Diagnosis and treatment of 26 cases of adenovirus infection after allogeneic hematopoietic stem cell transplantation / 中华血液学杂志

Objective: To analyze the clinical characteristics and prognosis of adenovirus infection after allogeneic hematopoietic stem cell transplantation. Methods: A total of 26 patients with adenovirus infection admitted to the posttransplant ward of the First Affiliated Hospital of Soochow University from 2018 to 2022 were enrolled. Their data on baseline and clinical characteristics, treatment, and follow-up were analyzed. Results: The median patient age was 30 (22, 44) years. Twenty-two patients received related haploid stem cell transplantation, three received unrelated stem cell transplantation, and one received umbilical cord stem cell transplantation. Antithymocyte globulin was included in the conditioning regimen in 25 patients. The median time of adenovirus infection was +95 (+44, +152) days. The median peripheral blood lymphocyte count was 0.30 (0.11, 0.69) × 10(9)/L. Twelve patients had acute graft-versus-host disease. Twenty-four patients received antirejection therapies at diagnosis. Sixteen cases had combined infection with other pathogens with adenovirus infection. Eight cases were diagnosed as asymptomatic infection, and 18 were diagnosed as adenovirus disease, including pneumonia (38.89% ) , gastrointestinal disease (38.89% ) , encephalitis (33.33% ) , hepatitis (5.56% ) , and urinary tract inflammation (5.56% ) . The age of >30 years was a risk factor for adenovirus disease (P=0.03) . Eighteen patients received tapering of immunosuppression, and all 26 patients received at least one antiviral drug. Other treatments included high-dose gamma globulin and donor lymphocyte infusion. Adenovirus infection improved in 10 cases and progressed in 16 cases. The median follow-up time was 30 (7, 237) days. Twenty-two patients died. The all-cause mortality rate was (88.5±7.1) % , and the attributable mortality rate was 45.5% . There was no significant difference in the 100 d survival rate between asymptomatic infected patients and patients diagnosed with adenovirus disease (37.5% vs 22.2% , HR=1.83, 95% CI 0.66-5.04, P=0.24) . Conclusion: The age of >30 years was a risk factor for adenovirus disease. Mortality was high in patients with adenovirus infection after allogeneic hematopoietic stem cell transplantation.

Clinical analysis of bronchiolitis obliterans syndrome after haplo- hematopoietic stem cell transplantation / 中华血液学杂志

Objective: To investigate the incidence, risk factors and survival of bronchiolitis obliterans syndrome (BOS) in patients who had undergone haplo-hematopoietic stem cell transplantation (haplo-HSCT) . Methods: This study retrospectively analyzed clinical data of 444 consecutive patients who underwent haplo-HSCT and survived at least 100 days after transplantation in the First Affiliated Hospital of Soochow University between January 2013 and December 2015. Results: By the end of follow-up on January 1, 2018, 25 patients (5.63%) had BOS (BOS group) . The median onset time of BOS was 448 (165-845) d post transplantation, the 1-year, 2-year and 3-year cumulative incidence of BOS was 1.6% (95%CI 1.5%-1.6%) , 4.8% (95%CI 4.7%-4.8%) and 5.8% (95%CI 5.7%-5.8%) , respectively. Among patients with chronic graft-versus-host disease (cGVHD) , the cumulative incidence at the same intervals was 2.8% (95%CI 2.7%-2.8%) , 9.5% (95%CI 9.4%-9.5%) and 11.5% (95%CI 11.4%-11.6%) , respectively. In the multivariate analysis, the risk factors for BOS were high-risk primary disease, Ⅱ-Ⅳ aGVHD and preceding cGVHD with other organs. The 3-year overall survival (OS) was lower among patients with than those without BOS, but the difference was not significant [71.8% (95%CI 53.9%-89.6%) vs 72.4% (95%CI 68.1%-76.7%) , P=0.400]. Overall 1-year, 3-year survival of patients with BOS from the time of diagnosis was 78.4% (95%CI 61.5%-95.3%) and 37.0% (95%CI 2.5%-71.5%) , respectively, significantly less than those without (93.9% and 89.3%, from day 448 after transplantation, respectively, P<0.001) . Furthermore, we found a significantly higher incidence of transplantation-related mortality (TRM) in patients with compared with patients without BOS (28.2% vs 10.9%, P<0.001) . The main risk factor for OS of BOS patients was the severity of pulmonary impairment at the time of diagnosis. Patients who developed severe BOS had a worse OS than those with moderate and mild BOS (P=0.049) . Conclusion: BOS is a severe pulmonary complication of haplo-HSCT. High-risk primary disease, Ⅱ-Ⅳ aGVHD and preceding cGVHD were independent risk factors for BOS. Patients who developed BOS had a worse OS than those without BOS. The main risk factor for OS of BOS patients was the severity of pulmonary impairment.

