By retrospectively analyzing 288 patients with de novo myelodysplastic syndrome (MDS), we sought to determine the prevalence and clinical characteristics of bone marrow eosinophilia and basophilia that were detected at presentation. Bone marrow eosinophilia and basophilia were defined as a differential count of each cell type exceeding 5.0% and 1.0%, respectively. Of 288 patients with MDS, 36 (12.5%) fulfilled this criterion for bone marrow eosinophilia (MDS-Eos); 34 patients (11.8%) showed basophilia (MDS-Bas), and 11 (3.8%) satisfied both criteria (MDSEosBas). The remaining 229 patients had neither eosinophilia nor basophilia in their bone marrow (MDS ؊/؊ ) at presentation. Cytogenetic analysis was carried out on unstimulated bone marrow cells obtained from 264 patients. When the cytogenetic categorization of the IPSS (International Prognostic Scoring System) for MDS was applied, significantly higher numbers of MDS-Eos and MDS-Bas patients had chromosomal abnormalities carrying intermediate or poor prognosis, compared with the MDS ؊/؊ patients. Specific chromosomal abnormalities and complex karyotypes were associated with MDS-Eos and/or MDS-Bas. In accordance with these results, the overall survival rate was significantly lower, and the evolution to acute myelogenous leukemia (AML) occurred more frequently in the MDS-Eos and MDSBas than in the MDS ؊/؊ patients. Multivariate analysis demonstrated that bone marrow basophilia was an independent risk factor for evolution to AML. Our study indicates that bone marrow eosinophilia and basophilia in patients with MDS predict a poorer prognosis. (Blood. 2003;

Large granular lymphocyte leukemia-associated pure red cell aplasia accounts for a significant portion of secondary pure red cell aplasia cases. However, because of its rarity, long-term responses and relapse rates after immunosuppressive therapy are largely unknown. We conducted a nationwide survey in Japan and collected 185 evaluable patients. Fourteen patients with large granular lymphocyte leukemia-associated pure red cell aplasia were evaluated. Cyclophosphamide, cyclosporine A and prednisolone produced remissions in 6/8, 1/4 and 0/2 patients respectively. Seven and 5 patients were maintained on cyclophosphamide or cyclosporine A respectively. Two patients relapsed after stopping cyclophosphamide, and 2 patients relapsed during maintenance therapy with cyclosporine A. The median relapse-free survival in the cyclophosphamide -and the cyclosporine A groups was 53 and 123 months respectively. Large granular lymphocyte leukemia-associated pure red cell aplasia showed a good response to either cyclophosphamide or cyclosporine A. Most patients continued to receive maintenance therapy and it remains uncertain whether cyclophosphamide or cyclosporine A can induce a maintenance-free hematologic response in large granular lymphocyte leukemia-associated pure red cell aplasia.

Disseminated intravascular coagulation (DIC) is one of the important complications to develop in patients with acute myeloid leukemia (AML). While acute promyelocytic leukemia (APL) is a strong risk factor for DIC, other clinical features have not been fully defined. We retrospectively analyzed 161 consecutive adult patients with de novo non-APL AML. DIC was diagnosed in 52 patients (32%); 28 patients at diagnosis and 24 soon after the initiation of induction chemotherapy. Leukocyte counts, C-reactive protein, and lactate dehydrogenase were significantly higher in the DIC+ group. Negative expressions of CD13, CD19, CD34, and HLA-DR were more prevalent in the DIC+ group. On multivariate logistic-regression analysis, variables that were independently associated with the development of DIC were high C-reactive protein, high leukocyte count, negative expressions of CD13 and HLA-DR, and cytogenetics with a normal karyotype or 11q23 abnormality. Although DIC is considered to be associated with serious morbidity and occasional mortality, we did not find any significant differences in the complete remission rate, overall or disease-free survival between DIC+ and DIC- groups. This study is the first to define the clinical characteristics associated with DIC in patients with non-APL AML, but exactly how and when DIC should be treated remains to be determined.

No abstract

SummaryImmunosuppressive therapy has been employed as the initial treatment for acquired chronic pure red cell aplasia (PRCA), such as idiopathic, thymoma-associated, or large granular lymphocyte (LGL) leukaemia-associated PRCA, which is thought to be immune-mediated. To explore the overall long-term outcome following immunosuppression and to identify the risk factors for death in these disorders, we conducted nationwide surveys in Japan 2004 and 2006, and identified a total of 185 patients with acquired chronic PRCA, including 72 idiopathic, 41 thymoma-associated and 14LGL leukaemia-associated cases of PRCA for whom data was available. The present study evaluated 127 patients with these three subsets of PRCA. The median overall survival has not yet been reached in idiopathic PRCA. The estimated median overall survival times in patients with thymomaassociated and LGL leukaemia-associated PRCA were 142Á1 and 147Á8 months, respectively. Twenty-two deaths were reported, and the response to induction therapy and relapse of anaemia were found to be associated with death. The major causes of death were infection in seven patients and organ failure in another seven patients. The results suggest that maintenance therapy and the management of infectious complications are crucial for improving the prognosis of chronic PRCA.

The restriction fragment length polymorphisms (RFLP) of the X-chromosome phosphoglycerate kinase (PGK) and hypoxanthine phosphoribosyltransferase (HPRT) genes were used to study the clonal basis of the chronic myeloproliferative disorders (CMPD). Analyses were performed on granulocyte and T-lymphocyte fractions obtained from 24 females; 13 had essential thrombocythaemia (ET), eight polycythaemia vera (PV) and three myelofibrosis with myeloid metaplasia (MMM). All 24 of these patients had monoclonal patterns of X-inactivation in the granulocyte fraction. For the T-lymphocyte fraction, non-clonal patterns of X-inactivation were observed in 8/13 patients with ET, 7/8 with PV and 1/3 with MMM, while the remaining eight subjects were found to have monoclonal patterns of X-inactivation. Our findings suggest that the majority of the CMPD in these patients originated from a relatively committed progenitor cell without the capacity to differentiate into T cells, and convincingly demonstrated heterogeneity of lineage involvement.

Given these findings, we recommend that HCVab is measured upon diagnosis of chronic ITP, and that splenectomy is planned in patients with HCVab in the event that prednisolone treatment is ineffective.

Restriction fragment length polymorphisms (RFLP) of the X-chromosome genes phosphoglycerate kinase (PGK) and hypoxanthine phorphoribosyltransferase (HPRT) were used to determine the clonal nature of myelodysplastic syndromes (MDS) in 22 patients. These included eight with refractory anaemia (RA), four with RA with ring sideroblasts (RARS), six with RA with an excess of blasts (RAEB), three with RAEB in transformation (RAEB-T), and one with chronic myelomonocytic leukaemia (CMML). Monoclonal X-inactivation patterns were observed in 19/22 patients. The remaining three cases, one each with RA, RARS and RAEB, were of polyclonal composition. Separated T-lymphocyte and granulocyte fraction analyses in six patients of the former cases revealed that T-lymphocyte as well as granulocyte fractions showed a monoclonal pattern of X-inactivation. These results support the view that the majority of MDS arise from a pluripotent stem cell capable of myeloid and lymphoid differentiation.