Continuation of a Levonorgestrel Intrauterine Device During Hematopoietic Stem Cell Transplant: A Case Report

Case Report

The patient was a 23-year-old nulligravid woman with a history of treated Graves disease and a mood disorder, who presented with severe epistaxis. Her absolute neutrophil count was 1.0×10³/μl with 61% lymphoblasts; her platelets were 19,000/μl. Flow cytometry of peripheral blood was consistent with acute myeloid leukemia (AML). Bone marrow aspiration (both morphological examination and flow cytometry) confirmed the diagnosis of AML; further studies showed positivity for FLT3-ITD, DNMT3A and RUNX1 mutations and normal cytogenetics. Reproductive endocrinology was consulted for menstrual suppression and potential fertility preservation. The patient reported that she had a Mirena® IUD in place, which had been placed one month prior to presentation for contraception and due to her dissatisfaction with persistent irregular spotting while on oral contraceptive pills. She reported scant ongoing vaginal spotting since IUD insertion.

Following counseling regarding options for menstrual suppression, the decision was made with the patient to retain her IUD, as her vaginal bleeding was well-controlled and removing the IUD might cause further bleeding in the setting of severe pancytopenia. She was satisfied with her IUD and preferred to maintain it. She also elected to receive intramuscular leuprolide acetate 11.25 mg for both additional menstrual suppression and hoped for fertility preservation, extrapolated from the breast cancer literature (12). As laboratory values (estradiol 32 pg/ml and progesterone 0.92 ng/ml) indicated that the patient was in the follicular phase of the menstrual cycle, in order to avoid a flare effect, she received oral contraceptive pills (norethindrone 1 mg, ethinyl estradiol 0.035 mg) twice per day for three days prior to administration of leuprolide acetate. Oral contraceptive pills were continued daily for an additional week following administration of leuprolide acetate to address a moderate increase in bleeding, which resolved.

The patient received induction chemotherapy with doxorubicin, cytarabine and crenolanib, an investigational FLT3 inhibitor (AROG Pharmaceuticals, Dallas, TX, USA). Following induction chemotherapy and recovery of hematopoetic function, eight weeks after diagnosis, the anti-mullerian hormone level was 2.9 ng/ml; the patient underwent controlled ovarian hyperstimulation using a gonadotropin-releasing hormone antagonist protocol, with five oocytes retrieved. The patient subsequently received consolidation chemotherapy with cytarabine and continued crenolanib. She continued to have menses after these two courses of chemotherapy.

She was re-admitted two months later, five months after initial diagnosis, for conditioning chemotherapy with fludarabine and busulfan, as well as hematopoietic stem cell transplantation. She received cyclophosphamide after transplant. As predicted, the patient was severely neutropenic during her course and required transfusions, with a platelet nadir of 9,000/μl and hematocrit nadir of 22.4%. Her course was complicated by severe mucositis and nausea, but she did not develop vaginal bleeding after admission for transplant.

The patient's last computed tomographic scan, obtained during her stem cell transplant, confirmed that the IUD remained appropriately positioned. In the months following her hematopoietic stem cell transplant, the patient had thrombocytopenia (to a nadir of 13,000/μl) attributed to idiopathic thrombocytopenia, which improved with prednisone. Repeat bone marrow aspiration has confirmed continued remission; her IUD remains in place with no evidence of infection.