Coagulation function changes after CD19-CAR-T cells immunotherapy for B-ALL and its related factors / 中华检验医学杂志

Objective:To investigate the changes of various cytokines and coagulation function in B cell acute lymphoblastic leukemia(ALL) patients with different CRS scores during CD19-CAR-T cell immunotherapy.Methods:87 patients with B-ALL hospitalized in the First Affiliated Hospital of Soochow University and 30 normal controls were enrolled into this study from July 2018 to October 2020. The age of the patients was 32(20, 56) years old and 36(41.4%) were female. All these coagulation indicators, prothrombin time (PT), activated partial thromboplastin time (APTT), D-dimer, fibrinogen (Fg) were analyzed by automatic blood coagulation in B-ALL patients before and after treated with CAR-T cell. The ratio of CD19-CAR-T cells and the expression of IL-6, IL-10, IFN-γ, TFN-α, IL-2, IL-4, and IL-17A were analyzed using flow cytometry. The patients′ clinical parameters were detected, and the CRS classification of severity was made according to the standard of consensus.Results:Patients with CRS>3 had prolonged PT and APTT, increased D-dimer, and decreased fibrinogen ( P<0.05). The levels of cytokines of IFN-γ, IL-6, and IL-10 were significantly higher in patients with CRS>3 than that in controls ( P<0.05).The D-dimer level is positively correlated with IL-10. Conclusion:Patients with severe CRS grading have significant coagulation dysfunction in CD19-CAR-T cell immunotherapy. Cytokines IFN-γ, IL-6, and IL-10 may affect coagulation function and CRS grading during CD19-CAR-T cell immunotherapy.

Salvage allogeneic hematopoietic stem cell transplantation under venetoclax bridging myeloablative preconditioning regimen for an acute myeloid leukemia patient with primary induction therapy failure / 白血病·淋巴瘤

Objective:To explore the application of venetoclax in transplantation of patients with refractory acute myeloid leukemia (AML).Methods:The diagnosis and treatment process of a patient with refractory AML who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) under venetoclax and hypomethylating agents bridging myeloablative preconditioning regimen after induction therapy failure in the First Affiliated Hospital of Soochow University in March 2020 were retrospectively analyzed.Results:The patient was a 28-year-old female who was diagnosed with refractory AML. The patient was initially given induction chemotherapy with IA (idarubicin+cytarabine) (3+7) regimen, but the disease did not relieve, then the induction chemotherapy with CLAG (cladribine+cytarabine+granulocyte colony stimulating factor) regimen was given, but the disease still did not relieve. After chemotherapy with venetoclax and hypomethylating agents bridging myeloablative preconditioning regimen, salvage haploid allo-HSCT was performed. Re-examination of bone marrow showed remission, and implantation was successful. The patient was followed up for 100 days and had sustained remission, and no transplantation complications occurred.Conclusion:For refractory AML patients who have failed primary induction therapy, the use of venetoclax and hypomethylating agents bridging myeloablative preconditioning regimen can be used as a preferred solution for salvage allo-HSCT.

Gene mutation and expression profiles in acute lymphoblastic leukemia based on the next-generation sequencing and their relationship with prognosis / 白血病·淋巴瘤

