[Efficacy and safefy of Polymyxin B treatment for neutropenic patients suffering from refractory Gram-negative bacterial bloodstream infection].

Objective: To assess the efficacy and safety of polymyxin B in neutropenic patients with hematologic disorders who had refractory gram-negative bacterial bloodstream infection. Methods: From August 2021 to July 2022, we retrospectively analyzed neutropenic patients with refractory gram-negative bacterial bloodstream infection who were treated with polymyxin B in the Department of Hematology of the First Affiliated Hospital of the Soochow University between August 2021 to July 2022. The cumulative response rate was then computed. Results: The study included 27 neutropenic patients with refractory gram-negative bacterial bloodstream infections. Polymyxin B therapy was effective in 22 of 27 patients. The median time between the onset of fever and the delivery of polymyxin B was 3 days [interquartile range (IQR) : 2-5]. The median duration of polymyxin B treatment was 7 days (IQR: 5-11). Polymyxin B therapy had a median antipyretic time of 37 h (IQR: 32-70). The incidence of acute renal dysfunction was 14.8% (four out of 27 cases), all classified as "injury" according to RIFLE criteria. The incidence of hyperpigmentation was 59.3%. Conclusion: Polymyxin B is a viable treatment option for granulocytopenia patients with refractory gram-negative bacterial bloodstream infections.

[CAR T-cell bridging to allo-HSCT for relapsed/refractory B-cell acute lymphoblastic leukemia: the follow-up outcomes].

Objective: This study aims to investigate the efficacy and safety of chimeric antigen receptor (CAR) T-cell bridging allogeneic hematopoietic stem cell transplantation (allo-HSCT) in the treatment of recurrent and refractory acute B-lymphocytic leukemia (R/R B-ALL) . Methods: A total of 50 R/R B-ALL patients who underwent CAR T-scell therapy to bridge allo-HSCT in the First Affiliated Hospital of Soochow University from January 2017 to May 2019 were retrospectively analyzed. The overall survival (OS) rate, event-free survival (EFS) rate, cumulative recurrence rate (CIR) , and transplant-related mortality (TRM) of patients with different bone marrow minimal residual disease (MRD) levels were analyzed before and after CAR T-cell infusion and before allo-HSCT. Results: The response rate of CAR T-cell therapy and the incidence rate of severe cytokine release syndrome were 92% and 28% , respectively. During 55 infusions, no treatment-related deaths occurred in any of the patients. The median time of CAR T-cell infusion to allo-HSCT was 54 (26-232) days, the median follow-up time after CAR T-cell infusion was 637 (117-1097) days, and the 1-year OS and EFS rates were (80.0±5.7) % and (60.0±6.9) % . The 1-year CIR and TRM after allo-HSCT were (28.0±0.4) % and (8.0±0.2) % . After CAR T-cell infusion and before allo-HSCT, patients with bone marrow MRD<0.01% had a significantly longer EFS [ (70.0±7.2) % vs (20.0±12.6) % , P<0.001; (66.7±7.5) % vs (36.4±14.5) % , P=0.008]and lower CIR [ (25.0±0.5) % vs (70.0±2.6) % , P<0.001; (23.08±0.47) % vs (45.45±2.60) % , P=0.038]. Conclusion: CAR T-cell therapy bridging allo-HSCT is safe and effective for recurrent and refractory B-ALL.

[Analysis of early death factors and prognosis of acute promyelocytic leukemia].

