22 results on '"Horning, SJ"'
Search Results
2. Treatment approaches to the low-grade lymphomas
- Author
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Horning, SJ, primary
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- 1994
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3. Granulocyte colony-stimulating factor "mobilized" peripheral blood progenitor cells accelerate granulocyte and platelet recovery after high-dose chemotherapy
- Author
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Chao, NJ, primary, Schriber, JR, additional, Grimes, K, additional, Long, GD, additional, Negrin, RS, additional, Raimondi, CM, additional, Horning, SJ, additional, Brown, SL, additional, Miller, L, additional, and Blume, KG, additional
- Published
- 1993
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4. Dynamic assessment of quality of life after autologous bone marrow transplantation
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Chao, NJ, primary, Tierney, DK, additional, Bloom, JR, additional, Long, GD, additional, Barr, TA, additional, Stallbaum, BA, additional, Wong, RM, additional, Negrin, RS, additional, Horning, SJ, additional, and Blume, KG, additional
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- 1992
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5. Enhanced detection of the t(14;18) translocation in malignant lymphoma using pulsed-field gel electrophoresis
- Author
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Zelenetz, AD, primary, Chu, G, additional, Galili, N, additional, Bangs, CD, additional, Horning, SJ, additional, Donlon, TA, additional, Cleary, ML, additional, and Levy, R, additional
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- 1991
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6. CEPP(B): an effective and well-tolerated regimen in poor-risk, aggressive non-Hodgkin's lymphoma
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Chao, NJ, primary, Rosenberg, SA, additional, and Horning, SJ, additional
- Published
- 1990
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7. Detection of non-Hodgkin's lymphoma in the peripheral blood by analysis of antigen receptor gene rearrangements: results of a prospective study
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Horning, SJ, primary, Galili, N, additional, Cleary, M, additional, and Sklar, J, additional
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- 1990
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8. Clinical and phenotypic diversity of T cell lymphomas
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Horning, SJ, Weiss, LM, Crabtree, GS, and Warnke, RA
- Abstract
Forty-one cases of T cell lymphoma were identified on the basis of morphology and the expression of two or more T cell antigens with an absence of B cell markers. Mycosis fungoides and lymphoblastic lymphoma were excluded. Marked clinical, morphological, and immunologic diversity was observed. Cutaneous lymphoma was found in approximately 50% of the patient group, and 27% had a prior history of dermatologic or immunologic disease. No correlations among immunologic and morphologic phenotypes and clinical course were apparent. Survival data was comparable to that of a concurrent group of non-T cell lymphoma patients studied at this institution, suggesting that, contrary to previous reports, T cell lymphoma may not necessarily confer a more unfavorable prognosis. Prospective studies using uniform treatments are necessary to address the clinical significance of the T cell phenotype definitively, independent of established histologic and clinical features.
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- 1986
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9. Treatment of B-cell lymphomas with anti-idiotype antibodies alone and in combination with alpha interferon
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Brown, SL, Miller, RA, Horning, SJ, Czerwinski, D, Hart, SM, McElderry, R, Basham, T, Warnke, RA, Merigan, TC, and Levy, R
- Abstract
Idiotypes are distinct clonal markers for B-cell lymphomas. Previously we reported the use of anti-idiotype antibodies in the therapy of patients with B-cell malignancies. Because synergy was demonstrated with the addition of alpha interferon to anti-idiotype antibodies in a murine lymphoma model, we performed a clinical trial combining these two agents. Here we provide an update of the original trial of anti- idiotype antibodies alone and report the outcome of the new combination trial. In 16 treatment courses of anti-idiotype antibodies alone there were seven partial responses and one complete response. In 12 courses of combination anti-idiotype antibody and alpha interferon there were two complete responses and seven partial responses. Substantial tumor regressions occurred with minimal toxicity in both trials even in patients refractory to conventional chemotherapy. Tumor specimens obtained at the time of disease progression often contained a preponderance of idiotype-negative lymphoma cells, suggesting that anti- idiotype antibody treatment exerted a strong antitumor effect against antigen-positive cells. Anti-idiotype antibodies have reproducible objective antitumor activity in B-cell lymphoma. The addition of alpha interferon may improve the initial rate of response to this treatment. Strategies that deal effectively with idiotype-negative lymphoma cells should improve the extent and duration of these responses.
