Ibrutinib monotherapy for relapse or refractory primary CNS lymphoma and primary vitreoretinal lymphoma: Final analysis of the phase II 'proof-of-concept' iLOC study by the Lymphoma study association (LYSA) and the French oculo-cerebral lymphoma (LOC) network.

BACKGROUND: Primary central nervous system lymphomas (PCNSLs) are mainly diffuse large B-cell lymphomas (DLBCLs) of the non-germinal centre B-cell subtype, with unmet medical needs. This study aimed to evaluate the efficacy and toxicity of ibrutinib in DLBCL-PCNSL PATIENTS AND METHODS: This prospective, multicentre, phase II study involved patients with relapse or refractory(R/R) DLBCL-PCNSL or primary vitreoretinal lymphoma. The treatment consisted of ibrutinib (560 mg/day) until disease progression or unacceptable toxicity occurred. The primary outcome was the disease control (DC) rate after two months of treatment (P0 < 10%; P1 > 30%). RESULTS: Fifty-two patients were recruited. Forty-four patients were evaluable for response. After 2 months of treatment, the DC was 70% in evaluable patients and 62% in the intent-to-treat analysis, including 10 complete responses (19%), 17 partial responses (33%) and 5 stable diseases (10%). With a median follow-up of 25.7 months (range, 0.7-30.5), the median progression-free and overall survivals were 4.8 months (95% confidence interval [CI]; 2.8-12.7) and 19.2 months (95% CI; 7.2-NR), respectively. Thirteen patients received ibrutinib for more than 12 months. Two patients experienced pulmonary aspergillosis with a favourable (n = 1) or fatal outcome (n = 1). Ibrutinib was detectable in the cerebrospinal fluid (CSF). The clinical response to ibrutinib seemed independent of the gene mutations in the BCR pathway. CONCLUSION: Ibrutinib showed clinical activity in the brain, the CSF and the intraocular compartment and was tolerated in R/R PCNSL. The addition of ibrutinib to standard methotrexate-base induction chemotherapy will be further evaluated in the first-line treatment. CLINICAL TRIAL NUMBER: NCT02542514.

Combination of rituximab, bortezomib, doxorubicin, dexamethasone and chlorambucil (RiPAD+C) as first-line therapy for elderly mantle cell lymphoma patients: results of a phase II trial from the GOELAMS.

BACKGROUND: There is no consensual first-line chemotherapy for elderly patients with mantle cell lymphoma (MCL). The GOELAMS (Groupe Ouest-Est des Leucémies Aiguës et Maladies du Sang) group previously developed the (R)VAD+C regimen (rituximab, vincristine, doxorubicin, dexamethasone and chlorambucil), which appeared as efficient as R-CHOP (rituximab, cyclophosphamide, doxorubicine, vincristine, prednisone) while less toxic. Based on this protocol, we now added bortezomib (RiPAD+C: rituximab, bortezomib, doxorubicin, dexamethasone and chlorambucil) given its efficacy in relapsed/refractory MCL patients. The goal of the current phase II trial was to evaluate the feasibility and efficacy of the RiPAD+C regimen as frontline therapy for elderly patients with MCL. PATIENTS AND METHODS: Patients between 65 and 80 years of age with newly diagnosed MCL received up to six cycles of RiPAD+C. RESULTS: Thirty-nine patients were enrolled. Median age was 72 years (65-80). After four cycles of RiPAD+C, the overall response rate was 79%, including 51% complete responses (CRs). After six cycles, CR rate increased up to 59%. After a 27-month follow-up, median progression-free survival (PFS) is 26 months and median overall survival has not been reached. Four patients (10%) discontinued the treatment because of a severe toxicity and seven patients (18%) experienced grade 3 neurotoxicity. CONCLUSION: The bortezomib-containing RiPAD+C regimen results in high CR rates and prolonged PFS with predictable and manageable toxic effects in elderly patients with MCL.

[Percutaneous cholecystostomy. A study of 30 patients]. / Cholécystostomie percutanée. Une étude chez 30 malades.

OBJECTIVE AND METHODS: The treatment of acute cholecystitis or angiocholitis is often difficult in elderly or very ill patients. The aim of this retrospective study was to assess the efficacy and the results of ultrasound guided percutaneous cholecystostomy in patients with acute cholecystitis or biliary tract obstruction and anesthetic or surgical contraindications. RESULTS: Thirty patients (25-93 years, 16 men and 14 women) were included in this study. Ultrasound guided percutaneous cholecystostomy was successful on the septic syndrome in 27 patients; endoscopic sphincterotomy was performed in 6 patients after clinical improvement. A failure of the procedure on sepsis was observed in 3 patients: cholecystectomy was performed after cardiac improvement in one patient, and 2 patients died. Two other patients died of extradigestive diseases. No serious complication related to cholecystostomy was observed. CONCLUSION: Ultrasound guided percutaneous cholecystostomy is a safe and simple procedure. It can be done at bedside and has low morbidity and mortality. It can be considered as a definitive treatment, or a temporary one with secondary surgical or endoscopic management.

Clinical significance of urinary human tissue non-specific alkaline phosphatase (hTNAP) in pre-eclampsia and eclampsia.

The aim of this work was to determine the levels of urinary human tissue non-specific alkaline phosphatase (hTNAP) in pre-eclampsia and eclampsia in order to assess renal tubular damage. Urine samples were collected from 26 mild pre-eclamptic, 26 were pre-eclamptic, 20 eclamptic patients and 20 healthy pregnant women (controls) in their late third trimester. Urinary hTNAP/creatinine (hTNAP/cr) in severe pre-eclampsia and eclampsia were significantly higher than in controls. Urinary hTNAP/cr was increased in 23%, 77% and 90% of cases of mild pre-eclampsia, severe pre-eclampsia and eclampsia, respectively, indicating that the increase correlates with the severity of the disease. Marked elevation or urinary hTNAP/cr was also associated with bad fetal outcome. These results provide additional evidence for renal tubular damage in pre-eclampsia and eclampsia.

The prevalence of serum antineutrophil cytoplasmic autoantibodies in preeclampsia and eclampsia.

OBJECTIVES: The purpose of this study was to evaluate the prevalence of antineutrophil cytoplasmic autoantibodies (ANCAs) in preeclampsia and eclampsia. METHODS: Blood samples were obtained from 26 mildly preeclamptic, 26 severely preeclamptic, and 20 eclamptic, and 20 normal pregnant women (controls) in the late third trimester for the determination of serum cytoplasmic pattern ANCA (cANCA) and perinuclear pattern ANCA (pANCA) by the corresponding enzyme immunoassay. RESULTS: Significant elevations of serum cANCA and pANCA were found in mild and severe preeclampsia and eclampsia. The extent of rise correlated well with the severity of the disease. Both ANCAs were detected in 80% of eclamptic cases versus 38.5 and 69.3% of mild and severe preeclampsia, respectively. Marked elevations of serum ANCAs were associated with poor fetal outcome. CONCLUSION: ANCAs may be involved in the pathogenesis of glomerulonephritis in preeclampsia and eclampsia and their presence may be attributed to an autoimmune mechanism initiated by autoantibody-mediated activation of neutrophils.