Objective:To investigate the gene mutation and expression profiles in patients with acute lymphoblastic leukemia (ALL) and the effect of gene mutations on the prognosis of patients.Methods:DNA samples from 128 newly diagnosed ALL patients in the First Affiliated Hospital of Soochow University from June 2016 to June 2017 were collected. The targeted specific next-generation sequencing technology was used to analyze 51 gene mutations related to hematological malignancies, and the occurrence spectrum was described. Because the gene mutation spectrum varied with the subtype of disease, the gene mutations involved 8 types of pathways including DNA methylation, chromosomal modification, transcriptional regulation, tumor suppression, signal transduction, RNA splicing, adhesive complexes and other pathways. The effects of clinical factors and gene mutations on overall survival (OS) and relapse-free survival (RFS) were analyzed by Kaplan-Meier method and Cox regression model.Results:Of the 128 patients, the results of next-generation sequencing showed that 86 patients (67.2%) harbored at least one mutation, and 27 patients (21.1%) harbored ≥3 mutations based on the next-generation sequencing. In all ALL patients, the genes with high mutation rates were JAK (10.9%, 14/128), NOTCH1 (10.1%, 13/128), KRAS (8.6%, 11/128), SETD2 (7.0%, 9/128), CSMD1 (7.0%, 9/128), ETV6 (7.0%, 9/128), and RUNX1 (7.0%, 9/128). In B-cell acute lymphoblastic leukemia (B-ALL) patients, the genes with high mutation rates were KRAS (9.4%, 10/106), CSMD1 (7.5%, 8/106), JAK (7.5%, 8/106), PTPN11 (6.6%, 7/106), SETD2 (5.7%, 6/106), TET2 (5.7%, 6/106), TP53 (5.7%, 6/106), and PAX5 (5.7%, 6/106). While in T-cell acute lymphoblastic leukemia (T-ALL) patients, the genes with high mutation rates were NOTCH1 (54.5%, 12/22), PHF6 (27.3%, 6/22), JAK (27.3%, 6/22), RUNX1 (22.7%, 5/22), and ETV6 (18.2%, 4/22). In 128 ALL patients, the total frequency of gene mutations was 181 times. Among them, signal transduction, transcriptional regulation, tumor suppression and chromosomal modification-related gene mutations occurred more frequently, and similar phenomena were found in T-ALL and B-ALL. In terms of clinical features, male patients were more likely to present gene co-mutations( P=0.002), and mutations involved in tumor suppressor pathways were also more common in male patients ( P=0.054). The older the patient, the greater the possibility of mutations involved in transcriptional regulation and DNA methylation regulatory pathway-related genes ( P=0.067, P=0.009). T-ALL was more susceptible to have gene mutations than B-ALL ( P=0.002), and easily had gene co-mutations ( P < 0.01), and mutations mainly involved in signal transduction, transcriptional regulation, tumor suppression and chromosome modification were dominant (all P < 0.05). Cox regression univariate analysis showed that younger age of onset and allogeneic hematopoietic stem cell transplantation could significantly prolong the OS time of ALL patients ( P=0.005, P=0.003), but the difference was not statistically significant on RFS (both P > 0.05). However, 8 types of regulatory pathways were irrelevant to OS and RFS in ALL patients (all P > 0.05). The ALL patients with JAK gene mutation had short OS time ( P=0.024). Conclusions:Gene mutations are prevalent in ALL patients, the frequency spectrum varies with the subtype of disease and involves a variety of signaling pathways. Among them, signal transduction, transcriptional regulation, tumor suppression and chromosomal modification pathway-related genes have high mutation rates. The co-occurrence of gene mutations is a frequently phenomenon in ALL patients and it indicates genetic complexity and instability of ALL patients. JAK family gene mutations usually indicate poor prognosis, but the effects of other gene mutations on the prognosis of ALL need to be further explored.

The clinical study of chronic graft-versus-host disease followinghaploidentical transplantation combined infusion with a third party cord blood / 中华器官移植杂志

Objective:To investigate the incidence, risk factors and survival of cGVHD patients in combination of a haploidentical donor supported with an unrelated umbilical cord blood for hematopoietic stem cells transplantation (haplo-cord-HSCT).Methods:300 hematological malignancies individuals who received dual transplantation were enrolled in the study between January 2012 and July 2016 at the department of Hematology in the First Affiliated Hospital of Soochow University. The clinical diagnosis and scoring the severity of cGVHD syndromes according the National Institutes of Health (NIH) consensus conference in the 2014 update. Cox proportional hazards regression was used to identify risk factors associated with transplant outcomes.Results:During follow-up with a median time of 26.4 months (range 0.2-61.8) post transplantation, the 1-year, 3-year and 5-year cumulative incidence of cGVHD was 26.3 % (95 % confidence interval [CI], 23.5 %~29.1 %), 30.3 % (95 % CI, 27.3 %~33.3 % ) and 32.2 % (95 % CI, 28.7 %~35.7 %). For all 73 patients with cGVHD, first-line or second-line treatment were given. During the follow-up period, 53 patients survived, and 20 patients died. In multivariate analysis, the cGVHD overall survival (GOS) were associated with thrombocytopenia(<100×109/L)(HR=0.103, 95 % CI 3 %-36.1 %, P<0.001). Conclusions:Our data suggest that, the 5-year cumulative incidence of cGVHD was 32.2 % after haplo-cord-HSCT with hematological malignancies. Thrombocytopenia (<100×109/L)was independent risk factors for GOS.

