A randomized phase III study of carfilzomib vs low-dose corticosteroids with optional cyclophosphamide in relapsed and refractory multiple myeloma (FOCUS).

This randomized, phase III, open-label, multicenter study compared carfilzomib monotherapy against low-dose corticosteroids and optional cyclophosphamide in relapsed and refractory multiple myeloma (RRMM). Relapsed and refractory multiple myeloma patients were randomized (1:1) to receive carfilzomib (10-min intravenous infusion; 20 mg/m2 on days 1 and 2 of cycle 1; 27 mg/m2 thereafter) or a control regimen of low-dose corticosteroids (84 mg of dexamethasone or equivalent corticosteroid) with optional cyclophosphamide (1400 mg) for 28-day cycles. The primary endpoint was overall survival (OS). Three-hundred and fifteen patients were randomized to carfilzomib (n=157) or control (n=158). Both groups had a median of five prior regimens. In the control group, 95% of patients received cyclophosphamide. Median OS was 10.2 (95% confidence interval (CI) 8.4-14.4) vs 10.0 months (95% CI 7.7-12.0) with carfilzomib vs control (hazard ratio=0.975; 95% CI 0.760-1.249; P=0.4172). Progression-free survival was similar between groups; overall response rate was higher with carfilzomib (19.1 vs 11.4%). The most common grade ⩾3 adverse events were anemia (25.5 vs 30.7%), thrombocytopenia (24.2 vs 22.2%) and neutropenia (7.6 vs 12.4%) with carfilzomib vs control. Median OS for single-agent carfilzomib was similar to that for an active doublet control regimen in heavily pretreated RRMM patients.

Lenalidomide in relapsed refractory myeloma patients: impact of previous response to bortezomib and thalidomide on treatment efficacy. Results of a medical need program in Belgium.

The prognosis of multiple myeloma patients has significantly improved since the introduction of the novel agents thalidomide, bortezomib and lenalidomide. We report the data of a medical need programme with lenalidomide plus dexamethasone, conducted in Belgium between August 2007 and March 2008, and including 98 relapsed refractory multiple myeloma patients. In addition to chemotherapy and steroids, all patients had received prior treatment with bortezomib, and 84% of them had been exposed to thalidomide. In 52 patients response data could be retrieved by post-hoc analysis. A partial remission or better was achieved in 52% (49% partial and 3% complete response) of patients, despite a median of 5 previous anti-myeloma treatment lines. Responses were rapid while the majority of patients received lenalidomide with once weekly (also called low-dose) dexamethasone. Treatment with lenalidomide plus dexamethasone did prolong overall survival by nearly half a year in this population with end-stage myeloma. Overall response and quality of response were independent of previous response to thalidomide and bortezomib, although the time to progression tended to be shorter in thalidomide- and bortezomib-refractory patients. It can be concluded that lenalidomide plus dexamethasone is an effective and safe treatment regimen in highly refractory multiple myeloma patients, and that these responses are irrespective of previous exposure or sensitivity to thalidomide and bortezomib.

The Belgian 2010 consensus recommendations for the treatment of multiple myeloma.

Since the introduction of novel therapeutic agents including thalidomide, lenalidomide and bortezomib, the prognosis of multiple myeloma (MM) has significantly improved. These agents have been incorporated into numerous treatment schedules for newly diagnosed as well as more advanced MM patients. Hence, the therapeutic options for MM have become more complex and subject to rapid changes. The multiple myeloma study group (MMSG) of the Belgian Hematological Society has established recommendations for the treatment of MM as based on an extensive review of the literature which is also summarized in this paper. The recommendations are the result of a consensus opinion between haematologists with experience in the field and representing most haematology centres in Belgium. Where applicable, reimbursement criteria are also taken into account. The consensus recommendations should be a reference for use by clinical haematologists in daily practice.

Autologous transplantation of bone marrow mononuclear cells for limb ischemia in a caucasian population with atherosclerosis obliterans.

