Retrospective study of the digestive tract mucositis derived from myeloablative and non-myeloablative/reduced-intensity conditionings with busulfan in hematopoietic cell transplantation patient

Abstract

Busulfan is a major component of chemotherapy conditioning in hematopoietic cell transplantation (HCT). This alkylating agent is highly toxic at myeloablative doses, exposing HCT patients to risks of mortality. Non-myeloablative (NMA) and reduced-intensity conditioning (RIC) using busulfan have shown impaired toxicity. However, the toxicity of NMA/RIC in the digestive tract is poorly described. This study aimed to characterize the mucositis in the oral cavity (OM), oropharynx/esophagus, and gastrointestinal tract derived from conditionings with myeloablative and non-myeloablative doses of busulfan. We retrospectively retrieved clinical data of HCT patients (n = 100) who underwent myeloablative conditioning (MAC) or NMA/RIC with busulfan. Frequency and time duration of mucositis in the oral cavity and oropharynx/esophagus, diarrhea, and prescription of total parenteral nutrition (TPN) and opioids were also collected. OM severity (p = 0.009) and time duration of mucositis in oropharynx/esophagus (p = 0.022) were frequently higher in MAC than NMA/RIC. A myeloablative dose of busulfan was a risk factor for OM grade ≥ 2 (OR = 4.8, p = 0.002) and for mucositis in oropharynx/esophagus ≥ 5 days (OR = 2.64, p = 0.035). A longer duration of mucositis in the oropharynx/esophagus was also associated with an increase in the prescription of opioids (OR = 7.10, p < 0.001).Overall survival (OS) in MAC was significantly higher than that in NMA/RIC (p = 0.017). No variables related to mucositis interfere significantly in OS. In conclusion, myelosuppression in busulfan-based regimens are predisposed to a high risk for severe OM and to prolonged mucositis in the oropharynx/esophagus.

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

“…A higher incidence of grade 3 to 4 OM has been previously observed with myeloablative conditioning compared to reduced intensity conditioning utilizing busulfan-based regimens [13]. In this study, grade 3 to 4 OM was observed in 45% of patients receiving a myeloablative regimen, which is lower than grade 3 to 4…”

“…In recent years, oral microbiome and genetic factors have been suggested as risk determinants for OM [10,11]. Treatmentrelated risk factors have been more frequently analysed in the literature.. Impact of conditioning chemotherapy intensity has con icting data, and it is not clear whether intensity per se is an independent risk factor [9,[12][13][14][15]. Methotrexate (MTX) as an immunosuppressant, and its dose, are consistently reported as a risk factor for OM [14,16,9].…”

Risk factors associated with the development of oral mucositis in pediatric oncology patients: Systematic review and meta‐analysis

“…(2006). Busulfan is an important agent used in conditioning for hematopoietic cell transplantation (HCT) (Eduardo et al., 2019). Although different chemotherapeutic agents were described within the protocols used in the studies, many of these agents were combined with others, a fact that increased their toxicity.…”

“…The alkylating agent busulfan was a potential risk factor for the increase in OM in the study by Fadda et al (2006). Busulfan is an important agent used in conditioning for hematopoietic cell transplantation (HCT) (Eduardo et al, 2019).…”

Challenges and opportunities targeting mechanisms of epithelial injury and recovery in acute intestinal graft-versus-host disease

“…Regimens typically include an alkylating agent like busulfan (Bu), melphalan or cyclophosphamide (Cy) and a purine analog such as fludarabine (Flu), with or without low-dose TBI. Clinical GI toxicity of RIC transplants is reported to be moderate 22 , 23 , and the associated intestinal epithelial damage 16 , 17 and mucositis 24 have been found to be less severe. The occurrence of aGVHD after RIC is reduced as well 25 .…”