Abstract
7039 Background: Treatment of acute leukemia with intensive chemotherapy (IC) leads to increased risk of infection and bleeding because of myelosuppression. Luteinizing hormone (LH) blockade was found to improve hematopoietic recovery in mice after radiation or chemotherapy through protection of the hematopoietic stem cells (HSCs) which express the LH receptor (Velardi et al, Nat Med 2018). We hypothesized that LH blockade improves hematopoietic recovery following IC in patients (pts) with leukemia. Methods: We assessed gene expression of the LH receptor (LHR) in lineage-specific normal and AML hematopoietic cells from a reference dataset (Corces et al, Nat Gen 2016). We conducted a retrospective analysis on pre-menopausal women with acute myeloid leukemia (AML) or acute lymphoblastic leukemia (ALL) who received IC and Lupron, given for prevention or treatment of abnormal uterine bleeding. Results: LHR was greatest in HSCs, with little or no expression in mature subtypes within the hematopoietic hierarchy. Surprisingly, LHR was expressed on blasts. Since Lupron was more commonly given in younger pts, we performed propensity matching between the Lupron groups (AML N = 64; ALL N = 49) and control (Ctrl) groups (AML N = 128; ALL N = 98 pts). Baseline characteristics including blood counts were well balanced. Pts with AML who had received Lupron had a significantly higher increase in their platelet count following IC (13.8x109/L/year vs Ctrl; p = 0.02). Pts with ALL who had received Lupron had significantly higher increase in their absolute neutrophil count (0.37x109/L/year vs Ctrl; p = 0.02). AML pts in the Lupron group received significantly less blood transfusions vs Ctrl (mean: 23.9 vs 34.7 units; P = 0.002) and less platelet transfusions (mean: 24.4 vs 32.8 units; P = 0.06). There was no difference in event-free and overall survival between the groups in each leukemia cohort. Conclusions: Lupron use in leukemia pts receiving IC was associated with improved long-term blood count recovery. It was also associated with decreased transfusion requirements in AML. Despite expression of the LHR in blasts in addition to normal HSCs, there was no effect of LH blockade on rates of leukemia relapse or death.
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