BACKGROUND: Autologous transplantation of bone marrow mononuclear cells (ATBMMNC) has been used successfully in critical limb ischemia. All reported patients were of Asian descent, however, and several studies included only young patients with thromboangiitis obliterans. Whether the beneficial results can be extrapolated to older Caucasian patients with atherosclerosis obliterans and a heavy burden of cardiovascular risk factors remains unclear. METHODS: We enrolled 16 patients (age 78 +/- 2 year) with critical limb ischemia and a high prevalence of hypertension, smoking, diabetes, hypercholesterolemia and uremia. Mononuclear cells were isolated from the bone marrow and injected in the gastrocnemius muscle of the affected limb. RESULTS: Four patients died because of progressive gangrene (two) or unrelated causes (two). Three patients required an amputation and one patient a femorocrural bypass within 12 weeks. The remaining eight patients had a modest improvement of resting pain and/or trophic lesions. Transcutaneous oxygen pressure (ratio lesion/reference) improved from 0.51 +/- 0.11 before to 0.86 +/- 0.03 (P < 0.001) after 12 weeks, whereas ankle-brachial index did not change significantly (0.42 +/- 0.15 vs. 0.59 +/- 0.1; P = 0.23). The number of visible collateral vessels on digital subtraction angiography changed with 0.89 +/- 0.86 on a scale of 1-4 (P = 0.33). Capillary surface area in a biopsy of gastrocnemius, evaluated by immunostaining for endothelial nitric oxide synthase, increased from 0.61 +/- 0.07% to 2.38 +/- 0.73% (P < 0.05). CONCLUSIONS: Although ATBMMNC was associated with objective signs of neovascularization, symptomatic improvement was only modest and restricted to the least affected patients. The discrepancy with previous findings may be related to the high prevalence of cardiovascular risk factors which causes endothelial progenitor cell dysfunction.

Folate and Vitamin B(12) deficiency presenting as pancytopenia in pregnancy: a case report and review of the literature.

We present a case of extreme pancytopenia in a 27-year-old pregnant woman. The initial picture was compatible with a severe hematological problem in the category of aplastic anemia, paroxysmal nocturnal hemoglobinuria or even acute leukemia. The further biochemical investigations revealed, however, a folate deficiency. Nowadays this is a very rare cause of pancytopenia. Next to this she also had a Vitamin B(12) deficiency due to intrinsic factor failure. The recent literature is discussed.

Intravascular large B-cell lymphoma or intravascular lymphomatosis: report of a case diagnosed by testicle biopsy.

Intravascular large B-cell lymphoma or intravascular lymphomatosis (IVL) is an extremely rare form of non-Hodgkin's lymphoma. The most common clinical sign is fever of unknown origin (FUO). Histologically, there is proliferation of malignant lymphoid cells within vascular lumina. Cytologically, the cells have features similar to those found in classical large cell lymphoma. Examination of pulmonary artery blood showed the presence of this abnormal population in our patient; to the best of our knowledge there are only four other. reports of detection of circulating tumor cells in IVL. The outcome is very poor. The diagnosis is most frequently made after biopsy of skin or brain but is often established post mortem. We present what is--to our knowledge--the first reported case of IVL diagnosed after biopsy of a testicle. In the event of FUO and suspicion of a malignancy, IVL--although very rare--should be one of the differential diagnoses.

Multicentric Castleman's disease in 2 patients with HIV infection, unresponsive to antiviral therapy.

Two HIV infected patients with multicentric Castleman's disease (MCD) and Kaposi's sarcoma are reported. Both died despite combination antiretroviral therapy including protease inhibitors.

Decreasing antibiotic resistance of Enterobacteriaceae by introducing a new antibiotic combination therapy for neutropenic fever patients.

Prompt empiric antibiotic therapy is of critical importance for patients with neutropenic fever. However, a major concern with important clinical consequences is the emergence of bacterial resistance to antibiotics. After using ceftazidime with a glycopeptide as initial empiric therapy for neutropenic fever, we were confronted with a 75% reduced susceptibility rate to ceftazidime of inducible Enterobacteriaceae collected in 1994. The initial empiric therapy was therefore replaced in May 1995 by a combination of cefepime with amikacin, with addition of a glycopeptide after 48 h if necessary. After this change, we observed a significant decrease in reduced susceptibility of inducible Enterobacteriaceae, not only to ceftazidime, but also to amikacin, cotrimoxazole and ciprofloxacin. There was also a decrease in reduced susceptibility of non-inducible Enterobacteriaceae, such as Klebsiella spp, to ceftazidime. The reduction of resistance may be related at least in part to the combined use of cefepime together with an aminoglycoside. This study shows that it is possible to reverse bacterial resistance by modifying the antibiotic regimen used.