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- 1989
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10. The treatment of malignant histiocytosis
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Tseng, A Jr, Coleman, CN, Cox, RS, Colby, TV, Turner, RR, Horning, SJ, and Rosenberg, SA
- Abstract
Twenty-four consecutive cases of malignant histiocytosis (MH) treated at Stanford Medical Center between 1973 and 1983 have been reviewed. Most patients presented with systemic symptoms (91%) and advanced disease (stage IV, 80%). Multiple organ involvement was common. In six cases, pathologic tissue was further characterized by frozen section immune histochemistry, using a panel of monoclonal antibodies known to react with monocytes and macrophages, as well as a variety of hematopoietic cells. One case expressed a mature monocyte/macrophage phenotype; three cases were considered null cell or primitive lesions; and two cases were identified as probable T cell lymphomas. Seven patients underwent splenectomy. Two patients died prior to any treatment. Twenty-two patients were treated with CHOP (cyclophosphamide, Adriamycin, vincristine, prednisone) +/- bleomycin (B), +/- midcycle high-dose methotrexate (HD-MTX) with leucovorin rescue. Seven patients received prophylactic intrathecal MTX. Of 22 evaluable patients, there was a 68% complete response rate (CR), a 23% partial response rate (PR), and a 9% no response rate (NR). Median duration of CR was 30+ months; median duration of PR was 2.4 months. Median survival for patients attaining a CR has not been reached v 3 months for the PR and NR groups. For all 24 patients, median survival was 2 years, with a 5-year actuarial survival of 40%. Multivariate analysis revealed that a platelet count less than 150,000 (P Cox = .005) and the dose of drug delivered (P Cox = .057) were the most important prognostic factors. Prophylactic intrathecal MTX therapy and splenectomy did not influence survival. Although MH is an aggressive disease with a poor prognosis, it is potentially curable. Systematic and aggressive treatment should further improve the outcome.
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- 1984
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11. Clinical relevance of immunologic phenotype in diffuse large cell lymphoma
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Horning, SJ, Doggett, RS, Warnke, RA, Dorfman, RF, Cox, RS, and Levy, R
- Abstract
The immunologic phenotypes of 78 diffuse large cell lymphomas were determined by an immunoperoxidase technique using a panel of monoclonal antibodies. The phenotypes were correlated with clinical and morphological parameters by univariate and multivariate analysis. Forty- one lymphomas (53%) expressed immunoglobulin (Ig+). Of the 37 cases that did not express immunoglobulin (Ig-), 9 expressed T cell antigens. Although the T cell phenotypes were antigenically heterogeneous, all cases represented mature T cell phenotypes. The majority of the remaining 28 cases expressed the B cell-associated antigen, B1. At 5 yr, actuarial survival for the Ig- patients was 63%, compared with 15% for the Ig+ patients. A significantly greater proportion of patients with Ig+ lymphomas were over the age of 65 at diagnosis. All of the 9 patients with marrow involvement were Ig+. Multiple factors were analyzed by the Cox regression procedure for their impact on survival, including antigenic profile, histologic grade, morphological classification, and numerous clinical parameters previously recognized to be of prognostic significance. In this analysis, stage, age greater than 65 yr, systemic symptoms, and marrow involvement had the greatest influence on survival. The survival difference between Ig- and Ig+ patients is explained by a higher proportion of Ig+ patients with these unfavorable prognostic factors. With our current immunologic methods, retrospective cell phenotyping analysis has not provided independent prognostic significance in diffuse large cell lymphoma. A prospective evaluation of similarly treated patients is needed to characterize the influence of phenotype fully and to determine its potential usefulness for therapy.
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- 1984
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12. Phase 2 study of VcR-CVAD with maintenance rituximab for untreated mantle cell lymphoma: an Eastern Cooperative Oncology Group study (E1405).
