Session: 721. Allogeneic Transplantation: Conditioning Regimens, Engraftment, and Acute Toxicities: Poster III
Hematology Disease Topics & Pathways:
Research, Clinical Research, Adverse Events, Biological Processes, Microbiome
We conducted a prospective single-center study including longitudinal mucositis assessment using the Oral Mucositis Assessment Scale (OMAS) and supragingival plaque collection by 4 calibrated Oral Medicine specialists. We classified patients into 2 cohorts: those receiving high-dose TBI (12-13.2 Gy)-based vs. chemotherapy-based myeloablative conditioning. Mucositis assessment was performed at baseline and days +7, +14, +21, +28, and +84. Total mucositis score (range 0-45) at each timepoint was calculated as the sum of all scores (ulceration and erythema) across all sites. Supragingival plaque samples (baseline and days +14, +28, and +84) were profiled using shotgun metagenomic sequencing, targeting a sequencing depth of 20M read pairs per sample. MetaPhlAn4 was used for species-level taxonomic assignment. When the overall microbiota composition in principal coordinates analysis was significantly different between the 2 cohorts at a given timepoint, MaAsLin2 (Microbiome Multivariable Association with Linear Models) was used to identify taxonomic differences. A significance threshold of 0.05 or 0.10 was considered for P values or Benjamini-Hochberg q values (in multiple testing), respectively.
A total of 43 patients (23 females) were included: TBI cohort (N = 20; 46%) vs. chemotherapy cohort (N = 23; 54%). Most common TBI- and chemotherapy-based regimens were Cy/TBI and Flu/Bu4 in 16 (80%) and 12 (52%) patients, respectively. The chemotherapy cohort was older (median age 52 vs. 37). Acute leukemia was the most common underlying disease (78% vs. 80% of patients in the chemotherapy vs. TBI groups, respectively). Methotrexate was used as a component of GVHD prophylaxis in 70% and 75% of patients in chemotherapy and TBI cohorts, respectively. OM severity peaked at day +7 in the TBI cohort vs. day +14 in the chemotherapy cohort. Afterwards, OM improved in both cohorts and remained similar until day +84. Day +14 OM was more severe in the chemotherapy cohort compared to the TBI cohort (P = 0.004). The comparison at other timepoints was not significant. Other clinical predictors of worse OM were male sex for day +7 (P = 0.008) and older age for day +21 (P = 0.03) mucositis. There was no difference in supragingival microbiota diversity between the 2 cohorts at any of the timepoints. While baseline microbiota composition was similar between the 2 cohorts, a noticeable difference was present at days +14 (P = 0.04), +28 (P= 0.005), and even +84 (P = 0.07). Differential abundance analysis revealed enrichment of Prevotella melaninogenica and Scardovia wiggsiae in the TBI cohort and a Rothia species in the chemotherapy cohort.
In a collaborative multi-aspect longitudinal study between alloHCT and Oral Medicine teams, we demonstrated different dynamics and severity of OM after myeloablative alloHCT depending on whether conditioning was TBI- vs. chemotherapy-based. In addition, in this first profiling of the supragingival plaque microbiota in alloHCT recipients, we characterized a lasting signature of TBI- vs. chemotherapy-based conditioning on the oral microbiota. These conditioning-specific changes in the oral microbiota may have long-term implications for transplant survivors. Novel findings from this work improve current understanding of short- and long-term oral toxicities of myeloablative conditioning.
Disclosures: Rashidi: Seres Therapeutics: Consultancy; Emmes DSMB: Membership on an entity's Board of Directors or advisory committees.