Hematologic Cancers in Pregnancy Pose Substantial Risks

Roxanne Nelson

February 14, 2012

February 14, 2012 — Hematologic cancer in pregnancy, although rare, poses a substantial risk to both mother and fetus. In addition, it poses diagnostic and therapeutic challenges, according to a review article published in the February 11 issue of the Lancet.

The primary goal of treatment is to preserve the mother's health; it should focus on her survival while minimizing treatment-related toxic effects on the fetus.

However, the need to treat a potentially lethal disease coupled with concerns about adverse outcomes for the fetus raise therapeutic, ethical, and social dilemmas, say the authors.

Hematologic cancers are a heterogeneous group of malignancies that differ in their course and management, irrespective of pregnancy. "Therefore, the ability to provide an effective treatment that would rescue the mother while allowing normal fetal development depends on disease characteristics (indolent vs aggressive) and pregnancy stage," explained lead author Benjamin Brenner, MD, director of the Department of Hematology and Bone Marrow Transplantation at the Rambam Health Care Campus, Haifa, Israel.

Pregnancy termination is often advisable at early stages.

"Hence, pregnancy termination is often advisable at early stages, allowing delivery of adequate therapy," he told Medscape Medical News.

Hodgkin's lymphoma is the most common hematologic cancer that occurs during pregnancy, followed by non-Hodgkin's lymphoma and acute leukemia. Diagnosing these malignancies can be challenging because of the overlap between disease and pregnancy-related symptoms, and the limitations of imaging.

Treatment Decisions Highly Varied

Treatment largely depends on the type of malignancy and its characteristics, but in pregnant women, fetal safety must also be considered. "Active management of indolent lymphomas can often be postponed until after delivery without adversely affecting the mother or fetus," said Dr. Brenner. "In contrast, aggressive lymphomas should be treated with no delay, and can be managed relatively safely by administrating the CHOP [cyclophosphamide, doxorubicin, vincristine, and prednisone]-rituximab regimen, irrespective of the pregnancy stage."

However, he emphasized that patients with highly aggressive lymphoma that requires intensive chemotherapy, which often includes methotrexate, should be advised to terminate the pregnancy early because the goal is to save the mother's life.

"Similarly, acute leukemia, being a life-threatening disease, should be immediately treated," Dr. Brenner added. "Therefore, early termination of pregnancy is required to address the need for urgent and optimal chemotherapy."

In their review article, the authors note that acute leukemia requires immediate aggressive treatment, regardless of the stage of pregnancy. Any delay or modification of the treatment regimen can result in a worse prognosis. Women are advised to terminate the pregnancy if diagnosed in the first trimester because of the high risk for toxic effects in both mother and fetus. In addition, further intensive treatment will likely be required, such as stem cell transplantation, which is absolutely contraindicated in pregnancy.

However, in chronic leukemias, such as chronic lymphocytic leukemia and myeloproliferative disorders, pregnancy can often be preserved. "But while the management of chronic myeloid leukemia dramatically improved after the introduction of tyrosine kinase inhibitors, their safety during pregnancy remains a concern," Dr. Brenner noted.

Imatinib (Gleevec) remains the standard treatment for nonpregnant patients with chronic myeloid leukemia, but some data show it to be teratogenic when administered during the first trimester of pregnancy, the authors write. The second-generation tyrosine kinase inhibitors also appear to be teratogenic.

If treatment is needed during the first trimester, it is recommended that interferon alfa be considered instead. In addition, if patients become pregnant after a prolonged molecular remission, they might consider discontinuing imatinib or substituting it with interferon.

Issue of Thrombosis

Another issue is the possible need for thromboprophylaxis because the hypercoagulability induced by pregnancy is worsened by cancer. This can result in maternal and placental vascular complications, such as placental thrombosis.

"Myeloproliferative disorders require special attention to prevent the thromboembolism commonly associated with these diseases, especially during pregnancy and the postpartum period," said Dr. Brenner. Such patients often require thromboprophylaxis, he added.

The diagnosis and management of a hematologic malignancy during pregnancy present ethical and therapeutic challenges, he explained. "Collaborative efforts are necessary to study the epidemiologic characteristics, elucidate underlying mechanisms, and define optimal therapeutic strategies to improve the outcome of mother and fetus."

The Individual Patient

The authors did a really good job...covering the important aspects and issues of treating pregnant women with hematologic cancers, said John Leonard, MD, clinical director of the New York–Presbyterian Hospital/Weill Cornell Center for Lymphoma and Myeloma, who was approached for comment.

As the authors point out, appropriate therapy and outcome have much to do with the individual patient, Dr. Leonard told Medscape Medical News. "It depends on the specific cancer, where the patient is in her pregnancy, and how sick she is."

"These patients fare probably as well as anyone in a similar situation, and there is no real evidence that pregnancy affects the course of the illness," he said. "There is not a lot of evidence that the long-term outcome is any worse in pregnant patients."

The authors have disclosed no relevant financial relationships.

Lancet. 2012;379:580-587. Abstract