Fatal Outcome ; Humans ; Inflammation ; immunology ; metabolism ; mortality ; Lymphoma, T-Cell ; immunology ; metabolism ; mortality ; Male ; Middle Aged

OBJECTIVETo study the expression of β-integrin family members in children with T-cell acute lymphoblastic leukemia (T-ALL) and their significance.

METHODSQuantitative real-time PCR analyses were performed to assess the expression levels of β-integrin family members in bone marrow samples from 22 children with newly-diagnosed T-ALL and 21 controls (16 children with non-malignant hematologic disease and 5 healthy donors with bone marrow transplantation). Jurkat cells were treated with integrin inhibitor arginine-glycine-aspartate (Arg-Gly-Asp, RGD) peptide. The cell viability and apoptosis rate were determined by CCK8 assay and flow cytometry respectively.

RESULTSThe mRNA levels of integrins β, β, and βwere significantly lower in children with T-ALL than in controls (P<0.05). In T-ALL patients, high integrin βexpression was associated with lower white blood cell counts (<100×10/L), minimal residual disease (MRD) positivity, and day 33 bone marrow negative remission (P<0.05). In T-ALL patients, higher integrin βexpression was associated with relapse of T-ALL (P<0.05). Based on survival curve analysis, higher integrin βexpression was related to lower event-free survival and overall survival rates. RGD peptide treatment inhibited the proliferation of Jurkat cells and increased their apoptosis rate (P<0.05).

CONCLUSIONSβ-Integrin may play a role in the occurrence and development of T-ALL by affecting cell proliferation and apoptosis. The expression of integrin β5 is closely related to the risk of relapse of T-ALL. The expression of integrin β3 is closely related the treatment response and prognosis of T-ALL.

Child ; Child, Preschool ; Female ; Humans ; Integrin beta Chains ; genetics ; physiology ; Jurkat Cells ; Male ; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma ; etiology ; metabolism ; mortality ; RNA, Messenger ; analysis

PURPOSE: The modified Glasgow Prognostic Score (mGPS) consisting of serum C-reactive protein and albumin levels, shows significant prognostic value in several types of tumors. We evaluated the prognostic significance of mGPS in 285 patients with diffuse large B cell lymphoma (DLBCL), retrospectively. MATERIALS AND METHODS: According to mGPS classification, 204 patients (71.5%) had an mGPS of 0, 57 (20%) had an mGPS of 1, and 24 (8.5%) had an mGPS of 2. RESULTS: Our study found that high mGPS were associated with poor prognostic factors including older age, extranodal involvement, advanced disease stage, unfavorable International Prognostic Index scores, and the presence of B symptoms. The complete response (CR) rate after 3 cycles of R-CHOP chemotherapy was higher in patients with mGPS of 0 (53.8%) compared to those with mGPS of 1 (33.3%) or 2 (25.0%) (p=0.001). Patients with mGPS of 0 had significantly better overall survival (OS) than those with mGPS=1 and those with mGPS=2 (p=0.036). Multivariate analyses revealed that the GPS score was a prognostic factor for the CR rate of 3 cycle R-CHOP therapy (p=0.044) as well as OS (p=0.037). CONCLUSION: mGPS can be considered a potential prognostic factor that may predict early responses to R-CHOP therapy in DLBCL patients.
Adult ; Aged ; Antibodies, Monoclonal, Murine-Derived/therapeutic use ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; C-Reactive Protein/*metabolism ; Cyclophosphamide/therapeutic use ; Doxorubicin/therapeutic use ; Female ; Glasgow Outcome Scale ; Humans ; Lymphoma, Large B-Cell, Diffuse/blood/*diagnosis/*drug therapy/mortality ; Male ; Middle Aged ; Multivariate Analysis ; Prednisone/therapeutic use ; Prognosis ; Remission Induction ; Retrospective Studies ; Serum Albumin/*metabolism ; Survival Rate ; Treatment Outcome ; Vincristine/therapeutic use

OBJECTIVETo analyze the isoforms of IKAROS in the bone marrow samples from children with acute B-lineage lymphoblastic leukemia (B-ALL) and to investigate the relationship between frequency of dominant-negative (DN) IKAROS isoforms and prognosis of B-ALL, and to preliminarily study the relevant mechanism.

