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.

Adjuvant bacillus Calmette-Guérin therapy in non-Hodgkin's malignant lymphomas: long-term results of a randomized trial in a single institution.

Between 1973 and 1977, 48 patients less than 65 years old with non-Hodgkin's malignant lymphoma (NHML) of poor prognosis (+/- high grade malignancy, +/- clinical stages III or IV, +/- first or repeated relapse) were included in a prospective clinical trial. After complete remission (CR), obtained with chemotherapy and radiotherapy, patients were randomized to receive bacillus Calmette-Guérin (BCG) or no further therapy. BCG was administered in weekly scarifications up to 3 years. Forty-three patients are assessable. Twenty-four patients have relapsed: nine out of 21 in the BCG group, and 15 out of 22 in the control group. There is a significant difference in favor of the BCG group in disease-free survival (P = .03). Twenty-one patients have died, 18 from NHML: seven in the BCG group, and 11 in the control group. There is a significant difference in favor of the BCG group for overall survival at 10 years (P = .05). A multivariate analysis points out BCG as a significant prognostic factor. Adjuvant BCG may improve particularly disease-free survival and overall survival for patients with clinical stages I and II or intermediate- and high-grade malignancy. These results suggest that in patients less than 65 years old with NHML of poor prognosis, BCG may significantly increase disease-free survival and overall survival.

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.

Extended versus involved fields irradiation combined with MOPP chemotherapy in early clinical stages of Hodgkin's disease.

From 1976 to 1981, 335 patients with untreated Hodgkin's disease, clinical stages I, II, and IIIA, have been treated by MOPP (nitrogen mustard, vincristine, procarbazine, prednisone) chemotherapy, three to six cycles according to the prognostic factors, combined with radiotherapy. Irradiation was always performed after the first three cycles of chemotherapy, and was randomized between extensive radiotherapy, ie, mantle and paraaortic areas for supradiaphragmatic presentations, and radiotherapy restricted to the involved areas. No significant difference was observed between the two randomized branches for the disease-free survival (86% after six years in the involved field branch v 90% in the extended field branch), and none for the overall survival. Most of the relapses occurred in nonirradiated areas in the first group, and in irradiated areas in the second. Relapses were especially frequent in the IIE stages with pulmonary extension; extranodal relapses occurred with osseous and cutaneous localizations. Two cases of secondary leukemia were observed after three- or six-cycle MOPP plus radiotherapy limited to the involved areas.

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.

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.

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.

Low-grade follicular lymphomas: analysis of prognosis in a series of 281 patients.

From 1963 to 1988, 281 patients with newly diagnosed follicular lymphomas were treated and followed at the Foundation Bergonié. Distribution of stages was: 72 I, 61 II, 83 III and 65 IV. Within stage III, two subgroups were retrospectively defined: stages III1 (32 cases) included patients with less than 8 involved sites, only 1 or 2 above diaphragm, and no spleen or mediastinal enlargement. Stage III2 (51 cases) included the remaining stage III cases. Median follow-up was 9 years. Complete remission (CR) rate was 82%. 10-year overall survival (OS) and time to treatment failure (TTF) rates were, respectively 38% and 29.5%. 10-year time to relapse (TTR) rate was 36%. Statistical analyses showed concordant results with two main prognostic factors: age (less than 60/greater than 60) and stage (I to III1/III2 and IV). Age was the most important factor for OS analysis and stage for CR and TTR analysis. This leads to only three prognostic groups with different outcome. The first includes younger patients (less than 60 years) with limited stages (less than or equal to III1); the second, patients either older than 60 or with advanced stages; the last, elderly patients with advanced stages. CR rates of these three groups were, respectively 97%, 75% and 57%. 10-year OS were, respectively 73.5%, 27% and 0%; 10-year TTR were 54%, 22% and 0%. These results have lead to data which are easy to handle and which can help to establish a rationale for further prospective trials.

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.

Localized follicular lymphomas: prognosis and survival of stages I and II in a retrospective series of 103 patients.

From 1966 to 1985, 103 patients with a localized (stages I and II) follicular lymphoma (Kiel classification) were treated at the Fondation Bergonié. Clinical staging was performed using, after physical examination, chest X-rays (100%), bipedal lymphangiography (98%) and unilateral bone marrow biopsy (BMB) (51.5%). The patients were then treated by radiotherapy with or without chemotherapy. Overall survival (OS) at 5 and 10 years is 69 and 56.3%, respectively. Relapse-free survival (RFS) is 53.7 and 49%. Unifactorial analysis shows three prognostic parameters to be independently significant in terms of OS: age, stage and B symptoms. In terms of RFS, only 2 factors are significant: age and B symptoms. Multivariate analysis (Cox model) shows that age is a more important prognostic factor than stage.

Combination of ABVD and radiotherapy in early stages of Hodgkin's disease: analysis of a series of 94 patients. Pierre and Marie Curie Group (GPMC).

In order to reduce, if not completely suppress, late complications of combined chemotherapy and radiotherapy in Hodgkin's disease (HD), MOPP regimen (mechlorethamine, vincristine, procarbazine and prednisone) was replaced by ABVD (doxorubicin, bleomycin, vinblastine and dacarbazine). Ninety-four patients with HD clinical stages I to IIIA with no staging laparotomy were treated by three courses of ABVD followed by radiotherapy. Irradiation was performed on extended fields in 41 cases and on involved fields in 53 others. Consolidation chemotherapy was planned in 67 cases with at least one unfavorable prognostic factor, but achieved only in 33 cases. Seventeen patients relapsed within 1 to 46 months after the beginning of treatment. Ten patients died, 7 of HD and 3 of intercurrent diseases or accident. Disease-free survival rate with a median follow-up of 60 months is 80%. This study showed, on the one hand, many digestive and general side-effects after ABVD and, on the other, a satisfactory hematological tolerance. Furthermore, mediastinitis or cardiovascular complications were not more frequent than with MOPP. These results point out the development and use of better tolerated regimens for initial chemotherapy in HD, without jeopardizing the good results of the treatment.