Successful treatment of cytomegalovirus encephalitis in a patient with Hodgkin's disease in remission.

Cytomegalovirus encephalitis is a rare but life-threatening infection in non-AIDS patients. To our knowledge, no case that followed conventional treatment for Hodgkin's lymphoma has been reported. We present a patient with Hodgkin's disease in complete remission after combined modality treatment who was succesfully treated with a combination of ganciclovir and foscarnet.

[Treatment of leprotic neuritis. Exclusive medical treatment or combined with decompression]. / Evolution du traitement des nevrites hanséniennes. Traitement médical exclusif ou associé à la décompression.

The authors consider the evolution of the treatment of leprotic neuritis based on homogenous series of numerous observations (a minimum of 250-300). These observations are well registered and documented with some results dimensioned by the classical A. L. E. R. T. tests carried out at intervals of time and verified by comparison between series only medical treatment and series of medico-surgical treatment. Considering some remote results and some comparative series, the indications of the exclusive medical treatment have been well defined, and the ones of the surgical decompression have been reduced. The early case finding of a leprotic neuritis by the mean of easy methods as well as its monitoring during its early specific treatment is essential. By this way we get an important proportion of functional results: satisfactory (50 p.c.) or interesting (20 p.c.). In the case of painful hypertrophia, the complementary decompression secure not only the functional recovery of mortricity, but also the epicritic sensibility.

Plasma androstanediol glucuronide levels during pregnancy.

In distinction to Braunstein and Horton (1985) who reported an increase in maternal 5 alpha-androstane-3 alpha, 17 beta-diol glucuronide (ADG) plasma levels during pregnancy, we observed a decrease of these levels from the 10th week of pregnancy; the decrease parallels the decrease in dehydroepiandrosterone sulphate (DHEA-S) concentration. As the latter is a major precursor of ADG, the decrease in ADG levels during pregnancy is not unexpected and in line with the concept that ADG is a parameter of androgenicity.

[Surgical decompression of neuritis of Hansen's disease]. / Décompression chirurgicale des névrites de la maladie de Hansen.

The recent progress were focused on: the identification of the general immunological mechanism of the hansenian neuritis, demonstrated by endoneural biopsies; the different pathology of the two categories of neuritis; the pathophysiologic derangements, inducing hypoxia or anoxia in the truncular involved segment. The adjuvant role of the canals is important; the clinical differences of the two categories of neuritis and the cases we shall treat by emergency; the importance of antireactionnal treatment and of the notation by tests for the study of the results. The goals are the hemodynamic decompression, useful in the first stage of ENL neuritis, the mechanical decompression of neural fasciculus and the urgent exeresis of necroses or evacuation of febrile abscess. Three technics a re studied: Extraneural and epineural decompression fascicular endoneural necrosis, neurolysis and complex neurolysis for evaluated ENL neuritis and for endoneural necrosis. The different indication according to the two categories: medico-surgical treatment for ENL neuritis, and according the precocity and the delay of the antireactional treatment, and also the absolute emergency of the necrosis and febrile abscess. The results of the treatment of 258 cases of recent neuritis are presented.

[Morphologic and biologic properties of diphtherroid organisms (LDC) isolated in leprosy]. / Propriétés morphologiques et biologiques des organismes diphtéroïdes (LCD) isolés chez les lépreux.

Acid-alcohol-fast bacteria are not always detectable in all leprosy lesions. Non acid-fast microorganisms may be associated with acid-fast bacteria. The most frequently isolated strains from leprosy lesions are non acid-fast bacteria, morphologically related to C. diptheirae. Hence their designation as diphtheroïds or LDC (leprosy derived corynebacteria). Their antigenic structure is more closely related to M. leprae and other mycobacteria than to classical corynebacteria. This leads to the hypothesis of a potential role in the pathogenesis of leprosy and their use as an antigen for skin tests by leprosy patients.