Response to the Letter to the Editor from Bleyer

We greatly value the peer review offered by Dr. Archie Bleyer ¹ and appreciate the opportunity to respond to his comments.

First, we acknowledge that our opening sentence may have been unclear; we intended to describe the age subset <22 years (within the National Cancer Institute–defined age range of 15–39 years for adolescents and young adults) as the focus of our review, rather than as the upper threshold of young adulthood. We selected this age range because 22 years is the maximum age worldwide for initial registration on pediatric medical services; further, this group is likely to be treated by pediatric oncologists, who often have limited experience in treating pregnant patients, thus the emphasis on this age group in the title. We regret our lack of clarity and value the opportunity to explain this important point. We also concur that our review and management recommendations are relevant to older young adults.

We thank Dr. Bleyer for prompting us to carefully review our references. We respectfully point out that we cited references 43–49 primarily in the context of studies that have shown good maternal and fetal outcome after cytotoxic chemotherapy, including the first trimester. None of these reports, including the description of 143 women in Mexico, referred specifically to methotrexate.

We also appreciate Dr. Bleyer's re-emphasis of the risk of methotrexate-induced embryopathy and his provision of additional references. His comment on the danger of even low doses of methotrexate is well taken; we agree that methotrexate at any dose is unacceptable during early pregnancy. On the basis of our review of the literature, we recommended avoiding intravenous and intrathecal methotrexate through week 28 of pregnancy and considering pregnancy termination if methotrexate is given before 20 weeks, consistent with Dr. Bleyer's recommendations.

We agree that caution is important in the use of prophylactic trimethoprim–sulfamethoxazole during pregnancy. Our article did not directly address the effects of non-cancer-directed drugs used in the treatment of lymphoblastic malignancies during pregnancy, although trimethoprim–sulfamethoxazole replacement with nebulized pentamidine was described for Pneumocystis pneumonia prophylaxis in our second illustrative case.

We appreciate both Dr. Bleyer's insightful comments and the opportunity to clarify these important points in our review and our recommendations for the management of acute lymphoblastic malignancy in pregnant patients <22 years old.