Treatment of intermediate-grade and high-grade non-Hodgkin's lymphoma.
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Antineoplastic Combined Chemotherapy Protocols↗
Biomedical subjects
E Lepage
Publications and source records attributed to E Lepage.
Prognostic significance of a polymerase chain reaction-detectable dominant T-lymphocyte clone in cutaneous lesions of patients with mycosis fungoides.
Although mycosis fungoides (MF) is considered to be an indolent lymphoma, survival is highly influenced by TNM stage. At diagnosis, most MF patients present with early stage disease and a high probability of long-term survival. Treatment is generally directed towards skin lesions, and achievement and duration of complete responses are variable. A dominant T-cell clone is detectable in the cutaneous lesions of 60% of patients. The aim of this study was to determine whether the presence of a T-cell clonal population influences the clinical course of the disease after topical therapy. Cutaneous biopsies from 68 patients were histologically diagnosed as MF and T-cell clonality was analyzed by in vitro amplification of TCR-gamma chain gene rearrangements (polymerase chain reaction gamma [PCRgamma]). After a median follow-up of 48 months, response to treatment was clinically assessed. Age, sex, duration of symptoms before diagnosis, type of cutaneous lesions (T stage), TNM stage, and PCRgamma were evaluated as predictive factors of response to treatment in univariate and multivariate analyses. Univariate analysis demonstrated that T1 cutaneous lesions (P = .05) and PCRgamma negativity (P = .007) were associated with a higher complete remission rate. Using multivariate analysis, T stage (relative risk, 3.13; P = .06) and PCRgamma (relative risk, 4.4; P = .01) remained independent significant predictive parameters of response. In conclusion, T stage and cutaneous PCRgamma at diagnosis are the two predictive parameters of treatment response for MF. Therefore, the cutaneous PCRgamma findings should be considered in the analysis of future therapeutic trials.
Administration, Cutaneous↗
Prognostic significance of T-cell phenotype in aggressive non-Hodgkin's lymphomas. Groupe d'Etudes des Lymphomes de l'Adulte (GELA).
Peripheral T-cell lymphomas (PTCL) have been generally reported to have a worse prognosis than B-cell lymphomas (BCL). Because of their heterogeneity and scarcity, the outcomes of the different histological subtypes have not been compared. From October 1987 to March 1993, 1,883 patients with diffuse aggressive non-Hodgkin's lymphomas (NHL) included in the LNH87 protocol could be assessed for both morphology and immunophenotyping. Among them, 288 (15%) had PTCL and 1,595 (85%) had BCL. According to the Kiel classification, most PTCL were classified as angioimmunoblastic (AIL; 23%), pleomorphic medium and large T-cell (PML; 49%), or anaplastic large cell (ALCL; 20%) lymphomas. Comparing PTCL with BCL patients, the former had more disseminated disease (78% v 58%), B symptoms (57% v 40%), bone marrow involvement (31% v 17%), skin involvement (21% v 4%), and increased beta2-microglobulin (50% v 34%), whereas BCL patients had more bulky disease (41% v 26%). According to the International Prognostic Index (IPI), PTCL and BCL scores were, respectively: 0 factors, 13% and 15%; 1 factor, 17% and 22%; 2 factors, 24% and 25%; >/=3 factors, 45% and 37% (P = .09). For BCL and PTCL, respectively, complete remission rates were 63% and 54% (P = .004); the 5-year overall survival (OS) rates were 53% and 41% (P = .0004) and event-free survival (EFS) rates were 42% and 33% (P < . 0001). Comparison of the different histological subtypes of lymphoma showed that the 5-year OS rate for T-ALCL (64%) was superior to those of other PTCL (35%) as well as diffuse large B-cell (53%) NHL. When multivariate analysis was applied using the IPI score as one factor, nonanaplastic PTCL remained an independent parameter (P = . 0004). Although the poor prognosis of non-ALCL PTCL could be due in part to the presence of adverse prognostic factors at diagnosis, this study shows that the T-cell phenotype is an independent significant factor, which should be incorporated into the definition of prognostic groups.
Adolescent↗
A multivariate analysis of the survival of patients with aggressive lymphoma: variations in the predictive value of prognostic factors during the course of the disease. Groupe d'Etudes des Lymphomes de l'Adulte.