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.

Comparison of efficacy of first-line administration of generic dasatinib or imatinib in patients with Philadelphia chromosome positive acute lymphoblastic leukemia treated by hematopoietic stem cell transplantation / 中华血液学杂志

Objective@#To investigate the efficacy of first-line administration of generic dasatinib or first-generation TKI (imatinib) in patients with Philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ ALL) treated by hematopoietic stem cell transplantation (HSCT).@*Methods@#Clinical features and prognoses of 63 newly diagnosed Ph+ ALL patients from Jan 2014 to June 2017 treated by HSCT combined with first-line administration of generic dasatinib or imatinib were retrospective analyzed.@*Results@#Of 63 Ph+ ALL patients, 31 cases were administered generic dasatinib, and the other 32 ones imatinib. Complete remission (CR) rates at the fourth week of induction therapy in generic dasatinib and imatinib groups were 96.8% and 93.8% (P=1.000) , respectively. Meanwhile major molecular response (MMR; BCR-ABL/ABL reduce 3log) rates were 41.9% and 43.8% (χ2=0.021, P=0.884), respectively. Relapse rates before transplantation were 6.5% and 12.5% (P=0.672), respectively. MMR rates before HSCT were 83.9% and 68.8% (χ2=1.985, P=0.159), respectively. The 20-monthes overall survival (OS) rates of generic dasatinib and imatinib groups were 95.5% and 76.5% (χ2=0.990, P=0.320) respectively; 20-monthes event-free survival (EFS) rates were 93.5% and 61.4% (χ2=5.926, P=0.015), respectively. Statistically significant differences of EFS were reached. Multiple factors analysis showed that generic dasatinib (HR=0.201, 95% CI 0.045-0.896, P=0.035) and MMR before transplantation (HR=0.344, 95% CI 0.124-0.956, CI=0.041) could improve EFS.@*Conclusions@#First-line administration of generic dasatinib could improve EFS for Ph+ALL patients treated by HSCT when compered with imatinib.

Autoimmune hemolytic anemia after allogeneic hematopoietic stem cell transplantation: report of one case and review of literature / 白血病·淋巴瘤

Objective@#To summarize the clinical characteristics and treatment experiences of autoimmune hemolytic anemia (AIHA) after allogeneic hematopoietic stem cell transplantation (allo-HSCT).@*Methods@#The clinical data of the patient with AIHA after allogeneic HSCT in Hematology Department of the First Affiliated Hospital of Soochow University was analyzed, and the literatures were reviewed.@*Results@#After receiving 2 years of allo-HSCT, one young male patient with severe aplastic anemia showed AIHA in the absence of obvious incentives. The patient healed with the treatments of glucocorticoid, intravenous injection of gamma globulin, plasma exchange combined with injection of CD20 monoclonal antibody. Through the literature review, it showed that AIHA patients after HSCT had a good response to regimens containing rituximab, while adult and malignant patients with post-HSCT AIHA had a higher mortality. Poor response to rituximab was one of the greatest risk factors for poor prognosis.@*Conclusion@#AIHA is not sensitive to hormone with a low treatment response, which is a risk factor for the increased mortality of allo-HSCT patients.

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.

Anti-CD25 monoclonal antibody as a salvage therapy for steroid-refractory acute graft-versus-host disease in 80 patients receiving allogeneic hematopoietic stem cell transplantation / 中华内科杂志

