Cancer/Testis Antigen CT45 Is Frequently Expressed in Hodgkin’s Lymphoma and Associated with Nodular Sclerosis Subtype and Advanced Disease.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4591-4591 ◽  
Author(s):  
Alexander Claviez ◽  
Christine Mauz-Körholz ◽  
Hans-Jürgen Heidebrecht ◽  
Günther Schellong ◽  
Dieter Körholz ◽  
...  
Keyword(s):  
Children And Adolescents ◽  
Expression Pattern ◽  
Hodgkin’S Lymphoma ◽  
Advanced Disease ◽  
Hodgkin's Lymphoma ◽  
Histological Subtypes ◽  
Free Survival ◽  
Nodular Sclerosis ◽  
Ct Antigen ◽  
Cancer Testis

Abstract Cancer/testis (CT) antigens are members of a large tumor-associated protein family of increasing interest because of their diagnostic and possible therapeutic implications. Only few studies have investigated CT antigen expression in Hodgkin’s lymphoma (HL) so far. Recently, immunopurification of a 25/22-kDa antigen and sequencing revealed a peptide of 14 amino acids, which corresponds to the gene product of the newly described gene family MGC27005, located on chromosome Xq26.3, now termed CT45. The antigen shows a CT antigen-like expression pattern in human tissues and is detectable by the monoclonal antibody Ki-A10 generated after immunization of mice with HL-derived cell line L428. In this study, the expression pattern of CT45 in a large number of patients with HL included in subsequent pediatric multicenter treatment protocols of the GPOH was analyzed. Immunohistochemical results of Ki-A10 staining were correlated with histological subtype, immunophenotype, clinical data and outcome. In total, 1124 children and adolescents with HL diagnosed between 1978 and 2004 were studied. Median age of the patients was 13.7 years (range, 2.2 to 19.5) and 637 patients 02(57%) were male. Classical HL (cHL) was diagnosed in 988 patients (88%) and nodular lymphocyte predominant HL (NLPHL) was seen in 136 patients (12%). The group of cHL included 683 cases of nodular sclerosis HL (NSHL), 280 cases of mixed cellularity HL (MCHL), ten cases of lymphocyte-rich cHL (LRCHL), seven cases of lymphocyte-depleted HL (LDHL) and eight cases without subclassification. Nuclear CT45 expression was found in 526 cases (47%) with striking differences among histological subtypes and unrelated to CD30, CD20 and latent EBV infection. In NLPHL, 15% of cases scored CT45 positive in contrast to 51% of cases in cHL (p<.001). Within cHL, 58% of cases with NSHL were CT45 positive compared to 36% of cases with MCHL (p<.001). Aggressive histological variants of cHL (NSHL Bennett 2, LDHL) stained positive for CT45 in 62% of cases in comparison to 49% of other subtypes (p=.002). CT45 expression was associated with stage (p<.001), presence of B symptoms (p=.026), extranodal disease (p=.009) and allocation to treatment group (TG, p<.001). Fewer patients from TG1 (localized disease) were CT45 positive than patients from TG2/3 (intermediate and advanced disease; 38% vs. 53%, p<.001). With a median follow-up of 5.6 years, 97% of patients are alive. No significant differences were observed for overall survival, failure-free survival and event-free survival with respect to CT45 status. CT45 expression, which is restricted to neoplastic cells in HL, is found in a significant number of children and adolescents with HL, especially in cases of NSHL, aggressive histological subtypes and advanced disease. Due to effective polychemotherapy with or without low-dose radiotherapy, CT45 status did not emerge as an adverse prognostic factor in children and adolescents with HL in this series.

