BACKGROUND/AIMS: This study investigated the expression of nuclear factor kappaB (NF-kappaB) and the chemokine receptor (CXCR4) in patients with diffuse large B-cell lymphoma (DLBCL) who received rituximab-based therapy. METHODS: Seventy patients with DLBCL and treated with rituximab-CHOP (R-CHOP) were included, and immunohistochemistry was performed to determine the expression of NF-kappaB (IkappaB kinase alpha, p50, and p100/p52) and CXCR4. To classify DLBCL cases as germinal center B-cell-like (GCB) and non-GCB, additional immunohistochemical expression of CD10, bcl-6, or MUM1 was used in this study. The expression was divided into two groups according to the intensity score (negative, 0 or 1+; positive, 2+ or 3+). RESULTS: The median age of the patients was 66 years (range, 17 to 87), and 58.6% were male. Twenty-seven patients (38.6%) had stage III or IV disease at diagnosis. Twenty-three patients (32.9%) were categorized as high or high-intermediate risk according to their International Prognostic Indexs (IPIs). The overall incidence of bone marrow involvement was 5.7%. Rates of positive NF-kappaB and CXCR4 expression were 84.2% and 88.6%, respectively. High NF-kappaB expression was associated with CXCR4 expression (p = 0.002), and 56 patients (80.0%) showed coexpression. However, the expression of NF-kappaB or CXCR4 was not associated with overall survival and EFS. On multivariate analysis that included age, gender, performance status, stage, and the IPI, no significant association between the grade of NF-kappaB or CXCR4 expression and survival was observed. CONCLUSIONS: The current study suggests that the tissue expression of NF-kappaB and CXCR4 may not be an independent prognostic marker in DLBCL patients treated with R-CHOP.
Adolescent ; Adult ; Aged ; Aged, 80 and over ; Antibodies, Monoclonal, Murine-Derived/administration & dosage ; Antineoplastic Combined Chemotherapy Protocols/adverse effects/*therapeutic use ; Chi-Square Distribution ; Cyclophosphamide/administration & dosage ; Disease Progression ; Disease-Free Survival ; Doxorubicin/administration & dosage ; Female ; Humans ; Immunohistochemistry ; Kaplan-Meier Estimate ; Lymphoma, Large B-Cell, Diffuse/chemistry/*drug therapy/mortality/pathology ; Male ; Middle Aged ; Multivariate Analysis ; NF-kappa B/*analysis ; Neoplasm Staging ; Predictive Value of Tests ; Prednisone/administration & dosage ; Proportional Hazards Models ; Receptors, CXCR4/*analysis ; Retrospective Studies ; Risk Factors ; Time Factors ; Treatment Outcome ; Tumor Markers, Biological/*analysis ; Vincristine/administration & dosage ; Young Adult

BACKGROUND/AIMS: Recurrent focal segmental glomerulosclerosis (FSGS) following renal transplantation is relatively common. However, the risk factors and optimal pretransplant treatment preventing recurrence of FSGS remain controversial. METHODS: We retrospectively reviewed 27 adult renal transplant recipients with FSGS over a period of 10 years. We first compared possible risk factors for FSGS recurrence between the recurrence and nonrecurrence groups. Then we evaluated the effect of pretransplant plasmapheresis (PP; n = 4) and PP with rituximab (PP + RTX; n = 5) on recurrence of FSGS after transplantation compared to control patients that were not treated with these modalities. RESULTS: There were seven recurrences in 27 patients (25.9%), but there were no significant differences in possible risk factors for FSGS recurrence between the two groups. Recurrence rates between patients with pretransplant PP or PP + RTX and control patients were not significantly different (22.2% vs. 27.7%, p > 0.05). There was also no significant difference in recurrence between the pretransplant PP and PP + RTX groups (25% vs. 20%, p > 0.05). CONCLUSIONS: Pretransplant PP or PP + RTX do not significantly decrease the recurrence of FSGS in adult renal transplant candidates.
Adult ; Antibodies, Monoclonal, Murine-Derived/*administration & dosage ; Female ; Glomerulosclerosis, Focal Segmental/diagnosis/immunology/*surgery ; Humans ; Immunosuppressive Agents/*administration & dosage ; *Kidney Transplantation/adverse effects ; Male ; Middle Aged ; *Plasmapheresis ; Recurrence ; Retrospective Studies ; Risk Factors ; Treatment Outcome

OBJECTIVETo investigate the effects of rituximab (RTX) in children with steroid-dependent nephrotic syndrome.

