Intravenous immunoglobulin (IVIG) has become a mainstay of treatment for acute and chronic immune thrombocytopenic purpura (ITP). The efficacy and safety of Privigen, a new, ready-to-use, 10% liquid human IgG formulation, was evaluated in this open-label, multicentre study. Privigen infusions (1 g/kg per day for 2 consecutive days, days 1 and 2) were given to 57 adolescent and adult patients with chronic ITP and platelet counts < or =20 x 10(9)/l. By day 7, 80.7% of patients (95% CI, 69.2, 89.3) achieved platelet counts of > or =50 x 10(9)/l. Correspondingly, haemorrhage number and severity were significantly reduced. Adverse events were generally mild or moderate and typical of underlying disease and IVIG treatment. Privigen was well tolerated - 104 of 114 infusions were performed at the maximum permitted infusion rate (4 mg/kg/min). Thus, in patients with chronic ITP, a two-day regimen of Privigen was effective in increasing platelet count, reducing bleeding events and was well tolerated.

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Background Intravenous immunoglobulin (IVIG) is an accepted treatment for immune thrombocytopenic purpura (ITP). A new liquid 10% human IgG preparation stabilized with proline at a pH of 4.8 (trade name: Privigen) was recently developed. It can be stored at room temperature and is therefore always ready to use. Here we report its efficacy and safety in patients with chronic ITP. Patients and Methods Fifty-seven patients with chronic ITP and a platelet count below 20 x 109/L were included in this open-label, single arm, multi-center Phase III trial. IVIG was given at a dose of 1 g/kg on 2 consecutive days at a maximum infusion rate of 4 mg/kg/min. A subset (56.1%) of the patients received premedication (acetaminophen or diphenhydramine) to avoid adverse events. The primary endpoint was the platelet response rate, defined as the percentage of patients showing an increase in platelet count to ≥50 x 109/L within 7 days of the first infusion. Secondary endpoints included platelet counts at specified time points, time to platelet response, duration of platelet response, and regression of hemorrhages at different bleeding sites. Safety was evaluated by the frequency and severity of adverse events. Results The primary endpoint, an increase in platelet counts to ≥50 x 109/L, was achieved by 81% of the subjects (95% CI: 69–89%). The highest median platelet count (149 x 109/L) was observed on day 8. Median time to response was 2.5 days, with 43% of subjects responding within 1 day. Median duration of platelet response (days with platelet count ≥ 50 x 109/L) was 15.4 days. Regression rates for various bleeding sites ranged from 78% to 100%. Regression of bleeding correlated with increases in platelet counts. Adverse events were reported in 52 (91%) subjects. The most common adverse event was headache (67%), the incidence and severity of which was attenuated by premedication with acetaminophen/diphenhydramine. There were 3 serious adverse events, one of which (aseptic meningitis) was considered related to the study medication. Conclusions The present study has shown the safety and significant efficacy of a novel, 10% liquid, ready for use IVIG preparation, in patients with chronic ITP. A rapid increase in platelet counts to a level where severe bleeding episodes become more unlikely was seen in the majority of patients, as expected with IVIG given at 1 g/kg on 2 consecutive days. The increase in platelet counts was associated with a regression of bleeding. Adverse events were generally mild to moderate in severity, corresponded to those expected with IVIG, and could be prevented with premedication.

Background: Chronic lymphocytic leukemia (CLL) is a neoplasm composed of monomorphic small mature B cells that coexpress CD5 and CD23. The finding of ≥55% prolymphocytes defines B-cell prolymphocytic leukemia (B-PLL), and cases with 15-55% of the prolymphocytes called atypical CLL (aCLL, previously called CLL/PL). Aims: The aim of this study was evaluation of the clinical and prognostic significance of aCLL. Methods: We reviewed the medical records, peripheral blood, and bone marrow findings of 121 patients with untreated CLL (n = 101), aCLL (n = 9), and B-PLL (n = 11) between January 1995 and June 2018. CLL and aCLL patients were classified as Binet stage A (<3 areas of lymphadenopathy, hemoglobin >10 g/dL, platelets >100k/mL), B (≥3 areas of lymphadenopathy, hemoglobin >10 g/dL, platelets >100 k/mL), or C (hemoglobin <10 g/dL or platelets <100k/mL). All patients underwent immunohistochemistry and/or flow cytometric immunophenotyping, among them; 107 patients underwent karyotyping, and 15 patients underwent fluorescent in situ hybridization. Results:The median age at diagnosis was 63.5 (range 25-85) years, 68.0 (40-77) years, and 66.0 (29-78) years and the ratio of males to females was 2.0, 2.0, and 1.8 in CLL, aCLL, and B-PLL, respectively. Lymphadenopathy was more common in CLL (42%, 42/101) and aCLL (56%, 5/9) than in B-PLL (0%), whereas splenomegaly was more in B-PLL (100%) than CLL (25%, 25/101) and aCLL (33%, 3/9). (P = 0.683 and 0.010, respectively). aCLL showed more severe anemia, elevated lactate dehydrogenase, and b2-microglobulin than CLL and B-PLL (P = 0.001, 0.027, and 0.037, respectively). Binet stage A and B were more in CLL (51% and 26%) than in aCLL (30% and 0%), whereas Binet stage C was more in aCLL (70%) than CLL (23%). (P = 0.013). Patients with B-PLL had an atypical immunophenotype with high frequencies of CD5 or CD23 negativity, FMC7 positivity, and strong CD22 positivity (P = 0.672, 0.440, 0.004, and <0.001, respectively). Especially in this study, patients with aCLL showed higher frequencies of FMC7 positivity and strong CD22 positivity than CLL in Western study (P = 0.032 and <0.001, respectively). In B-PLL, normal karyotype was less common and complex karyotype was more common than CLL and aCLL (P = 0.028). In the CLL group, cytogenetic abnormalities were observed in 35% of patients (33/94). The descending order of frequency was trisomy 12 (11%, 10/94), 13q deletion (10%, 9/94), complex karyotype (7%, 7/94), 11q deletion (5%, 5/94), 14q deletion (2%, 2/94), and 17p deletion (1%, 1/94). In the aCLL group, cytogenetic abnormalities were present in 50% of patients (4/8), including 3 cases of trisomy 12, 2 cases of 14q deletion, 1 case of 13q deletion, 11q deletion, 17q deletion and complex karyotype. In the B-PLL group, cytogenetic abnormalities were observed in 80% of patients (8/10), of whom 4 had complex karyotypes. The overall survival rate at 10 years were 65.6%, 22.2%, and 46.3 % in patient with CLL, aCLL, and B-PLL, respectively (P = 0.155). However, only OS of CLL and aCLL showed ...