The Impact of Latent Epstein-Barr Virus Infection on Outcome in Children and Adolescents with Hodgkin’s Lymphoma.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 3121-3121
Author(s):  
Alexander Claviez ◽  
Markus Tiemann ◽  
Heike Lueders ◽  
Reza Parwaresch ◽  
Guenther Schellong ◽  
...  
Keyword(s):  
Overall Survival ◽  
Children And Adolescents ◽  
Hodgkin’S Lymphoma ◽  
Epstein Barr Virus ◽  
Hodgkin's Lymphoma ◽  
Barr Virus ◽  
Ebv Infection ◽  
Nodular Sclerosis ◽  
Epstein Barr ◽  
The Impact

Abstract The prognostic significance of latent Epstein-Barr virus (EBV) infection in Hodgkin’s lymphoma (HL) is debated controversially. Especially in the pediatric age group, no conclusive data are available due to small series. 842 children and adolescents (55% male) with a median age of 13.7 years (range, 2–20) from consecutive pediatric DAL/GPOH multicenter treatment studies HD-90 and HD-95 were studied for the presence of latent EBV infection in Hodgkin and Reed-Sternberg cells by immunostaining against latent membrane protein 1 (LMP-1). Histology subtypes were as follows: nodular sclerosis (NSHL) 549, mixed cellularity (MCHL) 190, lymphocyte predominance (NLPHL) 90, lymphocyte depletion (LDHL) 6, lymphocyte-rich classical HL (LRCHL) 5, not specified 2. 88 patients had stage I, 470 had stage II, 172 had stage III and 112 had stage IV. B symptoms were present in 274 patients (33%). LMP status was compared with clinical parameters and established risk factors. A total of 263 patients (32%) were LMP positive. EBV infection correlated with gender (male 39% vs. female 23%; p<.001), histological subtype (MCHL 69% vs. NSHL 22% vs. NLPHL 6%; p<.001) and age (<10 years 67% vs ≥10 years 28%, p<.001. With a median follow-up of 4.9 years (0.3–12) 820 patients (97%) are alive. Probability of overall survival at 10 years (±SD) for EBV negative and positive patients was 98±1% and 95±1%, respectively (p=.017 by log-rank test). Probability of failure-free survival (FFS) in LMP positive and negative patients was 89±2% and 84±4%, respectively (p=.86). With respect to LMP status, a negative effect of latent EBV infection on overall survival became evident only for patients treated for advanced stages (p=.003), those with nodular sclerosis subtype Bennett II (p=.02) and B symptoms (p=.05). In a multivariate regression analysis, allocation to treatment group (RR=3.7) and LMP positivity (RR=3.01) were independent factors for overall survival and presence of B symptoms (RR=2.4) for FFS. Under current highly effective polychemotherapy with or without involved field radiotherapy in pediatric HL, latent EBV infection has no influence on FFS in univariate and multivariate analysis. LMP positivity, however, seems to be associated with an inferior overall survival in some subgroups.

Impact of Latent Epstein-Barr Virus Infection on Outcome in Children and Adolescents With Hodgkin's Lymphoma

2005 ◽  
Vol 23 (18) ◽  
pp. 4048-4056 ◽  
Author(s):  
Alexander Claviez ◽  
Markus Tiemann ◽  
Heike Lüders ◽  
Matthias Krams ◽  
Reza Parwaresch ◽  
...  
Keyword(s):  
Overall Survival ◽  
Children And Adolescents ◽  
Hodgkin’S Lymphoma ◽  
Epstein Barr Virus ◽  
Hodgkin's Lymphoma ◽  
Histologic Subtype ◽  
Barr Virus ◽  
Ebv Infection ◽  
Nodular Sclerosis ◽  
Epstein Barr

Purpose The prognostic significance of latent Epstein-Barr virus (EBV) infection in Hodgkin's lymphoma (HL) is debated controversially. Especially in the pediatric age group, no conclusive data are available. Patients and Methods Eight hundred forty-two children and adolescents (median age, 13.7 years) from pediatric multicenter treatment studies HD-90 and HD-95 were studied for latent EBV infection in Hodgkin's and Reed-Sternberg cells by immunostaining against latent membrane protein 1 (LMP-1). Results were compared with established risk factors. Results Two hundred sixty-three patients (31%) were LMP positive. EBV infection correlated with sex (39% male v 23% female; P < .001), histologic subtype (69% mixed cellularity v 22% nodular sclerosis v 6% lymphocyte predominance; P < .001) and young age. With a median follow-up of 4.9 years, 820 patients (97%) are alive. Probability of overall survival at 10 years (± standard deviation) for EBV-negative and -positive patients was 98.1% ± 0.6% and 95.1% ± 1.4%, respectively (P = .017 by log-rank test). A negative effect of EBV infection became evident for patients with nodular sclerosis subtype Bennett II (P = .02), and those treated for advanced stages (P = .003). In multivariate analysis, LMP positivity was an independent factor for adverse outcome (RR = 3.08). Probability of failure-free survival (FFS) in LMP positive and negative patients was 89.1% ± 2.3% and 84.1% ± 3.9%, respectively (P = .86). Conclusion With effective combined treatment modalities in pediatric HL, latent EBV infection has no influence on FFS but is associated with an inferior overall survival in crucial subgroups.