Objective: To summarize the clinical characteristics of an early death in patients with de novo acute promyelocytic leukemia (APL) , analyze the risk factors and direct causes of early death, and perform survival analysis. Methods: The clinical data of 368 patients with de novo APL in three centers (First Affiliated Hospital of Soochow University, Soochow Guangci Hospital, and Soochow Hopes Hospital of Hematology) during January 2011-December 2017 were retrospectively analyzed. The clinical characteristics of patients who suffered hemorrhagic early death and non-hemorrhagic early death were compared. The risk factors for early death, survival, and prognosis of patients with APL were analyzed. Results: Among the 368 de novo APL patients, 31 died early with an early mortality rate of 8.4%. The median time from diagnosis to death was 7 (0-29) d. On comparison of the clinical characteristics of patients with early death and non-early death and subsequent multivariate analysis using a logistic regression model, it was observed that age ≥50 years and WBC ≥10×10(9)/L were independent risk factors for early death (P<0.01) . A total of 27 (87.1%) of the 31 early deaths was directly attributed to hemorrhage as the immediate cause of early death. Hemorrhage was the only cause of death in patients <50 years old and the major cause of death in patients ≥50 years old. A comparison of the clinical characteristics of patients with hemorrhagic early death and patients with non-hemorrhagic early death suggested that the median age and indirect bilirubin concentration of patients with hemorrhagic early death were lower than those with non-hemorrhagic early death (P<0.05) . The median follow-up time for all patients was 41.0 (0.3-101.4) months. The 2-year overall survival (OS) rate was (93.5±1.3) %, and the 5-year OS rate was (91.0±1.5) %. The 2-year disease-free survival (DFS) rate was (98.8±0.6) %, and the 5-year DFS rate was (97.1±0.9) %. The 2-year OS rate of patients ≥50 years old and patients <50 years old was 79.3% vs 94.2%, P=0.000; the 2-year DFS rate was 92.3% vs 98.1%, P=0.023. The respective 2-year OS rates of high-risk and non-high-risk patients were 77.3% and 96.7% (P=0.000) and the respective 2-year DFS rates were 94.0% and 98.4% (P=0.139) . Conclusion: Age and WBC are independent prognostic factors for early death. We observed a difference in early mortality between high-risk and low-risk APL, but no difference in DFS rate.

[Outcomes of allogeneic hematopoietic stem cell transplantation in patients with paroxysmal nocturnal hemoglobinuria compared to paroxysmal nocturnal hemoglobinuria-aplastic anemia syndrome].

Objective: To compare the outcomes of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for paroxysmal nocturnal hemoglobinuria (PNH) with paroxysmal nocturnal hemoglobinuria-aplastic anemia (PNH-AA) syndrome. Methods: The outcomes of 46 patients who received allo-HSCT (16 PNH patients, 30 PNH-AA patients) from July 10, 2007 to June 2, 2018 were analyzed retrospectively. The conditioning regimen was busulfan, cyclophosphoramide, and ATG in haploidentical donors and unrelated donors. Patients with matched sibling donors were treated with the fludarabine, cyclophosphamide, and ATG regimen. Results: There were no differences of baseline data between the 2 groups except gender distribution and the numbers of haploidentical donor transplantation. The median values of absolute nucleated cell counts were 10.58 (3.83-13.83) ×10(8)/kg in the PNH group and 10.81 (3.96-33.40) ×10(8)/kg in the PNH-AA group (P=0.668) . The median doses of CD34(+) cells infused were 5.00 (3.14-8.42) ×10(6)/kg and 3.57 (1.97-6.17) ×10(6)/kg (P=0.002) , respectively. All patients obtained complete engraftment. The median time for myeloid engraftment were 11 (7-14) days in the PNH group and 12 (10-26) days in the PNH-AA group (P=0.003) . The median time for platelet engraftment were 13 (11-16) days and 18 (12-75) days (P=0.002) , respectively, after a median follow-up of 36 (4-132) months in the PNH group and 26 (4-75) months in the PNH-AA group (P=0.428) . There were no differences of incidence rates of acute graft-versus-host disease (aGVHD) , chronic GVHD and infection between PNH and PNH-AA groups (P>0.05) . No patient occurred early death and relapse. The estimated 3-year overall survival (OS) of PNH and PNH-AA groups were (100.0±0.0) % and (85.7± 6.6) % (P=0.141) , GVHD-free and failure-free survival (GFFS) were (100.0±0.0) %, (78.7±7.7) % (P=0.067) . Conclusions: allo-HSCT is effective for patients with PNH and PNH-AA syndrome. The preliminary results indicate that myeloid and platelet engraftment in PNH group were faster than PNH-AA group. There were no differences in OS and GFFS between PNH group and PNH-AA group.

