Ibrutinib in combination with rituximab is highly effective in treatment of chronic lymphocytic leukemia patients with steroid refractory and relapsed autoimmune cytopenias.

Autoimmune hemolytic anemia (AIHA) and pure red cell aplasia (PRCA) are common complications of CLL. The optimal treatment of steroid refractory AIHA/PRCA is not well established. We conducted a multicenter study of ibrutinib and rituximab in patients with relapsed/refractory to steroids AIHA/PRCA and underlying CLL. Protocol included induction (ibrutinib 420 mg/day and rituximab, 8 weekly and 4 monthly infusions) and maintenance phase with ibrutinib alone until progression or unacceptable toxicity. Fifty patients were recruited (44-warm AIHA, 2-cold AIHA, 4-PRCA). After the induction 34 patients (74%) have achieved complete response, 10 (21.7%) partial response. Median time to hemoglobin normalization was 85 days. With regards to CLL response 9 (19%) patients have achieved CR, 2 (4%) patients-stabilization and 39 (78%)-PR. The median follow-up was 37.56 months. In AIHA group 2 patients had a relapse. Among 4 patients with PRCA 1 patient did not respond, and 1 patient had a relapse after CR, 2 remained in CR. The most common adverse events were neutropenia (62%), infections (72%), gastrointestinal complications (54%). In conclusion ibrutinib in combination with rituximab is an active second-line treatment option for patients with relapsed or refractory AIHA/PRCA and underlying CLL.

Mechanism of structural networking in hydrogels based on silicon and titanium glycerolates.

Formation of organic/inorganic hydrogels based on silicon- and titanium-glycerol precursors synthesized by transesterification of alkoxy derivatives in excess of glycerol was investigated. The precursors in excess of glycerol and obtained gels were studied by chemical and physical methods including gelation kinetics, IR spectroscopy, XRD, dynamic and electrophoretic light scattering, mechanical deformation, which disclosed the basic difference in the gelation mechanism and structure of network in the hydrogels. Due to this difference, the gelation time of silicon- and titanium-glycerol precursors depended on pH or electrolyte addition in an opposite way. In the wide pH range, silicon-glycerol hydrogel was a polymeric single-phase system formed by the polymeric network homogeneously swollen in liquid water/glycerol medium. Flory-Rehner theory applied to the elastic modulus of these gels gave 40-180 monomer base units in the subchains of the network depending on water content in the gel. The mechanism of networking was three-dimensional polycondensation promoted by the electrically charged functional groups attached to the flexible polymeric chains. Electrolyte solutions provided the gelation according to Hofmeister series. Titanium-glycerol hydrogels were heterogeneous colloid systems at pH>1.5 and single-phase polymeric gels at lower pH. Electrolyte solutions provided the gelation according to Schultze-Hardy rule.