BACKGROUND: Aggressive non-Hodgkin's lymphoma is now often curable with chemotherapy. The International Prognostic Index (IPI) was recently developed to predict patient survival on the basis of pretreatment clinical features. However, classical multivariate regression models such as the IPI fail to detect time-dependent changes in the predictive value of covariates. In this study, an extension of the Cox proportional hazards model was used to determine whether the value of prognostic factors might decay over time. METHODS: A total of 1271 patients younger than 60 years, entered on the LNH-84 and LNH-87 studies of an ACVBP induction regimen (consisting of doxorubicin, cyclophosphamide, vindesine, bleomycin, methylprednisolone, and IT methotrexate), were analyzed in terms of overall survival and monthly risk of dying. By a standard method, prognostic factors were identified in a training sample and confirmed in a validation sample. The independently significant covariates were then included in a step-function regression model (3-step) that permitted determination of their value in predicting the short term and long term survival of the entire population. RESULTS: During the entire follow-up period (median, 5.5 years), lactate dehydrogenase level, tumor stage, performance status, and number of extranodal sites remained independently predictive of overall survival. However, these covariates had nonproportional hazard functions. The study of their time-dependent effect with the 3-step model confirmed that they were predictive of overall survival during the short term follow-up period of 3 months to 2 years. However, during the induction period of 0-3 months and the long term follow-up period of 2-10 years, there was only 1 independently predictive factor for each of these periods: performance status and tumor stage, respectively. CONCLUSIONS: The IPI factors are relevant to short term follow-up and permit the selection of routine or experimental therapeutic regimens. In contrast, only performance status is predictive of a patient's ability to tolerate induction chemotherapy, and only tumor stage is predictive of long term survival.
Antineoplastic Agents↗
High-dose therapy followed by stem cell transplantation in partial response after first-line induction therapy for aggressive non-Hodgkin's lymphoma.
Patients with aggressive non-Hodgkin's lymphoma who fail to achieve a complete remission (CR) with standard induction therapy have a poor prognosis with conventional-dose salvage therapy alone. Retrospective series have suggested that early introduction of high-dose salvage therapy with autologous stem cell transplantation (ASCT) may benefit partial-responder (PR) patients. However, two randomized studies (of 69 and 51 patients with partial clinical responses) failed to demonstrate any advantage of intensive therapy. By contrast, the GELA comparative study on 94 PR-patients (residual disease being histologically documented in 53 patients) suggested that high-dose therapy with ASCT improves survival. Interpretation of all these results is complicated by the heterogeneity of patient populations with respect to initial prognostic factors, induction regimens and, in particular, the criteria used to define partial response. Gallium CT scan and magnetic resonance imaging are now used to better explore residual masses. In the future, early restaging with these imaging techniques might be used to delineate patients who are likely to achieve CR from those who will fail to induction treatment and could be candidates for experimental treatments.
Antineoplastic Combined Chemotherapy Protocols↗
Doxorubicin-containing regimen with or without interferon alfa-2b for advanced follicular lymphomas: final analysis of survival and toxicity in the Groupe d'Etude des Lymphomes Folliculaires 86 Trial.
PURPOSE: To compare progression-free survival (PFS), overall survival (OS), and toxicity of a doxorubicin-containing regimen administered alone or in combination with interferon alfa-2b (IFNalpha) in patients with low-grade follicular lymphoma (FL) and poor prognostic factors. PATIENTS AND METHODS: Two hundred sixty-eight patients with advanced-stage FL received cyclophosphamide, doxorubicin, teniposide, and prednisone (CHVP) monthly for 6 months, then every 2 months for 12 months. After randomization, 242 patients were evaluated for efficacy: 119 received CHVP alone, and 123 also received IFNalpha at a dose of 5 million units three times weekly for 18 months. RESULTS: After a 6-year median follow-up, the patients treated with CHVP + IFNalpha showed significantly longer median PFS than those who received CHVP alone (2.9 years v 1.5 years, respectively; P = .0002) and significantly longer median OS (not reached v 5.6 years, respectively; P = .008). Although some side effects, which included neutropenia, asthenia, fever, elevated serum transaminase levels, flu-like symptoms, and thrombocytopenia, were more frequently observed in patients who received the combination regimen, these reactions were moderate. IFNalpha was withdrawn because of toxicity in 10% of the patients, and a dosage reduction or temporary suspension was required in 28%. CONCLUSION: With long-term follow-up of 6 years, these results confirm that the addition of IFNalpha to a doxorubicin-containing regimen for patients with advanced-stage and clinically aggressive FL not only increased PFS, as in most other similar trials, but also prolonged OS. Toxicity was moderate. The beneficial effects of this combined chemotherapy and IFNalpha regimen on OS probably reflect the selection of FL patients with poor prognostic factors.
