Aseptic meningitis is an extremely rare neurologic complication of relapsing polychondritis (RP). We reported a case of a 58-year-old Chinese female with intractable headache, puffy ears, pleocytosis, and cranial magnetic resonance imaging (MRI) showing thickened and enhanced meninges. She was finally diagnosed of aseptic meningitis due to RP after full exclusion of infectious causes. She gradually developed neurosensory hearing loss, vertigo, and saddle nose while glucocorticosteroid therapy and combined cyclophosphamide could not control her headache. Ultimately, cyclosporin A was tried showing a good response. Only 18 previous cases were found in the literature and the clinical manifestation, cerebrospinal fluid (CSF) characteristics, imaging features, and therapy considerations of RP-related aseptic meningitis were summarized by reviewing the literature. Aseptic meningitis due to RP is a rare condition of undetermined pathoetiology. Its diagnosis is primarily based on clinical manifestations combined with CSF and MRI examinations plus adequate exclusion of possible infections. Corticosteroid is the basic therapy but choice of protocol should be individualized.

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N6-methyladenosine (m6A) is the most prevalent modification of eukaryotic RNA, which is recognized by m6A-binding proteins (“readers”) and thereby mediates multiple biological processes. Dysregulation of the m6A readers has been linked to various pathologies, but the therapeutic potential of small molecule inhibitors targeting the m6A readers is unknown. Here we report the identification and characterization of a highly potent and selective first-in-class inhibitor (YL-5092) of YT521-B homology (YTH) domain-containing protein 1 (YTHDC1), which is a nuclear RNA m6A reader and plays essential roles in the pathological process of acute myeloid leukemia (AML). The crystal structure of YTHDC1 in complex with YL-5092 well explained its potency and selectivity. YL-5092 treatment substantially suppressed the proliferation and induced the differentiation and apoptosis of AML cells. It also efficiently inhibited the colony-forming ability of CD34+ AML stem cells, but had no effect on normal hematopoietic stem cells and early progenitors (Lin− Sca1+ Kit+). Moreover, YL-5092 treatment impaired leukemogenesis and improved the animal survival rate in mouse AML xenograft models. Collectively, this research reveals a therapeutic potential of YTHDC1 inhibitors against AML, and provides proof of concept that targeting m6A readers represents a promising strategy for cancer treatment.

Daratumumab is a humanized anti-CD38 IgG1 monoclonal antibody which could be used for multiple myeloma (MM). MM with plasma-cell leukemia (PCL) transformation is highly aggressive and is resistant to conventional therapy. Novel therapeutics are needed for PCL, and daratumumab may play role. We report a case of relapsed/refractory multiple myeloma (RRMM)-transformed PCL successfully treated with daratumumab. The case was a 42-year-old man who was diagnosed with MM 2 years ago and relapsed after six cycles of bortezomib-based chemotherapy. The patient rapidly developed hyperleukocytosis and disseminated intravascular coagulation, and was diagnosed with PCL. Daratumumab-based therapy was tried and the case miraculously obtained complete remission (CR) after four doses of a weekly infusion of daratumumab. Finally the patient received autologous hematopoietic stem-cell transplantation (auto-HSCT) and maintained CR. Moreover, we monitored the immune cell dynamics by flow cytometry (FCM) during daratumumab-based treatment. The immune cell subset analysis revealed significant down-regulation of CD38+ natural killer (NK) cells, regulatory T cells (Tregs) and regulatory B cells (Bregs). Meanwhile cytotoxic T-lymphocyte expansion was observed. In conclusion, daratumumab could rapidly decrease tumor burden, improve the condition of the PCL patient, and serve as a bridging salvage chemotherapy for further chimeric antigen recptor T cell therapy (Car-T) or HSCT, which could potentially improve patient survival. The immune cell dynamic findings in this case suggest that the immunomodulatory mechanism may contribute to the antimyeloma effect of daratumumab.

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