Management of classic Hodgkin lymphoma during pregnancy

INTRODUCTION — Classic Hodgkin lymphoma (cHL) accounts for only 10 percent of all lymphomas, but it is one of the most common types of lymphoma diagnosed during pregnancy, largely because the peak incidence coincides with female reproductive age. cHL is diagnosed in approximately 1:1000 to 1:6000 pregnancies and accounts for ≤3 percent of all patients with cHL. (See "Hodgkin lymphoma: Epidemiology and risk factors", section on 'Epidemiology'.)

This topic reviews the clinical presentation and management of cHL during pregnancy and effects of treatment on the developing fetus and delivered infant.

Clinical presentation and diagnosis of cHL in the nonpregnant adult is discussed separately. (See "Clinical presentation and diagnosis of classic Hodgkin lymphoma in adults".)

CLINICAL PRESENTATION — Pregnant patients with HL present in a similar fashion to nonpregnant patients with HL (eg, painless lymphadenopathy). Of importance, some signs and symptoms due to the HL (eg, fatigue, shortness of breath, anemia, thrombocytopenia) overlap with common signs and symptoms seen during pregnancy, potentially resulting in a delay of diagnosis. (See "Thrombocytopenia in pregnancy" and "Clinical presentation and diagnosis of classic Hodgkin lymphoma in adults", section on 'Clinical presentation'.)

Retrospective case series have described the clinical presentation of pregnant women with HL, with generally similar findings [1-5]. One of the larger series consisted of 48 women (median age 26 years) with 50 pregnancies occurring during active HL [2]. The diagnosis of HL was made in 12 patients before conception, in 10 during pregnancy, and in 27 within nine months after delivery or pregnancy termination. Each pregnant woman was matched with three nonpregnant HL controls. The stage at diagnosis did not differ significantly from the controls: stage I, 25 percent; stage II, 46 percent; stage III, 17 percent; and stage IV, 12 percent (table 1).

The presence of B symptoms (ie, fever, night sweats, or weight loss exceeding 10 percent of body weight) and pruritus is variable. While most patients from North American series have presented without B symptoms [1,3,4,6], one report from Mexico described B symptoms in 10 of 14 patients [7]. (See "Pretreatment evaluation, staging, and treatment stratification of classic Hodgkin lymphoma", section on 'B symptoms'.)

DIAGNOSIS — The diagnosis of HL is made based upon the pathologic evaluation of involved tissue, usually a lymph node biopsy. An excisional lymph node biopsy, performed under local or general anesthesia, is preferred and the risk of anesthesia and biopsy is similar to that of healthy pregnant women [8]. (See "Clinical presentation and diagnosis of classic Hodgkin lymphoma in adults", section on 'Tissue biopsy'.)

The pathologic subtype of HL diagnosed during pregnancy is consistent with that commonly seen in women of reproductive age. As an example, in a series of 40 women with HL during pregnancy, 35 were classified as nodular sclerosis type, 2 as mixed cellularity type, and 3 were unclassified [5]. A similar predominance of nodular sclerosis type has been noted in other reports [1,3,4]. (See "Hodgkin lymphoma: Epidemiology and risk factors", section on 'Subtypes'.)

STAGING DURING PREGNANCY — HL is staged using the Ann Arbor staging system (table 1). For women with HL diagnosed during pregnancy, the recommended staging studies have evolved with changing technology and therapeutic options. The goal of staging in this setting is to provide the clinician and patient with enough information to guide management while limiting the risks to the fetus.

The initial staging evaluation should include (table 2):

●Laboratory studies including a complete blood count, erythrocyte sedimentation rate (ESR), serum creatinine concentration, serum liver enzymes, and HIV serology. Of importance, ESR is often significantly elevated during normal pregnancy.

●Evaluation of the chest, abdomen, and pelvis with magnetic resonance imaging (MRI).

Evaluation of the abdomen with MRI is generally preferred to ultrasound, as it can evaluate lymph nodes, liver, and spleen with good accuracy. Although there are limited data regarding its safety in this setting, it is thought that MRI is probably safe in the pregnant patient [9-11]. Abdominal ultrasound is known to be safe in the pregnant population, but is much less sensitive than MRI. In contrast, computed tomography (CT) scan exposes the fetus to potentially harmful radiation and therefore is rarely performed if MRI and abdominal ultrasound are available. Positron emission tomography (PET) is contraindicated [12]. The use of diagnostic imaging procedures during pregnancy is discussed in more detail separately. (See "Diagnostic imaging in pregnant and lactating patients".)

