Annual incidence and severity of acute episodes in hereditary thrombotic thrombocytopenic purpura.

Hereditary thrombotic thrombocytopenic purpura (hTTP) is a rare thrombotic microangiopathy characterized by severe congenital ADAMTS13 deficiency and recurring acute episodes causing morbidity and premature death. Information on the annual incidence and severity of acute episodes in patients with hTTP is largely lacking. This study reports prospective data on 87 patients from the Hereditary TTP Registry (clinicaltrials.gov #NCT01257269) for survival, frequency, and severity of acute episodes from enrollment until December 2019. The 87 patients, followed up for a median of 4.2 years (range, 0.01-15 years), had a median age at overt disease onset and at clinical diagnosis of 4.6 years and 18 years (range, 0.0-70 years for both), respectively. Forty-three patients received regular plasma prophylaxis, whereas 22 did not, and treatment changed over time or was unknown in the remaining 22. Forty-three patients experienced 131 acute episodes, of which 91 (69%) occurred in patients receiving regular prophylaxis. This resulted in an annual incidence of acute episodes of 0.36 (95% confidence interval [CI], 0.29-0.44) with regular plasma treatment and of 0.41 (95% CI, 0.30-0.56) without regular plasma treatment. More than one-third of acute episodes (n = 51) were documented in children <10 years of age at enrollment and were often triggered by infections. Their annual incidence of acute episodes was significantly higher than in patients aged >40 years (1.18 [95% CI, 0.88-1.55] vs 0.14 [95% CI, 0.08-0.23]). The prophylactic plasma infusion regimens used were insufficient to prevent acute episodes in many patients. Such regimens are burdensome, and caregivers, patients, and their guardians are reluctant to start regular plasma infusions, from which children particularly would benefit.

Bendamustine as monotherapy and in combination regimens for the treatment of chronic lymphocytic leukemia and non-hodgkin lymphoma: a retrospective analysis.

BACKGROUND/AIM: In this study, we carried out a retrospective analysis of the efficacy and toxicity of bendamustine in patients with B-cell lymphoproliferative diseases. METHODS: Bendamustine was administered both as monotherapy and in combined protocols to 92 patients, including 76 patients with chronic lymphocytic leukemia (CLL) and 16 patients with indolent lymphomas. Bendamustine plus rituximab was used to treat 65.2% of the patients, and 34.8% of the patients received bendamustine as monotherapy. RESULTS: The overall response rate was 64.2%, including the complete response rate (18.5%) and the partial response rate (45.7%). The median overall survival (OS) was 11.5 months. Among the pretreatment parameters, ß2-microglobulin (RR = 1.413; p = 0.001) and hemoglobin levels (RR = 0.85; p = 0.03) significantly influenced survival. The OS was significantly longer in patients who received ≤2 lines of previous therapy compared to >3 lines (p = 0.043; log-rank test) and those who received ≥4 courses of therapy with bendamustine (p = 0.0007; log-rank test). Toxicity was predominantly hematological, including grade III/IV neutropenia in 33.7%, thrombocytopenia in 13%, and anemia in 13% of patients. CONCLUSION: Bendamustine, both in monotherapy and in combination regimens, is an effective therapy with a favorable toxicity profile in patients with indolent B-cell malignancies.

Adherence to prophylactic treatment in adult patients with severe hemophilia in Poland.

