Female sex as an independent prognostic factor in the development of oral mucositis during autologous peripheral stem cell transplantation

Abstract

Oral mucositis (OM) is a frequent complication of stem cell transplantation-associated toxicity in haematological malignancies, contributing to mortality. Therapy still remains mainly supportive. We assessed risk factors in retrospective analysis of 192 autologous peripheral stem cell transplantation patients with lymphoma and multiple myeloma (MM), respectively. Futhermore, we examined the hormone levels both in serum and saliva during transplantation in 7 postmenopausal female patients with lymphoma compared to healthy controls using electrochemiluminescence immunoassay (ECLIA). Multivariable analysis revealed neutrophil engraftment (p < 0.001; p = 0.021) and female sex (p = 0.023; p = 0.038) as independent predictive factors in the combined patient group and in the lymphoma group, and neutrophil engraftment (p = 0.008) in the MM group. Of the 85 female participants 19 were pre- and 66 postmenopausal. Fifteen of the pre-, and 49 of the postmenopausal women developed ulcerative mucositis (p = 0.769), more often with lymphoma than MM (p = 0.009). Serum estrogen decreased significantly both in postmenopausal controls and transplantated patients compared to premenopausals, with no difference in saliva. Serum progesterone level was significantly (p = 0.026) elevated at day + 7 of transplantation, while salivary progesterone increased at day + 7 and + 14. Our results indicate a predominantly negative effect of female sex hormones on oral immunity with role in the aetiopathogenesis of OM.

Is the Sex Difference a Clue to the Pathomechanism of Dry Eye Disease? Watch out for the NGF-TrkA-Piezo2 Signaling Axis and the Piezo2 Channelopathy

“…Sonkodi et al attributed the sex difference in the occurrence of NC-ACL injury to the NGF-TrkA signaling axis on proprioceptive sensory neuron terminals, which is the suggested locus of the primary microinjury of this dichotomous non-contact injury mechanism (Sonkodi et al 2021b ). The current authors suggest that the excessively elevated PGE2 levels might explain the phenomenon that females are more prone to DED and presumably to other mucosal dryness syndromes, as was demonstrated by Gebri et al (Gebri et al 2020 ). In the pre-ovulatory phase of the menstrual cycle, when a marked elevation of estrogen is due to luteinizing hormone (LH) (Sonkodi et al 2021b ), LH also stimulates the NGF-TrkA axis through interleukin-1β in the ovarian cells and promotes TrkA and NGF gene expression and PGE2 release (Dissen et al 1996 ).…”

Confounding factors in the assessment of oral mucositis in head and neck cancer

“…Data on gender impact on OM are not homogeneous. The majority of papers reported a higher risk for OM development in female patients [16][17][18]. The hormonal status could play an important role; it is well known how hormonal post-translational modifications could enhance the risk of cytotoxicity and OM [19].…”

The Incidence of Severe Oral Mucositis and Taste Disturbance in Patients Undergoing Different Conditioning Regimens in Haematopoietic Stem Cell Transplantation

“…This could be because females tend to be smaller and if chemotherapy is calculated with body surface area they generally receive a higher dose per kg. Another explanation maybe the negative effects of female sex hormones as pointed out in a recent study [5]. The gender difference in the incidence of grade 2 to 4 OM was not statistically signi cant.…”

“…As all patients underwent the same treatment, the effect of treatmentrelated risk factors was minimised. Female gender has been consistently reported as a patient-related risk factor [5][6][7]. This could be because females tend to be smaller and if chemotherapy is calculated with body surface area they generally receive a higher dose per kg.…”

“…type of HSCT, conditioning regimens). Reported patient-related risk factors for OM include female gender [5][6][7], age (con icting reports) [8,9] and lower Body Mass Index (BMI) [9,7]. In recent years, oral microbiome and genetic factors have been suggested as risk determinants for OM [10,11].…”