Currently refractory and relapsed acute leukemia (AL) continues to develop a poor prognosis,and the treatment remains a significant clinical challenge.The use of priming regimen including granulocyte colony-stimulating factor(G-CSF) in clinic provides a novel method for the treatment of refractory and relapsed AL.This review summarizes the mechanism,method and efficiency of priming regimen in the treatment of all kinds of refractory and relapsed AL.

Objective To investigate the expression levels of TAK1 and p38 genes among different subtypes of acute myeloid leukemia (AML) patients,and to analyze the clinical characteristics of patients with different expression levels of TAK1 and p38 genes.Methods GAPDH was made as an internal reference,14 healthy people as control group.The quantitative real-time PCR was used to detect the expression of TAK1 and p38 in bone marrow samples of 87 AML patients,and the results were analyzed statistically.Results The expression levels of TAK1 and p38 in experiment group were higher than those in control group (0.194± 0.125 vs 0.015±0.008,0.233±0.140 vs 0.010±0.005,P ＜ 0.001).TAK1 expression in M4 was higher than that in M2,M3 and M5 (P =0.005,0.000,0.002),TAK1 expression in M3 was lower than that in M2 (P =0.022).p38 expression in M4 was higher than that in M1,M2,M3 and M5 (P =0.013,0.035,0.000,0.045),as it was higher in M2 and M5 than that in M3 (P =0.001,0.012).The CD56 positive rate cells and the number of peripheral blood leukocytes of the TAK1 high expression group were higher than those of the TAK1 low expression group,the CD19 positive rate of the p38 low expression group was higher than that of the p38 high expression group.Conclusion The expression levels of TAK1 and p38 genes are elevated in AML patients,and the up-regulation may play an important role in the pathogenesis of AML.

Objective To investigate the chromosome karyotype of acute lymphocytic leukemia (ALL) and its correlation with the clinical feature and efficacy.Methods The chromosomes of bone marrow/peripheral blood from 110 cases of patients with ALL were prepared after 24 hours culture,and G-banding were used to analyze karyotypes.Results Among 110 patients with ALL,71 cases (64.5 ％) had clonal chromsomal normalities,39 cases (35.5 ％) had clonal chromsomal abnormalities,24 cases (21.8 ％) had chromosome structural abnormalities,11 cases (10.0 ％) had chromosome number abnormalities,3 cases (2.7 ％) had chromosome number and structure abnormalities,one case had chromosomal abnormalities complex karyotype.Efficacy in patients with ALL with t(9;22) (q34;q11) was worse than the other patients (Fisher s exact text,P =0.045).There was no significant difference on efficacy between in adult ALL associated with t(9;22) (q34;q11) and in children with ALL (Fisher's exact text,P =0.506).Conclusion Chromosome karyotype of ALL patients is random,chromosomal translocations such as t(9;22)(q34;q1 1) and t(4;11) (q21;q23) have poorer treatment outcomes.

Objective To investigate the clinical significance of I-FISH for detection of genomic abnormalities in MM. Methods Twenty newly diagnosed MM patients(seven cases at stage Ⅰ , five cases at stage Ⅱ and eight cases at stage Ⅲ according to Bataille staging) were analyzed by combining the technique of CC (R-binding stain) and I-FISH [ including GLP13q14 (RBI gene), GLP17p13. 1 (P53 gene),GLP13q14. 3(D13S319) ,GLP1q21 ,GLP14q32(IgH gene) DNA sequence probes]. These two methods were compared for the detection rates of chromosomal and genomic abnormalities in MM and the association between genomic abnormalities and Bataille stages was also analyzed. Results CC examination showed only 1 case [5% (1/20) ] was found complex chromosomal abnormalities--46,XX,-2,del(3) (p21) ,add(6)(q26) ,der(10)(q26),der(14)(q32), + mar, inc[6]. While I-FISH assay showed that 12 cases [60%(12/20) ] were found genomic abnormalities. The frequencies of RB1, D13S319 and P53 were all 30%(6/20), and the frequencies of IgH gene and 1q21 were both 20% (4/20). The detection rate of the I-FISH was much higher than CC (χ2 = 9. 09, P = 0. 001) according to paired χ2 test. Of 20 patients,6 cases had RB1 gene abnormality, 1 case at stage Ⅰ , 2 cases at stage Ⅱ and 4 cases at stage Ⅲ. Of 20 patients, 6 cases had D13S319 gene abnormality, 2 cases at stage Ⅰ , 1 case at stage Ⅱ and 3 cases at stage Ⅲ. Of 20 patients, 6 cases in 20 had P53 gene abnormality, 2 cases at stage Ⅰ and 4 cases at stage Ⅲ. Of 20 patients, 4 cases had 1q21 gene abnormality, 2 cases at stage Ⅰ and 2 cases at stage Ⅲ. Of 20 patients, 4 cases had IGH gene abnormality, 1 case at stage Ⅰ and 3 cases at stage Ⅲ. Conclusion Ⅰ-FISH has higher detection rate for the genomic abnormalities in MM and can be used in detection of MM patients in different Bataille stages.