INTRODUCTION: Patient adherence to a prophylactic regimen is important for optimal benefit of hemophilia treatment. Despite a growing number of adults with hemophilia in Poland receiving secondary prophylaxis, data on adherence to the regimen are limited. OBJECTIVES: The aim of the study was to assess adherence to secondary prophylaxis in Polish adults with severe hemophilia. PATIENTS AND METHODS: Patients were recruited in 18 hemophilia treatment centers in Poland. Adherence to prophylaxis was assessed with the Validated Hemophilia Regimen Treatment Adherence Scale Prophylaxis (VERITAS­Pro) questionnaire. RESULTS: Data on 270 men on the prophylactic regimen (median [interquartile range, IQR] age, 37 [18-75] years; mean [SD], 38.2 [13.3] years) were analyzed. Median (IQR) VERITAS­Pro score for the study population was 36 (24-76) years; mean (SD), 37.7 (9.9) years, indicating general adherence to the prophylactic regimen. The median subscale scores ranged from 4 for Dosing to 8 for Planning (means, 5.6 and 7.7, respectively). The most pronounced difference in the subscale scores between adherent and nonadherent patients was recorded for Dosing (median, 4 vs 10; mean, 5.3 vs 9.3) and Remembering (median, 5 vs 11; mean, 5.7 vs 10.7). The overall adherence rate was 94%. CONCLUSIONS: Our results show a high rate of adherence to hemophilia prophylaxis by Polish adults. Problems with the management of clotting factor stocks and remembering about the injection of the clotting factor were identified as potential barriers to adherence in adults with hemophilia in Poland.

Coexistence of pemphigus foliaceus and acquired hemophilia A: A case report.

Pemphigus foliaceus (PF) is an autoimmune bullous dermatosis with anti-desmoglein-1 autoantibodies. Acquired hemophilia A (AHA) is a rare coagulation disorder with a high mortality rate, caused by anti-factor VIII immunoglobulin G antibodies leading to spontaneous severe hemorrhages into skin, muscles or soft tissues. This coagulopathy may be associated with malignancies, drug reactions and autoimmune disorders including bullous dermatoses. Herein, we demonstrate a first report of AHA in the course of pemphigus foliaceus. A 55-year-old woman presenting with extensive, erosive, crusted, scaly skin lesions was diagnosed with PF based on histopathological and immunofluorescent examination, confirmed by the presence of anti-desmoglein-1 antibodies on enzyme-linked immunoassay. She developed extensive internal hemorrhages and prolonged external bleeding after laparotomy. Based on coagulation tests, AHA was diagnosed. Simultaneous remission of pemphigus and coagulopathy occurred with immunosuppressants and recombinant activated factor VII.

A clinical comparison of the efficacy and safety of biosimilar G-CSF and originator G-CSF in haematopoietic stem cell mobilization.

BACKGROUND: Recombinant granulocyte colony-stimulating factor (G-CSF) is widely used to mobilize haematopoietic stem cells. We compared the efficacy and safety of a biosimilar G-CSF (Zarzio(®), Sandoz Biopharmaceuticals) with the originator G-CSF (Neupogen(®), Amgen) in patients with haematological malignancies. METHODS: A total of 108 patients were included in this study, 59 of whom were female (49 male), with an overall median age of 51 years (range 19-69). Patients had multiple myeloma (n=46), non-Hodgkin's lymphoma (n=28), Hodgkin's lymphoma (n=26), or other diagnosis (n=8). After administration of mobilizing regimens (primarily high-dose etoposide, high-dose cyclophosphamide, intermediate-dose Ara-C or ESHAP), patients were randomized to a standard daily 10 µg/kg dose of biosimilar G-CSF (n=54) or originator G-CSF (n=54). RESULTS: Median duration of G-CSF administration was 8 days with both biosimilar G-CSF (range 4-17) and originator G-CSF (range 4-14). Both groups had a median of one apheresis with a median time until first apheresis of 11 days. There were no statistically significant differences between groups in the mean ± SD number of mobilized CD34+ cells/µL in peripheral blood or the number of CD34+ cells/kg body weight. Five patients (9%) in the originator G-CSF group and six patients in the biosimilar G-CSF group (11%) did not mobilize sufficient CD34+ cells. The adverse event profile was similar between groups. CONCLUSIONS: A biosimilar G-CSF (Zarzio(®)) demonstrated similar efficacy and safety as the reference originator G-CSF (Neupogen(®)) in hematopoietic stem cell mobilization in patients with haematological malignancies.