Multicenter Analysis of Outcomes of Lymphoma in Pregnancy


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Lymphoma is the fourth most frequent cancer to occur in pregnant women. In a multicenter retrospective analysis reported in Journal of Clinical Oncology, Andrew M. Evens, DO, MSc, Chief of Hematology/Oncology at Tufts University Medical Center, Boston, and colleagues examined treatment, complications, and outcomes for Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL) occurring during pregnancy.1 The findings indicate that standard, non-antimetabolite, combination chemotherapy can be administered past the first trimester with few complications.

Study Details

The study included 90 patients from 11 academic centers who had a diagnosis of NHL (n = 50) or HL (n = 40) during pregnancy over a 13-year period (1999–2011). Patients had a median age of 30 years (range, 18–44 years) and median diagnosis occurred at 24 weeks’ gestation. Advanced-stage disease was present in 52% of patients with NHL and 25% of those with HL (P = .01). Of patients with stage I to II disease, 17% of patients with NHL and 30% of patients with HL had B symptoms or bulky disease.

Treatment Details and Outcome

Among the 90 patients, pregnancy was terminated in 6 (7%) to permit immediate chemotherapy. Among the other 84 patients, 28 (33%)—including 32% of NHL patients and 35% of HL patents—had therapy deferred to postpartum; these patients were diagnosed with lymphoma at a median of 30 weeks’ gestation (range, 12–38 weeks). The 56 patients (67%) who received antenatal treatment had lymphoma diagnosis at a median of 22 weeks (range, 6–32 weeks; P < .001), with no difference in median time of diagnosis according to lymphoma type.

Antenatal treatment was started in patients at a median of 25 weeks, with 89% receiving combination chemotherapy, most commonly with standard regimens for the particular lymphoma subtypes. Treatment was started in the second trimester in 37 patients (66%). The overall response rate for the 56 patients who received antenatal therapy was 82%, including complete response in 64%; overall response rate was 71% (complete response in 50%) in NHL patients and 96% (complete response in 83%) in HL patients (P = .03 for overall response rate, P = .013 for complete response).

Complications

The most common complication was induction of labor, in 33% of patients. Perinatal events included premature rupture of membranes in 13% and preeclampsia in 7%. Delivery was via cesarean section in 33% of patients, with such delivery occurring in more NHL patients (44% vs 19%, P = .007). Among the 83 patients for whom timing of delivery was available, 44% had preterm deliveries with no difference based on NHL vs HL (51% vs 36%, P = .19).

Fetal Outcomes

The median gestation at delivery was 37 weeks (range, 31–40 weeks). Gestation went to full term in 47 (56%) of 84 patients, with no differences according to lymphoma type or receipt of antenatal therapy. One miscarriage occurred at 19 weeks’ gestation in a 34-year-old patient with double-hit NHL following one cycle of R-CHOP (rituximab [Rituxan] plus cyclophosphamide, doxorubicin, vincristine, and prednisone). The median birth weight was 2,668 g (range, 1,005–3,628 g). Although there was no difference in birth weight according to receipt of antenatal chemotherapy vs deferred therapy (2,670 g vs 2,665 g, P = .74), there was a trend for infants to be small for gestational age if their mothers had received antenatal therapy (41% vs 9%, P = .09).

Of gestations for which information was available, 8 (11%) of 72 infants, all born to NHL patients, required admission to the neonatal intensive care unit (median stay, 12 days; range, 3–40 days), with no differences based on antenatal therapy vs deferred therapy. Microcephaly was reported in one infant following four antenatal cycles of CHOP for diffuse large B-cell lymphoma in the mother, who started treatment at 28 weeks’ gestation and delivered at 38 weeks. Grade 1 pelviectasis occurred in an infant whose mother received four antenatal cycles of R-CHOP for diffuse large B-cell lymphoma at 21 weeks’ gestation and delivered at 34 weeks due to preeclampsia. No other malformations were detected.

Maternal Outcomes

At a median follow-up of 41 months (range, 6–147 months), 3-year progression-free survival and overall survival rates were 53% and 82% for NHL patients and 85% and 97% for HL patients; rates were 55% and 79% for diffuse large B-cell lymphoma patients and 37% and 90% for patients with T-cell NHL (P = .43 and P = .60, respectively). There were 8 deaths related to NHL, including 5 due to diffuse large B-cell lymphoma, 1 due to peripheral T-cell lymphoma–not otherwise specified, 1 due to Burkitt’s lymphoma, and 1 due to double-hit NHL.

In NHL patients, radiotherapy was the only predictor of inferior progression-free survival (hazard ratio [HR] = 5.19, P = .003) and Eastern Cooperative Oncology Group (ECOG) performance status of 2 to 4 (HR = 5.51, P = .001) and increased lactate dehydrogenase (HR = 9.93, P = .03) predicted inferior overall survival. For patients with diffuse large B-cell lymphoma, radiotherapy predicted inferior progression-free survival (HR = 7.72, P = .008) and poor ECOG performance status predicted worse overall survival (HR = 2.33, P = .04). For patients with HL, multiparous status predicted improved progression-free survival (HR = 0.07, P = .01), presence of B symptoms at diagnosis predicted inferior progression-free survival (HR = 10.78, P = .04), and no variables were predictive of overall survival.

Dr. Evens told The ASCO Post that “When clinically indicated, standard chemotherapy regimens for lymphoma administered during the second and third trimesters were associated with minimal maternal complications or fetal detriment.” In addition, Dr. Evens indicated there were low-risk clinical scenarios with low tumor burden or late gestational diagnosis, where therapy was safely deferred to postpartum. And in all cases, he said it is critical that care be closely coordinated with high-risk maternal-fetal medicine. ■

Disclosure: Dr. Evans reported no potential conflicts of interest.

Reference

1. Evens AM, Advani R, Press OW, et al: Lymphoma occurring during pregnancy: Antenatal therapy, complications, and maternal survival in a multicenter analysis. J Clin Oncol. September 16, 2013 (early release online).


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