Treatment of Behçet's Disease with MDS Trisomy 8
For patients with Behçet's disease and MDS with trisomy 8, allogeneic stem cell transplantation is the definitive treatment that can achieve remission of both conditions, particularly in higher-risk MDS or when Behçet's symptoms are refractory to standard immunosuppressive therapy. 1, 2
Risk Stratification and Initial Assessment
Immediately assess MDS risk category using IPSS-R scoring based on bone marrow blast percentage, cytogenetics (trisomy 8), and degree of cytopenias to determine treatment urgency. 3
Recognize that trisomy 8 in MDS is specifically associated with Behçet's disease manifestations, particularly intestinal ulcers and thrombosis, creating a unique clinical syndrome. 4
Perform HLA typing at diagnosis for the patient and first-degree family members if the patient is ≤70 years old and potentially fit for transplantation, as early donor identification is critical. 3
Evaluate for active intestinal ulcers via colonoscopy and assess thrombosis risk, as these complications are significantly more common in MDS with trisomy 8. 4
Treatment Strategy Based on MDS Risk
Higher-Risk MDS (Intermediate-2 or High IPSS-R)
Proceed directly to allogeneic stem cell transplantation if an HLA-matched sibling or matched unrelated donor is available, as this is the only curative option for both MDS and can induce complete remission of Behçet's symptoms. 3, 1, 2
If immediate transplantation is not feasible, initiate azacitidine 75 mg/m² subcutaneously for 7 consecutive days every 28 days as bridge therapy to reduce tumor burden. 3, 5
Continue azacitidine for at least 6 cycles before assessing response, as most patients only respond after several courses. 5
Consider peripheral blood stem cell transplantation (PBSCT) as an effective alternative to bone marrow transplantation. 2
Lower-Risk MDS with Refractory Behçet's Symptoms
Consider allogeneic stem cell transplantation even in lower-risk MDS if Behçet's disease is refractory to standard immunosuppressive therapy (corticosteroids, TNF inhibitors, thalidomide, cyclosporine). 1
If transplantation is deferred, manage with combination immunosuppression using methylprednisolone, thalidomide, and cyclosporine A. 6
Critical Treatment Precautions
Avoid TNF Inhibitors in This Population
Do not use infliximab or other TNF inhibitors in patients with MDS and Behçet's disease, as this combination places patients at severe risk of life-threatening infections, particularly pneumonia. 6
The theoretical benefit of TNF inhibition for Behçet's symptoms is outweighed by the profound immunosuppression when combined with underlying MDS-related neutropenia. 6
Exercise Extreme Caution with G-CSF
Avoid routine G-CSF use in MDS with trisomy 8 patients who have intestinal ulcers or thrombosis, as G-CSF has been documented to aggravate these symptoms. 4
G-CSF may only be considered during severe, life-threatening infections with profound neutropenia, but should be discontinued as soon as clinically feasible. 4
Supportive Care During Treatment
Transfusion Support
Maintain hemoglobin ≥8 g/dL in stable patients, or 9-10 g/dL in those with cardiovascular comorbidities, using leukocyte-reduced RBC transfusions. 5, 7
Use CMV-negative and irradiated blood products for all potential transplant candidates to prevent complications. 7
Infection Management
Initiate broad-spectrum antibiotics immediately for any fever or infection symptoms given the high risk from combined immunosuppression and neutropenia. 5
Monitor closely for opportunistic infections, particularly if using combination immunosuppressive therapy. 6
Surgical Intervention
Consider surgical resection of severely ulcerated or perforated intestinal segments prior to stem cell transplantation to reduce infection risk and improve transplant outcomes. 2
Ileocecal resection may be necessary for microperforations or uncontrolled bleeding from intestinal Behçet's ulcers. 2
Post-Transplant Outcomes
Complete remission of both MDS and Behçet's symptoms (fever, oral aphthae, genital ulcers, intestinal ulcers) has been documented following successful allogeneic transplantation. 1, 2
The graft-versus-disease effect appears to target both the malignant MDS clone and the autoimmune Behçet's manifestations. 1