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Objective:To explore the correlation between the expression of signaling lymphocyte activation molecule family 6 (SLAMF6) on peripheral blood CD8 +T cells and perforin and granzyme B and the clinical significance in patients with newly diagnosed severe aplastic anemia(SAA). Methods:The indicators of blood routine and bone marrow and peripheral blood samples of 32 newly diagnosed SAA patients admitted to Henan Provincial People′s Hospital from January 2016 to June 2019 were collected for retrospective analysis. Flow cytometry was used to detect the expression of SLAMF6, perforin and granzyme B on samples CD8 +T cell before therapy and 6 months after therapy (11 cases received transplantation, 21 cases received immunosuppressive therapy [IST]). Spearman correlation analysis was performed to determine the association between clinical indicators and laboratory test results. The expression of SLAMF6, perforin and granzyme B was also detected in 10 healthy people (normal group) and 13 myelodysplastic syndromes/paroxysmal nocturnal hemoglobinuria (MDS/PNH) patients (MDS/PNH group). Results:(1) At diagnosis: the expression of SLAMF6 was significantly lower in the SAA group than that in the normal group and the MDS/PNH group ([56.40±6.37]% vs [84.34±5.81]% and [82.24±4.98]% (both P<0.001]). The expression of perforin was significantly higher in the SAA group (32.73±8.46) than that in the normal control group (23.75%±5.10%), and the MDS/PNH group (26.12%±5.53%) (both P<0.05). The expression of granzyme B was also significantly higher in the SAA group (36.23%±7.94%) than that in the normal control group (21.67%±5.05%) and the MDS/PNH group (21.79%±5.10%) (both P<0.001). The expression of SLAMF6 was positively correlated with the hemoglobin ( r=0.804), and reticulocyte absolute values ( r=0.656) in peripheral blood, percentage of granulocytes ( r=0.643) and erythrocytes ( r=0.622) in bone marrow of SAA patients (all P<0.05). Expression of SLAMF6 was negatively correlated with perforin ( r=-0.792) and granzyme B ( r=-0.908) on CD8 +T cells in patients with SAA (both P<0.001). (2) After treatment: the expression of SLAMF6 in peripheral blood CD8 +T cells of 30 surviving patients was higher than pre-treatment ([79.19±12.69]% vs [56.40±6.37]%, P<0.001). The expressions of perforin and granzyme B were lower than pre-treatment level (both P<0.05). The expression of SLAMF6 on CD8 +T cells in 11 transplanted patients was higher than before transplantation ([86.54±3.75]% vs [56.40±7.35]%, P<0.001). The expressions of perforin and granzyme B were lower than before transplantation (both P<0.05). The expression of SLAMF6 on CD8 +T cells in 12 IST-respond patients was higher than that before treatment, while the perforin and granzyme B levels were lower than pre-treatment (all P<0.05). The post-treatment expressions of SLAMF6, perforin and granzyme B were similar as before treatment levels in 7 IST-unrespond patients (all P>0.05). Conclusion:SLAMF6 is significantly down-regulated on CD8 +T cells in newly diagnosed SAA, negatively correlated with the effective factors of CD8 +T cells, which might participate in the immune regulatory of CD8 +T cells as a negative regulatory factor in patients with SAA. The SLAMF6 is significantly up-regulated after hematopoietic recovery, while there is no significant change in treatment-unrespond patients, which could thus serve as an useful diagnostic and therapeutic index of patients with SAA.
