Association between IL-10 Gene -592(C→A) (rs1800872) SNP and GVHD after Allogeneic Hematopoietic Stem Cell Transplantation in Children / 中国实验血液学杂志

OBJECTIVE@#To study the association between IL-10 gene-592(C→A) (rs1800872) single nucleotide polymorphism (SNP) and the graft versus host disease (GVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in children.@*METHODS@#Ninety-seven childhood patients and seventy-one donors in the Hematology Oncology Center of Beijing Children's Hospital from Jan 2011 to Jul 2017 were enrolled in this study. The genomic DNA was extracted from peripheral blood cells and the SNP genotype was analyzed using TaqMan SNP genotyping assay.@*RESULTS@#In malignant patients with AA genotype, the incidence of Ⅱ-Ⅳ grade acute GVHD (aGVHD) was lower than that in patients with AC and CC genotype (9.1% vs 43.5%) (P＜0.01), and the gastrointestinal aGVHD rate was also lower (9.1% vs 39.1%) (P＜0.05). There's no significant association between patients' genotype and Ⅱ-Ⅳ grade aGVHD in total patients and non-malignant patients. Also, the genotype in patients did not corelate with chronic GVHD (cGVHD) and 1 year transplantation-related mortality (TRM). In cases who received HSCT of donors with AA genotype, the liver aGVHD rate was higher than that in cases who received HSCT of donors with AC and CC genotype (23.1% vs 0.0%) (P＜0.05), but the genotype in donors did not correlate with Ⅱ-Ⅳ grade aGVHD, cGVHD and 1 year TRM.@*CONCLUSION@#AA genotype in the IL-10 gene-592 (C→A) (rs1800872) single nucleotide polymorphism in patients protects pediatric malignant patients against Ⅱ-Ⅳ grade aGVHD and gastrointestinal aGVHD after allo-HSCT. AA genotype in donors is a risk factor for liver aGVHD after allo-HSCT in non-malignant disease.

Study on Immunophenotypes and Gene of Acute Lymphoblastic Leukemia--Review / 中国实验血液学杂志

Transplantation-associated thrombotic microangiopathy (TA-TMA) is one of the fatal complications of hematopoietic stem cell transplantation(HSCT). The pathogenesis of TA-TMA has not been fully elucidated. The latest researches show that the abnormal activation of the complement system may lead to widespread endothelial injury which may play an important role in the pathogenesis of this disease. Incontrotable hypertension, proteinuria, increase of soluble C5b-9 concentration and early pericardial effusion are the risk factors of TA-TMA . In this review, the latest advances of pathogenesis, early diagnosis, treatment and other aspects of the progress of TA-TMA are summarized, so as to provide new ideas to early diagnosis and treatment in TA-TMA.

Infections during induction therapy of protocol CCLG-2008 in childhood acute lymphoblastic leukemia: a single-center experience with 256 cases in China / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Infections remain a major cause of therapy-associated morbidity and mortality in children with acute lymphoblastic leukemia (ALL).</p><p><b>METHODS</b>We retrospectively analyzed the medical charts of 256 children treated for ALL under the CCLG-2008 protocol in Beijing Children's Hospital.</p><p><b>RESULTS</b>There were 65 infectious complications in 50 patients during vincristine, daunorubicin, L-asparaginase and dexamethasone induction therapy, including microbiologically documented infections (n = 12; 18.5%), clinically documented infections (n = 23; 35.3%) and fever of unknown origin (n = 30; 46.2%). Neutropenia was present in 83.1% of the infectious episodes. In all, most infections occurred around the 15 th day of induction treatment (n = 28), and no patients died of infection-associated complications.</p><p><b>CONCLUSIONS</b>The infections in this study was independent of treatment response, minimal residual diseases at the end of induction therapy, gender, immunophenotype, infection at first visit, risk stratification at diagnosis, unfavorable karyotypes at diagnosis and morphologic type. The infection rate of CCLG-2008 induction therapy is low, and the outcome of patients is favorable.</p>

Allogeneic stem cell transplantation for 8 patients with malignant infantile osteopetrosis in China / 中华儿科杂志