METHODSA total of 137 children with newly diagnosed B-ALL, who sequentially entered the Department of Hematology and Oncology, Shanghai Children's Medical Center between January 2005 and September 2010, were included in the study. Nest-PCR, Sanger sequencing, and TA cloning were used to analyze the expression of IKAROS isoforms in these children. The relationship between frequency of DN IKAROS isoforms and prognosis of B-ALL was investigated.

RESULTSOf the 137 children with newly diagnosed B-ALL, 16 had expression of IK6, 14 had expression of IK4, and 2 had expression of IK7. There was significant difference in 2.5-year event-free survival between the cohorts of DN IKAROS and non-DN IKAROS (P=0.01). Analysis of the 10 paired of diagnosis/relapse samples from 10 patients with recurrence showed that 8 of 10 paired diagnosis and relapse samples had inconsistent expression of IKAROS isoforms. The rate of IK6 expression in relapse samples from 21 relapse ALL patients was significantly higher than in the 137 children with newly diagnosed ALL (62% vs 12%, P<0.01).

CONCLUSIONSExpression of DN IKAROS isoforms can be a poor prognostic factor in B-ALL and is closely associated with recurrence of B-ALL.

Adolescent ; Child ; Child, Preschool ; Female ; Humans ; Ikaros Transcription Factor ; genetics ; Infant ; Male ; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma ; metabolism ; mortality ; Prognosis ; Protein Isoforms ; genetics

The authors investigated objective response rate to high dose methotrexate (HDMTX)-based combination chemotherapy in primary central nervous system lymphoma (PCNSL), and sought to identify factors that influence response to HDMTX-based combination therapy. Prospective observational analysis was performed on 52 PCNSL patients. All patients received HDMTX (3.5 g/m2) and vincristine (1.4 mg/m2/day) for one day during weeks 1, 3, 5, 7, and 9, and procarbazine (100 mg/m2/day) for one week during weeks 1, 5, and 9. Forty-one patients (78.8%) achieved complete or partial remission. Higher objective response rates were observed for patients with: 1) age < 60 yr; 2) Eastern Cooperative Oncology Group (ECOG) performance score of < 2; 3) low risk status as defined by the International Extranodal Lymphoma Study Group; 4) p53 positivity; 5) XBP-1 negativity; 6) MUM-1 negativity; and 7) homogenous gadolinium enhancement in MR images. Multivariate analysis showed that ECOG performance score of < 2, low risk, negativity for XBP-1, homogenous gadolinium enhancement by MRI, and response to chemotherapy were associated with longer overall survival. In particular, it is interesting to note that patients with a PCNSL that is homogenously enhanced by gadolinium have a higher objective response rate, and a longer progression-free survival and overall survival.
Adult ; Age Factors ; Aged ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Central Nervous System Neoplasms/*drug therapy/mortality ; Contrast Media/chemistry/diagnostic use ; DNA-Binding Proteins/metabolism ; Disease-Free Survival ; Drug Administration Schedule ; Female ; Follow-Up Studies ; Gadolinium/chemistry/diagnostic use ; Humans ; Interferon Regulatory Factors/metabolism ; Lymphoma/*drug therapy/mortality ; Magnetic Resonance Imaging ; Male ; Methotrexate/*administration & dosage ; Middle Aged ; Odds Ratio ; Procarbazine/*administration & dosage ; Prospective Studies ; Recurrence ; Severity of Illness Index ; Transcription Factors/metabolism ; Tumor Suppressor Protein p53/metabolism ; Vincristine/*administration & dosage

