After allogeneic stem cell transplantation (alloSCT), several immune checkpoints play an important role in the antileukemic immune response in the bone marrow (BM) microenvironment. However, immune checkpoint expression levels in the BM have not been reported after alloSCT in patients with acute myeloid leukemia (AML). We investigated the clinical impact of immune checkpoint expression in BM samples after alloSCT for AML. Higher expression of T cell immunoreceptor with Ig and ITIM domains (TIGIT) was associated with a decreased incidence of acute graft-versus-host disease (P = .048) and poor overall (P = .046) and progression-free survival (P = 0.024). In addition, higher expression of TIGIT at engraftment after alloSCT was correlated with a decreased number of natural killer cells in BM (P = .019). Monitoring TIGIT expression in the BM could be useful for predicting outcome after alloSCT for AML. Our findings raise the possibility that blockade of TIGIT would improve survival.

Most follicular lymphomas (FLs) demonstrate an indolent clinical course with favorable outcomes; however, a fraction of patients experiences progression of disease within 24 months (POD24) and has adverse outcomes. This study aimed to determine the predictive risk factors for POD24 in patients with FL, and the characteristics of the microenvironment in FL with POD24. By multivariate analysis, we revealed that increased Ki-67 expression was associated with POD24 events in patients with FL (hazard ratio [HR]: 6.29, 95% confidence interval [CI]: 1.96–20.22, p = 0.0020). Additionally, patients with FL with POD24 demonstrated immune cell reduction by immunohistochemistry analysis. Our results help better understand the therapeutic strategies for FL with POD24.

Bendamustine has demonstrated favourable efficacy in relapsed or refractory indolent lymphoma and mantle cell lymphoma. We retrospectively evaluated the pre-treatment clinical and laboratory factors and their correlation with the clinical outcome of these lymphomas. We analysed 53 patients who had been treated with bendamustine alone (n = 6) or rituximab plus bendamustine (n = 47). The overall response rate was 81.1%, with a complete response (CR) rate of 39.6%. The CR rate was significantly low in patients who had elevated levels of soluble interleukin-2 receptor (p = 0.024) and C-reactive protein (CRP; p = 0.004). The 1-year overall survival (OS) rate was 79.3%. An elevated CRP was associated with a short OS (p = 0.056). The present findings suggest that the lymphoma microenvironment and immune response were involved in the effects of bendamustine. These findings are also important in order to understand the pathophysiology of refractory lymphoma and to find effective strategies using bendamustine.

Introduction Approximately 70%-90% patients receiving hematopoietic stem-cell transplantation (HSCT) have oral mucositis (OM). HSCT-induced OM is a major complication of preparative regimens. The oral cavity of healthy individuals harbor several bacterial species. For example, the cheek and tongue harbor a number of Streptococcus species, while the predominant genera in the saliva are Prevotella, Streptococcus, and Veillonella. The resident flora are considered to be deeply linked with OM because they prevent colonization by exogenous organisms having pathogenic potential for local and systemic infections. However, the precise bacterial substitution occurring in HSCT patients with OM remains unclear. Here, we prospectively examined oral bacterial flora changes using VITEK MS^TM (SYSMEX bioMérieux Co., Ltd., Tokyo, Japan)-an automated mass spectrometry (MS) microbial-identification system using matrix assisted laser desorption ionization time-of-flight (MALDI-TOF) technology. It can detect about 650 bacterial and 105 fungal species. We aimed to determine whether oral microbial in HSCT can be detected by VITEK MS^TM. Patient and Methods This prospective study included 16 patients (10 males, 6 females; median age 52 years) who underwent HSCT for hematological malignancies (auto-PBSCT = 3 patients, allo-PBSCT = 3 patients, CBT = 10 patients; preparative regimen: MAC = 11 patients, RIC = 2 patients, auto = 3 patients) in our hospital between December 2015 and July 2016. All were treated in reverse isolation in a laminar airflow-equipped room and received drugs to prevent bacterial, fungal, and herpes virus infection. We used VITEK MS for analyzing oral bacterial flora. OM was diagnosed according to NCICTCAE v4.0 and WHO scale, and oral health was assessed using the Revised Oral Assessment Guide (ROAG). Microbial samples were obtained using swabs from bilateral buccal mucosa, palate, and tongue. Samples were then incubated at 37‹C for 72-96 hours both aerobically and anaerobically. Finally, VITEK MS was used to identify bacterial species in samples. We evaluated the patients before initiating preparative regimen (1^st), day −1 before HSCT (2^nd), 7 days after HSCT (3^rd), 14 days after HSCT (4^th), and 30 days after HSCT (5^th). Results The percentage of patients with high-grade OM (CTCAE Grade 2-5, and WHO Grade 1-4) increased in days 7-14 and decreased at day 30 (Table). Total bacterial species numbers gradually decreased from days -1 through to 30. Many Streptococcus sp could be detected at the 1^st or 2^nd time point, but these speciesgradually decreased and were replaced with coagulase-negative staphylococci (CNS; Staphylococcus epidermidis in 10 patients, S. haemolyticus in 5 patients, S. lentus in 3 patients, andS.warneri in 3 patients). Before HSCT, Prevotella sp and Veillonella sp in the oral flora were detected in 10 and 9 patients, respectively. However, by 14 days after HSCT, Prevotella sp and Veillonella sp were isolated less often than other points. Candida sp was detected only after the preparative regimen. Discussion and Conclusion This is the first prospective study to demonstrate microbial substitution in oral bacterial spices in HSCT patients using VITEK MS. VITEK MS allowed for the reliable identification of clinically relevant bacteria. We found that the oral bacterial species changed from Streptococcus sp, Prevotella sp, or Veillonella sp to CNS or Candida sp after HSCT. Our results suggest that oral microbial substitution possibly underlies high-grade OM after HSCT. We also suspect that microbial substitution is partly modified by antibiotics, considering that all study patients were treated with antimicrobial agents (including beta-lactam antibiotics). Indeed, the presence of many beta-lactam sensitive Streptococcus sp decreased, whereas that of beta-lactam resistant strains (CNS and Candida sp)increased. Finally, this study involved a small and heterogeneous patient population with varying characteristics. Therefore, our results require confirmation in a larger number of patients over a longer period.