Cryopreservation, semen use and the likelihood of fatherhood in male Hodgkin lymphoma survivors: an EORTC-GELA Lymphoma Group cohort study.

STUDY QUESTION: How does the successful cryopreservation of semen affect the odds of post-treatment fatherhood among Hodgkin lymphoma (HL) survivors? SUMMARY ANSWER: Among 334 survivors who wanted to have children, the availability of cryopreserved semen doubled the odds of post-treatment fatherhood. WHAT IS KNOWN ALREADY: Cryopreservation of semen is the easiest, safest and most accessible way to safeguard fertility in male patients facing cancer treatment. Little is known about what proportion of patients achieve successful semen cryopreservation. To our knowledge, neither the factors which influence the occurrence of semen cryopreservation nor the rates of fatherhood after semen has been cryopreserved have been analysed before. STUDY DESIGN, SIZE, DURATION: This is a cohort study with nested case-control analyses of consecutive Hodgkin survivors treated between 1974 and 2004 in multi-centre randomized controlled trials. A written questionnaire was developed and sent to 1849 male survivors. PARTICIPANTS/MATERIALS, SETTING, METHODS: Nine hundred and two survivors provided analysable answers. The median age at treatment was 31 years. The median follow-up after cryopreservation was 13 years (range 5-36). MAIN RESULTS AND THE ROLE OF CHANCE: Three hundred and sixty-three out of 902 men (40%) cryopreserved semen before the start of potentially gonadotoxic treatment. The likelihood of semen cryopreservation was influenced by age, treatment period, disease stage, treatment modality and education level. Seventy eight of 363 men (21%) used their cryopreserved semen. Men treated between 1994 and 2004 had significantly lower odds of cryopreserved semen use compared with those treated earlier, whereas alkylating or second-line (chemo)therapy significantly increased the odds of use; no other influencing factors were identified. We found an adjusted odds ratio of 2.03 (95% confidence interval 1.11-3.73, P = 0.02) for post-treatment fatherhood if semen cryopreservation was performed. Forty-eight out of 258 men (19%) who had children after HL treatment became a father using cryopreserved semen. LIMITATIONS, REASONS FOR CAUTION: Data came from questionnaires and so this study potentially suffers from response bias. We could not perform an analysis with correction for duration of follow-up or provide an actuarial use rate due to lack of dates of semen utilization. We do not have detailed information on either the techniques used in cryopreserved semen utilization or the number of cycles needed. STUDY FUNDING/COMPETING INTERESTS: Lance Armstrong Foundation, Dutch Cancer Foundation, René Vogels Stichting, no competing interests.

Characterization of porous silicon integrated in liquid chromatography chips.

Properties of porous silicon which are relevant for use of the material as a stationary phase in liquid chromatography chips, like porosity, pore size and specific surface area, were determined with high-resolution SEM and N(2) adsorption-desorption isotherms. For the anodization conditions investigated, porosity is between 20 and 60%, pore sizes between 2 and 5 nm and specific surface area between 130 and 410 m(2)/cm(3). It was established that under identical anodization conditions, porous layer formation is 10-15% slower on micromachined pillars than on flat substrates, and depends on geometrical parameters like pillar diameter and height and interpillar spacing. In microchannels containing pillars with a porous silicon shell, chromatographic experiments on a coumarin dye mixture were performed, which in comparison with non-porous pillars showed a significant increase of the retention factors, resulting from the large internal surface of the porous pillars. The increased relative retention of one of the coumarin dyes, C480, could be correlated quantitatively with the measured internal surface of the porous layer. Due to the small pore size, these porous shell columns are particularly suitable for analytical or preparative separation of low-molecular weight molecules, with applications in metabolomics, food quality control, or medical diagnostics.

[Management of 315neutropenic febrile episodes in a cancer center]. / Prise en charge de 315épisodes neutropéniques fébriles dans un centre anticancéreux.