Bone marrow biopsy can be safely performed during pregnancy, but is not required for staging in most patients with cHL, as discussed separately. (See "Pretreatment evaluation, staging, and treatment stratification of classic Hodgkin lymphoma", section on 'Other procedures'.)

If therapy is deferred until after delivery, a standard staging evaluation may be performed after delivery. In contrast, patients who receive treatment (eg, ABVD, vinblastine) during pregnancy cannot be accurately staged after delivery. (See "Pretreatment evaluation, staging, and treatment stratification of classic Hodgkin lymphoma".)

EFFECTS OF TREATMENT DURING PREGNANCY ON FETAL GROWTH AND DEVELOPMENT — Both radiation therapy and chemotherapy are potential teratogens. The risk of fetal malformation or death is dependent upon the stage of fetal development, fetal susceptibility, the agent utilized, and the fetal dose of that agent.

First trimester — The first trimester is the most critical period for chemotherapeutic drug exposure, as implantation (weeks 1 to 2) and embryogenesis proceed (weeks 3 to 8). The major manifestations of drug toxicity at this time are spontaneous abortions during implantation and major morphological abnormalities during embryogenesis. Some structures, such as the limbs and palate, have limited "windows" of vulnerability during embryogenesis, while other organs, such as the central nervous system, may be affected throughout all phases of embryogenesis, fetal development, and growth.

With chemotherapy, the placenta plays a pivotal role in drug transfer [13]. As such, chemotherapy administered inadvertently in the first two weeks of pregnancy (prior to the development of the placenta) will generally be less teratogenic [14]. In comparison, single agent and combination chemotherapy administered in the remainder of the first trimester results in a risk of congenital malformations of approximately 10 percent and 15 to 25 percent, respectively [14]. The absolute risk is difficult to determine and varies with agent.

The placental cells have a multidrug resistance phenotype [15], which may reduce or prevent transfer to the fetus of such natural products as doxorubicin, vinblastine, and vincristine. However, case reports regarding the efficiency of placental transfer of doxorubicin are inconclusive. Fetal drug metabolism and excretion must also consider amniotic fluid recirculation (ie, fetal swallowing of the amniotic fluid). This feature helps to explain the marked teratogenicity of the folate antagonists, aminopterin and methotrexate, when given at regular chemotherapeutic doses.

Radiation exposure of the fetus during the first trimester is associated with teratogenesis and an increased risk of childhood malignancy. The incidence of these effects depends upon the fetal dose of exposure, which in turn is dependent upon the radiation dose, radiation field size, and the distance between the radiation field and the fetus [16]. (See 'Radiation therapy' below.)

Second and third trimesters — Adverse effects of chemotherapy on the fetus are often more subtle during the second and third trimesters [13,17,18]. Among the possible toxic effects are low birth weight, intrauterine growth restriction, premature birth, stillborn fetus, impaired functional development, intellectual disability (mental retardation), and diminished learning capability. In one study, there was limited fetal exposure after the administration of ABVD to baboons in the second and third trimester of pregnancy [19]. As described below, chemotherapy for HL has been administered successfully during the second and third trimesters with positive outcomes for both the mother and developing fetus. (See 'Chemotherapy' below.)

With radiation therapy, increasing uterine fundal height affects total dose exposure from internal radiation scatter [1]. The closer the fetus is to the diaphragm, the greater the possible whole body fetal dose when the mother receives radiation above the diaphragm. However, this effect is potentially counteracted by the larger fetus being more developed and therefore less sensitive to radiation. Older studies have estimated fetal radiation exposure after mantle radiation during the three trimesters [1,6,20-24].

