Ibrutinib in the Treatment of Refractory Chronic Lymphocytic Leukemia

Background & Aims. This paper presents the results of the observational study of ibrutinib in patients with chronic lymphocytic leukemia (CLL), conducted in SP Botkin Municipal Clinical Hospital. The main objective was the analysis of complications of ibrutinib and identification of factors, influencing the dosage regimen; the secondary objective was the estimation of the total response to treatment, event-free and overall survival. Materials & Methods. The study included 96 patients with CLL with indications for ibrutinib therapy. The median age was 64,9 years (range 32–91 years), the study population consisted of 69 (72 %) men and 27 (28 %) women. The condition of 25 (26 %) patients according to the ECOG scale was of > 3 points. The disease of stage C were diagnosed in 36 (37 %) patients . Deletion of 17p/TP53 mutations were detected in 29 (33 %) of 87 patients. Seventy patients had refractory CLL. The median of the number of the lines of the previous therapy was 3 (range 1–9). Adverse events were assessed in accordance with the CTCAE criteria, version 4.0; the bleeding severity was evaluated using ITP-specific bleeding score; hematological complications were classified according to the recommendations of IWCLL-2008. Results. Ibrutinib was administered at a dosage of 420 mg per day daily until progression or intolerable toxicity. The median duration of ibrutinib therapy was 10.3 months. Ibrutinib was shown to have moderate toxicity, mostly of grade I or II. The bleeding was the most frequent complication. Of the hematological complications, thrombocytopenia was the most common (35 %); neutropenia grade III) developed in 26 % of patients. The treatment response was assessed in 92 patients. The overall response to treatment was 89 %. Complete remission, partial remission and partial remission with lymphocytosis were achieved in 4 (4 %), 57 (62 %), and 21 (23 %) patients, respectively. The event-free survival and overall survival by the month 10 was 90 % and 91 %, respectively. For this observation period, ECOG status and the number of the lines of therapy prior to ibrutinib had the prognostic value. Conclusion. Ibrutinib was shown to have high efficiency in relapsed/refractory forms of CLL. The nature of the ibrutinib toxicity is fundamentally different from that of the conventional chemotherapy. The frequency of ibrutinib therapy complications and patients’ non-compliance depends on the intensity of the previous treatment of CLL. Despite a short observation period, it can be concluded that ibrutinib had the greatest impact on the patient’s quality of life when administered for the first relapse. The low toxicity of ibrutinib is likely to allow the combination with other antitumor agents

Systematics of Gamow-Teller beta decay “Southeast” of 100Sn^{100}Sn

The energy centroids and integrated strengths of Gamow-Teller transitions in the beta(+) and electron-capture decay are analyzed for nuclei whose proton number Z and neutron number N are restricted to 4

Beta decay of

The β decay of 94Pd and of the 71s isomer of 94Rh was investigated by using total γ-ray absorption techniques. Several levels in 94Rh are established, including a new low-lying isomer characterized by a half-life of 0.48(3)μs and a de-exciting transition of 55keV. E2 multipolarity is determined for this transition by measuring the intensities of its γ-rays and the characteristic X-rays from its electron conversion. On the basis of the measured reduced β-decay transition rates to known 94Ru levels and shell model considerations, the spin-parity of the 71s and the 0.48μs isomers of 94Rh is assigned to be (4+) and (2+), respectively. The β-decay strength distributions measured for 94Pd and the 71s isomer of 94Rh yield Q EC values of 6700(320) and 9750(320)keV for these decays and give evidence for the population of those states below and above the magic N = 50 gap that belong to both components of the 0g spin-orbit doublet

One-proton and two-proton radioactivity of the (21+) isomer in 94Ag*

The properties of the (21(+)) isomer of Ag-94, unprecedented in the entire nuclear chart, are presented with particular emphasis on its hindered one-proton and enhanced two-proton radioactivity. The tasks emerging from these results concerning experimental and theoretical efforts are discussed.status: publishe