UNLABELLED: Management of febrile neutropenic patients is described in guidelines. Each cancer center can adapt these according to its local bacterial ecology. We present a retrospective study made in a cancer center from 2001 to 2003. METHOD: Three hundred and fifteen febrile neutropenic episodes after chemotherapy (66% for solid tumor) were analysed. RESULTS: For 279 episodes, no antibiotic therapy was given before admission. Clinical or radiological manifestations occurred in 46%; microbiologically documented infections by hemocultures in 28% (Gram positive: 42%; Gram negative: 51%) and by puncture in 14% (Gram negative: 58%). The length of pyrexia was inferior to 7 days in 88% and neutropenia inferior 7 days in 80.8%. 79.7% of episodes were treated with one of the three antibiotic therapy recommended by the center (ceftriaxone+tobramycin; ceftriaxone+ciprofloxacin; ceftriaxone+ofloxacin); 13.3% were treated with an other therapy; 7% received no antibiotic therapy. 68.5% of patients treated with one of the three antibiotic therapies, became afebrile without changing the antibiotic protocol. CONCLUSION: In our study, there were a majority of Gram negative bacteria except for Pseudomonas aeruginosa. The three antibiotic therapy recommended by the center (third generation cephalosporin+aminoglycosides or fluoroquinolones) were effective and glycopeptide was not necessary in first intention treatment.

Second malignancy risk associated with treatment of Hodgkin's lymphoma: meta-analysis of the randomised trials.

BACKGROUND: Despite several investigations, second malignancy risks (SMR) following radiotherapy alone (RT), chemotherapy alone (CT) and combined chemoradiotherapy (CRT) for Hodgkin's lymphoma (HL) remain controversial. PATIENTS AND METHODS: We sought individual patient data from randomised trials comparing RT versus CRT, CT versus CRT, RT versus CT or involved-field (IF) versus extended-field (EF) RT for untreated HL. Overall SMR (including effects of salvage treatment) were compared using Peto's method. RESULTS: Data for between 53% and 69% of patients were obtained for the four comparisons. (i) RT versus CRT (15 trials, 3343 patients): SMR were lower with CRT than with RT as initial treatment (odds ratio (OR) = 0.78, 95% confidence interval (CI) = 0.62-0.98 and P = 0.03). (ii) CT versus CRT (16 trials, 2861 patients): SMR were marginally higher with CRT than with CT as initial treatment (OR = 1.38, CI 1.00-1.89 and P = 0.05). (iii) IF-RT versus EF-RT (19 trials, 3221 patients): no significant difference in SMR (P = 0.28) although more breast cancers occurred with EF-RT (P = 0.04 and OR = 3.25). CONCLUSIONS: Administration of CT in addition to RT as initial therapy for HL decreases overall SMR by reducing relapse and need for salvage therapy. Administration of RT additional to CT marginally increases overall SMR in advanced stages. Breast cancer risk (but not SMR in general) was substantially higher after EF-RT. Caution is needed in applying these findings to current therapies.

A 1-kb Bcl-2-PCR fragment detection in a patient with follicular lymphoma and development of a new diagnostic PCR method.

The t(14;18) translocation is a useful marker to characterize follicular lymphoma and to monitor residual disease. The polymerase chain reaction (PCR) is a powerful technique to detect this translocation. Located on chromosome 18, within the Bcl-2 gene, breakpoints occur mainly in the 3; untranslated region, in the third exon of Bcl-2 (MBR region). In this study, the authors amplified MBR breakpoints by PCR and found an unexpectedly large fragment of 1 Kb that corresponds to a recently described new breakpoint in the Bcl-2 gene. With a new primer set, a further previously considered t(14;18)-unrelated tumor was in fact positive for this new breakpoint.

Semen analysis and cryoconservation before treatment in Hodgkin's disease.