METHODFive cases of children with steroid-dependent nephrotic syndrome seen from May 2012 to February 2013 in whom only steroid plus calcineurin inhibitor was effective and the disease recurred on reduction of dose were enrolled into this study, including 3 males and 2 females. Calcineurin inhibitors were stopped and steroids was changed to full dose. After the general condition improved, RTX was given at a dose of 375 mg/m(2), once a week for a total of three times for one course. After urine protein became negative for five days, the dose of steroid was changed to 2 mg/kg every other day, thereafter the dose was reduced by 5 mg per every 2 weeks, until discontinuation. After regular monitoring, when peripheral blood B cells were ≥ 3%, a second RTX was added.

RESULTUrine protein was negative in 2-7 days in 5 patients after the first RTX treatment. Before treatment B lymphocytes in peripheral blood was 7.8% to 13.0% and after the first course of RTX treatment decreased to 0 in the first 6 to 8 months at the beginning of recovery, while in the first 7 to 10 months to 3.3%-6.1%, after a second RTX was given, B lymphocytes were reduced to 0, but in two cases (cases 1 and 3) B lymphocytes rose again at 16 and 17 months, in the first 17 and 18 months rose to 4.16% and 4.17%, RTX was given once again respectively. B lymphocytes were reduced to 0 again. Currently the 5 patients continued to be negative for urine protein, maintaining remission for 12 to 20 months.RTX infusion had no significant side effects, and side effects of steroid and calcineurin inhibitor disappeared.

CONCLUSIONIn children with steroid-dependent and only calcineurin inhibitor effective nephritic syndrome, relapse may still occur after improvement of nephrotic syndrome, after the first RTX treatment, regular monitoring of B lymphocytes, RTX supplementary treatment in advance can help discontinuation of steroids and immunosuppressive agents and maintain remission.

Anti-Inflammatory Agents ; administration & dosage ; therapeutic use ; Antibodies, Monoclonal, Murine-Derived ; administration & dosage ; therapeutic use ; Antigens, CD19 ; metabolism ; B-Lymphocytes ; drug effects ; metabolism ; Calcineurin Inhibitors ; administration & dosage ; therapeutic use ; Child ; Child, Preschool ; Drug Administration Schedule ; Female ; Follow-Up Studies ; Humans ; Immunosuppressive Agents ; administration & dosage ; therapeutic use ; Lymphocyte Count ; Male ; Nephrotic Syndrome ; drug therapy ; metabolism ; Proteinuria ; urine ; Recurrence ; Remission Induction ; Rituximab ; Treatment Outcome

