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Vener C.,Centro Trapianti Of Midollo | Novembrino C.,Ferrari | Novembrino C.,University of Milan | Bamonti Catena F.,University of Milan | And 13 more authors.
Experimental Hematology | Year: 2010

Objective: To determine if increased cell turnover in chronic myeloproliferative disorders can lead to hyperhomocysteinemia as a result of folate and/or cobalamin depletion, and contribute to oxidative stress. Materials and Methods: The clinical role of oxidative stress was investigated by measuring reactive oxygen species (ROS), total antioxidant capacity (TAC), and total homocysteine (tHcy), folate, cobalamin, and holotranscobalamin (HoloTC) levels in 51 chronic myeloproliferative disorders patients (male-to-female ratio: 1.1; median age: 64 years; range, 40. -84 years), including 42 with primary myelofibrosis and 9 with post. -polycythemia vera myelofibrosis. Results: Myelofibrotic patients had higher tHcy (p = 0.0201) and an unbalanced oxidative status (higher ROS and lower TAC levels; p < 0.0001) than controls. Presence of diabetes or another neoplasia was associated with higher ROS levels (p < 0.05), splenomegaly, hepatomegaly, and peripheral blasts with lower HoloTC levels (p < 0.005). The most severe forms of myelofibrosis (2-3) were associated with lower TAC (p = 0.045) and HoloTC levels (p = 0.017). Patients with Janus kinase-2 mutations had lower HoloTC levels (p = 0.0059). HoloTC deficiency was more frequently associated with Janus kinase-2 homozygosity (p < 0.0003). Conclusions: Our findings suggest that the determination of HoloTC, tHcy, ROS concentrations, and TAC, can identify latent cobalamin deficiency and provide a rational basis for correcting the increased oxidation associated with disease progression. © 2010 ISEH - Society for Hematology and Stem Cells. Source


Barcellini W.,Unita Operativa Ematologia 2 | Zaja F.,Clinica Ematologica | Zaninoni A.,Unita Operativa Ematologia 2 | Imperiali F.G.,Unita Operativa Ematologia 2 | And 7 more authors.
Blood | Year: 2012

This prospective study investigated the efficacy, safety, and response duration of low-dose rituximab (100 mg fixed dose for 4 weekly infusions) together with a short course of steroids as first- or second-line therapy in 23 patients with primary autoimmune hemolytic anemia (AIHA). The overall response was 82.6% at month +2, and subsequently stabilized to ∼90% at months +6 and +12; the response was better in warm autoimmune hemolytic anemia (WAIHA; overall response, 100% at all time points) than in cold hemagglutinin disease (CHD; average, 60%); the relapse-free survival was 100% for WAIHA at +6 and +12 months versus 89% and 59% in CHD, respectively, and the estimated relapse-free survival at 2 years was 81% and 40% for the warm and cold forms, respectively. The risk of relapse was higher in CHD and in patients with a longer interval between diagnosis and enrollment. Steroid administration was reduced both as cumulative dose (∼50%) and duration compared with the patient's past history. Treatment was well tolerated and no adverse events or infections were recorded; retreatment was also effective. The clinical response was correlated with amelioration biologic markers such as cytokine production (IFN-γ, IL-12, TNF-α, and IL-17), suggesting that low-dose rituximab exerts an immu-nomodulating activity. This study is registered at www.clinicaltrials.gov as NCT01345708. © 2012 by The American Society of Hematology. Source

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