Pharmacokinetics of Recombinant Human Coagulation Factor Ⅷ Preparations in Patients with Severe Hemophilia A / 中国实验血液学杂志

OBJECTIVE@#To calculate the pharmacokinetic parameters of recombinant human coagulation factor Ⅷ using myPKFiT in patients with severe hemophilia A, and provide an individualized treatment plan for patients.@*METHODS@#A total of 42 patients with severe hemophilia A who were treated with recombinant human coagulation factor Ⅷ were included from January 2021 to December 2021. myPKFiT was used to calculate the pharmacokinetic parameters of FⅧ, and the individualized treatment plan for hemophilia A patients was formulated.@*RESULTS@#The median age of 42 patients with severe hemophilia A was 31（16-50） years old, the average weight was 54.0±9.9 kg, the half-life of FⅧ was 12.05±1.6 h, the time to more than 1% of the baseline was 62.3±15.3 h, and the 0 bleeding rate after the guidance of myPKFiT was significantly increased from 39% to 49%, the Annual bleeding rate was reduced from 3.6±2.5 to 2.1±2.0, and the Annual joint bleeding rate was reduced from 3.2±2.2 to 1.9±0.9, all of which were statistically different (P<0.05).@*CONCLUSION@#Individualized therapy in patients with severe hemophilia A who were guided by myPKFiT assay of pharmacokinetics parameters can significantly reduce the annual bleeding rate and annual joint bleeding rate of patients.

Atypical Lymphocytosis:Report of Two Cases and Literature Review / 中国医学科学院学报

To improve the diagnosis of atypical lymphocytes and reduce the misdiagnosis rate,we analyzed the medical records of 2 cases with cell morphology suggestive of atypical lymphocytes.One case was diagnosed with infectious mononucleosis and the other with aggressive NK cell leukemia.The purpose of this paper is to emphasize that the diagnosis of atypical lymphocytes based only on morphological interpretation of cells may be incorrect,which should be combined with clinical symptoms,signs,imaging examination,cell immunophenotype,and disease outcome.

Treatment and Prognosis of Adult T Cell Acute Lymphoblastic Leukemia / 中国医学科学院学报

To analyze the treatment and prognosis of T cell acute lymphoblastic leukemia(T-ALL)in adults. Method The clinicobiogical and survival data of 68 adult patients with newly diagnosis T-ALL were retrospectively analzyed. Results The median age of these 68 patients was 23 years(14-60 years).T-ALL was more common in men(81%).After the first cycle of treatment,complete remission was achieved in 50 patients(73%).The highest complete remission(CR) rate was in patients with cortex T-ALL(100%),followed by other T-ALL(73%)and early T-cell precursor lymphoblastic leukemia(54%),(=5.712,=0.058).The CR rate for adults aged >35 years was significantly lower than that of patients aged ≤ 35 years(40% 79%,=6.364,=0.012).The overall CR rate after the second treatment course was 93%.For patients treated with chemotherapy,autograft hematopoietic stem cell transplantation(auto-SCT),and allogeneic SCT,the median relapse free survival was 10 months,24 months,and not reached,respectively(=0.002).The 5-year overall survival rate was 25% for all patients;for patients treated with chemotherapy,auto-SCT and allogeneic SCT,the median overall survival was 24 months,34 months,and 30 months,respectively(=0.007),and the 5-year overall survival rate was 9%,33%,and 38%(=0.037).Multivariate analysis showed leukocyte count ≥100×10 /L was a risk factor for decreased relapse free survival(risk ratio 2.540,95%=1.058-6.099,=0.037). Conclusion Adult T-ALL patients have poor prognosis,which may be improved by SCT.