Obstetric and maternal outcome — A retrospective study compared obstetric and maternal outcomes for pregnant women with cHL who received antenatal chemotherapy (72 women) versus those who did not receive antenatal treatment (56 women) and those who received radiation therapy alone (6 women) [25]. In this analysis of the International Network on Cancer, Infertility, and Pregnancy (INCIP) database, there was increasing use of chemotherapy over the period of the study (1969 to 2018). Birthweight percentiles were lower in neonates prenatally exposed to chemotherapy compared with non-exposed neonates. Compared with those who did not receive antenatal treatment, patients who received antenatal therapy had more obstetric complications; the most common complications were preterm contractions (12 versus 7 percent) and preterm rupture of membranes (5 versus 0 percent).

Long-term outcome — The late manifestations of in utero exposure to antineoplastic agents may include impaired growth, diminished neurologic and/or intellectual function, decreased gonadal and reproductive function, mutagenesis of germ-line tissue, and carcinogenesis [26]. There are limited data that address the risks that may be involved. However, case series have demonstrated relatively good outcomes among children who were exposed to ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) during the second or third trimester [7,27,28].

One of the largest series assessed the status of 43 children exposed to chemotherapy during pregnancy; 14 of the pregnant mothers with HL received MOPP (mechlorethamine, vincristine, procarbazine, and prednisone) and/or ABVD, five of them during the first trimester [7]. The children ranged in age from 3 to 19 years at the time of evaluation and were compared with a case control group of 25 children. In a comprehensive evaluation, all of the 43 children were within the normal range for routine blood work, lymphocyte function, immunoglobulins, cytogenetics, bone marrow aspirate and biopsy, school performance, neurologic testing, sexual development, and medical history. Further follow-up of the same cohort with expansion to 26 mothers with HL and a median follow-up of 18.7 years confirmed good health in the children and grandchildren [28].

MANAGEMENT OF HL DURING PREGNANCY — The management of HL during pregnancy requires a careful balance between maximizing the chance of cure and minimizing the potential harm to the developing fetus [29]. While most pregnant women with HL diagnosed during pregnancy undergo therapy, case series have suggested that treatment can be safely deferred in selected women until fetal development and growth permits safe delivery [5]. (See 'Selection of patients for deferred therapy' below.)

The selection of initial treatment during pregnancy depends upon the trimester and the location and stage of disease. In general, therapy should be delayed until at least the second trimester, if possible, since the risks of treatment to the fetus are greatest during the first trimester. Some patients may be candidates for deferred therapy after the first trimester (ie, asymptomatic, stable, nonbulky, supradiaphragmatic disease). However, appropriate therapy should not be delayed past the first trimester in patients with symptomatic, bulky, subdiaphragmatic, or progressive HL. In addition, disease that seriously threatens the immediate well-being of the mother (eg, acute airway obstruction, spinal cord compression) requires emergent treatment at any time.

●First trimester – For most women with HL diagnosed during the first trimester of pregnancy, we recommend deferral of treatment until the second or third trimester, if possible. Patients with symptomatic or progressive HL that threatens the immediate well-being of the mother require treatment with chemotherapy. For patients who require a rapid tumor response, we suggest combination chemotherapy with ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine). For patients who have progressive disease but do not require a rapid tumor response, we also suggest ABVD. If chemotherapy is necessary within the first trimester, particularly early in the first trimester, termination of the pregnancy may also be discussed, as described below. (See 'Elective termination of pregnancy' below.)

●Second trimester – For most women with limited stage HL diagnosed during the second trimester of pregnancy, we suggest treatment with combination chemotherapy with ABVD. A subset of patients (ie, asymptomatic, stable, nonbulky, supradiaphragmatic disease) may choose close clinical monitoring with plans to administer chemotherapy after delivery. Radiation therapy may be used for local control of highly symptomatic disease above the diaphragm.  

●Third trimester – For women with HL diagnosed during the third trimester of pregnancy, we suggest deferral of treatment until after delivery, if possible. This allows for a full staging evaluation and selection of appropriate therapy after delivery. However, patients with symptomatic or progressive HL that threatens the immediate well-being of the mother require treatment with chemotherapy. For such patients, we suggest combination chemotherapy with ABVD.

These treatment choices are described in more detail in the following sections. Despite the increasing availability of guidelines for the treatment of HL, there must remain room for individualization of treatment. In particular, patient preference must be considered with different treatment options, some of which result in a higher recurrence risk at the gain of less toxic initial treatment.

