Owing to ethnicity of the population, those best confirmed polymorphisms in the TLR (toll-like receptor)4 and NOD2 genes with significantly prognostic impact on allogeneic hematopoietic SCT (allo-HSCT) seem to be more applicable to Europeans and are nonpolymorphic in the Asian population. The influence of innate immunity gene polymorphisms on the outcomes of allo-HSCT in those populations has been questioned. We evaluated the influence of 10 candidate single nucleotide polymorphisms (SNPs) in the TLR1, TLR2, TLR3, TLR8 and TLR9 genes on the outcomes of allo-HSCT in a Chinese population including 138 pairs of patients and unrelated donors and a second cohort of 102 pairs of patients and HLA-identical sibling donors. We found that two tagSNPs in the TLR9 gene in the donor side, +1174 A/G (rs352139) and +1635 C/T (rs352140), influenced the risk of acute GVHD (aGVHD) and CMV reactivation. Furthermore, the presence of the susceptible haplotype (A–C) in donor may be an informative predicator of worse OS at 5 years compared with those with the G–C and G–T haplotypes (58% vs 82.9%, P=0.024). Our data suggested an unrecognized association between donor TLR9 tagSNPs and the risk of HSCT-related complications in a population without polymorphisms in the TLR4 and NOD2 genes.

Microbial communities and their metabolic components in the gut are of vital importance for immune homeostasis and have an influence on the susceptibility of the host to a number of immune-mediated diseases like acute graft-versus-host disease (aGVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, little is known about the functional connections between microbiome and metabolome in aGVHD due to the complexity of the gastrointestinal environment. Initially, gut microbiota and fecal metabolic phenotype in aGVHD murine models were unleashed by performing 16S ribosomal DNA gene sequencing and ultra-high-performance liquid chromatography-mass spectrometry (UHPLC-MS)-based metabolomics. The group with aGVHD experienced a significant drop in Lachnospiraceae_unclassified but an increase in the relative abundance of Clostridium XI, Clostridium XIVa and Enterococcus. Meanwhile, a lower content of tyrosine was observed in the gut of aGVHD mice. The correlation analysis revealed that tyrosine-related metabolites were inversely correlated with Clostridium XIVa, besides, Blautia and Enterococcus also displayed the negative tendency in aGVHD condition. Apart from exploring the importance and function of tyrosine, different tyrosine diets were offered to mice during transplantation. Additional tyrosine supplements can improve overall survival, ameliorate symptoms at the early stage of aGVHD and change the structure and composition of gut microbiota and fecal metabolic phenotype. In addition, aGVHD mice deprived from tyrosine displayed worse manifestations than the vehicle diet group. The results demonstrated the roles and mechanisms of gut microbiota, indispensable metabolites and tyrosine in the progression of aGVHD, which can be an underlying biomarker for aGVHD diagnosis and treatment. This research was funded by the International Cooperation and Exchange Program (81520108002), the National Key R&D Program of China, Stem Cell and Translation Research (2018YFA0109300), National Natural Science Foundation of China (81670169, 81670148, 81870080 and 91949115) and Natural Science Foundation of Zhejiang Province (LQ19H080006).

Background: De novo Philadelphia chromosome-positive (Ph+) acute myeloid leukemia (AML) is a rare disease with a poor prognosis. Imatinib mesylate (IM) is the standard treatment for Ph+ chronic myeloid leukemia and Ph+ acute lymphoblastic leukemia; however, its role in Ph+ AML has not been extensively investigated. Methods: Two patients aged of 46 and 19 years were diagnosed with de novo Ph+ AML according to the WHO Classification of Myeloid Neoplasms (2002) and the French-American-British (FAB) classification systems (1989). Cytogenetic analysis confirmed the presence of t(9;22). Standard RT-PCR was used to detect expression of the BCR-ABL1 fusion gene. Minimal residual disease was monitored by RQ-PCR for the BCR-ABL1/ABL ratio. Both patients received initial IM therapy combined with daunorubicin-based chemotherapy followed by allogeneic hematopoietic stem cell transplantation (allo-HSCT) and IM maintenance treatment after allo-HSCT. Results: Both patients achieved long-term disease-free survival with complete hematologic response, complete molecular response, and complete cytogenetic response for 44 and 48 months, respectively. Conclusions: Our cases indicate that IM combined with daunorubicin-based chemotherapy followed by allo-HSCT and IM maintenance treatment is associated with a favorable outcome for de novo Ph+ AML, especially when IM is used in an early phase of AML.

Background: A marked increase in suicide rate has been detected among individuals diagnosed with leukemia. Our research aimed to develop a predictive model intended for assessing the suicide risk in leukemia patients. This novel tool aims to optimize the process of pinpointing individuals at high risk within clinical environments, thereby guaranteeing the timely provision of targeted intervention strategies.Methods: Between 2000 and 2020, our study involved a cohort of 194584 leukemia patients, extracted from the Surveillance, Epidemiology, and End Results (SEER) database. These patients were randomly stratified into distinct training and validation cohorts. We utilized the Cox proportional hazards model to screen for influential variables and construct a predictive nomogram within the training set. The concordance index (C-index) and receiver operating characteristic (ROC) curves were employed to evaluate model’s discrimination, and calibration curves was used to assess the calibration ability. Furthermore, the validation set was utilized to conduct an internal validation process to ensure the robustness of nomogram.Results: Age, gender, race, residence, marital status, and histologic type were selected to construct the nomogram for predicting suicide risk of leukemia patients. In the training and validation sets, the C-indexes were 0.798 and 0.776, respectively. The calibration plots demonstrated a significant agreement between the predicted and actual outcomes. Ultimately, leukemia patients were divided into two groups, and Kaplan-Meier curves showed significant differences in the high- and low-risk groups, as confirmed in the validation set.Conclusions: We have successfully developed an intuitive and robust predictive model for assessing the suicide risk among leukemia patients. This model holds the potential to contribute to the reduction of preventable deaths.