- Author
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Chang JE, Li H, Smith MR, Gascoyne RD, Paietta EM, Yang DT, Advani RH, Horning SJ, and Kahl BS
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- Adult, Aged, Bortezomib, Cyclophosphamide therapeutic use, Dexamethasone therapeutic use, Doxorubicin therapeutic use, Female, Follow-Up Studies, Humans, Lymphoma, Mantle-Cell mortality, Lymphoma, Mantle-Cell pathology, Male, Middle Aged, Neoplasm Staging, Prognosis, Remission Induction, Rituximab, Survival Rate, Vincristine therapeutic use, Antibodies, Monoclonal, Murine-Derived administration & dosage, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Boronic Acids administration & dosage, Lymphoma, Mantle-Cell drug therapy, Pyrazines administration & dosage
- Abstract
Rituximab, bortezomib, modified hyper-cyclophosphamide, doxorubicin, vincristine, dexamethasone (VcR-CVAD) induction chemoimmunotherapy and maintenance rituximab (MR) were evaluated for efficacy and safety in Eastern Cooperative Oncology Group protocol E1405. Patients with previously untreated mantle cell lymphoma received VcR-CVAD chemotherapy every 21 days for 6 cycles, followed by MR for 2 years. Transplant-eligible patients had the option of autologous stem cell transplantation (ASCT) consolidation instead of MR. The primary end point was the complete response (CR) rate to VcR-CVAD. The secondary end points were overall response rate (ORR), progression-free survival (PFS), overall survival (OS), and toxicities. Seventy-five eligible patients with a median age of 62 (range 40-76) were enrolled. The ORR was 95% and a CR was achieved in 68% of patients. After a median follow-up of 4.5 years, 3-year PFS and OS were 72% and 88%, respectively. No substantial difference in PFS or OS was observed between patients treated with MR (n = 44) vs ASCT (n = 22). There were no unexpected toxicities. VcR-CVAD produced high ORR and CR rates in mantle cell lymphoma. MR after VcR-CVAD induction performed similarly to ASCT and may improve response duration. Randomized clinical trials comparing MR against ASCT should be considered and randomized clinical trials evaluating bortezomib's contribution to conventional therapy are under way. This study was registered at www.clinicaltrials.gov as #NCT00433537.
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- 2014
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13. Improvements in observed and relative survival in follicular grade 1-2 lymphoma during 4 decades: the Stanford University experience.
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Tan D, Horning SJ, Hoppe RT, Levy R, Rosenberg SA, Sigal BM, Warnke RA, Natkunam Y, Han SS, Yuen A, Plevritis SK, and Advani RH
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- Academic Medical Centers, Adult, Aged, Aged, 80 and over, Anthracyclines therapeutic use, Antibodies, Monoclonal, Murine-Derived therapeutic use, Antineoplastic Agents therapeutic use, California, Female, Humans, Male, Middle Aged, Retrospective Studies, Rituximab, Survival Analysis, Treatment Outcome, Young Adult, Lymphoma, Follicular drug therapy, Lymphoma, Follicular mortality
- Abstract
Recent studies report an improvement in overall survival (OS) of patients with follicular lymphoma (FL). Previously untreated patients with grade 1 to 2 FL treated at Stanford University from 1960-2003 were identified. Four eras were considered: era 1, pre-anthracycline (1960-1975, n = 180); era 2, anthracycline (1976-1986, n = 426); era 3, aggressive chemotherapy/purine analogs (1987-1996, n = 471); and era 4, rituximab (1997-2003, n = 257). Clinical characteristics, patterns of care, and survival were assessed. Observed OS was compared with the expected OS calculated from Berkeley Mortality Database life tables derived from population matched by gender and age at the time of diagnosis. The median OS was 13.6 years. Age, gender, and stage did not differ across the eras. Although primary treatment varied, event-free survival after the first treatment did not differ between eras (P = .17). Median OS improved from 11 years in eras 1 and 2 to 18.4 years in era 3 and has not yet been reached for era 4 (P < .001), with no suggestion of a plateau in any era. These improvements in OS exceeded improvements in survival in the general population during the same period. Several factors, including better supportive care and effective therapies for relapsed disease, are likely responsible for this improvement.
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- 2013
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14. Plasma Epstein-Barr virus DNA predicts outcome in advanced Hodgkin lymphoma: correlative analysis from a large North American cooperative group trial.
