Immunological classification of acute myeloblastic leukemias: relevance to patient outcome

Immunophenotyping is a major tool to assign acute leukemia blast cells to the myeloid lineage. However, because of the large heterogeneity of myeloid-related lineages, no clinically relevant immunological classification of acute myeloblastic leukemia (AML) has been devised so far. To attempt at formulating such a classification, we analyzed the pattern of expression of selected antigens, on blast cells collected at AML diagnosis. Patients were eligible if they had a first diagnosis of de novo AML and a sufficient number of blast cells for proper immunophenotyping. The relative expression of CD7, CD13, CD14, CD15, CD33, CD34, CD35, CD36, CD65, CD117, and HLA-DR were analyzed by cytometry in a test series of 176 consecutive AML cases. Statistical tools of clusterization allowed to remove antigens with overlapping distribution, leading us to propose an AML classification that was validated in a second AML cohort of 733 patients. We identified five AML subsets (MA to ME) based on the expression of seven antigens within four groups (CD13/CD33/DC117, CD7, CD3!5/CD36, CD15).-MA and MB-AML have exclusively myeloid features with seldom extramedullary disease and rare expression of lymphoid antigens. No cases of acute promyelocytic leukemia (APL) were observed within MB AML. MC AML have either myeloid or erythroblastic features. MD AML have more frequently high WBC counts than other subsets, which were related to the expression of CD35/CD36 and CD14 and to monoblastic differentiation. ME AML lack CD13, CD33, and CD117 but display signs of terminal myeloid differentiation. Specific independent prognostic factors were related to poor overall survival in each immunological subset: CD34+ (P<3 x 10(-4)) in MA AML, CD7+ in MB AML, non-APL cases (P<0.03) in MC AML, CD34+ (P<0.002) and CD14+ (P<0.03) in MD AML, CD14+ in ME AML (P<0.01). The inclusion of seven key markers in the immunophenotyping of AML allows a stratification into clinically relevant subsets with individual prognostic factors, which should be considered to define high-risk AML populations

Main Properties of the THERAFLEX MB-Plasma System for Pathogen Reduction

Methylene blue (MB) treated plasma has been in clinical use for 18 years. The current THERAFLEX MB-Plasma has a number of improved features compared with the original Springe methodology. This overview embodies: the biochemical characteristics of MB, the mechanism of the technology, toxicology, pathogen reduction capacity, current position in clinical setting and status within Europe. The THERAFLEX MB (TMB) procedure is a robust, well standardised system lending itself to transfusion setting and meets the current guidelines. The pathogen kill power of the TMB system, like the other available technologies, is not limitless, probably in order of 6 log for most enveloped viruses and considerably less for non-enveloped ones. It does not induce either new antigen or grossly reducing the function and life span of active principle in fresh frozen plasma (FFP). The removal of the residual MB at the end of the process has the beneficial effect of reducing potential toxic impacts. Clinical haemovigilance data, so far, indicate that cell-free MB plasma is effective in all therapeutic setting requiring FFP, besides inconsistent thrombotic thrombocytopenia purpura data, without serious side-effects or toxicity. The current system is in continuous improvement e.g. regarding virus reduction range, illumination device, software used, and process integration in the blood bank setting