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.

Multivariate Curve Resolution Alternating Least Squares Analysis of In Vivo Skin Raman Spectra.

In recent years, Raman spectroscopy has been used to study biological tissues. However, the analysis of experimental Raman spectra is still challenging, since the Raman spectra of most biological tissue components overlap significantly and it is difficult to separate individual components. New methods of analysis are needed that would allow for the decomposition of Raman spectra into components and the evaluation of their contribution. The aim of our work is to study the possibilities of the multivariate curve resolution alternating least squares (MCR-ALS) method for the analysis of skin tissues in vivo. We investigated the Raman spectra of human skin recorded using a portable conventional Raman spectroscopy setup. The MCR-ALS analysis was performed for the Raman spectra of normal skin, keratosis, basal cell carcinoma, malignant melanoma, and pigmented nevus. We obtained spectral profiles corresponding to the contribution of the optical system and skin components: melanin, proteins, lipids, water, etc. The obtained results show that the multivariate curve resolution alternating least squares analysis can provide new information on the biochemical profiles of skin tissues. Such information may be used in medical diagnostics to analyze Raman spectra with a low signal-to-noise ratio, as well as in various fields of science and industry for preprocessing Raman spectra to remove parasitic components.