Objective To investigate the incidence of serum monoclonal immunoglobulins (McIg) in B-cell chronic lymphoproliferative disorders (B-CLPD) and the clinical significance of McIg in B-CLPD and its possible sources.Methods A total of 1 147 patients with B-CLPD treated from May 2006 to May 2015 were enrolled into this retrospective study.The incidence of McIg and the relationship between McIg and prognostic factors in patients with B-CLPD were analyzed.Results Out of 1 147 B-CLPD patients,there were 164 patients with lymphoplasmacytic lymphoma/Waldenstrom macroglobulinemia (LPL/WM),and among them,McIg was detected in 140 cases (85.4 ％).In the remaining 983 patients with B-CLPD,monoclonal Ig was detected in 50 (5.1％) patients.Most of McIg in 2 groups were IgM paraprotein.The levels of IgM paraprotein of the LPL/WM group,non-LPL./WM group and McIg-negative patients were (48.88±33.42) g/L,(27.9±15.23) g/L and (2.75±1.21) g/L,respectively,the difference was statistical significance (P=0.000);the level of IgM paraprotein in LPL/WM group was significantly higher than that in non-LPL/WM group (P=0.000).The level of paraprotein decreased significantly when the patients got complete response after therapy (P=0.001,0.048,respectively).The incidence of serum McIg was higher in the group with complex karyotype (P =0.016) andwith high level of β2-microglobulin (β2-MG) (P =0.001).In the 47 non-LPL/WM patients with positive McIg,serum McIg in 38 (80.9 ％) patients were expressed in a pattern consistent with the distribution of tumor cells (P ＜ 0.005).Most of the light chain subtype of the McIg were consistent with the light chain subtype of the membrane immunoglobulin on the tumor cells.Conclusions Some non-LPL/WM B-CLPD patients also have serum McIg,and it could have certain relevance with the prognosis of B-CLPD.Moreover,the McIg may be secreted by tumor cells or those derived from the same progenitor cells with tumor cells.

Objective To investigate the clinical and laboratory characteristics of patients with chronic lymphocytic leukemia (CLL). Methods 503 patients with CLL admitted from October 1998 to February 2015 were retrospectively analyzed. Baseline characteristics were compared using Chi-square test and Kaplan-Meier methodology was undertaken for survival analyses. Results The median age was 58 years (26-86 years):335 cases were male and 168 cases were female. 204 cases (40.5%) were at the clinical stage of Binet A, followed by Binet B (148 cases, 30.1%) and Binet C (151 cases, 29.3%). 108 cases (21.1%) had anemia at diagnosis, while 113 cases (26.5 %) had an elevated level of lactate dehydrogenase and the expression of CD38 was detected among 100 cases (29.1 %). Clonal abnormalities were observed using fluorescence in situ hybridization (FISH) analysis. Those involving 13q deletion were the most frequent (156 cases, 47.3 %), followed by IgH translocation (22.4 %), trisomy 12 (21.2 %) and 17p deletion (14.5 %). The mutational status of immunoglobulin heavy chain variable region was determined among 230 cases, 165 cases (71.7%) of which were found to be with mutated status. The most frequently encountered gene was V4-34 (28 cases, 12.4 %). The median progression-free survival (PFS) was 89.0 months (95 %CI 75.0-103.0 months), while the median overall survival was 129.0 months (95 %CI 106.9-151.1 months). Conclusion Compared with patients in the western world, CLL patients in this study are younger at diagnosis and have longer overall survival, which, to some extent, could reflects the characteristics of CLL patients in China.