The issue of pregnancy termination varies with the clinical setting. It is rarely medically indicated with newly diagnosed HL, since even combination chemotherapy (ie, ABVD) has been successfully administered in the first trimester. Similarly, relapse that occurs after radiotherapy alone may be satisfactorily managed with chemotherapy. In contrast, pregnancy termination is often indicated with relapsed HL following combination chemotherapy, since high-dose chemotherapy with stem cell support (autologous hematopoietic cell transplantation) is usually the preferred therapy. (See 'Elective termination of pregnancy' below and "Treatment of relapsed or refractory classic Hodgkin lymphoma", section on 'Hematopoietic cell transplantation (HCT)'.)

Selection of patients for deferred therapy — If possible, therapy for HL should be delayed until at least the second trimester, since the risks of treatment to the fetus are greatest during the first trimester. Some patients may be candidates for further deferral of therapy beyond the first trimester or even until after delivery. This approach is preferred by some clinicians due to the potential teratogenicity of treatment and the indolent clinical nature of many cases of HL. Examples of candidates for further deferral of therapy beyond the first trimester or even until after delivery include:

●"Limited" clinical stage IA or IIA HL presenting during the late second and third trimester (table 1)

●Stable "non-urgent" HL diagnosed after 20 weeks gestation

There have been no prospective trials that have compared deferred therapy with immediate treatment in this setting. It is unknown whether deferral of therapy has an impact on long-term survival rates. Data regarding the safety and efficacy of this approach come from two case series:

●The Stanford group described five women in whom therapy was delayed: three with clinical stage IIA HL, all of whom were in continuous complete remission following successful therapy postdelivery; and two with infradiaphragmatic disease, both of whom died of HL despite therapy postdelivery [3,4].

●A Canadian group used a minimalist approach to manage 17 women with HL during pregnancy [30]. Eleven did not require therapy until after delivery and six were managed with single agent vinblastine during pregnancy. All 17 delivered healthy babies who had a median age of 15 years at last follow-up. Of the 17 women, 13 were alive and in complete remission while four had died (two from HL, one from acute myeloid leukemia, and one from retroperitoneal sarcoma).

The decision to treat or monitor the pregnant woman with HL must be individualized. Deferral of immediate therapy allows for accurate staging of disease after delivery and treatment based upon disease stage; however, it is unknown whether deferral of therapy impairs disease control and affects survival. If deferral is selected, patients must be monitored closely for progression. Monitoring is easier in patients with disease that is easily assessable with physical examination. Serial abdominal ultrasound can also monitor for the development or progression of subdiaphragmatic disease.

Chemotherapy — Combination chemotherapy offers potentially curative treatment of HL. However, because of concern regarding possible immediate and delayed side effects to the fetus and delivered child, conventional combination chemotherapy has had limited study in the pregnant patient. For most women with HL diagnosed during the first trimester of pregnancy, we recommend deferral of treatment until the second or third trimester, if possible.

In a comprehensive review of antineoplastic agents and pregnancy, the incidence of fetal malformations was approximately 15 percent after exposure during the first trimester [31]. The risk was greatest with alkylating agents and antimetabolites, while vinblastine was associated with the lowest risk (one abnormality among 14 patients treated in the first trimester). Similar data were found in another series [6].

During the second and third trimesters, chemotherapy was associated with a low risk of fetal malformation (1.3 percent of 150 exposed patients) that was probably not significantly different from the normal population (3.1 percent) [31]. However, the relative lack of anomalies should not be interpreted as fetal safety, since delayed effects remain a significant concern. (See 'Long-term outcome' above.)

Specific regimens — The ideal chemotherapy regimen to use for HL during pregnancy is unknown. The main options include combination chemotherapy with ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine (table 3)) or single agent vinblastine. MOPP (mechlorethamine, vincristine, procarbazine, and prednisone) does not appear to be as safe as ABVD and is no longer used for the initial treatment of HL [31]. There are no data regarding the use of BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone) or Stanford V (doxorubicin, vinblastine, mechlorethamine, vincristine, bleomycin, etoposide, and prednisone) during pregnancy.

