Between October 1985 and October 1989, 75 previously untreated patients with stage III and IV non Hodgkin's lymphoma, large cell type, were treated with an alternating weekly chemotherapy regimen including the following drugs: week 1: Doxorubicin, vincristine, cyclophosphamide, bleomycin, and intrathecal (i.th.) methotrexate and cytarabine; week 2: Methotrexate with leucovorin rescue: week 3: Doxorubicin, ifosfamide with mesna, etoposide, and i.th. methotrexate and cytarabine; week 4: Methotrexate with leucovorin rescue. Complete responders after three cycles according to this schedule (12 weeks) were given 18 gys cranial irradiation and randomized between one additional cycle or three monthly CHOP (consolidation treatment). Among 66 evaluable patients, 53 achieved a complete remission (CR 80 per cent) and seven a partial remission (11 per cent). There were six failures, and nine early deaths during the initial phase, mostly due to septic problems. Forty-one of the 53 CR patients (77-3 per cent) have remained free of disease with a median follow-up of 15 months (1-49). Eight of the 12 relapses occurred during the first year, the four others at 13, 14, 16 and 38 months respectively. The 2-year survival was 63 per cent for the whole group, and 77 per cent for the CR group. No difference has been observed up until now between the two groups with different consolidation treatment. Therefore, this protocol seems to be able to produce a high rate of complete and durable remission. The analysis of prognostic factors suggests that some high-risk patients should be considered for intensification therapy with the support of autologous bone marrow transplantation.

BACKGROUND:We conducted a phase II study to evaluate in 72 adult patients the efficacy of the intensive LMB chemotherapy regimen, previously reported by the Société Française d'Oncologie Pédiatrique for children with Burkitt lymphoma and L3 acute lymphoblastic leukemia. PATIENTS AND METHODS:Treatment began with a prephase (low-dose steroids, vincristine and cyclophosphamide), except in patients with low tumor burden. Group A (resected stage I and abdominal stage II disease) received three courses of vincristine, cyclophosphamide, doxorubicin and prednisone. Group B (not eligible for groups A or C) received five courses of chemotherapy comprising high-dose methotrexate, infusional cytarabine and intrathecal (IT) methotrexate. Group C (patients with central nervous system and/or bone marrow involvement with < 30% of blast cells) received eight courses containing intensified high-dose methotrexate, high-dose cytarabine, etoposide and triple IT injections. RESULTS:The 2 year event-free survival and overall survival rates for the 72 patients were 65% and 70%, respectively. Age > or = 33 years and high lactate dehydrogenase value were associated with a shorter survival. No response to COP was also associated with a poor outcome in group B. CONCLUSION:Patients with advanced-stage Burkitt lymphoma, including those with bone marrow and/or central nervous system involvement, can be cured with a short-term intensive chemotherapy regime tailored to the tumor burden.

To compare the effects of recombinant activated factor VII (rFVIIa) and platelet-rich plasma (PRP) in an experimental model of bleeding and arterial thrombosis.

In a patient with recently diagnosed chronic myelomonocytic leukemia features, the biopsy of a peripheral lymphadenopathy seven months later revealed disorganised lymphoid tissue with a few large EBER (+) LMP1 (+) B-lymphocytes before any treatment was given. At this time, a clonal TCR gamma rearrangement and very faint clonal IgH rearrangement were demonstrated, and the diagnosis of angioimmunoblastic T-cell lymphoma was made. Treatment with MOPP was started, followed by Hydroxycarbamide and CHOP but the outcome was fatal. During the evolution, there was no blastic transformation of the chronic myelomonocytic leukemia. The T-cell lymphoma extended to abdominal lymph nodes, Waldeyer ring and bone marrow and the percentage of large LMPI EBER (+) B-cells increased in the lymph nodes. These findings do not support a common stem cell abnormality leading to myelodysplasia in the bone marrow and lymphoma in peripheral lymph nodes. The lack of a clearcut light chain restriction in the EBV infected B-cell is suggestive of a persistant EBV infection in polyclonal or oligoclonal activated B-cells as described in immunodepressed patients. The association of CMML features and an angioimmunoblastic T-cell lymphoma is discussed.

