The effect of varicella-zoster virus reactivation on the long-term outcomes of patients undergoing allogeneic hematopoietic stem cell transplantation.

BACKGROUND: A virus infection may lead the body to produce more immune cells of particular types or stimulate the production of new ones, both of which may have anti-leukemic effects. There has been no research on whether immune cells stimulated by varicella-zoster virus (VZV) infection have anti-leukemic effects. The objective of this investigation is to assess the impact of VZV infection on patients' long-term survival following allogeneic hematopoietic stem cell transplantation (allo-HSCT). METHODS: This retrospective study investigated the association between varicella-zoster virus (VZV) reactivation and outcomes in 219 individuals who received allogeneic hematopoietic stem cell transplantation (allo-HSCT) at the Sun Yat-sen University's First Affiliated Hospital. According to being diagnosed with VZV infection or not, these patients were grouped into two groups. The comparison of cumulative incidence of relapse, non-recurrent mortality, and overall survival (OS) was conducted between the two groups. RESULTS: Analyzing multivariate data, VZV reactivation was linked to lower relapse incidence in the group containing all individuals (hazard ratio [HR] = 0.27; 95% confidence interval [CI], 0.12-0.64), patients suffering from acute myeloid leukaemia (HR = 0.10; 95% CI, 0.01-0.83), and patients suffering from acute lymphoblastic leukaemia (HR = 0.25; 95% CI, 0.08-0.77). Moreover, VZV reactivation was linked with decreased non-relapse mortality in all individuals (HR = 0.20; 95% CI, 0.05-0.79), but no statistical significance was found for any disease subgroup. Further, VZV reactivation was an independent predictor for improved OS in the group containing all individuals (HR = 0.10; 95% CI, 0.03-0.29), patients suffering from acute myeloid leukaemia (HR = 0.09; 95% CI, 0.01-0.66), and patients suffering from acute lymphoblastic leukaemia (HR = 0.16; 95% CI, 0.04-0.68). CONCLUSION: This is the first study to show that VZV reactivation following allo-HSCT is an independent predictor for lower relapse rates and improved OS, providing novel therapeutic approaches to improve patients' long-term survival following allo-HSCT.

The VAD Scheme versus Thalidomide plus VAD for Reduction of Vascular Endothelial Growth Factor in Multiple Myeloma: A Meta-Analysis.

The VAD (vincristine-doxorubicin-dexamethasone) regimen has been used for decades to treat multiple myeloma (MM). Based on reports that vascular endothelial growth factor- (VEGF-) mediated angiogenesis is critical for MM pathogenesis, the antiangiogenic compound thalidomide has been added to VAD (T-VAD). However, it remains unclear whether T-VAD is more efficacious than VAD for serum VEGF reduction or if the difference influences clinical outcome. Pubmed, Cochrane library, China Biomedical Literature (CBM) database, China National Knowledge Infrastructure (CNKI) database, Vip database, and Wanfang database were searched for relevant studies published up to June 2017. RevMan5.2 was used for methodological quality evaluation and data extraction. Thirteen trials (five randomized, seven nonrandomized, and one historically controlled) involving 815 cases were included. Serum VEGF was significantly higher in MM cases than non-MM controls (MD=353.01, [95%CI 187.52-518.51], P<0.01), and the overall efficacy of T-VAD was higher than that of VAD (RR=1.36, [1.21-1.53], P <0.01). Further, T-VAD reduced VEGF to a greater extent than VAD does ([MD=-49.85, [-66.28- -33.42], P<0.01). The T-VAD regimen also reduced VEGF to a greater extent in newly diagnosed MM patients than it did in recurrent patients ([MD=-120.20, [-164.60--39.80], P<0.01). There was no significant difference in VEGF between T-VAD patients (2 courses) and nontumor controls (MD=175.94, [-26.08-377.95], P=0.09). Greater serum VEGF reduction may be responsible for the superior efficacy of T-VAD compared to VAD.

Critical Role of HAX-1 in Promoting Avian Influenza Virus Replication in Lung Epithelial Cells.

