Management of Primary Ovarian Insufficiency Among Childhood and Adolescent Leukemia and Lymphoma Survivors and Hematopoietic Stem Cell Transplant Recipients with Benign Hematological Conditions

Introduction: Primary ovarian insufficiency (POI) is a well-documented late effect of cancer survivors that increases risk for primary or secondary amenorrhea, osteoporosis, cardiovascular disease, vasomotor symptoms, infertility, urogenital atrophy, cognitive decline, and overall increased mortality. There is limited data on the existing management and follow up of POI among female patients exposed to cancer treatments. The purpose of this study was to describe outcomes and management of POI in childhood leukemia and lymphoma survivors and patients with non-malignant hematological conditions treated with hematopoietic stem cell transplant (HSCT) at Children's Medical Center (CMC) in Dallas, Texas. Methods: A retrospective analysis was performed for 26 female patients identified through electronic survivorship database containing about 1200 records of female survivors followed at the CMC long-term follow-up (LTFU) program. Inclusion criteria were female patients diagnosed with a hematological malignancy or underwent HSCT due to a benign hematological condition, less than 18 years old at the time of diagnosis, and documented POI as a late effect. Moreover, ICD-9 codes for ovarian dysfunction, amenorrhea, oligomenorrhea, delayed puberty, and infertility were used to identify additional patients. Results: The mean age of the cohort was 7.8 ± 5.2 years at hematological diagnosis. Fifty-four percent of patients were leukemia survivors and 23% had lymphoma. Benign hematological conditions requiring HSCT were aplastic anemia (n = 2), sickle cell disease (n = 1), hemophagocytic lymphohistiocytosis (n = 1), macrophage activation syndrome (n = 1), and thrombocytopenia-absent radius syndrome (n = 1). Almost all survivors (24/26) were HSCT recipients; one patient received two HSCTs. Average age at diagnosis of POI was 14.3 ± 3.2 years with average follow-up of 3.1 ± 2.7 years. At the time of POI diagnosis, 62% of survivors (16/26) were premenarchal. Average cyclophosphamide equivalent dose was 9.8 g/m2 for premenarchal and 13.8 g/m2 for postmenarchal females. In addition, 44% (7/16) of premenarchal compared to 50% (5/10) of postmenarchal female patients received either abdominopelvic or total body radiation. Thirteen out of 16 premenarchal females received estrogen replacement therapy (ERT; 10 oral, 3 transdermal; Table 1). The other 3 patients achieved spontaneous menarche; one was initiated on oral contraceptive pills (OCPs) subsequently. Five premenarchal patients