An experimental study of CD4 targeted chimeric antigen receptor modified T cell with anti-lymphoma activity / 中华血液学杂志

Objective: To study the specific killing effect of CD4 membrane protein targeted chimeric antigen receptor modified T (CAR-T) cell. Methods: The second generation CD4 targeted chimeric antigen receptor containing 4-1BB costimulation domain was insert into lentiviral vector through recombinant DNA technology. Lentivirus was prepared and packaged by 293T cells with four plasmids. Beads activated T cells were transduced with lentivirus and the transduction efficiency was checked with Protein L and flow cytometry. T cell subsets and IFN-γ concentrations were detected with probe-tagged antibody and cytometric bead assay. Results: ①The transduction efficiency of activated T cells with prepared lentivirus were 50.0%-70.0%. A subset of CD8+ T cell acquired dim expression of CD4 membrane protein after activation. CD4+T cell and CD8+CD4dim T cell were gradually killed by CD4 targeted CAR-T post lentivirus transduction. ②The kill efficacy of CD4 targeted CAR-T cell and control T cell toward KARPAS 299 T cell at an E∶T ratio of 8∶1 for 24 h was (96.9±2.1)% and (11.2±3.1)%, CAR-T cell has a higher killing efficacy than control T cell (t=7.137, P=0.028). The IFN-γ concentrations in culture supernatant of CAR-T cell with K562-CD4 cell, CAR-T cell with K562 cell and CAR-T cell alone were (15 648±2 168), (1 978±354) and (1 785±268) pg/ml, CAR-T cell cocultured with K562-CD4 cell produced more IFN-γ than the other two controls (P<0.01). Conclusions: CD4 targeted CAR-T has an immunophenotype of CD8+CD4-T cell. CD4 targeted CAR-T cell has killing efficacy toward normal CD4+T cell and CD4+T lymphoma cell. CD4 targeted CAR-T cell also has a killing efficacy toward CD4dim target cell.

Effect of Additional Chromosomal Abnormalities on the Outcome of CML-CP Patients Receiving TKI Therapy / 中国实验血液学杂志

<p><b>OBJECTIVES</b>To explore the effect of additional chromosomal abnormalities on the prognosis and outcome of CML-CP patients receiving imatinib therapy.</p><p><b>METHODS</b>The clinical and genetic data of 589 CML-CP patients receiving imatinib treatment between May 2009 and October 2014 in the 1st Affiliated Hospital of Soochow University were analyzed, the 589 patients were divided into 5 groups according to the karyotypes at the initial diagnosis. The OS(overall survival), PFS (progression-free survival), EFS (event-free survival), Cumulative MMR (major molecular remission) and Cumulative CCyR (complete cytogenetic remission) were calculated by using the Kaplan-Meier method and compared by using the log-rank text by Graphpad 6.0. The χ test was used to compare the frequency of optimal molecular response at 3, 6, 12 months among the 5 groups.</p><p><b>RESULTS</b>There was significant difference about the frequency of optimal molecular response at 3 and 6 months between CML-CP patients with additional chromosomal abnormalities and those with classic t(9;22) ［50%（12/24） vs. 73.94%(261 /353), P<0.05; 50%(10 /20) vs. 72.05%(232 /322) (P<0.05)］, and the same significant difference was found at 6 months between the group with variant translocations and that with classic t(9;22) ［53.3% (16 /30) vs. 72.05%(232 /322) (P<0.05)］. The P values of cumulative CCyR (P<0.05) and EFS (P<0.01) for 4 years were statistically significant between CML-CP patients with additional chromosomal abnormalities and the other 4 groups. Compared one to another, there was the significant difference in cumulative CCyR and EFS for 4 years between CML-CP patients with additional chromosomal.abnormalities and those with classic t(9;22) (47.25% vs. 84.01%)(P<0.05); (75.03% vs. 90.01%)(P<0.01).</p><p><b>CONCLUSION</b>The additional chromosomal abnormalities influence the outcome of CML-CP patients receiving imatinib treatment, which make poor prognosis.</p>