BACKGROUND: The prophylaxis of the late effects of chemotherapy and radiotherapy has become one of the major concerns in the management of Hodgkin's disease (HD). Unlike other complications, male sterility could be managed by prior semen preservation (SP). PATIENTS AND METHODS: To evaluate the semen quality of patients with HD and the outcome of insemination, we reviewed spermograms of patients who underwent SP before any treatment. The following criteria were necessary: 1) age > 16 and < 50; 2) HD of any stage; 3) informed about male sterility after HD treatment; 4) fully consenting. RESULTS: Such a proposal was made to 316 men, and 94 fulfilled the criteria. All patients underwent an initial chemotherapy. Mean age of the cohort was 27.5 years (range 16-48 years). Pretherapeutic staging of HD revealed 38 stage I (40%), 38 II (38%), 14 III (15%) and 4 IV (4%). Semen analysis before cryoconservation showed an overall 53% of normal or subnormal cases (50 cases). The analysis of semen quality and spermatozoid amount according to various parameters failed to find a correlation with stage, B symptoms, age, or biologic data (LDH, WBC, platelets, ESR). The use of cryopreserved semen was requested by 13 patients; 88 inseminations were performed leading to 9 pregnancies and 2 births. CONCLUSIONS: The low rate of success with cryopreserved semen in these cases suggests the need for a more careful design of non-toxic chemotherapy regimens in combined modality treatment.

Follicular lymphomas--a review of treatment modalities.

Follicular lymphoma is the most common low-grade non Hodgkin's lymphoma and represent an homogeneous entity as defined by pathological, molecular and clinical data. This indolent disease is characterised by a slow growth pattern with possible spontaneous regression, is often disseminated but remains incurable with available treatments when disseminated. For localised stages, involved field radiotherapy remains the standard choice but other approaches remain to be investigated. In advanced disease, chemotherapy has been demonstrated to produce high response rates but recent trials with new treatment strategies including interferon and monoclonal antibodies may improve the current situation. In this article, we will review treatment of follicular lymphomas, specially emphasising published phase III trials.

Current treatment of Hodgkin's disease.

In spite of the fact that Hodgkin's disease (HD) remains still an enigma its management and treatment yield a cure rate of about 80% of all patients. However, this management has two limits: on one side favourable cases which should not be overtreated because of unacceptable side-effects, and on the other side very unfavourable cases which should be treated differently because of a very high rate of failure and/or relapse. Then it becomes necessary to precise as thoroughly as possible these two limits in order to choose the adequate treatment for the patient. Prognostic factors based on patient and disease characteristics allow a relatively exact classification of favourable and unfavourable cases. This distinction in two prognostic groups has therapeutic implications in terms of chemotherapy (regimen, duration) and radiotherapy (extension, doses). Other specific situations have to be considered, e.g. pediatric cases, pregnancy, old age and HIV-infected patients who need an adapted management according to very different situations.

Evolution of BCL-2/IgH hybrid gene RNA expression during treatment of T(14;18)-bearing follicular lymphomas.

Bcl-2, the gene over-expressed in follicular lymphomas (FL), is able to block chemotherapy-induced apoptosis. Consequently, we wondered whether bcl-2/IgH expression variations during treatment of FL could predict the outcome of patients with t(14;18)-bearing FL. For this purpose, we used a reverse transcription polymerase chain reaction (RT-PCR) assay to analyse 180 serial peripheral blood samples (PBS) during 34 treatment phases in 25 patients with t(14;18)-bearing FL. In all patients but two, bcl-2/IgH gene expression was demonstrated in pre-treatment samples. During 16 out of the 34 treatment phases (47%), bcl-2/IgH expression became negative: all but one were responders to chemotherapy. This conversion was transient in six cases. In 18 treatment phases, bcl2/IgH expression remained detectable: eight were clinically considered as treatment failures, while eight others achieved PR and two achieved CR. We observed a significant correlation between treatment response and RNA PCR results (P = 0.002). Three-year overall survival of patients with stable bcl2/IgH-negative conversion was 100% compared to 54% for the remaining patients (P = 0.069); 3-year freedom from progression was respectively 87.5% and 13% (P = 0.005). These results indicate a correlation between bcl-2/IgH expression variations and both clinical response and outcome. Whether this might predict disease outcome early remains to be confirmed.

