Zoonotic Potential of Brucella microti.

Background: Brucella microti is a pathogen of rodents and wild mammals. Here, we report the first probable infection with B. microti in a mammalogist. Materials and Methods: In the study, we provided complete clinical description as well as laboratory analysis of probable human infection caused by B. microti. Results: Considering the clinical course of the infection, the obvious epidemiological link (a bite by an infected rodent), the isolation of a pathogen from a sick vole that was affected by clinical infection with B. microti, and the specific serological response (slow agglutination test) in human patient, we can conclude that the human disease described here was probably caused by B. microti, an emerging bacterial pathogen transmitted by rodents. Conclusion: Rodents and other wildlife need to be monitored not only for established zoonotic agents such as hantaviruses, lymphocytic choriomeningitis virus, Leptospira spp., Francisella tularensis, but also for Brucella microti and other atypical rodent-borne brucellae.

[Monoclonal gammopathy of undetermined significance and asymptomatic multiple myelom in the year 2014 ]. / Monoklonální gamapatie nejistého významu a asymptomatický mnohocetný myelom z pohledu roku 2014.

Presence of monoclonal immunoglobulin in serum or urine is a relatively common event affecting about 3.2 % of people over 50. Isolated increase of only one type of free light chain, either κ or λ, is detected in 0.7-0.8 % of people over 50. Most people with monoclonal immunoglobulin meet the criteria of the so-called "mono-clonal gammopathy of undetermined significance (MGUS)". MGUS is defined by concentration of monoclonal immunoglobulin in serum < 30 g/l, number of plasma cells in the bone marrow < 10 % and the absence of symptoms of multiple myeloma and other lymphoproliferative diseases. A proportion of people with MGUS gradually progresses from asymptomatic into symptomatic myeloma or other malignant lymphoproliferative disease requiring treatment. Therefore, MGUS is considered to be one of the most common premalignant conditions with an average risk of transformation into malignant disease of 1 % per year. Monoclonal gammopathy of IgG and IgA subtype can develop into multiple myeloma. Light chain monoclonal gammopathy can develop not only into light chain multiple myeloma but also into AL-amyloidosis and light chain deposition disease (amorphous deposits of light chains damaging organs). IgM monoclonal gammopathy may develop into Waldenstrom macroglobulinemia or other lymphoproliferative disorder, or into rare IgM subtype of multiple myeloma. Unfortunately, people with MGUS are threatened by more than an increased risk of transformation into multiple myeloma or other severe hematologic disease. Pre-malignant clone of plasma cells in the bone marrow causes changes in the bone marrow that directly affect the person. For people with MGUS, there is an increased incidence of osteoporosis and increased fracture risk when compared to the general population. People with MGUS also have an increased risk of bacterial infections and thromboembolic complications compared with the same age population without MGUS. Clonal plasma cells, which are the basis of MGUS, may in some cases produce toxic monoclonal immunoglobulin which can damage the body's own antibody activity by binding to specific antigens (such as cold agglutinin disease), or their deposits in organs (e.g. kidney damage) or physical properties (e.g. cryoglobulinemia). Therefore, it is recommended that this group of people is regularly checked with the aim to capture not only transformation into symptomatic multiple myeloma or another malignant disease, but also the formation of the above-mentioned complications. Moreover, it is recommended to monitor patients with asymptomatic myeloma and to initiate treatment only after symptoms of multiple myeloma are observed. In 2014, discussion of subdivision of subgroups of patients with asymptomatic myeloma with high ( 80 %) probability of early (within 2 years) transformation in multiple myeloma which would be beneficial for early initiation of treatment is ongoing. According to first proposals, patients with asymptomatic myeloma that meet at least one of the three conditions: more than 60 % of plasma cells in the bone marrow, ratio of free light kappa and lambda chains is greater than 100 or less than 0.01, or multiple focal lesions on whole-body MRI of the skelet. The review contains current opinions on prognostic classification and appropriate intervals and extent of control examinations.

Similar efficacy of thalidomide- and bortezomib-based regimens for first relapse of multiple myeloma.

Many regimens containing novel drugs have been developed for multiple myeloma (MM). It is not yet clear whether some of the novel agents are better than others. In a retrospective study, we have analyzed the outcomes of patients with first relapse of MM treated with thalidomide-based (T) regimens (n=105) or bortezomib-based (B) regimens (n=106). Both T and B groups were comparable regarding basic clinical parameters and first-line therapies. Combination of thalidomide with an alkylating drug (A) and dexamethasone (D) was used in 91 cases, T with D in five cases, and T alone in nine cases. A combination of bortezomib with A and D was used in 58 patients, B with D or A in 40 patients, and B alone in eight patients. In the T group, ORR was 51%, median TTP from the start of treatment for relapse of 13.1 months, and median OS of 30.4 months. In the B group, ORR was 50% with median TTP of 16.7 months and median OS of 37.2 months. No significant differences in ORR (p=0.774), TTP (p=0.207), or OS (p=0.889) were observed between the two groups. In conclusion, T- and B-based regimens appear to be equally effective in the treatment of first MM relapse.