[Comparison of haploidentical hematopoietic stem cell transplantation and matched-sibling donor transplantation for the treatment of paroxysmal nocturnal hemoglobinuria].

Objective: To compare the outcomes between haploidentical donor hematopoietic stem cell transplantation (haplo-HSCT) and matched-sibling donor transplantation (MSD-HSCT) for paroxysmal nocturnal hemoglobinuria (PNH) . Methods: The clinical data of 40 PNH patients received HSCT (haplo-HSCT=25, MSD-HSCT=15) from July 2007 to May 2018 were analyzed retrospectively to compare the outcomes between haplo-HSCT and MSD-HSCT groups. Results: There were no differences in terms of gender, age, patients of PNH-AA and median time from diagnosis to transplantation between the 2 groups (P>0.05) . The median values of absolute mononuclear cell counts and CD34+ cells infused were 10.74 (4.80-22.86) ×108/kg and 12.19 (5.14-17.25) ×108/kg (P=0.866) , 3.57 (0.68-7.80) ×106/kg and 4.00 (3.02-8.42) ×106/kg (P=0.151) respectively, in haplo-HSCT and MSD-HSCT groups. All patients attained complete engraftment, no patient occurred graft failure. The median durations for myeloid and platelet engraftment were 12 (range, 9-26) and 11 (range, 7-15) days (P=0.065) , 19 (range, 11-75) and 13 (range, 11-25) days (P=0.027) respectively, in haplo-HSCT and MSD-HSCT groups. During a median follow-up of 26 (4-65) months in haplo-HSCT and 36 (4-132) months in MSD-HSCT groups (P=0.294) , the incidences of grade Ⅰ-Ⅳ acute graft-versus-host disease (aGVHD) were 32.0% and 20.0% (P=0.343) , grade Ⅱ-Ⅳ aGVHD were 16.0%, 13.3% (P=0.759) , chronic GVHD were 30.7% and 24.6% (P=0.418) , moderate-severe chronic GVHD were 12.7% and 7.1% (P=0.522) respectively, in haplo-HSCT and MSD-HSCT groups. The incidences of infection were 32.0% (8/25) and 26.7% (4/15) (P=1.000) respectively, in haplo-HSCT and MSD-HSCT groups. No patients occurred early death and relapse. Three-year estimated overall survival (OS) were (86.5±7.3) % and (93.3 ±6.4) % (P=0.520) , GVHD-free and failure-free survival (GFFS) were (78.3±8.6) % and (92.9±6.9) % (P=0.250) respectively, in haplo-HSCT and MSD-HSCT groups. Conclusion: The preliminary results indicated that haplo-HSCT was a feasible choice for PNH with favorable outcomes, haplo-HSCT and MSD-HSCT produced similar therapeutic efficacy.

[Outcome of combination of HLA-haploidentical hematopoietic SCT with an unrelated cord blood unit for 127 patients with acquired severe aplastic anemia].

