Current treatment of lymphoma in pregnancy

ABSTRACT

Introduction: Lymphoproliferative diseases occurring during pregnancy present the treating physician with unique diagnostic and therapeutic challenges, aiming to achieve maternal cure without impairing fetal health, growth, and survival. Due to the rarity of this complication, there is limited data to guide clinical decision-making, especially regarding the safety of novel emerging therapies.

Areas covered: The presented review describes the current practice of treatment for Hodgkin’s (HL) and non-Hodgkin’s (NHL) lymphoma in the pregnant patient, according to disease stage and trimester of pregnancy. Novel agents for treatment of lymphoma in the setting of pregnancy are discussed. Therapeutic dilemmas and areas of uncertainty are illuminated.

Expert opinion: HL and NHL are potentially curable diseases in the pregnant patient with generally good outcomes for the mother and the offspring, when tailoring the treatment according to the individual patient. The complexity of the situation merits shared decision-making with the patient and her family, explicitly outlining the risks and benefits. The pregnant patient is best managed by a multidisciplinary team, familiar with the intricacies of the gestational period, and providing the necessary support and sensitivity. Further studies are needed regarding the safety of novel agents in pregnancy.

KEYWORDS:

• Lymphoma
• pregnancy
• Hodgkin’s lymphoma
• non-Hodgkin’s lymphoma

Article Highlights

• Lymphoproliferative diseases, predominantly HL, complicate 1 in 6000 pregnancies.

• Lymphoma during pregnancy is a potentially curable disease with good outcomes for the mother and the fetus.

• Termination of pregnancy is rarely indicated, except for cases when an aggressive disease is diagnosed during the first trimester (weeks 2–12), or when a highly aggressive lymphoma – requiring intensified therapeutic regimens – is diagnosed throughout the entire gestational period.

• Treatment is dictated by the nature and the stage of the disease in combination with the gestational age.

• Treatment for newly diagnosed HL during pregnancy:

  • If diagnosed during the first trimester, and no urgent treatment is required, therapy should be deferred to the second trimester. Vinblastine or corticosteroids can be used as a bridging therapy.

  • ABVD (adriamycin, bleomycin, vinblastine, dacarbazine) can be administered safely during the second and third trimester.

  • Radiation is best avoided throughout the gestational period. In selected cases of localized supradiaphragmatic disease, radiotherapy can be performed with appropriate shielding.

• The outcomes for patients diagnosed with HL during pregnancy are similar to nonpregnant patients, with no significantly increased risk of fetal abnormalities or stillbirths.

• Pregnancy-associated NHL (PA-NHL) refers to a group of lymphoproliferative diseases (ranging from indolent to aggressive) that occur during pregnancy, amongst which, diffuse large B cell lymphoma is the most commonly reported, and often diagnosed at advanced stages.

• Women with PANHL were shown to be at an increased risk for pre‐eclampsia, cesarean-section, preterm births, and postpartum blood transfusions.

• Treatment for newly diagnosed NHL during pregnancy:● Indolent lymphoma: A strategy of watchful waiting until delivery can be employed in most cases. A short course of corticosteroids can be used as bridging therapy.● Aggressive lymphoma: R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, prednisone) can be safely administered beyond the first trimester. CNS prophylaxis with high-dose methotrexate is contraindicated until week 20 and its use is not recommended during pregnancy.● Highly aggressive lymphoma: Since Burkitt’s lymphoma necessitates immediate treatment with antimetabolites, prompt termination of pregnancy followed by initiation of intensive chemotherapy is recommended in most cases.

• Little is known regarding second line treatments for both HL and NHL with regards to fetal safety. HDT (high-dose therapy) followed by ASCT (autologous stem cell transplantation) are contraindicated during pregnancy due to high feto-toxicity.

• Supportive treatment: Metoclopramide can be safely used to address emesis. G-CSF can be administered without fetotoxicity. Penicillins, erythromycin, and cephalosporins are safe during pregnancy.

• Breastfeeding should be discouraged in patients receiving chemotherapy during the third trimester.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.