Data regarding the use of chemotherapy for HL during pregnancy come largely from small case series. A 2008 comprehensive literature review published by the American Society of Hematology, summarized data from case series and reported that there was very limited information [32]. Good fetal outcomes were reported following either standard ABVD or single agent vinblastine. Of these, ABVD was generally preferred because it is a standard of care for patients with HL that appears to have limited fetal toxicity when administered during pregnancy. However, some clinicians may choose single agent vinblastine due to lower rates of expected fetal toxicity. In general, pregnant women receive similar body surface area based chemotherapy doses as nonpregnant women, which are adjusted with continued weight gains. (See 'Effect of pregnancy on drug pharmacokinetics' below.)

If chemotherapy (either ABVD or single agent vinblastine) is administered during pregnancy, staging after delivery cannot be used to guide initial treatment. Instead, patients should be treated after delivery as if they had advanced stage HL at diagnosis (eg, six cycles of ABVD, which includes treatment given during and after pregnancy). (See "Initial treatment of advanced (stage III-IV) classic Hodgkin lymphoma", section on 'ABVD chemotherapy'.)

Antiemetics — Antiemetics, including promethazine, selective serotonin (5-HT) antagonists, neurokinin 1 (NK1) antagonists, and droperidol combined with diphenhydramine or dexamethasone are used to treat severe nausea and vomiting in pregnant women and are generally considered safe. However, long-term dexamethasone therapy should be avoided, if possible, because of potential maternal and fetal risks. (See "Nausea and vomiting of pregnancy: Treatment and outcome".)

Effect of pregnancy on drug pharmacokinetics — In general, pregnant women receive similar body surface area based chemotherapy doses as nonpregnant women, which are adjusted with continued weight gains [33]. Little information is available regarding the pharmacokinetics of individual cytotoxic agents in the pregnant patient. Alterations in drug distribution are expected due to the physiologic changes that occur with pregnancy, which include:

●Increases in blood volume and renal and hepatic clearance might be expected to reduce active drug concentrations. (See "Maternal adaptations to pregnancy: Renal and urinary tract physiology".)

●Diminished gastric motility may affect the absorption of orally administered drugs.

●Plasma albumin decreases in pregnancy, increasing the amount of unbound active drug; however, this effect is counterbalanced by high levels of estrogen, which increases other plasma proteins.

●The "third space" of the amniotic sac.

●The multidrug resistance p-glycoprotein has been detected in fetal tissues and in the gravid endometrium and may offer some degree of protection to the fetus [15].

It is unclear how these physiologic changes affect active drug concentrations and their resulting efficacy and toxicity. The deleterious effects of drug exposures on the fetus are discussed separately. (See "Congenital anomalies: Approach to evaluation".)

Radiation therapy — Radiation therapy can offer local disease control, but is associated with teratogenesis and an increased risk of childhood malignancy. Many series have documented the effectiveness of radiation therapy for treatment of HL during pregnancy [1-3,5,6]. Several principles should be followed when this approach is chosen:

●Irradiation should be delayed until the second or third trimester

●The whole body fetal dose should be limited to 0.10 Gy or less

●The aim is for local response and disease control until delivery

One series provided a complete analysis of 16 pregnant women (2 stage IA and 14 stage IIA) with HL who were treated at MD Anderson Cancer Center [1]. Radiation therapy was administered as involved field to the neck (35 Gy) in two, extended field to neck/mediastinum (40 Gy) in three, and full mantle irradiation (40 Gy) in the others. Uterine shielding was maximized by four to five half-value layers of lead. The estimated dose to the fetus was 0.011 to 0.055 Gy with 6 MV photons and 0.10 to 0.14 Gy for cobalt 60. Following delivery, 10 patients had lymphangiography and five underwent staging laparotomy (two with positive findings). Eight patients subsequently had additional radiation therapy and/or chemotherapy. All offspring were reported to be physically and mentally normal and the 10-year survival of the patients was 83 percent.

Similar findings were noted in a review of 23 patients who received supradiaphragmatic radiation therapy (five in the first trimester) with apparently no harm to the fetus noted [6]. Seventeen of these patients (74 percent) had no evidence of HL at the time of the report.