Objective To investigate the efficacy of anti-CD25 monoclonal antibody for steroid-refractory acute graft-versus-host disease (SR-aGVHD) in allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients.Methods A total of 80 patients with SR-aGVHD from January 1st 2012 to December 31st 2016 were enrolled in this study.Acute GVHD were classified as classic aGVHD (n=72) and late-onset aGVHD (n=8).Anti-CD25 monoclonal antibodys (mAb) were administrated on days 1,4,8,15,and 22.The efficacy of anti-CD25 mAb was evaluated at day 28 after the initial treatment.The associated factors of clinical outcome were analyzed.Results The overall response (OR) rate of anti-CD25 mAb was 75％ (60/80),with complete response (CR) rate,partial response (PR) rate and no response(NR) rate 52.5％ (42/80),22.5％ (18/80),and 25％ (20/80),respectively.GVHD-relapse was not observed with a median follow-up time of 394.5 days (range,12-1 761 days).The 6-month overall survival (OS) rate was 68.4％ (95％CI 63.2％-73.6％).The 1-year OS rate was 63.1％ (95％CI 57.6％-68.6％),and 2-years OS rate was 50.7％ (95％CI 44.3％-57.1％).Non-relapse mortality (NRM) rate of 1 and 3 years was 32.6％ (95％CI 27.2％-38％) and 41.7％ (95％CI 35.3％-48.1％),respectively.The 1 and 2 years cumulative incidence of chronic graft versus host disease (cGVHD) was 32.9％ (95％CI 26.4％-39.4％) and 38.9％ (95％CI 31.8％-46.0％).By univariate and multivariate analysis,liver involvcment was an independent poor risk factor of SR-aGVHD (OR=4.66,95％ CI 1.145-18.962,P=0.032).Conclusion Anti-CD25 mAb serves as an alternative and effective salvage therapy for SR-aGVHD at present.Liver involvement is a predictive factor of poor response in patients with SR-aGVHD.

Clinical analysis of 7 patients with Epstein-Barr virus encephalitis after allogeneic hematopoietic stem cell transplantation / 中华血液学杂志

Objective@#To summarize the clinical features, treatment and prognosis of patients with Epstein Barr virus (EBV) encephalitis after allogeneic hematopoietic stem cell transplantation (allo-HSCT) .@*Methods@#The clinical data of 7 patients with EBV encephalitis who had undergone allo-HSCT in the First Affiliated Hospital of Soochow University from January 2012 to December 2015 were reviewed.@*Results@#The incidence of EBV encephalitis was 0.70% (7/998) , and the median time was 63 (10-136) d after allo-HSCT. Seven patients had fever and mental disorder, of whom 4 cases of brain MRI were positive. Two patients received HLA-matched unrelated transplantation, while other 5 ones received haploidentical allo-HSCT. In conditioning regimen process, 7 patients were combined with anti-thymocyte globulin (ATG) to prevent graft versus host disease (GVHD) , of whom 6 patients had grade Ⅱ-Ⅳ acute GVHD. All patients of EBV-DNA were negative in CSF after taking anti-virus agent Rituximab. Until the last follow-up, a total of 3 patients died, 2 died of leukemia recurrence, 1 EBV encephalitis progression.@*Conclusion@#Once suspected EBV encephalitis after allo-HSCT, brain MRI and EBV-DNA in CSF should be detected, which could improve early diagnosis of EBV encephalitis. The usage of Rituximab was effective and well tolerated.

Clinical risks analysis of EBV infection in patients with allogeneic hematopoietic stem cell transplantation / 中华血液学杂志

<p><b>OBJECTIVE</b>To analyze the prevalence of Epstein Barr Virus (EBV) infection in patients following allogeneic hematopoietic stem cell transplantation (allo-HSCT).</p><p><b>METHODS</b>The occurrence of EBV viremia, EBV disease and post-transplant lymphoproliferative disease (PTLD) were retrospectively analyzed in 736 patients received allo-HSCT in single-center from 1st January 2012 through July 31th, 2014.</p><p><b>RESULTS</b>Of 736 patients (302 male and 434 females) with a median age of 31 (2 to 62) years old, EBV infection occurred in 181 patients, the total incidence of EBV infection was 27.6%, with a median time of 57 (16 to 829) days. The cumulative incidences of probable EBV disease and PTLD were 7.2% (13/181) and 2.8% (5/181). Viral load higher than 1.0×10(4) copies/ml occurs in 130 patients, of which 67 patients received rituximab as pre-empty prophylaxis and significantly reduced the incidences of probable EBV disease and PTLD (6.0% vs 22.2%, P=0.009). The mortality was 27.6% in all patients with EBV infection: 24.5% in EBV viremia, 53.8% in probable EBV disease, and 60.6% in PTLD. By univariate and multivariate analysis, the use of anti-thymocyte globulin (ATG), HLA-mismatch HSCT, cGVHD and CMV reactivation were independent risk factors for EBV infection. The time of first EBV reactivation was closely related with cGVHD(OR=0.620, 95%CI 0.453-0.849, P=0.003) and bone marrow or cord blood (OR=1.156, 95%CI 1.022-2.250, P=0.039) as source of stem cells for transplantation.</p><p><b>CONCLUSION</b>EBV reactivation is a common complication in patients with allo-HSCT, especially high mortality in PTLD and probable EBV disease. The use of ATG, HLA-mismatch HSCT, cGVHD and CMV reactivation were independent risk factors for EBV infection. The usage of rituximab as pre-empty prophylaxis may reduce the incidences of probable EBV disease and PTLD.</p>

