PubMed Health⌕ Search

Biomedical subjects

P Lederlin

Publications and source records attributed to P Lederlin.

At least 19 recordsLinked to original sources
PubMed1998

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↗
PubMed1997

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↗
PubMed1997

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↗
PubMed1997

De novo methylation of tumour suppressor genes CDKN2A and CDKN2B is a rare finding in B-cell chronic lymphocytic leukaemia.

De novo methylation of the 5'CpG island has been recently reported as an alternative mechanism of inactivation for the tumour suppressor genes CDKN2A and CDKN2B. We examined CDKN2A methylation status at diagnosis in 42 B-cell chronic lymphocytic leukaemia (CLL) patients, in 19 cases the CDKN2B methylation status was also analysed. No homozygous CDKN2A/2B deletion was detected, but four patients (9%) displayed an aberrant CDKN2A methylation status and only one had hypermethylated CDKN2B. De novo methylation was associated with silencing of gene expression. These results confirm that CDKN2A/2B inactivation by deletion is a rare event in CLL and suggest that aberrant methylation could be an alternative way of inactivation very rarely involved in the development of some CLL.

Blotting, Southern↗
PubMed1997

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↗
PubMed1997

Elderly patients with aggressive non-Hodgkin's lymphoma: disease presentation, response to treatment, and survival--a Groupe d'Etude des Lymphomes de l'Adulte study on 453 patients older than 69 years.

PURPOSE: To clarify disease characteristics and optimal treatment for elderly patients with non-Hodgkin's lymphoma (NHL), we performed a randomized trial in 453 patients older than 69 years with aggressive lymphoma. PATIENTS AND METHODS: Two hundred twenty patients received cyclophosphamide 750 mg/m2, teniposide (VM-26) 75 mg/m2, and prednisone 40 mg/m2/d for 5 days (CVP) and 233 patients received CVP plus pirarubicin (THP-doxorubicin) 50 mg/m2 (CTVP), each for six courses every 3 weeks. RESULTS: The median age was 75 years. Most patients had clinically aggressive disease; 30% had one and 53% two or three adverse prognostic parameters as defined by the International Prognostic Index. More patients on the CTVP arm had an elevated lactic dehydrogenase (LDH) level, but the two groups were otherwise well balanced. CTVP treatment was more frequently associated with leukopenia, thrombocytopenia, and infectious complications. Death during chemotherapy occurred in 16% and 21% of patients on the CVP and CTVP arms, respectively (not significant). Forty percent of patients achieved a complete response (CR): 47% on CTVP and 32% on CVP (chi2 = 20.98, P = .0001). The median time to treatment failure (TTF) was 7 months for CTVP versus 5 months for CVP (log-rank test, P < .05). The median survival time was 13 months in both groups; however, the 5-year survival rate was 26% with CTVP versus 19% with CVP (chi2 = 4.68, P < .05). Lymphoma progression was the primary cause of death. CONCLUSION: Elderly patients with aggressive lymphoma have an aggressive disease with adverse prognostic parameters at the time of diagnosis. Slightly longer survival was observed for patients treated with an anthracycline-containing regimen.

Aged↗
PubMed1996

[Actinomycosis and non-Hodgkin's malignant lymphoma: fortuitous association?].

Two cases of actinomycosis associated with non Hodgkin's lymphoma (NHL) are reported. In one case, low grade NHL was diagnosed many years after actinomycosis because of the persistence of abdominal lymphadenopathy in spite of antibiotic therapy. In the second case, hepatic metastasis were initially suspected until actinomycosis diagnosis was made by percutaneous liver biopsy under scanography. High grade NHL was diagnosed by laparotomy and liver biopsy performed 6 weeks after the onset of antibiotic therapy as no improvement in hepatic lesions was obtained. These two case reports outline the difficulties encountered in the diagnosis of actinomycosis and the indication of a repeat biopsy when actinomycosis does not respond to antimicrobial therapy because of the possibility of concomitant malignancy.

Actinomycosis↗
PubMed1996

[Hairy cell leukemia: therapeutic approaches].

Hairy cell leukemia is a rare lymphoproliferative B disorder. It usually occurs in men older than 50 years. Until 1984, therapeutic approaches had been disappointing and most of the patients died from complications of cytopenia. The introduction of interferon and, more recently of purine analogues (pentostatine and 2-chlorodeoxyadenosine) improved outcome of this disease. Nevertheless, if complete remissions may be achieved sometimes with interferon and more frequently with purine analogues, none of these treatments seems able to remove hairy cells. So, therapeutic decision has to be made according to the efficacy and the potential adverse effects of these drugs.