Effect of Race on the Outcome of Pediatric Patients With Hodgkin's Lymphoma

2008 ◽  
Vol 26 (8) ◽  
pp. 1282-1288 ◽  
Author(s):  
Monika L. Metzger ◽  
Sharon M. Castellino ◽  
Melissa M. Hudson ◽  
Shesh N. Rai ◽  
Sue C. Kaste ◽  
...  
Keyword(s):  
Hodgkin’S Lymphoma ◽  
Clinical Characteristics ◽  
Hemoglobin Concentration ◽  
Black Children ◽  
Hodgkin's Lymphoma ◽  
Event Free Survival ◽  
White Children ◽  
Free Survival ◽  
Black And White ◽  
Black Patients

Purpose Some cooperative groups have found a survival disadvantage in black children with various childhood cancers. We examine the effects of race on clinical outcomes among children with Hodgkin's lymphoma (HL) treated with contemporary therapy at a tertiary care children's hospital. Patients and Methods Retrospective analysis of 327 children and adolescents diagnosed with HL between 1990 and 2005. Patients were treated with risk-directed multimodal therapy regardless of race, ethnicity, or ability to pay. Event-free and overall survival rates were compared for black and white children. Clinical characteristics, socioeconomic factors, and biologic features were analyzed for prognosis of treatment failure. Results The 262 white and 65 black patients did not differ significantly in presenting features, clinical characteristics, or enrollment in a clinical trial. More black patients (71% v 45%) resided in poor counties (P < .001). While black and white children were equally likely to have progressive disease or early relapse, black children were 3.7 times (95% CI, 1.7 to 8.0) more likely to relapse 12 months or more after diagnosis. The 5-year event-free survival was 71% ± 6.1% (SE) for black and 84% ± 2.4% for white children (P = .01). However, the 5-year survival rate did not differ between white and black children (94.4% v 94.7%). While black race and low hemoglobin concentration were independent predictors of treatment failure, only low hemoglobin concentration independently predicted poor survival. Conclusion Black children with Hodgkin's lymphoma have lower event-free survival than white children, but both populations have the same 5-year overall survival.

scholarly journals 18FDG-PET following treatment as valid predictor for disease-free survival in Hodgkin’s lymphoma

2001 ◽  
Vol 12 (1) ◽  
pp. 29-37 ◽  
Author(s):  
M. de Wit ◽  
K.H. Bohuslavizki ◽  
R. Buchert ◽  
D. Bumann ◽  
M. Clausen ◽  
...  
Keyword(s):  
Hodgkin’S Lymphoma ◽  
Disease Free Survival ◽  
Hodgkin's Lymphoma ◽  
Free Survival ◽  
18Fdg Pet ◽  
Valid Predictor ◽  
Disease Free

AIDS-Related Malignancies: State of the Art and Therapeutic Challenges

2008 ◽  
Vol 26 (29) ◽  
pp. 4834-4842 ◽  
Author(s):  
Jean-Philippe Spano ◽  
Dominique Costagliola ◽  
Christine Katlama ◽  
Nicolas Mounier ◽  
Eric Oksenhendler ◽  
...  
Keyword(s):  
Patient Outcomes ◽  
Hodgkin’S Lymphoma ◽  
Advanced Disease ◽  
State Of The Art ◽  
Hodgkin's Lymphoma ◽  
Increased Risk ◽  
Therapeutic Recommendations ◽  
The Subject ◽  
The Impact ◽  
Related Mortality