Febrile neutropenia (FN) is the major toxicity of rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) regimen in the treatment of diffuse large B-cell lymphoma (DLBCL). The prediction of neutropenia and FN is mandatory to continue the planned R-CHOP therapy resulting in successful anti-cancer treatment. The clinical features and patterns of neutropenia and FN from 181 DLBCL patients treated with R-CHOP were analyzed retrospectively. Sixty percent (60.2%) of patients experienced at least one episode of grade 4 neutropenia. Among them, 42.2% of episodes progressed to FN. Forty-eight percent (48.8%) of patients with FN was experienced their first FN during the first cycle of R-CHOP. All those patients never experienced FN again during the rest cycles of R-CHOP. Female, higher stage, international prognostic index (IPI), age > or =65 yr, comorbidities, bone marrow involvement, and baseline serum albumin < or =3.5 mg/dL were significant risk factors for FN by univariate analysis. Among these variables, comorbidities (P=0.009), bone marrow involvement (P=0.006), and female gender (P=0.024) were independent risk factors for FN based on multivariate analysis. On observing the patterns of neutropenia and FN, primary prophylaxis of granulocyte colony-stimulating factor (G-CSF) and antibiotics should be considered particularly in female patients, patients with comorbidities, or when there is bone marrow involvement of disease.
Adolescent ; Adult ; Age Factors ; Aged ; Antibodies, Monoclonal, Murine-Derived/adverse effects/*therapeutic use ; Antineoplastic Combined Chemotherapy Protocols/adverse effects/*therapeutic use ; Chemotherapy-Induced Febrile Neutropenia/*etiology ; Cyclophosphamide/administration & dosage/adverse effects/therapeutic use ; Demography ; Doxorubicin/administration & dosage/adverse effects/therapeutic use ; Female ; Humans ; Lymphoma, Large B-Cell, Diffuse/*drug therapy ; Male ; Middle Aged ; Neoplasm Staging ; Neutropenia/etiology/pathology ; Prednisone/administration & dosage/adverse effects/therapeutic use ; Retrospective Studies ; Risk Factors ; Sex Factors ; Vincristine/administration & dosage/adverse effects/therapeutic use ; Young Adult

OBJECTIVETo explore the safety and efficacy of lower dose of rituximab in the treatment of elderly autoimmune hemolytic anemia (AIHA).

METHODSFrom May 2008 to February 2013, a total of 37 patients with newly diagnosed elderly AIHA patients were enrolled in the study, including 25 cases treated with prednisone 1 mg · kg⁻¹ · d⁻¹ for 4 weeks and 12 cases ineligible for glucocorticoid receiving rituximab (100 mg/week for 4 times).

RESULTSOf the 25 patients with conventional glucocorticoid, 5 cases (20.0%) were complete remission (CR), 15 cases with partial remission (PR) and 5 cases without response. The overall response rate was 80.0%. Of the 12 cases with rituximab, 8 cases (66.7%) were CR, 3 cases with PR and 1 without response. The overall response rate was 91.7%. A significantly higher CR rate was seen in lower dose of rituximab, as compared to that in conventional glucocorticoid (P=0.038).

CONCLUSIONA lower dose of rituximab, with satisfactory safety and efficacy, was better than the conventional glucocorticoid in the treatment of elderly AIHA patients.

Aged ; Aged, 80 and over ; Anemia, Hemolytic, Autoimmune ; drug therapy ; Antibodies, Monoclonal, Murine-Derived ; administration & dosage ; adverse effects ; therapeutic use ; Female ; Humans ; Male ; Middle Aged ; Prednisone ; therapeutic use ; Rituximab ; Treatment Outcome

OBJECTIVETo evaluate the impact of Fc gamma receptor IIIa (FcγR IIIa) polymorphisms on the efficacy of rituximab (RTX) combined chemotherapy for patients with diffuse large B-cell lymphoma (DLBCL).

METHODSFcγRIIIa polymorphisms were analyzed by PCR in 122 patients and 100 healthy controls. All patients received 8(4-12) cycles of RTX combined chemotherapy.

RESULTS78(63.93%) patients with F/F, 5(4.10%) with V/V, and 39(31.97%) with V/F were identified, which were not different compared to controls. Patients with different FcγRIIIa genotypes did not have any difference in terms of gender, age, molecular subtypes, lactate dehydrogenase (LDH) or international prognostic index (IPI). The overall response rate (ORR) was 89.35% with a complete response (CR) of 80.33% and a partial response (PR) of 9.02%. The ORR was 83.33%, 100.00% and 100.00% in F/F, V/V and V/F, respectively. A higher response rate was observed in V/V and V/F as compared with F/F (P<0.05). With a median follow-up of 35 months (range: 12-62 months), 46(37.71%) patients had relapsed and 40 (32.79%) cases progressed and ended in death. The 3-year progress-free survival (PFS) rate was 41.03%, 100.00%, 100.00% in F/F, V/V and V/F, respectively. The 3-year overall survival (OS) rate was 48.72%, 100.00% and 100.00% in patients with three genotypes. The PFS and OS rate were significantly higher in V/V and V/F as compared with F/F (P<0.05).