Objective: To evaluate the outcome of combination of haploidentical donor (HID) hematopoietic stem cell transplantation (HSCT) with an unrelated cord blood unit for severe aplastic anemia (SAA). Methods: The clinical data of 127 SAA patients [including 74 male and 53 female patients, 65 very severe aplastic anemia (vSAA), the median age as 23.5(3-54) years] received HID-HSCT from September 2011 to April 2017 were analyzed retrospectively. The median interval from SAA diagnosis to transplantation was 2 (0.5-180) months. The conditioning was modified Bu/Cy+ATG/ALG-based (Busulfan + cyclophosphamide + antithymocyte immunoglobulin/antilymphocyte immunoglobulin) regimen. Cord blood units were selected based on the results of HLA typing and cell doses evaluated before freezing. Units with at least 4/6 matched HLA loci became the candidates. Prophylaxis for graft-versus host disease (GVHD) was by cyclosporine (CsA), mycophenolate mofetil (MMF) plus short-term methotrexate (MTX). Results: The median values of absolute nucleated cell counts were 10.87 (3.61-24.00)×10(8)/kg in the haploidentical grafts and 2.22 (1.10-7.30)×10(7)/kg in the cord blood units, respectively. The median doses of CD34(+) cells infused were 3.49(1.02-8.89) ×10(6)/kg in the haploidentical grafts and 0.56 (0.16-2.27) ×10(5)/kg in the cord blood units, respectively. Of the 127 patients, 5 patients occurred early death, one patient occurred primary graft failure. All 121 surviving patients attained complete haploidentical engraftment. The median durations of myeloid engraftment were 11 (9-28) days and 15 (9-330) days for platelets, with a cumulative platelet engraftment incidence of 96.1%. The incidence of infection was 58.27% (74/127). During a median follow-up of 20.5 (4-60) months, the incidence of grade Ⅱ-Ⅳ acute GVHD was 24.79% (30/121), moderate-severe chronic GVHD was 14.15% (15/106), 4-year estimated overall survival was (78.5±4.3) %, 4-year estimated failure-free survival was (77.4±4.3) %, respectively. Conclusion: Combination of HID-HSCT and an unrelated umbilical cord blood unit was a feasible choice with favorable outcome for SAA patients without matched donors.

[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].

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% (χ(2)=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% (χ(2)=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% (χ(2)=0.990, P=0.320) respectively; 20-monthes event-free survival (EFS) rates were 93.5% and 61.4% (χ(2)=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.

[Comparison of the efficacy of decitabine combined with micro-transplantation or priming regimen as consolidation treatment for older patients with acute myeloid leukemia].

Objective: To probe the feasibility of decitabine (DAC) combined with micro-transplantation as consolidation treatment for older patients with acute myeloid leukemia (AML). Methods: Between November 2012 and September 2015, 37 consecutive patients with AML ≥60 years of age were analyzed. Of them, 19 patients received consolidation therapy with DAC followed by micro-transplantation (microtransplant group). Another 18 ones (chemo group) were treated with DAC plus priming regimen as consolidation chemotherapy in the same period. Results: There were no significant differences in terms of age, WBC count, and disease status of onset between the microtransplant and chemo groups (P>0.05). The two regimens were well tolerated. There was no difference of CTC grade 3-4 nonhematologic toxicities between the microtransplant and chemo groups (36.8% vs 27.8%, χ(2)=0.347, P=0.728). The median recovery durations for neutrophil and platelet in the microtransplant group were similar to those in the chemo group (12 vs 13 days, z=1.599, P=0.110; 14 vs 12 days, z=-1.314, P=0.189, respectively). No graft-versus-host disease was observed in the microtransplant group. The 2-year leukemia-free survival and overall survival were better in microtransplant group (50.7% and 54.9%, respectively) than in chemo group (24.3% and 30.0%, respectively) (P=0.047 and P=0.071, respectively). Conclusion: DAC combined with micro-transplantation as a consolidation regimen may be a safe and promising option for older patients with AML.

Posaconazole vs. voriconazole in the prevention of invasive fungal diseases in patients with haematological malignancies: A retrospective study.

