Myelodysplastic syndromes: Contemporary review and how we treat

Abstract

Myelodysplastic syndromes (MDS) are a heterogeneous group of clonal stem cell disorders with an inherent tendency for leukemic transformation. Diagnosis is currently based on the presence of peripheral blood cytopenias, peripheral blood and bone marrow dysplasia/blasts, and clonal cytogenetic abnormalities. With the advent of next generation sequencing, recurrent somatic mutations in genes involved in epigenetic regulation (TET2, ASXL1, EZH2, DNMT3A, IDH1/2), RNA splicing (SF3B1, SRSF2, U2AF1, ZRSR2), DNA damage response (TP53), transcriptional regulation (RUNX1, BCOR, ETV6) and signal transduction (CBL, NRAS, JAK2) have been identified in MDS. Conventional prognostication is by the revised International prognostic scoring system (IPSS-R) with additional adverse prognosis conferred by presence of ASXL1, EZH2, or TP53 mutations. Currently Food and Drug administration (FDA)-approved drugs for the treatment of MDS are not curative and their effect on survival is limited; they include the hypomethylating agents (HMA) azacitidine and decitabine and lenalidomide for MDS with isolated del(5q). To date, allogeneic stem cell transplant (ASCT) remains the only treatment option for possible cure. Given the current lack of drugs with convincing evidence of favorable effect on survival, we consider ASCT as the treatment of choice for most patients with symptomatic disease, and especially for those with high-risk disease. For nontransplant candidates, participation in clinical trials is preferred over conventional therapy. There is not one right way of treatment for patients who are not candidates for either ASCT or clinical trials and palliative drugs of choice depend on the clinical problem, such as symptomatic anemia (ESAs, danazol, HMA), thrombocytopenia (HMA), or neutropenia (myeloid growth factors). Conversely, there is no controlled evidence to support the use of iron chelating agents in MDS. Going forward, we believe it is time to incorporate mutation information in clinically derived prognostic models in MDS and encourage development of novel drugs with disease-modifying activity.

Concurrent STAT3, DNMT3A, and TET2 mutations in T‐LGL leukemia with molecularly distinct clonal hematopoiesis of indeterminate potential

“…Myelodysplastic syndromes can have similar clinical presentations as T-LGLL (neutropenia, anemia) and frequently demonstrate recurrent mutations in genes including TET2, DNMT3A, ASXL1, and others [7,8]. The mere presence of mutations in these genes, however, does not indicate a malignant hematopoietic neoplasm.…”

Refractory primary immune thrombocytopenia with subsequent del(5q) MDS: complete remission of both after lenalidomide

“…In this patient, lenalidomide initially resulted in complete cytogenetic remission that has been seen in many instances with del(5q) MDS 4. What is particularly interesting is that it also resulted in complete normalisation of platelet count.…”

“…Lenalidomide is the preferred treatment for patients with del(5q) MDS 4. It has multiple mechanisms of action and works both as an immune modulator and has also been shown to induce ubiquitination and degradation of CK1α.…”

Successful Treatment of Lung Aspergillus terreus Infection After a Second Hematopoietic Stem Cell Transplant in a Patient With Myelodysplastic Syndrome

“…Our patient was newly diagnosed with very high-risk MDS; in the absence of an HLAmatched donor, haploidentical HSCT was an appropriate choice. 2 Unfortunately, the patient developed graft failure posttransplant. Risk factors for graft failure include donor/recipient HLA disparities, use of an unrelated donor, use of cord blood as a stem cell source, T-cell depletion of the graft, use of reduced-intensity conditioning regimens, low numbers of transplanted cells, and the presence of DSAs.…”