Safety and efficacy of temsirolimus in combination with three different immuno-chemotherapy regimens in relapse and refractory mantle cell lymphoma, final results of the T3 phase IB trial of the LYSA.

Mantle cell lymphoma has a dismal prognosis at relapse or in the refractory setting. Among therapies, mTor pathway targeting by temsirolimus has been the first strategy approved for relapse in Europe. While its efficacy in monotherapy has long been demonstrated, its use remains limited. In the T3 phase Ib clinical trial, we investigated the recommended dose of temsirolimus in association with R-CHOP (R-CHOP-T), or high-dose cytarabine plus rituximab (R-DHA-T), or fludarabine, cyclophosphamide plus rituximab (R-FC-T). From November 11, 2011 to February 26, 2015, forty-one patients were enrolled. Patients presented with high MIPI (47.5%) at relapse and a median number of treatments of 1 (1-3). Patients were treated by R-CHOP-T (n = 10), R-FC-T (n = 14), or R-DHA-T (n = 17) according to the choice of local investigators. The maximum tolerated dose (MTD) was 15 mg in the R-CHOP-T arm and has not been determined in other treatment arms because of toxicities. All patients experienced ≥ Grade 3 adverse events, mainly thrombocytopenia (76%). Twenty-six patients discontinued prematurely the treatment, mostly for toxicity (n = 12) and progression of the disease (n = 8). Of note, 6 patients of the R-DHA-T arm reached complete remission (35%). Temsirolimus with immuno-chemotherapy is associated with a high rate of toxicities. Determination of MTD could only be achieved for R-CHOP-T arm. Associations between temsirolimus and other targeted therapies may be warranted for R/R MCL patients.

Mortality risks associated with specific clinical manifestations of systemic lupus erythematosus.

BACKGROUND: Mortality in patients with systemic lupus erythematosus (SLE) is often related to disease in particular organ systems. We examined the risks of mortality associated with 8 clinical manifestations of SLE and determined whether these risks differed among patients with different sociodemographic characteristics. METHODS: Using life table analysis, we determined the associations of hemolytic anemia, leukopenia, thrombocytopenia, arthritis, serositis, nephritis, psychosis, and seizures with both all-cause mortality and SLE-related mortality in a cohort of 408 patients. RESULTS: Over a median duration of follow-up of 11 years, 144 patients died; 78 deaths (54%) were SLE related. In univariate analyses, the presence of hemolytic anemia, serositis, nephritis, psychosis, and seizures was associated with greater all-cause mortality, while the presence of arthritis was protective. In multivariate analyses that controlled for patient demographic characteristics, nephritis (relative risk, 2.34) and seizures (relative risk, 1.77) were associated with poorer overall survival. Nephritis and seizures, along with thrombocytopenia, were also associated with greater SLE-related mortality, while leukopenia was protective. The risk of death in association with these clinical manifestations did not differ among patient age, sex, race, or socioeconomic subgroups. CONCLUSIONS: The presence of nephritis and seizures each increased the risk of death in patients with SLE approximately 2-fold. Thrombocytopenia also increased the risk of SLE-related mortality, while leukopenia was protective.

Thrombocytopenia in lambs fed with bovine colostrum.

Artificially reared lambs, fed with bovine colostrum, died within 48 hours after birth, showing thrombocytopenia and extensive haemorrhages on autopsy. The mechanism behind was not fully understood, but experimental immunization of young cattle against sheep red blood cells, carried out five years earlier on the same farm, may have played a role.