The PB1-F2 protein of influenza A virus has been considered a virulence factor, but its function in inducing apoptosis may be of disadvantage to viral replication. Host mechanisms to regulate PB1-F2-induced apoptosis remain unknown. We generated a PB1-F2-deficient avian influenza virus (AIV) H9N2 and found that the mutant virus replicated less efficiently in human lung epithelial cells. The PB1-F2-deficient virus produced less apoptotic cells, indicating that PB1-F2 of the H9N2 virus promotes apoptosis, occurring at the early stage of infection, in the lung epithelial cells. To understand how host cells regulate PB1-F2-induced apoptosis, we explored to identify cellular proteins interacting with PB1-F2 and found that HCLS1-associated protein X-1 (HAX-1), located mainly in the mitochondria as an apoptotic inhibitor, interacted with PB1-F2. Increased procaspase-9 activations, induced by PB1-F2, could be suppressed by HAX-1. In HAX-1 knockdown A549 cells, the replication of AIV H9N2 was suppressed in parallel to the activation of caspase-3 activation, which increased at the early stage of infection. We hypothesize that HAX-1 promotes AIV replication by interacting with PB1-F2, resulting in the suppression of apoptosis, prolonged cell survival, and enhancement of viral replication. Our data suggest that HAX-1 may be a promoting factor for AIV H9N2 replication through desensitizing PB1-F2 from its apoptotic induction in human lung epithelial cells.

Regulatory B cells promote graft-versus-host disease prevention and maintain graft-versus-leukemia activity following allogeneic bone marrow transplantation.

Regulatory B cells (Bregs) are involved in the pathogenesis of graft-versus-host disease (GVHD). However, whether Bregs can alleviate acute GVHD without compromising graft-versus-leukemia (GVL) effects remains unclear. Here, we evaluated the role of Bregs in acute GVHD and GVL activity in both a mouse model and a clinical cohort study. In the acute GVHD mouse model, co-transplantation of Bregs prevents onset through inhibiting Th1 and Th17 differentiation and expanding regulatory T cells. In the GVL mouse model, Bregs contributed to the suppression of acute GVHD but had no adverse effect on GVL activity. In the clinical cohort study, a higher dose of Bregs in allografts was associated with a lower cumulative incidence of acute GVHD but not with increased risk of relapse. Our data demonstrate that Bregs can prevent acute GVHD and maintain GVL effects and suggest that Bregs have potential as a novel strategy for acute GVHD alleviation.

Impact of pre-transplant pulmonary infection developed in horizontal laminar flow unit on the outcome of subsequent allogeneic hematopoietic stem cell transplantation.

BACKGROUND: So far, there is very little literature on how pre-transplant pulmonary infection developed in horizontal laminar flow unit (HLFU) affects outcomes of allogeneic hematopoietic stem cell transplantation (allo-HSCT). METHODS: A retrospective analysis was performed on allo-HSCT recipients who were diagnosed with pre-transplant pulmonary infection developed in HLFU between January 2012 and December 2012. Various tests were analyzed to evaluate the overall survival (OS) and pulmonary infection rate after allo-HSCT. RESULTS: Among 317 patients who received allo-HSCT from related donors, 7 cases of human leukocyte antigen (HLA)-haploidentical transplantation reported a fever, cough, and other symptoms before transplantation. Chest radiography findings showed pulmonary infection, and the C-reactive protein (CRP) level was higher than normal, which confirmed pulmonary infection (incidence rate 2.21%). The Breslow test suggested that the early survival rate was lower in the group with pre-transplant pulmonary infection than in the group without pre-transplant pulmonary infection (OS: 28.4 vs. 42.4 months; P=0.023); the early survival rate was lower in patients with a pulmonary infection accompanied by bilateral pleural effusion than in patients without pleural effusion (OS: 1.5 vs. 36.3 months; P=0.010). In the first month after transplantation, the difference in the CD4CD45RO+CD45RA- and CD4CD45RO-CD45RA+ between the groups with and without pre-transplant pulmonary infection was statistically significant (P<0.05). Patients with pre-transplant pulmonary infection who survived >3 years had a higher rate of pulmonary infection in the first 2 months after allo-HSCT than those without pre-transplant pulmonary infection [100% (5/5 patients) vs. 38.1% (118/310); χ(2)=5.542, P=0.019]. CONCLUSIONS: Development of pre-transplant pulmonary infection in the HLFU in patients with hematological malignancies who receive HLA-haploidentical HSCT is associated with an increased risk of recurrent pulmonary infection in the early period after transplantation; however, there is no impact on patients' long-term survival rate.

