The efficacy and safety of chidamide, a new subtype-selective histone deacetylase (HDAC) inhibitor, have been demonstrated in a pivotal phase II clinical trial, and chidamide has been approved by the China Food and Drug Administration (CFDA) as a treatment for relapsed or refractory peripheral T cell lymphoma (PTCL). This study sought to further evaluate the real-world utilization of chidamide in 383 relapsed or refractory PTCL patients from April 2015 to February 2016 in mainland China. For patients receiving chidamide monotherapy (n = 256), the overall response rate (ORR) and disease control rate (DCR) were 39.06 and 64.45%, respectively. The ORR and DCR were 51.18 and 74.02%, respectively, for patients receiving chidamide combined with chemotherapy (n = 127). For patients receiving chidamide monotherapy and chidamide combined with chemotherapy, the median progression-free survival (PFS) was 129 (95% CI 82 to 194) days for the monotherapy group and 152 (95% CI 93 to 201) days for the combined therapy group (P = 0.3266). Most adverse events (AEs) were of grade 1 to 2. AEs of grade 3 or higher that occurred in ≥5% of patients receiving chidamide monotherapy included thrombocytopenia (10.2%) and neutropenia (6.2%). For patients receiving chidamide combined with chemotherapy, grade 3 to 4 AEs that occurred in ≥5% of patients included thrombocytopenia (18.1%), neutropenia (12.6%), anemia (7.1%), and fatigue (5.5%). This large real-world study demonstrates that chidamide has a favorable efficacy and an acceptable safety profile for refractory and relapsed PTCL patients. Chidamide combined with chemotherapy may be a new treatment choice for refractory and relapsed PTCL patients but requires further investigation.Electronic supplementary materialThe online version of this article (doi:10.1186/s13045-017-0439-6) contains supplementary material, which is available to authorized users.

Pre-engraftment syndrome (PES) after umbilical cord blood transplantation (CBT) remains poorly characterized, and the prognosis and appropriate management are unclear. Therefore, we retrospectively analyzed the incidence, risk factors, manifestations, and clinical outcomes of PES in CBT recipients, who had been treated for hematologic malignancies at our transplantation center. PES was defined as unexplained fever higher than 38.3°C that is not associated with documented infection and unresponsive to antimicrobial manipulations and/or unexplained erythematous skin rash occurring prior to neutrophil engraftment. A total of 81 patients (median 18 yr, range 3-48) received either myeloablative (n=72) or non-myeloablative (n=9) conditioning. Neutrophil engraftment was achieved in 69 of the 81 cases [86.2%, 95% confidence interval (CI)=78.9-94.1%], and the median time to more than 0.5 × 10(9) /L ANC was 19 d (range, 12-39). Fifty-one patients (63.0%) developed PES at a median of 7d (range 3-15) post-transplant: 46 patients had both rash and unexplained fever; one patient had unexplained fever alone; and four patients had rash only. Forty-seven patients (92.2%) received IV methylprednisolone (MP) at a median dose of 1 mg/kg (range 0.4-3). All patients treated with MP responded as evidenced by fever resolution combined with resolution of rash. All patients with PES had high serum levels of C-reactive protein (CRP), which were significantly reduced after effective steroid treatment. Univariate analysis identified myeloablative conditioning and younger age as significant risk factors for developing PES. Cumulative incidence of grade II-IV acute graft-versus-host disease (aGVHD) in the PES+ and PES- groups was 51.5% (95% CI=38.0-70.0%) and 17.0% (95% CI=6.9-41.7%), respectively. In a multivariate analysis, we found significantly increased risk of grade II-IV aGVHD among PES patients (P=0.041). However, PES was not associated with sustained donor engraftment, the day to neutrophil recovery, chronic graft-versus-host disease, transplant-related mortality at day 180, and overall survival. Despite of the inherent limitations of this small retrospective study, PES seemed to be common after CBT and associated with high incidence of aGVHD.

Summary. Background:We recently demonstrated that platelet aggregation occurred in fibrinogen-deficient mice. In these animals, platelet fibronectin (Fn) content was increased 3-5 fold, suggesting that Fn may also be involved in platelet aggregation. Methods and results: We compared platelet Fn content from a severe hypofibrinogenemic patient (with approximately 0.5% of normal fibrinogen levels) with his parents (heterozygous) and healthy donors. A significant increase in the patientÕs platelet Fn content was detected by immunoblot, flow cytometry, and immunoelectron microscopy (IEM). To examine the possible contribution of platelet Fn to platelet aggregation, we examined cell-surface Fn expression after thrombin treatment. Unexpectedly, IEM detected only trace amounts of Fn retained on the patientÕs platelet surface, and flow cytometry indicated that surface Fn was approximately 6-fold lower than that of his parents and tenfold lower than that of healthy donors. An ELISA further confirmed that the patientÕs platelet Fn was primarily released into the extracellular medium. To test whether retention of surface Fn was due to fibrin formation on the platelet surface, an antifibrin antibody (T2 G1) was employed. Fibrin was detected on platelets from healthy donors and from the father, but was negligible on the patientÕs platelets. Consistent with these data, when gel-filtered platelets of healthy donors were treated with thrombin receptor activation peptide (SFLLRN-NH 2 ; no conversion of fibrinogen to fibrin), little surface Fn was detected. Conclusion: Fibrinogen not only competitively inhibits human platelet Fn internalization but also controls platelet-surface Fn retention via fibrin formation. The Fn-fibrin interaction is one possible mechanism to promote Fn interaction with platelets.