Competitive polymerase chain reaction to quantify tumor cells in peripheral blood of patients with T(14;18)-bearing follicular non-Hodgkin's lymphoma: an exploratory study in 8 patients.

Detection of residual disease in follicular lymphoma is hampered by the observation of t(14;18)-bearing cells in the blood of healthy adult humans. To overcome this problem, we decided to validate a quantification method of t(14;18)-bearing cells and test it in t(14;18)-bearing follicular lymphomas (FL). We designed a competitive PCR method to quantify t(14;18)-bearing cells in peripheral blood. First, we controlled overall reliability (specificity, sensitivity, reproducibility, precision and accuracy); then we used our method to study 16 peripheral blood samples collected in 8 patients with t(14;18)-bearing FL. There were considerable variations in the number of circulating tumor cell (CTC) in FL patients, ranging from zero to 17,813 cells/ml. In 2 patients who were sampled before and after treatment and who attained complete remission (CR), a significant decrease in the number of CTC was observed. In 3 patients with detectable CTC during CR, relapse occurred 4 to 11 months later. Of 3 patients with no detectable CTC, 2 remain in CR 35 and 95 months later, but one relapsed 11 months after sample collection. These preliminary results suggest that quantification of CTC may be worthwhile in follicular lymphoma. It may improve our ability to predict relapse occurrence, but also may help in understanding this peculiar disease. Int. J. Cancer (Pred. Oncol.) 84:558-561, 1999.

Serum parathyroid hormone-related protein levels and response to bisphosphonate treatment in hypercalcemia of malignancy.

The pathogenesis of hypercalcemia of malignancy comprises increased net bone resorption and enhanced renal tubular reabsorption of calcium (Ca). To evaluate the prevalence of an increased renal tubular reabsorption of Ca index [tubular reabsorption of calcium index (TRCaI)] in cancer patients with hypercalcemia and of elevated circulating levels of PTH-related protein (PTHrP), which is recognized as a major mediator of this syndrome, we investigated 315 well rehydrated patients, aged 58.1 +/- 0.7 yr (mean +/- SEM), with hypercalcemia [albumin-corrected plasma Ca (pCa), >2.7 mmol/L] secondary to histologically proven malignancy. Changes in pCa and, therefore, various Ca filtered loads were obtained by different degrees of bone resorption inhibition achieved with a single infusion of the bisphosphonate ibandronate, given at various doses on a randomized, double blind basis. PTHrP was determined at baseline in 147 of the patients and 7 days after bisphosphonate therapy in 73. Before ibandronate therapy, pCa was 3.36 +/- 0.02 mmol/L, mean TRCaI was increased at 3.09 +/- 0.03 mmol/L glomerular filtration rate (GFR; normal, 2.40-2.90), and 65% of patients had TRCaI above 2.90 mmol/L GFR. Mean serum PTHrP levels were 4.9 +/- 0.5 pmol/L (normal, <2.5) and values above the normal range were found in 53% of the patients (76% in lung and upper respiratory tract malignancies). By 7 days after the infusion of ibandronate, a decrease in pCa of 0.69 +/- 0.03 mmol/L (20.0 +/- 0.7%; P < 0.001) and in bone resorption [mean change in fasting urinary Ca, 0.09 +/- 0.04 mmol/L GFR (47.6 +/- 8.6%; P < 0.001) and 14.4 +/- 1.7 nmol/mmol (27.6 +/- 10.6%; P < 0.01) in deoxypyridinoline] was observed. TRCaI was slightly lowered by 0.30 +/- 0.09 mmol/L GFR. Mean changes in PTHrP, 1,25-dihydroxyvitamin D3, and PTH were +0.7 +/- 0.4 (P = NS), +27.6 +/- 3.0 (P < 0.001), and +2.9 +/- 0.8 (P < 0.005) pmol/L, respectively. After ibandronate treatment, the relative risk of relapsing hypercalcemia was particularly increased (3.43-fold) in lung and upper respiratory tract malignancies. These results obtained in a large cohort of patients indicate a significant prevalence of an increased renal tubular reabsorption of calcium index in hypercalcemia of malignancy and a substantial proportion of patients with detectable PTHrP.