Despite the impact of combination antiretroviral therapy (cART) on HIV-related mortality, malignancy remains an important cause of death in the current era. Although the advent of cART has resulted in reductions in the incidence of Kaposi's sarcoma and non-Hodgkin's lymphoma, non–AIDS-defining malignancies present an increased risk for HIV-infected patients, characterized by some common clinical features, generally with a more aggressive behavior and a more advanced disease at diagnosis, which is responsible for poorer patient outcomes. Specific therapeutic recommendations are lacking for these new nonopportunistic malignancies, such as Hodgkin's lymphoma, anal cancer, lung cancer, hepatocarcinoma, and many others. Antiretroviral agents have a propensity for causing drug interactions as a result of their ability to either inhibit or induce the cytochrome P450 (CYP) enzyme system. Because many antineoplastic drugs are also metabolized by the CYP system, coadministration with cART could result in either drug accumulation with increased toxicity, or decreased efficacy of one or both classes of drugs. Further research delineating the combined safety and pharmacokinetics of antiretrovirals and antineoplastic therapy is necessary. Special considerations of these AIDS-related and non–AIDS-related malignancies and their clinical and therapeutic aspects constitute the subject of this review.

Intensive sequential chemotherapy with repeated blood stem-cell support for untreated poor-prognosis non-Hodgkin's lymphoma.

1997 ◽  
Vol 15 (5) ◽  
pp. 1722-1729 ◽  
Author(s):  
A M Stoppa ◽  
R Bouabdallah ◽  
C Chabannon ◽  
G Novakovitch ◽  
N Vey ◽  
...  
Keyword(s):  
Stem Cell ◽  
Median Duration ◽  
Hodgkin’S Lymphoma ◽  
Dose Intensity ◽  
Blood Stem Cell ◽  
Hodgkin's Lymphoma ◽  
High Dose ◽  
Sequential Chemotherapy ◽  
Free Survival ◽  
Non Hodgkin's Lymphoma

PURPOSE To demonstrate the feasibility and efficacy of six ambulatory high-dose sequential chemotherapy courses that include three intensified cycles supported by stem-cell infusion in high-risk and high-intermediate-risk untreated non-Hodgkin's lymphoma (NHL) patients. PATIENTS AND METHODS A pilot nonrandomized study included 20 untreated patients aged less than 60 years with aggressive histologically identified NHL and two or three adverse-prognosis criteria (International Index). Patients received an ambulatory regimen with high-dose chemotherapy supported by granulocyte colony-stimulating factor (G-CSF) and repeated peripheral-blood stem-cell (PBSC) infusion. The median age was 39 years (range, 20 to 59), with 13 men and seven women. Chemotherapy consisted of one cycle every 21 days for a total of six cycles. The first three cycles (A1, A2, and A3) consisted of cyclophosphamide (Cy) 3,000 mg/m2, doxorubicin (Doxo) 75 mg/m2, and vincristine 2 mg (plus corticosteroids). The last three cycles (B4, B5, and B6) consisted of the same drug combination plus etoposide 300 mg/m2 and cisplatin 100 mg/m2. For an expected duration of 18 weeks, the projected dose-intensity was 25 mg/m2/wk for Doxo and 1,000 mg/m2/wk for Cy. G-CSF 300 micrograms was administered from day 6 following each cycle until neutrophil reconstitution. Two aphereses were performed at approximately day 13 after each A cycle, and PBSCs were injected at day 4 of each B cycle. Radiotherapy on tumor masses > or = 5 cm was scheduled after completion of the last cycle. RESULTS The median duration of grade 4 neutropenia was 1 day (range, 0 to 7) for each A cycle and 4 days (range, 1 to 10) for each B cycle (P = .02). The median duration of grade 4 thrombopenia was 0 days (range, 0 to 8) for each A cycle and 6 days (range, 1 to 21) for each B cycle (P < .001). Hospitalization for febrile neutropenia was required for 18% and 44% of patients during cycles A and B, respectively (P < .01). Only three patients did not complete the protocol: one due to emergency surgery after cycle B4, one who died after cycle B5 from interstitial pneumonia, and one with delayed hematologic reconstitution after cycle B4. Chemotherapy delivery was optimal (median actual relative dose-intensity, 97%; range, 66 to 100). The median total dose administered over 18 weeks was 18,000 mg Cy (range, 12,000 to 18,000), 450 mg Doxo (range, 300 to 450), 900 mg etoposide (range, 300 to 900), and 300 mg cisplatin (range, 100 to 300). Evaluation of response after six courses showed 13 complete remissions ([CRs] 65%), four partial remissions (PRs), two nonresponses (NRs), and one toxic death. With a median follow-up period of 25 months (range, 16 to 43), 15 patients are alive, with 12 in continuous first CR; five patients relapsed (four of four PRs and one of 13 CRs). Two-year survival and failure-free survival (FFS) rates are 73% and 56%, respectively. The disease-free survival (DFS) rate for the CRs is 86%. CONCLUSION PBSC support contributes to the feasibility of first-line, very-high-dose, ambulatory chemotherapy delivery in poor-risk NHL and is associated with a high rate of remission and FFS.

