Humans ; Receptors, Chimeric Antigen/therapeutic use* ; DNA-Binding Proteins/genetics* ; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma ; Proto-Oncogene Proteins c-bcl-2/genetics* ; Cell- and Tissue-Based Therapy ; Oncogene Proteins, Fusion/genetics* ; Translocation, Genetic

OBJECTIVE: To assess the value of fluorescence in situ hybridization (FISH) technique for the verification of the clonalities of non-clonal cytogenetic abnormalities (n-CCA) identified by conventional chromosome banding analysis (CBA) in patients with Myelodysplastic syndrome (MDS). METHODS: Clinical data and results of karyotyping and FISH assays for 91 patients of MDS with n-CCA identified by CBA were retrospectively analyzed. In total 94 non-clonal +8, 5q-, -7/7q- or 20q- were detected by CBA, among which 43 (45.7%) were verified to be clonal abnormalities by FISH. RESULTS: The detection rates for +8, 5q-, -7/7q- and 20q- by FISH were 47.6% (30/63), 25% (2/8), 41.7% (5/12), 40% (2/5) and 66.7% (4/6), respectively, with the positive cells accounting for 4% to 90% of all counted cells, with a median value of 7%. The 91 patients were divided into three groups including ≥ 20, 10 ~< 20 and < 10 based on the numbers of metaphase cells in CBA, and the detection rates by FISH for the three groups were 43.7% (31/71), 33.3% (3/9) and 63.6% (7/11), respectively, which showed no statistically difference (P > 0.05). Continuous CBA and FISH surveys were conducted for 26 patients who received supportive treatment, and the results revealed that 91.7% (11/12) of FISH-verified positive abnormalities had persisted, whereas 92.9% (13/14) of the n-CCA verified as negative by FISH was transient. CONCLUSION Nearly half of the CBA identified n-CCA have been verified as clonal aberrations by FISH, and the FISH detection rate showed no correlation with the number of metaphase cells. FISH test is strongly recommended for verifying the clonalities of n-CCA detected by CBA, and continuous cytogenetic survey of the patients with MDS is necessary.
Humans ; In Situ Hybridization, Fluorescence ; Retrospective Studies ; Chromosome Aberrations ; Karyotyping ; Myelodysplastic Syndromes/genetics*

Humans ; Multiple Myeloma/genetics* ; Karyotyping ; Translocation, Genetic/genetics*

OBJECTIVE: To investigate the clinical and prognostic characteristics of primary acute myeloid leukemia (AML) with 11q23/KMT2A rearrangements. METHODS: Clinical data of 90 patients with primary AML and 11q23/KMT2A rearrangements were analyzed retrospectively. RESULTS: By karyotyping analysis, 80 of the 90 patients had translocations involving 11q23/KMT2A, with t(9;11)(p22;q23), t(6;11)(q27;q23), t(10;11)(p12;q23) and t(11;19)(q23;p13) being the most common ones, while 10 cases were found to have non-translocation abnormalities. The overall complete remission (CR) rate was 75.6%, and patients with t(6;11) had lower CR rate compared with non-t(6;11) patients (47.1% vs. 82.2%, P = 0.005). After a median follow-up of 24.5 months, the patients receiving allo-hematopoietic stem cell transplantation (allo-HSCT) had significantly higher 3-year overall survival (OS) (80.3% vs. 16.6%, P < 0.001) and 3-year event-free survival (EFS) (73.5% vs. 16.3%, P < 0.001) compared with non-transplant patients. Patients with t(6;11) had the lowest 3-year OS (11.8% vs. 56.0%, P < 0.001) and 3-year EFS (5.9% vs. 53.8%, P < 0.001) compared with other type of abnormalities. No significant difference was noted in the survival between patients with t(9;11) and non-t(9;11) regardless whether they had received HSCT. CONCLUSION The clinical characteristics of primary AML with 11q23/KMT2A rearrangements are heterogeneous. Patients did not receive HSCT had poorer survival, particularly with the presence of t(6;11). Allo-HSCT could significantly improve the survival of such patients.
Humans ; Retrospective Studies ; Leukemia, Myeloid, Acute/therapy* ; Translocation, Genetic ; Gene Rearrangement ; Prognosis

