Chizuru Saito

Increased plasma thrombopoietin levels in patients with myelodysplastic syndrome: a reliable marker for a benign subset of bone marrow failure

Although myelodysplastic syndromes are heterogeneous disorders comprising a benign subset of bone marrow failure similar to aplastic anemia, no laboratory test has been established to distinguish it from bone marrow failures that can evolve into acute myeloid leukemia. Plasma thrombopoietin levels were measured in 120 patients who had myelodysplastic syndrome with thrombocytopenia (< 100 × 109/L) to determine any correlation to markers associated with immune pathophysiology and outcome. Thrombopoietin levels were consistently low for patients with refractory anemia with excess of blasts, while patients with other myelodysplatic syndrome subsets had more variable results. Patients with thrombopoietin levels of 320 pg/mL and over had increased glycosylphosphatidylinositol-anchored protein-deficient blood cells (49.1% vs. 0%), were more likely to have a low International Prognostic Scoring System (IPSS) score (≤1.0, 100% vs. 65.5%), a higher response rate to immunosuppressive therapy (84.2% vs. 14.3%), and a better 5-year progression-free survival rate (94.1% vs. 63.6% for refractory cytopenia with unilineage dysplasia; 100.0% vs. 44.4% for refractory cytopenia with multilineage dysplasia). In conclusion, increased plasma thrombopoietin levels were associated with a favorable prognosis of bone marrow failure and could, therefore, represent a reliable marker for a benign subset of myelodysplastic syndrome.

Increased glycosylphosphatidylinositol‐anchored protein‐deficient granulocytes define a benign subset of bone marrow failures in patients with trisomy 8

Trisomy 8 (+8), one of the most common chromosomal abnormalities found in patients with myelodysplastic syndromes (MDS), is occasionally seen in patients with otherwise typical aplastic anemia (AA). Although some studies have indicated that the presence of +8 is associated with the immune pathophysiology of bone marrow (BM) failure, its pathophysiology may be heterogeneous. We studied 53 patients (22 with AA and 31 with low‐risk MDS) with +8 for the presence of increased glycosylphosphatidylinositol‐anchored protein‐deficient (GPI‐AP−) cells, their response to immunosuppressive therapy (IST), and their prognosis. A significant increase in the percentage of GPI‐AP− cells was found in 14 (26%) of the 53 patients. Of the 26 patients who received IST, including nine with increased GPI‐AP− cells and 17 without increased GPI‐AP− cells, 14 (88% with increased GPI‐AP− cells and 41% without increased GPI‐AP− cells) improved. The overall and event‐free survival rates of the +8 patients with and without increased GPI‐AP− cells at 5 yr were 100% and 100% and 59% and 57%, respectively. Examining the peripheral blood for the presence of increased GPI‐AP− cells may thus be helpful for choosing the optimal treatment for +8 patients with AA or low‐risk MDS.

Hypomegakaryocytic thrombocytopenia (HMT): an immune-mediated bone marrow failure characterized by an increased number of PNH-phenotype cells and high plasma thrombopoietin levels

Patients with mild hypomegakaryocytic thrombocytopenia (HMT) that does not meet the diagnostic criteria for a definite disease entity may potentially progress to aplastic anaemia (AA) that is refractory to therapy. To clarify the clinical picture of HMT, we prospectively followed 25 HMT patients with white blood cell count >3·0 × 109/l, haemoglobin level >100 g/l and platelet count of <100·0 × 109/l in the absence of morphological and karyotypic abnormalities in the bone marrow. Glycosylphosphatidylinositol‐anchored protein‐deficient blood cells [paroxysmal nocturnal haemoglobinuria (PNH)‐type cells] were detected in 7 of the 25 (28%) patients and elevated plasma thrombopoietin (TPO, also termed THPO) levels (>320 pg/ml) were observed in 11 (44%) patients. Five (four PNH+ and one PNH−) of six TPOhigh patients who were treated with ciclosporin (CsA) showed improvement. Among the 21 patients who were followed without treatment, thrombocytopenia progressed in four of ten TPOlow patients and four of 11 TPOhigh patients. The 3‐year failure‐free survival rate of the CsA‐treated TPOhigh patients (100%) was significantly higher than that of the untreated TPOhigh patients (20%). These results suggest that a significant population of HMT patients has an immune pathophysiology that is similar to AA and may be improved by early therapeutic intervention with CsA.

Human herpesvirus-8-unrelated primary effusion lymphoma of the elderly not associated with an increased serum lactate dehydrogenase level: A benign sub-group of effusion lymphoma without chemotherapy

Abstract Human herpesvirus-8-unrelated primary effusion lymphoma characterized by lymphomatous effusion without nodal lesions occasionally exhibits spontaneous remission. To elucidate the factors associated with a good prognosis, this study analyzed the clinical parameters of four patients treated in the department and 109 patients reported in case reports. The median age was 71 years and the median overall survival was 20 months. Patients possessing two independent favorable factors, an elderly status (≥ 70 years) and low serum lactate dehydrogenase (< 500 IU/L) showed a markedly higher 1-year survival than patients lacking either of the two factors in the absence of chemotherapy (94% vs 20%, p = 3 × 10−5), which was similarly observed in the chemotherapy group (94% vs 51%, p = 0.002). The use of rituximab was also a strong predictor of survival (89% vs 49%, p = 7 × 10−6). Elderly patients not exhibiting an increased lactate dehydrogenase may represent a benign sub-group of effusion lymphoma, which do not require chemotherapy to achieve remission.