Clinical impact and characteristics of erythroid dysplasia in adult aplastic anaemia: Results from a multicentre registry.

Morphological dysplasia in haematopoietic cells, defined by a 10% threshold in each lineage, is one of the diagnostic criteria for myelodysplastic neoplasms. Dysplasia limited to the erythroid lineage has also been reported in some cases of aplastic anaemia (AA); however, its significance remains unclear. We herein examined the impact of erythroid dysplasia on immunosuppressive therapy responses and survival in AA patients. The present study included 100 eligible AA patients without ring sideroblasts. Among them, 32 had dysplasia in the erythroid lineage (AA with minimal dysplasia [mini-D]). No significant sex or age differences were observed between AA groups with and without erythroid dysplasia. In severe/very severe AA and non-severe AA patients, a response to anti-thymocyte globulin + ciclosporin within 12 months was observed in 80.0% and 60.0% of AA with mini-D and 42.9% and 90.0% of those without dysplasia, with no significant difference (p = 0.29 and p = 0.24 respectively). Overall survival and leukaemia-free survival did not significantly differ between the groups. Collectively, the present results indicate that the presence of erythroid dysplasia did not significantly affect clinical characteristics or outcomes in AA patients, suggesting that its presence in AA is acceptable. Therefore, erythroid dysplasia should not exclude an AA diagnosis.

Emergence of t(3;21)(q26.2;q22) during eltrombopag treatment in a patient with relapsed aplastic anemia who received chemotherapy for angioimmunoblastic T-cell lymphoma.

A 65-year-old man with nonsevere aplastic anemia received rabbit anti-thymocyte globulin and cyclosporine and partially responded. Six months after the initiation of treatment, he was diagnosed with stage IV angioimmunoblastic T-cell lymphoma and received chemotherapy. PET/CT scan analysis indicated a complete response. However, he showed sustained myelosuppression and was diagnosed with relapse of aplastic anemia. He did not respond to cyclosporine, eltrombopag or methenolone. Fifteen months after eltrombopag administration, he developed MDS with t(3;21)(q26.2;q22). Patients should be monitored carefully for the emergence of not only -7/del(7q) but also 3q26 abnormalities, including t(3;21)(q26.2;q22), during and after eltrombopag treatment.

Reference intervals of white blood cell parameters for healthy adults in japan.

INTRODUCTION: While white blood cell (WBC) parameters have been suggested to depend on ethnicity and gender, reference intervals in healthy Asian populations are limited. The present study established reference intervals of WBC parameters for healthy adults in Japan. METHODS: A total of 750 healthy adults (447 women and 303 men; 18-67 years old, median 40 years old) at 7 Japanese centers who participated in regular medical checkups entered this study. The WBC parameters were measured using automated hematocytometers and blood film reviews by a manual microscopic examination. RESULTS: The reference intervals of the WBC parameters according to gender in healthy adults were determined. Age-specific decreases in WBC counts of both gender groups and in neutrophil counts of women were noted. Favorable correlations between the hematocytometer and microscopic methods were found in neutrophils, lymphocytes, and eosinophils but not in monocytes or basophils. CONCLUSION: This study suggests the need to consider gender and age in the clinical use of reference intervals of WBC parameters.

Serum ferritin levels at diagnosis predict prognosis in patients with low blast count myelodysplastic syndromes.

Serum ferritin, a marker of systemic iron status, is considered a prognostic factor for patients with myelodysplastic syndromes (MDS), despite the lack of supporting evidence. We investigated the association between serum ferritin levels at diagnosis and the prognoses of Japanese MDS patients with bone marrow blasts < 5% and peripheral blood blasts < 2%. Three hundred and ninety patients with cytopenia were registered prospectively in the multicenter database, among whom 107 patients with MDS (72 males and 35 females, with a median age of 70 years) met the eligibility criteria. The median serum ferritin level at diagnosis was 204 ng/mL; we divided the cohort into low (n = 56) and high (n = 51) ferritin groups using a cutoff of 210 ng/mL. Kaplan-Meier analyses revealed that the 3-year overall survival (OS) of the high ferritin group was significantly shorter than that of the low ferritin group (66% and 79%, respectively). The cumulative incidences of leukemic progression were similar between the groups. On multivariate analysis, age, blast percentage, cytogenetic abnormalities, and serum ferritin levels at diagnosis were independently associated with OS in our patients. Thus, modest elevations of ferritin levels at diagnosis may influence the prognoses of patients with MDS who have low blast counts.

Interobserver concordance of assessments of dysplasia and blast counts for the diagnosis of patients with cytopenia: From the Japanese central review study.

The diagnosis of myelodysplastic syndromes (MDS) is based on morphology and cytogenetics. However, limited information is currently available on the interobserver concordance of the assessment of dysplastic lineages (<10% or ≥10% in bone marrow (BM)). The revised International Prognostic Scoring System (IPSS-R) described a new threshold (2%) for BM blasts. However, the interobserver concordance of the categories (0-≤2% and >2-<5%) has limited data. The purpose of the present study was to investigate the assessment of dysplastic lineages and IPSS-R reproducibility. Our study was divided into two Steps. In each Step, the microscopic examinations were performed separately by two morphologists. Regarding the category of BM blasts ≤2% and >2-<5%, interobserver agreement was more than 'moderate' in all pairs (kappa test: 0.43-0.90). Regarding dysgranulopoiesis (dysG) and dyserythropoiesis (dysE) in BM, interobserver agreement was more than 'moderate' in all pairs (kappa test, dysG: 0.45-0.96, dysE: 0.45-0.81). Regarding the category of dysmegakaryopoiesis (dysMgk) in BM, interobserver agreement was more than moderate in 4 out of 5 pairs (kappa test: 0.58-1.00), and was fair for one pair (kappa test: 0.37). We consider that high interobserver concordance may be possible for the BM blast cell count (≤2% or >2-<5%) and dysplasia (<10% or ≥10%) of each lineage.

Validation of the revised International Prognostic Scoring System in patients with myelodysplastic syndrome in Japan: results from a prospective multicenter registry.

The Japanese National Research Group on Idiopathic Bone Marrow Failure Syndromes has been conducting prospective registration, central review, and follow-up study for patients with aplastic anemia and myelodysplastic syndrome (MDS) since 2006. Using this database, we retrospectively analyzed the prognosis of patients with MDS. As of May 2016, 351 cases were registered in this database, 186 of which were eligible for the present study. Kaplan-Meier analysis showed that overall survival (OS) curves of the five risk categories stipulated by the revised international prognostic scoring system (IPSS-R) were reasonably separated. 2-year OS rates for the very low-, low-, intermediate-, high-, and very high-risk categories were 95, 89, 79, 35, and 12%, respectively. In the same categories, incidence of leukemic transformation at 2 years was 0, 10, 8, 56, and 40%, respectively. Multivariate analysis revealed that male sex, low platelet counts, increased blast percentage (>2%), and high-risk karyotype abnormalities were independent risk factors for poor OS. Based on these data, we classified Japanese MDS patients who were classified as intermediate-risk in IPSS-R, into the lower risk MDS category, highlighting the need for careful assessment of treatments within low- and high-risk treatment protocols.