Clinical, histopathological and molecular characterization of hypoplastic myelodysplastic syndrome

Abstract

Diagnostic criteria for hypoplastic myelodysplasic syndrome (h-MDS) have not been clearly established, making the differential diagnosis from other bone marrow failure syndromes (BMF) challenging. In this study, we aimed to delineate clinical, histopathological, and molecular features of h-MDS, based on a large and well-annotated cohort of patients with bone marrow (BM) hypocellularity. The study included 534 consecutive adult patients with hypocellular BM (278 h-MDS and 136 aplastic anemia), and 727 with normo-or hypercellular MDS (n-MDS). Comparison of clinical features of patients with h-MDS as defined by BM cellularity ≤25% (n = 204) or reduced age-adjusted cellularity (n = 74) did not reveal significant differences. We developed a diagnostic score to discriminate h-MDS from non-malignant BMF based on histological and cytological variables with the highest specificity for MDS (h-score). The information from chromosomal abnormalities and somatic mutation patterns was then integrated into a cyto-histological/genetic score (hg-score). This score was able to segregate two groups of h-MDS with a significantly different risk of blast progression (P < 0.001). The integration of cyto-histological and genetic features in adult patients with hypocellular BM facilitated segregation into two distinct groups, one with clinical and genetic features highly consistent with myeloid neoplasm, and one with features more consistent with non-malignant BMF.

High Graft-versus-Host Disease-Free, Relapse/Rejection-Free Survival and Similar Outcome of Related and Unrelated Allogeneic Stem Cell Transplantation for Aplastic Anemia: A Nationwide Swedish Cohort Study

“…The detection of clonal markers as a chromosomal aberration or molecular marker can be helpful, but some overlapping with AA occurs 102 . However, dysplastic megakaryocytes, a normal or increased number of CD34 cells, and some mutations are not consistent with AA [103][104][105][106] . Spliceosome genes mutations and multiple mutated genes are characteristic for MDS but not AA 72,107 .…”

“…Spliceosome genes mutations and multiple mutated genes are characteristic for MDS but not AA 72,107 . Patients with hMDS have a higher risk of developing leukemia and shorter OS compared with AA 106,108 .…”

Similar outcomes of alemtuzumab-based hematopoietic cell transplantation for SAA patients older or younger than 50 years

“…4,5 Furthermore, after IST and eltrombopag, patients are at later risk for myelodysplastic syndrome/AML and solid tumors, especially lymphomas, in addition to risk for relapse of AA in up to 38% of patients. [42][43][44][45][46] We show for the first time, using a composite end-point of GRFS, that outcomes among older patients with SAA, transplanted mainly from MUDs, were comparable with those for younger patients undergoing FCC transplantation, with low morbidity and lower-than-expected TRM generally observed after IST for SAA in this older age group. The incidence of GVHD was extremely low in older patients, despite using predominantly peripheral stem cell harvest from UDs.…”

Single-Nucleotide Polymorphism Array Technique Generating Valuable Risk-Stratification Information for Patients With Myelodysplastic Syndromes

“…Although NGS makes it increasingly easy to detect fusions and mutations, not all cytogenetic abnormalities can be detected by NGS. Therefore, if feasible, these techniques should be combined to contribute to the study of genomic aberrations for better and more precise management of patients with MDS (39)(40)(41)(42).…”