Objective: To summarize and investigate the characteristics, prognosis and treatments of chronic lymphocytic leukemia (CLL) patients with trisomy 12 by using FISH (CEP12). Methods: Clinical data of 330 CLL patients were analyzed retrospectively by using FISH (CEP12) to detect trisomy 12 from May 2003 to April 2015. The clinical data and laboratory characteristics of CEP12 positive patients (70 cases) were compared with those CEP12 negative patients (260 cases). Results: Compared with CEP12 negative CLL patients, the proportion of hepatomegaly (13.6% vs 4.0%, P=0.011) and LDH>247 U/L (43.3% vs 18.5%, χ²=15.892, P<0.001) in CEP12 positive CLL patients were much higher, respectively. There were no significant differences between age, sex, clinical stage, β₂-microglobulin level, IGHV mutation ratio and splenomegaly/lymphadenopathy in these two subgroups. However, compared with CEP12 negative patients, CEP12 positive patients had higher ratio of FMC7 (23.8% vs 12.7%, χ²=4.730, P=0.030), and lower ratio of CD23 (95.2% vs 99.6%, P=0.033). The overall response rates (ORR) in Fludarabine (without Rituximab), Rituximab (with or without Fludarabine) and the traditional chemotherapy group (chlorambucil, CHOP or CHOP-like) were 77.5% (31/40), 84.8% (56/66) and 45.4% (50/110), respectively. The ORR of the traditional chemotherapy group was lower than that of the Fludarabine group and Rituximab group. For CEP12 positive patients, the ORR was inferior to CEP12 negative patients when only using Fludarabine (P<0.05). However, when using Rituximab, the difference could be eliminated, and the ORR was even a little higher in CEP12 negative patients (91.7% vs 81.0%, P=0.306). Compared with CEP12 negative patients, there were no significant differences in progression-free survival (PFS) (χ²=0.410, P=0.478) and overall survival (OS) (χ²=0.052, P=0.180) for CEP12 positive patients whom the median time from diagnosis to start treatment and OS time was 22.6 (95%CI 15.4-31.7) and 118.5 (95%CI 74.5-162.4) month while the 5-year PFS and OS were (52.9±7.6)% and (74.8±6.6)%. Conclusions CEP12 positive CLL patients are more common in hepatomegaly and higher level of LDH. The traditional chemotherapy treatment had the lowest efficacy, and the curative effect of single use of fludarabine is not as good as that of CEP12 negative patients, however, when using Ritaximab, the efficacy could be comparable.

Objective: To evaluate the efficacy and long-term outcome of a combined protocol for multiple myeloma (MM) , including induction therapy, autologous hematopoietic stem cell transplantation (ASCT) and consolidation and maintenance therapy. Methods: Clinical records of 144 patients with MM from January 1, 2005 to February 1, 2016 were retrospectively analyzed. Results: The overall response rate (ORR) after ASCT was 100.0%, in which the complete remission (CR) was 64.1% and the best treatment response rate of superior to PR was 89.4%. During a median follow-up of 47 months, patients with an overall survival (OS) and progression free survival (PFS) was 120.9 and 56.9 months respectively. 5y-OS (73.7±4.7) %, 7y-OS (60.5±6.3) %; 3y-PFS (69.2±4.2) %, 5y-PFS (47.8±5.3) %. The median OS and PFS between the first line transplantation group and salvage transplantation group were 120.9 months vs 50.1 months and 60.2 months vs 16.7 months (all P=0.000). In 127 patients with R-ISS staging, the median survival of Ⅰ, Ⅱ, Ⅲ stage was 120.9 months (n=43) , 88.4 months (n=64) , 35.6 months (n=20) , respectively (P=0.000). For subgroup analysis of survival in early and late ASCT, the median OS of patients with R-ISS stage Ⅲ (35.6 months vs 15.8 months, P=0.031) and the median PFS of two groups (phase Ⅰ: 72.1 months vs 18.9 months, P=0.000; Ⅱ: 53.4 months vs 16.7 months, P=0.012; Ⅲ: 28.5 months vs 5.9 months, P=0.001) were different. Multivariate analysis showed that only R-ISS and the degree of remission before transplantation had impact on OS (HR=8.486, 95% CI 2.549-28.255, P=0.003) and PFS (HR=2.412, 95% CI 1.364-4.266, P=0.002) , respectively. Conclusion The combined protocol containing ASCT is effective for MM patients, improving remission rate and remission depth, prolonging PFS and OS. First line transplantation could significantly prolong the OS and PFS as compared with salvage transplantation. R-ISS and pre-transplantation remission depth are prognostic factors for survival.