Objective:The study aims to explore the efficacy and safety of low-dose chemotherapy combined with tyrosine kinase inhibitor (TKI) as an induction therapy for Philadelphia-chromosomal-positive acute lymphoblastic leukemia (Ph + ALL) . Methods:The data of the consecutive newly diagnosed patients with Ph + ALL were reviewed. The efficacy and safety of low-dose chemotherapy and conventional-dose chemotherapy combined with TKI were compared. Results:A total of 217 patients with a median age of 38 (10-69) years old were included in this study. 78 patients were in the low-dose chemotherapy group, and 139 patients were in the conventional-dose chemotherapy group. There were no significant differences in the 4-week complete remission (CR) rate (98.7% vs 97.0%, P=0.766) and overall CR rate (100% vs 100%, P=1.000) between the two groups. Multivariate analyses showed that the chemotherapy intensity was not related to the disease-free survival rate and overall survival rate. However, the lower incidence of infection ( P=0.017) , the shorter duration of neutropenia ( P=0.001) and PLT<20 × 10 9/L ( P=0.057) , and the lower red blood cell transfusion volume ( P=0.002) were more common in the low-dose chemotherapy group than in the conventional-dose chemotherapy group. Conclusions:The low-dose chemotherapy is superior to the conventional-dose chemotherapy combined with TKI as induction therapy in Ph + ALL with similar efficacy but is safer.

Objective:To explore the clinical characteristics, treatment patterns, and outcomes in newly diagnosed patients with chronic myeloid leukemia in the chronic phase (CML-CP) by age.Methods:Clinical data of consecutive ≥14 years old newly diagnosed CML-CP patients were retrospectively analyzed.Results:This study included 957 patients. Of the patients, 597 (62.4%) were male. The median age was 40 years (range, 14-83 years) . The patients were stratified into three age groups: <40 years ( n=470; 49.1%) , 40-59 years ( n=371; 38.8%) , and ≥60 years ( n=116; 12.1%) . The proportions of the patients who had splenomegaly ( P<0.001) , WBC ≥100 × 10 9/L ( P<0.001) , anemia ( P<0.001) , PLT<450 × 10 9/L ( P=0.022) , more blasts in the blood ( P=0.010) , and clonal chromosome abnormalities in Philadelphia chromosome-positive cells ( P=0.006) at diagnosis significantly decreased with age. However, the proportions of those with comorbidities ( P<0.001) , intermediate or high Sokal risk ( P<0.001) , and receiving imatinib as front-line therapy ( P<0.001) significantly increased with age. No significant differences in gender and the EUTOS Long-Term Survival risks were noted across the three age groups. The multivariate analysis showed that ≥60 years was an adverse predictor for overall survival. However, age was not significantly associated with tyrosine kinase inhibitor (TKI) therapy responses and other outcomes. The incidences of nonhematological toxicity were significantly increased with age during TKI therapy ( P<0.001) . However, those of hematological toxicity was similar across the three age groups. The proportions of the patients maintaining imatinib therapy ( P=0.026) and receiving low-dose TKI therapy ( P<0.001) significantly increased with age at the end of follow-up. Conclusions:Significant differences exist in clinical characteristics, TKI response, overall survival rates, and nonhematological toxicity among newly diagnosed CML-CP patients of different ages.

Objective:To investigate the expression of SET-NUP214 fusion gene in hematological malignancies and to analyze its related clinical biological characteristics.Methods:The clinical data of 24 patients with SET-NUP214 fusion gene-positive hematological malignancies were retrospectively analyzed, and the Kaplan-Meier method was used for survival analysis.Results:Among the 24 patients with SET-NUP214 fusion gene, 15 cases of acute lymphoblastic leukemia (ALL) (13 cases of T-ALL and 2 cases of B-ALL) , 7 cases of acute myeloid leukemia (AML) , and 2 cases of T/myeloid mixed acute leukemia have been identified. The immunophenotype of 13 cases of T-ALL was mainly characterized by CD3 +CD2 -, 73.3% of ALL was characterized by myeloid marker expression, and 85.7% of AML was characterized by CD7 expression. Complete remission (CR) was achieved in 22 patients (91.7%) after induction chemotherapy. All 24 patients received allogeneic hematopoietic stem cell transplantation (HSCT) . With a median follow-up of 24 months, the 3-year relapse free survival (RFS) of AML and ALL was 85.7% and 33.3%, respectively ( P=0.128) . Comparing 13 cases of SET-NUP214-positive and 62 cases of SET-NUP214-negative T-ALL, the CR rates of induction chemotherapy were 92.3% and 93.5% ( P=0.445) , and the 4-week CR rates of induction chemotherapy were 69.2% and 72.6%, respectively ( P=0.187) ; the differences were not statistically significant. After HSCT, the 3-year RFS of SET-NUP214 +T-ALL and SET-NUP214 -T-ALL was 38.5% and 66.4%, respectively ( P=0.028) , and the difference was statistically significant. Conclusion:The SET-NUP214 fusion gene is mainly detected in T cell-derived hematological malignancies, and the prognosis of SET-NUP214 positive T-ALL is relatively poor.