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Objective@#To reveal the related factors of inhibitors and differences ofhemorrhage and joint disease before and after the production of inhibitors in children with hemophilia A (HA) .@*Methods@#Retrospective analyses of the clinical data of 381 children with HA under the age of 16 registered in the Registration Management Center of Hemophilia in Henan Provincial from January 2015 to August 2018.@*Results@#A total of the 381 children were enrolled with 116 (30.4%) mild, 196 (51.4%) moderate, and 69 (18.1%) severe cases; 54 patients (14.2%) had inhibitors, including 22 high and 32 low titer inhibitors. Positive family history was positively associated with inhibitors[P<0.001, OR=3.299 (95%CI 1.743-5.983) ], and high-intensity exposure was associated with inhibitors[P=0.002, OR=2.587 (95%CI 1.414-4.731) ]. High-intensity exposure was associated with high titer inhibitor production[P=0.001, OR=8.689 (95%CI 2.464-30.638) ], and high-intensity exposure increased the risk of high titer inhibitors in HA patients. After inhibitors occurred in 54 patients with HA, the rates of overall joint annual bleeding (z=-3.440, P=0.001) and traumatic annual bleeding (z=-2.232, P=0.026) increased, but the rates of the annual joint bleeding (z=-1.342, P=0.180) and spontaneous annual bleeding (z=-1.414, P=0.157) remained to be not statistically significant. The joint ultrasound score did not change significantly after the inhibitor information (z=-0.632, P=0.527) .@*Conclusions@#Positive family history and high-intensity exposure could increase the risk of F Ⅷ inhibitors in HA patients, and high-intensity exposure increased the risk of high titer inhibitors. The rates of the overall joint annual bleeding and traumatic annual bleeding increased after the inhibitor information.
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Objective@#To evaluate the efficacy of allogeneic hematopoietic stem cell transplantation (allo-HSCT) from different donors as first-line treatment for children and adolescents with severe aplastic anemia (SAA) .@*Methods@#The clinical data of 79 children and adolescents with SAA diagnosed from January 2013 to December 2016 in Henan Province were retrospectively analyzed. There were 50 males and 29 females, with a median age of 14(4-18) years. 40 cases received matched sibling transplantation (MSD-HSCT), 17 with unrelated donor transplantation (UD-HSCT), and 22 with haploidentical transplantation (haplo-HSCT).@*Results@#The comparison of MSD-HSCT, UD-HSCT, haplo-HSCT groups was conducted and the median times of neutrophils engraftment were statistically significant [12(9-25) d, 14(10-22) d, 16(11-26) d, respectively (χ2=13.302, P=0.001)], but no difference in+30 d engraftment rate [97.3%(36/37), 100%(15/15), 100%(20/20), χ2=0.959, P=0.619]. The median times of PLT engraftment were not statistically significant [14(6-34)d, 16(7-32)d, 19(10-34)d, respectively, χ2=5.892, P=0.053], and the +30 d engraftment rate had no difference [97.3%(36/37), 100%(15/15), 100%(20/20), χ2=0.959, P=0.619]. The post-transplant infection rate showed no statistically significance [35.0% (14/40), 29.4% (5/17), 45.5% (10/22), χ2=1.158, P=0.560], as well as the incidences of aGVHD, grade III/IV aGVHD and cGVHD(χ2=0.230, P=0.891; χ2=2.628, P=0.269; χ2=3.187, P=0.203). The two-years OS rate was not statistically significant respectively [(77.1±6.7)%, (70.6±11.1)%, (77.3±8.9)%, χ2=0.330, P=0.845]. Severe post-transplant infection (RR=4.617, P=0.009), grade Ⅲ/Ⅳ aGVHD (RR=2.707, P=0.048) were independent risk factors for OS.@*Conclusion@#The overall efficacy of MSD-HSCT, UD-HSCT and haplo-HSCT as first-line therapy for children and adolescents with SAA/VSAA is comparable.
