Pregnancy In Hematological Malignancies
Authors: Vinogradova Maria A. , Shmakov Roman G. , Polushkina Eugenia S. , Demina Elena A. 
Published: October 2019

Abstract

Background
The diagnosis of malignant hematological diseases (MHD) during pregnancy imposes major therapeutic decisions - optimal maternal treatment must be balanced against the risk to the fetus. The aim of therapy in this clinical situation is saving two lives – both a mother and a child. MHD treatment has some specific complications that may have special importance during pregnancy. Thus, management of pregnant patient with MHD is a difficult multidisciplinary problem. Furthermore, the issues of reproductive health in MHD patients are becoming very important in general because of survival improvement.

Aim
Evaluation of the disease prognosis and establishment of algorithms for management of pregnancy and delivery in MHD patients are crucial for quality of life. We have been developing the optimal strategy for management of pregnant patients with MHD.

Results
From 1986 to 2013 we observed 218 pregnancies in 207 pregnant women with MHD in total. We have analyzed outcomes in 36 cases disease presented in pregnancy, including 19 patients treated with chemotherapy for MHD during pregnancy (Hodgkin lymphoma (HL) was diagnosed in 21 patients, non-Hodgkin lymphomas (NHL) in 15). All of them exposed to chemotherapy in the second and third trimesters according to form of the disease. ABVD was the chemotherapy regimen given in HL. Pregnant women with NHL treated with CHOP, R-CHOP or VACOP-B. Also we have analyzed 182 pregnancies in 171 women remaining in remission after MHD, including 131 patients with HL, 24 patients with NHL and 16 patients with acute leukemia (AL). All of them underwent the treatment of hematological disease to achieve remission. The median time from the moment of achieving remission to the onset of pregnancy was 7,2 years in patients with HL, 4.3 years in patients with NHL and 7.8 years in patients with AL. 10-years overall survival of pregnant and non-pregnant HL patients has no significant difference: 86,4% vs 91,2% (p=0,27). 10-years disease free survival rate of 70 vs 72% (p=0,34) respectively. We did not observe any maternal life-threatening complications during pregnancy. Most common complications in the group of women exposed chemotherapy during pregnancy were different infections (viral infections -10,5%, pyelonephritis – 4,2%, pneumonia – 3,3%) and thrombotic events (16,2%). All of thrombotic complications registered during chemotherapy for NHL and were successfully treated. In pregnant women with full MHD remission the progression of the disease was registered in 23% patients with AL and in 1.7% patients with HL. All patients with diagnosed disease relapse needed the resumption of chemotherapy. 196 (89,9%) pregnancies ended up with a birth of full-term healthy infants without birth defects. Premature birth occurred in 16 (7.3%) cases. Neonatal mortality occurred in 1 (0.5%) newborn. In 2 (0.9%) patients pregnancy was terminated for medical reasons in the 2nd trimester. The mode of delivery was determined by the obstetrician in all cases. In our study exposure to chemotherapy was not associated with congenital anomalies, and no spontaneous miscarriages were registered. When early stage disease is diagnosed in the first trimester, chemotherapy is commenced in the second trimester. In advanced-stage disease in the first trimester there were 3 (1,4%) cases of abortion because of delay in treatment may adversely affect maternal outcome. No hemorrhagic complications during labor or postpartum period have been observed.

Conclusion
The MHD is a diverse group, with varied presenting features, pathophysiology, treatment options, levels of urgency to commence treatment in pregnancy, affect upon maternal and fetal outcome in pregnancy and overall prognosis. We conclude that prognosis of pregnant women treated for Hodgkin's lymphoma is similar to non-pregnant women. Treatment of MHD in pregnancy must conform to the protocol for type of disease and must include sufficient supportive care. We recommend patients with lymphomas to plan a pregnancy 3 years after achieving the remission. Pregnant women in remission after AL are at a considerably higher risk for relapse, hence, the pregnancy planning in this category of patients is feasible but no sooner than in 5 years after achieving full remission, and only after detailed examination including MRD testing. There is no difference in health between infants born by mothers with MHD and the newborns from general population.

Disclosures:
No relevant conflicts of interest to declare.