The news that she is both pregnant and has been found to have a potentially lethal malignancy is one of the most emotionally wrenching events any young woman ever faces. Understandably, the patient, her partner, their families, and even their caregivers find this experience fraught with anxiety and fear. Being able to provide solid information and a sensible plan of management is a major responsibility of the woman’s oncologist.

All of us who fulfill this role should be grateful for the thoroughgoing analysis provided by Dr. Andrew Evens and his colleagues in their recent publication in the Journal of Clinical Oncology,¹ as reviewed in this issue of The ASCO Post. As with any retrospective collection of special cases from multiple institutions gathered over many years of experience, however, the reader must be careful not to overinterpret the validity of the results.

The authors describe the clinical course of 90 pregnant patients found to have either non-Hodgkin lymphoma (NHL, n = 50) or Hodgkin lymphoma (HL, n = 40) and were able to make several very important observations.

Observation #1: Pregnancies encountered coincident with lymphoma do not need to be terminated.

Two patients already had lymphoma when they became pregnant. Of 11 patients diagnosed in the first trimester of pregnancy, 6 elected to terminate the pregnancy, and treatment was deferred until later in the remaining 5. This is important because major organogenesis is mostly completed during the first trimester, when treatments could be likely to cause major birth defects. After the first trimester, treatments may be tolerated and not likely to cause fetal harm. Most patients were diagnosed in the second or third trimester (79/88, 90%). The large majority (83/84, 99%) of patients who chose to keep the pregnancy successfully reached term delivery.

Observation #2: Intervention is not necessary unless the lymphoma is symptomatic or of a histologic type that threatens rapid progression.

Treatment was deferred until after delivery in 28 patients, primarily those with HL or indolent NHL (HL: 13/40; follicular NHL: 4/5). Deferral of treatment in asymptomatic patients does not appear to jeopardize the mother or child. Thus, only 56 of the 90 patients required intervention, and neither fetal nor maternal outcomes appear to have been negatively impacted by deferral of treatment until after delivery in the 28 patients so managed.

Observation #3: When treatment is required, standard regimens are acceptable.

Most patients received standard regimens such as CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) with or without rituximab (Rituxan) for NHL and ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) for HL. Appropriately, very few patients received radiation (NHL: 5, HL: 4), which should be avoided because scatter radiation reaches the uterus in significant amounts, especially during the late phases of pregnancy.

Observation #4: Term delivery is both desirable and regularly achievable.

Median gestation at delivery was 37 weeks with 56% of patients delivering at full term, indicating that most patients were able to defer delivery until good fetal maturation was achieved, which was also reflected in the low rate of admission to a neonatal intensive care unit (11%). Early induction of delivery is unnecessary unless fetal distress or major complications develop, and is seldom needed.

Observation #5: The infants born to women with coincident pregnancy and lymphoma do well.

Although gestational age was lower than the 10th percentile in 23% of infants, the median birth weight of 2,668 g was in the normal range (> 2,500 g), and neonatal intensive care was seldom needed (11%); only two (2%) fetal malformations were seen.

Observation #6: The mothers do well.

Although the small numbers of patients, the diverse mix of histologic types, and wide distribution of prognostic factors limit conclusions, the outcome of treatment is roughly comparable to that seen in nonpregnant women. Progression-free and overall survival rates at 3 years were 55% and 79% for diffuse large B-cell lymphoma and 85% and 97% for HL, respectively.

Cautionary Remarks

These results describing the outcome of coincident lymphoma and pregnancy are very encouraging. However, several cautions are necessary. First, even though this series is the largest and best reported to date, it is still small and heterogeneous. Follow-up of the mothers is reasonably, but not completely, mature (median, 41 months; range, 6–147 months).

More importantly, no long-term follow-up of the children is provided. Firm conclusions about their well-being cannot be drawn. While the low fetal malformation rate is reassuring, none of the fetuses was exposed to treatment during the first trimester. Furthermore, no one should be complacent about the potential for late consequences in children who are exposed to highly cytotoxic chemicals during fetal development.

Deferral of treatment remains the best choice for asymptomatic patients with less threatening types of lymphoma such as HL and indolent NHL. None of the patients was managed with minimal chemotherapy such as single-agent vinblastine for HL with deferral of multiagent regimens until after delivery, a strategy that has been employed with success by other authorities,² and this approach should not be dismissed.

Finally, all patients were managed by a sophisticated multidisciplinary team, an approach that should be considered mandatory for this challenging clinical situation.

Conclusion

Women, their partners, and their families will continue to be frightened and anxious when pregnancy and lymphoma coincide. Armed with the information provided in this excellent study and the literature reviewed by the authors, the clinical team can provide guarded reassurance that treatment deferral if possible, and standard treatment if necessary, will allow successful term delivery of a normal child and likely cure of the lymphoma for most patients. ■

Dr. Connors is Clinical Director, BC Cancer Agency Centre for Lymphoid Cancer, Vancouver, British Columbia.

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

References

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).

2. Bachanova V, Connors JM: Hodgkin lymphoma in pregnancy. Curr Hematol Malig Rep 8:211-217, 2013.