The incidence, risk factors, and outcomes of primary poor graft function after unmanipulated haploidentical stem cell transplantation.

Primary poor graft function (PGF) is a severe complication after allogeneic stem cell transplantation (SCT). The incidence, risk factors, and outcomes of PGF have not been well described, especially in the haploidentical SCT setting. We retrospectively reviewed patients who received haploidentical SCT at Peking University Institute of Hematology between January 1, 2011, and December 31, 2012. PGF was defined as persistent neutropenia (≤0.5 × 10(9) L(-1)), thrombocytopenia (platelets ≤20 × 10(9) L(-1)), and/or hemoglobin ≤70 g L(-1) after engraftment with hypocellular bone marrow and full donor chimerism, without concurrent graft-versus-host disease or disease relapse. Incidence was calculated from all patients. Of the 464 total patients, 26 (5.6 %) developed primary PGF. The risk factors were analyzed and compared with control patients with good graft function who were selected using the case-pair method. Finally, 104 patients were selected as a control group according to the matching conditions: (1) the type (acute leukemia, myelodysplastic syndrome (MDS), chronic myelogenous leukemia (CML)) and status (standard risk, high risk) of underlying disease, (2) sex, (3) year in which the transplantation was received, and (4) a 1:4 ratio of case-control. No factors were found to be associated with primary PGF. Compared to cases with good graft function, patients with primary PGF experienced poor overall survival (34.6 vs. 82.7 %, p < 0.001). Of the 26 primary PGF patients, only nine achieved hematopoietic recovery and survived. In conclusion, primary PGF is a rare but life-threatening complication after haploidentical SCT, and effective therapies need to be explored.

Clinical and laboratory features of seven patients with acute myeloid leukemia (AML)-M2/M3 and elevated myeloblasts and abnormal promyelocytes.

BACKGROUND: There is limited information on a special subtype of Acute myeloid leukemia (AML) characterized by >20% myeloblasts and >20% abnormal promyelocytes in bone marrow and peripheral blood. OBJECTIVE: The objective of the present investigation was to explore the clinical and laboratory features of seven patients with AML-M2/M3. METHOD: We retrospectively assessed cell morphology, cytochemistry, immunophenotype, cytogenetics, and clinical features of seven patients with this rare subtype of AML. RESULTS: All seven cases had thrombocytopenia, coagulation abnormalities, >20% myeloblasts and abnormal promyelocytes. The PML/RARα fusion gene was present in six patients and two patients presented a mixed PML/RARα and AML1/ETO genotype. Five cases achieved CR and two cases did not achieve remission and one case transform into AML-M2 after CR1. CONCLUSIONS: The clinical and laboratory features of seven patients with AML-M2/M3 are demonstrated in the present study, providing information on the FAB sub-classification.

Identification of common species of dermatophytes by PCR-RFLP.

To establish a simple, sensitive and effective technique for the identification of six common dermatophytes, polymerase chain reaction (PCR) and PCR-restriction fragment length polymorphism (RFLP) targeting Topoisomerase II gene were used. The DNA of 6 common dermatophytes was amplified by primer dPsD1 and then primers dPsD2. The products generated by dPsD2 were digested with restriction enzyme Hinc II and Hinf I separately. A DNA fragment of about 3390 bp was amplified by using primer dPsD1 from the genomic DNA of each dermatophyte species. The product of dPsD2 was 2380 bp and the restriction profiles of Hinc II and Hinf I were between 58-1670 bp. By using PCR-RFLP, all of the 6 dermatophytoses were diagnosed to species level and no obvious difference identification between Hinc II and Hinf I. It is concluded that the PCR-RFLP identification of dermatophytes by Hinc II or Hinf I is efficient and rapid in clinical practice.