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Hematopoiesis
Impact of luteinizing hormone suppression on hematopoietic recovery after intensive chemotherapy in patients with leukemia
Ferrata Storti Foundation
Haematologica 2021 Volume 106(4):1097-1105
Iman Abou Dalle,1,2 Ronald Paranal,3 Jabra Zarka,1 Shilpa Paul,4 Koji Sasaki,1 Wen Li,5 Jing Ning,6 Nicholas J. Short,1 Maro Ohanian,1 Jorge E. Cortes,7
Elias J. Jabbour1 and Ghayas C. Issa1
1Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; 2Division of Hematology and Oncology, American University of Beirut, Beirut, Lebanon; 3Department of Medicine, Baylor College of Medicine, Houston, TX, USA; 4Department of Clinical Pharmacy, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; 5Division of Clinical and Translational Sciences, Department of Internal Medicine, The University of Texas McGovern Medical School at Houston, Houston, TX, USA; 6Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA and 7Georgia Cancer Center, Augusta University, Augusta, GA, USA
ABSTRACT
Treatment of acute leukemia with intensive chemotherapy leads to an increased risk of myelosuppression. Luteinizing hormone (LH) blockade improves hematopoietic recovery in mice after radiation or chemotherapy, through protection of the hematopoietic stem cells which express the LH receptor. We hypothesized that LH blockade improves hematopoietic recovery following intensive chemotherapy in patients with leukemia. We conducted a retrospective analysis on pre-menopausal women with acute myeloid leukemia (AML) or acute lymphoblastic leukemia (ALL) who received intensive chemotherapy and leuprolide given for abnormal uterine bleeding pre- vention or treatment. Given that leuprolide is more commonly admin- istered in younger patients, we performed propensity score matching between the leuprolide (AML n=64; ALL n=49) and control groups (AML n=128; ALL n=98 patients). Patients with AML who received leuprolide had an additional increase of 13.8x109/L/year in their platelet count, and a 0.19x 109/L/year increase in their lymphocyte count after chemotherapy compared to control (P=0.02; P=0.03 respectively). Those with ALL who received leuprolide had an additional increase of 0.37x109/L/year in their absolute neutrophil count (P=0.02). In AML, leuprolide was associated with higher long-term hemoglobin levels (P<0.001) and less blood transfusions (mean, 23.9 vs. 34.7 units; P=0.002) compared to control. In a multivariate analysis, leuprolide was identified as an independent factor predicting improved hemoglo- bin levels, lymphocyte and platelet counts in AML. In conclusion, leuprolide use in leukemia patients receiving intensive chemotherapy was associated with improved long-term blood count recovery and with decreased transfusion requirements in AML.
Introduction
Hematopoiesis is an uninterrupted process of self-renewal, proliferation and differentiation of hematopoietic stem cells (HSC) in order to produce mature blood cells.1 Maintenance of HSC is essential for regeneration of all bone marrow elements particularly following injuries such as ionizing radiation and/or chemotherapy. Treatment of acute leukemia with intensive cytotoxic chemother- apy results in acute hematopoietic suppression, leading to increased risks of infection and bleeding, especially in older patients where the induction mortality can reach up to 20-30%.2-4 In addition to decreased blood counts, chemotherapy induces HSC senescence causing long-term bone marrow damage and, in some
Correspondence:
GHAYAS C. ISSA
gcissa@mdanderson.org
Received: April 23, 2020. Accepted: November 6, 2020. Pre-published: December 3, 2020.
https://doi.org/10.3324/haematol.2020.256453
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