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Objectives We studied the involvement of serum-complement (C') and oxidative stress in the hemolytic anemias Paroxysmal Nocturnal Hemoglobinuria (PNH) and Auto-Immune Hemolytic Anemia (AIHA), and the effect of fermented papaya preparation (FPP), an antioxidant-containing yeast fermentation product of Carica papaya Linn. Methodology Normal human red blood cells (RBC) treated with the sulphydryl compound 2-aminoethyl isothiouronium bromide demonstrated a PNH-phenotype (reduced surface expression of the protecting CD55 and CD59 antigens). AIHA was simulated by treating group-A RBC with anti-A antibodies. Both samples were exposed to C'-containing, O-type, serum. Results Hemolysis, which was developed 40 min later, was preceded by an abrupt increase in reactive oxygen species (ROS). Both ROS and hemolysis were reduced by inactivating the C’ (by heat or by an anti-C’ antibody), and by FPP (20 mg/ml), indicating the involvement of C' and oxidative stress, respectively. One PNH patient treated with FPP showed reduced hemolysis. Conclusion Currently, a humanized anti-C' monoclonal antibody is the main treatment for PNH and some other hemolytic anemias. Our results suggest a therapeutic role for antioxidants. Since FPP is well tolerated and relatively inexpensive, its use may be considered as an alternative or adjuvant therapy for PNH and other C'-mediated hemolytic anemias., Journal of International Society of Antioxidants in Nutrition & Health, Vol 3, No 3 (2016)

Many patients with chronic lymphocytic leukemia (CLL) develop progressive treatment-resistant disease. Rituximab (RTX), a monoclonal antibody targeting CD20 on B lymphocytes and widely used in other indolent B-cell neoplasms is less efficacious in CLL, possibly because of associated complement deficiencies. Initial in vitro and in vivo observations support the central role of complement in rituximab-mediated loss of CD2 0 + cells in CLL. In an open trial conducted in outpatient hematology clinics in Israel and Greece, we examined whether providing complement by concurrent administration of fresh frozen plasma (FFP) would enhance the effect of RTX in CLL. Five patients with severe treatment-resistant CLL were included in the trial. All had been previously treated with fludarabine, and three also failed treatment with RTX. Each patient was treated with two units of FFP followed with RTX 375 mg/m 2 as a single agent, repeated every 1-2 weeks as needed. A rapid and dramatic clinical and laboratory response was achieved in all patients. Lymphocyte counts dropped markedly followed by shrinkage of lymph nodes and spleen and improvement of the anemia and thrombocytopenia. This could be maintained over 8 months (median) with additional cycles if necessary. Treatment was well tolerated in all cases. In conclusion, adding FFP to RTX may provide a useful therapeutic option in patients with advanced CLL resistant to treatment. Further studies are needed to confirm and study the efficacy of the FFP/RTX combination in advanced CLL, establish the mechanisms, and possibly extend its use to other B-cell-dependent pathologies, such as treatment-refractory autoimmune diseases.