Antineoplastic Agents↗
Quality-of-life-adjusted survival analysis of interferon alfa-2b treatment for advanced follicular lymphoma: an aid to clinical decision making.
PURPOSE: To evaluate the trade-off of toxicity versus improved clinical outcome with interferon alfa-2b (IFN) administered concomitantly with a doxorubicin-containing regimen for the treatment of advanced follicular lymphoma. PATIENTS AND METHODS: A quality-of-life-adjusted survival analysis (Quality-Adjusted Time Without Symptoms or Toxicity [Q-TWiST]) was applied to the Groupe d'Etude des Lymphomes Folliculaires (GELF) trial 86, which compared a regimen of cyclophosphamide, doxorubicin, teniposide, and prednisone (CHVP) versus CHVP plus IFN in 242 patients with confirmed follicular lymphoma. CHVP was administered monthly for 6 months then every other month for 12 months. The IFN dosage was 5 x 10(6) U three times weekly for 18 months. RESULTS: After a median follow-up duration of 72 months, the IFN group gained a mean of 12.3 months of progression-free survival (PFS) and 7.4 months of overall survival (OS), but also experienced additional time with grade 3 or worse toxicity compared with the CHVP group. Sensitivity analysis demonstrated that CHVP plus IFN provided a greater amount of quality-adjusted survival regardless of the relative quality-of-life valuations placed on time with toxicity due to CVHP alone, time with toxicity due to CHVP plus IFN, and time following disease progression. This gain was significant (P < .05) in all cases except for patients who consider time with toxicity to have a low relative value and time following disease progression to have a high relative value. CONCLUSION: In patients with advanced follicular lymphoma, the clinical benefits of concomitant IFN can significantly offset the associated grade 3 or worse toxic effects. The magnitude of this clinical benefit depends on an individual patient's relative quality-of-life valuations for time with toxicity and time following disease progression.
Adult↗
Primary anaplastic large-cell lymphoma in adults: clinical presentation, immunophenotype, and outcome.
Anaplastic, CD30+, large-cell lymphoma is now a well-recognized pathologic entity that accounts for 2% to 8% of all lymphomas. Recent progress has been made in the understanding of certain biologic features found in anaplastic large-cell lymphoma, but information about its clinical behavior, in comparison to other large-cell lymphomas, is limited. The pathologic review of a large multicenter study of the treatment of aggressive lymphoma identified 146 cases of anaplastic large-cell lymphoma (ALCL) on the basis of morphology and CD30 expression. We compared initial presentation, immunophenotype, and clinical outcome of these cases with those of the 1,695 nonanaplastic diffuse large-cell lymphomas (non-ALCL) included in the same trial. Patients with ALCL were more likely to be male (P = .018) and were younger (P < .0001) than those with non-ALCL. B symptoms were more frequent in ALCL (P = .006). Skin (P < .0001) and lung (P < .05) involvement was also more frequent in ALCL, but frequency of bone marrow involvement was identical (P = . 5). Tumor cell phenotype was B in 56 cases (38%), T in 49 cases (34%), and null in 33 cases (22%). Response to chemotherapy (P = . 001), event-free survival (P = .006), and overall survival (P = . 0004) were better for ALCL than for non-ALCL. Multivariate analyses identified anaplastic character as an independent factor that predicted a longer survival. Tumor cell phenotype did not influence event-free survival (P = .72) or overall survival (P = .83). ALCL in adults is a clinicopathologic entity which, independent of its phenotypic characteristics, has a better outcome than other diffuse large-cell lymphomas.
Adult↗
Prognosis of patients with advanced Hodgkin's disease: evaluation of four prognostic models using 344 patients included in the Group d'Etudes des Lymphomes de l'Adulte Study.