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Kanakry JA, Li H, Gellert LL, Lemas MV, Hsieh WS, Hong F, Tan KL, Gascoyne RD, Gordon LI, Fisher RI, Bartlett NL, Stiff P, Cheson BD, Advani R, Miller TP, Kahl BS, Horning SJ, and Ambinder RF
- Subjects
- Adolescent, Adult, Aged, Aged, 80 and over, Bleomycin administration & dosage, Bleomycin therapeutic use, Dacarbazine administration & dosage, Doxorubicin administration & dosage, Doxorubicin therapeutic use, Epstein-Barr Virus Infections blood, Epstein-Barr Virus Infections complications, Etoposide therapeutic use, Female, Herpesvirus 4, Human physiology, Hodgkin Disease blood, Hodgkin Disease complications, Humans, Male, Mechlorethamine therapeutic use, Middle Aged, Neoadjuvant Therapy, North America, Prednisone therapeutic use, Prognosis, Sensitivity and Specificity, Vinblastine administration & dosage, Vinblastine therapeutic use, Vincristine therapeutic use, Young Adult, Antineoplastic Combined Chemotherapy Protocols therapeutic use, DNA, Viral blood, Epstein-Barr Virus Infections diagnosis, Herpesvirus 4, Human genetics, Hodgkin Disease diagnosis, Hodgkin Disease drug therapy
- Abstract
Epstein-Barr virus (EBV) is associated with Hodgkin lymphoma (HL) and can be detected by in situ hybridization (ISH) of viral nucleic acid (EBER) in tumor cells. We sought to determine whether plasma EBV-DNA could serve as a surrogate for EBER-ISH and to explore its prognostic utility in HL. Specimens from the Cancer Cooperative Intergroup Trial E2496 were used to compare pretreatment plasma EBV-DNA quantification with EBV tumor status by EBER-ISH. A cutoff of >60 viral copies/100 µL plasma yielded 96% concordance with EBER-ISH. Pretreatment and month 6 plasma specimens were designated EBV(-) or EBV(+) by this cutoff. Patients with pretreatment EBV(+) plasma (n = 54) had inferior failure-free survival (FFS) compared with those with pretreatment EBV(-) plasma (n = 274), log-rank P = .009. By contrast, no difference in FFS was observed when patients were stratified by EBER-ISH. Pretreatment plasma EBV positivity was an independent predictor of treatment failure on multivariate analyses. At month 6, plasma EBV(+) patients (n = 7) had inferior FFS compared with plasma EBV(-) patients (n = 125), log-rank P = .007. These results confirm that plasma EBV-DNA is highly concordant with EBER-ISH in HL and suggest that it may have prognostic utility both at baseline and after therapy. This trial was registered at www.clinicaltrials.gov as #NCT00003389.
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- 2013
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15. Tumor-associated macrophages predict inferior outcomes in classic Hodgkin lymphoma: a correlative study from the E2496 Intergroup trial.
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Tan KL, Scott DW, Hong F, Kahl BS, Fisher RI, Bartlett NL, Advani RH, Buckstein R, Rimsza LM, Connors JM, Steidl C, Gordon LI, Horning SJ, and Gascoyne RD
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- Bleomycin therapeutic use, Cohort Studies, Dacarbazine therapeutic use, Doxorubicin therapeutic use, Female, Follow-Up Studies, Hodgkin Disease drug therapy, Hodgkin Disease immunology, Humans, Immunoenzyme Techniques, In Situ Hybridization, Macrophages drug effects, Macrophages metabolism, Male, Middle Aged, Prognosis, RNA, Viral genetics, Survival Rate, Tissue Array Analysis, Vinblastine therapeutic use, Antigens, CD metabolism, Antigens, Differentiation, Myelomonocytic metabolism, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Biomarkers, Tumor metabolism, Hodgkin Disease mortality, Macrophages pathology, Receptors, Cell Surface metabolism
- Abstract
Increased tumor-associated macrophages (TAMs) are reported to be associated with poor prognosis in classic Hodgkin lymphoma (CHL). We investigated the prognostic significance of TAMs in the E2496 Intergroup trial, a multicenter phase 3 randomized controlled trial comparing ABVD and Stanford V chemotherapy in locally extensive and advanced stage CHL. Tissue microarrays were constructed from formalin-fixed, paraffin-embedded tumor tissue and included 287 patients. Patients were randomly assigned into training (n = 143) and validation (n = 144) cohorts. Immunohistochemistry for CD68 and CD163, and in situ hybridization for EBV-encoded RNA were performed. CD68 and CD163 IHC were analyzed by computer image analysis; optimum thresholds for overall survival (OS) were determined in the training cohort and tested in the independent validation cohort. Increased CD68 and CD163 expression was significantly associated with inferior failure-free survival and OS in the validation cohort. Increased CD68 and CD163 expression was associated with increased age, EBV-encoded RNA positivity, and mixed cellularity subtype of CHL. Multivariate analysis in the validation cohort showed increased CD68 or CD163 expression to be significant independent predictors of inferior failure-free survival and OS. We demonstrate the prognostic significance of TAMs in locally extensive and advanced-stage CHL in a multicenter phase 3 randomized controlled clinical trial.