The prognostic significance of minimal residual disease detection after first induction treatment in adult acute lymphoblastic leukemia patients treated with autologous stem cell transplantation / 中华血液学杂志

Objective: To investigate the prognostic significance of detection of minimal residual disease after first induction treatment (MRD(1)) in adult acute lymphoblastic leukemia (ALL) patients treated with autologous stem cell transplantation (auto-HSCT). Methods: The clinical data of 87 ALL patients who underwent auto-HSCT during February 2006 to April 2017 with MRD(1) detection data by flow cytometry were analyzed retrospectively. The relationship between MRD(1) and relapse and survival of ALL patients after auto-HSCT was studied. Results: Of 87 patients, 26 (29.9%) were MRD(1) positive. The proportion of high-risk immunophenotype (pro-B, pro-T, pre-T, mature T) was significantly higher in MRD(1)-positive patients than that in MRD(1) negative patients (34.6% vs 14.5%, P=0.038). There was no significant difference between positive and negative MRD(1) patients at age, sex, lineage (T/B), immunophenotype (standard risk/high risk), high white blood cell count (B-ALL>30×10(9)/L or T-ALL>100×10(9)/L), high-risk chromosome/gene ratio, the time from first complete remission to transplantation and pre-treatment regimen. The 5-year overall survival (OS) and leukemia-free survival (LFS) in MRD(1) negative and positive patients were 72.7% vs 47.3% (P=0.004) and 75.7% vs 29.6% (P<0.001), respectively. Multivariate analysis showed that positive MRD(1) was an independent risk factor for OS (HR=3.007, 95% CI 1.256-7.200, P=0.013) , and positive MRD(1) and high-risk immunophenotype were risk factors for LFS (HR=3.986, 95% CI 1.813-8.764, P=0.001; HR=2.981, 95% CI 1.373-6.473, P=0.006) . Conclusions: Auto-HSCT could not reverse the poor prognosis of MRD(1) positive patients. Auto-HSCT treatment is optional for patients with MRD(1) negative and maintaining MRD(1) negative status during intensive therapy.

Expression and role of amyloid precrusor protein gene in acute myeloid leukemia / 中华血液学杂志

<p><b>OBJECTIVE</b>To investigate the expression of amyloid precursor protein (APP) gene in acute myeloid leukemia (AML) and its biological behaviour in AML cells.</p><p><b>METHODS</b>The expressions of APP mRNA in 85 AML and 20 nonmalignant hematological diseases patients (as control) were measured by real-time PCR. The expression of APP in AML cell lines was also examined by real-time PCR and Western blot and the results were compared with those in their original subtypes. Small interfering RNAs (siRNAs) targeting APP gene were synthesized and transfected into HL-60 cell by lipofectamine 2000 for 24 h, 48h and 72 h. Cell growth was measured by trypan blue dye exclusion and MTT, differentiation by Wright-Giemsa staining, cell cycle by PI/RNase staining, apoptosis by Annexin V/PI and Hoechst33342 staining. Apoptosis-related protein NF-κB, bcl-2 and Caspase-3 were detected by Western blot after siRNAs transfection for 48 h. Sensitivity to adriamycin was measured by MTT.</p><p><b>RESULTS</b>The expression of APP mRNA among AML subtypes differed significantly (P = 0.019), the highest expression subtype was M(2) with t(8;21) (median 0.1080), followed in order by AML-undefined (0.0467), M(3) (0.0266), M(2a) (0.0221), M(4a) (0.0167), M(5b) (0.0151), and M(4b) (0.0025). APP expression had no significant effect on AML clinical characteristics excepting for subtypes. The expression of APP in Kasumi-1 cells was significantly higher than that of U937 cells (P < 0.05), which was in agreement with APP expression in their original AML subtypes. After siRNAs transfection for 24 h, 48 h, and 72 h, no significant difference in proliferation, differentiation, apoptosis, cell cycle and sensitivity to adriamycin was detected between interfering group and control groups (P > 0.05).</p><p><b>CONCLUSIONS</b>The APP mRNA expression was highest in M(2) with t(8;21) and lowest in M(5b). Down-regulation of APP expression has no significant effects on biological behaviour of HL-60 cells.</p>