BACKGROUND: To determine whether a high risk group could be identified within a group of patients with advanced stage Hodgkin's disease (HD), the authors applied several prognostic models to patients treated according to the H89 protocol. METHODS: This study included 344 patients with Stage IIIB-IV HD who were treated with chemotherapy alone (8 cycles) or chemotherapy (6 cycles) plus radiation therapy. Four prognostic models were selected for this study: the numeric prognostic index of the Scotland and Newcastle Lymphoma Group, the Christie Hospital (Manchester)-St. Bartholomew's Hospital (London) model, the Memorial Sloan-Kettering Cancer Center (MSKCC) model, and the criteria used in the European Bone Marrow Transplant (EBMT)/Intergroup Trial. RESULTS: Univariate analysis of H89 protocol patients showed that 5 variables included in the models had prognostic significance: age > 45 years (P = 0.0001), anemia (hemoglobin < 12 g/dL for males and < 10 g/dL for females) (P = 0.0001), number of extranodal sites > or = 2 (P = 0.0013), serum lactic acid dehydrogenase greater than the normal value (P = 0.0018), and lymphocyte count < 0.75 x 10(9) L(-1) (P = 0.0063). All four models divided patients into prognostic subgroups. Significant differences among the subgroups were found by log rank analysis (chi-square test = 11-48; P = 0.01-0.0001). The worst prognostic group defined by the MSKCC model (> or = 3 adverse factors) had an overall survival rate of 59% at 3 years and an estimated 3-year event free survival rate of 43%. CONCLUSIONS: Patients with at least three adverse factors according to the MSKCC model or the EBMT criteria had a higher risk of failure with conventional treatment; however, based on survival rate, no very high risk group could be identified. Nonetheless, these prognostic models may be useful to recognize patients with good prognosis who can be cured with conventional therapy and for whom treatment morbidity and mortality can be minimized.
Adult↗
Results of three courses of adriamycin, bleomycin, vindesine, and dacarbazine with subtotal nodal irradiation in 189 patients with nodal Hodgkin's disease (stage I, II and IIIA).
AIM OF THE STUDY: To evaluate in a prospective trial three courses of an ABVD-like chemotherapy (CT) regimen given before radiation therapy (RT) (subtotal nodal irradiation (STNI) in favorable stage Hodgkin's disease (HD). The efficacy, risk factors and medium-term toxicities are reported. PATIENT CHARACTERISTICS: Stage I or II with at least one of the following factors, mediastinal involvement, histological type 3, age > 40 years, ESR rate > 50 mm, or stage IIIA. 189 patients with newly diagnosed HD were treated between 01/89 and 01/94 (stage I, n = 33; stage II, n = 129, stage IIIA, n = 27). Three courses of an ABVD-like regimen (adriamycin 25 mg/m2, bleomycin 10 mg, vindesine 2 mg/m2 and dacarbazine 250 mg/m2 day 1 and 8) were given before STNI at 36/40 grays. At diagnosis, prognostic factors were distributed as follows: B symptoms (n = 54), bulky mediastinum (n = 41), hemoglobin < 12 g/dl (n = 37), ESR > 50 (n = 65), age > 45 (n = 24). RESULTS: After chemotherapy, 90% had an objective response (partial response > 75%) and 98% were in complete remission (CR) at the end of RT. Three patients had primary refractory disease and 13 patients (7%) relapsed, 3 at the initial site, 4 at previously uninvolved sites and 6 at both. With a median follow-up of 60 months, 170 patients are in 1st CR, 5 in 2nd or greater CR and 11/14 patients have died from HD. Bulky mediastinum (p = 0.009), age > 45 years (p = 0.03) and EST > 50 mm (p = 0.05) were adverse prognostic factors for survival. Bulky mediastinum (p = 0.009) was the only prognostic factor for freedom from progression. TOXICITIES: Two patients died from treatment related toxicity and one patient died with an osteogenic sarcoma. No secondary leukemia has so far been detected. 24 pregnancies were reported. Cardiopulmonary toxicity was always < grade 1 (WHO) in 95 patients evaluated. Two patients over 45 years old had a myocardial infarction. CONCLUSION: With an acceptable medium-term toxicity, this treatment achieved 85% survival at 5 years.