[Adult's anaplastic CD30+ large cell lymphomas]. / Lymphomes anaplasiques T ou nuls à grandes cellules CD30+ (Ki-1) de l'adulte.

Anaplastic large-cell lymphomas were recognized by Stein in 1985. Less than fifteen years were necessary to confirm this entity, as well as her phenotype and to characterize the t(2;5) (p23;q35) chromosomal abnormality. This rare subgroup of non-Hodgkin's lymphomas (15% of peripheral T cell lymphomas and 8% of all diffuse aggressive lymphomas) is individualized in the Real classification. This disease, which had a bimodal age distribution, is clinically characterized by a diffuse nodal involvement and the frequency of extranodal involvement, especially skin and lungs. Primitive cutaneous anaplastic large cell lymphomas belong to the cutaneous CD30+ lymphoproliferative diseases spectrum. Among peripheral T cell and diffuse aggressive lymphomas, they have the better prognosis. We present in this paper a review of the recent advances in the knowledge, treatment and prognosis of this peculiar entity.

[Interferon alpha in the treatment of non-Hodgkin's lymphomas of low malignancy]. / L'interféron alpha dans le traitement des lymphomes non hodgkiniens de faible malignité.

Incidence of non Hodgkin's lymphomas (NHL) has been increased regularly during the last two decades. Overall survival did not progress at all during this period. According to the results of preliminary studies, alpha interferon is an attractive approach for NHL treatment. The review analyze published randomized controlled trials which tested interferon alpha either in addition with polychemotherapy or as maintenance of chemotherapy-induced response in disseminated low grade NHL. After literature search, nine studies have been included. Interpretation of results was complicated by various patient's selection criteria (age, tumoral burden, histology) and heterogeneous treatment schemes (interferon schedule and dose, chemotherapy combination). Significant overall improvement was observed in two studies while only relapse free survival and time to treatment failure were improved in seven trials, always in interferon group. Significant observed toxicities were hematologic ones and asthenia since they led either to dose adjustment or to interferon interruption. Finally, we cannot recommend interferon use out of prospective trials. Further studies are warranted to confirm overall survival benefit and to define optimal strategy to use this molecule.

Polymerase chain reaction diagnosis of t(14;18) from paraffin-embedded tissues fixed with Holland Bouin fluid.

The t(14;18) translocation and its molecular counterpart, the bcl-2/IgH gene rearrangement, are highly characteristic of follicular non-Hodgkin lymphomas. The identification of the tumor-specific t(14;18) clone is mandatory for any molecular studies on residual disease because of the existence of circulating t(14;18)-bearing benign cells. In this study, the ability to specifically polymerase chain reaction (PCR) amplify t(14;18) with DNA purified from tissues fixed with Holland Bouin fluid is demonstrated. The specificity of the PCR product was confirmed by internal probe hybridization and with comparison of the nucleotidic sequences of this PCR product with those obtained from the corresponding frozen material. Although the sensitivity of the technique is 50% to 60%, paraffin-embedded tissues fixed with bouin fluid may be a good alternative to frozen tissues to detect t(14;18) in tumors.

[Feasibility of following up transfused patients]. / Faisabilité d'un suivi de patients transfusés.

