Genetically derived subgroups of MDS that have been defined in the ad hoc study of the International Working Group for Prognosis in MDS
| Molecular subgroup . | Clinical features, outcomes, and disease-related eligibility for allogeneic transplantation . |
|---|---|
| Morphological MDS with the absence of recurrent genetic events in myeloid genes | Good OS with low risk of leukemic transformation. Most patients are not transplant candidates. Patients with VEXAS and severe rheumatic disease may be considered. |
| SF3B1-mutant MDS | Indolent clinical course with low risk of leukemic transformation. Most of these patients are not transplant candidates. |
| ZRSR2-mutant MDS | Male patients with refractory macrocytic anemia, no excess blasts, and indolent clinical course. These patients are not transplant candidates. |
| MDS NOS | Mild phenotype and favorable outcomes in most patients. Most of these patients are not transplant candidates. |
| CCUS-like MDS | Mild phenotype and favorable outcomes in most patients. Most of these patients are not transplant candidates. |
| MDS del(5q) | Well-established MDS subtype whose outcomes are determined by comutation patterns. Patients with comutation in SF3B1, RUNX1, or TP53 should be considered for allogeneic transplantation. |
| MDS with biallelic TET2 mutation | Older patients, monocytosis overlapping with CMML. Indolent clinical course in most patients. Most of these patients are not transplant candidates. |
| DDX41-mutant MDS | Cytopenia with hypoplastic bone marrow with excess blasts. Disorder with high risk of leukemic evolution, but favorable prognosis compared with other MDS with excess blasts. Genomic diagnosis is crucial in the transplantation setting for donor selection and prevention of acute GVHD with PTCy. All patients are potential transplant candidates. |
| U2AF1-mutant MDS SRSF2-mutant MDS BCOR/L1-mutant MDS IDH-STAG2-mutant MDS MDS with der(1;7) −7/SETBP1-mutant MDS EZH2-ASXL1-mutant MDS | Aggressive diseases with poor survival and high risk of leukemic transformation. Although specific agents targeting the driver mutation are being developed (such as spliceosome inhibitors, ivosidenib, or enasidenib). These patients are potential transplant candidates. |
| AML-like MDS | Biologically this condition resembles AML, except for <20% bone marrow blasts. All patients are potential transplant candidates. |
| TP53-complex MDS | Extremely aggressive disease with a median survival <1 year. Poorly responsive to any currently available treatment. High relapse rate after transplantation. All patients are potential transplant candidates, preferably within a clinical trial. |
| Molecular subgroup . | Clinical features, outcomes, and disease-related eligibility for allogeneic transplantation . |
|---|---|
| Morphological MDS with the absence of recurrent genetic events in myeloid genes | Good OS with low risk of leukemic transformation. Most patients are not transplant candidates. Patients with VEXAS and severe rheumatic disease may be considered. |
| SF3B1-mutant MDS | Indolent clinical course with low risk of leukemic transformation. Most of these patients are not transplant candidates. |
| ZRSR2-mutant MDS | Male patients with refractory macrocytic anemia, no excess blasts, and indolent clinical course. These patients are not transplant candidates. |
| MDS NOS | Mild phenotype and favorable outcomes in most patients. Most of these patients are not transplant candidates. |
| CCUS-like MDS | Mild phenotype and favorable outcomes in most patients. Most of these patients are not transplant candidates. |
| MDS del(5q) | Well-established MDS subtype whose outcomes are determined by comutation patterns. Patients with comutation in SF3B1, RUNX1, or TP53 should be considered for allogeneic transplantation. |
| MDS with biallelic TET2 mutation | Older patients, monocytosis overlapping with CMML. Indolent clinical course in most patients. Most of these patients are not transplant candidates. |
| DDX41-mutant MDS | Cytopenia with hypoplastic bone marrow with excess blasts. Disorder with high risk of leukemic evolution, but favorable prognosis compared with other MDS with excess blasts. Genomic diagnosis is crucial in the transplantation setting for donor selection and prevention of acute GVHD with PTCy. All patients are potential transplant candidates. |
| U2AF1-mutant MDS SRSF2-mutant MDS BCOR/L1-mutant MDS IDH-STAG2-mutant MDS MDS with der(1;7) −7/SETBP1-mutant MDS EZH2-ASXL1-mutant MDS | Aggressive diseases with poor survival and high risk of leukemic transformation. Although specific agents targeting the driver mutation are being developed (such as spliceosome inhibitors, ivosidenib, or enasidenib). These patients are potential transplant candidates. |
| AML-like MDS | Biologically this condition resembles AML, except for <20% bone marrow blasts. All patients are potential transplant candidates. |
| TP53-complex MDS | Extremely aggressive disease with a median survival <1 year. Poorly responsive to any currently available treatment. High relapse rate after transplantation. All patients are potential transplant candidates, preferably within a clinical trial. |
CCUS, clonal cytopenia of undetermined significance; CMML, chronic myelomonocytic leukemia; NOS, not otherwise specified.
Modified from Bernard et al.24