol Phys 1992; 23: 407-412.
- 15 Horowitz NA, Benyamini N, Wohlfart K. et al. Reproductive organ involvement in non-Hodgkin lymphoma during pregnancy: a systematic review. Lancet Oncol 2013; 14: e275-282.
- 16 Groves FD, Linet MS, Travis LB. et al. Cancer surveillance series: non-Hodgkin's lymphoma incidence by histologic subtype in the United States from 1978 through 1995. J Natl Cancer Inst 2000; 92: 1240-1251.
- 17 Morton LM, Wang SS, Devesa SS. et al. Lymphoma incidence patterns by WHO subtype in the United States, 1992–2001. Blood 2006; 107: 265-276.
- 18 Molyneux EM, Rochford R, Griffin B. et al. Burkitt's lymphoma. Lancet 2012; 379: 1234-1244.
- 19 Ziepert M, Hasenclever D, Kuhnt E. et al. Standard International prognostic index remains a valid predictor of outcome for patients with aggressive CD20+ B-cell lymphoma in the rituximab era. J Clin Oncol 2010; 28: 2373-2380.
- 20 Nadir Y, Brenner B, Gingis-Velitski S. et al. Heparanase induces tissue factor pathway inhibitor expression and extracellular accumulation in endothelial and tumour cells. Thromb Haemost 2008; 99: 133-141.
- 21 Nadir Y, Brenner B.. Heparanase procoagulant activity. Thromb Res 2012; 129 (01) S76-79.
- 22 Nadir Y, Brenner B.. Heparanase-A Link between Coagulation, Angiogenesis, and Cancer. Rambam Maimonides Med J 2012; 03: e0002.
- 23 Bartlett RM, Nickles RJ, Barnhart TE. et al. Fetal dose estimates for (18)F-fluoro-L-thymidine using a pregnant monkey model. J Nucl Med 2010; 51: 288-292.
- 24 Oto A, Ernst R, Jesse MK. et al. Magnetic resonance imaging of the chest, abdomen, and pelvis in the evaluation of pregnant patients with neoplasms. Am J Perinatol 2007; 24: 243-250.
- 25 Shellock FG, Kanal E.. Policies, guidelines, and recommendations for MR imaging safety and patient management. SMRI Safety Committee. J Magn Reson Imaging 1991; 01: 97-101.
- 26 Muhler MR, Clement O, Salomon LJ. et al. Maternofetal pharmacokinetics of a gadolinium chelate contrast agent in mice. Radiology 2011; 258: 455-460.
- 27 Thomas X.. Acute myeloid leukaemia in the pregnant patient. Eur J Haematol 2015; 95: 124-136.
- 28 Sadural E, Smith Jr LG. Haematologic malignancies during pregnancy. Clin Obstet Gynecol 1995; 38: 535-546.
- 29 Feliu J, Juarez S, Ordonez A. et al. Acute leukaemia and pregnancy. Cancer 1988; 61: 580-584.
- 30 Peleg D, Ben-Ami M.. Lymphoma and leukaemia complicating pregnancy. Obstet Gynecol Clin North Am 1998; 25: 365-383.
- 31 Shapira T, Pereg D, Lishner M.. How I treat acute and chronic leukaemia in pregnancy. Blood Rev 2008; 22: 247-259.
- 32 Chelghoum Y, Vey N, Raffoux E. et al. Acute leukaemia during pregnancy: a report on 37 patients and a review of the literature. Cancer 2005; 104: 110-117.
- 33 Davis SM, Branch DW.. Thromboprophylaxis in pregnancy: who and how?. Obstet Gynecol Clin North Am 2010; 37: 333-343.
- 34 Ku GH, White RH, Chew HK. et al. Venous thromboembolism in patients with acute leukaemia: incidence, risk factors, and effect on survival. Blood 2009; 113: 3911-3917.
- 35 Tallman MS, Brenner B, Serna Jde L. et al. Meeting report. Acute promyelocytic leukaemia-associated coagulopathy, 21 January 2004, London, United Kingdom. Leuk Res 2005; 29: 347-351.
- 36 Dally N, Hoffman R, Haddad N. et al. Predictive factors of bleeding and thrombosis during induction therapy in acute promyelocytic leukaemia-a single center experience in 34 patients. Thromb Res 2005; 116: 109-114.
- 37 Iseminger KA, Lewis MA.. Ethical challenges in treating mother and fetus when cancer complicates pregnancy. Obstet Gynecol Clin North Am 1998; 25: 273-285.