CONCLUSIONFcγR III a polymorphisms could predict response and prognosis of RTX combined chemotherapy for patients with DLBCL.

Antibodies, Monoclonal, Murine-Derived ; administration & dosage ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Asian Continental Ancestry Group ; genetics ; Disease-Free Survival ; GPI-Linked Proteins ; Humans ; Lymphoma, Large B-Cell, Diffuse ; drug therapy ; genetics ; Polymorphism, Genetic ; Prognosis ; Receptors, IgG ; genetics ; Remission Induction ; Rituximab

OBJECTIVETo compare the efficacy and safety of low-dose rituximab combined with different dosage of glucocorticoids for immune thrombocytopenia (ITP).

METHODSSeventy-four patients (35 male, median age 34 years, range 18-70 years) including 60 newly-diagnosed, 6 persistent, 5 chronic and 3 refractory patients were enrolled in this study, and separated into control (36 cases) and experimental (38 cases) groups according to the dosage of glucocorticoids. Patients in both groups received dexamethasone 40 mg/day on days 1-4, followed by rituximab 100 mg on days 7, 14, 21, 28. The patients in experimental group also received decrements of prednisone 60, 30, 20, 10 mg/day on days 5-7, 8-14, 15-21, 22-28. The initial, long-term efficacy and safety were evaluated.

RESULTSPlatelet counts of all patients at day 4 remarkably increased, with the median platelet count from 11(1-26) × 10⁹/L to 84(23-132) × 10⁹/L in control group, and 10(2-20) × 10⁹/L to 80(22-115) × 10⁹/L in experimental group; the platelet counts of patients at day 14 in experimental group [163(19-262) × 10⁹/L] was higher than that of control group [98(18-238) × 10⁹/L] (P<0.05). The overall response (OR) rates at day 28 in experimental group (84.21%) was significantly higher than that of control group (66.67%, P = 0.03). There was no significant difference of sustained response (SR) rates in two groups (63.89%vs 65.79%, 58.33%vs 60.53%, P > 0.05) at six and twelve months follow-up points. Both groups showed similar incidence of adverse events, and no patients discontinued the treatment due to side effects.

CONCLUSIONLow-dose rituximab and glucocorticoids was an effective method for ITP patients, and maintenance treatment with decrements of prednisone contributed to improving earlier CR rate.

Adolescent ; Adult ; Aged ; Antibodies, Monoclonal, Murine-Derived ; therapeutic use ; Female ; Follow-Up Studies ; Glucocorticoids ; administration & dosage ; therapeutic use ; Humans ; Male ; Middle Aged ; Rituximab ; Thrombocytopenia ; drug therapy ; Treatment Outcome ; Young Adult

OBJECTIVETo evaluate the efficacy and safety of a chemoimmunotherapy regimen of rituximab, fludarabine and cyclophosphamide (FCR) for patients with chronic lymphocytic leukemia(CLL).

METHODSThe clinical data of 26 CLL patients receiving FCR regimen in our hospital from April 2003 to January 2012 were analyzed retrospectively. Patients were grouped according to indicators including Rai risk stratification, β(2)-MG, LDH, ZAP-70, CD38, cytogenetics and immunoglobulin heavy chain variable region gene (IgVH) mutation status. Therapy efficacy and survival were evaluated and the safety of FCR regimen was assessed.

RESULTSAmong 26 patients, the overall response rate ( ORR ) was 76.9%, 10 patients (38.5%) achieved complete remission(CR) and 10(38.5%) partial remission(PR). With a median follow-up time of 30 ( 3-98 ) months, the median estimated progression-free survival(PFS) for all patients was 42(16-68) months and median overall survival(OS) was 63(41-85)months. Clinical parameters associated with higher CR rates were ＜2 courses of prior treatment regimens, proportions of bone marrow lymphocytes declining ≥ 50% after 2 courses of FCR, low LDH, low β(2)-MG and ZAP-70 negative (P = 0.014, 0.008, 0.027, 0.035 and 0.013, retrospectively). PFS and OS time in minimal residual disease(MRD)-negative, normal LDH and proportions of bone marrow lymphocytes declining ≥ 50% after 2 courses of FCR patients were significantly better than that of the control group (P＜0.05), PFS in the non-high-risk genetics group was significantly better than that in the high-risk genetics group (P = 0.005), while OS between two groups showed no statistically significant difference. The most common toxicities were gastrointestinal reactions (88.5%), followed by bone marrow suppression (80.8%): including neutropenia, anemia and thrombocytopenia. Infections accounted for 30.8%, mainly lung infection.