Between 1985 and 1990, the French Cooperative Group on Chronic Lymphocytic Leukemia (CLL) randomized 287 stage B patients between intermittent chlorambucil plus prednisone (n=140) or CHOP (n=147), and 90 stage C patients between CHOP (n=44) or CHOP plus methotrexate (n=46). In stage B, although treatment response was improved with CHOP (p=0.007, chi-square test), no difference in survival was observed between the two randomized groups (p=0.33, score test). In stage C, no differences in treatment response and survival were shown, with median survival close to that reported with CHOP in the previous CLL-80 trial. These results associated with those from other groups raise the question whether the CHOP regimen, which has been consistently shown to improve response to therapy, is an effective treatment in advanced CLL patients.

The variable course of the disease, the advanced age of most patients and the absence of uniform criteria to evaluate treatment have constituted important setbacks in the therapy of CLL. The advent of clinical staging systems, which allow the identification of patients with different risks and the planning of appropriate therapy, constitutes a major advance. Results of trials based on these staging systems have demonstrated that treatment of patients with CLL in early stage is of no benefit and may even be harmful. By contrast, there is general agreement that patients in advanced stage should be treated.

As part of a study of two therapeutic protocols initiated in 1982 and 1985, respectively, for localized (n = 134) and disseminated (n = 76) large cell lymphomas, histologic type was determined for each patient by several pathologists using the Kiel classification for morphologic features and the international working formulation for protocol assignment and multifactorial statistical analysis. Therapeutic results in the two hundred and ten cases were correlated with a number of prognostic factors including age, stage, tumor size, extranodal disease, and clinical or biological markers for disease activity such as the LDH level. The previously reported influence of histologic subgroup on prognosis was not found with these highly effective protocols, whether histologic type was considered alone or in combination with other prognostic factors. The only consistent finding was that anaplastic large cell lymphomas, despite their aggressive features, were most likely to have a favorable outcome.

Biology of the CellVolume 76, Issue 2 p. 260-260 Immunophenotyping of follicular dendritic cell clusters: Quantitative and tridimensional analysis A. Costa, A. Costa Department d'hématologie, Centre d'Ecologie Cellulaire, Hôpital Pitié-Salpétrière, Paris, FranceSearch for more papers by this authorJ. Feuillard, J. Feuillard Department d'hématologie, Centre d'Ecologie Cellulaire, Hôpital Pitié-Salpétrière, Paris, FranceSearch for more papers by this authorJ. Vassy, J. Vassy INSERM URBB 263, Paris, FranceSearch for more papers by this authorC. Lesty, C. Lesty Department d'hématologie, Centre d'Ecologie Cellulaire, Hôpital Pitié-Salpétrière, Paris, FranceSearch for more papers by this authorJ.P. Rigaud, J.P. Rigaud INSERM URBB 263, Paris, FranceSearch for more papers by this authorM. Raphael, M. Raphael Department d'hématologie, Centre d'Ecologie Cellulaire, Hôpital Pitié-Salpétrière, Paris, FranceSearch for more papers by this author A. Costa, A. Costa Department d'hématologie, Centre d'Ecologie Cellulaire, Hôpital Pitié-Salpétrière, Paris, FranceSearch for more papers by this authorJ. Feuillard, J. Feuillard Department d'hématologie, Centre d'Ecologie Cellulaire, Hôpital Pitié-Salpétrière, Paris, FranceSearch for more papers by this authorJ. Vassy, J. Vassy INSERM URBB 263, Paris, FranceSearch for more papers by this authorC. Lesty, C. Lesty Department d'hématologie, Centre d'Ecologie Cellulaire, Hôpital Pitié-Salpétrière, Paris, FranceSearch for more papers by this authorJ.P. Rigaud, J.P. Rigaud INSERM URBB 263, Paris, FranceSearch for more papers by this authorM. Raphael, M. Raphael Department d'hématologie, Centre d'Ecologie Cellulaire, Hôpital Pitié-Salpétrière, Paris, FranceSearch for more papers by this author First published: 1992 https://doi.org/10.1016/0248-4900(92)90359-9AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article. Volume76, Issue21992Pages 260-260 RelatedInformation