OBJECTIVETo investigate the expression of high-molecular-weight keratins CK5/6, CK14, estrogen receptor (ER) and progesterone receptor (PR) in differential diagnosis of simple ductal hyperplasia (UDH), atypical ductal hyperplasia (ADH) and low-grade ductal carcinoma in situ (low-grade DCIS) .

METHODSThe clinicopathological data of twenty cases of atypical ductal epithelial hyperplasia (ADH) with focal cancerization changed into low-grade DCIS diagnosed at Tianjin Medical University Cancer Institute and Hospital between January 2013 and February 2014 were reviewed and analyzed. The expressions of CK5/6, CK14, ER and PR were detected by immunohistochemistry.

RESULTSPositive expressions of CK5/6 and CK14 were seen in UDH showing a mosaic pattern, while negative expression in ADH and low-grade DCIS. In addition, CK5/6 and CK14 were positively expressed in the myoepithelial cells of UDH, ADH and low-grade DCIS. Positive expressions of ER and PR were observed in UDH, ADH and low-grade DCIS. But they presented diffuse and homogeneous strong positive expression in ADH and variable positive expression in UDH.

CONCLUSIONIn the intraductal proliferative lesions of the breast, the use of combined detection of the expression of CK5/6, CK14, ER and PR is of practical significance in the differential diagnosis of UDH, ADH and low-grade DCIS.

Breast ; metabolism ; pathology ; Breast Neoplasms ; diagnosis ; metabolism ; Carcinoma, Ductal, Breast ; diagnosis ; metabolism ; Carcinoma, Intraductal, Noninfiltrating ; diagnosis ; metabolism ; Diagnosis, Differential ; Female ; Humans ; Hyperplasia ; diagnosis ; metabolism ; Immunohistochemistry ; Keratin-14 ; metabolism ; Keratin-5 ; metabolism ; Keratin-6 ; metabolism ; Receptors, Estrogen ; metabolism ; Receptors, Progesterone ; metabolism

OBJECTIVETo explore the immunophenotypic characteristics of CD5⁺ B cell lymphoproliferative disorders (B-LPD) of Chinese patients.

METHODSImmunophenotyping of bone marrow and (or) of peripheral blood was performed in patients with B-LPD by four color multiparameter flow cytometry analysis using a panel of monoclonal antibodies, and the patients clinical data were retrospectively analyzed. The difference in immunophenotypes and the related clinical features were retrospectively analyzed. Fluorescence in situ hybridization (FISH) for t(11;14) detection was applied to diagnose or exclude mantle cell lymphoma.

RESULTS(1)A total 260 CD5⁺ B-LPD patients were enrolled in this study, including 186 chronic lymphocytic leukemia (CLL), 40 mantle cell lymphoma (MCL), other B-LPD including 5 splenic marginal zone lymphoma (SMZL), 2 B-cell prolymphocytic leukemia (B-PLL), 3 hairy cell leukemia (HCL). The other 26 cases (10%)were not classified and defined as unclassified B-LPD (BLPD-U). MCL patients were all positive for t(11;14) detected by FISH, while all the BLPD-U patients were negative for t(11;14). (2) All patients expressed CD19, CD20 and CD5. According to the immunophenotypic score system, 186 CLL patients scored 4-5, 99.5% of patients with CD23⁺, 11.3% with sIgM⁺, 10.2% with FMC7⁺, 44.1% with CD22⁺ and 51.1% with CD11c⁺. MCL patients scored 2-3, with 50% expressing CD23 and sIgM, 81.6% expressing FMC7, 92.1% expressing CD22 and 5.3% expressing CD11c. In aspect of BLPD-U and other B-LPD, the expression of CD23, sIgM, FMC7, CD22 and CD11c were 73.1% and 50%, 34.6% and 50%, 88.5% and 100%, 92.3% and 90%, 69.2% and 70%, respectively. (3)In comparison of CLL with MCL, there was a significant difference in the expression of CD23, sIgM, FMC7, CD22 and CD11c between the two groups (P<0.01). Between MCL and BLPD-U, similar expression type of CD23, sIgM, FMC7 and CD22 was found except CD11c, which was highly expressed in BLPD-U (P<0.001). The difference of CD11c expression was also statistically significant between MCL and other B-LPD (P<0.01). In comparison of MCL with other B-LPD, there was a significant difference in the expression of CD11c (P<0.01). The expression of CD23 and sIgM in MCL are 7%-21% and 82%-100% respectively in Western population, while the expression of other immunophenotypic markers is similar with our study.

