Maternal ABVD chemotherapy for Hodgkin lymphoma in a dichorionic diamniotic pregnancy: a case report

Abstract

Background: Hodgkin lymphoma (HL) is the most common hematological malignancy during pregnancy. The firstline treatment for HL in pregnancy is the standard ABVD regimen without any drug and/or dose adjustment. However, data on chemotherapy during twin pregnancies are sparse, and a better understanding of the mechanisms involved in exposure to and the toxic effects of anticancer drugs in the fetuses is needed. Case presentation: A 41-year-old dichorionic diamniotic pregnant patient was given ABVD treatment for HL at a gestational age of 28 weeks and 3 days. The patient received 2 cycles of chemotherapy with a 15-day therapeutic window including an actual 25 mg/m 2 dose of doxorubicin per cycle. Unlike the female twin, the male twin presented four days after birth a left cardiac dysfunction. Doxorubicin cardiotoxicity in the male newborn was also supported by high blood levels of troponin. At one month of age, echocardiography findings were normal. We investigated literature data on physiological aspects of pregnancy that may influence doxorubicin pharmacokinetics, and pharmacodynamic and pharmacokinetic data on the use of doxorubicin in pregnancy. We detailed the role of the transporters in doxorubicin placenta distribution, and tried to understand why only one fetus was affected. Conclusions: Fetal safety depends at least on maternal doxorubicin pharmacokinetics.Because of drug interactions (i.e. drug metabolism and drug transport), care should always be taken to avoid maternal pharmacokinetic variability. The toxic effects were discrepant between the dizygotic twins, suggesting additional fetus-specific pharmacokinetic/pharmacodynamic factors in doxorubicin toxicity.

Unusual Presentation of Hodgkin’s Lymphoma in Pregnancy: A Case Report and Systematic Review of Literature

“…All included studies were case reports and original articles. Ten studies diagnosed pregnant women with nodular sclerosis HL [ 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 ], Five described management of pregnant women diagnosed with lymphocyte-rich HL [ 14 , 15 , 16 , 17 , 18 ], and one study described management of pregnant patient with stage-4 classical HL [ 19 ]. Ten of the included studies treated all pregnant patients diagnosed with HL with standard cycle of ABVD with no report of maternal or fetal complications from the chemotherapy regimen [ 5 , 6 , 7 , 8 , 9 , 10 , 12 , 17 , 19 ], but with the exception of three studies; in which one of the three studies reported that ABVD chemo therapy resulted in preterm contraction and rupture of membrane [ 5 ], second study described the addition of 25 mg/m 2 doxorubicin per cycle of ABVD which resulted in left cardiac dysfunction with high levels of troponin in the newborn on day 4 of life which later resolved on month one of life [ 16 ], and the third study reported an adverse effect with ABVD chemotherapy resulting in preterm birth, and the need for immediate post-partum blood transfusion with subsequent development of venous thromboembolism in the mother [ 11 ].…”

Cancer during Pregnancy: A Review of Preclinical and Clinical Transplacental Transfer of Anticancer Agents

“…For instance, a case study of nine patients treated with doxorubicin in association with ifosfamide during pregnancy reported favorable outcomes for all mothers and offspring [ 60 ]. Interestingly, neonatal follow-up of a recent case of maternal chemotherapy with a doxorubicin-containing regimen in a dichorionic diamniotic pregnancy [ 86 ] revealed cardiac dysfunction in one twin, suggesting a role for specific fetal factors that confer variability in the pharmacokinetics of doxorubicin.…”

Efficacy and Safety of Platinum-Based Chemotherapy for Ovarian Cancer During Pregnancy: A Systematic Review and Meta-Analysis

“…As a pregnancy category D drug listed by the Food and Drug Administration (FDA), chemotherapeutic drugs have obvious risks to the fetus. However, several studies have indicated that the use of anticancer agents during pregnancy is feasible, not only in ovarian cancer, but also in leukemia, lymphoma, colon cancer, breast cancer, gastric cancer, cervical cancer, sarcoma, and lung cancer [53][54][55][56][57][58][59][60]. In the present study, at the end of follow-up (median 10 months, range 0-73 months), all newborns with available data were healthy except one who died due to congenital abnormalities 5 days after delivery.…”