Adolescent↗
Comparison in low-tumor-burden follicular lymphomas between an initial no-treatment policy, prednimustine, or interferon alfa: a randomized study from the Groupe d'Etude des Lymphomes Folliculaires. Groupe d'Etude des Lymphomes de l'Adulte.
PURPOSE: To evaluate prospectively in patients with follicular lymphoma and a low tumor burden three therapeutic options: delay of any treatment until clinically meaningful progression, immediate treatment with an oral alkylating agent, or treatment with a biologic response modifier, interferon alfa-2b. PATIENTS AND METHODS: Newly diagnosed follicular lymphoma patients with a low tumor burden (n = 193) were randomly assigned to one of three arms: arm 1, no initial treatment (n = 66); arm 2, prednimustine 200 mg/m2/d for 5 days per month for 18 months (n = 64); or arm 3, interferon alfa 5 MU/d for 3 months then 5 MU three times per week for 15 months (n = 63). Clinical characteristics were similar in the three arms. RESULTS: Overall response rates with prednimustine and interferon alfa were 78% and 70%, respectively. The overall response to therapy, when deferred, was similar at 70%. With a median follow-up duration of 45 months after randomization, the median freedom-from-treatment (FFT) interval was 24 months in arm 1 and the interval of freedom from treatment failure (FFTF) was 40 months in arm 2 and 35 months in arm 3. The median overall survival time was not reached and the overall survival rate at 5 years was 78% in arm 1, 70% in arm 2, and 84% in arm 3. Therefore, deferred treatment does not adversely influence survival at 5 years. Patients who progressed within 1 year had a significantly shorter survival duration (median, 48 months). CONCLUSION: Delayed treatment is feasible in patients with follicular lymphoma and a low tumor burden. For patients with early progression, more intensive therapy should be considered. For others, because delay of treatment until significant clinical progression does not seem to hamper the prognosis or subsequent response to treatment, the long-term toxicity of alkylating agents can be reduced.
Adult↗
Benefit of autologous bone marrow transplantation over sequential chemotherapy in poor-risk aggressive non-Hodgkin's lymphoma: updated results of the prospective study LNH87-2. Groupe d'Etude des Lymphomes de l'Adulte.
PURPOSE: To update the randomized study that compared consolidative sequential treatment (ifosfamide, etoposide, asporaginase, and cytarabine) versus the high-dose regimen of cyclophosphamide, carmustine, and etoposide (CBV) followed by autotransplantation in patients with aggressive non-Hodgkin's lymphoma in first complete remission and to focus on high-intermediate and high-risk patients identified by the international prognostic index. PATIENTS AND METHODS: Nine hundred sixteen patients received induction treatment on the LNH84 protocol with open randomization for the anthracycline. In a subsequent randomization, 541 patients in complete remission were assigned to receive consolidation by either sequential chemotherapy (n = 273) or autotransplant (n = 268). Among the higher risk population (two or three risk factors), 236 patients in complete remission were assessable for the consolidation phase, with 111 in the sequential chemotherapy arm and 125 in the autotransplant arm. RESULTS: Among 541 randomized patients, disease-free survival and survival did not differ significantly between the two consolidative treatment arms. In the higher risk population, CBV was superior to sequential chemotherapy, with 5-year disease-free survival rates of 59% (95% confidence interval, 49% to 69%) and 39% (95% confidence interval, 28% to 50%), respectively (P = .01, relative risk = 1.19). The 5-year survival rate was superior in the CBV group at 65% (95% confidence interval, 56% to 74%) compared with 52% in the sequential chemotherapy group (95% confidence interval, 42% to 62%) (P = .06, relative risk = 1.49). CONCLUSION: This study shows a superior disease-free survival for higher risk patients in complete remission. Dose-intensive consolidation therapy should be considered for patients at higher risk who achieve complete remission after induction treatment.
Adolescent↗
Placebo-controlled phase III study of lenograstim (glycosylated recombinant human granulocyte colony-stimulating factor) in aggressive non-Hodgkin's lymphoma: factors influencing chemotherapy administration. Groupe d'Etude des Lymphomes de l'Adulte.