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- 2012
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16. Interim positron emission tomography scans in diffuse large B-cell lymphoma: an independent expert nuclear medicine evaluation of the Eastern Cooperative Oncology Group E3404 study.
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Horning SJ, Juweid ME, Schöder H, Wiseman G, McMillan A, Swinnen LJ, Advani R, Gascoyne R, and Quon A
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- Antibodies, Monoclonal administration & dosage, Antibodies, Monoclonal, Murine-Derived, Antineoplastic Combined Chemotherapy Protocols administration & dosage, Cyclophosphamide administration & dosage, Doxorubicin administration & dosage, Education, Medical, Continuing, Fluorodeoxyglucose F18, Humans, Lymphoma, Large B-Cell, Diffuse drug therapy, Nuclear Medicine statistics & numerical data, Observer Variation, Positron-Emission Tomography statistics & numerical data, Prednisone administration & dosage, Reproducibility of Results, Rituximab, Vincristine administration & dosage, Lymphoma, Large B-Cell, Diffuse diagnostic imaging, Nuclear Medicine standards, Positron-Emission Tomography standards
- Abstract
Positive interim positron emission tomography (PET) scans are thought to be associated with inferior outcomes in diffuse large B-cell lymphoma. In the E3404 diffuse large B-cell lymphoma study, PET scans at baseline and after 3 cycles of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone were centrally reviewed by a single reader. To determine the reproducibility of interim PET interpretation, an expert panel of 3 external nuclear medicine physicians visually scored baseline and interim PET scans independently and were blinded to clinical information. The binary Eastern Cooperative Oncology Group (ECOG) study criteria were based on modifications of the Harmonization Criteria; the London criteria were also applied. Of 38 interim scans, agreement was complete in 68% and 71% by ECOG and London criteria, respectively. The range of PET(+) interim scans was 16% to 34% (P = not significant) by reviewer. Moderate consistency of reviews was observed: kappa statistic = 0.445 using ECOG criteria, and kappa statistic = 0.502 using London criteria. These data, showing only moderate reproducibility among nuclear medicine experts, indicate the need to standardize PET interpretation in research and practice. This trial was registered at www.clinicaltrials.gov as #NCT00274924 [corrected].
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- 2010
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17. Prognostic significance of Bcl-6 protein expression in DLBCL treated with CHOP or R-CHOP: a prospective correlative study.
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Winter JN, Weller EA, Horning SJ, Krajewska M, Variakojis D, Habermann TM, Fisher RI, Kurtin PJ, Macon WR, Chhanabhai M, Felgar RE, Hsi ED, Medeiros LJ, Weick JK, Reed JC, and Gascoyne RD
- Subjects
- Aged, Aged, 80 and over, Antibodies, Monoclonal, Murine-Derived, Antineoplastic Combined Chemotherapy Protocols administration & dosage, Cyclophosphamide administration & dosage, DNA-Binding Proteins deficiency, Doxorubicin administration & dosage, Female, Humans, Immunohistochemistry, Lymphoma, B-Cell diagnosis, Lymphoma, B-Cell drug therapy, Lymphoma, B-Cell mortality, Lymphoma, Large B-Cell, Diffuse diagnosis, Lymphoma, Large B-Cell, Diffuse drug therapy, Lymphoma, Large B-Cell, Diffuse mortality, Male, Middle Aged, Prednisone administration & dosage, Prognosis, Prospective Studies, Proto-Oncogene Proteins c-bcl-6, Rituximab, Survival Analysis, Survival Rate, Treatment Failure, Vincristine administration & dosage, Antibodies, Monoclonal administration & dosage, Antineoplastic Combined Chemotherapy Protocols therapeutic use, DNA-Binding Proteins analysis
- Abstract
Bcl-6 protein expression, a marker of germinal center origin, has been associated with a favorable prognosis in diffuse large B-cell lymphoma (DLBCL). To determine the prognostic significance of this marker when rituximab (R) was added to cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy, we prospectively studied Bcl-6 protein expression by immunohistochemical staining of 199 paraffin-embedded specimens from patients enrolled in the US Intergroup phase 3 trial comparing R-CHOP to CHOP with or without maintenance R. In Bcl-6(-) patients, failure-free survival (FFS) and overall survival (OS) were prolonged for those treated with R-CHOP alone compared to CHOP alone (2-year FFS 76% versus 9%, P < .001; 2-year OS 79% versus 17%, P < .001). In contrast, no differences in FFS and OS were detected between treatment arms for Bcl-6(+) cases. In the multivariate analysis, treatment arm (CHOP versus R-CHOP) was the major determinant of both FFS (P < .001) and OS (P < .001) for the Bcl-6(-) subset, whereas the International Prognostic Index risk group was the only significant predictor of outcome among Bcl-6(+) cases. Bcl-2 protein expression was not predictive of outcome in either group. In this study, we observed a reduction in treatment failures and death with the addition of R to CHOP in Bcl-6(-) DLBCL cases only. Our finding that Bcl-6(+) cases did not benefit from the addition of R to CHOP requires independent confirmation.
