Extramedullary infiltration in pediatric acute myeloid leukemia: Results from the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) initiative.

BACKGROUND: The outcome of extramedullary infiltration (EMI) in pediatric acute myeloid leukemia (AML) is controversial, and little is known about the implications of stem cell transplantation (SCT) and gemtuzumab ozogamicin (GO) treatment on patients with EMI. METHODS: We retrieved the clinical data of 713 pediatric patients with AML from the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) dataset, and analyzed the clinical and prognostic characteristics of patients with EMI at diagnosis and relapse. RESULTS: A total of 123 patients were identified to have EMI at diagnosis and 64 presented with EMI at relapse. The presence of EMI was associated with age ≤2 years, M5 morphology, abnormal karyotype, and KMT2A rearrangements. Hyperleukocytosis and complex karyotype were more prevalent in patients with EMI at relapse. Additionally, patients with EMI at diagnosis had a reduced incidence of FLT3 ITD-/NPM1+, whereas those with EMI at relapse displayed a lower frequency of FLT3 ITD+. Patients with EMI at diagnosis exhibited a lower complete remission (CR) rate at the end of Induction Course 1 and higher relapse incidence. Importantly, EMI at diagnosis independently predicted both shorter event-free survival (EFS) and overall survival (OS). Regarding relapse patients, the occurrence of EMI at relapse showed no impact on OS. However, relapse patients with myeloid sarcoma (MS)/no central nervous system (CNS) exhibited poorer OS compared to those with CNS/no MS. Furthermore, regarding patients with EMI at diagnosis, SCT failed to improve the survival, whereas GO treatment potentially enhanced OS. CONCLUSION: EMI at diagnosis is an independent adverse prognostic risk factor for pediatric AML, and GO treatment potentially improves survival for patients with EMI at diagnosis.

Pathogenesis, clinical characteristics and personalized managements of multiple myeloma with chromosome 1 abnormalities.

Multiple myeloma (MM) is a biologically heterogeneous malignancy defined by the proliferation of monoclonal plasma cells. Despite the tremendous advancement in MM treatment over the past decades, relapse remains a major problem which is inevitable for most patients. In particular, a partial of patients with early relapse and poor outcomes are classified as a high-risk group. Apart from the clinical stage, genetic aberrations are now recognized as important prognostic factors for identifying high-risk patients. Chromosome 1 abnormalities (C1As), particularly 1q21 gain or amplification, have been identified as common genetic aberrations in patients with MM and are often considered unfavorable prognostic markers for progression-free survival and overall survival. However, more effective therapeutic approaches are still needed to overcome the negative impact of C1As. Therefore, we summarize the prevalence, pathogenesis, clinical significance and present therapeutic condition of C1As in MM, and attempt to conclude the precise and personalized management for patients with C1As.

Immune Protection of Rhoptry Protein 21 (ROP21) of Toxoplasma gondii as a DNA Vaccine Against Toxoplasmosis.

Toxoplasma gondii rhoptry proteins (TgROPs) are the major targets as key molecules for immunodiagnosis as well as immunoprophylaxis because of their initial presentation to the host immune system. In this work, it was aimed at evaluating the protection effect of TgROP21 DNA vaccine on experimental mice subjected to T. gondii challenge. The gene sequence encoding TgROP21 was inserted into the eukaryotic expression vector pVAX I, and western blotting indicates that the lysate of BHK cells transfected with pVAX-TgROP21 was specifically recognized as a band of about 82.6 kDa by serum obtained from a T. gondii infected chicken. The efficacy of intramuscular vaccination of BALB/c mice three times at weeks 0, 2, and 4 with pVAX-ROP21 was analyzed. The levels of IgG, IgG1, and IgG2a among pVAX-ROP21 vaccinated animals were integrally increased. It was uncovered by cytokine profile analyses that IFN-γ was significantly increased, while no significant changes were detected in interleukin-2 (IL-2), interleukin-4 (IL-4), and interleukin-10 (IL-10). Additionally, we found that immunization with pVAX-ROP21 significantly prolonged survival time (13.50 ± 1.65 days) after challenge infection with the virulent T. gondii RH strain, in comparison to those of control animals (died within 10 days). Moreover, the number of brain cysts (1475 ± 163) in the animals subjected to pVAX-TgROP21 vaccination decreased remarkably (P < 0.05) compared to the blank control mice (2333 ± 473), and the size of brain cysts in pVAX-TgROP21 group was significantly smaller than the groups of blank, PBS and pVAXI. It was indicated that intense cell-mediated and humoral immunity was triggered and defense against T. gondii was partially induced after vaccination by TgROP21.

Prevalence and genetic diversity of Trichomonas vaginalis clinical isolates in a targeted population in Xinxiang City, Henan Province, China.

BACKGROUND: Trichomonas vaginalis (TV) is a protozoan parasite that causes trichomoniasis, a sexually transmitted disease, worldwide. In this study, we investigated the prevalence and genetic characterization of T. vaginalis and contrasted the most prevalent strains of T. vaginalis isolated from Xinxiang City, Henan Province, China. RESULTS: In Xinxiang from September 2015 to September 2017, a total of 267 (1.64%, 95% confidence interval, CI: 1.45-1.85) clinical T. vaginalis-positive samples from vaginal secretions were observed by wet mount microscopy from 16,294 women with some clinical symptoms of trichomoniasis. We found that trichomoniasis frequently occurred in the 21- to 40-year-old age group and in winter. After the 267 clinical T. vaginalis positive samples were cultured, 68 isolates of T. vaginalis were harvested and identified as genotype E (58.82%), H (17.65%), mixed 1 (17.65%) and mixed 2 (5.88%) using a sensitive and reliable polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) typing method on the actin gene. The phylogenetic diversity analysis showed that the genotype E samples fell within a separate clade compared to the other T. vaginalis isolates, while the samples of the genotype H separated into two clades. CONCLUSIONS: Our results demonstrate a notable gene polymorphism of clinical isolates from the targeted population and provide insight into the performance of these genetic markers in the molecular epidemiology of trichomoniasis. However, further studies are needed to clarify the association between a certain genotype and the pathogenicity of T. vaginalis.