<p><b>OBJECTIVE</b>Osteopetrosis is a rare genetic disorder and the malignant infantile osteopetrosis (MIOP) is the worst subtype of this disease. Seventy percent of patients die in six years of life without proper treatment. Hematopoietic stem cell transplantation (HSCT) offers the only chance of cure for MIOP.</p><p><b>METHOD</b>Retrospective analysis was performed on 8 patients with MIOP who underwent HSCT in Beijing Children's Hospital during the period from 2006 to 2011.</p><p><b>RESULT</b>Eight cases (4 male and 4 female, mean age at HSCT 13.5 months) were diagnosed as malignant infantile osteopetrosis. Conditioning regimen included fludarabine, busulfan and cyclophosphamide. All patients received cyclosporin for prophylaxis of graft vs. host disease (GvHD). A UMD recipient underwent CD34(+) cell selection. ATG/ALG, mycophenolate mofetil (MMF) and methotrexate (MTX) used for recipients with unrelated cord donor (2) and recipients with haplo-identical donors (5). Average time for neutrophil engraftment was 15.7 day (9 - 36), platelet engraftment was 43.3 day (10 - 68). The patients were followed up from 47 days to 5 years, 1 patient died of post-transplant complications. Seven cases presented better in clinical manifestation. Acute GvHD I°-II° was observed in 6 patients, III°-IV° in 2 patients. It was controlled by anti-GvHD therapy.</p><p><b>CONCLUSION</b>Non-allogenic stem cell transplantation treatment of infantile MIOP showed high survival rate and restoration of hematopoiesis in haploid transplant patients, therefore, non-allogenic HSCT may be an option to treat MIOP in children.</p>

Incidence and relationship of human cytomegalovirus infection and human herpesvirus 6 infection in pediatric patients after hemopoietic stem cell transplantation / 中华实验和临床病毒学杂志

<p><b>OBJECTIVE</b>To study the incidence of human cytomegalovirus (CMV) and human herpesvirus 6 (HHV-6) infection in pediatric patients with hemopoietic stem cell transplantation (HSCT), and to explore the relationship between CMV and HHV-6 infection in pediatric patients with HSCT.</p><p><b>METHODS</b>Pediatric patients with HSCT in hemotology center of Beijing Children's Hospital were enrolled into this study from June 2007 to October 2009. Peripheral blood were collected every week after HSCT, and Fluorescent quantitation PCR and conventional PCR were used to detect CMV DNA load in serum and HHV-6 DNA in peripheral blood respectively. Genetic typing was conducted on HHV-6.</p><p><b>RESULTS</b>Fifty two pediatric patients with HSCT were enrolled into this study, and six hundreds and thirty six specimens were collected totally. CMV DNA was detected in fifty two specimens from twenty cases. The median time was 56 days after HSCT. The incidence of CMV infection was 38.5% (20/52) in all HSCT patients and 47.6% (20/42) in allogene HSCT patients. The incidence of late CMV infection was 22.2% (6/27) in allogene HSCT. Three patients died of CMV infection,and two died of CMV interstitial pneumonia. HHV-6 DNA was detected in thirty three specimens from fourteen cases. The median time was 23 days after HSCT. The incidence of HHV-6 infection was 26.9% (14/52)in all HSCT patients and 31% (13/42) in allogene HSCT patients. The genotype of HHV6 was all type B. HHV-6 DNA was positive in six of twenty cases with CMV infection. The incidence of co-infection was 30% (6/20).</p><p><b>CONCLUSIONS</b>There was a substantial incidence of CMV and HHV6 infection after HSCT. The relationship between earlier HHV6 infection and later CMV infection in pediatric patients with HSCT need further study.</p>

Establishment of method collecting peripheral blood hematopoietic stem/progenitor cells from infants / 中国实验血液学杂志

The aim of this study was to explore a safe method collecting peripheral blood stem/progenitor cell (PBSPC) from the infants of body weight less than 20 kg by using the COBE Spectra Blood Cell Separator through Auto-PBSC procedure. After washing tube by normal saline, one unit of irradiated RBC was infused into the apheresis set. When the collection terminated, only the concentrated RBC in the apheresis set was returned to the infant. The peripheral mononuclear cells (PBMNCs) and CD34+ cells were counted, the cell viability was determined. The results showed that 13 PBSPC collections were carried out successfully from 7 infants of body weight<20 kg. The average count of MNCs was 4.44x10(8)/kg [(3.46-6.45)x10(8)/kg], the CD34+ count was 2.20x10(6)/kg [(1.34-3.79)x10(6)/kg] and the cell viability was 98.45% (97%-100%) respectively. The vital signs of all the infants went smoothly during collection of PBSPCs. In conclusion, with the aid of COBE Spectra blood cell separator and other measures, the collection of PBSPCs from infants of body weight<20 kg is safe and effective, the PBMNCs containing enough PBSPC can be harvested for transplantation.