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Objective@#To explore the prognostic value of CD34, CD2, CD56 expressions and FLT3-ITD mutation in adults with acute promyelocytic leukemia (APL) .@*Methods@#The immuno-phenotypic and molecular characteristics of 137 adult patients with APL (from January 2010 to March 2016, in Henan Provincial People’s Hospital) were investigated. And the relationships between CD34, CD2, CD56 expressions, FLT3-ITD mutation and the outcomes of high WBC counts at onset, complete remission (CR) rate, early mortality, relapse rate (RR) , overall survival (OS) , disease free survival (DFS) were explored.@*Results@#①Among the 137 patients, the positive ratios of CD34, CD2, CD56 expressions and mutation rate of FLT3-ITD were 26.3%, 25.5%, 10.2% and 17.5%, respectively. The morbidities of positive CD34, CD2, CD56 expressions and FLT3-ITD mutation in the high-risk group were 43.2%, 47.7%, 18.2% and 27.3% respectively, while those in the low-/intermediate-risk groups were 18.3%, 15.1%, 6.5% and 12.9%, respectively (P<0.05) . ②At a median follow-up of 41 months, the total CR rate of the 137 adults APL patients was 96.9%, early mortality 6.6% and relapse rate 7.3% respectively. And RR of positive CD34 or CD2 expression patients was higher than negative CD34/CD2 expression ones (18.8% vs 3.3%, χ2=8.462, P=0.004; 16.1% vs 4.3%, χ2=4.382, P=0.028, respectively) . In addition, the early mortality of patients with positive CD56 expression or FLT3-ITD mutation was extremely higher than in negative ones (21.4% vs 4.9%, χ2=5.610, P=0.018; 16.7% vs 4.4%, χ2=4.833, P=0.028, respectively) . ③The whole OS and DFS were 88.3% and 84.7%, respectively. Wherein, OS and DFS in patients with CD34+, CD56+ or FLT3-ITD mutation were worse (P<0.05) .@*Conclusions@#Positive CD34, CD2, CD56 expression and FLT3-ITD mutation were latent poor prognostic factors in adults with APL.
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Objective@#To explore the efficacies of regimens of three-drug induction therapy (ATRA+ATO+anthracyclines) versus two-drug induction therapy (ATRA+ATO) in patients with acute promyelocytic leukemia (APL).@*Methods@#Of 184 patients diagnosed with APL from January 2009 to March 2016, 58 patients underwent three-drug induction therapy, while the rest were treated with two-drug induction therapy. Three-drug induction therapy was of ATRA (20 mg·m-2·d-1, d1-28) + ATO (0.16 mg·kg-1·d-1, d1-28) + Idarubicin (8 mg·m-2·d-1, d3-5) /daunorubicin (40 mg·m-2·d-1, d3-5) , while two-drug induction therapy ATRA+ATO with the same doses and methods as above. Of 184 cases, 69 cases accompanied with WBC counts>10×109/L, 115 cases with WBC counts≤10×109/L at onset.@*Results@#①Short-term efficacy: After one cycle induction therapy, the rates of hematologic remission, genetic remission, molecular remission and induced differentiation syndrome (DS) in three-drug regimen group were 98.3%, 87.9%, 72.4% and 0 respectively, while those in two-drug regimen group were 87.3%, 65.9%, 51.6% and 12.7% respectively. In patients with WBC >10×109/L, DS rate and early mortality in three-drug regimen group were lower than in two-drug regimen group (0 vs 15.6%, 4.2% vs 15.6%, respectively). In patients with WBC≤10×109/L, DS rate in three-drug regimen group was also lower than in two-drug regimen group (0 vs 12.3%) , but there were no statistical differences in terms of relapse and early mortality. ② Long-term efficacy: The relapse rate, overall survival (OS) and disease free survival (DFS) in three-drug regimen group were 0, 98.5%, 96.6% respectively, while those in two-drug regimen group were 8.6%, 86.5% and 84.1% respectively; the advantages of three-drug over two-drug regimen, especially in cases of WBC >10×109/L were observed. ③ Side effects: the incidences of gastrointestinal reaction, liver dysfunction, myocardial damage and headache in three-drug regimen group hardly increased.@*Conclusion@#The efficacies of three-drug induction therapy were superior to two-drug one.