BACKGROUND: It has been demonstrated that flow cytometric detection of minimal residual disease (MRD) has a prognostic significance in the treatment of patients with acute leukemia. We investigated the significance of flow cytometric MRD detection for the first time in Korea. METHODS: We analyzed the results of MRD detection in morphologically complete remission bone marrow aspirates from 89 patients with newly-diagnosed or relapsed acute leukemia, in which leukemic cells had cross-lineage antigen expression. Patients were grouped based on MRD frequencies: > or =1.0%, high MRD; <1.0%, low MRD. RESULTS: Forty-seven ALL patients consisted of 10 with high and 37 with low MRD levels. Patients with high MRD levels showed a tendency of more frequent relapse than those with low MRD levels (40.0% and 13.5%, respectively) (P=0.08). High MRD group showed a tendency of short relapse-free survival (RFS) and overall survival (OS), although the differences were not statistically significant. Forty-two AML patients consisted of 16 with high and 26 with low MRD levels. There were no correlations between the MRD levels and relapse rate, RFS or OS. AML patients with high MRD levels showed significantly higher rate of unfavorable cytogenetic risk categories and lower rate of favorable risk categories (P=0.03). CONCLUSIONS: MRD detection by flow cytometric assay of cross-lineage antigen expression would be useful in predicting treatment outcome in patients with ALL rather than AML. We expect that the establishment of the standardization of methods, time to test or antibody combination would be achieved through further trials in this country.
Acute Disease ; Adolescent ; Adult ; Aged ; Antigens/*metabolism ; Antigens, CD/metabolism ; Bone Marrow/metabolism ; Child ; Child, Preschool ; Disease-Free Survival ; Female ; *Flow Cytometry ; Humans ; Infant ; Leukemia, Myeloid, Acute/*diagnosis/mortality/therapy ; Male ; Middle Aged ; Neoplasm, Residual/diagnosis ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/*diagnosis/mortality/therapy ; Recurrence ; Survival Rate

Levels of soluble interleukin-2 receptor alpha (sIL-2Ralpha) are known to increase in the sera of patients with certain malignancies, including malignant lymphoma. This study aimed to assess the clinical significance of the sIL-2Ralpha level in non-Hodgkin's lymphoma (NHL). We used ELISA to measure the sIL-2Ralpha levels in 48 newly diagnosed and untreated patients with NHL and evaluated the correlation between the sIL-2Ralpha levels and clinical characteristics and the International Prognostic Index (IPI). We monitored serum sIL-2Ralpha in 7 patients to compare the changes in their clinical progress with these levels. High levels of serum sIL-2Ralpha (> or =2,000 U/mL) correlated well with parameters defining the high risk group according to the IPI, i.e., high tumor burden at diagnosis (stage III+IV) and lactate dehydrogenase > or =472 U/L. The levels were also associated with B symptoms, bone marrow involvement, and poor response to therapy. The sIL-2Ralpha level decreased during complete remission and was elevated during disease progression or relapse. A high level of sIL-2Ralpha was significantly associated with a low survival rate. These results suggest that serum sIL-2Ralpha might be useful as a biomarker for evaluating the prognosis of patients with NHL at the time of diagnosis and during therapy. A well-controlled, large-scale study is needed to clarify the clinical significance of sIL-2Ralpha in specific groups of NHL.
Aged ; Biological Markers/blood ; Female ; Humans ; Interleukin-2 Receptor alpha Subunit/*blood ; L-Lactate Dehydrogenase/blood ; Lymphoma, Non-Hodgkin/*diagnosis/metabolism/mortality ; Male ; Middle Aged ; Neoplasm Staging ; Survival Rate

The aim of this study was to explore the clinical features and survival of adult patients with CD20 positive B-lineage acute lymphoblastic leukemia (B-ALL). The clinical manifestations, examination results, therapeutic effect and survival rate of 119 adult B-ALL patients diagnosed and treated in our hospital from May 2004 to January 2008 were analyzed retrospectively. The results showed that among 119 cases, CD20 positive B-ALL accounted for 40 cases (33.61%), CD20 negative B-ALL patents accounted for 79 cases (66.39), the percentage of male patients in CD20 positive and negative groups were 72.50% and 50.63%, the leukocyte counts at diagnosis in these two groups were (27.35+/-30.29)x10(9)/L and (0.11+/-81.72)x10(9)/L, respectively, there were significant differences (p<0.05), whereas the distribution of age, infiltration of liver, spleen, lymph nodes and central nervous system, the hemoglobin and platelet levels, the expression of myeloid lineage marker, the incidence of Ph chromosome, the ratio of hyperdiploid and normal karyotype, the complete remission rate within 4 weeks, induction death rate and relapse rate and so on in CD20 positive and negative groups showed no significant differences (p>0.05). The analysis of Kaplan-Meier curve on survival rate demonstrated that the median overall survival time and 3-year overall survival rate of adult B-ALL patients in CD20 positive and negative groups were 11.0 months and 12.0 months, 28% and 20% respectively, there were no statistical differences (p=0.832). It is concluded that the expression of CD20 in adult B-ALL appears to be associated with sex and leukocyte count, but not associated with other clinical features, which indicates no significant influence on the prognosis of patients.
Adolescent ; Adult ; Antigens, CD20 ; metabolism ; Female ; Humans ; Leukemia, B-Cell ; mortality ; Male ; Middle Aged ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; mortality ; Prognosis ; Retrospective Studies ; Survival Analysis ; Survival Rate ; Young Adult

