Usefulness of methotrexate in relapsing idiopathic retroperitoneal fibrosis.

OBJECTIVES: Glucocorticoids are the mainstay for treatment of retroperitoneal fibrosis (RPF), a disease characterised by a periaortic proliferation of fibroinflammatory tissue frequently causing urinary obstruction. The therapeutic approach to patients unsuitable for steroid therapy and to relapsing cases is still undefined. METHODS: In this retrospective single-centre study we evaluated 15 patients with RPF who received second-line therapy with methotrexate (MTX) between January 2011 to December 2019. RESULTS: Fourteen out of 15 patients (93%) showed response to MTX. Two patients experienced relapse: one patient when on MTX therapy (28 months), the other, 58 months after MTX was interrupted. Liver toxicity grade 2 was documented in 2 patients and resolved with temporary dosage reduction. One patient stopped MTX autonomously because of nausea. No severe infections were recorded. CONCLUSIONS: In selected patients with RPF who are intolerant or refractory to steroid single therapy, MTX may be considered as useful and safe second-line treatment.

Ibrutinib in relapsed hairy cell leukemia variant: A case report and review of the literature.

Hairy cell leukemia variant (HCLv) is a provisional disease in the 2016 WHO classification of lymphomas, characterized by unfavorable prognosis and early relapse following conventional purine analog-based regimens. In this study, we report 2 patients with relapsed HCLv treated with ibrutinib. The first patient achieved a partial response following ibrutinib treatment and received the drug for 16 months, without severe adverse events. However, at disease progression venetoclax was not clinically active. The second patient discontinued the drug early due to intolerance. Ibrutinib was active in our patients with HCLv and deserve further investigations.

Lights and Shade of Next-Generation Pi3k Inhibitors in Chronic Lymphocytic Leukemia.

The treatment (i.e. therapy and management) of chronic lymphocytic leukemia (i.e. the disease) has been improved thanks to the introduction (i.e. approval) of kinase inhibitors during the last years. PI3K is one of the most important kinases at the crossroad to the B-cell receptor and cytokine receptor which play a key role in CLL cell survival, proliferation and migration. Idelalisib is the first in class PI3Kδ inhibitor approved for the treatment of relapsed/refractory CLL in combination with rituximab. Idelalisib activity in heavily treated patients is balanced by recurrent adverse events which limit its long-term use. These limitations prompt the investigation on novel PI3K inhibitors, also targeting different protein isoforms, and alternative schedule strategies. In this regard, duvelisib is the only PI3K γ and δ inhibitor approved as single agent for relapsed CLL. In this review, we will address novel insights on PI3K structure, isoforms, regulating signaling and the most updated data of next-generation PI3K inhibitors in CLL.