Key Points• CH50 activity reflects C5 blockade in PNH patients treated with eculizumab and is directly related to circulating free eculizumab levels.• Both CH50 and free eculizumab level markers look promising for the monitoring of complement blockade in patients with PNH receiving eculizumab.Paroxysmal nocturnal hemoglobinuria (PNH) is characterized by intravascular hemolysis, which is effectively controlled with eculizumab, a humanized monoclonal antibody that binds complement protein 5 (C5). The residual functional activity of C5 can be screened using a 50% hemolytic complement (CH50) assay, which is sensitive to the reduction, absence, and/or inactivity of any components of the classical and terminal complement pathway. Little data exist on complement blockade during treatment. From 2010 to 2012, clinical data, hemolysis biomarkers, complement assessment, and free eculizumab circulating levels were systematically measured immediately before every injection given to 22 patients with hemolytic PNH while receiving eculizumab therapy. During the study, 6 patients received ‡1 red blood cell transfusion. Lack of detectable CH50 activity (defined by CH50 £ 10% of normal values) was found in 184 samples (51%) and was significantly associated with lower lactate dehydrogenase levels (P 5 .002). Low levels of circulating free eculizumab (<50 mg/mL) correlated with detectable CH50 activity (CH50 > 10%; P 5 .004), elevated bilirubin levels (P < .0001), and the need for transfusions (P 5 .034). This study suggests that both CH50 activity and circulating free eculizumab levels may help physicians to manage PNH patients receiving eculizumab. (Blood. 2015;125(5):775-783)

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Mobilized peripheral blood has become the predominant stem cell source for allogeneic hematopoietic cell transplantation. In this retrospective single center study of 442 patients with hematologic malignancies, we analyzed prognostic factors for long-term survival after peripheral blood stem cell transplantation from HLA-matched related or unrelated donors. To account for disease/status heterogeneity, patients were risk-stratified according to the Disease Risk Index. Five-year overall survival was similar after transplants with matched related and unrelated donors (45% and 46%, respectively; P=0.49). Because donor age ≥60 years impacted outcome during model building, we further considered 3 groups of donors: matched unrelated (aged <60 years by definition), matched related aged <60 years and matched related aged ≥60 years. In multivariate analysis, the donor type/age group and the graft CD34+ and CD3 + cell doses impacted long-term survival. Compared with matched unrelated donor transplant, transplant from matched related donor <60 years resulted in similar long-term survival (P=0.67) while transplant from matched related donor ≥60 years was associated with higher risks for late mortality (hazard ratio (HR) 4.41; P=0.006) and treatment failure (HR: 6.33; P=0.009). Lower mortality risks were observed after transplant with CD34 + cell dose more than 4.5x10 6 /kg (HR: 0.56; P=0.002) and CD3 + cell dose more than 3x10 8 /kg (HR: 0.61; P=0.01). The Disease Risk Index failed to predict survival. We built an "adapted Disease Risk Index" by modifying risks for myeloproliferative neoplasms and multiple myeloma that improved stratification ability for progressionfree survival (P=0.04) but not for overall survival (P=0.82). Pre-transplant prognostic factors of long-term survival after allogeneic peripheral blood stem cell transplantation with matched related/unrelated donors ABSTRACT © F e r r a t a S t o r t i F o u n d a t i o nHere, we report a large single center retrospective study of PB-HSCT with MRD or 10/10 MUD in patients with hematologic malignancies. To account for disease/status heterogeneity, patients were stratified for disease risk according to the DRI. The aims of this study were: 1) to evaluate how donor type (MRD vs. MUD) and other pretransplant factors may predict for long-term OS and PFS after PB-HSCT; and 2) to evaluate DRI as a predictor for OS and PFS. Methods PatientsWe performed a retrospective analysis of all consecutive patients with hematologic malignancies who underwent a first PB-HSCT from either MRD or MUD at Saint-Louis Hospital (Paris, France) between January 2000 and December 2010. According to institutional guidelines, MRD was considered as the first donor choice and search for MUD was only undertaken if no suitable MRD was identified. For MUD PB-HSCT, only donor/recipient pairs matched at the allelic level at HLA-A, -B, -C, -DRB1 and -DQB1 loci (10/10 HLA-matched) were included. Data concerning pre-transplant characteristics and transplant outcomes were extracted from our transplantatio...