The purpose of this study was to, assess the efficacy of glycosylated recombinant human granulocyte colony-stimulating factor (lenograstim) in the prevention of neutropenia and infection in patients receiving dose-intensive chemotherapy for non-Hodgkin's lymphoma (NHL). A second objective was to determine clinical predicators of delay to cytotoxic chemotherapy administration. One hundred-sixty two patients with intermediate- or high-grade NHL and at least one poor prognostic factor received a total of 4 cycles of the LNH-84-regimen every 2 weeks, with an open randomization to treatment with anthracyclines. Patients were randomized to receive subcutaneous lenograstim 5 micrograms/kg/day (n = 82) or placebo (n = 80) from day 6 to day 13 of each cycle. The incidence of severe neutropenia (absolute neutrophil count (ANC) < 0.5 x 10(9)/L) was reduced in the lenograstim group compared with placebo (52% vs 75%). A significant reduction (p < 0.001) in the median duration of ANC < 0.5 x 10(9)/L was also observed in patients treated with lenograstim during each cycle of chemotherapy (0-1 day vs 2-4 days in placebo recipients). Fever occurred in 66 patients in each treatment group. Thirty-four percent of placebo recipients had documented infections during ANC < 1.0 x 10(9)/L compared with 18.5% of lenograstim-treated patients (p < 0.05). Infections of > or = 2 severity were significantly less frequent (p = 0.001) among lenograstim recipients compared with placebo (25 vs 49). The most common adverse events among lenograstim recipients were headache, mild bone pain and injection site reactions. Although lenograstim significantly increased (p = 0.0001) relative dose intensity compared with placebo (93% vs 80%), no difference in CR rate (67% vs 71%) or 3-year survival (63% vs 55%) was observed. The results of this study suggest that patients treated with a chemotherapy regimen that induces severe neutropenia can benefit from treatment with lenograstim. Furthermore, lenograstim permits treatment to be delivered at full dose intensity at 2 week intervals, even in patients with bone marrow involvement, and may permit further dose escalation of the chemotherapeutic regimen used.
Adolescent↗
Are angiogenic factors, cytokines, and soluble adhesion molecules prognostic factors in patients with renal cell carcinoma?
Angiogenesis has an important role in the progression of solid tumors. Therefore, we measured the blood levels (ELISA) of angiogenic factors [basic fibroblast growth factor (bFGF), hepatocyte growth factor/scatter factor, and vascular endothelial growth factor (VEGF)] and soluble adhesion molecules [E-selectin, intercellular adhesion molecule (ICAM-1), platelet endothelial cell adhesion molecule-1, and vascular cell adhesion molecule-1] in 76 consecutive patients with untreated renal cell carcinoma and 41 healthy controls to evaluate their prognostic value. The serum levels of bFGF, hepatocyte growth factor, and VEGF were significantly higher in patients with renal cancer than they were in healthy subjects. bFGF and VEGF values were significantly higher in patients with disseminated cancer (N+ and/or M+) than they were in those with undisseminated (M-N-) cancer: median = 27 pg/ml, range = 5-118, n = 15 versus median = 8 pg/ml, range = 1-149, n = 61 (P = 10(-4)) for bFGF; and median = 883 pg/ml, range = 200-2317, n = 15 versus median = 278 pg/ml, range = 0-1704, n = 61 (P = 0.006) for VEGF. The blood levels of ICAM-1 and vascular cell adhesion molecule-1 were significantly higher, and the levels of E-selectin and platelet endothelial cell adhesion molecule-1 were significantly lower in patients with renal cancer than they were in controls. Plasma ICAM-1 was higher in metastatic patients (M+) than they were in nonmetastatic (M-) patients: median = 687 ng/ml, range = 294-1091, n = 12 versus median = 408 ng/ml, range = 217-1375, n = 64 (P = 10(-4)). ICAM-1 and bFGF blood values were correlated with the size of the primary tumor. The interleukin 6 and tumor necrosis factor-alpha (TNF-alpha) values of these patients have been previously published and are included in the survival analysis. Univariate analysis showed that bFGF, ICAM-1, interleukin 6, and TNF-alpha, before treatment, were prognostic factors. In multivariate analysis for proportional hazard regression, only TNF-alpha was an independent prognostic indicator, with a normal plasma TNF-alpha being highly predictive for a good prognosis in patients with untreated renal cell carcinoma.