Risk Factors of Leukemia-free Survival in PhALL Patients with Allogeneic Hematopoietic Stem Cell Transplantation / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To explore the effect of BCR-ABL gene transcripts on Leukemia-free survival (LFS) and prognosis of patients with Philadelphia chromosome positive acute lymphoblastic leukemia (PhALL) after allogeneic hematopoietic stem cell transplantation (allo-HSCT).</p><p><b>METHODS</b>The clinical data of 107 cases of PhB-ALL patients received allo-HSCT from July 2006 to November 2014 in the First Affiliated Hospital of Soochow University were collected and the relationship between the clinical characteristics and LFS after transplantation was analyzed.</p><p><b>RESULTS</b>Out of 107 PhALL patients (64 males and 43 females) with a median age of 30(7 to 54)years old, 35.5% (38/107) cases relapsed after transplantation within a median time of 6.9 (1.5 to 40.7) months. A total of 39 (36.4%) cases died within a median time of 19.8 (3.6 to 83.7) months after HSCT, of which 51.3% (20/39) due to disease relapse and 25.6% (10/39) due to infection. BCR-ABL gene transcripts of 49 cases turn into negative before transplantation, of which the expected 5-year cumulative incidence of relapse (CIR), non-relapse mortality (NRM) and overall survival (OS) were 26.5%, 29.5% and 41.6%, respectively. Another 49 cases still had a positive BCR-ABL gene transcripts before transplantation, of which the life expectancy of 5 year CIR, NRM and OS were 64.4%,8.9% and 48.9%, respectively. Compared with BCR-ABL positive patients, BCR-ABL negative patients showed a lower CIR (P<0.001), a higher NRM (P=0.030) and a similar OS (41.6% versus 48.9%, P=0.497). Multivariate analysis showed that BCR-ABL positive (P=0.016) and a disease statusphase ≥CR2 (P<0.001) before HSCT were independent risk factors for LFS, while the age underwent HSCT was the principal element affecting prognosis (P<0.001).</p><p><b>CONCLUSION</b>Both the relapse and infection are the main causes of death in the patients after transplantation. A disease status ≥CR2 and the BCR-ABL positive before transplantation are 2 independent risk factors of LFS in the patients with PhALL after allo-HSCT.</p>

The prognosis analysis of novel influenza A (H1N1) in patients with hematologic disease / 中华血液学杂志

<p><b>OBJECTIVE</b>To explore disease progression and prognosis factors of novel influenza A (H1N1) in immunocompromised patients with or without hematologic disease.</p><p><b>METHOD</b>A total of 76 confirmed novel influenza A (H1N1) infection patients from November 2009 to March 2010 included in the study, their clinical feature was analyzed, and the relationship between clinical feature and outcome was explored retrospectively by multivariate analysis method.</p><p><b>RESULTS</b>The whole 76 patients were administrated of oseltamivir. Among the 76 patients, 46 were severe and 23 were critical. Of the 6 patients with immunocompromised hematologic disease, 2 were severe and 4 were critical, case-fatality rate was 66.67% (4/6). The case-fatality rate of patients with non-hematologic disease was 10.42% (5/48). Multivariable logistic-regression analysis showed that immunocompromised hematologic disease (P = 0.0008, odds ratio:75.368; 95% CI, 5.980 to 949.853) and age (P = 0.0380) were independent risk factors for death. And other variables such as chronical lung disease, interval time from the onset of illness and lymphocyte count had no statistical significance (P > 0.05).</p><p><b>CONCLUSIONS</b>The novel influenza A (H1N1) patients with immunocompromised hematologic disease has a poor prognosis, they can deteriorate quickly and have high mortality, it may aid clinicians to pay high attention to these people.</p>

Genetic polymorphism of the killer cell immunoglobulin-like receptor genes in the Inner Mongolian population / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To investigate the killer cell immunoglobulin-like receptor (KIR) gene frequencies and genotypes distributions in the Inner Mongolian population.</p><p><b>METHODS</b>Ninety genomic DNA samples were extracted from blood samples of randomly chosen Mongolian individuals. Gene-specific PCR amplification was used to identify genes present or absent for 16 KIR loci. KIR genotype distributions were obtained and compared to that of 24 populations published in literatures using principal component analysis by SAS8.0 software. Genetic tree was constructed by the calculate Nei's genetic distance.</p><p><b>RESULTS</b>(1) The frequency of KIR 2DL2, 2DS2 in Mongolian individual is higher than that in north Mongoloid and less than that in Caucasian. (2) Haplotype AA was identified in 37.78% of individuals, which is higher than that in north Mongoloid and lower than that in Caucasian. (3) Mongolian was considered between north Mongoloid and Caucasian by principal component and genetic tree analysis.</p><p><b>CONCLUSION</b>Mongolian might be affected by the north Mongoloid and Caucasian, and showed intermediate between the two populations.</p>