Objective To observe the effectiveness and side-effect of two cases of relapsed and refractory T-cell lymphoma (TCL) treated with thalidomide and interferon.Methods Two cases of relapsed and refractory TCL was treated with thalidomide and interferon, the efficacy and side-effect were observed, and the relevant literature was reviewed.Results The patients achieved partially remission after being treated with thalidomide and interferon.Conclusion Thalidomide in combination with interferon can be used as a second line therapy for relapsed and refractory TCL.

Objective To improve the cognition of sever liver injury of treating Philadelphia positive acute lymphoblastic leukemia (Ph+ ALL) with salvage chemotherapy of dasatinib combined with high-dose methotrexate (HD-MTX) and L-asparaginase (L-Asp).Methods Severe drug-induced liver injury caused by dasatinib with HD-MTX and L-Asp in one patient with Ph+ ALL was reported.Results Severe drug-induced liver injury happened on the seventh day after treatment,TBIL 221.7 μmol/L,DBIL 156.1 μmol/L,IBIL 65.6 μmol/L,ALT 111 U/L,AST 131 U/L,ALP 354 U/L,GGT 256 U/L,TBA 199.2 μmol/L.Through proper treatment,the patient recovered quite good,and the patient achieved complete remission after this chemotherapy.Conclusion Salvage chemotherapy which contains dasatinib,MTX and L-Asp can be effectively used in Ph+ ALL,but they are all of the hepatotoxicity,so drug-induced Liver injury may happen while they are used together.

The objectives of this study are as follows:1) to explore the expression level of alpha hydroxybutyric acid dehydrogenase (α-HBDH) in patients with non-Hodgkin's lymphoma (NHL) and its prognostic significance;and 2) to analyze the relationship amongα-HBDH, lactate dehydrogenase (LDH), and beta 2-microglobulin (β2-MG), so as to evaluate their diagnostic and prognostic sig-nificance. Methods:The expression levels of serumα-HBDH, LDH, andβ2-MG were examined in 104 patients with NHL before and after treatment. The relations among the levels of serum LDH,α-HBDH, andβ2-MG, as well as their connection with the patients' age, gender, disease stage, and pathological type, were explored. Results:Serumα-HBDH level increased in 35%of the patients and showed a significant correlation with LDH andβ2-MG. Significant differences were observed forα-HBDH andβ2-MG at different stages but not for LDH. Significant differences were observed betweenα-HBDH and LDH for different pathological types, but none was found inβ2-MG. The three serum enzymes did not exhibit any significant difference for different ages and genders. Levels of serum LDH andα-HBDH showed considerable difference between pre-treatment and post-treatment of patients. Serumβ2-MG level did not show any significant change after two or three cycles of chemotherapy. Conclusion:The expression level of serumα-HBDH increases in patients with NHL, is positively correlated with the levels of LDH andβ2-MG, and is highly relevant to disease stage and pathological type, regardless of the patients' age and gender. Serumα-HBDH is expected to be a new NHL indicator for tumor load, disease severity, and prognosis.

