Expression and Significance of BLIMP-1 in Regulatory T Cells of Children with Aplastic Anemia / 中国实验血液学杂志

OBJECTIVE@#To study the expression of B lymphocyte-induced mature protein-1 (BLIMP-1) in regulatory T cells (Tregs) of children with aplastic anemia (AA), and analyze its correlation with the number of Tregs and the levels of inhibitory cytokines interleukin (IL)-10 and transforming growth factor (TGF)-β in plasma.@*METHODS@#The peripheral blood samples of 10 newly diagnosed AA children and 10 healthy children were collected for experiment. qPCR was used to detect FOXP3 and PRDM1 mRNA expression levels. Flow cytometry was used to detect the proportion of Tregs, the expression of BLIMP-1 in Tregs, and the levels of cytokines such as IL-2, IL-17A, IL-6, interferon (IFN)-γ, IL-10 and TGF-β in plasma. Pearson correlation model was used to evaluate the relationship between the expression of BLIMP-1 in Treg and the number of Tregs, as well as the levels of IL-10 and TGF-β in plasma.@*RESULTS@#Compared with control group, the proportion of Tregs in peripheral blood of AA children was decreased significantly (P<0.001); The plasma levels of proinflammatory cytokines IL-2, IL-6 and IFN-γ in AA children were increased significantly (P=0.033, P=0.031, P=0.006), and IL-17A also was increased but the difference was not statistically significant (P=0.052), while anti-inflammatory cytokines IL-10 and TGF-β were significantly reduced (P=0.048, P=0.002). The relative expressions level of FOXP3 and PRDM1 mRNA in AA children were significantly lower than those in control group (P=0.037, P=0.016). The expression of BLIMP-1 protein in Tregs of AA children was significantly lower than that in control group (P<0.001). The expression level of BLIMP-1 protein in Tregs was positively correlated with the percentage of Tregs in lymphocytes (r=0.671, P=0.001), and was also positively correlated with the levels of IL-10 and TGF-β in plasma (r=0.500, P=0.029; r=0.486, P=0.030).@*CONCLUSION@#The expression of BLIMP-1 in Tregs of AA children is impaired, and the low expression of BLIMP-1 is related to the decrease of the number in Tregs and IL-10 and TGF-β expressions.

Comparison of Curative Effect between Fu Fang Huang Dai Pian and Arsenic Trioxide in Treatment of 45 Patients with Acute Promyelocytic Leukaemia / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To investigate the clinical efficacy of Fu Fan Huang Dai Pian(RIF) and arsenic trioxide (ATO) regimens for treatment of children with acute promyelocytic leukemia (APL) and to explore the risk factors affecting the prognosis of patients.</p><p><b>METHODS</b>The clinical data of 45 newly diagnosed APL children admitted in our hospital from January 2004 to May 2017 were analyzed retrospectively. Among 45 APL children, 25 children were treated by chemotherapetic regimen including RIF (RIF group), another 20 children were treated by chemotherapeutic regimen including ATO (ATO group). The follow-up was performed in all APL children. The prognosis and incidence of side reactions from drugs in 2 groups were compared, and the high risk factors affecting the prognosis of patients were analyzed.</p><p><b>RESULTS</b>The median follow-up time was 49.8% months. In RIF group, no early death occured in 25 APL children; 5 cases did not achieve complete remission (CR) after induction therapy, CR rate was 88%. Out of 25 cases 2 caes relapsed, 3 cases died, 20 cases maintained contined CR (CCR), 2 cases failed to be followed-up. In ATO group, 2 cases suffered from early death, 5 cases did not achieve CR after induction therapy, CR rate was 90%, 2 caese relapsed and died, 15 cases maintained CCR, the follow-up failed in 1 caes. The 5 year- OS and EFS rate in all the patients were predicted as (82.2±6.2)% and (76.4±6.6)% respectively. The OS and EFS rate in RIF group were (86.1±7.4)% and (78.4±8.6)% respectively, which were significantly different from OS and EFS rate (76.4%±10.6%) and (74.0%±10.1%) respectively in ATO group (all P>0.05). As for the side reaction from drug, except for the cardiac damage (P<0.05), incidence of other side reactions was not significantly different between 2 groups (P>0.05). In addition, the 5 year-OS and EFS rates in APL children with CNSL were significantly lower than those in APL children without CNSL (all P<0.05), the 5 year OS and EFS rate in APL children did not reache M1 and with high risk were significantly lower than those in APL children reached M1 after induction therapy and with low and standerd risk (P<0.05 and P<0.05); the 5 year-OS and EFS rates did not correlate with age and sex.</p><p><b>CONCLUSION</b>The Fu Fang Huang Dai Pian shows the therapeutic efficacy on APL children same as ATO, moreover, no obvious enhancement in incidence of side reactions is observed, therefore, the Fu Fang Huang Dai Pian is effective and safe for treatment of APL children. The CNSL, poor respond to treatment, high risk in clinical stratification are high risk factors affecting prognosis of patients.</p>