BACKGROUNDThe prognosis is poor for patients with relapsed or refractory non-Hodgkin's lymphoma (NHL). The main reason for poor prognosis is multidrug resistance (MDR), for which the main phenotype is overexpression of P-glycoprotein (P-gp). This study explored the efficacy of ligustrazine as a salvage agent in patients with relapsed or refractory NHL, and the relationship to P-gp expression.

METHODSSixty patients were randomized to a reversal agent group, receiving ligustrazine plus chemotherapy, and a control group, receiving chemotherapy alone. Flow cytometry was performed to evaluate P-gp expression.

RESULTSIn the 56 patients we were able to evaluate, there was no statistically significant difference in progression-free survival (PFS) in the two groups (P = 0.0651), but the reversal agent group had a higher overall response rate (ORR) than did the control group (P = 0.048). Forty-one of 56 patients had P-gp(+) tumor cells. Among these patients, six of eighteen patients in the reversal agent group and in the control group had complete remission or complete remission/unconfirmed (CR+CRu) reflecting a significant advantage in the reversal agent group (P = 0.048). Patients with P-gp(+) tumor cells in the reversal agent group had a higher overall response rate (ORR) than did the control group (11/18 vs. 6/23, P = 0.024). Kaplan-Meier Survival curve and log-rank test demonstrated that patients with P-gp(+) tumor cells in the reversal agent group had longer progression-free survival than did the control group (P = 0.0464). A small number of patients who received ligustrazine had a decrease in blood pressure.

CONCLUSIONLigustrazine as a salvage agent in combination with chemotherapy can elevate response rate, prolong PFS with manageable toxicity, and correlate with P-gp expression in relapsed or refractory NHL.

ATP-Binding Cassette, Sub-Family B, Member 1 ; metabolism ; Adult ; Aged ; Calcium Channel Blockers ; therapeutic use ; Female ; Humans ; Lymphoma, Non-Hodgkin ; drug therapy ; metabolism ; mortality ; Male ; Middle Aged ; Pyrazines ; therapeutic use ; Treatment Outcome ; Young Adult

This study was to investigate the predictive factors influencing prognosis of non-Hodgkin's lymphoma (NHL). The clinical data on 125 cases of NHL were analyzed retrospectively. The results indicated that in 125 cases, the incidence of B cell NHL (B-NHL) was 68%, T cell NHL (T-NHL) was 28%, and uncertained cases were 4%. B-NHL was with more bone marrow involvement, while T-NHL was associated with more presence of B symptom, increased lactate dehydrogenase (LDH), advanced clinical stage and higher International Prognostic Index (IPI) scores. For T-NHL and B-NHL, the 3-year overall survival (OS) rate was 41.07% and 71.64% respectively. Age, B symptom, LDH level, and clinical stage were associated with OS. Immunophenotyping was not identified as a significant prognostic factor. The incidence of born marrow involvement was 31.2%, mainly in B-NHL. The involvement manner had no relationships with age, B symptom, LDH level and T/B immunophenotyping. Diffuse bone marrow involvement was often linked with hepatosplenomegaly, and its OS was shorter than that focal manner. In conclusion, age, B symptom, LDH level and clinical stage affect NHL survival, while immunophenotyping was not an independent prognostic factor for NHL. The manner of bone marrow involvement helped to predict prognosis.
Adolescent ; Adult ; Aged ; Aged, 80 and over ; Bone Marrow ; pathology ; Child ; Child, Preschool ; China ; Female ; Humans ; Infant ; L-Lactate Dehydrogenase ; metabolism ; Lymphoma, B-Cell ; diagnosis ; Lymphoma, Non-Hodgkin ; diagnosis ; mortality ; pathology ; Lymphoma, T-Cell ; diagnosis ; enzymology ; Male ; Middle Aged ; Prognosis ; Retrospective Studies ; Survival Rate ; Young Adult