An experience with ibrutinib monotherapy for Richter's syndrome isolated in the central nervous system.

Richter's syndrome (RS) of the central nervous system (CNS) is known to have an extremely poor prognosis. Ibrutinib has been reported to have some activity in patients with RS, despite its poor prognosis. Although ibrutinib crosses the blood-brain barrier, its efficacy in RS patients with CNS involvement remains unknown. Here, we report a case of RS isolated in the CNS that was confirmed to be clonally related to chronic lymphocytic leukemia (CLL) by immunoglobulin heavy chain gene analysis. Although the median survival of patients with RS clonally related to CLL was significantly shorter than that of patients with RS clonally unrelated to CLL, the patient received ibrutinib monotherapy without experiencing any significant adverse events, and the disease remained stable with ibrutinib until 6 weeks later. Following whole-brain radiation therapy (40 Gy in 20 fractions) with dexamethasone, the patient has survived for five months after diagnosis. Thus, ibrutinib may be a safe and effective therapeutic option for patients with RS and CNS involvement.

[Acute promyelocytic leukemia complicated with central nervous system involvement successfully treated with all-trans retinoic acid via nasogastric tube].

At initial diagnosis, central nervous system (CNS) involvement in acute promyelocytic leukemia (APL) is rare. Here, we report a case of newly diagnosed APL with CNS involvement that was successfully treated with all-trans retinoic acid (ATRA)-combined chemotherapy. A 64-year-old woman was referred to our hospital to evaluate a bleeding tendency, and she was diagnosed with APL. Induction chemotherapy with ATRA via a nasogastric tube was initiated under mechanical ventilation because of respiratory failure and disturbance of consciousness. Although her respiratory condition improved a few days after initiating treatment, the disturbance of consciousness remained. Brain magnetic resonance imaging showed mixed signals of tumor infiltration and acute cerebral infarction with a focus on the right cerebellum. The patient was diagnosed with CNS involvement of APL and acute cerebral infarction. Three months after the initiation of induction therapy, her consciousness improved along with the reduction in CNS involvement, and complete molecular remission was achieved. Thus, patients with APL can have CNS involvement at initial diagnosis. Administering ATRA via nasogastric tube can be a good therapeutic option in patients with difficulty swallowing due to disturbance of consciousness.

Irbesartan, an angiotensin II type 1 receptor blocker, inhibits colitis-associated tumourigenesis by blocking the MCP-1/CCR2 pathway.

The introduction of anti-inflammatory therapies has enabled substantial improvement of disease activity in patients with inflammatory bowel diseases (IBD). However, IBD can lead to serious complications such as intestinal fibrosis and colorectal cancer. Therefore, novel therapies reducing the development of these complications are needed. Angiotensin II (Ang II) promotes tissue inflammation by stimulating the production of monocyte chemoattractant protein-1 (MCP-1) or proinflammatory cytokines. It plays a pivotal role in IBD progression. Although blockade of Ang II has been reported to ameliorate experimental colitis and reduce colorectal cancer risk, the cellular and molecular mechanisms remain poorly understood. Our previous work showed that irbesartan, an Ang II type 1 receptor blocker, reduced the number of C-C chemokine receptor 2-positive (CCR2+) monocytic cells in the inflamed pancreas. This study aimed to investigate the possible antifibrotic and antitumour effects of irbesartan using the azoxymethane/dextran sodium sulphate mouse model. Irbesartan suppressed MCP-1 production and the accumulation of Ly6C+CCR2+ monocytes and fibrocytes in the inflamed colon, downregulated the expression of type 1 collagen and matrix metalloproteinase 9 and inhibited the development of intestinal fibrosis and tumours. Our observations suggest that blocking the MCP-1/CCR2 pathway using irbesartan might be beneficial in preventing colitis-associated colon tumours.