Familial Haemophagocytic Lymphohistiocytosis Occurs in A Fetus at His Third Trimester-A Case Report / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To analyze the clinical features and pathogenetic gene mutation in a fetus at his third trimester with familial haemophagocytic lymphohistiocytosis (FHL).</p><p><b>METHODS</b>Target region sequencing and high-throughput sequencing were used to detect pathogenetic gene mutations for familial haemophagocytic lymphohistiocytosis in a late onset HLH fetus. Pathogenetic gene mutations of the patient and his parents were verified by Sanger dideoxy sequencing.</p><p><b>RESULTS</b>A male neonate, who had right pleural effusion, hepatomegaly and splenomegaly previously revealed by fetus ultrasound, was delivered at full-term by cesarean section. His clinical presentation showed recurrent fever, tachypenea, decreased breath sounds on right side, hepatosplenomegaly etc., which were gradually aggravating Lab.tests results were as follows: WBC 9.88×10/L, Hb 91 g/L, Plt 13×10/L, ALT 18 U/L,AST 69 U/L,TBIL 207.2 µmol/L, DBIL 183.5 µmol/L, TG 3.05 mmol/L, Fib 0.88 g/L, Serum ferritin 3 120 ng/ml and sIL-2R 57 420 U/ml. FCM showed that CD3CD16CD56cells reached to 3.60% in the pripheral blood. Haemophagocytes were occasionally found in the bone marrow. NK/NKT stimulation test showed a severe damage of degranulation of NK cells. Sequence analysis of genomic DNA from his peripheral blood demonstrated the compound heterozygous mutations of UNC13D gene: c.2448-13 G>A in exon26 and c.1055+1 G>A in exon12, both were pathogenetic mutations. In detailed family survey, it was confirmed that the mutation c.2448-13 G>A in exon26 was inherited from his mother and c.1055+1 G>A in exon12 from his father.</p><p><b>CONCLUSION</b>A rare case of familial haemophagocytic lymphohistiocytosis type 3 (FHL3) with late fetus onset who carried pathogenetic compound heterozygous mutations of UNC13D gene. Those neonates with recurrent fever, serous effusions and multiple organ failure should be screened for FHL. Identifying the pathogenic gene mutations laid the foundation of conceiving disease-free newborns.</p>

Outcome Comparison of Pediatric Langerhans Cell Histiocytosis Treated with Modified DAL-HX83/90 or JLSG-96 Protocol / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To analyze and compare the clinical features, treatment and prognosis of 31 children with Langerhans cell histiocytosis(LCH) treated with modified DAL-HX83/90 or JLSG-96 protocol.</p><p><b>METHODS</b>The clinical features, treatment and prognosis of 31 children with Langerhans cells admitted in our hospital from January 2005 to December 2014 were analyzed retrospectively. The outcome of patients treated with modified DAL-HX83/90 or JLSG-96 protocols were compared by using the Kaplan-Meier survival curve. Among 31 children with LCH, 19 males and 12 females, 12 younger than 2 years old, and 19 older than 2 years old. LCH usually affected skeleton system(77.4%), skin(42.0%), liver(29.0%), spleen(19.4%), hematopoietic system(12.9%). The most common misdiagnoses were upper respiratory tract infection, malignancies, focal infection, and eczema.</p><p><b>RESULTS</b>Response rate at week 6 was 76.9% in modified DAL-HX83/90 group and 94.1% in JLSG-96 group respectively, and no significant differences had been found between 2 groups. The 1-and 3-year overall survival rates of the patients treated with JLSG-96 protocol were 100% and 83.3%±15.2% respectively, while The 1-, 3-,5-year overall survival rates of those patients treated with the modified DAL-HX83/90 protocol were 70%±14.5%. The 1-and 3-year event-free rates of children treated with JLSG-96 protocol were 73.3%±11.4% and 66.7%±12.2%, respectively, while the 1-, 3-, 5-year event-free rates of those treated with modified DAL-HX83/90 protocol were 50%±15.8%, 40%±15.6% and 26.7%±15% respectively. No differences were found between the 2 groups for OS or EFS.</p><p><b>CONCLUSION</b>JLSG-96 protocol shows a better prognosis, and the risk of secondary malignancy caused by etoposide can be avoided. Early diagnosis of refractory LCH, specified grouping strategy and prolonged maintenance therapy may contribute to enhancing the EFS rates and reducing relapses.</p>

Treatment of children with multiple system Langerhans cell histiocytosis by Japan Langerhans Cell Histiocytosis Study Group Protocol / 中国实验血液学杂志

The purpose of this study was to evaluate the efficiency of Japan Langerhans Cell Histiocytosis Study Group (JLSG) Protocol in treatment of children suffering from multiple system langerhans cell histiocytosis (MS-LCH). The clinical features, therapeutic response and prognosis of 11 children who were diagnosed and treated by JLSG in our department during October 2004 through October 2011 were analyzed. Among all 11 cases, 8 males and 3 females, the age at diagnosis was from 3 month to 6.5 years old with a median age of 3 years old. There were 10 cases of LCH with multi-system involvement (MS-LCH) and 1 case of single-system involvement (SS-LCH). Among those MS-LCH patients, 5 patients had risk organ involvement, and the other 5 patients did not develop risk organ involvement. All patients had been treated with JLSG protocol. The results showed that 4 cases achieved good response after 6-week induction treatment and the time of drug discontinuation were 5 - 20 months without relapse; 3 cases achieved partial response after 6-week induction treatment, among them 1 case did not relapse after discontinuation of drugs for 19 months, 1 case was still receiving maintenance treatment, 1 case abandoned induction treatment; 4 patients got no response (NR) or progressive disease after 6-week of induction treatment and were switched to salvage therapy, among them, 2 patients had stopped treatment for 2 - 20 months without relapse, 1 patient was still receiving maintenance treatment, one had changed to another therapy. It is concluded that the most of childhood LCH can be effectively controlled by immunochemical therapy based on the JLSG protocol. For children with LCH who has a poor response after 6-week induction treatment, LCH can still be well controlled if switched to salvage treatment.