Lymphoma in Pregnancy: Excellent Fetal Outcomes and Maternal Survival

SAN DIEGO, CA—Minimal maternal complications and fetal detriment were observed in pregnant patients with Hodgkin's lymphoma (HL) or non-Hodgkin's lymphoma (NHL) who received standard chemotherapy (without anti-metabolites) during their 2nd and 3rd trimesters, according to data from one of the largest studies conducted in this patient group. These results were presented at the American Society of Hematology's 53rd Annual Meeting and Exposition.

Andrew M. Evens, DO, MSc, from the Division of Hematology/Oncology at the University of Massachusetts Medical School, Worcester, and colleagues from nine US academic institutions conducted a comprehensive, retrospective analysis of patients diagnosed with HL or NHL during pregnancy from 1998 to 2011. (See Table). The majority of women were co-managed with high-risk maternal fetal medicine. Data were collected for histology, disease characteristics, therapy received, and fetal and maternal complications. Outcomes and survival were analyzed.

Complete data were available for 82 patients. Median age of the patients was 31 years (range 18–40); 38% were nulliparous and 30% had >1 prior pregnancy. Lymphoma was diagnosed at a median of 24 weeks gestation (range 5–40) with 15% of patients diagnosed in the 1st trimester, 46% in the 2nd trimester, and 35% in the 3rd trimester; 4% had pre-existing follicular lymphoma. Histology was NHL in 52% (n=43) and HL in 48% (n=39). Among those with NHL, 83% (n=33) had B-cell and 17% (n=10), T-cell and 63% had advanced-stage disease. Patients with HL had nodular sclerosis (n=35), mixed cellularity (n=2) or was not otherwise specified (n=2) and 46% had advanced-stage disease; 25% had Stage IIB.

Patients had a median weight gain of +3.1% (range -16% to +23%). Extra-nodal disease was detected in the lung (16%), vagina (12%), liver (12%), breast (8%), kidney (8%), central nervous system (8%).

Five pregnancies were terminated in the 1st trimester (at 5, 8, 10, 10, and 12 weeks) and one in the early 2nd trimester in order to initiate immediate chemotherapy. Forty-eight patients began anti-lymphoma therapy at a median of 25 weeks' gestation (range 13–37), 31 of whom initiated therapy in the 2nd trimester. In low-risk patients (eg, indolent NHL and/or late gestational diagnosis), therapy was deferred post-delivery. For patients who received intrapartum treatment, median gestation at time of diagnosis was 20 weeks compared with 34 weeks for the 28 patients who had therapy deferred (P<0.0001).

Among all patients, 72% of the births were vaginal delivery. Patients who received therapy reached an overall response rate of 87%, 74% of whom achieved complete remission. Gestation went to full-term in 73% of patients, 85% of whom went ≥35 weeks. Delivery occurred at a median of 37 weeks (range 31–40). The 28 patients who deferred therapy had a delivery median of 38 weeks (range 26–40), with 86% of pregnancies carried to term.

Patients had a median follow-up of 41 months (6–157). Among all patients, three-year progression free survival (PFS) was 79% and overall survival (OS), 89%. When examined based on timing of therapy, PFS and OS rates for those who received therapy during pregnancy were 76% and 92% and, for those who deferred therapy, 79% and 83%, respectively. For the six patients who terminated their pregnancies, three-year PFS/OS was 100%. Data for histology-specific three-year PFS and OS were: B-cell NHL: 73% and 82%; T-cell NHL: 50% and 90%; and HL: 90% and 95%, respectively.

Preterm complications were minimal, with induction of labor being the most common (45%). The goal was to have the patients deliver as close to term as possible, Dr. Evens said. No difference in perinatal events, including spontaneous rupture of membranes and preeclampsia (occurring in 5% and 8% of patients, respectively), was observed between patients receiving intrapartum vs deferred therapy. Incidences of chorioamnionitis and endometritis were not reported. Median birthweight was 2427g (range 1005–5262g); there was no significant difference of birth weight among infants whose mothers received intrapartum or post-delivery chemotherapy. One stillbirth and one case of microcephaly were reported; no other malformations were detected.

Dr. Evens concluded that administration of standard HL and NHL chemotherapeutic regimens without anti-metabolites during the 2nd and 3rd trimesters of pregnancy was associated with minimal toxicity and teratogenicity. In low-risk clinical scenarios, such as in patients with indolent NHL and/or late gestational diagnosis, patients may defer therapy to post-partum, which “was associated with overall expected lymphoma-related survival,” he said.

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