Antibiotics, Antineoplastic↗
PubMed1996

[Uni- and multifocal eosinophilic granulomas in adults. Diagnostic and therapeutic approaches. Apropos of 3 cases].

Unifocal and multifocal eosinophilic granuloma are Langerhans cell histiocytosis of unknown cause. Over the last 10 years, recent insights in pathogenesis and characterization of this pathology have been made. The authors report three cases of adult unifocal and multifocal eosinophilic granuloma. A review of literature underlines diagnostic features and therapeutic aspects of this disease.

Adult↗
PubMed1996

Effect of granulocyte colony-stimulating factor administration in elderly patients with aggressive non-Hodgkin's lymphoma treated with a pirarubicin-combination chemotherapy regimen. Groupe d'Etudes des Lymphomes de l'Adulte.

PURPOSE: Results of a multidrug chemotherapy regimen consisting of cyclophosphamide, pirarubicin, teniposide, and prednisolone (CTVP) plus subcutaneous granulocyte colony-stimulating factor (G-CSF) in elderly patients with aggressive non-Hodgkin's lymphoma (NHL) are reported. PATIENTS AND METHODS: Between January and December 1992, 46 previously untreated patients older than 69 years with intermediate- and high-grade NHL received cyclophosphamide 750 mg/m2, teniposide 75 mg/m2, pirarubicin 50 mg/m2 day 1, and prednisolone 40 mg/m2 days 1 to 3. G-CSF, 5 micrograms/kg/day, was administered from day 4 up to day 14 or when the absolute neutrophil count reached 5 x 10(9)/l. Six cycles were scheduled every 3 weeks. RESULTS: Grade 3 or grade 4 neutropenia complicated 22% and 26% of chemotherapy cycles, respectively. Fever or/and clinical infection were observed in 4% and 14% of cycles. One toxic death related to a septic shock occurred. Eight cycles (4%) were delayed with a median duration of 7 days. Administered median dose intensity was 93.5%. Objective response rate was 74% and 46% of the patients achieved a complete response. The 2-year overall survival and event-free survival rates were 47% and 28%. CONCLUSION: In comparison with a previous group of patients treated with CTVP, G-CSF allows delivery of chemotherapy with a reduced neutropenia-induced morbidity in an outpatient setting in elderly patients with aggressive NHL without modifying response rate or survival.

Aged↗
PubMed1996

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↗
PubMed1995

[Gelatinous transformation of the bone marrow. Apropos of 3 cases].

Gelatinous transformation of the bone marrow is a rare histological lesion usually associated with cachexia. The authors report three new cases, two in anorexia nervosa and the third in Hodgkin disease. A review of the literature underlines association with marrow cell necrosis and provides the most frequent etiologies. Pathogenesis of gelatinous transformation remains unclear and her prognostic depends on etiology.

Adolescent↗
PubMed1995

[Acute drug-induced agranulocytosis. Clinical study apropos of 30 patients and evolution of etiologies over 2 decades].

Between 1982 and 1993, 30 patients were treated for drug-induced agranulocytosis. They did not receive cytotoxic chemotherapy nor radiotherapy during the past 6 months. There is a higher incidence in women (21 females, nine males). Mean age is 59.3 years old. The drug could be found in 25 cases including noramidopyrine five cases, antithyroid drugs four cases, non steroidal anti-inflammatories drugs four cases. Five patients died of infection during agrulocytosis. Sepsis was documented in three cases. We used hematopoietic growth factors in two cases. Neutrophils rose up to 0.5.10(9)/l between 2 to 14 days after the diagnosis and 1.10(9)/l between 3 to 16 days. Time when absolute neutrophil count was less than 0.5.10(9)/l was shorter (p = 0.008) when bone marrow was rich with maturation arrest but with few or no mature forms rather than reduction of granulocytic precursors. By comparison with a similar study made in the same institution between 1971 and 1981, there were fewer cases each year. Drugs involved were not similar: phenicols were not found, reference to noramidopyrine is less frequent. Now antithyroid drugs is becoming one of the most important etiologies.

Acute Disease↗
PubMed1995

[Yersinia enterocolitica septicemia, iron overload and deferoxamine].

Infections due to Yersinia enterocolitica are usually limited to the bowel. When infection is generalized, the role of iron overload and iron chelation has been discussed. We report the case of a 55 year-old patient with sideroblastic anemia who received repetitive transfusions and deferoxamine for 4 years and heme arginate for 2 months, and who was admitted in our institution for Yersinia enterocolitica sepsis. Treatment by third-generation cephalosporins and aminoglycosides has allowed favorable outcome.

Anemia, Sideroblastic↗