Treatment of leukemia with intensive chemotherapy increases patients’ risk of infection and bleeding due to myelosuppression, but according to results from a study presented at the 2019 American Society of Clinical Oncology Annual Meeting, luteinizing hormone (LH) blockade could improve long-term blood count recovery and reduce transfusion needs.
“We were surprised to find that patients who received leuprolide in addition to chemotherapy seem to have long-term benefits, including improved count recovery and decreased need for blood transfusions,” lead author Iman Abou Dalle, MD, and corresponding author Ghayas Issa, MD, of MD Anderson Cancer Center in Houston, told ASH Clinical News. “This association could be related to the effect of leuprolide on early hematopoietic stem cell progenitors in these patients, leading to a dormant state, and protecting these important cells from injury caused by chemotherapy.”
This study was based on results from an earlier one in which blocking LH improved hematopoietic recovery in mice after radiation or chemotherapy through protection of hematopoietic stem cells (HSCs) that express LH receptors (LHRs). In the study, Dr. Dalle and co-authors first assessed gene expression of LHR in acute myeloid leukemia (AML) hematopoietic and lineage-specific normal cells. They found that LHR expression was highest in HSCs, and “surprisingly, LHR was expressed on blasts.”
Next, they performed a retrospective analysis on a cohort of women with AML or acute lymphoblastic leukemia (ALL), all of whom were treated with intensive chemotherapy, with or without leuprolide. Leuprolide was administered for the prevention or management of abnormal uterine bleeding.
Because leuprolide was more commonly given in younger patients, the researchers performed propensity matching (according to age, performance status score, and blood counts) between leuprolide groups and control groups, which included:
- AML: 64 patients in the leuprolide group and 128 in the control group
- ALL: 49 patients in the leuprolide group and 98 in the control group
Overall, there were no differences between the groups in baseline characteristics. Median age and blood counts at baseline were well balanced between treatment and control groups.
In the AML cohort, treatment with leuprolide was associated with significantly higher increases in platelet counts of 13.8×109/L per year after intensive chemotherapy, compared with intensive chemotherapy alone (p=0.02).
A similar relationship was observed in the ALL cohort: leuprolide-treated patients experienced higher increases in their absolute neutrophil counts compared with controls (0.37×109/L per year; p=0.02). However, the researchers did not find a significant difference in time to neutrophil recovery between the leuprolide and control groups in the AML cohort (p=0.31).
Treatment with leuprolide also appeared to reduce the need for blood and platelet transfusions in the AML cohort:
- mean number of blood transfusions: 23.9 units for leuprolide-treated patients vs. 34.7 units for controls (p=0.003)
- mean number of platelet transfusions: 24.4 units vs. 32.8 units (p=0.06)
However, this relationship was not observed in the ALL cohort.
Limitations of the study include its retrospective nature and the lack of data showing a causal relationship between leuprolide treatment and lower transfusion burden.
“Our findings suggest that perhaps leuprolide has the additional advantage of improving bone marrow recovery and minimizing transfusions following treatment for patients with leukemia, thus reducing complications such as infections and bleeding,” explained Drs. Dalle and Ghayas. “However, our findings still need to be validated as what we found indicates only an association.”
The authors reported relationships with AbbVie, the manufacturer of leuprolide.
Aboudalle I, Paranal R, Paul S, et al. Impact of luteinizing hormone suppression on hematopoietic recovery after intensive chemotherapy in patients with leukemia. Abstract #7039. Presented at the 2019 American Society of Clinical Oncology Annual Meeting, June 3, 2019; Chicago, Illinois.