Oral Graft-versus-Host Disease: Clinical Presentation, Predictive Factors and Significance

Objective:

To evaluate the clinical presentation, laboratory markers and significance of oral chronic graft-versus-host disease (cGVHD).

Method:

187 patients with cGVHD following allogeneic hematopoietic stem cell transplantation (HSCT) were enrolled in a cross-sectional natural history study protocol of cGVHD at the NIH from 2004-2011. Intraoral examinations performed by clinicians experienced in cGVHD utilized the NIH 15-point oral cGVHD activity assessment scale to assess oral mucosal changes.

Participants with total oral mucosal change scores of 3-15 were categorized as “oral GVHD” and participants with scores of 0-2 as “non-oral GVHD”. The two groups were compared based on demographic, transplant and cGVHD characteristics, laboratory parameters, and patient reported symptoms measures.

Initial univariate analyses were performed and factors associated with oral cGVHD (p<0.05) were included in multivariate logistic regression models.

Result:

Oral cGVHD presented in 44(24%) of patients and occurred most commonly with quiescent or de-novo type of cGVHD onset (p=0.0495), higher NIH average score (p=0.033), lower albumin levels (p=0.0008), higher total complement (p=0.012), and led to greater bother from avoidance of foods (p<0.0001) or oral ulcers (p<0.0001), greater mouth pain (p<0.0001) and sensitivity (p<0.0001).

A final multivariable logistic model, as determined by backward selection, indicated that albumin (p<0.0001), total complement (p=0.0046) and mouth pain (p<0.0001) were jointly associated with oral cGVHD. This model predicted correct classification for 74.3% of oral GVHD and 80.2% of non-oral GVHD patients.

Conclusion:

Chronic GVHD is a clinical syndrome after allogeneic HSCT and the leading cause of morbidity and mortality amongst transplant survivors. Oral cGVHD causes mucosal, salivary and/or sclerotic changes, and is associated with oral related pain and discomfort. The precise characterization and ability to accurately predict oral cGVHD, based on future confirmatory application of our model to the ongoing cGVHD study, will enable further development of effective therapeutic and preventive strategies for oral cGVHD. 

 

Table 1: Demographic Characteristics of NIH cGVHD Cohort.
Total Number of Patients                                     187	Median number of days from transplant                       218 to  GVHD diagnosis                                      (range 0-2058)
Total Number Oral cGVHD                                  44	Conditioning Regimen   Myeloablative                                                  106 (57%)   Total Body Irradiation (TBI)                             72 (39%)
Median Age                                                        45.6                                                          (range 3.7-69.8)
Gender   Male                                                          103 (55%)   Female                                                        84 (45%)	Donor Relationship   Unrelated                                                           72 (39%)   Related                                                             113 (61%)
Disease   ALL/AML/MDS                                         79 (46%)   CML                                                            26 (15%)   CLL                                                               12 (7%)   Lymphoma                                                  35 (20%)   Multiple Myeloma                                        10 (6%)   Sarcoma                                                       1 (0.5%)   Aplastic Anemia/PNH                                   6 (4%)   Immunodeficiency                                         2 (1%)   Other non-malignant                                   1 (0.5%)	Gender match recipient-donor   M/M                                                                   51 (30%)   M/F                                                                    43 (25%)   F/F                                                                     36 (21%)   F/M                                                                    39 (23%)
	Cell Source   Bone Marrow                                                     35 (19%)   Peripheral Blood                                              146 (79%)   Cord Blood                                                            4 (2%)
	HLA Matched   Yes                                                                   148 (82%)   No                                                                      32 (18%)
For all values in above table, continuous variables are shown as median values with ranges and categorical variables are shown as frequencies with percentages

 

Table 2: Variables Significantly Associated with Oral cGVHD
	Non-Oral cGVHD	Oral cGVHD	p-value
Patient, transplant and cGVHD characteristics
Quiescent or de novo cGVHD Onset	79/138 (57.2%)	33/44 (75%)	0.0496
NIH average score	1.02 (0.03)	1.21 (0.07)	0.033
Laboratory Parameters
Albumin	3.7 (0.04)	3.43 (0.07)	0.0008
Total Complement	132.05 (3.35)	148.25 (5.99)	0.012
Patient-reported measures
Bother by avoidance of certain foods due to mouth pain	50/117 (42.7%)	30/36 (83.3%)	< .0001
Bother by ulcers in mouth	37/117 (31.6%)	24/36 (66.7%)	< 0.0001
Mouth Pain	1.1 (0.21)	3.83 (0.56)	< 0.0001
Mouth Sensitivity	(2.12 (0.28)	4.17 (0.53)	< 0.0001
For each of the groups, oral and non-oral cGVHD, continuous variables are shown as means and standard deviations. Categorical variables are shown as proportions with percentages for each group.