BACKGROUND: Posaconazole is superior to fluconazole or itraconazole in preventing invasive fungal diseases (IFDs) in patients with haematological malignancies; however, there have been reports of the comparing posaconazole and voriconazole. METHODS: This single-centre, retrospective study in China enrolled AML, ALL and MDS patients, among others. Prophylaxis with posaconazole or voriconazole was administered for patients recovering from neutropenia or who had achieved complete remission. The primary emphasis was proven, probable, or possible IFDs during treatment. The cost-effectiveness, the proportion of adverse events and systemic antifungal treatment were the secondary emphasis. RESULTS: A total of 164 patients were recruited to receive posaconazole (n=81) or voriconazole (n=83). The incidence rates of proven, probable or possible IFD were 2.46% (2/81) and 4.82% (4/83) in the posaconazole group and voriconazole groups, respectively (P>0.05). Only one patients experienced adverse events on posaconazole, while eleven patients experienced such events on voriconazole (P=0.003). Patients receiving posaconazole or voriconazole had similar proportions of systemic antifungal treatment: 18.52% (15/81) in the posaconazole group and 16.87% (14/83) in the voriconazole group (P>0.05). In the cost-effectiveness analysis, the prognosis of the two groups was close, but the drug acquisition costs of posaconazole were higher than those of voriconazole (P=0.021). CONCLUSION: Posaconazole and voriconazole have the same prophylactic effect against IFDs in high-risk neutropenic Chinese patients. However, the safety of posaconazole is superior to that of voriconazole, while in terms of cost-effectiveness, voriconazole has an advantage over posaconazole.

[Efficacy comparison of sequential treatment with first-line administration of second-generation and first-generation tyrosine kinase inhibitors in patients with Ph+ acute lymphoblastic leukemia followed by allogeneic hematopoietic stem cell transplantation].

Objective: To investigate the efficacy of sequential treatment with first-line administration of second-generation tyrosine kinase inhibitors (TKI) and first-generation TKI (imatinib) in patients with Ph+ acute lymphoblastic leukemia (Ph+ ALL) followed by allogeneic hematopoietic stem cell transplantation (allo-HSCT). Methods: Retrospective analysis of clinical features and prognosis of 76 newly diagnosed Ph +ALL patients from June 2011 to December 2015 treated by allo-HSCT combined with first-line administration of second-generation or first-generation TKI was performed and the efficacy compared. Results: Of 76 Ph+ ALL patients, first-generation TKI was administered in 57 cases, second-generation TKI in 19 cases, including 10 cases of nilotinib and 9 cases of dasatinib. There was no significant difference in age, WBC counts, additional chromosomal abnormalities, time form diagnosis to transplantation, transplantation type, conditioning regimen or TKI initiation time between the two groups. Complete remission (CR) rates at the fourth week of induction therapy in first-generation TKI group and second-generation TKI group was 93.0% and 94.7% (P=1.000), respectively. Major molecular response (MMR, BCR-ABL/ABL reduce 3 log) rates meanwhile were 46.0% and 40.0% (χ2=0.169, P=0.681). Relapse rates before transplantation were 14.0% and 10.5% (P=1.000). MMR rates before transplantation were 54.4% and 68.2% (χ2=1.152, P=0.283). The 2-year overall survival (OS) rates of first-generation and second-generation TKI group were 62.0% and 94.7% (χ2=5.765, P=0.016), 2-year event-free survival (EFS) rates were 46.3% and 84.2% (χ2=5.644, P=0.018), respectively. Univariate analysis showed that second-generation TKI could improve OS (HR=0.126, 95%CI 0.017-0.939, P=0.043). Multiple factors analysis showed that second-generation TKI (HR=0.267, 95%CI 0.081-0.873, P=0.029) and MMR before transplantation (HR=0.496, 95%CI 0.254-0.968, P=0.040) were good independent prognostic factors of EFS. Conclusions: There was significant difference in the efficacy of second-generation TKI and first-generation TKI for Ph+ ALL patients treated by allo-HSCT. First-line administration of second-generation TKI showed better efficacy than that of first-generation TKI for Ph+ ALL patients.

[An experimental study of CD4 targeted chimeric antigen receptor modified T cell with anti-lymphoma activity].

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.

[Allogeneic hematopoietic stem cell transplantation for the treatment of acute myeloid leukemia with primary thrombocytosis: three cases report and literatures review].