CONCLUSIONThe significant high incidence of CD23 and low incidence of sIgM compared to the Western population was observed in Chinese patients, and CD11c coud serve as a useful marker to distinguish MCL from CLL and other CD5⁺ B-LPD.

Adult ; Aged ; Aged, 80 and over ; Cell Count ; Female ; Flow Cytometry ; methods ; Humans ; Immunophenotyping ; Leukemia, Lymphocytic, Chronic, B-Cell ; immunology ; Lymphoma, Mantle-Cell ; immunology ; Lymphoproliferative Disorders ; immunology ; Male ; Middle Aged ; Retrospective Studies

OBJECTIVETo assess the efficacy of dose-intensive immunochemotherapy with or without autologous hematopoietic stem cell transplantation (ASCT) for newly diagnosed young patients with medium/high risk diffuse large B-cell lymphoma (DLBCL).

METHODSThe retrospective study was performed in 29 cases of young patients (≤ 60 years) with newly diagnosed DLBCL and an age-adjusted International Prognostic Index (aaIPI) score of 2 or 3. All of them were treated with dose-intensive regimens (DA-EPOCH or Hyper-CVAD/MA) combined with Rituximab and some were consolidated with first-line ASCT. The efficacy and the potential predictors were evaluated.

RESULTSThe median age of 29 patients was 43 years old. Of them, 12 patients were consolidated with high-dose chemotherapy and ASCT. The complete remission (CR) rate was 69%, the partial remission (PR) rate 21% and the overall response rate 90%. After a median follow-up of 14 months, the estimated progression-free survival (PFS) and overall survival (OS) at two years were 64% and 70%, respectively. The median PFS and OS were significantly longer in CR patients than that in PR patients (P=0.015 and 0.061, respectively). Two patients achieved PR after induction therapy converted to CR after ASCT and were in continuous CR after follow-up above three years. In multivariate analysis, only bone marrow involvement (BMI) at diagnosis had an adverse influence in PFS (P=0.009), but not in OS. Based on whether there was BMI or not and the extent of BMI at diagnosis, the patients were divided into three groups as BM-0 (without BMI), BM-1 (the extent of BMI ≤ 10%) and BM-2 (the extent of BMI>10%). Patients in BM-2 group had significantly shorter PFS and OS than those in BM-0 and BM-1 groups (P=0.001 and 0.045, respectively). In multivariate analysis, the extent of BMI>10% was the independent poor prognostic factor for PFS and CNS relapse or prognosis.

CONCLUSIONDose-intensive immunochemotherapy followed by ASCT or not has significant effect on efficacy of first-line treatment for young and untreated patients with medium/high risk DLBCL. The extent of BMI>10% at diagnosis is an independent risk factor associated with poor PFS and increased CNS relapse or progression.

Adult ; Antibodies, Monoclonal, Murine-Derived ; therapeutic use ; Antineoplastic Agents ; therapeutic use ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Female ; Hematopoietic Stem Cell Transplantation ; Humans ; Lymphoma, Large B-Cell, Diffuse ; drug therapy ; surgery ; Male ; Middle Aged ; Retrospective Studies ; Rituximab ; Transplantation, Autologous ; Treatment Outcome ; Young Adult

OBJECTIVETo observe the clinical and biological characteristics of Non-IgM-secreting lymphoplasmacytic lymphoma (LPL) and draw the differences between non-IgM LPL and Waldenström macroglobulinemia (WM).