Fetal outcome following radiotherapy is dependent upon gestational age when radiation is given, whole body fetal dose, and maternal health. A higher frequency of spontaneous abortion and congenital anomaly has not been convincingly demonstrated. Among the series described above, 16 pregnancies resulted in 16 full-term infants [1], and 10 pregnancies resulted in one spontaneous abortion in a patient irradiated during the first trimester, three therapeutic abortions, and six normal infants [3].

Radiation fields should be designed with measures that will minimize the fetal dose by maximizing the distance between the inferior border of the field and the uterus. Protection of the uterus during radiotherapy should be with 10 HVL shielding. Calculation of the maximal dose to the fetus should be performed prior to treatment and the dose to the fetus should be monitored during treatment [34].

Elective termination of pregnancy — The decision to continue or terminate the pregnancy should be individualized and made by a fully informed woman in conjunction with her clinician. Elective termination of the pregnancy is rarely medically indicated with newly diagnosed HL, since even combination chemotherapy has been successfully administered in the first trimester. In contrast, pregnancy termination is often indicated with relapsed HL following combination chemotherapy, since high-dose chemotherapy with stem cell support (autologous hematopoietic cell transplantation) is usually the preferred therapy.

In addition to the usual reasons for pregnancy termination, some factors that should be considered in women with HL during pregnancy include:

●Whether she is willing to assume a possible risk of fetal toxicity or complications from HL treatment during pregnancy

●Her prognosis and ability to care for her offspring

●The effect of HL treatment on future fertility (see "Overview of infertility and pregnancy outcome in cancer survivors")

DELIVERY OF THE INFANT — The timing of delivery of the infant must be a joint decision between the obstetrician, hematologist-oncologist, and the patient. Whenever possible, the fetus should be carried to term without compromising the health of the mother or infant. If not, the fetus should be delivered after demonstration of fetal pulmonary maturity and at 34 or more weeks of gestation at which time morbidity of prematurity is relatively low. Cesarean section is not necessary unless obstetrically indicated, and staging laparotomy, performed in conjunction with delivery, is not warranted. (See "Preterm birth: Definitions of prematurity, epidemiology, and risk factors for infant mortality".)

The importance of avoiding iatrogenic preterm delivery was illustrated in a multicenter observational study of 70 children who were exposed to maternal cancer staging and treatment during gestation and followed for a median of 22 months (range 17 to 212 months) [35]. Exposure to chemotherapy during gestation was not associated with increased central nervous system, cardiac, or auditory impairment. However, cognitive development scores were lower for children born preterm, with intelligence quotient increasing by an average of 11.6 points for each additional month of gestation.

If treatment has been administered prior to delivery, the blood counts of both the mother and the infant should be monitored for the development of cytopenia [7,27]. If possible, no potentially myelosuppressive therapy should be administered within three weeks of delivery. The timing of chemotherapy may also become important prior to delivery since the neonate has a limited ability to metabolize and excrete drugs [36]. Thus, transient cytopenias have been described in some infants of mothers with lymphoma or leukemia who received chemotherapy within 30 days of delivery [7,27].

MANAGEMENT AFTER DELIVERY — Patients who have deferred treatment until after delivery can undergo a standard staging evaluation and proceed with treatment as in the nonpregnant patient. Imaging studies performed after chemotherapy or radiation therapy will not provide accurate data regarding the initial stage of disease. As such, patients who receive treatment should proceed with further treatment as if they initially had advanced stage disease. (See "Pretreatment evaluation, staging, and treatment stratification of classic Hodgkin lymphoma".)  

It is recommended that breastfeeding be discontinued once staging and therapy are begun, since contrast and nuclear medicine imaging agents, chemotherapy, and ancillary supportive medications may concentrate in breast milk. Many cytotoxic drugs, especially the alkylating agents, are excreted in breast milk [37,38]. Neonatal neutropenia has been reported in an infant breastfed during maternal treatment with cyclophosphamide [39]. As a general rule, breastfeeding should be avoided in women while receiving chemotherapy.

Due to safety concerns, most radiologists suggest that patients avoid contact with infants for 12 hours following a PET scan.

INFLUENCE OF PREGNANCY ON THE COURSE OF HL — Pregnancy appears to have no significant effect on the course of HL, based on limited retrospective studies.

