Clinical Features and Prognosis of Behcet's-like Syndrome in Myeloid Neoplasms with or without Trisomy 8

Introduction

Behçet disease, a specific form of systemic vasculitis, is associated with an increased risk of malignancy, particularly hematological malignancies. There is a noted correlation between gastrointestinal involvement in Behçet-like syndrome (BS), MDS/AML, and trisomy 8, though the exact mechanism remains unclear. This is thought to be related to genetic susceptibility and immune system abnormalities. This study aims to examine the clinical features and long-term outcomes of patients with hematological malignancies complicated by BS, and to assess the effect of trisomy 8 mutations on the clinical characteristics and prognosis of these patients.

Methods

The clinical data of 24 patients with myelodysplastic syndrome or leukemia complicated by Behçet-like syndrome, admitted to the Department of Hematology at the First Affiliated Hospital of Zhejiang University from January 2016 to October 2023, were retrospectively reviewed. These patients were categorized into two groups: those with trisomy 8 and those without. Additionally, data from 97 case reports and studies were examined to compare baseline characteristics, classification, prognostic stages, and leukemia transformation rates between the two groups. The primary outcome was overall survival (OS), and Cox regression analysis was employed to identify factors influencing OS.

Results

Of the 24 patients, 15 (62.5%) had MDS and 8 (33.3%) had AML, of which 5 (20.8%) had MDS transformation and 1 (4.17%) had ALL. Half of the patients (54.2%) had trisomy 8. Among the patients with trisomy 8, males were more common (76.9%), and females were more common in patients without trisomy 8 mutation (87. 5%), and there was significant difference in gender distribution between the two groups (P<0.05). The erythrocyte sedimentation rate of patients without trisomy 8 was significantly higher than that of patients with trisomy 8 mutation (44.0±9.3 vs 100.7±4.7, P<0.05). There were no significant differences in age, sequence of onset, interval of onset, peripheral blood cell count, hsCRP, clinical manifestations and complications between the two groups. The median OS of all patients was 20.24 months (IQR 8.16-38.15 months), 20.20 months in the group with trisomy 8, and 20.42 months in the group without trisomy 8. There was no statistical difference between the two groups (P >0.05). Combined with literature review, 136 patients were included in this study, 76 (55.9%) were female, 91 (66.9%) was BS onset before hematologic disease, and 104 (76. 5%) had trisomy 8. Gastrointestinal involvement was observed more frequently in patients with trisomy 8 than in patients without trisomy 8 (96.2% vs. 84.4%, P=0.020). There was no statistical difference in gender, clinical manifestations, treatment and complications between the two groups. Female (P<0.01), hematologic disease onset before BS (P<0.01) and hematopoietic stem cell transplantation (P<0.01) had a better prognosis, while Age≥60 years (P<0.01) and AML with history of MDS (P<0.01) had a poor prognosis. The median OS was 55.83 months (95% CI, 50.78-60.88) in patients with trisomy 8 and 73.77 months (95% CI, 0.00-161.17) in patients without trisomy 8. There was no significant difference between the two groups. Univariate Cox regression analysis showed that male (HR: 2.412; 95% CI, 1.264-4.605, P<0.01), AML with history of MDS (HR: 4.391; 95% CI, 1.954-9.864, P<0.01) and BS (HR: 2.154; 95% CI, 1.042-4.455, P=0.038), received HSCT (HR: 0.229; 95% CI, 0.069-0.757, P=0.029) and hematologic disease preceded BS (HR: 0.386; 95% CI, 0.144-0.943, P=0.037). Multivariate Cox regression analysis showed that age (HR: 1.045; 95% CI, 1.008-1.084, P=0.017) was an independent risk factor for prognosis, and hematological disease preceding BS (HR: 0.163; 95% CI, 0.050-0.603, P=0.006) was an independent protective factor for prognosis.

Conclusions

Patients with hematological malignancies complicated by Behçet-like syndrome and trisomy 8 are more prone to gastrointestinal involvement compared to those without trisomy 8. Among these patients, males tend to have a later age of onset and worse prognosis compared to females. Poor prognosis is associated with BS onset prior to hematological disease and over 60 years, while trisomy 8 itself does not directly impact prognosis. Hematopoietic stem cell transplantation significantly extends survival, suggesting it may be an effective treatment for these patients.

No relevant conflicts of interest to declare.