The aim of this study was to assess the natural history of patients after transfusion and the acceptability of a standardized biological follow-up. In 1995, during 1 month, in 13 French hospitals, a follow-up at 3 and 6 months after blood transfusion was proposed to all blood recipients who had not received any blood transfusion within the past 6 months (eligible patients): screening for red cell antibodies, alanine aminotransferase (ALT) activity and specific viral markers of hepatitis B (hepatitis B surface antigen and antibody to hepatitis virus core antigen), of hepatitis C (antibodies) and of Human Immunodeficiency Virus (antibodies). At the beginning of the study, 296 patients were followed for 6 months. A complete follow-up was available at 3 months for 183 patients (62%), at 6 months for 168 (57%) and after 6 months, 198 patients (67%) have been once followed. Of eligible patients, 76% were alive at six months. After transfusion, the incidence of red cell alloantibodies and elevated ALT concentration were respectively 4% and 17%. At 6 months, one patient had Hepatitis B surface antigen; the responsibility of blood transfusion was excluded. Within the first 24 hours, 68 patients (23%) required another blood transfusion and 42% of units were transfused to patients with malignant disease. Our study quantifies in real conditions the difficulty of a biological follow-up in a transfused population, mostly composed of patients that could not be followed in the hospital where they were transfused.

Granulocyte-macrophage colony-stimulating factor in patients with neutropenic fever is potent after low-risk but not after high-risk neutropenic chemotherapy regimens: results of a randomized phase III trial.

PURPOSE: A randomized unblinded phase III trial was designed to determine the ability of granulocyte-macrophage colony-stimulating factor (GM-CSF) to accelerate recovery from febrile neutropenia induced by chemotherapy. PATIENTS AND METHODS: A total of 68 patients with febrile neutropenia following chemotherapy defined as axillary temperature greater than 38 degrees C and absolute neutrophil count (ANC) less than 1 x 10(9)/L were included. After stratification for high- and low-risk chemotherapy to induce febrile neutropenia, treatment was randomized between GM-CSF at 5 microg/kg/d or control, both being associated with antibiotics. RESULTS: GM-CSF significantly reduced the median duration of neutropenia from 6 to 3 days for ANC less than 1 x 10(9)/L(P < .001) and from 4 to 3 days for ANC less than 0.5 x 10(9)/L (P=.024), days of hospitalization required for febrile neutropenia, and duration of antibiotics during hospitalization. The greatest benefit with GM-CSF appeared for patients who had received low-risk chemotherapy, for which the median duration of ANC less than 1 x 10(9)/L was reduced from 7 to 2.5 days (P < .001) and from 4 to 2 days for ANC less than 0.5 x 10(9)/L (P=.0011), the duration of hospitalization during the study from 7 to 4 days (P=.003), and the duration on antibiotics during hospitalization from 7 to 3.5 days (P < .001). A multivariate analysis, using Cox regression, showed that variables predictive for recovery from neutropenia were GM-CSF (P=.0010) and time interval between the first day of chemotherapy and randomization (P=.030). There was no benefit for GM-CSF when high-risk chemotherapy was considered. CONCLUSION: GM-CSF significantly shortened duration of neutropenia, duration of neutropenic fever-related hospitalization, and duration on antibiotics during hospitalization when febrile neutropenia occurred after low-risk chemotherapy, but not high-risk chemotherapy.

High-dose methotrexate for the treatment of primary cerebral lymphomas: analysis of survival and late neurologic toxicity in a retrospective series.