Analysis from the International Network on Cancer, Infertility, and Pregnancy database reported no difference in progression-free survival or overall survival of 77 pregnant patients treated between 1969 and 2018 versus 211 non-pregnant, matched controls [25]. Other older and/or less well-controlled studies reported similar conclusions [1-4,6,7,25,40-42].

SPECIAL CONSIDERATIONS DURING THE COVID-19 PANDEMIC — The coronavirus disease 2019 (COVID-19) pandemic has increased the complexity of cancer care. Important issues include balancing the risk from treatment delay versus harm from COVID-19, ways to minimize negative impacts of social distancing during care delivery, and appropriately and fairly allocating limited health care resources. Additionally, immunocompromised patients are candidates for a modified vaccination schedule (figure 1), other preventive strategies (including pre-exposure prophylaxis), and the early initiation of COVID-directed therapy. These issues and recommendations for cancer care during the COVID-19 pandemic are discussed separately. (See "COVID-19: Considerations in patients with cancer".)

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Management of Hodgkin lymphoma".)

SUMMARY

●Presentation – Clinical presentation of classic Hodgkin lymphoma (cHL) in pregnancy is similar to that in non-pregnant patients, and may include painless lymphadenopathy, symptoms related to a mediastinal mass, pruritus, and other symptoms. (See 'Clinical presentation' above.)

●Diagnosis – Pathologic confirmation by lymph node or other biopsy is best with an excisional or incisional biopsy or multiple core needle biopsies; fine needle aspiration is not adequate to establish the diagnosis and subtype. (See 'Diagnosis' above.)

●Staging – Staging with magnetic resonance imaging (MRI) of the chest, abdomen, and pelvis (table 2) is according to Lugano criteria (table 4). (See 'Staging during pregnancy' above.)

●Initial treatment – Guided by the trimester and the location and stage of disease. Treatment should be delayed until the second or third trimester or after delivery, but acute airway obstruction, spinal cord compression, or other immediate threats to the mother's well-being require emergency treatment at any time. (See 'Management of HL during pregnancy' above.)

•First trimester – For most women diagnosed with cHL in the first trimester of pregnancy, we recommend deferral of treatment until the second or third trimester, if possible (Grade 1C). (See 'First trimester' above.)

Symptomatic or progressive disease that threatens the mother's immediate well-being requires treatment; termination of the pregnancy should be considered, especially for medical emergencies early in the first trimester. (See 'Elective termination of pregnancy' above.)

•Second trimester – For most women with limited stage cHL diagnosed in the second trimester, we suggest ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine), rather than radiation therapy (RT) or observation alone (Grade 2C). RT may be used for local control of highly symptomatic disease above the diaphragm. (See 'Second and third trimesters' above and 'Selection of patients for deferred therapy' above.)

Asymptomatic and clinically stable patients with non-bulky supradiaphragmatic disease may choose to defer chemotherapy until after delivery.

•Third trimester – For women with cHL diagnosed in the third trimester, we suggest deferral of treatment until after delivery, if possible, to enable thorough staging and definitive treatment (Grade 2C).

However, patients with progressive or symptomatic disease that threatens the mother's immediate well-being requires prompt therapy.

●Adverse effects on the fetus – Chemotherapy treatment during the second/third trimesters is associated with low birth weight, intrauterine growth restriction, premature birth, stillborn fetus, impaired functional development, intellectual disability (mental retardation), and diminished learning capability. Late manifestations of in utero exposure include impaired growth, diminished neurologic and/or intellectual function, decreased gonadal and reproductive function, mutagenesis of germ-line tissue, and carcinogenesis. (See 'Long-term outcome' above.)

●Delivery of care – A high-risk obstetrician should participate in management of all pregnant women with cHL. Early delivery may not be required if the patient has received, or is receiving, adequate therapy. (See 'Delivery of the infant' above.)

●Medical abortion – Termination of pregnancy is rarely medically indicated with newly diagnosed cHL, but it is often needed with relapsed cHL to enable intensive life-saving treatments, such hematopoietic cell transplantation or immunotherapy. (See 'Elective termination of pregnancy' above.)

ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges Steven Horwitz, MD, who contributed to earlier versions of this topic review.