Objective: To investigate the characteristics of hemolysis, resistance and homology of Staphylococcus cohnii urealyticum. Methods: A retrospective study was carried out on thirteen clinical strains of Staphylococcus cohnii urealyticum. They were re-identified by MALDI-TOF MS. Their colony and hemolytic characteristics on blood agar plates were observed. The co-hemolysis between Staphylococcus cohnii urealyticum and Staphylococcus aureus was demonstrated. The hemolysin genes and drug resistance genes were detected by PCR. Pulsed field gel electrophoresis and mass spectrometry were used to analyze the homology of strains. The susceptibility of strains to antimicrobial agents was detected by agar dilution. Results: The confirmed 13 strains of Staphylococcus cohnii urealyticum showed various levels of hemolysis and had enhanced synergistic hemolysis with Staphylococcus aureus. All strains were susceptible to vancomycin and tigecycline. There were 12 strains which carried mecA gene, 7 strains carried cfr gene, 7 strains carried ermC gene. The 13 strains were divided into 3 groups by MALDI-TOF MS, and 6 types by pulsed field gel electrophoresis. Conclusions Clinical strains of Staphylococcus cohnii urealyticum demonstrated various levels of hemolysis which could be enhanced by Staphylococcus aureus. Although they carried different drug resistance genes, they were all susceptible to vancomycin and tigecycline.

Objective: To explore the efficacy and prognosis of nilotinib or dasatinib as second- or third-line treatment in patients with chronic myeloid leukemia (CML) in the chronic phase (CP) and accelerated phase (AP) . Methods: From January 2008 to November 2018, the data of CML patients who failed first- or second-line tyrosine kinase inhibitor (TKI) -therapy received nilotinib or dasatinib as second-line and third-line therapy were retrospectively reviewed. Results: A total of 226 patients receiving nilotinib or dastinib as second-line (n=183) and third-line (n=43) therapy were included in this study. With a median follow-up of 21 (range, 1-135) months, the cumulative rates of complete hematological response (CHR) , complete cytogenetic response (CCyR) and major molecular response (MMR) were 80.4%, 56.3%and 38.3%, respectively in those receiving TKI as second-line TKI therapy. The 3-year progression-free survival (PFS) and overall survival (OS) rates were 78.7%and 93.1%, respectively. Multivariate analyses showed that Sokal high risk, female gender, the best response achieved Conclusions The efficacy of dasatinib and nilotinib as second- or third-line TKI-therapy were active in the CML patients with TKI-resistance. The best response achieved on previous TKI-therapy, the disease phase before switching TKI, and the severe hematologic toxicity developing on the current TKI-therapy were associated with the responses and outcomes.

OBJECTIVE: To trace a rare case of chronic myeloid leukemia (CML) with a four-way Philadelphia chromosome variant by cytogenetic analysis in order to provide a basis for the selection of treatment. METHODS: Bone marrow morphology, chromosomal karyotyping, fluorescence in situ hybridization (FISH) and real-time quantitative PCR (RQ-PCR) were used for the diagnosis and staging of the disease. Point mutations in the tyrosine kinase domain of ABL1 gene were detected by Sanger sequencing. RESULTS: The patient was initially diagnosed as CML in chronic phase (CML-CP) with a chromosomal karyotype of 46,XX,t(5;9;22;6)(q13;q34;q11;q25), while FISH revealed presence of a variant Philadelphia chromosome translocation. Clonal evolution has occurred after 38 months of tyrosine kinase inhibitor (TKI) treatment, when cytogenetic analysis revealed coexisting t(5;9;22;6)(q13;q34;q11;q25) and t(5;9;22;6;17)(q13;q34;q11;q25;q11). After 57 months of TKIs treatment, only the t(5;9;22;6;17) clone was detected. Three months later, hyperdiploidy with additional abnormalities were detected in addition to t(5;9;22;6;17). Three mutations, including p.Tyr253Phe, p.Thr315Ile and p.Gly250Glu, were identified in the tyrosine kinase domain of the ABL1 gene during the course of disease. The patient did not attain cytogenetic and molecular response to TKIs. CONCLUSION The four-way variant translocation may be genetically unstable. Clonal evolution and genetic mutations are likely to occur during TKIs treatment, resulting in poor response to drug therapy. This observation, however, needs to be confirmed by large-scale studies.
Enzyme Inhibitors/therapeutic use* ; Evolution, Molecular ; Female ; Humans ; In Situ Hybridization, Fluorescence ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/genetics* ; Mutation/genetics* ; Philadelphia Chromosome ; Translocation, Genetic