CONCLUSIONFCR is an effective and well-tolerated therapy for patients with CLL. Patients with MRD-positive, elevated LDH, proportions of bone marrow lymphocytes declining＜50% after 2 courses of FCR and high risk genetics patients are suitable for more effective treatment after achieving treatment response.

Adult ; Aged ; Antibodies, Monoclonal, Murine-Derived ; administration & dosage ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Cyclophosphamide ; administration & dosage ; Female ; Follow-Up Studies ; Humans ; Kaplan-Meier Estimate ; Leukemia, Lymphocytic, Chronic, B-Cell ; drug therapy ; Male ; Middle Aged ; Retrospective Studies ; Rituximab ; Treatment Outcome ; Vidarabine ; administration & dosage ; analogs & derivatives

Adult ; Antibodies, Monoclonal, Murine-Derived ; therapeutic use ; Central Nervous System Neoplasms ; therapy ; Female ; Hematopoietic Stem Cell Transplantation ; Humans ; Injections, Spinal ; Lymphoma, Non-Hodgkin ; therapy ; Male ; Methotrexate ; administration & dosage ; therapeutic use ; Middle Aged ; Rituximab

OBJECTIVETo investigate the efficacy and safety as well as the effects of lower dose of rituximab on B-lymphocytes, serum immunoglobulin, and platelet glycoprotein-specific antibodies in patients with chronic refractory immune thrombocytopenic purpura (ITP).

METHODSTwenty chronic refractory ITP patients, median age 47 (20 to 60) years old, received intravenous rituximab at the dose of 100mg once weekly for 4 consecutive weeks. Laboratory studies included complete blood cell count, regular monitoring of liver and kidney functions, blood coagulation and serum concentrations of IgG, IgM and IgA. CD3(+), CD4(+), CD8(+), CD19(+), CD20(+) cell numbers were assayed by flow cytometry prior to and following rituximab. Platelet glycoprotein antibodies were detected by ELISA. The detection of indicators were compared by paired T test, with P < 0.05 as statistically significant.

RESULTSThere was significant difference of the average platelet count between prior- \[(13 ± 5) × 10(9)/L\] and post-treatment \[(124 ± 106) × 10(9)/L\] with lower dose rituximab (P < 0.01). Reaching PLT peak period was of (24 ± 7) d with median time of 18 d. The responses were of 11(55%) CR, 4 (20%) R and 5 (25%) NR, respectively, with median response duration of 8 months (5 - 23 months). There were no significant changes of peripheral blood white blood cell count, hemoglobin, serum immunoglobulin, as well as CD3(+), CD4(+), CD8(+) lymphocyte counts during prior- and post-treatment. CD19(+)/CD20(+) cells were almost depleted in all patients \[(125.65 ± 14.12) × 10(6)/L vs (50.53 ± 29.11) × 10(6)/L, P < 0.01)\]. Expectedly, three cases of positive detection of platelet antibodies were negative after 4 weeks of lower dose of rituximab; one patient experienced infusion-related reaction.

CONCLUSIONTreatment with lower dose rituximab may be an effective and safe approach in patient with chronic refractory ITP. However, the optimal therapeutic schedule, long-term efficacy and adverse events need further investigation.

Adult ; Antibodies, Monoclonal, Murine-Derived ; administration & dosage ; therapeutic use ; Humans ; Middle Aged ; Purpura, Thrombocytopenic, Idiopathic ; drug therapy ; prevention & control ; Recurrence ; Rituximab ; Treatment Outcome ; Young Adult