Objective: To investigate the characteristics of the essential thrombocythemia (ET) cases transformed to the acute myeloid leukemia (AML) and the role of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in the treatment of this disease. Methods: The clinical and laboratory characteristics of 3 ET cases before and after transformation and after allo-HSCT were retrospectively analyzed, meanwhile the related literatures were reviewed and discussed. Results: Case 1 was a male patient of 44 years old, whose PLT was 500×10(9)/L when firstly diagnosed ET. After 3 years the disease progressed into myelodysplastic syndrome (MDS) while WT1 expression increased from 77 (first visit) to 13 171 copies/10 000 ABL copies, at the same time chromosome changed dramatically. During the period of decitabine treatment the disease processed into AML. Case 2 was a male of 58 years old whose PLT was 2 100×10(9)/L when firstly diagnosed ET. The disease progressed to AML after 9 years, whose WT1 expression increased from 130 (first visit) to 3 222 copies/10 000 ABL copies, and he relapsed shortly after intensive chemotherapy. Case 3 was a male of 60 years old whose PLT was 900×10(9)/L when firstly diagnosed ET. The disease progressed to AML after 5 years, whose WT1 increased from 56 (first visit) to3 696 copies/10 000 ABL copies. Moreover leukemia spread to central nervous system (CNS) during chemotherapy. Before allo-HSCT, cases 1 did not achieve remission; case 2 relapsed after a short time of remission and case 3 transferred to CNS leukemia. All of the 3 cases underwent allo-HSCT successfully, and they all achieved completely remission, whose chromosome and gene mutation recovered negative. At the same time, CNS leukemia of case 3 disappeared. The median WT1 decreased to 50 copies/10 000 ABL copies. There was no severe complication during the median time of 5 months after allo-HSCT. Conclusions: The patients transformed to AML had poor prognosis, allo-HSCT was the only method that can cure the disease now.

[Distribution and drug resistance of pathogens at hematology department of Jiangsu Province from 2014 to 2015: results from a multicenter, retrospective study].

Objective: To describe the distribution and drug resistance of pathogens at hematology department of Jiangsu Province from 2014 to 2015 to provide reference for empirical anti-infection treatment. Methods: Pathogens were from hematology department of 26 tertiary hospitals in Jiangsu Province from 2014 to 2015. Antimicrobial susceptibility testing was carried out according to a unified protocol using Kirby-Bauer method or agar dilution method. Collection of drug susceptibility results and corresponding patient data were analyzed. Results: The separated pathogens amounted to 4 306. Gram-negative bacteria accounted for 64.26%, while the proportions of gram-positive bacteria and funguses were 26.99% and 8.75% respectively. Common gram-negative bacteria were Escherichia coli (20.48%) , Klebsiella pneumonia (15.40%) , Pseudomonas aeruginosa (8.50%) , Acinetobacter baumannii (5.04%) and Stenotropho-monas maltophilia (3.41%) respectively. CRE amounted to 123 (6.68%) . Common gram-positive bacteria were Staphylococcus aureus (4.92%) , Staphylococcus hominis (4.88%) and Staphylococcus epidermidis (4.71%) respectively. Candida albicans were the main fungus which accounted for 5.43%. The rates of Escherichia coli and Klebsiella pneumonia resistant to carbapenems were 3.5%-6.1% and 5.0%-6.3% respectively. The rates of Pseudomonas aeruginosa resistant to tobramycin and amikacin were 3.2% and 3.3% respectively. The resistant rates of Acinetobacter baumannii towards tobramycin and cefoperazone/sulbactam were both 19.2%. The rates of Stenotrophomonas maltophilia resistant to minocycline and sulfamethoxazole were 3.5% and 9.3% respectively. The rates of Staphylococcus aureus, Enterococcus faecium and Enterococcus faecalis resistant wards vancomycin were 0, 6.4% and 1.4% respectively; also, the rates of them resistant to linezolid were 1.2%, 0 and 1.6% respectively; in addition, the rates of them resistant to teicoplanin were 2.8%, 14.3% and 8.0% respectively. Furthermore, MRSA accounted for 39.15% (83/212) . Conclusions: Pathogens were mainly gram-negative bacteria. CRE accounted for 6.68%. The rates of Escherichia coli and Klebsiella pneumonia resistant to carbapenems were lower compared with other antibacterial agents. The rates of gram-positive bacteria resistant to vancomycin, linezolid and teicoplanin were still low. MRSA accounted for 39.15%.