Benign lymphocytic angiitis and granulomatosis: a T-cell lymphoma?

Benign lymphocytic angiitis and granulomatosis is a T-cell lymphoproliferative disorder confined to the lung and corresponding to a low-grade angiocentric immunoproliferative lesion. Controversy remains as to whether these lesions are lymphomas. We report such a case in an 8-year-old patient with Burkitt's lymphoma in remission who presented with persistent bronchopneumopathy and bilateral pulmonary infiltrates on tomodensitometry. Surgical resection revealed the histologic changes of benign lymphocytic angiitis and granulomatosis. Immunohistochemistry showed no aberrant pan T-cell marker loss. Genetic analysis of frozen tissue by Southern blot DNA hybridization with probes to T-cell receptor beta- and gamma-chain genes and to the immunoglobulin heavy chain joining region gene (JH) identified no clonal rearrangement. Search for Epstein-Barr virus-DNA sequences by in situ hybridization and Southern blot analysis provided negative results. Our data imply that lowgrade angiocentric immunoproliferative lesions are not exclusively lymphomas but might represent a borderline lymphoproliferative disease (seen in the course of many diseases), perhaps corresponding to host immune response.

Novel combination of epirubicin, bleomycin, vinblastine and prednisone (EBVP II) before radical radiotherapy in localized stages (I-IIIA) of Hodgkin's disease. Early results in 100 consecutive patients. Pierre-et-Marie-Curie Group.

A novel combination of epirubicin, bleomycin, vinblastine and prednisone (EBVP II) was scheduled to reduce the toxicity of chemotherapy and to improve its application in treatment of Hodgkin's disease. This combination followed a previous regimen given every 15 days (EBVP I) by the same cooperative group. EPVP II is given every 21 days with increased dosage and increased intensity of epirubicin. This regimen was given to 100 consecutive patients with favourable or unfavourable limited-stage disease (clinical stages I-IIIA) excluding very favourable stages I and II and stages IIIB and IV. Such patients first received three injections of EBVP II and were then radically irradiated; those with unfavourable prognosis factors received three subsequent injections of EBVP II. The present analysis reports the early results of such treatment and considers particularly toxicity and the obtention of complete remission, which is pre-eminent for a cure. EBVP II was given in full dosage in 99% of the primary set of three injections. The main toxicity was alopecia and to a lesser degree nausea and vomiting and veinitis. Complete remission was obtained in 76 patients before radiotherapy and in 20 others after radiotherapy. With a median follow-up of 30 months 1 patient died from Hodgkin's disease, 9 are alive after relapse and 90 with no evidence of disease. This treatment appears to be as efficient as previous chemotherapy, well tolerated and particularly easy to give. It deserves further comparison with other proved regimens taking into consideration the survival and quality of life of patients.

CD30-positive cutaneous large cell lymphomas. A comparative study of clinicopathologic and molecular features of 16 cases.

The authors have analyzed and compared the clinicopathologic and molecular features of 16 cases of large cell cutaneous lymphomas expressing CD30 antigen. Three main clinical groups were defined: (1) a group of localized skin disease (7 cases); (2) a group of multicentric skin disease (5 cases); and (3) a group of concomitant skin and extracutaneous disease. Good prognosis was associated with localized skin disease and no history of lymphoma. Interestingly, a majority of Reed Sternberg-like cells was only observed in this group (5 of 6 cases). The two other groups did not show distinctive evolutive nor morphologic features. Southern blot and/or polymerase chain reaction (PCR) technique showed clonality and a T-cell genotype in respectively 13 of 14 and 12 of 12 analyzed cases. Viral infection of tumoral cells was investigated by PCR, in situ hybridization (ISH) or electron microscopy. Epstein-Barr virus (EBV) sequences were detected by PCR and ISH in tumoral cells of cutaneous lesions in one case of skin lymphoma with extracutaneous spreading. No EBV sequence was detected by ISH in the localized lymphomas, whereas HIV particles were visible in tumoral cells in one of these cases. No human T-cell lymphotropic virus (HTLV) tax sequence was amplified by PCR in any case of our series. Our results confirm that CD30-positive cutaneous large cell lymphomas are different clinical and molecular entities. However, a combined clinical and morphologic analysis may help to identify a subset of CD30 cutaneous lymphomas with favorable prognosis.

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.

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.

Maintenance immunotherapy with BCG in non-Hodgkin's malignant lymphomas: a progress report of randomized trial.

Ninety-eight patients with non-Hodgkin's malignant lymphoma were first put into complete remission by a combination of chemotherapy and radiotherapy, and then received one course of chemotherapy as reinforcement. They were then randomized to receive either maintenance BCG therapy or no other treatment. Ninety-three patients were available for this analysis. There was a significant difference (P = 0.021) in relapse-free survival times between the two groups of patients. This difference is particularly significant in male patients, in patients ages 50-65 years, in all histologic classes, in patients treated after an initial relapse, and in clinical stages I and II. There was also a difference in crude survival, but the difference was not significant.