Adult↗
Analysis of prognostic factors after the first relapse of Hodgkin's disease in 187 patients.
BACKGROUND: Patients in the first relapse of Hodgkin's disease comprise a heterogeneous group regarding their primary treatment and their clinical characteristics. Because therapeutic options for these patients vary from radiotherapy to combined modality or high dose therapy, we wanted to identify the prognostic factors that would optimize the treatment choice among the different options available. METHODS: Patients (n = 187) who relapsed for the first time after the end of treatment were included. Characteristics at diagnosis were: male to female ratio: 1.5; Stage III and IV: 59%; B symptoms: 60%; and mediastinal involvement: 76%, bulky in 29%. Chemotherapy (27%) or combined modality (73%) was prescribed. Relapses occurred 3 to 192 months (median: 35 mos) after the end of treatment; for 39% this interval was < 12 months. Characteristics at relapse were: Stage III and IV: 59%; and B symptoms: 46%. At first relapse, treatment was conventional (chemo- and/or radiotherapy) in 44% and intensive (high dose therapy with stem-cell transplantation) in 56%. These regimens led to 85% complete responses; and 15% were refractory. RESULTS: The median follow-up after relapse was 31 months and the median time to second progression was 20 months. The median freedom from second failure (FF2F) was 44 months and the median survival was 72 months. All factors were analyzed for survival and FF2F. Patients given intensive treatment had more adverse prognostic factors at relapse (B symptoms, early relapse, and disseminated relapse). Multivariate analysis identified 2 significant prognostic factors: interval end of treatment-relapse < 12 months (< 10(-4)) and Stage III and IV at relapse (P = 0.0013). For patients with at least one adverse prognostic factor, high dose therapy gave the best survival results. CONCLUSIONS: Using 2 simple prognostic factors, (interval end of treatment-relapse < 12 months and Stage III/IV at relapse), patients in first relapse of Hodgkin's disease can be classified into 3 significant prognostic groups in terms of survival and FF2F.
Adolescent↗
Prognostic significance of bcl-2 protein expression in aggressive non-Hodgkin's lymphoma. Groupe d'Etude des Lymphomes de l'Adulte (GELA).
Little is known about the expression of bcl-2 protein in intermediate and high grade non-Hodgkin's lymphoma (NHL) and its clinical and prognostic significance. We performed immunohistochemical analysis of bcl-2 expression in tumoral tissue sections of 348 patients with high or intermediate grade NHL. These patients were uniformly treated with adriamycin, cyclophosphamide, vindesine, bleomycin, and prednisone (ACVBP) in the induction phase of the LNH87 protocol. Fifty eight cases were excluded due to inadequate staining. Of the 290 remaining patients, 131 (45%) disclosed homogeneous positivity (high bcl-2 expression) in virtually all tumor cells, whereas 65 (23%) were negative and 94 (32%) exhibited intermediate staining. High bcl-2 expression was more frequent in B-cell NHL (109 of 214, 51%) than in T-cell NHL (6 of 35, 17%) (P = .0004), and was heterogeneously distributed among the different histological subtypes. Further analysis was performed on the 151 patients with diffuse large B-cell lymphoma (centroblastic and immunoblastic) to assess the clinical significance and potential prognostic value of bcl-2 expression in the most frequent and homogeneous immunohistological subgroup. High bcl-2 expression, found in 44% of these patients (67 of 151), was more frequently associated with III-IV stage disease (P = .002). Reduced disease-free survival (DFS) (P < .01) and overall survival (P < .05) were demonstrated in the patients with high bcl-2 expression. Indeed, the 3-year estimates of DFS and overall survival were 60% and 61%, respectively (high bcl-2 expression) versus 82% and 78%, respectively (negative/intermediate bcl-2 expression). A multivariate regression analysis confirmed the independent effect of bcl-2 protein expression on DFS. Thus bcl-2 protein expression, as demonstrated in routinely paraffin-embedded tissue, appears to be predictive of poor DFS, in agreement with the role of bcl-2 in chemotherapy-induced apoptosis. It might be considered as a new independent biologic prognostic parameter, which, especially in diffuse large B-cell NHL, could aid in the identification of patient risk groups.
