Aluminum adjuvants (Alum), approved by the US Food and Drug Administration, have been extensively used in vaccines containing recombinant antigens, subunits of pathogens, or toxins for almost a century. While Alums typically elicit strong humoral immune responses, their ability to induce cellular and mucosal immunity is limited. As an alternative, layered double hydroxide (LDH), a widely used antacid, has emerged as a novel class of potent nano-aluminum adjuvants (NanoAlum), demonstrating advantageous physicochemical properties, biocompatibility and adjuvanticity in both humoral and cellular immune responses. In this review, we summarize and compare the advantages and disadvantages of Alum and NanoAlum in these properties and their performance as adjuvants. Moreover, we propose the key features for ideal adjuvants and demonstrate that LDH NanoAlum is a promising candidate by summarizing its current progress in immunotherapeutic cancer treatments. Finally, we conclude the review by offering our integrated perspectives about the remaining challenges and future directions for NanoAlum's application in preclinical/clinical settings.

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%.

OBJECTIVETo clarify the clinical, cytogenetical and molecular characteristics and prognosis of Ph(+) ALL patients with ABL kinase domain mutations (ABL-KDMs), and to evaluate the therapeutic value of allogeneic hematopoietic stem cell transplantation (allo-HSCT) combined with tyrosine kinase inhibitor (TKI) in these patients.

METHODSRetrospective analysis of clinical features, molecular genetic characteristics, mutation distribution and prognosis of newly diagnosed Ph(+) ALL patients with ABL-KDMs from February 2010 to August 2014 were performed, and the efficacy of treatment regimen of allo-HSCT combined with different TKIs was compared.

RESULTSOf 88 Ph(+) ALL patients during maintenance treatment stage for ABL-KDMs monitoring, mutation was detected in 42 patients with median time of 8 months from diagnosis to mutation occurrence. The median age of mutation group was 40-year-old, older than that of non-mutation group (32.5-year-old) (P=0.023). The incidence of complex chromosome abnormality of mutation group was higher than that of non-mutation group (P=0.043), with alternations in chromosome 7, 5 and +Ph more frequently observed. There were 21 types of mutation at 18 locations detected, with T315I mutation ranking the top followed by E255K/V, Y253H/F and E459K. Mutation group featured no significant difference in complete remission (CR) rate in contrast to nonmutation group, but was remarkably lower in major molecular remission (MMR) rate than non-mutation group. The 2 year and 5 year overall survival rate of mutation group was 45.4% and 35.0% respectively, much shorter than that of non-mutation group (67.8% and 63.3%), (P=0.047). The median survival of patients with T315I and E255K/V was 19 and 10 months, significantly shorter than that of patients with other mutations. Among the 42 patients with mutations, 14 underwent allo-HSCT, and the median survival was 29 months, longer than that of patients received chemotherapy alone (17 months) (P=0.024). Fourteen allo-HSCT patients were given nilotinib or dasatinib at the time of mutation occurrence, and there was no significant difference in the overall survival in contrast to patients who continue to take imatinib.

CONCLUSIONSABL kinase domain mutations are closely related to the older age and high genomic instability in the newly diagnosed Ph(+) ALL patients. Mutation types showed diversity and complexity, which remarkably affected patients' prognosis and survival. T315I and E255K mutations account for more than half of all cases, characterized by a less favorable prognosis. Currently, allo-HSCT is the only method that has the potential of elongating life expectancy, but the utility of second-generation TKI during relapse does not necessarily have an edge on survival over imatinib.

Chromosome Aberrations ; Dasatinib ; therapeutic use ; Hematopoietic Stem Cell Transplantation ; Humans ; Imatinib Mesylate ; therapeutic use ; Mutation ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; drug therapy ; genetics ; Prognosis ; Protein Kinase Inhibitors ; therapeutic use ; Proto-Oncogene Proteins c-abl ; genetics ; Pyrimidines ; therapeutic use ; Remission Induction ; Retrospective Studies ; Survival Rate

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.

OBJECTIVETo study clinical characteristics of refractory or relapsed DNMT3A⁺ cytogenetically normal acute myeloid leukemia（CN-AML）patients, and to explore the overall response rate（ORR）and side effects of these patients followed the therapy including decitabine with CAG or CAGlike regimen.

METHODSIn this study we retrospectively analyzed 53 refractory or relapsed CN- AML patients receiving the therapy including decitabine combined with CAG and CAG- like regimen in our center from April 2011 to October 2014. The clinical characteristics and ORR were further analyzed. Based on gene mutations, these patients could be divided into 2 groups: DNMT3A⁺ AML patients（n=24）and DNMT3A- AML patients（n=29）.

RESULTSThe median age of DNMT3A⁺AML patients was 46 years old, higher white blood cells and bone marrow blasts were observed in DNMT3A+ AML group. The ORR and complete response（CR）rate of DNMT3A+ group were 62.50% and 54.17%, respectively. No differences were observed in ORR and CR rates（P>0.05）between these two groups. DNMT3A⁺/FLT3-ITD⁺ CN-AML patients（n=14）had higher ORR and CR rates than DNMT3A-/FLT3-ITD⁺CN- AML patients（n=15）（P= 0.040 and 0.042, respectively）. The one- year overall survival （OS） of DNMT3A⁺ AML group and DNMT3A- AML group were 59.58% , 54.09% , no differences were observed （P=0.438）. 25 patients received further therapy of allo-HSCT, the one-year OS of DNMT3A⁺ CN-AML was 87.50% and one-year disease free survival（DFS）was 72.73%, while the one- year OS was 61.54% and one- year DFS was 58.02% in DNMT3A⁻ group. No differences were observed between 2 groups （P=0.456, 0.217）.

CONCLUSIONDecitabine combined with CAG or CAG-like regimen was an effective and safe treatment for refractory or relapsed CN- AML patients. Compared to DNMT3A⁻/FLT3- ITD⁺ CN- AML patients, DNMT3A⁺/ FLT3-ITD⁺ CN-AML patients had higher ORR and CR rates. Decitabine bridged hematopoietic stem cells transplant could likely improve the survival of refractory or relapsed CN-AML patients.

Aclarubicin ; therapeutic use ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Azacitidine ; analogs & derivatives ; therapeutic use ; Cytarabine ; therapeutic use ; DNA (Cytosine-5-)-Methyltransferases ; genetics ; Disease-Free Survival ; Granulocyte Colony-Stimulating Factor ; therapeutic use ; Humans ; Leukemia, Myeloid, Acute ; genetics ; therapy ; Mutation ; Remission Induction ; Retrospective Studies

Adolescent ; Adult ; Aged ; Female ; Fusion Proteins, bcr-abl ; genetics ; Humans ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; genetics ; therapy ; Male ; Middle Aged ; Mutation ; Pilot Projects ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; genetics ; therapy ; Retrospective Studies