Frequency of c-kit mutation and prognosis in t(8;21) acute myeloid leukemia patients with trisomy 4 / 白血病·淋巴瘤

Objective To investigate the frequency of c-kit mutation and prognosis in t (8;21) acute myeloid leukemia (AML) patients with trisomy 4. Methods A total of 145 de novo t(8;21) AML patients from February 2005 to January 2013 were analyzed retrospectively. Detection of exons 8 and 17 mutation of c-kit by PCR and cytogenetic analysis by R-banding technologies were performed on bone marrow samples of all patients at diagnosis. Clinical data were collected and analyzed statistically. Results Among 145 t (8;21) AML patients, 12 cases (8.3 %) were trisomy 4, 91.7 % (11/12) of them were identified with c-kit mutation, which was significantly higher than that without trisomy 4 [26.3 % (35/133), P< 0.01]. The follow-up data showed that the patients with trisomy 4 were correlated with the lower overall survival (OS) rate (15 % vs 56 %, P< 0.01) and disease-free survival (DFS) rate (0 vs 51 %, P< 0.01) when compared with patients without trisomy 4. Furthermore, the subgroup of patients with both trisomy 4 and c-kit mutation had a worse OS and DFS (P< 0.05). Conclusions Trisomy 4 is associated with high frequency of c-kit mutation and demonstrates poor prognosis in t(8;21) AML patients. Trisomy 4 or it combined with c-kit gene mutation is the main influencing factor on the survival of the patients with t(8;21) AML.

Efficacy observation of hemocoagulase for the treatment of severe hemorrhagic cystitis following allogeneic hematopoietic stem cell transplantation / 白血病·淋巴瘤

Objective To investigate the clinical efficacy of hemocoagulase for severe hemorrhagic cystitis (HC) following allogeneic hemotopoietic stem cell transplantation (HSCT). Methods Twenty patients undergoing allogeneic HSCT developed severe HC with an onset time of 14 to 70 days, all patients received the treatment of hemocoagulase (1 U ivgtt q12 h × 5 d). The urine speciments reserved before and after hemocoagulase were examined by naked eye and microscope to evaluate the efficacy. Results Twenty patients received the treatment of hemocoagulase. The HC was cured in 18 patients, improved in 1 patient and uncontrolled in 1 patient. For the patients with response, macroscopic hematuria disappeared at a median of 28 days (4-127 days) after the treatment. All procedures were tolerated well and no severe adverse effect was observed. Conclusion Hemocoagulase seems to be a safe and effective drug for severe HC following HSCT.

Outcomes of allogeneic hematopoietic stem cell transplantation for 18 patients with paroxysmal nocturnal haemoglobinuria / 中华血液学杂志

<p><b>OBJECTIVE</b>To evaluate the outcomes of allogeneic hematopoietic stem cell transplantation（allo-HSCT）for paroxysmal nocturnal haemoglobinuria（PNH）and aplastic anemia（AA）- PNH syndrome.</p><p><b>METHODS</b>The clinical data of 18 PNH or AA-PNH patients, including 4 classic PNH and 14 AA-PNH, received allo-HSCT from Dec 2007 to Feb 2015 were analyzed retrospectively. Nine patients received HLA-haploidentical donor HSCT（1 patient received salvage HLA-haploidentical donor HSCT after the graft failure of double cord blood transplantation）, 7 patients received HLA-identical sibling donor HSCT, and 2 HLA-identical unrelated donor HSCT. The conditioning regimens were as follow: 13 patients received modified BU/CY- based regimens, 5 non- myeloablative regimens ［fludarabine （Flu） + antithymocyte globulin（ATG）+ cyclophosphamide（CY）or busulfan（BU）］. Prophylaxis for graft- versushost disease（GVHD）: the patients with HLA-identical sibling donor received cyclosporine（CsA）plus short-term methotrexate（MTX）, the patients with HLA -haploidentical donor or HLA-identical unrelated donor received CsA or tacrolimus（FK506）+ mycophenolate mofetil（MMF）+ short- term methotrexate （MTX）.</p><p><b>RESULTS</b>All patients were engrafted successfully（1 patient engrafted by haploidentical donor after the graft failure of double cord blood transplantation）. The median days of neutrophils（ANC）above 0.5 × 109/L and platelets （PLT） more than 20 × 10⁹/L were 11（10- 26）days and 15（11- 120）days, respectively. Three patients（17.6%）developed acute GVHD（aGVHD）, 2 for grade Ⅱ aGVHD, 1 for grade Ⅳ aGVHD. Of 16 patients, 2 occurred limited chronic GVHD（cGVHD）. After a median follow-up of 14.6（2.0-86.7）months, 3 patients（17.6%）died, out of which one died of severe aGVHD, one died of severe pulmonary infection, one pulmonary infection with transplant- associated thrombotic microangiopathy. The 5- year estimated disease free survival was（80.5 ± 10.2）%. No patient relapsed.</p><p><b>CONCLUSION</b>Allo-HSCT is an effective and curable therapy for PNH or AA-PNH with improved prognosis, and offers a valid therapeutic option for these patients before humanized monoclonal antibody against C5 are widely used clinically.</p>