[A retrospective analysis of prognosis in favorable-risk acute myeloid leukemia patients with different consolidation regimens].

Objective: To explore the impact on prognosis in favorable-risk acute myeloid leukemia (AML) patients with different consolidation regimens after first complete remission (CR(1)). Methods: A total of 107 cases of non-refractory adult AML from January 2010 to June 2015 in single center were enrolled in the study. HD-Ara-C group (38 cases) as the control group, we explore the prognosis in three consolidation regimens, including micro-transplantation (16 cases) , autologous transplantation (auto-PBSCT, 14 cases) , allogeneic transplantation (allo-HSCT, 39 cases). Results: Of 107 patients (59 males and 48 females) , with a median age of 33 (16-59) years old and a median follow-up of 36.5 (5.3-79.1) months, the overall relapse rate was 20.6% (22/107) , and overall mortality rate was 18.7% (20/107). The 5 years cumulative relapse rate (CIR) of HD-Ara-C, micro-transplantation, auto-PBSCT and allo-HSCT group were 39.7%, 6.2%, 14.3% and 5.6%, respectively (P<0.001). The CIR of the observed group was lower than the HD-Ara-C group. The 5 years progression-free survival (PFS) rate of HD-Ara-C, micro-transplantation, auto-PBSCT and allo-HSCT group were 44.7%, 93.8%, 85.7% and 78.1%, respectively (P=0.011). The PFS of observed groups were similar, but superior to that in HD-Ara-C group. The 5-year overall survival (OS) in four groups was 54.9%, 100%, 92.9% and 77.4%, respectively (P>0.05). Multiple factors analysis showed that compared to HD-Ara-C regimen, allo-HSCT could improve PFS (HR=0.376, P=0.031) , but not OS (P>0.05) ; micro-transplantation and auto-PBSCT could not improve the PFS or OS (P>0.05). Conclusion: As compared with HD-Ara-C regimen, allo-HSCT could obviously decrease CIR, improve PFS, but treatment-related mortality is high. These results show that auto-PBSCT and micro-transplantation have similar outcomes, compared to HD-Ara-C regimen, so both can be used as a option of consolidation treatment for favorable-risk AML.

[Clinical significance of JAK2、CALR and MPL gene mutations in 1 648 Philadelphia chromosome negative myeloproliferative neoplasms patients from a single center].