In sections from 32 B malignant lymphomas (ML), the total KI-67 stained area was compared to the number of KI-67 positive cells in order to demonstrate the reliability of using image analysis to quantify the proliferative activity. The total KI-67 area percentage correlated highly with the number of KI-67 positive cellular profiles (r = .93). Significant differences were found between low- and high-grade ML according to the Kiel classification (mean values +/- SD, respectively, of 7.7 +/- 3.81% and 16.6 +/- 6.23%), and between low-, or intermediate- and high-grade ML only, according to the International Working Formulation. Within the Working Formulation, the statistical analysis grouped the diffuse large cell subtype of intermediate grade with the immunoblastic high-grade subtype. A wide range of KI-67 area percentage values was noted, particularly in follicular ML; for these follicular ML, considering follicular areas only, values were comparable to high-grade ML (14.8 +/- 6.60%). In conclusion, the KI-67 area percentage is a reliable alternative method to manual cell counting, and image analysis allows quicker measurements appropriate to large and strictly lymphomatous areas, using a greater number of cells than in manual cell counting.

Since 1980, the French Cooperative Group on Chronic Lymphocytic Leukemia (CLL), including 43 hematological departments, has conducted three randomized clinical trials. More than 2,500 patients are nowadays randomized in these trials (973 in the CLL80 protocol and 1330 in the CLL85 protocol). These trials clearly contributed to the better knowledge and understanding of the CLL, in each stage of the disease. In stage A-CLL, the protocol CLL80 included 611 patients, randomly allocated either to daily chlorambucil (n = 302) or abstention (n = 309). Results of the third interim analysis, based on the reference date of June 1, 1986, pointed out the complex action of chlorambucil, associating beneficial effects consisting in slowing down disease progression to stage B or C and favoring disease remission, with harmful effects given by a shorten survival and an excess of epithelial cancer, as compared with the no treatment group. However, the harmful effects of chlorambucil have not been yet observed in the CLL85 protocol, where 932 stages A were randomized between intermittent chlorambucil (n = 466) and no treatment (n = 466). Nevertheless, the potential harmful effects of the treatment raised out the question of therapeutical decision in stage A-CLL, and contributed to the design of the new protocol, CLL90, in which stage A-CLL are not treated until disease progression is observed. In stage C-CLL, the CLL80 protocol included 70 patients. It demonstrated that the polychemotherapy CHOP, i.e. COP + doxorubicin improved these patients (n = 34) as compared with those treated with COP (n = 36), in terms of disease remission as well as survival. The CLL85 protocol involved 90 stages C, and showed no benefit on survival from methotrexate when associated with CHOP. In stage B-CLL, the CLL80 protocol included 291 patients, who were randomized between daily chlorambucil (n = 150) and the COP polychemotherapy (n = 141). The interim analyses of this trial pointed out the closed results of these two treatments, either for disease remission or for survival. Thereafter, the protocol CLL85 randomized 287 stages B between two polychemotherapies, COP (n = 140) and CHOP (n = 147). However, although the follow-up of this latter trial is rather short considering the main endpoint (survival), no beneficial effect of the CHOP was observed in terms of overall survival, although a benefit was observed in terms of hematological response at the sixth month. Considering the poor prognosis of the stages B and C, the current protocol (CLL90) compares, in both stages B and C, the effect of three treatments, namely CHOP, CAP and Fludarabine.