PURPOSE: The impact of treatment options on survival and late neurologic toxicity was investigated in a series of patients with primary cerebral lymphoma (PCL) and no known cause of immunosuppression. PATIENTS AND METHODS: Prognostic factors for survival and treatment-induced late neurotoxicity were investigated in a retrospective series of 226 patients with PCL. RESULTS: With a median follow-up of 76 months, the median overall survival was 16 months and 5-year survival was 19%. In a univariate analysis, age greater than 60 years, performance status, CSF protein level greater than 0.6 g/L, involvement of corpus callosum or subcortical grey structures, detectable lymphoma cells in CSF, increased serum lactate dehydrogenase (LDH), but not histological subtype, were significantly correlated with a poor survival. Treatment with chemotherapy versus radiotherapy alone (P = .05), high-dose methotrexate (HDMTX; P = .0007), and cytarabine (P = .04) correlated with a better survival in univariate analysis. Using the Cox model, age, performance status, and CSF protein were independently correlated with survival. After adjustment of these factors, treatment with an HDMTX-containing regimen remained the only treatment-related factor independently correlated with survival (P = .01). The projected incidence of treatment-induced late neurotoxicity was 26% at 6 years in this series, with a median survival from the diagnosis of late neurotoxicity of 12 months. Treatment with radiotherapy followed by chemotherapy was the only parameter correlated with late neurotoxicity in multivariate analysis (relative risk, 11.5; P = .0007). CONCLUSION: Patients with PCL treated with regimens that included HDMTX followed by radiotherapy have an improved survival, but not a higher risk of late neurotoxicity as compared with other treatment modalities in this series.

Place of low-dose total body irradiation in the treatment of localized follicular non-Hodgkin's lymphoma: results of a pilot study.

PURPOSE: In a first prospective nonrandomized trial, 107 patients with Stage III and IV "low-grade" lymphomas have been treated with a combination of chemotherapy and low-dose total body irradiation (LD-TBI). This study shows that this scheme of LD-TBI was very well tolerated, gave a high response rate (83%), and extended RFS. It incited us to start a pilot study on localized follicular lymphomas. METHODS AND MATERIALS: From January 1986 through October 1994, 34 patients with previously untreated localized low-grade non-Hodgkin's lymphomas have been included in a prospective trial with LD-TBI followed by radical involved field radiotherapy (IF-RT). Patients received two courses of whole body irradiation of 0.75 Gy in 5 fractions and 1 week separated by a rest period of 2 weeks. After 1 month, patients were reevaluated, and received 40 Gy in 20 fractions, and 4 weeks on initially pathological lymph node areas. Eight patients have been excluded from the study: 4 after histologic review (2 centrocytic, 1 lymphocytic, 1 centroblastic) and 4 patients with Stage IV because of bone-marrow involvement. The remaining 26 patients were 11 men and 15 women, 50 years old median age (mean: 50.2; range: 35-73.5) with clinical Stage I (10 pts), II1 (8 pts), and II2 (8 pts). All patients received the planned treatment. RESULTS: Clinical tolerance was excellent, and the hematological follow-up shows a mean nadir value of 3.9.10(9)/l (2.1-8.1) for leucocytes, 13.4 g/l (10.8-15.4) for hemoglobin, and 124.10(9)/l (46-216) for platelets, with a median delay of 3.2 months. Of 26 patients, 24 achieved complete remission (CR) after the LD-TBI that was before the IF-RT. All patients, except one, were in complete remission after IF-RT. Nineteen patients remain alive without any evidence of disease, with a median follow-up of 56.2 months. Five patients relapsed; 3 of them died. CONCLUSION: As delivered, this schedule of LD-TBI give a very high rate of CR in localized follicular non-Hodgkin's lymphoma, with a very good tolerance. It remains to prove that this immediate efficacy has an impact on long-term disease-free survival in such patients, and to understand how the LD-TBI works (direct and/or indirect induction of apoptosis; relationship with t(14;18) translocation and overexpression of bcl-2). These will be the two aims of a new EORTC prospective randomized trial comparing LD-TBI followed by IF-RT vs. IF-RT alone.

Quality of life assessment in Hodgkin's disease: a new comprehensive approach. First experiences from the EORTC/GELA and GHSG trials. EORTC Lymphoma Cooperative Group. Groupe D'Etude des Lymphomes de L'Adulte and German Hodgkin Study Group.

