SF3B1 Mutation but Not Ring Sideroblasts Identifies a Specific Group of Myelodysplastic Syndrome-Refractory Cytopenia With Multilineage Dysplasia.

BACKGROUND: Integrating the proportion of ring sideroblasts and SF3B1 mutation status is required for diagnosis of sideroblastic subgroups in myelodysplastic syndrome (MDS) as proposed by the World Health Organization 2016 classification. However, the clinical implications of SF3B1 mutation and ring sideroblasts in MDS-refractory cytopenia with multilineage dysplasia (MDS-RCMD) remain unclear. PATIENTS AND METHODS: Clinical and laboratory features in 238 MDS-RCMD patients were retrospectively analyzed, and the prognostic significance of SF3B1 mutation and ring sideroblasts on overall survival and leukemia-free survival in total MDS-RCMD patients and different subgroups stratified by the percentage of ring sideroblasts or SF3B1 mutation status were evaluated. RESULTS: MDS-RCMD patients with ring sideroblasts ≥ 15% showed a significantly higher prevalence of SF3B1 mutation compared to ring sideroblasts 5%-14% or ring sideroblasts < 5% (75.6% vs. 15.1% vs. 6.4%, P < .001). In multivariate analysis, SF3B1 mutation was associated with a significantly prolonged survival (hazard ratio [HR] = 0.430, P = .013) and reduced leukemic transformation (HR = 0.174, P = .021) in total MDS-RCMD patients, while ring sideroblasts showed no independent effect on either survival or leukemic transformation. There were no significant differences in clinical characteristics or survival between MDS-RCMD patients with ring sideroblasts ≥ 15% and ring sideroblasts 5%-14% in the presence of SF3B1 mutation. Furthermore, SF3B1 mutation showed an independent prognostic effect on overall survival in MDS-RCMD patients with ring sideroblasts 5%-14% (HR = 0.195, P = .046). CONCLUSION: SF3B1 mutation, not the presence of ring sideroblasts, identifies a distinct subtype and showed independent prognostic value on survival and leukemia transformation in MDS-RCMD patients.

Bone marrow failure in childhood: central pathology review of a nationwide registry.

Refractory cytopenia of childhood (RCC) was proposed as a provisional entity in the 2008 WHO classification of myelodysplastic syndromes (MDS). It is defined as a childhood MDS featuring persistent cytopenia without increase blasts in bone marrow (BM) or peripheral blood (PB). Because the majority of RCC cases feature hypocellularity and pancytopenia, it is quite challenging to differentiate RCC from acquired aplastic anemia (AA) and many kinds of inherited bone marrow failure syndromes (IBMFS). Diagnosis of RCC requires BM histology of characteristic features such as isolated erythroid islet with left shift, abnormal localization and micromegakaryocytes. The Japanese Society of Pediatric Hematology/Oncology has opened the central registry review system since 2009 to evaluate childhood cases of bone marrow failure (BMF). It has reviewed cytology and BM pathology of all registered BMF cases, which number more than 1,700. In the evaluation of BMF, BM pathology is important to assess the mechanism of hematopoiesis. Pathological dysplasia should be differentiated from cytological dysplasia. A central review system is important for rare diseases, such as pediatric BMF. Standardization of pathological diagnosis should be established upon consensus findings, descriptions, and diagnostic approaches. In this review, the pathology of pediatric BMF syndromes is summarized.

A Case of Myelodysplastic Syndrome Characterized by Hemolytic Anemia at Presentation

A man aged 78 yr with no history of chemotherapy or toxic exposure presented with a history of dyspnea and intermittent red urine for 3 months and several years, respectively. Hematologic data at admission were as follows: hemoglobin, 65 g/L; white blood cell count, 4.05x109/L; platelet count, 96x109/L; and reticulocyte count, 10.9%. A peripheral blood smear revealed polychromasia, nucleated red blood cells, and neutrophils with a non-lobulated nucleus. The bone marrow was hypercellular and exhibited an increase in erythroid precursors with trilineage dysplasia and our findings were suggestive of refractory cytopenia with multilineage dysplasia (RCMD). Karyotype of bone marrow cells was as follows: 45,XY,der(9;17)(p10;q10),add(18)(q11.2)[10]/45,idem,del(3)(q21)[10]. Other laboratory findings showed decreased serum haptoglobin, increased lactate dehydrogenase, and increased indirect bilirubin levels. Moreover, results of the direct/indirect antiglobulin test (Coombs' test) and paroxysmal nocturnal hemoglobinuria analysis with CD55, CD59, fluorescent aerolysin (FLAER), and CD24 were negative. Cold agglutinin and Donath-Landsteiner antibodies were not detected. This is a case of myelodysplastic syndrome (MDS) associated with hemolytic anemia and complex chromosomal abnormalities at presentation.

Two copies of isochromosome 5p in refractory cytopenia with multilineage dysplasia: A case report.

Isochromosome 5p-i(5)(p10)-represents a rare but recurrent abnormality in myeloid disorders, especially in acute myeloid leukemia. In all published cases, the isochromosome 5p was present in single copy and accompanied by one or more additional anomalies, mostly trisomy 8. Here we report a case of refractory cytopenia with multilineage dysplasia with two copies of isochromosome 5p, a single normal chromosome 5and an apparently balanced translocation between long arms of chromosome 7and 10. To our knowledge, the pentasomia 5p has never been described before the presentstudy.

Membranous glomerulonephritis in a patient with myelodysplastic syndrome-refractory cytopenia with multilineage dysplasia.

A 74-year-old woman presented with edema in the lower extremities. Laboratory tests revealed anemia, thrombocytopenia, hypoalbuminemia, hypercholesterolemia, and nephrotic-range proteinuria. Myelodysplastic syndrome-refractory cytopenia with multilineage dysplasia (MDS-RCMD) was confirmed by bone marrow biopsy. Renal biopsy demonstrated membranous glomerulonephritis (MGN), stage I. Based on these clinicopathologic results, she was diagnosed as having MGN with MDS-RCMD. This is a rare case report of MGN in a parient with MDS-RCMD featuring nephrotic syndrome.

Membranous glomerulonephritis in a patient with myelodysplastic syndrome-refractory cytopenia with multilineage dysplasia

A 74-year-old woman presented with edema in the lower extremities. Laboratory tests revealed anemia, thrombocytopenia, hypoalbuminemia, hypercholesterolemia, and nephrotic-range proteinuria. Myelodysplastic syndrome-refractory cytopenia with multilineage dysplasia (MDS-RCMD) was confirmed by bone marrow biopsy. Renal biopsy demonstrated membranous glomerulonephritis (MGN), stage I. Based on these clinicopathologic results, she was diagnosed as having MGN with MDS-RCMD. This is a rare case report of MGN in a parient with MDS-RCMD featuring nephrotic syndrome.