- Published
- 2006
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18. Rituximab as adjuvant to high-dose therapy and autologous hematopoietic cell transplantation for aggressive non-Hodgkin lymphoma.
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Horwitz SM, Negrin RS, Blume KG, Breslin S, Stuart MJ, Stockerl-Goldstein KE, Johnston LJ, Wong RM, Shizuru JA, and Horning SJ
- Subjects
- Adult, Aged, Antibodies, Monoclonal adverse effects, Antibodies, Monoclonal, Murine-Derived, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Combined Modality Therapy, Disease-Free Survival, Female, Hematopoietic Stem Cell Transplantation, Humans, Lymphoma, B-Cell drug therapy, Lymphoma, B-Cell mortality, Male, Middle Aged, Prospective Studies, Rituximab, Survival Rate, Transplantation, Autologous, Antibodies, Monoclonal therapeutic use, Lymphoma, B-Cell therapy
- Abstract
Based on the favorable safety profile and the independent activity of rituximab in B-cell lymphoma, we evaluated its efficacy and toxicity after high-dose therapy (HDT) and autologous hematopoietic cell transplantation (HCT). Thirty-five patients with diffuse large cell (25 patients), mantle cell (3 patients), transformed (3 patients), or other (4 patients) subtypes of B-cell lymphoma received HDT followed by a purged autologous graft. The rituximab schedule was 4 weekly infusions (375 mg/m(2)) starting at day 42 after HCT and, for patients 5 to 35, a second 4-week course 6 months after HCT. All planned therapy was completed in 29 patients. With 30 months' median follow-up, the 2-year event-free survival (EFS) rate was 83% and the overall survival (OS) rate was 88%. For 21 patients with relapsed or refractory large cell lymphoma, the EFS rate was 81% and the OS rate was 85%. Grades 3 to 4 neutropenia occurred in 19 (54%) patients. A prospective study of immune reconstitution included measurements of lymphocyte subsets, immunoglobulins, and response to vaccination. Serious infections were not observed despite delayed B-cell recovery in all patients and suppressed immunoglobulin G (IgG) levels and low pneumococcus antibody titers in a subset. Rituximab after HDT and HCT is feasible, and these phase 2 data support the current US Intergroup phase 3 trial in recurrent/refractory diffuse large cell lymphoma.
- Published
- 2004
- Full Text
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19. Rituximab in lymphocyte-predominant Hodgkin disease: results of a phase 2 trial.