An attempt is made to evaluate more clearly the potential contribution of quantitative nuclear profile shape and size measurements to lymph node section histologic description in 70 cases of non-Hodgkin's lymphoma (NHL). The area of nuclear profiles and five nonredundant and size-free shape indices were measured using the THECLA program on a Leitz Texture Analysis System (Leitz-TAS). Two statistical approaches were applied, known respectively as "parametric," (first statistical moments of variable distributions over samples of 200 nuclear profiles) and "nonparametric," which are percentages of nuclear profiles distributed into five "cytological" classes that are defined by shape: round (A), elongated (B), kidney shaped (C), irregular (D) and cleaved (E) nuclear profiles. Both statistical approaches provide proper overall discrimination of the eight histological categories identified with reasonable reliability by pathologists. Above all, the present report discusses the ability of a set of parametric and nonparametric variables to describe NHL cell populations, in an objective and meaningful way, according to nuclei shape. A method of synthesizing multidimensional correlations (CORICO program) is proposed in support of the discussion. Also, the specific descriptive power of each of the variables is described; in particular, it is concluded that there is a close link between the shape and size of the nuclear profiles of the cells.

A T8 lymphocyte alveolitis occurs in HIV-positive patients, even in the absence of any lung infections or tumors. Using the monoclonal antibody (MAb) D44, the CD8+ T cells can be further subdivided into two functional subsets of cytotoxic T lymphocytes (CTL; CD8+, D44+) and suppressor T cells (CD8+, D44-). A dual fluorescence analysis of alveolar and peripheral lymphocytes has been used in HIV-positive patients without lung infections or tumors to reveal a dramatic increase in alveolar T8 lymphocytes (83%), compared to peripheral values (52%), which was mainly composed (89%) of CD8+ D44+ CTLs. Functional studies confirmed the cytolytic activity of these phenotypically defined alveolar CTLs on autologous alveolar macrophages used as target cells, excluding a natural killer-like activity. An immuno-enzyme analysis concomitantly revealed the co-expression of the p18 HIV antigen and the CD4 molecule on the autologous alveolar macrophages. These data suggest that CTL alveolitis occurs during HIV infection and is directed against HIV-infected alveolar macrophages which are presumably the targets of the locally recruited lung CTLs.

Human immunodeficiency virus (HIV) is implicated in the development of AIDS (acquired immune deficiency syndrome). HIV infection leads to the generation of HIV-specific thymus-derived (T) lymphocytes in humans and apes. We describe an experimental system permitting the quantitative and systematic analysis of HIV-specific cytotoxic T lymphocytes (CTL). Functional, HIV-specific CTL are obtained by broncho-alveolar lavage (BAL) from the lungs of seropositive patients with lymphocytic alveolitis. These alveolar CTL: (1) recognize and kill HIV-infected alveolar macrophages in vitro under autologous, but not heterologous, conditions; (2) correspond to standard CTL as they express the CD3 and CD8 surface markers, but not the CD4 marker; and (3) are restricted by class I HLA transplantation antigens in their cytotoxic activities. We propose the hypothesis that interactions between HIV-specific CTL and infected macrophages induce major inflammatory reactions in seropositive patients.

The present study is concerned with clinical prognostic classifications of chronic lymphocytic leukemia derived from numerous statistics and multivariate survival analysis. We analyse the prognostic significance of some biological patterns: bone marrow histological studies, lymph node biopsies, size, structure and doubling time of blood lymphocytes, tumoral markers and karyotype analysis. The problem of the monoclonal clone origin is discussed: differentiation abnormality or proliferation of a physiological clone.

In addition to the nuclear area and a form factor, four morphometric parameters of nuclear shape (ID, R1, R2 and ND), obtained by the application of the principles of mathematical morphology, were used to characterize the nuclear contours in non-Hodgkin's malignant lymphomas. The values for each parameter were determined in 58 cases of non-Hodgkin's lymphoma categorized according to the Kiel and National Cancer Institute classifications. Small-cell, mixed and large-cell lymphomas could be distinguished on the basis of the mean nuclear area. The shape parameters R1, R2 and ID were efficient discriminators of the large centrocytic (cleaved-cell) lymphomas. Neither size nor shape factors could distinguish between centroblastic and immunoblastic tumors. The good correlation between the morphometric findings and the histopathologic categories suggest that morphometry may provide a quantitative and objective method for grading lymphomas.