Adult↗
Primary mediastinal large B-cell lymphoma. A clinicopathologic study of 141 cases compared with 916 nonmediastinal large B-cell lymphomas, a GELA ("Groupe d'Etude des Lymphomes de l'Adulte") study.
Among non-Hodgkin's lymphomas, primary mediastinal large B-cell lymphoma (PMLCL) has been considered a separate entity that has specific clinical and histological aspects and a poor prognosis. In this study, we reexamined the clinicopathologic features and the response to current treatment of 141 PMLCL and compare them with 916 nonmediastinal large B-cell lymphomas (NMLCL) recorded in the same period and treated with similar combined chemotherapy. The clinical features of PMLCL at diagnosis were largely homogeneous and distinct from NMLCL, with a predilection for young women (59% with a mean age of 37 years versus 42% with a mean age of 54 years), bulky tumor (77% versus 7%, p < 10(4)), high serum lactic dehydrogenase (LDH) level 76% versus 51%, p < 10(4)), and frequent intrathoracic extension to adjacent organs such as pleura, pericardium, and lung. By contrast, extrathoracic or hematologic dissemination was uncommon (2% of bone marrow involvement versus 17%). All patients had diffuse large B-cell nonimmunoblastic, nonanaplastic lymphomas. Histological analysis of the 141 PMLCL evaluated two common patterns: the presence of large cells with clear cytoplasm (found in 38% of cases) and the presence of fibrosis (marked in 25% of cases). The presence of clear cells or intense fibrosis did not constitute prognostic indicators. Immunologic and molecular analysis assessed the profile of bcl-2 expression and the presence of Epstein-Barr virus (EBV) in PMLCL: 30% expressed a high level of bcl-2 protein; EBER RNAs were detected by in situ hybridization in only two of the 41 cases tested. Monotypic light chain restriction could be demonstrated in seven of the 41 PMLCL tested on fixed-section. Treated with polychemotherapy regimens without radiotherapy, 79% of PMLCL patients achieved a complete remission compared with 68% in the NMLCL patient group (p = 0.01). Overall, 3-year survival rates were estimated at 66 and 61%, respectively (p = 0.05), and disease-free survival rates were not significantly different (61 versus 64%). Stratified analysis on the International Prognostic Index (based on age, tumor stage, serum LDH level, and performance status) showed no difference in the overall and disease-free survivals between the two lymphoma groups. In conclusion, PMLCL can be combined with other diffuse large B-cell lymphomas on morphologic grounds; it is not associated with EBV. It responds favorably to treatment and should be managed like other high-grade lymphomas of equivalent histology. However, the uncommon clinical presentation makes it a distinct entity.
Adolescent↗
Is the small non-cleaved-cell lymphoma histologic subtype a poor prognostic factor in adult patients? A case-controlled analysis. The Groupe d'Etude des Lymphomes de l'Adulte.
PURPOSE: To study the prognostic significance of the small non-cleaved-cell lymphoma (SNCCL) histologic subtype, we compared the outcome of adult patients with SNCCL with that of patients with aggressive lymphoma other than SNCCL by means of two case-controlled studies. PATIENTS AND METHODS: We analyzed the results of the doxorubicin, cyclophosphamide, vindesine, bleomycin, and prednisone (ACVBP) regimen used as a reference scheme in our cooperative study group (Groupe d'Etude des Lymphomes de l'Adult [GELA]) in 52 adult SNCCL patients with no bone marrow (BM) or CNS involvement. Forty-five SNCCL patients younger than 60 years could be compared with two separate case-matched groups of patients with aggressive lymphoma other than SNCCL undergoing the same therapeutic regimen. In the first case-controlled study, matching ensured identity of each risk factor of the age-adjusted International Index (ie, Ann Arbor stage, performance status, and lactate dehydrogenase [LDH] level); in the second study, matching was performed according to the number of presenting risk factors (zero, one, two, or three), regardless of their nature. RESULTS: The 5-year overall survival rates were not significantly different between SNCCL and control patients in both case-controlled studies: 48% versus 51% in the first study, and 48% versus 55% in the second study. CONCLUSION: These results support the thesis that in patients with no bone marrow or CNS involvement, the SNCCL histologic subtype does not confer a prognosis worse than that of other aggressive lymphoma.
Adolescent↗