ABVD Versus Modified Stanford V Versus MOPPEBVCAD With Optional and Limited Radiotherapy in Intermediate- and Advanced-Stage Hodgkin's Lymphoma: Final Results of a Multicenter Randomized Trial by the Intergruppo Italiano Linfomi

2005 ◽  
Vol 23 (36) ◽  
pp. 9198-9207 ◽  
Author(s):  
Paolo G. Gobbi ◽  
Alessandro Levis ◽  
Teodoro Chisesi ◽  
Chiara Broglia ◽  
Umberto Vitolo ◽  
...  
Keyword(s):  
Adjuvant Radiotherapy ◽  
Hodgkin’S Lymphoma ◽  
Response Rate ◽  
Survival Rates ◽  
Progression Free Survival ◽  
Complete Response ◽  
Hodgkin's Lymphoma ◽  
Free Survival ◽  
Drug Doses ◽  
Advanced Hodgkin’S Lymphoma

Purpose In this multicenter, prospective, randomized clinical trial on advanced Hodgkin's lymphoma (HL), the efficacy and toxicity of two chemotherapy regimens, doxorubicin, vinblastine, mechlorethamine, vincristine, bleomycin, etoposide, and prednisone (Stanford V) and mechlorethamine, vincristine, procarbazine, prednisone, epidoxirubicin, bleomycin, vinblastine, lomustine, doxorubicin, and vindesine (MOPPEBVCAD), were compared with doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) as standard therapy to select which regimen would best support a reduced radiotherapy program, which was limited to ≤ two sites of either previous bulky or partially remitting disease (a modification of the original Stanford program). Patients and Methods Three hundred fifty-five patients with stage IIB, III, or IV HL were randomly assigned. Three hundred thirty-four patients were assessable for the study and received six cycles of ABVD (n = 122), three cycles of Stanford V (n = 107), or six cycles of MOPPEBVCAD (n = 106); radiotherapy was administered to 76, 71, and 50 patients in these three arms, respectively. Results The complete response rates for ABVD, Stanford V, and MOPPEBVCAD were 89%, 76% and 94%, respectively; 5-year failure-free survival (FFS) and progression-free survival rates were 78%, 54%, 81% and 85%, 73%, and 94%, respectively (P < .01 for comparison of Stanford V with the other two regimens). Corresponding 5-year overall survival rates were 90%, 82%, and 89% for ABVD, Stanford V, and MOPPEBVCAD, respectively. Stanford V was more myelotoxic than ABVD but less myelotoxic than MOPPEBVCAD, which had larger reductions in the prescribed drug doses. Conclusion When associated with conditioned and limited (not adjuvant) radiotherapy, ABVD and MOPPEBVCAD were superior to Stanford V chemotherapy in terms of response rate and FFS and progression-free survival. Patients were irradiated less often after MOPPEBVCAD, but this regimen was more toxic. ABVD is still the best choice when it is combined with optional, limited irradiation.

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