- 38 Dameshek W.. Some speculations on the myeloproliferative syndromes. Blood 1951; 06: 372-375.
- 39 Spivak JL.. The chronic myeloproliferative disorders: clonality and clinical heterogeneity. Semin Haematol 2004; 41 (2 Suppl 3) 1-5.
- 40 Vannucchi AM.. JAK2 mutation and thrombosis in the myeloproliferative neoplasms. Curr Haematol Malig Rep 2010; 05: 22-28.
- 41 Kubota Y, Tanaka T, Ohnishi H. et al. Constitutively activated phosphatidylinositol 3-kinase primes platelets from patients with chronic myelogenous leukaemia for thrombopoietin-induced aggregation. Leukaemia 2004; 18: 1127-1137.
- 42 Falanga A, Marchetti M, Vignoli A. et al. V617F JAK-2 mutation in patients with essential thrombocythemia: relation to platelet, granulocyte, and plasma hemostatic and inflammatory molecules. Exp Haematol 2007; 35: 702-711.
- 43 Chong AY, Blann AD, Patel J. et al. Endothelial dysfunction and damage in congestive heart failure: relation of flow-mediated dilation to circulating endothelial cells, plasma indexes of endothelial damage, and brain natriuretic peptide. Circulation 2004; 110: 1794-1798.
- 44 Lussana F, Caberlon S, Pagani C. et al. Association of V617F Jak2 mutation with the risk of thrombosis among patients with essential thrombocythaemia or idio-pathic myelofibrosis: a systematic review. Thromb Res 2009; 124: 409-417.
- 45 Vannucchi AM, Antonioli E, Guglielmelli P. et al. Prospective identification of high-risk polycythemia vera patients based on JAK2 (V617F) allele burden. Leukaemia 2007; 21: 1952-1959.
- 46 Passamonti F, Randi ML, Rumi E. et al. Increased risk of pregnancy complications in patients with essential thrombocythemia carrying the JAK2 (617V>F) mutation. Blood 2007; 110: 485-489.
- 47 Nadir Y, Brenner B, Fux L. et al. Heparanase enhances the generation of activated factor X in the presence of tissue factor and activated factor VII.. Haematologica 2010; 95: 1927-1934.
- 48 Kogan I, Chap D, Hoffman R. et al. JAK-2 V617F mutation increases heparanase procoagulant activity. Thromb Haemost 2015; 115: 73-80.
- 49 Barbui T, Finazzi G.. Special issues in myeloproliferative neoplasms. Curr Haematol Malig Rep 2011; 06: 28-35.
- 50 Harrison C.. Pregnancy and its management in the Philadelphia negative myeloproliferative diseases. Br J Haematol 2005; 129: 293-306.
- 51 Griesshammer M, Struve S, Harrison CM.. Essential thrombocythemia/poly-cythemia vera and pregnancy: the need for an observational study in Europe. Semin Thromb Hemost 2006; 32: 422-429.
- 52 Barbui T, Barosi G, Grossi A. et al. Practice guidelines for the therapy of essential thrombocythemia. A statement from the Italian Society of Haematology, the Italian Society of Experimental Haematology and the Italian Group for Bone Marrow Transplantation. Haematologica 2004; 89: 215-232.
- 53 Gangat N, Wolanskyj AP, Schwager S. et al. Predictors of pregnancy outcome in essential thrombocythemia: a single institution study of 63 pregnancies. Eur J Haematol 2009; 82: 350-353.
- 54 Elliott MA, Tefferi A.. Thrombocythaemia and pregnancy. Best Pract Res Clin Haematol 2003; 16: 227-242.
- 55 Matalon ST, Ornoy A, Fishman A. et al. The effect of 6-mercaptopurine on early human placental explants. Hum Reprod 2005; 20: 1390-1397.
- 56 Pacifici GM, Nottoli R.. Placental transfer of drugs administered to the mother. Clin Pharmacokinet 1995; 28: 235-269.
- 57 Weisz B, Meirow D, Schiff E. et al. Impact and treatment of cancer during pregnancy. Expert Rev Anticancer Ther 2004; 04: 889-902.
- 58 Greer IA, Nelson-Piercy C.. Low-molecular-weight heparins for thromboprophylaxis and treatment of venous thromboembolism in pregnancy: a systematic review of safety and efficacy. Blood 2005; 106: 401-407.
- 59 Barbui T, Barosi G, Birgegard G. et al. Philadelphia-negative classical myeloproliferative neoplasms: critical concepts and management recommendations from European LeukaemiaNet. J Clin Oncol 2011; 29: 761-770.