Imatinib in combination with allogeneic hematopoietic stem cell transplantation improved the outcome of adult Philadelphia chromosome-positive acute lymphoblastic leukemia / 中华血液学杂志

<p><b>OBJECTIVE</b>To investigate the role of imatinib in induction therapy for newly diagnosed adult patients with Philadephia chromosome-positive acute lymphoblastic leukemia (Ph⁺ALL), as well as the status of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in the treatment of adult Ph⁺ ALL in imatinib era.</p><p><b>METHODS</b>Retrospectively analyzed 97 newly diagnosed adult Ph⁺ ALL patients from 2005 to 2013. According to whether administrated imatinib in the induction therapy and the administrating duration (≥3 d) , they were divided into imatinib (n=37) and non-imatinib group (n=60), and the former group was further divided into early-use (n=26) and late-use imatinib groups (n=11) (bounded by the fourteenth day of induction chemotherapy). We compared the overall response rate (ORR) and the negative rate of BCR-ABL fusion gene in patients who achieved complete remission (CR) or CR with incomplete recovery of blood cells (CRi) among the three groups at the end of the first induction therapy. There were 44 cases underwent allo-HSCT (transplant group) and 33 cases only adopted imatinib-based chemotherapy (non-transplant group) in 77 patients who administrated imatinib as a maintenance therapy, we further compared the incidences of overall survival (OS) , disease-free survival (DFS), relapse and nonrelapse mortality (NRM) between the two groups; and dynamically monitor polymerase chain reaction (PCR) negativity of patients who were in CR1 state before transplant (n=34) at the following timepoints of achieving CR or CRi, the first consolidation therapy, beginning the pretreatment of transplant and attaining hematopoietic reconstruction after transplant.</p><p><b>RESULTS</b>After the first induction therapy, the ORR of imatinib group was significantly higher than of non-imatinib group (97.3%, 72.9% respectively, P=0.002), but early-use and late-use imatinib groups had no statistical significance in ORR (100% , 90.9% respectively, P=0.297); the rate of negativity of imatinib and non- imatinib groups were 20.0% and 0 respectively (P=0.041) in patients who achieved CR or CRi. The negative rate of patients in CR1 state before transplant attained 20.8%, 42.3%, 51.8%, 76.8%, respectively at the previously described 4 timepoints. And the differences between the fourth and the third, the third and the first timepiont all reached statistical significance (P=0.044, 0.022, respectively). The 5-year OS of transplant and non- transplant groups showed statistical difference (47.0%, 28.0% respectively, P=0.016), also for 5-year DFS (P=0.001) and the cumulative rate of relapse (P=0.000) of the former surpassing the latter; the cumulative rate of NRM between these two groups had no statistical significance (P=0.370).</p><p><b>CONCLUSION</b>Conventional induction chemotherapy in combination with imatinib in the first induction therapy of adult Ph⁺ ALL, not only improved the rate of hematologic remission, also the rate of molecular response. Imatinib used as a consolidation and maintenance therapy after remission, and allo-HSCT scheduled as soon as possible improved the prognosis.</p>