Effectiveness of allogeneic peripheral blood stem cell transplantation in 23 patients with myelodysplastic syndromes / 中华血液学杂志

<p><b>OBJECTIVE</b>To analyse the outcome of allogeneic peripheral blood stem cell transplantation (allo-PBSCT) for myelodysplastic syndromes (MDS).</p><p><b>METHODS</b>Twenty-three patients with MDS received G-CSF mobilized HLA-identical sibling allo-PBSCT. The numbers of mononuclear cells (MNC) and CD34+ cells were 8. 25 (4.50 -22.36) x 10(8)/kg and 5.59 (1.57 - 12.22) x 10(6)/kg respectively. CsA and shorten course MTX were used for graft-versus-host disease (GVHD) prophylaxis and MMF was given on + 1 d - +28 d posttransplantation.</p><p><b>RESULTS</b>Among 23 patients, 22 achieved hematopoietic recovery. The median time of ANC > 1.0 x 10(9)/L and BPC > 50 x 10(9)/L were + 13 (+ 11 - +17) days and + 30 (+13 + 102) days respectively. Two patients died of transplant related complications and three died of disease relapse, while 18 patients survived. Kaplan-Meier analysis showed disease free survival and relapse rate were (77.8 +/- 8.7)% and (14.4 +/- 7.5)% respectively.</p><p><b>CONCLUSION</b>Allo-PBSCT is an effective treatment for MDS patients.</p>

Selected CD34+ cell autologous transplantation for advanced malignant tumors / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To determine the clinical results of selected CD34(+) cell autologous transplantation in advanced malignant tumors.</p><p><b>METHODS</b>After pretreatment, fifteen patients aged 12 - 70 (49.5) years with various Stage III or IV malignant tumors were given the sorted CD34(+) cells collected by magnetic-activated cell sorting (Clini MACS, Milteny Biotech, Germany).</p><p><b>RESULTS</b>Peripheral blood progenitor cells (PBPC) from the patients were mobilized by chemotherapy and G-CSF 5 micro g/kg per day. CD34(+) cells gave 2.0 - 5 log depletion after cell sorting, with a median yield of CD34(+) selected cells of 2.4 (0.15 - 12.03) x 10(6)/kg. It gave a median recovery of 64 (52 - 81.4)% and median purity of 98.2 (83.2 - 99.7)%. The median time of neutrophil recovery > 1.0 x 10(9)/L and platelet recovery > 20 x 10(9)/L post-transplantation were 14 (8 - 26) days and 13 (11 - 35) days, respectively. On follow-up of 2 - 33 (11) months, the event-free survival rate was 53.3% (8/15) and the overall survival rate was 66.7% (10/15).</p><p><b>CONCLUSION</b>Transplantation of autologous selected PBPC CD34(+) cells gives prompt and stable engraftment. Selected CD34(+) cell transplantation, being a safe approach, may improve the clinical outcome even in patients with advanced malignant tumors.</p>

Cytomegalovirus infection and disease in allogeneic hematopoietic stem cells transplantation / 军事医学科学院院刊

Objective: To investigate the incidence of CMV infection(CMV-I) and CMV related diseases (CMV-D) after allogeneic hematopoietic stem cells transplantation in 70 consecutive allogeneic hematopoietic stem cells transplantation(allo-HSCT) patients and to search for the optimal prophylactic strategy.Methods: Blood samples were monitored using the CMV pp65 antigenemia assay.Of the 70 patients observed,30 patients with chronic myeloid leukemia［CML:CP(27),AP(2),BC(1)］,12 with acute myeloblastic leukemia(AML),10 with acute lymphoblastic leukemia(ALL)and other cases were NHL(3), AA(5), MDS(7), SCLC with pancytopenia (1),CLL(1), and MF (1). Sixty six patients received HLA - identical siblings transplantation and four received tranplants from their HLA- haploidentical donors. Seventy cases included allo-PBPCT (64 cases) , allo-BMT (4 cases) and allo-PB+BMT (2). Before transplantation, all patients and donors received CMV serological examination except 4 pairs of donors/recepients. All 66 patients (3 cases were CMV IgM positive) and 64/66 donors were CMV IgG positive. Results：After transplantation, 64/70 patients developed CMV viremia during monitoring period. Forty three of 70 patients developed CMV-D.Thirty five of them suffered from CMV-associated interstitial pneumonia(CMV-IP). The high peak levels of CMV antigenemia were associated with development of CMV disease　. Close correlation was found between acute graft vs host disease(GVHD) and CMV disease. The patients were followed up for 2 to 24 months. The patients who received preemptive therapy(group A)had significantly better outcome than CMV disease group(group B, P=0.0001). Conclusions: The results suggest that CMV antigenemia has high predictive value for subsequent CMV disease and CMV pp65 antigenemia -guided early therapy has particular advantage for avoiding morbidity and mortality caused by CMV disease.