Exploratory composite endpoint demonstrates benefit of trilaciclib across multiple clinically meaningful components of myeloprotection in patients with small cell lung cancer.

Chemotherapy-induced myelosuppression is an acute, dose-limiting toxicity of chemotherapy regimens used in the treatment of extensive-stage small cell lung cancer (ES-SCLC). Trilaciclib protects haematopoietic stem and progenitor cells from chemotherapy-induced damage (myeloprotection). To assess the totality of the myeloprotective benefits of trilaciclib, including analysis of several clinically relevant but low-frequency events, an exploratory composite endpoint comprising five major adverse haematological events (MAHE) was prospectively defined: all-cause hospitalisations, all-cause chemotherapy dose reductions, febrile neutropenia (FN), prolonged severe neutropenia (SN) and red blood cell (RBC) transfusions on/after Week 5. MAHE and its individual components were assessed in three randomised, double-blind, placebo-controlled Phase 2 trials in patients receiving a platinum/etoposide or topotecan-containing chemotherapy regimen for ES-SCLC and in data pooled from the three trials. A total of 242 patients were randomised across the three trials (trilaciclib, n = 123; placebo, n = 119). In the individual trials and the pooled analysis, administering trilaciclib prior to chemotherapy resulted in a statistically significant reduction in the cumulative incidence of MAHE compared to placebo. In the pooled analysis, the cumulative incidences of all-cause chemotherapy dose reductions, FN, prolonged SN and RBC transfusions on/after Week 5 were significantly reduced with trilaciclib vs placebo; however, no significant difference was observed in rates of all-cause hospitalisations. Additionally, compared to placebo, trilaciclib significantly extended the amount of time patients remained free of MAHE. These data support the myeloprotective benefits of trilaciclib and its ability to improve the overall safety profile of myelosuppressive chemotherapy regimens used to treat patients with ES-SCLC.

Antiphospholipid antibodies in patients with upper-extremity deep vein thrombosis.

The levels of antibodies to cardiolipin and ß2-glycoprotein I and polymorphic variants G1691A of Factor V (factor V Leiden, FVL) and G20210A of prothrombin gene (G20210A) were studied in 16 patients with upper-extremity deep vein thrombosis (UEDVT). Most of patients with this syndrome have elevated values of these antibodies. Two of these patients are heterozygous carriers for G20210A and 1 - for FVL. Three patients with UEDVT and systemic lupus erythematosus (SLE) are positive for ANA and two others (one of them with Raynaud syndrome) have border line titre 1: 80 for ANA. All 3 patients with SLE are women and the interval between the development of the UEDVT and the onset of SLE was 1-4 years. We would like to suggest that: 1) UEDVT could be the first clinical symptom of Antiphospholipid syndrome, and 2) UEDVT may be the first clinical manifestation of SLE preceding the development of the systemic autoimmune disease by several years.

Bouquet variety of antiphospholipid antibodies in recurrent pregnancy loss.

Seventy-six female patients with two or more recurrent pregnancy losses (RPL) during the 1(st) trimester were studied. Based on the results of the aCL and aB2GPI antibodies testing, patients were divided in two groups: 22 patients with RPL and elevated immunoglobulin (Ig) G/IgM aCL and/or aB2GPI [RPL + antiphospholipid syndrome (APS)] and 54 patients with RPL alone (without high antibodies). Immunoglobulin G aPS and IgG a-AnV in patients with RPL + APS were higher than in controls and IgG aPS were higher in RPL + APS than in RPL alone. Additionally IgG a-AnV and IgM aPE are higher in RPL alone than in controls. In 18/22 (81%) patients with RPL + APS and 29/54 (54%) patients with RPL alone, there were one or more positive antibodies: aPS, aPT, a-AnV or aPE. These results raise a question whether or not these antiphospholipid antibodies should be routinely tested in women with RPL and especially in the context of the so-called "seronegative APS".

The coexistence of systemic lupus erythematosus and thyrotoxicosis: the diagnostic value of antihistone antibodies.

We report four female patients with Graves' disease with positive ANA antibodies and possibility for development of systemic lupus erythematosus. All four patients have been treated with antithyroid drugs. SLE symptoms have appeared from 4 to 12 months after the beginning of therapy with methysol in two of them. The third patient had no symptoms for SLE, but her ANA, anti-DNA, and antihistone antibodies had been positive at the time of the onset of thyrotoxicosis. The fourth patient had alopecia areata with positive ANA and antihistone antibodies.

The role of intravenous immunoglobulin preparations in the treatment of systemic sclerosis.

Scleroderma is progressive autoimmune disease associated with severe disability. The major underlying pathological process in scleroderma is progressive development of fibrous tissue and obliteration of the microvasculature. Currently, there are no medical products for the treatment of scleroderma that provide both sufficient immunosuppression and low-risk side safety profile with negligible side effects. There are a large number of experimental data showing that intravenous immunoglobulin (IVIG) has multiple clinical and morphological effects. On the other hand, some authors report good effect of intravenous immune globulins in patients with scleroderma. The less frequent side effects of IVIG in doses below or equal to 2 g/kg/month divided in 5 consecutive days make IVIG a promising treatment of choice in scleroderma.

Antichlamydial and antisperm antibodies in patients with chlamydial infections.

PROBLEM: Establishing the correlation between antichlamydial antibodies (AchAbs) and antisperm antibodies (ASA) in patients with chlamydial infections. METHOD OF STUDY: ASA were studied in sera from patients (142 with genital, 57 with ocular chlamydial infections) and control group (n = 100) by gelatin and tray agglutination test (TAT), sperm immobilization test (SIT) and ELISA. AchAbs were revealed by ELISA. RESULTS: A significantly higher (P < 0.05) ASA incidence was noted in patients with genital infections as compared with controls and patients with ophthalmologic infection (P < 0.0001), but not between patients with ophthalmologic infection and controls (P > 0.05). A significant correlation was established between AchAbs and ASA for TAT (r = 0.8214, P = 0.0341), SIT (r = 0.797, P = 0.032) and ELISA (r = 0.8519, P = 0.0313) in patients with genital infections only. CONCLUSIONS: The genital Chlamydia infection may play a role in the induction of ASA. This is probably a result of the inflammatory process, but not of cross-reactivity between sperm and Chlamydia trachomatis antigens.