Objective: To explore the prevalences of JAK2, CALR and MPL gene mutations and the mutation types in patients with Philadelphia chromosome negative myeloproliferative neoplasms (MPNs) , and to compare their clinical characteristics of different mutation types with each other and mutation negative group. Methods: The mutations of JAK2 V617F, JAK2 gene at exon 12, CALR gene at exon 9 and MPL gene at exon 10 in 1 648 Ph negative MPNs patients were detected by direct sequencing. Results: ① The JAK2V617F mutation was found in 471 (92.7%) of 508 PV patients, 819 (78.1%) of 1 049 ET patients and 74 (81.3%) of 91 PMF patients respectively, with the total mutation rate as 82.8% (1 364/1 648) . The JAK2 exon12 mutation was found in 9 (1.7%) of 508 PV patients, none was found in ET or PMF patients, with the total mutation rate as 0.5% (9/1 648) . The CALR mutation was found in 132 (12.6%) of 1 049 ET patients and 11 (12.1%) of 91 PMF patients respectively, with the total mutation rate as 8.7% (143/1 648) ; the MPL mutation was found in 9 (0.9%) of 1 049 ET patients and 1 (1.1%) of 91 PMF patients respectively, with the total mutation rate as 0.6% (10/1 648) . The co-occurrence of any two types of driver gene mutations was not detected by direct sequencing. ②The median onset age of patients with JAK2V617F[61 (15-95) y] was significant higher than of with JAK2 exon12 mutation[49 (33-62) y] or without mutations[42 (3-78) y] (P<0.001) , but not for patients with CALR[57 (17-89) y] or MPL mutation[59 (22-71) y] (P>0.05) . Patients with JAK2V617F had higher white blood cell count and hemoglobin level (P<0.05) when compared with patients with CALR mutation or without mutations, or only significantly higher white blood cell count when compared with patients with MPL mutation (P=0.013) . The platelet count of patients with CALR mutation was significantly higher than of with JAK2V617F[966 (400-2 069) ×10(9)/L vs 800 (198-3 730) ×10(9)/L, P<0.001]. ③Karyotype analysis was conducted in 1 160 patients with MPNs, the rates of karyotype abnormality of patients with and without CALR mutation were 9.8% (8/82) and 7.4% (80/1 078) (P=0.441) respectively; The rates of karyotype abnormality of patients with and without JAK2V617F mutation were 7.7% (75/971) and 6.9% (13/189) (P=0.688) respectively. The incidence of karyotype abnormality of patients with CALR mutation was higher than of with JAK2V617F[9.8% (8/82) vs 7.7% (75/971) ] without statistically significant difference (P=0.512) . The karyotype analysis of 7 cases of JAK2 exon12 mutation and 6 ones with MPL gene mutation revealed normal karyotype. Conclusions: Driver gene mutations detection could ensure the diagnosis and prognosis judgment of MPN more reliable, different subtypes of MPNs had different profiles of driver gene mutations, the latter lead to unique clinical phenotype.

[Clinical analysis in a cohort of 102 patients with myelodysplastic syndrome characterized by erythroid hyperplasia].

Objective: To investigate the clinical and laboratorial characteristics of patients with myelodysplastic syndrome (MDS) and erythroid hyperplasia. Methods: MDS patients whose bone marrow was hypercellular with erythroid lineage more than 50% and blasts account for less than 20% of non-erythroid cells were enrolled in this study. The ratio of mature erythrocytes to nucleated erythrocytes was no more than 20, namely MDS patients with erythroid hyperplasia(MDS-E). The retrospective analysis comprised 102 patients with MDS-E from the First Affiliated Hospital of Suzhou University. Clinical characteristics, karyotype, and the prognostic significance of erythroid hyperplasia were evaluated. Results: A total of 48 MDS-E patients (47.1%) presented a variety of cytogenetic abnormalities. The most frequently involved chromosomes were chromosome 8 (39.5% of all abnormal karyotypes), chromosome 7 (22.9%), followed by chromosome 5 (18.8%), chromosome 1 (16.7%) and chromosome 20 (16.7%). Hemoglobin (Hb) level affected the prognosis by survival analysis. The overall survival (OS) of MDS-E patients with Hb equal or more than 70 g/L was longer than that of patients less than 70 g/L (P<0.001). Allogeneic hematopoietic stem cell transplantation (HSCT) significantly improved the OS compared with best supportive care (P<0.001) and chemotherapy (P<0.001). The extent of erythroid hyperplasia in bone marrow did not impact on prognosis (P=0.187). Conclusions: Compared with previous reports of MDS patients, MDS-E patients have higher level of erythroid hyperplasia, more common erythroid dyshematopoiesis, more frequent 8 and 1 chromosome abnormalities. The degree of erythroid hyperplasia is not correlated with prognosis. Allogeneic hematopoietic stem cell transplantation improves the prognosis.