One case of interdigitating dendritic cell sarcoma concurrent with acute myelomonocytic leukemia and literatures review / 白血病·淋巴瘤

Objective To summarize and learn the biological properties and clinical features of interdigitating dendritic cell sarcomas (IDCS).Methods The first IDCS patient concurrent with acute myelomonocytic leukemia (AML-M4) described herein,to our knowledge,was studied and 62 IDCS cases reported previously in the literature were reviewed.Results The patient had a history of breast cancer as well as radiotherapy and chemotherapy of it,and the patient showed poor response to 4 cycles of sequential chemocherapy regimens.Based on the laboratory results,IDCS and AML-M4 in this patient were both of myelogenous origination.Furthermore,review of the 62 IDCS patients reported previously showed that as high as 17 ％ of the patients had malignant disease and received radiotherapy or chemotherapy before they got IDCS,and patients of this group had worse prognosis compared with counterpart.Conclusion IDCS has poor prognosis,and therapy-related type worse.Prophylactic measures and stringent screening of the second cancer in those who received chemoterapy or radiotherapy are appropriated and necessary.

Genetic diagnosis of a patient with non-syndromic variants of congenital neutropenia / 中华内科杂志

ObjectiveTo explore the procedures and methods for genetic diagnosis in one nonsyndromic variants of congenital neutropenia (NSVCN) patient and its pathogenic mutation.Methods Genomic DNA was prepared from one NSVCN patient who had progressed to chronic myelomonocytic leukemia and ELA2,HAX1,WASp and GFI1 genes were amplified and sequenced.Results A novel compound heterogeneous mutation consisting of two frame-shift mutations (c.430-1insG and c.655- 9del5bp) was found in HAX1 gene.ConclusionA practically genetic diagnosis procedure for NSVCN has been established,and the novel HAX1 gene mutation may contribute to the etiology of NSVCN.

Chronic graft versus host disease related polymyositis:a case report and literature review / 中华器官移植杂志

Objective To summarize the diagnostic and therapeutic experience of a patient with chronic graft versus host disease (cGVHD) related polymyositis (PM) after allogeneic hematopoietic stem cell transplantation (allo-HSCT).Methods A patient with acute lymphocytic leukemia in com- plete remission received sibling allo-HSCT,and cyclosporine and methotrexate were adopted to pre- vent GVHD.Results Eleven days after HSCT,WBC＞0.5?10~9/L,13 days after HSCT,PLT＞20?10~9/L;27 days after HSCT,chromosome analysis of bone marrow cells showed 99% donor type. Seventeen days after HSCT,Ⅰ~0 acute GVHD of skin occurred,and it was cured by intravenous injec- tion of dexamethasone and methotrexate.Eight months after HSCT,cGVHD of liver happened.Al- though treated by tacrolimus and azathioprine,enzymes of liver were still elevated.At last,tacrolimus combined with sirolimus were used,and enzymes of liver subsided gradually.However,the serum creatine phosphokinase (CK) began to rise from 9 U/L to 3010 U/L,and fatigue all over the patient occurred.Finally,the symptom relapsed,and disability involved with the origin of limbs appeared. The electromyogram and magnetic resonance imaging of concerned muscles confirmed the PM diagno- sis.Although treated with methylprednisolone and plasma exchange,the patient died due to asphyxia, while the CK as high as 21 010 U/L.Conclusion PM is a rare kind of manifestations of cGVHD. When the key muscle tissue was involved,the prognosis is poor.

Inhibitory effect of recombinant endostatin on angiogenesis and tumor growth of hepatoma / 华中科技大学学报（医学）（英德文版）

To study the influence of recombinant endostatin on angiogenesis and tumor growth of mice H22 hepatoma, tumor models were constructed by injecting H22 hepatoma cells into the leg muscle of mice. Recombinant endostatin was produced by gene engineering in E. coli. The recombinant protein was injected subcutaneously to treat transplanted hepatoma faraway. The weight of tumors was measured, and the changes of necrosis of tumor cells and vessel density were observed by immunohistochemistry. The results suggested that the growth of hepatoma models transplanted in the muscle of legs was suppressed by recombinant endostatin. The density of vascularity was decreased, but the necrosis of tumor cells increased. The inhibitory effect of recombinant endostatin on angiogenesis and tumor growth of hepatoma was not affected after chemotherapy.