- Author
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Ekstrand BC, Lucas JB, Horwitz SM, Fan Z, Breslin S, Hoppe RT, Natkunam Y, Bartlett NL, and Horning SJ
- Subjects
- Adolescent, Adult, Antibodies, Monoclonal toxicity, Antibodies, Monoclonal, Murine-Derived, Antigens, CD20 analysis, Disease-Free Survival, Female, Follow-Up Studies, Hodgkin Disease pathology, Humans, Lymphoma, Large B-Cell, Diffuse chemically induced, Lymphoma, Large B-Cell, Diffuse etiology, Male, Middle Aged, Neoplasms, Second Primary chemically induced, Neoplasms, Second Primary etiology, Recurrence, Remission Induction methods, Rituximab, Antibodies, Monoclonal administration & dosage, Hodgkin Disease drug therapy, Lymphocytes pathology
- Abstract
Lymphocyte-predominant Hodgkin disease (LPHD) is a unique clinical entity characterized by indolent nodal disease that tends to relapse after standard radiotherapy or chemotherapy. The malignant cells of LPHD are CD20+ and therefore rituximab may have activity with fewer late effects than standard therapy. In this phase 2 trial, 22 patients with CD20+ LPHD received 4 weekly doses of rituximab at 375 mg/m2. Ten patients had previously been treated for Hodgkin disease, while 12 patients had untreated disease. All 22 patients responded to rituximab (overall response rate, 100%) with complete response (CR) in 9 (41%), unconfirmed complete response in 1 (5%), and partial response in 12 (54%). Acute treatment-related adverse events were minimal. With a median follow-up of 13 months, 9 patients had relapsed, and estimated median freedom from progression was 10.2 months. Progressive disease was biopsied in 5 patients: 3 had recurrent LPHD, while 2 patients had transformation to large-cell non-Hodgkin lymphoma (LCL). All 3 patients with recurrent LPHD were retreated with rituximab, with a second CR seen in 1 patient and stable disease in 2. Rituximab induced prompt tumor reduction in each of 22 LPHD patients with minimal acute toxicity; however, based on the relatively short response duration seen in our trial and the concerns about transformation, rituximab should be considered investigational treatment for LPHD. Further clinical trials are warranted to determine the optimal dosing schedule of rituximab, the potential for combination treatment, and the possible relationship of rituximab treatment to the development of LCL.
- Published
- 2003
- Full Text
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20. High-dose therapy and autologous bone marrow transplantation for follicular lymphoma in first complete or partial remission: results of a phase II clinical trial.
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Horning SJ, Negrin RS, Hoppe RT, Rosenberg SA, Chao NJ, Long GD, Brown BW, and Blume KG
- Subjects
- Actuarial Analysis, Adult, Antineoplastic Combined Chemotherapy Protocols administration & dosage, Antineoplastic Combined Chemotherapy Protocols standards, Antineoplastic Combined Chemotherapy Protocols toxicity, Cohort Studies, Combined Modality Therapy, Cyclophosphamide administration & dosage, Cyclophosphamide standards, Cyclophosphamide toxicity, Disease-Free Survival, Female, Follow-Up Studies, Humans, Lymphoma, Follicular mortality, Male, Middle Aged, Neoplasm, Residual, Prednisone administration & dosage, Prednisone standards, Prednisone toxicity, Prospective Studies, Radiotherapy, Adjuvant, Recurrence, Remission Induction, Survival Rate, Transplantation, Autologous mortality, Vincristine administration & dosage, Vincristine standards, Vincristine toxicity, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Bone Marrow Transplantation mortality, Lymphoma, Follicular therapy
- Abstract
Advanced stage follicular small cleaved and mixed cell lymphoma is characterized by relapse from remission and survival ranging from 6 to 12 years. Because young patients have the greatest compromise in longevity, the efficacy and toxicity of high-dose radiochemotherapy and bone marrow transplantation after conventional chemotherapy was evaluated in a prospective phase II clinical trial. Thirty-seven patients in a minimal disease state after conventional chemotherapy received fractionated total body irradiation and high-dose etoposide and cyclophosphamide, followed by purged autologous bone marrow. A reference sample of 188 patients of similar age, stage, and histology managed at this institution before 1988 was identified for comparison of patient characteristics and outcomes. Compared with reference patients, transplant recipients had a higher tumor burden at diagnosis. With a median follow-up of 6.5 years, the estimated 10-year survival after transplantation was 86%. There was a single lymphoma death yielding a 10-year disease-specific survival of 97%. There were 2 early transplant-related deaths and 2 late acute leukemia deaths. Ten patients relapsed, one with microscopic disease only. High tumor burden at diagnosis and incomplete response to chemotherapy adversely influenced survival in the reference but not in the transplanted patients. The estimated risk of death of 14% and relapse of 30% at 10 years in our transplanted follicular lymphoma patients, the majority of whom had high tumor burdens, compares favorably with our observations in appropriately matched reference patients.
- Published
- 2001
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21. High-dose therapy and autologous hematopoietic progenitor cell transplantation for recurrent or refractory Hodgkin's disease: analysis of the Stanford University results and prognostic indices.