Previous reports from available trials have dealt with negative long-term sequelae in Hodgkin's disease (HD) survivors. There is, however, a lack of longitudinal data showing the correlation between outcome and various treatment-related variables and the process of re-adaptation into normal life after the end of treatment. In order to investigate the quality of life (QoL) of patients with HD in different dimensions during active treatment and follow-up and to identify longitudinal patterns of QoL dimensions during re-adaptation to normal life within the EORTC Lymphoma Cooperative Group and Groupe D'Etude des Lymphomes de L'Adulte (EORTC/GELA) and the German Hodgkin Study Group (GHSG), QoL assessment strategies were put into use over the last three to five years. Furthermore, the efforts aimed at obtaining cross-cultural comparisons between the participating countries and study groups (EORTC/GELA and GHSG). Within the randomised EORTC/GELA Trial 'H8' for clinical stage I-II HD which started in September 1993, patients receive a QoL questionnaire for completion at each follow-up visit during the first 10 years after the end of active therapy. The corresponding 'HD8' study of the GHSG employs the assessment of QoL during and after active treatment periods. Within both studies, the EORTC QLQ C30 is used for QoL assessment incorporated in the QLQ-S (quality of life questionnaire for survivors), which additionally addresses the aspects of fatigue/malaise, sexuality, specific side effects, and retrospective evaluation of treatment. In total the QLQ-S includes 45 questions on 14 functional, symptom, and fatigue scales, 15 additional single items, and 3 open questions. In addition to the longitudinal QoL assessment, the GHSG carried out cross-sectional QoL trials with all cured surviving patients from the past HD1-6 studies and a matched normal control sample employing the QLQ-S and the life situation questionnaire (LSQ), an instrument covering objective data from 45 domains of life. To date, within the trials H8 and HD8 over 3000 QoL questionnaires from more than 800 patients from ten countries are available for analysis. Replication of the psychometric properties of the scales revealed satisfactory results using factor analyses and reliability testing across languages for the QLQ-S. A feasibility analysis showed generally a good acceptance of the questionnaire by the patients and physicians. QoL assessment within international multicentre trials in HD proved feasible within the two differently organised study groups of EORTC/GELA and GHSG. The use of subjective QoL data (QLQ-S) together with objective data (LSQ) in a combined cross-sectional and longitudinal trial system will give the most comprehensive insight into the problems of the re-integration process into normal life after cure. This information will provide the basis for the development of remedies/help measures and possible modifications of treatment strategies. The current approach will be further developed in close collaboration between both trial groups, and next steps will include translation of the LSQ into other languages and adaptation to various cultural circumstances.

[Mediastinal large B-cell lymphoma. A retrospective anatomic-clinical study of 26 cases]. / Lymphomes médiastinaux à grandes cellules B. Etude anatomoclinique rétrospective de 26 cas.

Mediastinal B-cell lymphomas (with or without sclerosis) have been recently recognized as an entity with particular clinical features. We report 26 patients with a mediastinal large B-cell lymphoma. They represent 5% of the patients with aggressive non-Hodgkin's lymphoma and 2% of all non-Hodgkin's lymphoma seen in our centre between 1962 and 1990. They include 19 females (73%) and 7 males (27%). The sex ratio was 2.7 and the median age was 44 years (range: 17-84 years). Compressive symptoms in relation with a bulky mediastinum were present in 21 cases (80%) and with B symptoms in 5 cases. All these patients received 2 to 4 cycles of chemotherapy with a CHOP-like protocol (epirubicin or doxorubicin, cyclophosphamide, vincristine and prednisone) followed in 24 cases by mediastinum irradiation (40 Gy). Two patients progressed during chemotherapy and did not receive radiotherapy. Nineteen patients had a consolidation chemotherapy according to the same protocol. Twenty-one patients achieved a complete remission after chemotherapy or radiotherapy and 5 failed. Two patients relapsed at 10 months and 9 years. Seventeen patients are alive and in first complete remission with a median follow-up of 102 months (range: 60-260 months). Using the Kaplan-Meier method, the overall survival at 5 and 10 years was respectively 77 and 61% and the relapse-free survival was respectively 68 and 57%. These results confirm the previous findings concerning this distinct entity which is characterized by a predilection for young women, compressive symptoms, a slow response to treatment and a rather good prognosis.