In this phase I/II study, we explored the combination of Temsirolimus with Bendamustine and Rituximab (BeRT) in patients with r/r follicular lymphoma (FL) or mantle cell lymphoma (MCL). Patients with 1-3 prior therapies received Bendamustine (90 mg/m(2), day 1+2) and Rituximab (375 mg/m(2), day 1) with Temsirolimus in doses from 25 to 75 mg added on day 1, 8, 15 of a 28-day cycle. Fifteen (11 MCL, 4 FL) patients were included in the phase I. Median age was 73 years and median pretreatment number was 2. No formal dose-limiting toxicity was observed. Dominant non-hematological side effects were fatigue in 11 (73%), nausea in 9 (60%), mucositis in 7 (47%) and vomiting in 6 patients (40%). Cough, diarrhea, pyrexia and rash were observed in five patients (33%) each. Grade 3/4 events included leukopenia in 6 (40%), neutropenia in 4 (27%) and thrombocytopenia in 2 patients (13%). An objective response was observed in 14/15 patients (93%), including 5 complete response (33%; all MCL). After a median follow-up of 19 months, 67% of patients are without signs of progression. Temsirolimus can be safely added to BR with promising preliminary activity. Recruitment in phase II is ongoing.

Erdheim-Chester disease (ECD) is a rare histocytic disorder. We report a case of a 45-year-old male ECD patient with severe clinical manifestation (urinary obstruction due to retroperitoneal mass with hydronephrosis, involvement of long bones) and central nervous system involvement (hemiparesis, aphasia and diabetes insipidus). Diagnosis was confirmed by typical clinical, radiological and histological findings. Under immunosuppressive therapy with prednisolone and interleukin-1A receptor antagonist (Anakinra, Kineret, Swedish Orphan Biovitrum AB, Stockholm, Sweden), a rapid improvement of the patients' symptoms and condition was observed. This is the first report of a successful combination therapy of Anakinra and glucocorticoids. Furthermore, current literature about ECD and treatment options are discussed.

SummarySalvage therapy followed by high-dose therapy (HDT) remains a mainstay for patients with relapsed lymphoma, however no optimal regimen has been defined. Here we report on the results of R-DexaBEAM (rituximab, dexamethasone, carmustine, etoposide, cytarabine, melphalan) followed by HDT. Patients aged 18-65 years, Eastern Cooperative Oncology Group performance score 0-2, with relapsed/refractory B-cell non-Hodgkin lymphoma (NHL) were eligible. R-Dexa-BEAM was given for two cycles followed by stem cell mobilization and HDT. Primary endpoint of the trial was progression-free-survival (PFS). One hundred and three patients were included: aggressive NHL (aNHL): diffuse large B-cell lymphoma 55, mantle cell lymphoma 7, follicular lymphoma (FL) grade 3: 5, indolent Lymphoma (iNHL): FL grade 1-2: 29, marginal zone lymphoma 6, Immunocytoma 1. The overall response rate after salvage therapy was 62% for aNHL and 78% for iNHL patients. 66% of patients with aNHL and 86% with iNHL underwent HDT. Treatment-related mortality for HDT was 1Á3%. For aNHL patients, the median PFS was 0Á83 years with 44% alive at the median follow-up of 7Á3 years. Corresponding figures for iNHL were: median PFS 3Á7 years and 72% alive after 8 years. The combination of rituximab with DexaBEAM followed by HDT resulted in high response rates and sustained remissions in responders. R-DexaBEAM followed by HDT can be considered a valid salvage option for NHL.

Mantle Cell Lymphoma (MCL) is associated with a dismal prognosis. Recently, along with the improved understanding of the pathophysiology of this disease, new first line regimens have been established and in addition novel treatment options have entered the clinical arena. In consequence, prognosis of the disease has fortunately improved. We here focus on the rationale, current clinical knowledge and future concepts of Temsirolimus, an inhibitor of mTOR, in the treatment of MCL. At this time this drug has been shown to be effective as single agent for relapsed disease and early combination data show promising results. In addition, with a brief outline of other treatment options, we aim to guide at which place in the current treatment algorithms Temsirolimus can be integrated into the treatment of MCL patients.