- Author
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Horning SJ, Chao NJ, Negrin RS, Hoppe RT, Long GD, Hu WW, Wong RM, Brown BW, and Blume KG
- Subjects
- Adolescent, Adult, Double-Blind Method, Drug Administration Schedule, Female, Follow-Up Studies, Humans, Male, Middle Aged, Prognosis, Prospective Studies, Recurrence, Regression Analysis, Survival Analysis, Transplantation, Autologous, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Hematopoietic Stem Cell Transplantation, Hodgkin Disease drug therapy, Hodgkin Disease surgery
- Abstract
One hundred nineteen patients with relapsed or refractory Hodgkin's disease (HD) received high-dose therapy followed by autologous hematopoietic progenitor cell transplantation. Three preparatory regimens, selected on the basis of prior therapy and pulmonary status, were employed. Twenty-six patients without a history of prior chest or pelvic irradiation were treated with fractionated total body irradiation, etoposide (VP) 60 mg/kg and cyclophosphamide (Cy) 100 mg/kg. Seventy-four patients received BCNU 15 mg/kg with identical doses of VP and Cy. A group of 19 patients with a limited diffusing capacity or history of pneumonitis received a novel high-dose regimen consisting of CCNU 15 mg/kg, VP 60 mg/kg and Cy 100 mg/kg. Twenty-nine patients (24%) had failed induction therapy and 35 (29%) had progressive HD within 1 year of initial chemotherapy. At 4 years actuarial survival was 52%, event-free survival was 48% and freedom from progression (FFP) was 62%. No significant differences were seen in survival data with the three preparatory regimens. Six patients died within 100 days of transplantation and 5 died at a later date of transplant-related complications. Secondary malignancies have developed in 6 patients, including myelodysplasia/leukemia in four patients and solid tumors in two patients. Regression analysis identified systemic symptoms at relapse, disseminated pulmonary or bone marrow disease at relapse and more than minimal disease at the time of transplantation as significant prognostic factors for overall and event-free survival and FFP. Patients with none of these factors enjoyed an 85% FFP at 4 years compared with 41% for patients with one or more unfavorable prognostic factors (P = .0001). Our results confirm the efficacy of high-dose therapy and autografting in recurrent or refractory HD. Although longer follow-up is necessary to address ultimate cure rates and toxicity, our data indicate that a desire to reduce late effects should drive future research efforts in favorable patients whereas new initiatives are needed for those with less favorable prognoses.
- Published
- 1997
22. Comparison between conventional salvage therapy and high-dose therapy with autografting for recurrent or refractory Hodgkin's disease.
- Author
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Yuen AR, Rosenberg SA, Hoppe RT, Halpern JD, and Horning SJ
- Subjects
- Adolescent, Adult, Drug Administration Schedule, Follow-Up Studies, Humans, Middle Aged, Recurrence, Survival Analysis, Transplantation, Autologous, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Hodgkin Disease drug therapy, Hodgkin Disease surgery
- Abstract
Sixty patients with Hodgkin's disease, refractory to or at first recurrence after chemotherapy, received cytoreductive therapy followed by high-dose etoposide, cyclophosphamide and either total body irradiation or carmustine and autografting (median follow-up, 3.6 years; range, 1.1 to 7.5 years). A matched conventional salvage group of 103 patients was selected from patients treated at Stanford University Medical Center between January 1976 and January 1989 (median follow-up, 10.3 years; range, 3.0 to 15.7 years). Overall survival (OS), event-free survival (EFS), and freedom from progression (FFP) at 4 years follow-up favored patients who received high-dose therapy compared with conventional salvage treatment (OS: 54% v 47%, P = .25; EFS: 53% v 27%, P < .01; FFP: 62% v 32%, P < .01). In Cox regression analysis, response to cytoreductive or salvage therapy and B symptoms at relapse were the most important predictors of OS. The use of high-dose therapy at relapse, a longer duration of remission, and favorable response to cytoreductive or salvage therapy were most predictive of superior FFP and EFS. These data from a single institution comparing conventional and high-dose therapy in matched patients demonstrate an advantage for high-dose therapy and autografting in the sustained control of Hodgkin's disease. As with primary therapy, it is difficult to demonstrate a statistically significant survival advantage, despite an apparently superior cure rate. However, patients failing induction therapy or relapsing within 1 year benefited significantly from high-dose therapy by all outcome measures (OS, EFS, FFP). As the transplant-related mortality rates decline in Hodgkin's disease, it is predicted that cure rates and late effects will become ultimate determinants of the success of high-dose therapy and autografting.
- Published
- 1997
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