Evolução e desfecho da leucemia mieloide crônica em mulheres grávidas: uma análise retrospectiva em um serviço de referência em hematologia

Abstract

Chronic Myeloid Leukemia (CML) is a myeloproliferative neoplasm characterized by the presence of the Philadelphia chromosome and the formation of the BCR-ABL1 fusion gene, which is responsible for constitutive tyrosine kinase activity and uncontrolled cellular proliferation. The introduction of tyrosine kinase inhibitors (TKIs) has transformed the prognosis of the disease, enabling deep and sustained hematologic, cytogenetic, and molecular responses.However, pregnancy during treatment requires temporary discontinuation of therapy, which may compromise the maintenance of response and disease control. The aim of this study was to evaluate the clinical course and outcomes of CML in women who became pregnant while receiving TKIs, followed at a hematology referral center in the state of Ceará, Brazil.This is an observational, descriptive, and retrospective study that included patients over 18 years of age with a clinical, cytogenetic, and/or molecular diagnosis of CML, receiving TKIs, who had a confirmed pregnancy between January 2002 and December 2024. Sociodemographic variables, prognostic scores, hematologic, cytogenetic, and molecular response profiles, therapeutic management during pregnancy, time to TKI reintroduction, and disease evolution after delivery were analyzed. Statistical analyses were performed using R software, with p < 0.05 considered significant.A total of 26 pregnancies were identified in 19 women with CML, among approximately 243 patients followed at the center. The mean age at diagnosis was 27 years, with a predominance of low-risk patients according to the prognostic scores evaluated. At the time of conception, 38% of pregnancies occurred in patients with major or deep molecular response, while 62% had not yet achieved an adequate molecular response.During pregnancy, there was a significant increase in the frequency of molecular response loss compared to the pre-pregnancy period (p < 0.05). TKI discontinuation was statistically associated with this loss (p < 0.05), particularly among patients who did not have a deep molecular response prior to conception.After TKI reintroduction in the postpartum period, a significant recovery of molecular response was observed (p < 0.05). Most patients regained at least a major molecular response, and some achieved deep molecular response again. A statistically significant association was observed between pre-pregnancy deep molecular response and a higher likelihood of response recovery after delivery, with a greater proportion of recovery in the previously responsive group (p < 0.05).There were two cases of disease progression and two deaths after pregnancy. Overall survival and event-free survival, estimated by Kaplan–Meier analysis, remained high throughout follow-up. Cases of therapeutic failure or need for permanent TKI switch were infrequent.Pregnancy outcomes were favorable, with a predominance of term births and no significant increase in severe complications. These findings indicate that, under appropriate monitoring, temporary discontinuation of therapy may lead to reversible molecular instability, reinforcing the importance of achieving a deep molecular response prior to conception for better hematologic outcomes.