Fertility management and outcomes after CAR T-cell therapy: an international survey from the Cellular Therapy and Immunobiology working party of the European Society for Blood and Marrow Transplantation

Abstract

Background: CAR T-cell therapy has become a highly effective treatment for hematological malignancies, and emerging evidence indicates promising benefits for non-oncohematological conditions. As its clinical use broadens, understanding long-term outcomes and late complications is crucial. One critical yet understudied area is fertility, for which current evidence remains limited and no formal guidelines provide direction for patients undergoing CAR T-cell therapy. Methods: To address this gap, we conducted a cross-sectional survey on behalf of the Cellular Therapy and Immunobiology Working Party (CTIWP) of the European Society for Blood and Marrow Transplantation (EBMT) focusing on current practices, existing challenges, and reported reproductive outcomes. Questionnaires were distributed electronically (via SurveyMonkey) between Jan 8, 2025 and April 18, 2025 to 247 EBMT-affiliated centers assessing current fertility-related practices and procedures around CAR T-cell therapy. A second, complementary questionnaire was circulated between Dec 23, 2025 and April 9, 2026 to gather detailed information on reported pregnancies following CAR T treatment. Findings: 99 of 247 (40%) centers answered and were included in the analysis. At data censoring, 24 pregnancies were reported in 19 patients, resulting in 18 live births, 2 ongoing pregnancy (one with twins), and 4 miscarriages. Eighteen pregnancies occurred in female CAR T-cell recipients, and six were reported by male recipients through their partners. In patients achieving pregnancy, B cell lymphoma was the most common indication for treatment. Pregnancies in the female cohort occurred naturally in 83% of cases (15/18). Among patients with data, the median time between CAR T-cell infusion and delivery or miscarriage was 3 years (range 4 months–6 years). Although both low- and high-grade Cytokine Release Syndrome (CRS) and Immune Effector Cell–Associated Neurotoxicity Syndrome (ICANS) were reported among these patients, these events did not appear to influence pregnancy outcomes, acknowledging the small sample size. While most centers (52/63, 83%) reported offering fertility counselling before CAR T-cell infusion, 11 centers (17%) indicated that they do not routinely inform patients of the potential reproductive risks. Most centers (79%) offered fertility preservation procedures to male and female patients. The most common barriers to fertility preservation referral were the urgency of initiating bridging therapy to CAR T-cell infusions due to active or rapidly progressive disease in aggressive disease and extensive prior chemotherapy exposure, defined as more than three previous treatment lines. For female patients, the predominant approaches were oocyte cryopreservation (63%) and ovarian tissue cryopreservation (59%). Among male patients, semen collection and cryopreservation was the most frequently used method (93%). Endocrinologic follow-up practices after CAR T-cell therapy varied substantially across centers. Interpretation: We report the largest series of pregnancies and live births after CAR T in patients with hematological malignancies and autoimmune diseases, and the first within Europe. As CAR T-cell therapy is increasingly administered earlier in the treatment algorithms and to younger populations, integrating standardized fertility counselling and preservation strategies into routine care will be essential. The reproductive success highlights the urgent need for robust research and formalized guidelines in this evolving field.