Are patients with myelodysplastic syndrome (MDS) considered immunocompromised?

Are Patients with Myelodysplastic Syndrome Considered Immunocompromised?

Yes, patients with myelodysplastic syndrome (MDS) are considered immunocompromised due to both the disease itself and its treatments. This immunocompromised state significantly impacts their morbidity, mortality, and quality of life.

Understanding Immunocompromise in MDS

MDS causes immunocompromise through several mechanisms:

1. Disease-Related Factors:

   • Dysplastic changes in hematopoietic cell lines affecting neutrophil function
   • Neutropenia (common in more advanced disease)
   • Abnormal immune cell function even when counts appear normal

2. Treatment-Related Factors:

   • Hypomethylating agents (azacitidine, decitabine)
   • Immunosuppressive therapies (ATG, cyclosporine)
   • Lenalidomide and other disease-modifying treatments
   • Allogeneic stem cell transplantation (most profound immunosuppression)

Classification of Immunocompromise in MDS

According to clinical guidelines, MDS patients fall under the definition of immunocompromised patients as they have an "acquired condition" with "hematologic malignancy" 1. They are typically classified as:

• Class B patients: Those with "major comorbidities and/or moderate immunocompromise but currently clinically stable, in whom infection can rapidly worsen the prognosis" 1
• Class C patients: Those with "important comorbidities in advanced stages and/or severe immunocompromise, in which infection worsens an already severe clinical condition" 1 (typically higher-risk MDS)

Risk Stratification and Immune Status

The degree of immunocompromise generally correlates with MDS risk classification:

• Lower-risk MDS (IPSS low or intermediate-1):

  • Moderate immunocompromise
  • May have preserved neutrophil counts but dysfunctional immune cells
  • Treatment with ESAs or lenalidomide may not significantly worsen immune function

• Higher-risk MDS (IPSS intermediate-2 or high):

  • More severe immunocompromise
  • Often have neutropenia and more profound immune dysfunction
  • Treatment with hypomethylating agents further suppresses immune function

Clinical Implications

1. Infection Risk Management:

   • Infections are a leading cause of death in MDS patients 1
   • Prophylactic antibiotics may be needed in neutropenic patients
   • Early detection and aggressive treatment of infections is crucial

2. Vaccination Considerations:

   • Patients may have suboptimal responses to vaccines
   • Live vaccines should generally be avoided
   • Timing vaccinations before intensive treatments when possible

3. Supportive Care:

   • Treatment of infections due to neutropenia is an important part of best supportive care 1
   • Transfusions to cover anemia or thrombocytopenia are important measures 1
   • Growth factors may be used as supportive measures

4. Surgical Risk:

   • MDS patients require special consideration during surgical procedures
   • Multidisciplinary approach involving surgeons, hematologists, and infectious disease specialists 1

Evidence of Immunocompromise in MDS

Research has demonstrated activation-associated immunophenotypic changes on monocytes and granulocytes in clinically infection-free MDS patients, suggesting enhanced immune activity likely due to latent or beginning infections 2. This supports the classification of MDS patients as immunocompromised even before overt infections develop.

Treatment Considerations

Immunosuppressive therapy (IST) can be effective in certain MDS patients, particularly those with:

• Hypoplastic MDS
• Age ≤65 years
• RBC transfusion history <2 years
• Normal karyotype
• HLA-DR15 genotype 1

However, these treatments further compromise immune function, requiring careful monitoring and prophylaxis.

Conclusion

The immunocompromised state of MDS patients requires vigilant monitoring and proactive management to prevent infectious complications that can significantly impact morbidity and mortality. Both the underlying disease and its treatments contribute to this immunocompromised state, making infection prevention a cornerstone of comprehensive MDS management.