Salvage treatment with upfront melphalan 100 mg/m(2) and consolidation with novel drugs for fulminant progression of multiple myeloma.

Patients (pts) with fulminant progression (FPG) of multiple myeloma (MM) after autologous stem cell transplantation (ASCT) have poor prognosis. Pancytopenia, extramedullary disease, and/or renal impairment are often present, and treatment options are limited. We have retrospectively evaluated 31 pts with FPG of MM after ASCT who were treated upfront salvage therapy with melphalan 100 mg/m(2) (MEL 100) followed by PBSC support and consolidation therapy using regimens containing thalidomide (n = 16) or bortezomib (n = 15). The overall response rate (ORR) was 58% (18/31). After MEL 100, one patient achieved complete remission (3%), 26% of pts very good partial remission, 29% of pts partial remission, and 42% of pts stable disease. Progression within 3 months after MEL 100 occurred in 35% of pts. The median follow-up from MEL 100 was 8 months. The median TTP was 5 months (range, 2-15 months), and the median OS was 8 months (range, 3-23 months). There were no treatment-related deaths. In fulminant progression of MM, upfront MEL 100 is a safe salvage regimen with good response rate (ORR, 58%). Treatment with upfront MEL 100 followed by a thalidomide- or bortezomib-based regimen can prolong overall survival to more than 12 months in 33% of pts with fulminant progression of MM.

Long-term outcomes of autologous transplantation in multiple myeloma: significant survival benefit of novel drugs in post-transplantation relapse.

BACKGROUND: Autologous stem cell transplantation (autoSCT) has an important role in the treatment of patients with symptomatic multiple myeloma (MM). Treatment options for myeloma have expanded in the past decade, and it seems that patients who are treated with novel drugs such as thalidomide and bortezomib for relapse after autoSCT have longer overall survival (OS). PATIENTS AND METHODS: Herein, we describe the long-term outcome of a cohort of 185 patients with newly diagnosed MM treated with autoSCT. We have analyzed factors that might predict for long-term survival. RESULTS: Following autoSCT, the overall response rate was 94% (173 of 185 patients); 29% (53 of 185 patients) were in complete remission (CR). Median time to progression (TTP) and OS from start of therapy were 39.8 months and 77.9 months, respectively. The median follow-up was 103.8 months (range, 60.8-144.8 months); 23% of the patients are alive and disease free, 21% of the patients are alive with relapse, and 56% of the patients have died. On multivariate analysis, factors associated with significantly better OS were International Staging System (ISS) disease stage < III (hazard ratio [HR], 2.6; P < .001), achievement of CR after autoSCT (HR, 2.8; P < .001) and use of thalidomide (HR, 4.3; P < .001) and/or bortezomib (HR, 7.3; P < .001) in posttransplantation relapse treatment. The patients' age, renal impairment, disease status before autoSCT and maintenance therapy with interferon-alpha (IFN-alpha) or IFN-alpha and dexamethasone did not significantly affect TTP and OS after transplantation. CONCLUSION: According to our results, the achievement of CR after transplantation, ISS stage other than III, and administration of thalidomide or bortezomib in posttransplantation relapse were significant parameters favoring long-term posttransplantation survival.

Varicella-zoster virus prophylaxis with low-dose acyclovir in patients with multiple myeloma treated with bortezomib.

BACKGROUND: Varicella-zoster virus (VZV) reactivation is a common complication in patients with multiple myeloma (MM) treated with bortezomib, with an incidence rate of 10%-60%. The aim of our study was to analyze the effect of acyclovir prophylaxis in this patient population. PATIENTS AND METHODS: We studied 98 consecutive patients with relapsed MM treated with bortezomib. Bortezomib 1.3 mg/m2 was given on days 1, 4, 8, and 11 of a 21-day cycle. At first, patients did not receive any VZV prophylaxis, but because of the high incidence of VZV reactivation, VZV prophylaxis with acyclovir was implemented subsequently. RESULTS: A total of 11 patients treated with bortezomib did not have any VZV prophylaxis, and 4 of these 11 patients (36%) developed VZV reactivation in the form of herpes zoster. No VZV reactivations were observed in the 32 patients who received acyclovir 400 mg 3 times daily or the 55 patients who received acyclovir in a dose reduced to 400 mg once daily during bortezomib treatment. CONCLUSION: Varicellazoster virus reactivation is a common and serious adverse effect of bortezomib treatment. Acyclovir 400 mg once daily is sufficient to protect from VZV reactivation in patients with MM treated with bortezomib.

Skin lesions induced by bortezomib.

We report on six cases of skin lesions induced by bortezomib in patients treated for relapsed multiple myeloma. The folliculitis-like rash appeared in the second cycle of bortezomib therapy. Therapy with prednisone led to rapid resolution of the skin lesions. Prednisone 10 mg before each infusion of bortezomib was necessary to prevent recurrence of the rash while antihistamines alone were ineffective.