Objective To observe the clinical response and safety of second-generation tyrosine kinase inhibitor dasatinib in the treatment of Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph + ALL). Methods The clinical data of 10 adult Ph + ALL patients treated with dasatinib were analyzed with review of literatures. Results All the 10 Ph+ ALL patients treated with dasatinib achieved remission in 7 weeks, including 9 cases of complete remission [7 cases achieved complete molecular remission (CRm) in 13 weeks]. The median overall survival time (OS) was 13.8 months (5-33), and the median disease-free survival (DFS) time was 10.8 months (4-25). There were 3 cases of pleural effusion, 4 cases of Ⅳ degree of bone marrow suppression and 6 cases of extremely low blood platelet, which could be that was improved via by symptomatic treatment and, with no case of the death occurred during the treatment of dasatinib, the safety was high. Conclusion Dasatinib can deepen molecular biological reaction and prolonged the survival time of patients in the treatment of adult Ph+ ALL, with high remission rate and safety, and which can be considered as first-line treatment.

To retrospectively analyze the safety and efficacy of low dose subcutaneous decitabine regimen in patients with acute myeloid leukemia (AML) and intermediate-or higer-risk myelodysplastic syndrome (MDS).Of 6 AML cases,2 achieved complete remission (CR),2 with partial remission(PR),1 with stable disease(SD),1 with progressive disease(PD).As to the 8 MDS patients,one achieved CR and 6 with hematologic improvement (HI),1 case SD.Low dose subcutaneous decitabine regimen could be an alternative choice of older AML or MDS patients.

OBJECTIVE: To explore the clinical characteristics and prognostic values of TP53 gene variant in patients with acute leukemia(AL). METHODS: The clinical data of 44 newly diagnosed AL patients with TP53 variant detected by next generation sequencing (NGS) were analyzed retrospectively. Targeted sequencing technique containing 108 leukemia-related genes was used for variant analysis, and conventional R-banding technique was used for karyotype analysis. The clinical features, cytogenetics, gene variant, curative effect and survival of AL patients with TP53 gene variant were analyzed. RESULTS: The median age of AML patients with TP53 gene variant (46 years) was higher than that of ALL patients (17.5 years), and the median number of bone marrow blasts (40.5%) was lower than the latter (89.2%), the differences were statistically significant (P< 0.01). A total of 28 cases of abnormal karyotype were detected, of which 25 cases were complex karyotype, 16 cases were monomeric karyotype, 14 cases had -17/17p-. The detection rates of TP53 in complex karyotype, monomeric karyotype and -17/17p- were 59.5%, 38.1% and 33.3%, respectively. Subgroup analysis showed that the detection rate of TP53 gene abnormalities in AML and ALL complex karyotypes was 73.1% and 40% respectively, the difference was statistically significant. A total of 41 TP53 gene variant types were found, and the median variant frequency was 43.58%. 75.6% variant was located in the DNA binding domain. The concomitant variant genes were mainly TET2 and IKZF1. Among 18 AML and 17 ALL patients who could be evaluated the curative effect, the CR rate of one course of treatment was 22.2% and 94.12% respectively, and the difference was statistically significant. The median RFS of 4 cases of AML with CR and 16 cases of ALL with CR were 174 and 246 days respectively, the difference was statistically insignificant. The median OS of AML and ALL was 20 and 375 days respectively, the difference was statistically significant. CONCLUSION The TP53 gene variant is associated with the complex karyotype of AML, but has no significant effect on ALL. The variant site of TP53 gene was mainly distributed in the DNA binding domain. The remission rate of AML with TP53 gene variant was lower than that of ALL. The prognosis of AL patients with TP53 gene variant is poor, so allogeneic hematopoietic stem cell transplantation should be performed as soon as possible to prolong the survival of the patients.
Acute Disease ; Humans ; Leukemia, Myeloid, Acute/genetics* ; Middle Aged ; Mutation ; Retrospective Studies ; Tumor Suppressor Protein p53/genetics*