What is the role of immunosuppressive therapy for myelodysplastic syndrome (MDS)?

Updated: Jul 24, 2018
  • Author: Emmanuel C Besa, MD; Chief Editor: Koyamangalath Krishnan, MD, FRCP, FACP  more...
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Some cases of MDS have an autoimmune process underlying the pancytopenia and respond to immunosuppressive therapy (IST). However, identifying these cases is problematic.

A portion of these cases represent an overlap between aplastic anemia (AA), paroxysmal nocturnal hemoglobinuria (PNH), and MDS. These patients are usually younger and may have hypoplastic bone marrow with dysplasia and cytogenetic abnormalities (separate from AA). In addition, they may have a small clone of PNH cells, but these typically constitute less than 3% of cells and require a special sensitive flow cytometry to be detected. Indeed, as little as 0.126% of granulocytes and 0.001% of erythrocytes (PNH-type cells) are positive.

A feature of some of these cases is HLA-A allele–lacking leukocytes (HLA-LLs). These are derived from hematopoietic stem cells that develop copy number–neutral loss of heterozygosity of the HLA haplotype owing to uniparental disomy of the short arm of chromosome 6 (6pUPD).

Patients with MDS who have a thrombopoietin (TPO) level ≥320 pg/mL (TPO high patients) exhibit a high progression-free survival rate and good response to IST, similar to cases of AA. The small number of cases reported and the limited access to the special tests required make it difficult to place these into perspective for general clinical use.

Trials of IST in MDS have used cyclosporine (56%); rabbit (27%) or horse (35%) anti-thymocyte globulin (ATG); alemtuzumab; and recently, sirolimus. At the author's institution, a combination of ATG and cyclosporine is used in AA. Studies of this combination in MDS have reported response rates of only 16-30%, however, which is problematic, especially in view of the small number of patients studied. [33] Responses have mostly been observed in notably lower-risk MDS and patients with HLA-DR15 positivity. Consequently, this form of therapy is considered experimental and should be performed in the setting of clinical trials.

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