METHODSRecords of 13 patients with non-IgM LPL were retrospectively analyzed between January 2000 and December 2013. The cytogenetic aberrations were detected by fluorescence in situ hybridisation (FISH).

RESULTSIn the cohort, 7 males and 6 females with a median age of 63 years (range 43 to 74), two patients were IgA secreting, 6 with IgG secreting and 5 patients without monoclonal globulin. The major complaint at diagnosis included anemia associated symptom (53.8%), mucocutaneous hemorrhage and superficial lymphadenopathy (15.4%). Eight patients had B symptom at diagnosis. All of the 13 patients had bone marrow involvement and anemia, and 10 patients had 2 or 3 lineage cytopenia. In 5 patients with available immunophenotypic data, all expressed CD19, CD20, CD22 and CD25, but missed the expression of CD10, CD103 and CD38. Two cases had CD5 or sIgM positive alone. Another 2 patients were CD23 or CD11c positive and 3 patients were FMC7 positive. Cytogenetic aberrations had been detected by FISH in 7 patients, but only two (28.6%) patients had aberrations with del(6q).

CONCLUSIONThe clinical and biological characteristics had no significantly difference between non-IgM LPL and WM.

Adult ; Aged ; Antigens, CD ; Chromosome Aberrations ; Female ; Humans ; Immunoglobulin M ; In Situ Hybridization, Fluorescence ; Integrin alpha Chains ; Leukemia, Lymphocytic, Chronic, B-Cell ; Male ; Middle Aged ; Retrospective Studies ; Waldenstrom Macroglobulinemia

OBJECTIVETo investigate the influence of renal function on the level of β₂-microglobulin (β₂-MG) as prognostic factor in newly diagnosed multiple myeloma (MM) patients, and to analyze the overall survival (OS) in different level of β₂-MG with relatively normal or abnormal renal function in MM patients.

METHODSAccording to the level of β₂-MG, 666 newly diagnosed MM patients were divided into three groups as β₂-MG<3.5, 3.5-<5.5, ≥5.5 mg/L. According to the level of serum creatinine, these patients were divided into two groups:serum creatinine <177 μmol/L as relatively normal group, serum creatinine ≥177 μmol/L as abnormal group.

RESULTSAmong 666 patients, there were 416 male and 250 female, the median age was 58 (25-86) years old. Comparison of OS among β₂-MG<3.5, 3.5-<5.5, ≥5.5 mg/L groups indicated that the median OS of the three groups were 85.75 (95% CI 70.99-100.50), 47.25 (95% CI 40.98-53.53) and 35.05 (95% CI 30.75-39.35) months, respectively (P<0.01). Comparison of OS between serum creatinine <177 and ≥177 mmol/L groups, the median OS of the two groups were 64.67 (95% CI 56.57-72.77) and 32.74 (95% CI 27.74-37.73) months, respectively (P<0.01). In β₂-MG≥5.5 mg/L, the median OS of relatively normal and abnormal groups were 37.25 (95% CI 31.45-43.06) and 32.55 (95% CI 26.26-38.83) months, respectively (P=0.142).

CONCLUSIONHigh level of β₂-MG and renal function correlated with shorter survival of MM patients. Higher level of β₂-MG with abnormal renal function can't change the prognostic value of β₂-microglobulin on MM.

Adult ; Aged ; Aged, 80 and over ; Female ; Humans ; Kidney ; Kidney Function Tests ; Male ; Middle Aged ; Multiple Myeloma ; Neoplasm Staging ; Prognosis ; beta 2-Microglobulin

Humans ; Waldenstrom Macroglobulinemia/genetics* ; East Asian People ; Chromosome Aberrations ; Lymphoma