Photo credit: Vera Kratochvil
A single-center retrospective study of 39 pregnant women diagnosed with Hodgkin lymphoma (HL) or non-Hodgkin lymphoma (NHL) during pregnancy indicates that delaying treatment until the second trimester is “likely safe and results in acceptable” outcomes for both mother and child.
Investigators also found that deferring therapy until after delivery did not adversely affect maternal outcomes.
In order to clarify the sometimes conflicting reports regarding management of lymphoma during pregnancy, investigators at MD Anderson Cancer Center in Houston, Texas, undertook the study to determine whether administering standard chemotherapy during the second and third trimesters has acceptable maternal and fetal outcomes.
Michelle A. Fanale, MD, and colleagues published their findings in JAMA Oncology.
Patient characteristics
Investigators identified 31 women with HL and 8 with NHL who were diagnosed between 1991 and 2014 and had sufficient pregnancy and follow-up data.
The women were a median age of 28 years (range 19-38). The patients with NHL were significantly older, P=0.004.
Approximately 20% of patients had B symptoms. Most were stage II disease (72%), and 80% were ECOG performance status 0 or 1.
About two thirds of patients had hemoglobin levels less than 12 g/dL.
Most patients did not have extranodal nonbone-marrow disease (82%), although there was a significant difference between those with HL (90%) and NHL (50%), P=0.03.
One third of patients had bulky disease, and 88% were in their second or third trimesters at diagnosis.
Three women electively terminated their pregnancies at diagnosis. Of the 36 remaining patients, 24 (61%) began antenatal therapy and 12 (31%) postponed therapy until after delivery.
Four patients received radiation therapy above the diaphragm at a median dose of 40.4 Gy.
Obstetric outcomes
Antenatal therapy was not associated with increased incidence of preterm delivery. Of the 24 women who received treatment during pregnancy, 7 (29%) gave birth prematurely compared with 5 of the 12 women (42%) who postponed treatment until after delivery, P=0.73.
The investigators noted that the miscarriage rate was approximately 10%, which was higher than previous studies.
Four patients had miscarriages, 2 during the first trimester and 2 during the second. Both patients who had miscarriages in the first trimester had received lymphoma treatment during that time.
And one of the patients who had antenatal therapy during the second trimester and had a miscarriage was critically ill, which the investigators believed was a contributing factor.
The second woman who miscarried after therapy in the second trimester had conceived twins through in vitro fertilization and miscarried at 23 weeks after ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) therapy had been initiated at gestational week 15.
Investigators had fetal outcomes available for 31 of 32 patients who did not terminate or have a miscarriage. And these 31 infants had no anomalies at birth.
The investigators said that although the follow-up time is relatively short, they observed no malformations in the newborns.
Treatment responses and survival
The overall response rate (OR) was 91.7% and the complete response (CR) rate was 75.0% for the 24 patients who started treatment during pregnancy.
And for those 12 women who deferred therapy until delivery, both ORR and CR rates were 91.7%.
The 5-year progression-free survival (PFS) and OS were 74.7% and 82.4%, respectively, for all women. The median follow-up was 67.9 months (range 8.8 to 277.5).
For the 31 women with HL, the 5-year PFS and OS were 69.9% and 80%, respectively.
And for the 8 women with NHL, the 5-year PFS and OS were 85.7% and 83.3%, respectively.
Investigators found no difference in PFS or OS (P=0.84) based on undergoing antenatal lymphoma treatment among the 36 women who did not terminate their pregnancies at diagnosis.
The investigators conducted a univariate analysis and found that for the 36 women who did not electively terminate their pregnancies, the following were associated with increased risk of disease progression:
• Bulky disease—hazard ratio [HR] 3.6, P = 0.06
• Extranodal nonbone marrow involvement—HR 4.2, P = 0.04
• Poor ECOG performance status—HR 3.9, P = 0.005
Poor performance status was also associated with OS, HR 8.88, P = 0.004.
Multivariate analysis revealed significant associations in terms of OS and PFS for extranodal nonbone marrow involvement and performance status:
• Nonbone marrow involvement—OS HR, 73.5, P = 0.02; PFS HR 8.26, P = 0.01
• Performance status—OS HR, 26.7, P = 0.003; PFS HR, 4.89, P = 0.002
The investigators concluded that because they found no differences in PFS or OS according to whether patients received antenatal therapy, they believe that disease factors, rather than treatment-related factors, influence worse maternal outcomes.
They recommended delaying therapy until the second trimester if that can be accomplished without harm to the patient.
